Artículos de revistas: "378.1/2/092 b"

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Yin, X. Y., R. L. Zhang, H. Y. Zheng, Y. Q. Bai, Q. Yu, P. F. He, X. LI y S. X. Zhang. "OP0159 GENETICALLY DETERMINED CAUSAL RELATIONSHIP BETWEEN GOUT AND CARDIOVASCULAR DISEASE". Annals of the Rheumatic Diseases 82, Suppl 1 (30 de mayo de 2023): 105. http://dx.doi.org/10.1136/annrheumdis-2023-eular.4227.

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BackgroundGout is a common inflammatory arthritis caused by monosodium urate deposits around the joints[1]. The risk of cardiovascular events, including death, is substantially higher in people with gout than in those without gout[2]. Although epidemiological studies have reported a positive correlation between circulating urate levels and cardiac metabolic diseases, the causal relationship between gout and cardiovascular diseases(CVD) is still uncertain[3].ObjectivesThis study aimed to explore the causal relationship between gout and CVD from the genetic level. We examined the potential effects of gout on coronary heart disease(CHD), coronary artery disease(CAD), atrial fibrillation(AF), myocardial infarction(MI), pulmonary embolism(PE), any stroke, ischemic stroke and its subtypes [cardioembolic(CES), small-vessel(SVS), extensive artery atherosclerosis(LAS)].MethodsWe obtained genetic information related to gout from the Global Urate Genetics Consortium (GUGC), including 2115 cases and 67259 healthy controls with 5057528 single nucleotide polymorphisms(SNPs). SNPs significantly associated with CVD were obtained from large genome-wide association(GWAS) meta-analyses and the UK Biobank as instrumental variables(IVs) for Mendelian randomization(MR). The inverse variance weighting (IVW), MR Egger, and weighted median were used to estimate the effect size. MR-PRESSO was used to detect and eliminate SNPs that may bring significant pleiotropy.ResultsMR results supported that gout had significant causal effects in CHD, CAD, and MI. There was a significant positive correlation between the genetic responsibility of gout and the risk of CVD(CHD: OR=1.031, 95%CI:1.007-1.057, P=0.012; CAD: OR=1.031, 95%CI:1.007-1.057, P=0.012; MI: OR=1.037, 95%CI: 1.037-1.009, P=0.009). In reverse MR, we only observed that any stroke would increase the risk of gout(OR=1.265, 95%CI: 1.010-1.585, p=0.041). No pleiotropy was detected in the sensitivity analysis(all p>0.05).ConclusionThe responsibility of gout had a significant causal relationship with CHD, CAD, and MI, suggesting adequate management of gout could reduce the risk of CVD.References[1] Lai, B. et al. Assessing the causal relationships between gout and hypertension: a bidirectional Mendelian randomisation study with coarsened exposures. Arthritis Res Ther 24, 243, doi:10.1186/s13075-022-02933-4 (2022).[2] White, W. B. et al. Cardiovascular Safety of Febuxostat or Allopurinol in Patients with Gout. N Engl J Med 378, 1200-1210, doi:10.1056/NEJMoa1710895 (2018).[3] Keenan, T. et al. Causal Assessment of Serum Urate Levels in Cardiometabolic Diseases Through a Mendelian Randomization Study. J Am Coll Cardiol 67, 407-416, doi:10.1016/j.jacc.2015.10.086 (2016).Acknowledgements:NIL.Disclosure of InterestsNone Declared.

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Abdallah, Abdullah I., Nicola J. Commander, Martin J. Woodward, Steve Spencer, C. Anthony Hart y Craig Winstanley. "Type III Secretion Homologs Are Present in Brucella melitensis , B. ovis , and B. suis biovars 1, 2, and 3". Current Microbiology 46, n.º 4 (1 de abril de 2003): 241–45. http://dx.doi.org/10.1007/s00284-002-3789-3.

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Ghoneim, M. M. y A. Tawfik. "Voltammetric studies and assay of the anti-inflammatory drug ketoprofen in pharmaceutical formulation and human plasma at a mercury electrode". Canadian Journal of Chemistry 81, n.º 8 (1 de agosto de 2003): 889–96. http://dx.doi.org/10.1139/v03-092.

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The electrochemical reduction of the anti-inflammatory drug ketoprofen was studied in a Britton-Robinson (B-R.) buffer series of pH 211 using dc-polarography, cyclic voltammetry, and coulometry techniques. The electrode reaction pathway of the drug at the dropping mercury electrode was proposed and discussed. A new adsorptive cathodic stripping square-wave voltammetric procedure was optimized for the assay of bulk drug in a B-R. buffer of pH 2.0. The peak current was linear with the drug concentration over the ranges 2 × 109 to 2 × 107 M of the bulk drug, using a 60 s accumulation time period at 0.6 V (vs. Ag/AgCl/KCls). The percentage recovery of the bulk drug was 99.57 ± 0.54 and a detection limit of 0.10 ng mL1 was achieved. The proposed procedure was successfully applied for the assay of ketoprofen in pharmaceutical formulation (Ketofan®) and human plasma. The percentage recoveries were 99.66 ± 0.47 and 101.76 ± 0.64 in pharmaceutical formulation and human plasma, respectively. A detection limit of 0.14 ng mL1 plasma was achieved which was below that reported in literature using the different analytical techniques.Key words: ketoprofen (Ketofan®) determination, polarography, cyclic voltammetry, adsorptive cathodic stripping square-wave voltammetry, human plasma.

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Gachango, E., W. Kirk, L. Hanson, A. Rojas y P. Tumbalam. "First Report of Fusarium torulosum Causing Dry Rot of Seed Potato Tubers in the United States". Plant Disease 95, n.º 9 (septiembre de 2011): 1194. http://dx.doi.org/10.1094/pdis-04-11-0291.

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Fusarium dry rot of potato (Solanum tuberosum L.) is a postharvest disease caused by several Fusarium species and is of worldwide importance. Thirteen species of Fusarium have been implicated in fungal dry rots of potatoes worldwide. Among them, eight species have been reported in the northern United States (2). In Michigan potato production, F. sambucinum was the predominant species reported to be affecting seed potato in storage and causing seed piece decay after planting (3). Some previous identifications of F. sambucinum as dry rot may have been F. torulosum since F. torulosum was previously classified within F. sambucinum (4). To further investigate this, dry rot symptomatic tubers were collected from Michigan seed lots in the summers of 2009 and 2010. Small sections from the margins of necrotic regions were cut with a scalpel, surface sterilized in 0.5% sodium hypochlorite for 10 s, rinsed twice in sterile distilled water, and blotted with sterile filter paper. The tissue pieces were plated on half-strength potato dextrose agar (PDA) amended with 0.5 g/liter of streptomycin sulfate and incubated at 23°C for 5 to 7 days. Cultures resembling Fusarium species were transferred onto water agar, and single hyphal tips from actively growing isolates were removed and plated either on carnation leaf agar (CLA) or on half-strength PDA to generate pure cultures. Among the Fusarium isolates obtained, five isolates were identified as F. torulosum (GenBank Accessions Nos. JF803658–JF803660). Identification was based on colony and conidial morphology on PDA and CLA, respectively. These features included slow growth (2.8 ± 0.2 cm in 5 days), white mycelium that became pigmented with age, narrow concentric rings, red or white pigmentation on agar, macroconidia (32.4 ± 0.4 μm average length) with five septa, a pointed apical cell, and a foot-shaped basal cell (4). The identity was confirmed through DNA extraction followed by amplification and sequencing of the translation elongation factor (EF-1α) gene region (1). The Fusarium-ID.v (1) and the NCBI database were used to obtain the closest match (99%) to previously sequenced materials (GenBank Accession No. AJ543611). Pathogenicity testing was done on disease-free potato tubers cv. Red Norland. Tubers were surface sterilized for 10 min in 0.5% sodium hypochlorite and rinsed twice in distilled water. Three tubers per isolate were injected with 20 μl of a conidial suspension (106 conidia/ml) made from F. torulosum cultures grown on PDA for 7 to 10 days. Control tubers were injected with 20 μl of sterile distilled water. All tubers inoculated with F. torulosum developed typical potato dry rot symptoms consisting of a brown and dry decay. There was no disease incidence on the control tubers. F. torulosum was reisolated from the symptomatic tubers. To our knowledge, this is the first report of F. torulosum causing potato dry rot in the United States. References: (1) D. Geiser et al. Eur. J. Plant Pathol. 110:473, 2004. (2) L. E. Hanson et al. Phytopathology 86:378, 1996. (3) M. L. Lacy and R. Hammerschmidt. Fusarium dry rot. Extension Bulletin. Retrieved from http://web1.msue.msu.edu/msue/iac/onlinepubs/pubs/E/E2448POT , 23 May 2010. (4) J. F. Leslie and B. A. Summerell. The Fusarium Laboratory Manual. Wiley-Blackwell, Hoboken, NJ, 2006.

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Gidney, M. A. J., D. R. Bundle, A. Godard y B. W. Griffiths. "Development and characterization of monoclonal antibodies to pregnancy-specific β1-glycoprotein". Canadian Journal of Biochemistry and Cell Biology 63, n.º 7 (1 de julio de 1985): 737–42. http://dx.doi.org/10.1139/o85-092.

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Six monoclonal antibodies were developed to pregnancy-specific β1-glycoprotein (PSβ1G). Studies of ascitic fluid antibodies by a double-antibody radioimmunoassay (RIA) included an evaluation of titers, dose–response parameters, and mass action properties. Four of the antibodies demonstrated moderate to high titers ranging from 1/40 000 to > 1/120 000, as determined by the specific binding of 125I-labeled PSβ1G. In inhibition studies utilizing a standard containing known quantities of placental PSβ1G, two of the antibodies (AR#11 and B#2) were highly sensitive and only slightly lower in this regard than a high affinity polyclonal antiserum. The binding affinities of AR#11 and B#2 monoclonals were greater than 109 mol−1 which underline their importance as potential clinical reagents for the RIA of PSβ1G. The Scatchard plots, for several of the antibodies, were linear and in full agreement with a single order of binding sites predicted for specific monoclonal reagents. Immunodiffusion results provide preliminary evidence that at least three distinct determinants on PSβ1G are recognized by a number of the monoclonal antibodies. Further studies on the fine specificities of the antibodies by solid-phase RIA, as well as a detailed evaluation of their clinical applications, are in progress.

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Yang, Xu, Bowen Chen, Yanyu Wang, Yunchao Wang, Junyu Long, Nan Zhang, Jinnan Xue et al. "Lenvatinib plus PD-1 inhibitors in 378 unresectable hepatocellular carcinoma: A large real-world study from two centers." Journal of Clinical Oncology 40, n.º 16_suppl (1 de junio de 2022): e16155-e16155. http://dx.doi.org/10.1200/jco.2022.40.16_suppl.e16155.

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e16155 Background: Combining lenvatinib (a multikinase inhibitor) with programmed cell death protein-1 (PD-1) inhibitor has been explored in Unresectable hepatocellular carcinoma (uHCC) in phase 1b trials. This study aimed to investigate the real-word efficacy and safety of lenvatinib plus PD-1 inhibitor for large Chinese patients uHCC cohorts. Methods: BCLC stage B or C uHCC patients were included. Data was collected from Oct 2017 to Nov 2021 retrospectively. Patients were treated with lenvatinib and PD-1 inhibitor (pembrolizumab or nivolumab or camrelizumab or sintilimab or toripalimab or tislelizumab). The primary endpoint was overall survival (OS) and secondary endpoints were progression-free survival (PFS) and objective response rate (ORR) evaluated by RECIST v1.1 criteria. Adverse events (AEs) were assessed using CTCAE v5.0. Prognostic factors of survival were also analyzed. Results: 378 uHCC patients of BCLC stage B (12.7%) and C (87.3%) from two medical centers were included in China. The median age was 55 (range 18-89) years and 86.5% patients were male. ECOG scores were 0 (43.7%), 1 (43.4%) and 2 (13.0%), while Child-pugh grade were A (77.5%) and B (22.5%) respectively. The median OS was 17.8 (95% CI 14.0-21.6) months. The median PFS was 6.9 (95% CI 6.0-7.9) months. The best objective response rate (ORR) and disease control rate (DCR) was 74/378 (19.6%) and 278/378 (73.5%) respectively. Child-pugh grade (A vs. B), ECOG score (0 vs. 1-2), BCLC stage (B vs. C) and achieve response (yes vs. no) were the prognostic factors for both OS and PFS. All (100%) experienced all-grade adverse events (AE). The most frequent AEs were fatigue, diarrhea, hypertension, decreased appetite. The most common ≥Grade 3 AEs were hypertension (13.2%), fatigue (7.1%), decreased platelet count (6.3%), increased blood bilirubin (6.1%), diarrhea (6.1%) and gastrointestinal hemorrhage (4.8%). Conclusions: This real-world study of lenvatinib plus PD-1 inhibitors achieved long survival and considerable ORR for uHCC patients in China. The tolerability of combination therapy was acceptable but should be still monitored closely. Clinical trial information: NCT03892577. [Table: see text]

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Harb, Wael, Mansoor N. Saleh, Kyriakos P. Papadopoulos, Feng Chai, Maria Larmar, Giovanni Abbadessa, Brian Schwartz y Anthony Tolcher. "Clinical Trial Results from the Subgroup of Lymphoma/CLL in a Phase 1 Study of ARQ 092, a Novel Pan AKT-Inhibitor". Blood 126, n.º 23 (3 de diciembre de 2015): 5116. http://dx.doi.org/10.1182/blood.v126.23.5116.5116.

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Abstract Background: ARQ 092 is an oral allosteric, potent and selective AKT inhibitor with in vitro and in vivo activity in solid and hematological tumors. ARQ 092-101, the first clinical trial of ARQ 092, has enrolled more than 100 subjects with advanced solid tumors or recurrent malignant lymphoma. As reported previously, the dose escalation portion of the study has been completed and two dosing schedules (intermittent and weekly), are recommended for phase 2 studies. The recommended phase 2 dose (RP2D) for the intermittent dosing schedule is 200 mg once daily (QD) (one week on, one week off) and for the weekly dosing schedule is 300 mg twice daily (BID) (one day on, six days off). [1, 2] Enrollment in an expansion cohort at RP2Ds is ongoing. Here we report the results from 11 subjects with lymphoma/CLL. Material and Methods: Subjects with lymphoma/CLL have been enrolled and treated in the dose escalation and expansion cohorts with intermittent or weekly dosing schedule at the RP2Ds. Tumor responses for subjects with lymphoma were evaluated based on the Revised Response Criteria for Malignant Lymphoma. Adverse events were evaluated based on the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Blood samples were collected for PK analysis. Archival or biopsy tumor tissue samples were collected for genetic analysis. Results: As of 15 Jun 2015, 11 subjects with lymphoma/CLL (73% male; median age 78 years; 5 follicular, 3 mantle cell, 2 diffuse large B cell, 1 CLL; 4 in dose escalation cohorts, 7 in expansion cohort) have been enrolled and treated at initial doses of 120 to 270 mg QD intermittently (n=7) or 300 mg BID weekly (n=4). All subjects have received at least one prior systemic therapy (median 2, range 1-6). Median duration on study treatment for all 11 subjects was 8 weeks (range 1 to 30 weeks). One subject with CLL and two with follicular lymphoma experienced durable partial responses, respectively with times to response of 8, 8 and 24 weeks and response durations of 16, 8+, and 2+ weeks. The two follicular PR subjects, one of whom had an AKT1 (E17K) mutation, remain on study treatment. In addition, one subject with follicular and one with mantle cell lymphoma experienced stable diseases. Four subjects experienced progressive diseases and two were not evaluable for tumor responses due to early consent withdrawal and clinical disease progression. Table 1. Common drug-related adverse events (≥10%) included macula-papular rash 45%, hyperglycemia 36%, mucosal inflammation 18% and stomatitis 18%. Response Follicular N=5 CLL N=1 Mantle cell N=3 Diffuse large B cell N=2 Total N=11 PR 2 1 3 SD 1 1 2 PD 1 2 1 4 NE 1 1 2 ORR 40% 100% 0% 0% 27% DCR 60% 100% 33% 0% 45% Conclusions: The safety profile of lymphoma subjects is consistent with subjects with solid tumors enrolled in this study. Preliminary signs of single agent activity have been documented with 3 PRs in heavily pretreated lymphoma/CLL including one with AKT1 (E17K) mutation. [1] First-in-human study with ARQ 092, a novel pan AKT-inhibitor: Results from the advanced solid tumors cohorts. M. Saleh et al., Abstract LB-197, AACR 104th Annual Meeting, 6-10 Apr 2013. Washington, D.C. U.S. [2] First-in-human study with ARQ 092, a novel pan AKT-inhibitor, in subjects with advanced solid tumors or recurrent malignant lymphoma. M. Saleh et al., Abstract 320, EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics , 18-21 Nov 2014, Barcelona, Spain Disclosures Harb: Onyx Pharmaceuticals: Consultancy. Chai:ArQule, Inc.: Employment. Larmar:ArQule, Inc.: Employment. Abbadessa:ArQule, Inc.: Employment. Schwartz:ArQule, Inc.: Employment.

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Shen, Jian, Chun Chang, Jie Ma y Qiang Feng. "Potential of Circulating Proangiogenic MicroRNAs for Predicting Major Adverse Cardiac and Cerebrovascular Events in Unprotected Left Main Coronary Artery Disease Patients Who Underwent Coronary Artery Bypass Grafting". Cardiology 146, n.º 3 (2021): 400–408. http://dx.doi.org/10.1159/000509275.

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Objective: This study aimed to explore the association of 14 proangiogenic microRNAs (miRNAs) with major adverse cardiac and cerebrovascular events (MACCE) occurrence in unprotected left main coronary artery disease (ULMCAD) patients who underwent coronary artery bypass grafting (CABG). Methods: A total of 196 ULMCAD patients who underwent first ever CABG were recruited. The peripheral blood samples were collected prior to CABG, and then plasma samples were separated to detect expressions of 14 proangiogenic miRNAs by the reverse transcription quantitative PCR. Patients were regularly followed up to MACCE occurrence or 36 months after CABG. Results: MACCE occurrence at 1 year, 2 years, and 3 years was 7.1, 11.2, and 14.3%, respectively, and accumulating MACCE occurrence time was 32.7 (95% confidence interval: 31.5–33.9) months. Both Kaplan-Meier curves and univariate Cox’s regression analyses displayed that miR-let-7f, miR-19a, miR-126, miR-130a, and miR-378 high expressions were associated with lower accumulating MACCE occurrence. Furthermore, forward stepwise multivariate Cox’s regression disclosed that miR-let-7f high expression and miR-378 high expression independently predicted decreased accumulating MACCE occurrence, whereas BMI (>25.0 kg/m2), diabetes, previous stroke, and higher disease extent were independent predictive factors for elevated accumulating MACCE occurrence. Conclusion: Measurement of circulating proangiogenic miRNAs especially miR-let-7f, miR-19a, miR-126, miR-130a, and miR-378 helps predict MACCE risk in ULMCAD patients who underwent CABG.

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Santoshkumar, S., N. D. Satyanarayana, R. Anantacharya y P. Sameer. "SYNTHESIS, ANTIMICROBIAL, ANTITUBERCULAR AND CHEMINFORMATIC STUDIES OF 2-(1-BENZOFURAN-2-YL)-N'-[(3Z)-2-OXO-1, 2-DIHYDRO-3H-INDOL-3-YLIDENE] QUINOLINE-4-CARBOHYDRAZIDE AND ITS DERIVATIVES". International Journal of Pharmacy and Pharmaceutical Sciences 9, n.º 5 (1 de mayo de 2017): 260. http://dx.doi.org/10.22159/ijpps.2017v9i5.17564.

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Objective: Synthesis of novel 2-(1-benzofuran-2-yl)-N'-[(3Z)-2-oxo-1, 2-dihydro-3H-indol-3-ylidene] quinoline-4-carbohydrazide and its derivatives for antimicrobial and antitubercular activity.Methods: Synthesis was carried out using the general method and the structures were confirmed by IR, 1H-NMR, [13]C-NMR and mass spectral analysis. The antibacterial activity was carried by agar well diffusion method, antifungal activity was performed by poison food technique and antitubercular activity was carried out by Microplate Alamar Blue Assay (MABA) method with the help of H37Rv. In silico absorption, distribution, metabolism, excretion, toxicity (ADMET) study of the drug, likeliness was carried out in ACD/lab-2.Results: The results revealed that at 25 mg/ml concentration, compounds 3a and 5a showed good antibacterial activity at 3.5±0.1, 3.8±0.3, 3.6±0.2 respectively against E. coli, K. pneumonia and S. typhimurium, when compared with drug streptomycin with similar concentration. The percentage of inhibition found at 50 µg/ml concentration, compounds 2b and 6a exhibited good antifungal activity at 53±1.15, 57±1.52 against A. flavus and C. neoformans, compared with standard drug fluconazole. The increase in activity was found to be dose dependent. The analogue 2a showed good antitubercular activity at 12.5±0.5 µg/ml, compounds 2b, 3a, 4a-b, 5a-b and 6a-b exhibited significant activity at 25±0.57 µg/ml and compound 3b showed moderate activity at 50±0.57 µg/ml. The mean value of P<0.05 were considered to be statistically significant. The absorption, distribution, metabolism, excretion and toxicity studies of the entitled molecules were analyzed and found to be in acceptable range.Conclusion: The study reveals that compounds containing benzofuran coupled nitrogen heterocycles are essential for activity as they possess excellent drug-like characteristics, suggesting to be potentially best inhibitor of H37Rv strain. The in silico ADME analysis also revealed that all the compounds were in acceptable range to obey the pharmacokinetic parameters.

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Semenova, Lioubov I. y Allan H. White. "Structural Systematics of Rare Earth Complexes. XVII Hydrated 1 : 1 Adducts of 2,2′:6′,2″-Terpyridine with the Lanthanoid(III) Bromides and Some Binuclear Hydroxy-Bridged Dimers". Australian Journal of Chemistry 52, n.º 6 (1999): 539. http://dx.doi.org/10.1071/ch98048.

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Room-temperature single-crystal X-ray structural characterizations are recorded for hydrated lan- thanoid(III) bromide/2,2′:6′,2″-terpyridine (tpy) (1 : 1) complexes, showing all to be ionic and of the form [(tpy)Ln(OH2)x]Br3.yH2O, where x and y are 6 and 1 for the isomorphous series Ln = La(-)Er (and intermediate members, by presumption), and 5 and various values for Ln = Tm, Yb, Lu. Crystals of [(tpy)Ln(OH2)6]Br3.H2O are monoclinic, P 21/c, a ≈ 8·5, b ≈ 18, c ≈ 16·3 Å, β ≈ 108°, Z = 4; for Ln = La, Er, conventional R values on |F| were 0·048, 0·080 for No 4027, 1347 ‘observed’ (I > 3σ(I)) diffractometer reflections respectively. The complex [(tpy)Tm(OH2)5]Br3.H2O is monoclinic, P 21/c, a 8·506(4), b 17·376(1), c 15·951(6) Å, β 106·87(3)°, Z = 4, (quasi-)isomorphous with the Ln = La-Er array, R 0·065 for No 2067. [(tpy)Yb(OH2)5]Br3.4H2O is triclinic, P 1, a 11·902(2), b 11·639(3), c 9·831(2) Å, α 98·92(2), β 106·84(2), γ 92·42(2)°, Z = 2, R 0·062 for No 3422, while [(tpy)Lu(OH2)5]Br3.H2O is monoclinic, P 21/n, a 13·635(8), b 9·022(5), c 19·03(1) Å, β 99·02(5)°, Z = 4, R 0·043 for No 3139. Despite a common N3LnO5 coordination sphere in the last three compounds, subtle differences are found in stereochemistry; in the N3LnO6 array, one of the outer water molecules becomes progressively detached as the lanthanoid radius contracts. Some tendency is found toward the end of the lanthanoid series toward the formation of di(hydroxy-bridged) neutral dimers, Ln(OH)Br2/tpy/H2O(1 : 1 : 8)(×2), [(tpy)(H2O)3Ln(µ-OH)2Ln(OH2)3(tpy)]Br4.10H2O, monoclinic, C 2/c, a ≈ 19·5, b ≈ 14·5, c ≈ 17·1 Å, β ≈ 92°, Z = 4 dimers, thus far defined by full determinations for the extrema Lu = Er, Lu (and Y), R 0·055, 0·043, (0·047) for No 3141, 4591, (2991) respectively; the dimer is disposed about a crystallographic 2 -axis. An Ln = Dy example, seemingly isomorphous, has also been characterized by cell determination.

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GLENDINNING, PAUL y NIKITA SIDOROV. "The doubling map with asymmetrical holes". Ergodic Theory and Dynamical Systems 35, n.º 4 (14 de noviembre de 2013): 1208–28. http://dx.doi.org/10.1017/etds.2013.98.

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AbstractLet $0\lt a\lt b\lt 1$ and let $T$ be the doubling map. Set $ \mathcal{J} (a, b): = \{ x\in [0, 1] : {T}^{n} x\not\in (a, b), n\geq 0\} $. In this paper we completely characterize the holes $(a, b)$ for which any of the following scenarios hold: (i) $ \mathcal{J} (a, b)$ contains a point $x\in (0, 1)$; (ii) $ \mathcal{J} (a, b)\cap [\delta , 1- \delta ] $ is infinite for any fixed $\delta \gt 0$; (iii) $ \mathcal{J} (a, b)$ is uncountable of zero Hausdorff dimension; (iv) $ \mathcal{J} (a, b)$ is of positive Hausdorff dimension. In particular, we show that (iv) is always the case if $$\begin{eqnarray*}b- a\lt \frac{1}{4} { \mathop{\prod }\nolimits}_{n= 1}^{\infty } (1- {2}^{- {2}^{n} } )\approx 0. 175\hspace{0.167em} 092\end{eqnarray*}$$ and that this bound is sharp. As a corollary, we give a full description of first- and second-order critical holes introduced by N. Sidorov [Supercritical holes for the doubling map. Preprint, see http://arxiv.org/abs/1204.1920] for the doubling map. Furthermore, we show that our model yields a continuum of ‘routes to chaos’ via arbitrary sequences of products of natural numbers, thus generalizing the standard route to chaos via period doubling.

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Pavić, Slađana, Marija Antić, Radmila Sparić y Aleksandra Pavić. "Clinical course of coxsackievirus B (1-6) infection". PONS - medicinski casopis 17, n.º 1 (2020): 3–7. http://dx.doi.org/10.5937/pomc17-25015.

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Objective. Coxsackievirus B (1-6) infections are the common infections of children and adults. Clinical manifestations include fever, aseptic meningitis, pleurodinia, myocarditis, gastroenterocolitis, maculous exanthem. The clinical course of the infection is influenced by the characteristics of the host, as well as the virus serotype. The pathogenesis of the diseases is explained by the immune mediated mechanism and the direct cytotoxic effect of the virus. Methods. Retrospectively analyzed virus serotype, clinical and biochemical data in patients with coxsackievirus B (1-6) infection. Patients who had an unclear febrile condition for more than six months were tested for autoantibodies. Results. We examined a total of 378 patients with coxsackievirus B (1-6) infection (302 women, 76 men), age 19 to 79 years. The dominant symptoms were weakness, elevated body temperature, fatigue and muscle aches. In 55% the clinical course was fever of unknown origin, in 13% myalgia/pleurodinia, 9% acute gastroenterocolitis and acute myocarditis/ pericarditis, 2% aseptic meningitis, 2.4% respiratory disease, 3% acute pancreatitis and 1% diabetes mellitus. Autoantibodies were detected in 69% of patients with fever of unknown origin. Antinuclear antibodies were most common, in 67%. Serotype B2 had 36% of these patients. Serotype B2 had 36% of these patients and serotype B4 had 14%. Conclusion. The most common clinical form of coxsackievirus B (1-6) infection is an fever of unknown origin caused by a B2 serotype of the virus. In most of these patients, an elevated titre of antinuclear antibodies can be detected.

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Caldwell, Gary, Richard Renneboog y Paul Kebarle. "Gas phase acidities of aliphatic carboxylic acids, based on measurements of proton transfer equilibria". Canadian Journal of Chemistry 67, n.º 4 (1 de abril de 1989): 611–18. http://dx.doi.org/10.1139/v89-092.

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Measurements of the gas phase proton transfer equilibrium [1]: AH + B− = A− + BH with a pulsed electron high pressure mass spectrometer (PHPMS) lead to [Formula: see text] and [Formula: see text] data. These relative acidities are converted to the absolute acidities [2]: AH = A− + H+bycalibration of the relative [Formula: see text] and [Formula: see text] scale to the known values for [Formula: see text] and [Formula: see text] of a reference compound(HCl). Earlier determinations that included 16 aliphatic AH are extended in the present work and provide data for 47 aliphatic carboxylic acids. These include halogen, OH, CH3O, C2H5O, PhO, and NH2 substituted acetic acids, and halogen substituted, unsaturated, and cyclic RCO2H of higher carbon number. The effects of the various substituents on the gas phase acidity are briefly examined. Keywords: acidities in gas phase, proton transfer equilibria, ion-molecule equilibria, mass spectrometry.

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Bowmaker, Graham A., Frances M. M. Hannaway, Peter C. Junk, Aaron M. Lee, Brian W. Skelton y Allan H. White. "Synthetic, Structural and Vibrational Spectroscopic Studies in Bismuth(III) Halide/N,N′-Aromatic Bidentate Base Systems. IV Bismuth(III) Halide/N,N′-Bidentate Ligand (1 : 1) Systems". Australian Journal of Chemistry 51, n.º 4 (1998): 325. http://dx.doi.org/10.1071/c97039.

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Room-temperature single-crystal X-ray studies are recorded for a number of adducts of BiX3 and N,N′-bidentate ligand (2,2′-bipyridine (bpy) or 1,10-phenanthroline (phen)), devoid of coordinated solvent. BiBr3/bpy/MeCN (1 : 1 : 1) is triclinic P-1, a 12·129(2), b 9·955(4), c 7·748(1) Å, α 73·14(2), β 77·34(1), γ 69·79(2)°, Z = 2; conventional R on |F| was 0·036 for No 2252 independent ‘observed’ (I > 3σ(I)) reflections. The phen analogue is isomorphous, a 11·586(3), b 10·839(6), c 7·769(10) Å, α 73·70(7), β 76·67(7), γ 70·34(4)°, Z = 2, R 0·042 for No 800. BiI3/bpy (1 : 1) is triclinic, P-1, a 11·742(4), b 9·261(1), c 8·261(3) Å, α 86·46(2), β 71·48(3), γ 67·25(2)°, Z = 2, R 0·043 for No 1164. All complexes are centrosymmetric binuclear [(N,N′-bidentate)X2Bi(µ-X)2BiX2(N,N′-bidentate)] with six-coordinate pseudo-octahedral bismuth(III). Attempts to produce a chloride analogue have resulted, in the case of N,N′-bidentate = bpy, in a novel adduct of BiCl3/bpy 1 : 1·5 stoichiometry, monoclinic, P21/c, a 9·377(8), b 17·699(5), c 21·58(1) Å, β 107·82(6)°, Z = 8, R 0·055 for No 1804. The complex is [(bpy)2Cl2Bi(µ-Cl)BiCl3(bpy)], containing seven- and six-coordinate bismuth. Bands in the far-infrared spectra due to the v(BiX) vibrations in [(bpy)2Cl2Bi(µ-Cl)BiCl3(bpy)] and [(bpy)I2Bi(µ-I2)BiI2(bpy)] are assigned and discussed in relation to the structures of the complexes.

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15

Nozaki, Kenji, Hiroyuki Sugahara, Shuji Ueda, Jun Ishikawa, Shigeo Fuji, Hiroaki Masaie, Yuma Tada et al. "Elevated Serum Soluble Interleukin-2 Receptor Level Is a Useful Prognostic Factor for Disease-Specific Overall Survival in Patients with Newly Diagnosed Follicular Lymphoma before Initiation of Treatment". Blood 134, Supplement_1 (13 de noviembre de 2019): 3985. http://dx.doi.org/10.1182/blood-2019-126399.

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Introduction: Serum soluble interleukin-2 receptor (sIL-2R) is recognized as a tumor-related biomarker of malignant lymphomas, including follicular lymphoma (FL). The objective of this study is to assess the prognostic significance of pretreatment serum sIL-2R level for disease-specific overall survival (DSS) in patients with FL. Methods: We retrospectively analyzed medical records of our 10 individual institutions to identify all patients (pts) ≥ 18 years old with newly diagnosed FL between 01/01/2008 and 12/31/2018. Only pts with FL grade 1-3b, confirmed at pathological review, were included. Pts with histological transformation at diagnosis were excluded. Serum sIL-2R was determined by sandwich enzyme-linked immunosorbent assay. Clinical characteristics, therapies, response, relapse patterns and follow up status were collected and analyzed in the cohort. DSS was defined from the time of initial diagnosis to death due to lymphoma or last follow up. DSS was analyzed according to Kaplan Meier method and differences between subgroups were compared with log-rank test. Multivariate cox regression analysis was used to investigate associations of sIL-2R, FL International Prognostic Index (FLIPI) and progression or relapse within 24 months after diagnosis (POD24) with DSS. Serum levels of sIL-2R was measured before initiation of treatment and the data on the nearest date of the diagnostic biopsy within six months was adopted. Results: We recorded 565 pts and 535 pts of them with pretreatment serum sIL-2R levels available were included in the analysis with median age 64 years (range: 30-90) and 305 females (57%). Clinical characteristics are summarized in Table 1. The median of the serum sIL-2R level was 896 IU/mL (range: 145 - 23800). We decided an optimal cutoff value of 1800 IU/mL by using receiver operating characteristic (ROC) analysis, which showed it was 1830 IU/mL (AUC : 0.76, 95%CI : 0.67 - 0.84). Various poor prognostic indicators, such as bulky mass, increased LDH, ≥5 nodal lesions, poor performance status (PS), bone marrow invasion, FLIPI and FLIPI-2 high-risk, decreased Hb, advanced disease, high tumor burden, increased β2MG and existence of B symptoms, were strongly associated with high serum sIL-2R level (≥1800 IU/mL), and high sIL-2R level correlated with POD24 (P<0.001, Chi-squared test). The estimated 10-year DSS rate was 87.2% with a median follow up duration of 4.4 years. In pts with POD24 (96 pts, 18%), DSS was significantly worse than those with non-POD24; 64.3% vs 93.0% (P<0.001) and rituximab maintenance did not improve DSS in both groups (P=0.85 and 0.98, respectively). In patients with sIL-2R level of ≥1800 (high sIL-2R, 378 pts, 71%), DSS was significantly worse than those with sIL-2R level of <1800 IU/mL (low sIL-2R, 157 pts, 29%); 68.2% vs 96.0% (P<0.001), respectively (Figure 1). Multivariate analyses employing sex, PS, sIL-2R, FLIPI and POD24 demonstrated that high sIL-2R was an independent prognostic factor for DSS (HR : 2.88, 95% CI : 1.15-7.21, P<0.05). Regardless of POD24 status, pts with high sIL-2R had significantly worse DSS than those with low sIL-2R; 44.6% vs 91.5% in pts with POD24 (P<0.05) and 82.6% vs 96.8% in pts without POD24 (P<0.001), respectively. Among pts treated with rituximab plus anthracycline-containing chemotherapy as the 1st line regimen (222 pts, 41%), pts with high sIL-2R had significantly worse DSS than those with low sIL-2R; 68.1% vs 97.2% (P<0.001). Among pts treated with rituximab-bendamustine as the 1st line regimen (48 pts, 9%), there was no significant difference between high and low sIL-2R populations (P=0.2), however, among pts treated with bendamustine-containing regimen at least once in their life time (180 pts, 34%), there was significant difference between them; 63.1% vs 87.8% (P<0.05). Even in pts achieving complete metabolic response after 1st line treatment (178 pts, 33%), high pretreatment sIL-2R level was a significant factor affecting poor DSS; 75.9% vs 94.3% (P<0.05). Conclusions: High sIL-2R level ( ≥1800 IU/mL) is a significant and independent adverse prognostic factor for DSS in pts with newly diagnosed FL. This study provides us useful information to predict population with worse DSS before initiation of treatment. Disclosures Nozaki: Chugai: Honoraria; Celgene: Honoraria. Kida:Eisai Co., Ltd: Honoraria. Kosugi:Novartis Pharma Co.: Honoraria; Bristol-Myers Squibb Co.: Honoraria; Eisai Co., Ltd: Honoraria; Takeda Pharmaceutical Company Limited: Honoraria; Kyowa Kirin Co., Ltd: Honoraria; Chugai Pharmaceutical Co., Ltd.: Honoraria; ONO PHARMACEUTICAL CO., LTD.: Honoraria; NIPPON SHINYAKU CO.,LTD.: Honoraria; Janssen Pharmaceutical K.K.: Honoraria; Celgene K.K.: Honoraria; Pfizer Inc.: Honoraria. Shibayama:Astellas, Teijin, MSD, Shionogi, Eisai, Sumitomo Dainippon, Taiho, Nippon Shinyaku: Research Funding; Celgene, Chugai, Eisai, AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Takeda, Novartis, Janssen, Chugai, Eisai, Mundi Pharma, Ono, Otsuka, Kyowa Kirin, Sumitomo Dainippon, AstraZeneca, Avvie, DaiichiSankyo, Fujimoto, Nippon Shinyaku, Sanofi, Bristol-Myers Squibb, Pfizer: Honoraria.

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Rajendran, Rajam y Yoshiyuki Ohta. "Binding activity of Natto (a fermented food) and Bacillus natto isolates to mutagenic-carcinogenic heterocyclic amines". Canadian Journal of Microbiology 47, n.º 10 (1 de octubre de 2001): 935–42. http://dx.doi.org/10.1139/w01-094.

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The fermented food, whole meal Natto, viscous polymeric material from Natto, Natto bean, cooked soya bean, and 28 bacterial isolates from Natto were studied for their binding capacity to foodborne mutagenic-carcinogenic heterocyclic amines. The mutagenic heterocyclic amines used were Trp-P-1 (3-amino-1,4-dimethyl-5H-pyrido(4,3-b)indole); Trp-P-2 (3-amino-1-methyl-5H-pyrido(4,3-b)indole); Glu-P-1 (2-amino-6-methyldipyrido(1,2-a:3'2'-d)imidazole); PhIP (2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine); IQ (2-amino-3-methylimidazo(4,5-f)quinoline); MeIQ (2-amino-3,4-dimethylimidazo(4,5-f)quinoxaline); MeIQx (2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline); and MeAαC (2-amino-3-methyl-9H-pyrido(2,3)indole). The lyophilized Natto and other fractions of Natto exhibited high binding activity towards Trp-P-1, Trp-P-2, PhIP, and MeAαC, while Glu-P-1, IQ, and MeIQ were not effectively bound. The binding capacity of bacterial isolates (Bacillus natto) were isolate-mutagen dependent. Heat treated lyophilized cells, cell wall, and cytoplasmic contents of the bacterial isolate with the highest binding capacity were analyzed for their ability to bind different heterocyclic amines. The results indicate the importance of the cell wall in binding to heterocyclic amines, whereas the cytoplasmic contents were less effective. Heat-treated cells were not much different from that of viable cells in their binding. The impact of different factors, such as pH, incubation time, metal ions, different concentrations of sodium chloride and alcohol, various enzymes, and acetylation of mutagens on binding of Trp-P-1 and IQ, were discussed. The significance of the present results is also discussed from the viewpoint that Natto, a fermented food, is able to scavenge dietary mutagenic heterocyclic amines through binding.Key words: fermented food, mutagens, heterocyclic amines, Natto, binding.

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17

Burkhardt, Birgit, Ilske Oschlies, Wolfram Klapper, Martin Zimmermann, Andrea Meinhardt, Eva Landmann, Wilhelm Woessmann et al. "Non-Hodgkin Lymphoma in Adolescents: Experiences in 378 Adolescent NHL Patients Treated According to Pediatric NHL-BFM Protocols." Blood 114, n.º 22 (20 de noviembre de 2009): 102. http://dx.doi.org/10.1182/blood.v114.22.102.102.

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Abstract Abstract 102 There are considerable differences with respect to incidence, biology, treatment and outcome of Non-Hodgkin Lymphoma (NHL) between children and adults. Patients of adolescent age are forming a separate group that falls between those categories. Even though recent reports pay increasing attention to these patients, the impact of adolescent age on the characteristics and outcome of NHL remains yet to be determined. Therefore, the current analyses aimed to analyze the outcome of adolescents treated according to BFM protocols for childhood NHL. Patients were treated according to the subsequent protocols NHL-BFM 86, 90, 95, 04, ALCL 99, and EURO-LB 02. Treatment subgroups were: 1) lymphoblastic lymphoma (LBL), 2) mature B-cell NHL including Burkitt lymphoma/leukemia (BL/B-AL), diffuse large B-cell lymphoma of centroblastic subtype (DLBCL-CB) and primary mediastinal B-cell lymphoma (PMLBL), and 3) anaplastic large cell lymphoma (ALCL). From October 1986 to December 2007, a total of 2915 protocol patients (pts) were registered in the NHL-BFM study center. Of these, 378 pts (13%) were of adolescent (15-18 years (y)) at diagnosis. Within the adolescent age group BL/B-AL were the largest subgroup (101 pts), followed by ALCL (74 pts), DLBCL-CB (55 pts), T-LBL (45 pts), PMLBL (24 pts), pB-LBL (13 pts) and other rare or not further specified NHL subtypes (66 pts). The 5-year event free survival (pEFS) was 79±2% for adolescents compared to 85±1% in pts aged <15y (p 0.014). Regarding histological subtypes, pEFS was inferior in adolescents compared to children in BL/B-AL pts (82±4% vs 88±1%, p 0.06) and in DLBCL-CB (pEFS 85±5% vs 96±2%, p 0.002). There was no difference in outcome for adolescents compared with children in T-LBL (pEFS (5y) 87±6% vs 82±2%, p 0.24), ALCL (70±6% vs 70±3%) and PMLBL (57±10% vs 68±8%, p 0.55). Further analyses in adolescents revealed a higher frequency of advanced stages of disease (> stage II) in females (94/119) vs males (177/259, p 0.04), but less frequent CNS disease in females (3/119 vs 23/259; p 0.03). pEFS (5y) was inferior for adolescent females (70±5% vs 84±2% in males, p 0.004). This was mainly due to the unfavorable pEFS for adolescent female pts with T-LBL (pEFS 57±17% vs 97±3%, p 0.001) and DLBCL-CB (pEFS 71±9% vs 97±3%, p 0.007). For the other histological NHL-subtypes there were no statistically significant differences in outcome according to gender. Adolescents with NHL treated according to pediatric NHL-BFM protocols have an acceptable outcome that is marginally inferior to that in children. Within the adolescent age group, female pts are diagnosed more frequently with advanced stages of disease. In adolescent pts with T-LBL and DLBCL-CB, female gender is associated with a worse prognosis. Disclosures: No relevant conflicts of interest to declare.

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18

Bowmaker, Graham A., Peter C. Junk, Aaron M. Lee, Brian W. Skelton y Allan H. White. "Synthetic, Structural and Vibrational Spectroscopic Studies in Bismuth(III) Halide/N,N′-Aromatic Bidentate Base Systems. I Large-Cation (2,2′-Bipyridinium and 1,10-Phenan- throlinium) Salts of Polyhalobismuthate(III) Ions". Australian Journal of Chemistry 51, n.º 4 (1998): 293. http://dx.doi.org/10.1071/c97036.

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Syntheses and room-temperature single-crystal X-ray studies are recorded for a variety of salts of cations derived from protonated 2,2′-bipyridine and 1,10-phenanthroline (bpyH+ and phenH+) with polyhalobismuthate(III) anions. ‘[(phenH)(phenH2)(H2O)2] [BiCl6]’ is triclinic, P-1, a 9·791(1), b 9·338(3), c 8·311(3) Å, α 73·46(3), β 69·71(2), γ 86·36(2)°, Z = 1; conventional R on |F| was 0·027 for No 4852 independent ‘observed’ (I > 3σ(I)) reflections. [BiCl6]3- is closely octahedral, accompanied by an interesting protonation/hydrogen-bonding array among the other moieties. The latter comment applies also to ‘[(phenH2)(H2O)][BiCl5](∞|∞)’, monoclinic, P2/c, a 8·388(1), b 12·004(1), c 17·146(3) Å, β 98·26(1)°, Z = 4, R 0·047 for No 2670, the anion array being a one-dimensional polymer with bridging chlorine atoms occupying cis sites in the pseudo-octahedral coordination sphere of the bismuth. [bpyH2]4 [Bi4Cl20] is monoclinic, P21/c, a 14·228(4), b 14·217(2), c 16·254(4) Å, β 110·14(2)°, Z = 2, R 0·045 for No 2777; in the novel centrosymmetric tetramer, the four bismuth atoms are bridged into a square array by four linearly coordinated halogen atoms at the centres of the edges, a pair of these lying cis in the pseudo-octahedral coordination sphere of each bismuth. [bpyH]3 [Bi2Cl9] is triclinic, P-1 a 19·288(7), b 14·251(3), c 7·644(3) Å, α 75·02(2), β 80·15(3), γ 72·76(2)°, Z = 2, R 0·072 for No 3600, the two pseudo-octahedrally coordinated bismuth atoms being bridged by three chlorine atoms on a mutual octahedral face, [Cl3Bi(µ-Cl)3BiCl3]3-. [phenH] [BiCl4](∞|∞),H2O is triclinic, space group P-1, a 12·119(7), b 10·169(6), c 7·247(4) Å, α 69·30(4), β 75·05(4), γ 77·92(5)°, Z = 2, R 0·035 for No 2348. The anion is a one-dimensional polymer, successive metal atoms being bridged by pairs of chlorine atoms lying cis in the pseudo-octahedral coordination sphere. [bpyH]4 [Bi2I10] is monoclinic, P21/n, a 13·426(4), b 14·396(6), c 14·539(5) Å, β 101·31(3)°, Z = 2, R 0·11 for No 1862; the anion is of the form [I4Bi(µ-I)2BiI4]4- with quasi-octahedral bismuth. [bpyH] [BiI4](∞|∞) is monoclinic, C2/c, a 12·442(5), b 18·41(2), c 7·714(2) Å, β 92·80(3)°, Z = 4, R 0·080 for No 850, with a polymeric one-dimensional anion comparable to that in [phenH] [BiCl4](∞|∞),H2O. The structure of the 2,6-dimethylpyridinium salt of [BiCl6]3- is also recorded, as its acetonitrile solvate; triclinic, P-1, a 15·025(2), b 10·357(3), c 9·964(1) Å, α 83·14(2), β 89·32(1), γ 86·61(2)°, Z = 2, R 0·046 for No 3601; there is also an isomorphous bromide, and also an isostoichiometric bromide modelled as monoclinic, Cm, a 18·128(6), b 10·348(2), c 10·241(2) Å, β 121·31(3)°, Z = 2, R 0·050 for No 1379. Bands in the far-infrared and Raman spectra due to the v(BiCl) modes are assigned in [(phenH)(phenH2)(H2O)2] [BiCl6] and [bpyH2]4 [Bi4Cl20], and are discussed in relation to the structures of the complexes.

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McDonagh, Andrew M., Mark G. Humphrey y David C. R. Hockless. "Preparation of cis- and trans-[OsCl2(Me2SO)4], and X-Ray Crystal Structures of the All-S-Bound Isomers". Australian Journal of Chemistry 51, n.º 9 (1998): 807. http://dx.doi.org/10.1071/c98017.

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Efficient syntheses of the cis and trans isomers of [OsCl2(Me2SO)4] are reported. While a structural study of thetrans isomer confirms the spectroscopically assigned all-S-bound Me2SO configuration, a crystallographic determination of the cis isomer reveals a previously unheralded all-S-bound Me2SO geometry, in contrast to the spectroscopically inferred configuration predominant in solution which has one O-bound ligand. Fortrans-[OsCl2(Me2SO)4], crystals are tetragonal, space group I 4/m, with a 9·092(2), c 11·212(3) Å, Z 2, 566 unique reflections (34 parameters), converging at R 0·026 and Rw 0·032. For cis-[OsCl2(Me2SO)4], crystals are triclinic, space group P-1, with a 8·193(2), b 8·941(3), c 13·837(3) Å, α 79·77(2), β 79·91(2), γ 65·03(2)°, Z 2, 4152 unique reflections (173 parameters), converging at R 0·021 and Rw 0·018.

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20

Sulistyorini, Anik, Tjandrakirana Tjandrakirana y Soetjipto Soetjipto. "PENGEMBANGAN PERANGKAT PEMBELAJARAN IPA MODEL GUIDED INQUIRY UNTUK MELATIHKAN KETERAMPILAN PROSES SAINS DAN MENINGKATKAN HASIL BELAJAR SISWA SMP". JPPS (Jurnal Penelitian Pendidikan Sains) 6, n.º 1 (31 de enero de 2017): 1167. http://dx.doi.org/10.26740/jpps.v6n1.p1167-1174.

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This research was done by developing science learning materials (lesson plans, student’s worksheets, student’s book, and learning achivement test) based on guided inquiry learning model using 4D development model to facilitate student’s science process skills and improving student’s learning achivement on environmental pollutions matter. The objective of this research was to trial learning materials in 35 of junior high school’s students with one group pretest-postest design. Results were analyzed by descriptive quantitative-qualitative are: (1) Validity of learning material valid category (3.00); (2) Practicalitybased on: a) Feasibility of instruction good category (3,8); b) Readability of worksheets and student’s book students stating that the content and appearance of worksheets and student’s book is interesting; c) The response of students very positively (85.6%); (3) Effectiveness based on: a) Student’s activities who stand out were practice science process skills is high category (38,5%); b) Student’s science process skill in very high category as shown by student’s worksheet achivement (3,46); c) student learning achivement increased (N-Gain: 0.2-1.0). The conclusion of this research that science learning material depeloped base on guided inquiry learnig model, eligible to facilitate student’s science process skills and improve student learning achivement in junior high school. Telah dilakukan penelitian dengan mengembangkan perangkat pembelajaran (RPP, LKS, Materi Ajar, dan Tes Hasil Belajar) model guided inquiry dengan model pengembangan 4D untuk melatihkan keterampilan proses sains pada pokok bahasan pencemaran lingkungan dengan tujuan meningkatkan hasil belajar siswa. Sasaran penelitian adalah perangkat pembelajaran yang diujicobakan pada 35 siswa SMP dengan rancangan One Group Pretest-Postest Design. Kelayakan perangkat pembelajaran yang dikembangkan dianalisis secara deskriptif kuantitatif-kualitatif dengan hasil : (1) Validitas perangkat kategori valid (3,00); (2) Kepraktisan perangkat yang meliputi: a) Keterlaksanaan baik (3,8); b) Keterbacaan LKS dan buku siswa menyatakan bahwa isi LKS dan buku menarik, c) Respon siswa sangat positif (85,6 %); (3) Keefektifan perangkat permbelajaran yang meliputi: a) Aktivitas siswa yang menonjol adalah berlatih keterampilan proses sains dengan kategori tinggi (38,5 %); b) Hasil keterampilan proses siswa dalam mengerjakan LKS sangat tinggi (3,46); c) Hasil belajar siswa meningkat (N-Gain: 0,2-1,0). Simpulan penelitian ini adalah perangkat pembelajaran IPA model guided inqury layak untuk melatih keterampilan proses sains dan meningkatkan hasil belajar siswa SMP

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Magid Diefenbach, Catherine S., Jonathan B. Cohen, Wael A. Harb, Stephen M. Ansell, Loretta J. Nastoupil, Jeremy S. Abramson, Nehal J. Lakhani et al. "Results of a completed phase I study of LAM-002 (apilimod dimesylate), a first-in-class phosphatidylinositol-3-phosphate 5 kinase (PIKfyve) inhibitor, administered as monotherapy or with rituximab or atezolizumab to patients with previously treated follicular lymphoma or other B-cell cancers." Journal of Clinical Oncology 38, n.º 15_suppl (20 de mayo de 2020): 8017. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.8017.

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8017 Background: LAM-002 is a selective inhibitor of PIKfyve that disrupts lysosomal homeostasis, inducing cytotoxicity in B-cell lymphoma models as monotherapy or with anti-CD20 or anti-PDL1 antibodies (Gayle et al., Blood 2017;129(13):1768). Methods: In this study, patients received LAM-002 orally 2-3 times per day (BID or TID) in a 3+3 escalation. Additional patients received LAM-002 125 mg BID as monotherapy; with rituximab 375 mg/m2 intravenously (IV) and or subcutaneously weekly (Q1W) x 4 → Q8W x 4; or atezolizumab 1200 mg IV Q3W until disease progression or unacceptable toxicity. Pharmacokinetics (PK) were assessed for 8 hours postdose on Days 1 and 8. Efficacy was evaluated Q6-12W. Results: The study enrolled 62 patients (M:F n = 32/30); median [range] age = 69 [46-89] years; with diagnoses (n) of diffuse large B-cell lymphoma (25), follicular lymphoma (19), marginal zone lymphoma (8), mantle cell lymphoma (5), or chronic lymphocytic leukemia (5) to receive LAM-002 alone (n) at 50 mg BID (3), 100 mg BID (8), 150 mg BID (8), 75 mg TID (4), or 125 mg BID (20); LAM-002/rituximab (12); or LAM-002/atezolizumab (7). During LAM-002 dose-ranging (50 mg BID → 100 mg BID → 150 mg BID → 75 mg TID → 125 mg BID) transient, reversible nausea and/or diarrhea occurred at 150 mg BID and 75 mg TID, resulting in a LAM-002 recommended Phase 2 dosing regimen (RP2DR) of 125 mg BID. Among 39 patients receiving LAM-002, 125 mg BID, alone or in combination for up to 22 cycles (1.9 years), adverse events were typically low-grade. LAM-002 PK showed rapid absorption, dose proportionality, minimal accumulation, and no substantive changes with rituximab or atezolizumab coadministration. In patients with follicular lymphoma and median [range] prior therapies = 3 [1-9] treated with the RP2DR, objective response rates were 2/7 (29%; 1 complete response [CR], 1 partial response [PR]) with LAM-002, 5/8 (63%; 1 CR, 4 PRs) with LAM-002/rituximab, and 2/2 (100%; 2 PRs) with LAM-002/atezolizumab. Conclusions: LAM-002, the first clinical PIKfyve inhibitor, is safe alone or with full-dose anti-CD20 or anti-PD-L1 inhibition. LAM-002 does not cause the myelosuppressive or immune adverse events associated with lenalidomide or PI3K inhibitors. Promising efficacy supports registration-directed Phase 2/3 testing of LAM-002 monotherapy and combination therapy for patients with previously treated follicular lymphoma. Clinical trial information: NCT02594384 .

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Fernandes, Tiago, Valério G. Baraúna, Carlos E. Negrão, M. Ian Phillips y Edilamar M. Oliveira. "Aerobic exercise training promotes physiological cardiac remodeling involving a set of microRNAs". American Journal of Physiology-Heart and Circulatory Physiology 309, n.º 4 (15 de agosto de 2015): H543—H552. http://dx.doi.org/10.1152/ajpheart.00899.2014.

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Left ventricular (LV) hypertrophy is an important physiological compensatory mechanism in response to chronic increase in hemodynamic overload. There are two different forms of LV hypertrophy, one physiological and another pathological. Aerobic exercise induces beneficial physiological LV remodeling. The molecular/cellular mechanisms for this effect are not totally known, and here we review various mechanisms including the role of microRNA (miRNA). Studies in the heart, have identified antihypertrophic miRNA-1, -133, -26, -9, -98, -29, -378, and -145 and prohypertrophic miRNA-143, -103, -130a, -146a, -21, -210, -221, -222, -27a/b, -199a/b, -208, -195, -499, -34a/b/c, -497, -23a, and -15a/b. Four miRNAs are recognized as cardiac-specific: miRNA-1, -133a/b, -208a/b, and -499 and called myomiRs. In our studies we have shown that miRNAs respond to swimming aerobic exercise by 1) decreasing cardiac fibrosis through miRNA-29 increasing and inhibiting collagen, 2) increasing angiogenesis through miRNA-126 by inhibiting negative regulators of the VEGF pathway, and 3) modulating the renin-angiotensin system through the miRNAs-27a/b and -143. Exercise training also increases cardiomyocyte growth and survival by swimming-regulated miRNA-1, -21, -27a/b, -29a/c, -30e, -99b, -100, -124, -126, -133a/b, -143, -144, -145, -208a, and -222 and running-regulated miRNA-1, -26, -27a, -133, -143, -150, and -222, which influence genes associated with the heart remodeling and angiogenesis. We conclude that there is a potential role of these miRNAs in promoting cardioprotective effects on physiological growth.

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Ritchlin, C. T., P. Rahman, P. Helliwell, W. H. Boehncke, I. Mcinnes, A. B. Gottlieb, S. Kafka et al. "AB0538 POOLED SAFETY RESULTS FROM TWO PHASE-3 TRIALS OF GUSELKUMAB IN PATIENTS WITH PSORIATIC ARTHRITIS THROUGH 1 YEAR". Annals of the Rheumatic Diseases 80, Suppl 1 (19 de mayo de 2021): 1300–1301. http://dx.doi.org/10.1136/annrheumdis-2021-eular.1334.

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Background:DISCOVER 1 & 2, two double-blind, phase-3, psoriatic arthritis (PsA) trials of guselkumab (GUS, an IL-23 inhibitor), demonstrated significant improvement with GUS vs placebo (PBO) in signs and symptoms of PsA, with good tolerability, at week (w) 24 during the PBO-controlled period.1,2 Beyond w24, all patients (pts) switched to GUS. Continued treatment maintained efficacy through w52.3,4Objectives:To describe pooled safety results from the DISCOVER 1 & 2 trials through 1-year of GUS treatment.Methods:Adults with active PsA (DISCOVER 1: ≥3 tender/swollen joints and C-Reactive protein [CRP] ≥0.3 mg/dL; DISCOVER 2: ≥5 tender/swollen joints and CRP ≥0.6 mg/dL) were randomized to subcutaneous GUS 100 mg at w0, w4, then every 8 w (q8w); GUS 100 mg q4w; or PBO. At w24, PBO pts switched to GUS 100 mg q4w. Pts were biologic naive except ~30% pts in DISCOVER 1. Safety was reported through w60 in DISCOVER 1 and through w52 in DISCOVER 2.Results:Baseline characteristics were similar between treatment groups in the pooled studies. Through w24 and 1 year, numbers of pts per 100 patient years with ≥1 event were similar among treatment groups for adverse events (AEs), serious AEs, infections, serious infections, and discontinuations due to AE (Table 1). At 1 year, there were no cases of active tuberculosis, opportunistic infections (including candida), or inflammatory bowel disease in GUS-treated pts; 2 deaths in PBO pts; and low incidences that were similar across treatment groups for malignancy, major adverse cardiac events, and injection-site reactions. Incidence of anti-GUS antibodies was 4.5%, and most were not neutralizing. Mild elevations in serum hepatic transaminases and decreases in neutrophil counts were consistent at 1 year with the results at w24 (Table 1).Conclusion:GUS regimens of q8w and q4w were well tolerated in PsA pts through 1 year of treatment in the phase-3 DISCOVER trials, consistent with the w24 results. No meaningful differences between incidences of AEs were reported in the q8w and q4w groups. The safety profile of GUS in PsA pts is generally comparable with the previously established safety profile of GUS.References:[1]Deodhar A et al. Lancet. 2020;395:1115[2]Mease P et al. Lancet. 2020;395:1126[3]Ritchlin C et al. EULAR 2020 # SAT0397[4]McInnes I et al. EULAR 2020 # SAT0402Table 1.Number of Patients with AEs per 100 PY and Incidence of AEs of InterestTime Period24 Weeks1 Year*Treatment GroupPBOGUS SC 100 mgPBO to GUS‡GUS SC 100 mgDosing ScheduleMatchingq8wq4wGUSCombined†q4wq8wq4wGUSCombined‡ N3723753737483523753731100Total PY Follow-Up173173172346204384385589Patients with AEs per 100 PY, n (95% CI)≥1 AE143 (123, 166)148 (127, 171)154 (132, 178)151 (136, 167)92 (77, 108)114 (100, 130)115 (101, 131)109 (100, 117)≥1 Serious AE7.1 (3.7, 12)4.1 (1.6, 8.4)4.7 (2.0, 9.3)4.4 (2.5, 7.3)7.0 (3.8, 11.8)4.8 (2.9, 7.6)4.0 (2.2, 6.6)4.9 (3.6, 6.6)≥1 Infection50 (39, 62)47 (37, 59)52 (42, 65)49 (42, 58)39 (31, 49)41 (34, 48)38 (31, 45)39 (35, 44)≥1 Serious Infection1.7 (0.4, 5.1)0.6 (0.0, 3.2)1.8 (0.4, 5.1)1.2 (0.3, 3.0)2.5 (0.8, 5.8)1.3 (0.4, 3.1)0.8 (0.2, 2.3)1.3 (0.7, 2.3)Discontinued due to AE4.1 (1.6, 8.4)2.9 (1.0, 6.8)4.7 (2.0, 9.3)3.8 (2.0, 6.5)3.5 (1.4, 7.1)2.1 (0.9, 4.1)2.6 (1.3, 4.8)2.6 (1.7, 3.8)AEs of Interest§, n (%)Death2 (0.5)0000000Malignancy1 (0.3)2 (0.5)02 (0.3)1 (0.3)2 (0.5)03 (0.3)Major Adverse Cardiac Events1 (0.3)01 (0.3)1 (0.1)001 (0.3)1 (0.1)Opportunistic Infections00000000Tuberculosis00000000Inflammatory Bowel Disease1 (0.3)0000000Injection-Site Reaction1 (0.3)5 (1.3)4 (1.1)9 (1.2)4 (1.1)6 (1.6)9 (2.4)19 (1.7)Anti-GUS Antibody+-6/373 (1.6)9/371 (2.4)15/744 (2.0)14/350 (4.0)18/373 (4.8)17/371 (4.6)49/1094 (4.5)*Through w60 for DISCOVER 1 and w52 for DISCOVER 2; †Combined GUS q8w and q4w; ‡For patients who switched from PBO to GUS, only data on and after first GUS administration were included in this group; §PBO N=370.AE, adverse event; CI, confidence interval; GUS, guselkumab; PBO, placebo; PY, patient year; q4w, every 4 weeks; q8w, every 8 weeks; SC, subcutaneous; w, weekDisclosure of Interests:Christopher T. Ritchlin Grant/research support from: Received grant/research support from UCB Pharma, AbbVie, Amgen, consultation fees from UCB Pharma, Amgen, AbbVie, Lilly, Pfizer, Novartis, Gilead, Janssen, Proton Rahman Speakers bureau: Received speakers fees from Abbott, AbbVie, Amgen, BMS, Celgene, Lilly, Janssen, Novartis, Pfizer, Grant/research support from: Received grant/research support from Janssen and Novartis, consultation fees from Abbott, AbbVie, Amgen, BMS, Celgene, Lilly, Janssen, Novartis, and Pfizer., Philip Helliwell Consultant of: Consultation fees paid to charity (AbbVie, Amgen, Pfizer, UCB) or himself (Celgene, Galapagos), Grant/research support from: Received grants/research support paid to charity (AbbVie, Janssen, Novartis), Wolf-Henning Boehncke Consultant of: Received consultation fees from Janssen, Grant/research support from: Received grant/research support from Janssen Research & Development, LLC, Iain McInnes Consultant of: Received consultation fees from AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Gilead, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: Received grant/research support from Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Janssen, and UCB, Alice B Gottlieb Speakers bureau: Received speakers fees from Pfizer, AbbVie, BMS, Lilly, MSD, Novartis, Roche, Sanofi, Sandoz, Nordic, Celltrion and UCB, Consultant of: Received consultation fees from Pfizer, AbbVie, BMS, Lilly, MSD, Novartis, Roche, Sanofi, Sandoz, Nordic, Celltrion and UCB, Grant/research support from: Received grant/research support from Pfizer, AbbVie, BMS, Lilly, MSD, Novartis, Roche, Sanofi, Sandoz, Nordic, Celltrion and UCB, Shelly Kafka Shareholder of: Shareholder of Johnson & Johnson, Employee of: Employee of Janssen Research & Development, LLC, Alexa Kollmeier Shareholder of: Shareholder of Johnson & Johnson, Employee of: Employee of Janssen Research & Development, LLC, Elizabeth C Hsia Shareholder of: Shareholder of Johnson & Johnson, Employee of: Employee of Janssen Research & Development, LLC, Xie L Xu Shareholder of: Shareholder of Johnson & Johnson, Employee of: Employee of Janssen Research & Development, LLC, May Shawi Shareholder of: Shareholder of Johnson & Johnson, Employee of: Employee of Janssen Research & Development, LLC, Shihong Sheng Shareholder of: Shareholder of Johnson & Johnson, Employee of: Employee of Janssen Research & Development, LLC, Prasheen Agarwal Shareholder of: Shareholder of Johnson & Johnson, Employee of: Employee of Janssen Research & Development, LLC, Bei Zhou Shareholder of: Shareholder of Johnson & Johnson, Employee of: Employee of Janssen Research & Development, LLC, Paraneedharan Ramachandran Shareholder of: Shareholder of Johnson & Johnson, Employee of: Employee of Janssen Research & Development, LLC, Philip J Mease Speakers bureau: Received speakers fees from Abbott, Amgen, Biogen Idec, BMS, Eli Lilly, Genentech, Janssen, Pfizer, UCB – speakers bureau, Consultant of: Received consultation fees from Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB, Grant/research support from: Received grant/research support from Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB.

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Wondmagegn, Bereket, Zerihun Achiso y Abate Abera. "Effects of NPSB Fertilizers Rate on the Yield of Common Bean (Phaseolus vulgaris L.) at Tocha District, Southern Ethiopia". European Journal of Theoretical and Applied Sciences 2, n.º 3 (1 de mayo de 2024): 639–45. http://dx.doi.org/10.59324/ejtas.2024.2(3).48.

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Use of balanced nutrition means supplying other essential plant nutrients in adequate amount and proportion along with N and P. This implies N and P fertilizers are not the only yield determining nutrients but also S, B, and Cu nutrients are important nutrient for crop production. A trial was conducted in Tocha District to evaluate the rate of blended fertilizers to improve Common bean yield during main cropping season of 2019 and 2020. The experiment consists of seven treatment including (1) control, (2) NPSB: 18.9-37.7-6.95-0.1 (3) NPSB: 28.35-56.55-10.425-0.15 (4) NPSB: 37.8-75.4-13.9-0.2, (5) NPSB: 18.9-37.7-6.95-0.1+0.4kgCu, (6) NPSB: 28.35-56.55-10.425-0.15+0.4kgCu and (7) NPSB: 37.8-75.4-13.9-0.2+0.4kgCu. Soil physic chemical properties of the experimental site had moderately acidic, moderate level of OC and total N, high level of exchangeable K, very high level of CEC, low level of available P and clay loam textural class. In generally, application of blended fertilizer yielded better when compared with control. NPSB with the ratio of 37.8-75.4-13.9-0.2 (200kg NPSB) gave significantly optimum yield (4368.83 kg ha-1) compared to other treatments and also the highest net benefit (18725 ETB/ha) was obtained with acceptable marginal rate of return (MRR) (375.91%) which is more than the minimum acceptable MRR (100%) considered in this experiment. Similarly, NPSB 18.9-37.7-6.95-0.1 gave considerable net benefit with acceptable MRR. Therefore, based on the yield response and economic indicators, 200kg NPSB (37.8-75.4-13.9-0.2) is recommended as the best option and 100kg NPSB (18.9-37.7-6.95-0.1) as an alternative option for common bean producers at Tocha district and areas with the same soil conditions and agro-ecology.

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Javed, Muhammad Babar, Zaffar Malik, Muhammad Kamran, Ghulam Hassan Abbasi, Asma Majeed, Muhammad Riaz, Muhammad Adnan Bukhari et al. "Assessing Yield Response and Relationship of Soil Boron Fractions with Its Accumulation in Sorghum and Cowpea under Boron Fertilization in Different Soil Series". Sustainability 13, n.º 8 (9 de abril de 2021): 4192. http://dx.doi.org/10.3390/su13084192.

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Boron (B) is an essential micronutrient in the growth of reproductive plant parts. Its deficiency and/or toxicity are widespread in arid and semi-arid soils with low clay contents. This study was planned to determine the response of sorghum (Sorghum bicolor L., non-leguminous crop) and cowpea (Vigna sinensis L., leguminous crop) to boron (0, 2, 4, and 16 µg g−1) on four distinct soil series from Punjab, Pakistan i.e., Udic Haplustalf (Pindorian region), Typic Torrifluvent (Shahdra region), Halic Camborthid (Khurianwala region), and Udic Haplustalf (Gujranwala region). Overall, there was a significant difference (p < 0.05) in yield between the sorghum (3.8 to 5.5 g pot−1 of 5 kg dry soil) and cowpea (0.2 to 3.2 g pot−1 of 5 kg dry soil) in response to B application. The highest yield was observed in both sorghum and cowpea either in control or at 2 µg g−1 B application in all four soils. Cowpea showed the same yield trend in all four soils (i.e., an increase in yield at 2 µg g−1 B application, followed by a significant decrease at the higher B levels). In contrast, sorghum exhibited greater variability of response on different soils; Udic Haplustalf (Pindorian region) produced the greatest yield at low levels of B application. However, Halic Camborthid produced its lowest yield at that level. Boron concentration in shoots increased with the levels of B application, particularly in sorghum. In cowpea, the plant growth was extremely retarded—and most of the plants died at higher levels of B application even if a lower concentration of B was measured within the shoot. Hot water-extractable B was the most available fraction for cowpea (R2 = 0.96), whereas the easily exchangeable B was most available for sorghum (R2 = 0.90). Overall, these results have implications for micronutrient uptake for both leguminous and non-leguminous crops.

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Murayama, Kayoko, Toru Kiguchi, Koji Izutsu, Yoshihiro Kameoka, Michihiro Hidaka, Harumi Kato, Shinya Rai et al. "Bendamustine plus rituximab in Japanese patients with relapsed or refractory diffuse large B-cell lymphoma". Annals of Hematology 101, n.º 5 (4 de marzo de 2022): 979–89. http://dx.doi.org/10.1007/s00277-022-04801-2.

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AbstractThis single-arm phase 3 study was conducted to confirm the results of our phase 2 study of bendamustine (B)-rituximab (R) in patients with relapsed/refractory diffuse large B cell lymphoma (rrDLBCL). The primary endpoint was overall response rate (ORR). Autologous stem cell transplantation-ineligible rrDLBCL patients with ≤ 2 prior chemotherapy regimens received R 375 mg/m2 IV on day 1 and B 120 mg/m2/day IV on days 2 and 3 every 21 days up to 6 cycles. Thirty-eight patients with a median age of 74 years (range, 43–86) received BR. The ORR and complete response rates were 76.3% and 47.4%, respectively. With a median follow-up of 19.5 months including long-term follow-up, median progression-free survival was 11.9 months. Median OS was 29.2 months. Discontinuation of treatment due to Gr3-5 TEAE was observed among 13 of 38 patients (34.2%). One patient with cytomegalovirus enterocolitis died during follow-up. This BR regimen was confirmed to be effective and tolerable in studied patients. ClinicalTrials.gov Identifier: NCT03372837 registered on 14 December 2017, NCT04354402 registered on 21 April, 2020.

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DesRuisseaux, Libby A., Namita Mahtta y Yana Suchy. "36 Dispersion vs. inconsistency: Investigating the relationship between different forms of intra-individual variability in community-dwelling older adults". Journal of the International Neuropsychological Society 29, s1 (noviembre de 2023): 716–17. http://dx.doi.org/10.1017/s1355617723008949.

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Objective:There are two forms of intra-individual variability (IIV) in the literature: inconsistency, or variability on one task across many time points, and dispersion, or variability across many tasks at one time point. These forms of IIV are often lumped together into one construct, but there is limited evidence supporting this practice, as few studies have examined the relationship between these measures. Additionally, it is not clear how stable these constructs are over time. Therefore, the goal of the present study was (1) to explore the relationship between (a) inconsistency and dispersion and (b) IIV and mean performance, and (2) to determine whether these relationships are stable over a one- to two-year follow-up interval.Participants and Methods:A total of 123 community-dwelling older adults (Mage=69.5, Meducation=15.6 years) from an archival database completed the Push-Turn-Taptap task to assess inconsistency and the Delis-Kaplan Executive Functioning System (D-KEFS) to assess dispersion. These measures were selected because both are highly executive, thereby allowing us to hold the cognitive domain constant across forms of IIV. Dispersion was calculated by taking the standard deviation of the executive conditions of four D-KEFS subtests (Verbal Fluency, Design Fluency, Trail Making, and Color Word Interference). Follow-up data were collected one to two and a half years after baseline. Bivariate and partial correlations controlling for time to follow-up were examined.Results:Inconsistency and dispersion were not correlated at baseline but were weakly correlated at follow-up (r=.281, p=.012). Additionally, both forms of IIV were moderately correlated with themselves across the follow-up interval (inconsistency: r=.450, p<.001; dispersion: r=.448, p<.001). The partial correlations were nearly identical to bivariate correlations.Additionally, inconsistency was correlated with poorer mean executive functioning (EF) performance on both the PTT (baseline: r=.281, p<.001, follow-up: r=.435, p<.001) and D-KEFS (baseline: r= -.270, p=.003, follow-up: r=-.573, p<.001). In contrast, dispersion was correlated with mean EF performance only on the D-KEFS at baseline (r= -.292, p<.001) but with both measures at follow-up (PTT: r=.232, p=.039; D-KEFS: r= -.378, p<.001). When controlling for follow-up interval, inconsistency was no longer correlated with baseline mean PTT performance, but all other relationships remained the same (i.e., dispersion and inconsistency displayed the same pattern of correlations with mean EF).Conclusions:Although inconsistency and dispersion are both forms of IIV, they are weakly related. In other words, although they may have shared mechanisms, these two methods of measuring IIV likely represent different constructs. In the future, authors should take care to specify the form of IIV being investigated in their publications rather than referring to either form as IIV generally. Additionally, both forms of IIV are weakly to moderately correlated with mean EF performance, indicating that IIV is related to but separate from mean-level performance. Interestingly, IIV and mean performance were more strongly correlated at follow-up, which may be suggestive of incipient cognitive decline. Lastly, it seems that both inconsistency and dispersion are somewhat stable across a one- to two-year follow-up interval, suggesting that IIV may be a trait-level construct to some extent. However, IIV may also be influenced by state-level contextual factors, and more research examining the stability of and contributors to IIV is necessary.

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Hallek, Michael, Guenter Fingerle-Rowson, Anna Maria Fink, Raymonde Busch, Jiri Mayer, Manfred Hensel, Georg Hopfinger et al. "Immunochemotherapy with Fludarabine (F), Cyclophosphamide (C), and Rituximab (R) (FCR) Versus Fludarabine and Cyclophosphamide (FC) Improves Response Rates and Progression-Free Survival (PFS) of Previously Untreated Patients (pts) with Advanced Chronic Lymphocytic Leukemia (CLL)". Blood 112, n.º 11 (16 de noviembre de 2008): 325. http://dx.doi.org/10.1182/blood.v112.11.325.325.

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Abstract Introduction: Previous phase II studies have suggested that a combination of FCR may increase the outcome of both untreated and relapsed CLL pts. In order to validate this concept the German CLL study group (GCLLSG) initiated a multicentre, multinational phase III trial, CLL8, to evaluate the efficacy and tolerability of FCR versus FC for the first-line treatment of pts with advanced CLL. Methods and Patients: 817 pts with good physical fitness as defined by a cumulative illness rating scale (CIRS) score (Extermann et al., JCO 1998) of up to 6 and a creatinine clearance (cr cl) □d 70 ml/min were enrolled between July 2003 and March 2006. Pts were randomly assigned to receive 6 courses of either FC (N=409; F 25mg/m2 i.v. d1–3 and C 250 mg/m2 i.v. d1–3; q 28 days) or FC plus R (N=408; 375 mg/m2 i.v. d 0 at first cycle and 500 mg/m2 d1 all subsequent cycles; q 28 days). Both treatment arms were well balanced with regard to age, stage, genomic aberrations and VH status. 64% were Binet B, 32% Binet C and 5% Binet A. The median age was 61 years (range 30 to 81), the median CIRS score was 1 (range 0–8). The overall incidences of trisomy 12 and abnormalities of 13q, 11q23, and 17p13 detected by FISH were 12%, 57%, 25%, and 8%, respectively, with no statistically significant differences between treatment arms. A mean number of 5.2 courses was given in the FCR arm versus 4.8 courses in the FC arm (p=0.006). 74% (FCR) and 67% (FC) of pts received 6 cycles. Dose was reduced by more than 10% in at least one treatment course in 43% (FCR) and 30% (FC) of pts, and in 21% (FCR) and 17% (FC) of all treatment courses given. 17 pts did not receive any study medication, 10 due to violation of enrolment criteria (4 decreased renal function, 2 active secondary malignancies, 2 active infections, 1 autoimmune thrombocytopenia, 1 pt not requiring treatment), 3 due to withdrawal of consent, 2 due to worsened concomitant diseases. 2 pts were lost before start of treatment. 56 pts were not evaluable for response: 17 did not receive any study medication, 16 withdrew consent before interim staging, 7 due to violation of enrolment criteria, 4 discontinued treatment due to toxicity and 12 due to early death (caused by toxicity, progression or secondary malignancy). Prophylactic use of antibiotics or growth factors was not generally recommended in the protocol. Results: At the time of analysis, June 2008, the median observation time was 25.5 months (mo). 761 pts (FCR 390; FC 371) were evaluable for response, 787 pts (FCR 400; FC 387) for PFS and all for OS. The overall response rate (ORR) was significantly higher in the FCR arm (95%; 370/390) compared to FC (88%; 328/371 (p=0.001). The complete response rate of the FCR arm was 52% as compared to 27.0% in the FC arm (p<0.0001). PFS was 76.6% at 2 years in the FCR arm and 62.3% in the FC arm (p<0.0001). There was a trend for an increased OS rate in the FCR arm (91% vs 88% at 2 years p=0.18). Hazard Ratio for PFS was 0.59, for OS 0.76. The largest benefit for FCR was observed in Binet stage A and B with regard to CR, ORR and PFS (A: p=0.01, B: p<0.0001). FCR treatment was more frequently associated with CTC grade 3 and 4 adverse events (47% of FC vs 62% of FCR treated pts). Severe hematologic toxicity occurred in 55% (FCR) versus 39% (FC) of all patients. Significant differences were observed for neutropenia (FCR 33,6%; FC 20,9% p=0.0001) and leukocytopenia (FCR 24%; FC 12,1% p<0.0001) but not for thrombocytopenia (FCR 7,4%; FC 10,8% p=0.09) and anemia (FCR: 5,4% FC 6,8% p=0.42). The incidence of CTC grade 3 or 4 infections was not significantly increased in the FCR arm (18,8% versus 14,8% in the FC arm, p=0.68). Tumor lysis syndrome (FCR 0,2% FC 0,5%) and cytokine release syndrome (FCR 0,2% FC 0,0%) were rarely observed in both arms. Treatment related mortality occurred in 2.0% in the FCR and 1.5% in the FC arm. Multivariate analyses were performed to evaluate factors predicting outcome. Amongst these variables age, sex, Binet stage, CIRS score, renal function (cr cl < 70 ml/min) were independent prognostic factors predicting OS or PFS. Conclusion: Treatment with FCR chemoimmunotherapy improves response rates and PFS when compared to the FC chemotherapy. FCR caused more neutropenia/leukopenia without increasing the incidence of severe infections. These results suggest that FCR chemoimmunotherapy might become the new standard first-line treatment for physically fit CLL patients.

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Abdalla, Marwah, Sumayya Shurovi, Michelle David, Talea Cornelius, Ari Shechter y Joseph Schwartz. "0912 The Association Between Somatization and Sleep". SLEEP 47, Supplement_1 (20 de abril de 2024): A391—A392. http://dx.doi.org/10.1093/sleep/zsae067.0912.

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Abstract Introduction Somatization, the experience of having somatic symptoms (e.g., pain, fatigue, dizziness) with resultant psychological distress, has been described among working adults and contributes to work-related absences. Whether somatization affects employees’ sleep quality and sleep duration is unclear. We examined the association of somatization with sleep quality and duration. Methods Data came from the 4th wave of the multi-site Worksite Blood Pressure Study, which assessed psychological factors and ambulatory blood pressure. A total of 472 participants without major cardiovascular disease from 10 worksites in NYC were recruited across 4 waves and ~11 years. At Wave 4, participants completed the Brief Symptom Inventory (BSI) and a sleep questionnaire derived from the Sleep Heart Health Study. Items from the BSI were averaged and T-scored (normed to mean=50, SD=10). Items assessing sleep quality were averaged (higher scores indicated worse sleep quality). Weekday sleep duration was also reported using a one-time sleep diary. Analyses were restricted to participants providing complete data (N= 238). Linear regression models were specified predicting (1) sleep quality and, separately (2) sleep duration from somatization. Covariates were age, sex, race/ethnicity, body mass index, marital status, years of education, family income, employment status, and average work hours per week. Results Of the 238 participants, 79.8% were male, 11.8% were Black, 5.9% were Hispanic/Latinx, and 76.5% were married. Median family income was $70,000-$79,999. Mean age was 52.4 years (SD=8.1), mean years of education was 17.9 (SD=3.1), mean body mass index was 27.9 kg/m2 (SD=3.8), and mean hours worked per week (among those currently employed; n=191) was 42.0 (SD=10.9). Mean somatization score was 49.5 (SD=9.3), mean sleep quality was 8.4 (SD=4.3), and mean sleep duration was 6.5 hours/night (SD=1.1). Higher somatization scores were significantly associated with worse sleep quality, B=0.15, 95% CI 0.09, 0.20, p< 0.001. The association of somatization with sleep duration was not significant, B= 0.01, 95% CI -0.00, 0.02, p=0.18. Conclusion There was an association between somatization and sleep quality but not with sleep duration. Future research should examine whether treatment modalities for somatization among working adults improve sleep quality and overall occupational health. Support (if any) P01HL47540, NIH/NHLBI K23HL141682

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Katsuya, Yuki, Kan Yonemori, Toshio Shimizu, Takafumi Koyama, Sigehisa Kitano, Kazuki Sudo, Shunsuke Kondo, Jun Sato, Hiroaki Hozumi y Noboru Yamamoto. "Abstract CT062: A phase 1 study of tamnorzatinib (ONO-7475), an Axl/Mer dual inhibitor, alone and in combination with nivolumab in patients with advanced or metastatic solid tumors". Cancer Research 84, n.º 7_Supplement (5 de abril de 2024): CT062. http://dx.doi.org/10.1158/1538-7445.am2024-ct062.

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Abstract Background: Tamnorzatinib (ONO-7475) is an orally active small molecule Axl/Mer dual inhibitor that not only directly acts on cancer cells to suppress their proliferation, but also on immune cells and exerts characteristics of cancer immunotherapy. Methods: We performed a phase 1 study to assess the tolerability, safety, and pharmacokinetics of ONO-7475 alone (Part A) and in combination with nivolumab (NIVO) (Part B) in Japanese patients (pts) with advanced or metastatic solid tumors (NCT03730337). Patients received once-daily ONO-7475 (3-10 mg, orally) as a monotherapy or in combination with NIVO (240 mg, i.v., every 2 weeks). Results: Twelve pts in both Part A and Part B (three each at 3 and 6 mg, and six at 10 mg ONO-7475) received the study treatment. Baseline characteristics, safety, and efficacy outcomes are summarized in the Table. While one of six pts in the Part B 10-mg cohort developed dose-limiting toxicities of grade 4 nephritis, grade 3 colitis, and grade 3 hepatic function abnormal, no others did. In biomarker analyses, activation of T cell function and an increase in T cell number, an increase in inflammatory (M1) macrophages/immunosuppressive (M2) macrophages ratio, and suppression of epithelial-to-mesenchymal transition were observed after treatment. Conclusion: ONO-7475 was tolerated at repeated once-daily oral doses up to 10 mg as a monotherapy and in combination with NIVO in pts with advanced or metastatic solid tumors. TABLE 1. NAND Table. Baseline Characteristics, Safety Outcomes, and Efficacy Outcomes Part A (ONO-7475 alone) N = 12 Part B (ONO-7475 + NIVO) N = 12 Baseline Characteristics Median age, years (range) 63.5 (31–76) 56.0 (39–72) Female, n (%) 8 (66.7) 9 (75.0) ECOG PS, n (%) 0 8 (66.7) 10 (83.3) 1 4 (33.3) 2 (16.7) Safety Outcomes Number of patients with AEs (%) Any grade 11 (91.7) 11 (91.7) Glade ≥3 0 2 (16.7) *2 Number of patients with SAEs (%) 2 (16.7) *1 1 (8.3) *3 *1 Pyrexia and diverticulitis (1 patient each) *2 Grade 4 neutrophil count decreased (1 patient), grade 4 lymphocyte count decreased and nephritis (1 patient each), and grade 3 colitis, enterocolitis infectious, device related infection, anemia, hyperglycemia, and hepatic function abnormal (1 patient) *3 Colitis, hepatic function abnormal, and nephritis Efficacy Outcomes Objective Response Rate, n (%) [95% CI] 0 [0.0, 26.5] 1 (8.3) [0.2, 38.5] Disease Control Rate, n (%) [95% CI] 3 (25.0) [5.5, 57.2] 4 (33.3) [9.9, 65.1] Best Overall Response, n (%) [95% CI] Complete Response 0 [0.0, 26.5] 0 [0.0, 26.5] Partial Response 0 [0.0, 26.5] 1 (8.3) [0.2, 38.5] Stable Disease 3 (25.0) [5.5, 57.2] 3 (25.0) [5.5, 57.2] Progressive Disease 9 (75.0) 5 (41.7) Not Evaluable 0 3 (25.0) Median OS, months [95% CI] 12.21 [4.93, not reached] 16.99 [5.98, not reached] Median PFS, months [95% CI] 1.86 [0.92, 3.84] 2.17 [0.95, 3.78] Citation Format: Yuki Katsuya, Kan Yonemori, Toshio Shimizu, Takafumi Koyama, Sigehisa Kitano, Kazuki Sudo, Shunsuke Kondo, Jun Sato, Hiroaki Hozumi, Noboru Yamamoto. A phase 1 study of tamnorzatinib (ONO-7475), an Axl/Mer dual inhibitor, alone and in combination with nivolumab in patients with advanced or metastatic solid tumors [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 CT062.

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31

Cox, Gregory R., Ben Desbrow, Paul G. Montgomery, Megan E. Anderson, Clinton R. Bruce, Theodore A. Macrides, David T. Martin et al. "Effect of different protocols of caffeine intake on metabolism and endurance performance". Journal of Applied Physiology 93, n.º 3 (1 de septiembre de 2002): 990–99. http://dx.doi.org/10.1152/japplphysiol.00249.2002.

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Competitive athletes completed two studies of 2-h steady-state (SS) cycling at 70% peak O2uptake followed by 7 kJ/kg time trial (TT) with carbohydrate (CHO) intake before (2 g/kg) and during (6% CHO drink) exercise. In Study A, 12 subjects received either 6 mg/kg caffeine 1 h preexercise (Precaf), 6 × 1 mg/kg caffeine every 20 min throughout SS (Durcaf), 2 × 5 ml/kg Coca-Cola between 100 and 120 min SS and during TT (Coke), or placebo. Improvements in TT were as follows: Precaf, 3.4% (0.2–6.5%, 95% confidence interval); Durcaf, 3.1% (−0.1–6.5%); and Coke, 3.1% (−0.2–6.2%). In Study B, eight subjects received 3 × 5 ml/kg of different cola drinks during the last 40 min of SS and TT: decaffeinated, 6% CHO (control); caffeinated, 6% CHO; decaffeinated, 11% CHO; and caffeinated, 11% CHO (Coke). Coke enhanced TT by 3.3% (0.8–5.9%), with all trials showing 2.2% TT enhancement (0.5–3.8%; P < 0.05) due to caffeine. Overall, 1) 6 mg/kg caffeine enhanced TT performance independent of timing of intake and 2) replacing sports drink with Coca-Cola during the latter stages of exercise was equally effective in enhancing endurance performance, primarily due to low intake of caffeine (∼1.5 mg/kg).

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32

Cassone, Antonio. "Immunogenic and immunomodulatory properties of mannoproteins from Candida albicans". Canadian Journal of Botany 73, S1 (31 de diciembre de 1995): 1192–98. http://dx.doi.org/10.1139/b95-378.

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Candida albicans is a human commensal and opportunistic fungal organism that expresses on its surface and releases into the external milieu a variety of mannoprotein molecules that are relevant in many aspects of host–Candida relationship. We have attempted to relate mannoprotein constituents to the microbial function and (or) host response. For instance, we have recently found that a protein moiety of a 65-kDa mannoprotein is a major target of cell-mediated immune response. The pattern of cytokines produced by mannoprotein-stimulated human mononuclear cell cultures and mannoprotein-specific T cell lines demonstrated abundant interferon-γ and interleukin-2 production with very low or no production of interleukin-4 and interleukin-10, which suggests that MP-65 is recognized by CD4+ cells of T helper 1 subset. A similar cytokine pattern was seen in splenocyte cultures of mice chronically infected with a low-virulence Candida strain (CA-2) and then stimulated in vitro with MP-65-containing mannoprotein fractions, or also in mice immunized with these fractions. On the other hand, the mannan moieties of mannoproteins bear major B cell epitopes that are responsible for serological specificity, and the ordinary antibody response mounted during normal host colonization. Indirect evidence for the importance of this response for the host–Candida relationship is the dramatic modulation of mannan epitopes on the cell surface during growth and morphological development in vivo. One such epitope is a phosphorylated β-1,2-oligomannoside recognized by the monoclonal antibody AF1, which is present on the surface of infecting yeast cells but then lost during an experimental vaginal infection. Finally, mannan moieties also exert powerful activation of the antimicrobial activity of polymorphonuclear cells and release of a variety of pro-inflammatory and immunomodulatory cytokines, in particular interleukin-1β and tumor necrosis factor-α. Overall, these studies emphasize the need for further definition of individual mannoprotein constituents to dissect the multiple biological actions of these highly complex, multifunctional molecular within C. albicans. Key words: mannoproteins, Candida albicans, immunogenicity, immunomodulation.

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33

Pawlak, Zenon y Michal Sojka. "The amphoteric cartilage surface tested in the pH Range from 2.0 to 9.0". Journal of Clinical Case Reports and Studies 3, n.º 1 (4 de enero de 2022): 01–04. http://dx.doi.org/10.31579/2690-8808/092.

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Background: Phospholipids adsorbed to negatively-charged proteoglycan matrix form phospholipid (membrane), have negatively charged surface (-PO4-) and are hydrophilic. Strong adsorption and strong cohesion are necessary for phospholipids to provide a good lubricant. The surface energy of spherical lipid bilayers have "bell-curve" shaped has amphoteric character and lowest surface energy at a pH 7.4 ± 1 of the natural joint. Objectives: The amphoteric character of the natural surface of the articular cartilage was determined by measuring the surface energy of the model spherical bilayer lipid membrane. It was found that the friction (f) vs. pH 2.0 to 9.0 of the pair (cartilage/cartilage) has the amphoteric character by exposing "bell-curve" shaped with an isoelectric point (IEP). Methods: The friction coefficient (f) was measured with the sliding pin-on-disc tribotester the friction between two surfaces (cartilage/cartilage) pair. The method of interfacial tension measurements of the spherical lipid bilayer model vs the pH over the range 0.2 to 9.0 was used. Results: The dependence of friction coefficient between two cartilage surfaces on the pH over the range 2.0 to 9.0 is demonstrated by a “bell - curve” in Fig. 2(A). The surface energy of a model spherical bilayer lipid membrane vs. the pH has the character of a “bell - curve” with an (IEP) is shown in Fig. 2(B). Conclusion: The amphoteric effect on friction between the bovine cartilage/cartilage contacts has been found to be highly sensitive to the pH of an aqueous solution. In this paper we demonstrate experimentally that the pH sensitivity of cartilage to friction provides a novel concept in joint lubrication on charged surfaces. The change in friction was consistently related to the change of charge density of an amphoteric surface.

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34

Fiegl, Michael, Andreas Falkner, Michael Fidrik, Gerhard Postner, Alois Lang, Niklas Zojar, Guenther Gastl y Richard Greil. "Alemtuzumab in B-Cell Prolymphoytic Leukemia (B-PLL) and Richter’s Transformation." Blood 108, n.º 11 (16 de noviembre de 2006): 4733. http://dx.doi.org/10.1182/blood.v108.11.4733.4733.

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Abstract Alemtuzumab is the standard therapy for treatment of patients with relapsed/refractory B-CLL. Significant responses have also been documented in the front-line CLL setting, and as well as in first-line therapy of patients with T-PLL, a population with an exceptionally poor prognosis and few available therapeutic options. Limited data available on the therapeutic benefit of alemtuzumab in other aggressive lymphomas such as B-PLL, which is rare, with a heterogeneous clinical course, and often chemoresistant, as well as CLL with Richter’s transformation, which is also characterized by a poor clinical outcome. Here, we present data on safety and efficacy of alemtuzumab in 6 patients with B-PLL, and 2 cases of B-CLL with Richter’s transformation, both of which developed into DLBCL; one B-CLL case was atypical due to negative CD5 expression (CD19+, CD5−, CD23−). Median age for all 8 patients was 62 years (range, 58–72 years), 5 were male, and all had received a median of 3.5 prior therapies (range, 0–11). Two patients were Rai stage II and III, respectively, and 4 had Rai stage IV disease. At baseline, 3 of the 6 patients with B-PLL had poor performance status, as evidenced by exceptionally high leukocyte counts with clinical signs of hyperleukocytosis and fever of unclear origin. IV alemtuzumab 30 mg was administered according to guidelines (3 times a week, 12 weeks scheduled), but in the majority of cases, dosing was individualized. The median duration of therapy was 4.5 weeks (range, 1–12 weeks), and the median dose was 348 mg (range, 3–793 mg). Therapeutic response was determined according to NCI-WG criteria. In the 2 of 3 patients with poor PS at initiation of therapy an objective response could not be determined due to an early death (septicemia with staphylococcus); 1 patient died prior to achieving a full response due to a suspected apoplectic insult, and another patient died due to progressive disease, shortly after starting alemtuzumab. However, 2 (33%) patients with B-PLL achieved stable disease, lasting 7 months in both cases. Both patients gained a clear clinical benefit from treatment with alemtuzumab as evidenced by CR and PR in peripheral blood, individually, and transfusion independence in both patients. These 2 patients appeared to have favourable disease characteristics, as has been described by other investigators (Leukemia & Lymphoma1999; 33:169), and were diagnosed 9 and 11 years before alemtuzumab, respectively. In the 6 B-PLL patients, overall survival (OS) after start of alemtuzumab therapy was very heterogeneous (0.1; 0.2; 0.3; 1; 27+; 28 months), with a longer OS in the 2 patients with SD. In the 2 patients with B-CLL/Richters’s syndrome (as multifocal DLBCL), PD was observed in one after 2 months on alemtuzumab (survival 15 months). The patient with atypical features was receiving alemtuzumab as an 8th line of therapy and achieved a PR lasting for 13 months (OS 31+ months). In summary, we are adding evidence of therapeutic efficacy of alemtuzumab in a subset of patients with rare, chemotherapy refractory B-lymphoproliferative diseases.

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35

Shao, Yu Yun, Chi-Huang Hsiao, Ray Lee, Oscar Puig, Soa-Yu Chan, Yong-Shi Li y Chih-Hung Hsu. "Tumor c-Met expression and prognosis of advanced hepatocellular carcinoma patients treated with sorafenib." Journal of Clinical Oncology 33, n.º 3_suppl (20 de enero de 2015): 317. http://dx.doi.org/10.1200/jco.2015.33.3_suppl.317.

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317 Background: Overexpression of c-Met signaling has been associated with development and progression of hepatocellular carcinoma (HCC). We explored the prognostic role of tumor c-Met expression in patients with advanced HCC. Methods: Patients who had received sorafenib alone as first-line therapy for advanced HCC and had available archival tumor tissues were enrolled. Expression of total c-Met was determined by immunohistochemical staining using CONFIRM anti-total c-MET (SP44) rabbit monoclonal primary antibody (Ventana) on the BenchMark ULTRA staining platform. We evaluated c-Met expression by H scores and by a clinical score as defined in the table. Results: The study enrolled 62 patients, all with Child-Pugh class A status. The HCC etiology was hepatitis B in 48 patients, and hepatitis C in 12 patents; 57 had BCLC disease; 40 had extrahepatic metastasis, and 37 had macrovascular invasion. Clinical scores of c-Met were 0 in 30 (48%) patients, 1 in 31 (50%) patients, 2 in 1 (2%) patients, and 3 in 0 patients. Patients with different clinical scores of c-Met had similar PFS (p = 0.821) or OS (p = 0.533). The median membranous H score and cytoplasmic score were 32.5 and 5, respectively. Patients with higher (≥ median) and lower c-Met membranous H scores or cytoplasmic H scores also had similar PFS and OS. Conclusions: High c-Met expression was rare in this advanced HCC cohort. Tumor expression of c-Met had no obvious associations with the prognosis of advanced HCC. (This study was supported by National Science Council, Taiwan (NSC-102-2314-B-002-120, NSC-103-2314-B-002-181-MY2, NSC-103-2314-B-002-092)). [Table: see text]

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36

Bazié, Bazoin Sylvain Raoul, Adjima Bougma, Aminata Séré, Judicael Thomas Ouilly, Hassane Sangaré, Elie Kabré, Aly Savadogo, Djidjoho Joseph Hounhouigan, Marie-Louise Scippo y Imaël Henri Nestor Bassole. "Assessment of heterocyclic aromatic amines contents in flamed and braised chicken in Burkina Faso". PLOS ONE 17, n.º 12 (30 de diciembre de 2022): e0278712. http://dx.doi.org/10.1371/journal.pone.0278712.

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The nutritional status of meat is tarnished by its association with the induced cooking contaminants. The aim of this study was to assess the heterocyclic aromatic amines profile and contents in processed chicken in Burkina Faso. Eight polar and apolar heterocyclic aromatic amines (HAAs) including 2-mino-3-methylimidazo[4,5-f]quinolone (IQ), 3-amino-1,4-dimethyl-5H-pyrido[4, 3-b]indole (Trp-P1), 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P2), 2-mino-9H-pyrido-[2,3-b]indole (AαC), 2-amino-1-methyl-6-phenylimidazo[4, 5– ]pyridine (PhIP), 2-amino-3-methyl-9H-pyrido[2,3-b] indole (MeAαC), 2-amino-3,4,8-rimethylimidazo[4,5-f]quinoxaline (4,8-DiMeIQx) and 2-amino-3,8-imethylimidazo[4,5–]quinoxaline (MeIQx) were screened by high performance liquid chromatography from 29 samples of flamed chicken and 66 samples of braised chicken collected in Ouagadougou city. Apolar HAAs and polar HAAs were respectively 12 and 3 times more abundant in flamed chickens (32.66±10 and 3.48±10.39 ng/g, respectively) than in braised chickens (2.70±9.67 and 0.92 ng/g, respectively). The maximum levels of AαC were in the same proportions in flamed (12.01 ng/g) and braised chickens (14.13 ng/g). Flamed chicken had the highest Trp-P1 content (530.31 ng/g). The 4,8-DiMeIQx was not detected in braised chicken. The AαCs were more abundant in flamed than in braised chicken. The profile and the contents of the HAAs in processed chicken are related to cooking methods. Because of the high variability observed on the obtained concentrations, investigations on the contents of precursors in raw chicken, the effect of marinating ingredients on the formation of HAAs are needed.

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37

Harrowfield, Jack M., Raj Pal Sharma, Brian W. Skelton y Allan H. White. "Structural Systematics of 2/4-Nitrophenoxide Complexes of Closed-Shell Metal Ions. IV [Acid Salts] of the 4-Nitrophenoxides of Group 1". Australian Journal of Chemistry 51, n.º 8 (1998): 747. http://dx.doi.org/10.1071/c97101.

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Room-temperature single-crystal X-ray studies are recorded for a number of ‘acid salts’ formed between Group 1 salts of 4-nitrophenol, M(4-np), and the parent ligand 4-npH, variously hydrated. The 1 : 1 salts M(4-np)(4-npH).x H2O are found for all of M = Li, Na, K, Rb and Cs. The lithium adduct (tetrahydrate) is monoclinic, C2/c, a 19·438(4), b 11·207(2), c 7·421(2) Å, β 91·38(2)°, Z = 4, conventional R on |F| being 0·043 for 1369 independent ‘observed’ (I > 3σ(I)) diffractometer reflections. The sodium adduct (dihydrate) is monoclinic, C2, a 2·174(3), b 3·674(2), c 10·358(1) Å, β 117·21(1)°, Z = 2, R 0·035 for No 1092; the potassium adduct (monohydrate) is monoclinic, C 2/c, a 22·10(1), b 3·798(3), c 21·270(6) Å, β 120·97(4)°, Z = 4, R 0·050 for No 1065. The isomorphous rubidium and caesium monohydrates are triclinic, P-1, a ≈ 11·9, b ≈ 10·2,c ≈ 6·3 Å, α ≈ 90, β ≈ 92, γ ≈ 112°, Z = 2, R 0·042, 0·028 for No 2340, 3053 respectively. For M = Rb, a 1 : 3 adduct Rb(4-np).3(4-npH) is also obtained (with an isomorphous thallium counterpart recorded elsewhere): a 12·143(5), b 11·50(1), c 11·36(1) Å, α 114·38(9), β 110·54(6), γ 96·73(6)°, Z = 2, R 0·034 for No 3945. The lithium salt may be represented as [Li(OH2)4]+ (4-npH.4-np)½-. The cation lies disposed about a crystallographic 2 axis; the anion, close to an axis, confronts its rotational image, with the associated hydrogen atom modelled as disordered between them, rather than located on the 2 axis. The sodium salt is a sheet structure, the six-coordinate sodium atoms being disposed on a crystallographic 2 axis and linked up that axis ... Na(µ-O)2Na(µ-O)2Na ... by bridging water molecule oxygen atoms, while symmetry-related trans O-nitrophenoxide moieties are bridged by confronting phenoxide oxygen atoms about an associated hydrogen atom provisionally disposed on a 2 axis also. The potassium salt structure is developed from this array, modelled with disordered potassium atoms, now lying off the 2 axis, 0·922(2) Å apart. In the rubidium/caesium structure, columns of oxygen-bridged metal ions are disposed about c, crosslinked by O-nitro-bonded phenoxide moieties, with confronting phenoxide oxygen atoms about a shared associated hydrogen.

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38

Zhuo, Lang, S. L. Sajdak y R. B. Phillips. "Minimal intraspecific variation in the sequence of the transcribed spacer regions of the ribosomal DNA of lake trout (Salvelinus namaycush)". Genome 37, n.º 4 (1 de agosto de 1994): 664–71. http://dx.doi.org/10.1139/g94-094.

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Intraspecific variation in the sequence of the transcribed spacer regions of the ribosomal DNA (rDNA) in lake trout was examined by restriction mapping and sequencing of these regions amplified by the polymerase chain reaction. The length of the first internal transcribed spacer region (ITS-1) was 566 bases and the second internal transcribed spacer region (ITS-2) was 368 bases in lake trout. When the 1.4-kb region including the ITS-1, the 5.8S coding region, and the ITS-2 was amplified from 12 individuals from four populations and digested with eight different enzymes only one intraindividual polymorphism was found that occurred in each population. When the amplified ITS-1 region was sequenced from an additional 10 individuals from five populations, no interindividual variation was found in the sequence. A 6-kb portion of the rDNA repeat unit including 1.6 kb of the 18S coding region, the 5′ external spacer region (5′ ETS), and part of the adjacent intergenic spacer was cloned and a restriction map was prepared for these regions in lake trout. No intraspecific variation was found in the region adjacent to the 18S rDNA, which includes the 5′ ETS, although intraspecific and intraindividual length variation was found in the intergenic spacer region 3–6 kb from the 18S. Sequencing of a 609-b segment of the 5′ ETS adjacent to the 18S coding region revealed the presence of two 41-b repeats. The 198-b sequence between the repeats had some similarity to the 18S coding region of other fishes. Primers were designed for amplification of 559 b of the 5′ ETS using the polymerase chain reaction. No intraspecific variation in this region in lake trout was found when the DNA amplified from this region in 12 individuals from four populations was digested with eight restriction enzymes.Key words: ribosomal DNA, internal transcribed spacer regions, 5′ external spacer region, transcribed spacer, lake trout.

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39

Peslin, R., C. Duvivier, H. Bekkari, E. Reichart y C. Gallina. "Stress adaptation and low-frequency impedance of rat lungs". Journal of Applied Physiology 69, n.º 3 (1 de septiembre de 1990): 1080–86. http://dx.doi.org/10.1152/jappl.1990.69.3.1080.

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At transpulmonary pressures (Ptp) of 7-12 cmH2O, pressure-volume hysteresis of isolated cat lungs has been found to be 20-50% larger than predicted from their amount of stress adaptation (J. Hildebrandt, J. Appl. Physiol. 28: 365-372, 1970). This behavior is inconsistent with linear viscoelasticity and has been interpreted in terms of plastoelasticity. We have reinvestigated this phenomenon in isolated lungs from 12 Wistar rats by measuring 1) the changes in Ptp after 0.5-ml step volume changes (initial Ptp of 5 cmH2O) and 2) their response to sinusoidal pressure forcing from 0.01 to 0.67 Hz (2 cmH2O peak to peak, mean Ptp of 6 cmH2O). Stress adaptation curves were found to fit approximately Hildebrandt's logarithmic model [delta Ptp/delta V = A - B.log(t)] from 0.2 to 100 s, where delta V is the step volume change, A and B are coefficients, and t is time. A and B averaged 1.06 +/- 0.11 and 0.173 +/- 0.019 cmH2O/ml, respectively, with minor differences between stress relaxation and stress recovery curves. The response to sinusoidal forcing was characterized by the effective resistance (Re) and elastance (EL). Re decreased from 2.48 +/- 0.41 cmH2O.ml-1.s at 0.01 Hz to 0.18 +/- 0.03 cmH2O.ml-1.s at 0.5 Hz, and EL increased from 0.99 +/- 0.10 to 1.26 +/- 0.20 cmH2O/ml on the same frequency range. These data were analyzed with the frequency-domain version of the same model, complemented by a Newtonian resistance (R) to account for airway resistance: Re = R + B/ (9.2f) and EL = A + 0.25B + B . log 2 pi f, where f is the frequency.(ABSTRACT TRUNCATED AT 250 WORDS)

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40

Fidias, P., T. A. Ciuleanu, O. Gladkov, G. M. Manikhas, I. N. Bondarenko, A. Pluzanska, R. Ramlau y T. J. Lynch. "A randomized, open-label, phase III trial of NOV-002 in combination with paclitaxel (P) and carboplatin (C) versus paclitaxel and carboplatin alone for the treatment of advanced non-small cell lung cancer (NSCLC)." Journal of Clinical Oncology 28, n.º 18_suppl (20 de junio de 2010): LBA7007. http://dx.doi.org/10.1200/jco.2010.28.18_suppl.lba7007.

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LBA7007 Background: NOV-002 is a formulation of disodium glutathione disulfide (GSSG). GSSG is a naturally occurring substance that functions as a component of the glutathione (GSH) pathway, vital to the regulation of the intracellular redox state. A key function of the GSH/GSSG redox couple is to dynamically regulate protein functions, including cell signaling pathways, through the reversible formation of mixed disulfides between protein cysteines and GSH (S-glutathionylation). Based on positive results from a randomized, phase I/II study of carboplatin and paclitaxel (CP) with or without NOV-002, as well as positive results from 2 ex-U.S. phase II studies with cisplatin-based chemotherapy, an international phase III randomized trial was launched. Methods: Patients with advanced NSCLC (stages wet IIIB and IV, inclusive of all histological subtypes) were eligible if they had a PS of 0-1 and adequate end-organ function. Patients with CNS metastases were excluded. Eligible patients were randomized to C (AUC 6), P (200 mg/m2), and NOV-002 (Group A) or C and P alone (Group B). NOV-002 was administered as two-60 mg IV boluses on day -1 of cycle 1 and as one IV bolus on day 1 of each cycle, followed by daily 60-mg subcutaneous injections. A total of 725 events were required to detect a difference in overall survival (OS) from 10.0 to 12.5 months with 85% power and a two-sided significance level of 0.05. No interim analysis was performed. Results: From 11/06 until 9/09, 903 patients were randomized, with target enrollment reached in March 2008. Patient characteristics for Groups A and B were as follows: stage IV (91.5/90.8%), PS 1 (76.6/72.6%), male (69.9/72.4%), never smoker (22.3/19.1%) median age (59.6/59.5), and histology (adenocarcinoma [40.0/36.8%] squamous [41.2/40.8%]). The median overall survival for Groups A and B was 10.2/10.8 months (p = 0.375), median progression-free survival was 5.3/5.6 months, objective response rate was 26.6/26.0% and 54/53% of patients completed at least six cycles of chemotherapy. Major toxicities for Groups A and B included grade 3/4 neutropenia (29.7/26.3%), febrile neutropenia (2.2/1.8%), grade 3/4 thrombocytopenia (3.8/2.9%), and grade 3/4 neuropathy (2.9/2.4%). Adverse events resulting in death in Groups A and B were reported in 5.6 and 3.1%, respectively. Conclusions: The addition of NOV-002 to CP does not improve overall survival in patients with advanced NSCLC. NOV002 does not appear to add to the overall toxicity of chemotherapy. [Table: see text]

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Rusconi, Chiara, Maria Luisa Guerrera, Alessandra Tedeschi, Michelle Zancanella, Manuel Gotti, Michele Nichelatti, Sara Rattotti et al. "Outcome of Transformed Marginal Zone Lymphomas Treated in the Rituximab Era". Blood 126, n.º 23 (3 de diciembre de 2015): 5098. http://dx.doi.org/10.1182/blood.v126.23.5098.5098.

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Abstract Introduction: Transformation of Marginal Zone Lymphoma (MZL) into an aggressive histology is uncommon phenomenon that can occur at any time after diagnosis and is expected to have a detrimental impact on prognosis. Biological and clinical knowledge on transformed Marginal Zone Lymphoma (tMZL) is poor and no standard treatment is established in the Rituximab era for these patients (pts). We retrospectively analyzed all consecutive biopsy proven tMZL in two Italian Hematological Divisions from 2002 to 2014 and we focused on post-transformation treatment and outcome. Methods: The dataset included 378 MZL pts diagnosed between 2002 and 2014 at Division of Hematology in Pavia and in Milan (Niguarda Hospital): 204 pts (53.9%) by extranodal MALT lymphomas, 113 pts (29.8%) by splenic MZL, and 61 pts (16.3%) by nodal MZL. Histological transformation (HT) was defined as transformation into an aggressive lymphoma at any time from previous MZL diagnosis; only cases with biopsy confirmed HT were comprised in the present analysis, while cases with only clinical suspicion of transformation were not counted as tMZL. Results: HT was documented in 18 of the 378 pts (4.8%), 6.5% in nodal MZL, 7.0% in splenic MZL and 2.9% in MALT. Histology at transformation was Diffuse Large B-Cell lymphoma in all but one case; the remaining pt was diagnosed as high-grade B-cell lymphoma, unclassifiable. CD20 was negative only in one Rituximab-naïve pt. Median time from first diagnosis to HT was 31 months (range: 10-124) and median number of previous therapies was 1 (range 0-1); pts received first line therapy listed in table 1. Median age at transformation was 68 years (range: 46-85), M/F ratio was 0.8. In the tMZL population, first diagnosis was nodal MZL in 4 pts (22%), splenic MZL in 8 pts (45%) and MALT in 6 pts (33%). At first diagnosis of MZL, 72% of t-MZL pts had stage IV disease, 17% had B symptoms, 11% had elevated LDH and ECOG performance status was lower than 2 in all the cases. HCV serology was positive in 5/17 cases; HCV status was not available for one pt. At HT disease stage was III or IV in 14 pts (78%), B symptoms were present in 7 pts (39%), LDH and beta2microglobulin were both elevated in 7 pts (39%) and ECOG performance status was lower than 2 in all the cases. Pts received post-HT treatment listed in table 2. At time of analysis 6 pts died (33%), and the main cause of death was progressive disease. With a median post-transformation follow-up of 16.6 months (range: 2-98), the 2-years Progression-Free Survival (PFS) was 45,4 % and the 2-years Overall Survival (OS) was 56.75%. No correlation was found between the following characteristics and survival: MZL type at first diagnosis, stage, symptoms, LDH and ECOG at HT, number and types of pre-HT therapies. Conclusions: This large cohort confirms that HT is a relatively rare and early event in MZL. At present time, we did not identify any feature predictive of outcome for transformed MZL. Chemotherapy in combination with Rituximab showed to be an effective treatment for tMZL. Table 1 First line treatment N. of patients % Therapy strategy CVP 7 39 Anthracycline-containing regimen 2 11 Chlorambucil monotherapy 5 28 Splenectomy 1 5.5 H.pylori eradication 1 5.5 Watch and wait strategy 2 11 Rituximab incorporation Included in first line therapy 6 33 Maintenance 0 0 Response ORR (%) 67 CRR (%) 33 Table 2. Post-HT treatment N. of patients % Therapy strategy CHOP regimen 16 89 Platinum-containing regimen 1 5.5 Missing 1 5.5 Rituximab incorporation Included in first line therapy 17 94 Maintenance 0 0 ASCT consolidation 3 17 Response ORR (%) 61 CRR (%) 59 Disclosures Rusconi: Roche: Honoraria.

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Vose, Julie M., Shelly Carter, Linda J. Burns, Ernesto Ayala, Oliver W. Press, Craig H. Moskowitz, Edward A. Stadtmauer et al. "Phase III Randomized Study of Rituximab/Carmustine, Etoposide, Cytarabine, and Melphalan (BEAM) Compared With Iodine-131 Tositumomab/BEAM With Autologous Hematopoietic Cell Transplantation for Relapsed Diffuse Large B-Cell Lymphoma: Results From the BMT CTN 0401 Trial". Journal of Clinical Oncology 31, n.º 13 (1 de mayo de 2013): 1662–68. http://dx.doi.org/10.1200/jco.2012.45.9453.

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PurposeThis clinical trial evaluated standard-dose radioimmunotherapy with a chemotherapy-based transplantation regimen followed by autologous hematopoietic cell transplantation versus rituximab with the same regimen in patients with relapsed diffuse large B-cell lymphoma (DLBCL).Patients and MethodsPatients with chemotherapy-sensitive persistent or relapsed DLBCL were randomly assigned to receive iodine-131 tositumomab (dosimetric dose of 5 mCi on day −19 and therapeutic dose of 0.75 Gy on day −12), carmustine 300 mg/m2(day −6), etoposide 100 mg/m2twice daily (days −5 to −2), cytarabine 100 mg/m2twice daily (days −5 to −2), and melphalan 140 mg/m2(day −1; B-BEAM) or rituximab 375 mg/m2on days −19 and −12 and the same chemotherapy regimen (R-BEAM).ResultsTwo hundred twenty-four patients were enrolled, with 113 patients randomly assigned to R-BEAM and 111 patients assigned to B-BEAM. Two-year progression-free survival (PFS) rates, the primary end point, were 48.6% (95% CI, 38.6% to 57.8%) for R-BEAM and 47.9% (95% CI, 38.2% to 57%; P = .94) for B-BEAM, and the 2-year overall survival (OS) rates were 65.6% (95% CI, 55.3% to 74.1%) for R-BEAM and 61% (95% CI, 50.9% to 69.9%; P = .38) for B-BEAM. The 100-day treatment-related mortality rates were 4.1% (95% CI, 0.2% to 8.0%) for R-BEAM and 4.9% (95% CI, 0.8% to 9.0%; P = .97) for B-BEAM. The maximum mucositis score was higher in the B-BEAM arm (0.72) compared with the R-BEAM arm (0.31; P < .001).ConclusionThe B-BEAM and R-BEAM regimens produced similar 2-year PFS and OS rates for patients with chemotherapy-sensitive relapsed DLBCL. No differences in toxicities other than mucositis were noted.

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Fernández, M., M. L. Ruiz, C. Linares, A. Fominaya y M. Pérez de la Vega. "5S rDNA genome regions of Lens species". Genome 48, n.º 5 (1 de octubre de 2005): 937–42. http://dx.doi.org/10.1139/g05-052.

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The length variability of the nontranscribed spacer (NTS) of the 5S rDNA repeats was analyzed in species of the genus Lens by means of PCR amplification. The NTS ranged from ~227 to ~952 bp. The polymorphism detected was higher than previous NTS polymorphisms described in this genus. Three NTS length variants from Lens culinaris subsp. culinaris and 2 from Lens culinaris subsp. orientalis were sequenced. The culinaris NTS fragment lengths were 239, 371, and 838 bp, whereas the orientalis ones were 472 bp and 506 bp, respectively. As a result of sequence similarities, 2 families of sequences were distinguished, 1 including the sequences of 838 and 506 bp, and others with the sequences of 239, 371, and 472 bp. The 1st family was characterized by the presence of a repeated sequence designated A, whereas the 2nd family showed a single A sequence and other repeated sequences designated B, C, and D. The presence of an (AT)n microsatellite was also observed in the 2nd family of sequences. The fragments, which included the 239-bp and 838-bp NTS sequences, as well as the intergenic spacer (IGS) of the 18S–5.8S–26S ribosomal DNA also from L. culinaris subsp. culinaris, were used to localize the nucleolar organizer region (NOR) and the 5S rDNA loci in the chromosomes of several species of the genus Lens by means of fluorescence in situ hybridization (FISH). The selective hybridization of the 2 NTS probes allowed us to distinguish between different 5S rDNA chromosomal loci.Key words: Lens, lentil, ribosomal loci, 5S, FISH, NTS polymorphism, NOR.

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Ma, Fei, Lixi Li, Zongbi Yi, Jianming Shi, Hua Jiang, Chen Chen, Pingping Dai et al. "The prevalence of BRCA1/2 germline mutation in Chinese pan-cancer." Journal of Clinical Oncology 38, n.º 15_suppl (20 de mayo de 2020): e13684-e13684. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.e13684.

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e13684 Background: Pathogenic variants in cancer predisposition genes BRCA1/2 confer susceptibility to breast and ovarian cancer and well-studied. But the characteristics of BRCA in other cancers is unknown, we identified and characterized BRCA germline variants in a large pan-cancer in China. Methods: NGS was performed on genomic DNA from 29,676 pan-cancer patients. Large fragment deletions were all verified by QPCR. We integrated guidelines of ACMG/AMP, ENIGMA and China expert consensus. Based on the in-house system, variants were interpreted one-by-one and classified into 5 grades: Benign (B), Likely Benign(LB), Variant of Uncertain significance(VUS), Likely pathogenic (LP), Pathogenic (P). Results: Among 29,676 patients, 300 BRCA1 mutations and 440 BRCA2 mutations were detected in our study. The proportion among P/LP/VUS/LB/B were 36.1%, 11.6%, 36.6%, 11.1% and 4.6%. Consistent with previous reports, the mutations spread around the whole genes. Missense and frameshift were most common types in BRCA1 (40%, 25.3%) and BRCA2 (42.3%, 29.3%). 192(25.9%) mutations were not reported in any of the databases. Among these newly reported mutations, 32 (16.7%) were classified as P, 62 (32.3%) LP and 98 (51%) VUS. Totally, 522 (1.8%) patients were identified with P/LP BRCA1/2 mutations. No founder mutations in Chinese population were defined, but BRCA1 5470_5477delATTGGGCA (I1824Dfs*3) and BRCA2 3109C > T (Q1037*) had the highest prevalence indicating the common P/LP mutations in Chinese. On the whole, BRCA-associated hereditary cancer harbored higher P/LP percent than other cancer types (11.1% vs 0.7%). Different distribution and percent were observed in BRCA1 and BRCA2, the P/LP mutations were found in double primary cancers of breast and ovary (76.9% vs 38.5%), followed by ovarian cancer (15.5% vs 6.3%), breast cancer(3.8% vs 4.0%), endometrial cancer(1.6% vs 2.4%), prostatic cancer(1.3% vs 1.9%), pancreatic cancer (0.3% vs 1.8%), biliary tract tumor (0% vs 1%), thyroid cancer (0% vs 0.9%), NSCLC(0.2% vs 0.5%) and colorectal cancer(0.08% vs 0.4%). Except for SNV/Indels, large range heterozygous deletions were found in 9 patients, including 4 (0.6%) OC, 4 (0.2%) BC and 1 NSCLC, almost all interfering with BRCA1. Conclusions: This analysis depicted a comprehensive landscape of germline BRCA1/2 variants in Chinese pan-cancer. Besides breast and ovarian cancer, lots of other cancers also harbor BRCA germline mutation, retrospective family history and hereditary cancer risk assessment needs further study.

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Lapierre, Jean-Marc, Sudharshan Eathiraj, David Vensel, Yanbin Liu, Cathy O. Bull, Susan Cornell-Kennon, Shin Iimura et al. "Discovery of 3-(3-(4-(1-Aminocyclobutyl)phenyl)-5-phenyl-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine (ARQ 092): An Orally Bioavailable, Selective, and Potent Allosteric AKT Inhibitor". Journal of Medicinal Chemistry 59, n.º 13 (29 de junio de 2016): 6455–69. http://dx.doi.org/10.1021/acs.jmedchem.6b00619.

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Perez-Villar, Juan J., Gena S. Whitney, Michael A. Bowen, Derek H. Hewgill, Alejandro A. Aruffo y Steven B. Kanner. "CD5 Negatively Regulates the T-Cell Antigen Receptor Signal Transduction Pathway: Involvement of SH2-Containing Phosphotyrosine Phosphatase SHP-1". Molecular and Cellular Biology 19, n.º 4 (1 de abril de 1999): 2903–12. http://dx.doi.org/10.1128/mcb.19.4.2903.

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ABSTRACT The negative regulation of T- or B-cell antigen receptor signaling by CD5 was proposed based on studies of thymocytes and peritoneal B-1a cells from CD5-deficient mice. Here, we show that CD5 is constitutively associated with phosphotyrosine phosphatase activity in Jurkat T cells. CD5 was found associated with the Src homology 2 (SH2) domain containing hematopoietic phosphotyrosine phosphatase SHP-1 in both Jurkat cells and normal phytohemagglutinin-expanded T lymphoblasts. This interaction was increased upon T-cell receptor (TCR)-CD3 cell stimulation. CD5 co-cross-linking with the TCR-CD3 complex down-regulated the TCR-CD3-increased Ca2+ mobilization in Jurkat cells. In addition, stimulation of Jurkat cells or normal phytohemagglutinin-expanded T lymphoblasts through TCR-CD3 induced rapid tyrosine phosphorylation of several protein substrates, which was substantially diminished after CD5 cross-linking. The CD5-regulated substrates included CD3ζ, ZAP-70, Syk, and phospholipase Cγl but not the Src family tyrosine kinase p56 lck . By mutation of all four CD5 intracellular tyrosine residues to phenylalanine, we found the membrane-proximal tyrosine at position 378, which is located in an immunoreceptor tyrosine-based inhibitory (ITIM)-like motif, crucial for SHP-1 association. The F378 point mutation ablated both SHP-1 binding and the down-regulating activity of CD5 during TCR-CD3 stimulation. These results suggest a critical role of the CD5 ITIM-like motif, which by binding to SHP-1 mediates the down-regulatory activity of this receptor.

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de Oliveira, Rosilane Gomes de Souza, Arley Faria José de Oliveira y Marle Angélica Villacorta Correa. "Sperm abnormalities in matrinxã Brycon amazonicus after hormonal treatment with carp pituitary extract and Ovaprim™". Zygote 26, n.º 4 (agosto de 2018): 279–85. http://dx.doi.org/10.1017/s0967199418000199.

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SummaryThe aim of this study was to evaluate if hormonal treatment causes changes in the morphology of matrinxã Brycon amazonicus spermatozoa. Twelve males were randomized into three treatment groups: 1, Ovaprim™ (0.5 ml/kg); 2, carp pituitary extract (CPE; 2.0 mg/kg); and 3, NaCl solution 0.9% – control group (0.5 ml/kg); with four replicates. Morphological sperm analysis was performed using an optical and scanning electron microscope. The percentage of normal spermatozoa (49.6±4.6% to 60.8±2.8%), with primary (26.1±6.4% to 45.3±4.5%) and secondary abnormalities (4.4±2.9% to 13.9±3.5%) did not differ significantly between treatment groups. There were no significant differences between treatments in relation to the primary abnormalities found in the head (10.5±3.8% to 25.5±6.3%), the midpiece (0.1±0.1% to 0.2±0.2%) and in the flagellum (18.9±3.8% to 15.5±3.1%), as well as in the secondary abnormalities, located in the head (0.8±0.4% to 7.8±4.6%) and in the flagellum (2.2±1.1% to 6.1±1.5%). When each abnormality was evaluated individually, only the percentage of degenerated head was higher in the CPE-induced group (24.9±5.9%) than the control group (7.2±3.1%). We concluded that the use of pituitary extract of carp or Ovaprim™ under the conditions of this experiment does not influence the percentage of sperm abnormalities in B. amazonicus.

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Winkler, U., M. Jensen, O. Manzke, H. Schulz, V. Diehl y A. Engert. "Cytokine-Release Syndrome in Patients With B-Cell Chronic Lymphocytic Leukemia and High Lymphocyte Counts After Treatment With an Anti-CD20 Monoclonal Antibody (Rituximab, IDEC-C2B8)". Blood 94, n.º 7 (1 de octubre de 1999): 2217–24. http://dx.doi.org/10.1182/blood.v94.7.2217.419k02_2217_2224.

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Eleven patients with relapsed fludarabine-resistant B-cell chronic lymphocytic leukemia (CLL) or leukemic variants of low-grade B-cell non-Hodgkin’s lymphoma (NHL) were treated with the chimeric monoclonal anti-CD20 antibody rituximab (IDEC-C2B8). Peripheral lymphocyte counts at baseline varied from 0.2 to 294.3 × 109/L. During the first rituximab infusion, patients with lymphocyte counts exceeding 50.0 × 109/L experienced a severe cytokine-release syndrome. Ninety minutes after onset of the infusion, serum levels of tumor necrosis factor- (TNF-) and interleukin-6 (IL-6) peaked in all patients. Elevated cytokine levels during treatment were associated with clinical symptoms, including fever, chills, nausea, vomiting, hypotension, and dyspnea. Lymphocyte and platelet counts dropped to 50% to 75% of baseline values within 12 hours after the onset of the infusion. Simultaneously, there was a 5-fold to 10-fold increase of liver enzymes, d-dimers, and lactate dehydrogenase (LDH), as well as a prolongation of the prothrombin time. Frequency and severity of first-dose adverse events were dependent on the number of circulating tumor cells at baseline: patients with lymphocyte counts greater than 50.0 × 109/L experienced significantly more adverse events of National Cancer Institute (NCI) grade III/IV toxicity than patients with less than 50.0 × 109/L peripheral tumor cells (P= .0017). Due to massive side effects in the first patient treated with 375 mg/m2 in 1 day, a fractionated dosing schedule was used in all subsequent patients with application of 50 mg rituximab on day 1, 150 mg on day 2, and the rest of the 375 mg/m2 dose on day 3. While the patient with the leukemic variant of the mantle-cell NHL achieved a complete remission (9 months+) after treatment with 4 × 375 mg/m2 rituximab, efficacy in patients with relapsed fludarabine-resistant B-CLL was poor: 1 partial remission, 7 cases of stable disease, and 1 progressive disease were observed in 9 evaluable patients with CLL. On the basis of these data, different infusion schedules and/or combination regimens with chemotherapeutic drugs to reduce tumor burden before treatment with rituximab will have to be evaluated.

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Pereira, Márcia Cristina de Araújo, Carlos Alberto Vieira de Azevedo, José Dantas Neto, Mariana de Oliveira Pereira, Jailton Garcia Ramos y Beatriz de Araújo Tomaz. "CRESCIMENTO DE CULTIVARES DE PALMA FORRAGEIRA IRRIGADA SOB DIFERENTES NÍVEIS DE SALINIDADE EM REGIÃO SEMIÁRIDA". IRRIGA 26, n.º 4 (22 de diciembre de 2021): 814–26. http://dx.doi.org/10.15809/irriga.2021v26n4p814-826.

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CRESCIMENTO DE CULTIVARES DE PALMA FORRAGEIRA IRRIGADA SOB DIFERENTES NÍVEIS DE SALINIDADE EM REGIÃO SEMIÁRIDA MÁRCIA CRISTINA DE ARAÚJO PEREIRA1; CARLOS ALBERTO VIEIRA DE AZEVEDO 2; JOSÉ DANTAS NETO 3; MARIANA DE OLIVEIRA PEREIRA 4; JAILTON GARCIA RAMOS 5 E BEATRIZ DE ARAÚJO TOMAZ 6 1 Programa de Pós-Graduação em Engenharia Agrícola, Universidade Federal de Campina Grande, Rua Aprígio Veloso, 882, Bairro Universitário, 58428-830, Campina Grande, Paraíba, Brasil. E-mail: marciacristina794@gmail.com. 2 Programa de Pós-Graduação em Engenharia Agrícola, Universidade Federal de Campina Grande, Rua Aprígio Veloso, 882, Bairro Universitário,58428-830, Campina Grande, Paraíba, Brasil. E-mail: cvieiradeazevedo@gmail.com. 3 Programa de Pós-Graduação em Engenharia Agrícola, Universidade Federal de Campina Grande, Rua Aprígio Veloso, 882- Bairro Universitário,58428-830, Campina Grande, Paraíba, Brasil. E-mail: zedantas1955@gmail.com. 4 Pós-doutoranda em Engenharia Agrícola, Rua Aprígio Veloso, 882 -Universitário, Campina Grande -PB, Brasil. 58428-830, E-mail: marianapereira.agri@gmail.com 5 Programa de Pós-Graduação em Engenharia Agrícola, Universidade Federal de Campina Grande, Rua Aprígio Veloso, 882, Bairro Universitário,58428-830, Campina Grande, Paraíba, Brasil. E-mail: jailtonbiossistemas@gmail.com. 6 Unidade Acadêmica de Engenharia Agrícola, Universidade Federal de Campina Grande, Rua Aprígio Veloso, 882, Bairro Universitário, 58428-830, Campina Grande, Paraíba, Brasil. E-mail: beatrizatomaz2@gmail.com 1 RESUMO A palma forrageira se destaca por ser uma cultura bem adaptada às condições edafoclimáticas do semiárido brasileiro, pois apresenta características anatômicas, morfofisiológicas e químicas que possibilitam seu desenvolvimento. Objetivou-se nesse trabalho avaliar o efeito de diferentes níveis de salinidade da água de irrigação, no crescimento de cultivares de palma forrageira na região do semiárido. O delineamento experimental foi em blocos casualizados em esquema fatorial 4 x 3, com quatro níveis salinos (0,2; 2,0; 3,8 e 5,6 dS m-1) e três cultivares (Miúda, Orelha de Elefante Mexicana e IPA-Sertânia), quatro repetições. Foram avaliadas as variáveis altura de planta, largura de planta, comprimento, largura, perímetro e espessura dos cladódios primários. As variáveis foram submetidas a análise de variância pelo teste F ao nível de 1 e 5% de probabilidade, quando significativo foram submetidos à análise de regressão linear e quadrática para variáveis quantitativas e teste de Tukey (p < 0,05) para a variável qualitativa. O desenvolvimento da palma forrageira irrigada com diferentes níveis salinos foi influenciado com o aumento da salinidade, sendo que a melhor condição para a cultivar Miúda foi a salinidade de 3,8 dS m-1, já para Baiana e Orelha de Elefante Mexicana foi a salinidade de 2,0 dS m-1. Palavras-chave: Opuntias, Napolea, Águas Salinas, Semiárido. PEREIRA, M. C. de A.; AZEVEDO, C. A. V. de; DANTAS NETO, J.; PEREIRA, M. de O.; RAMOS, J. G.; TOMAZ, B. de A. GROWTH OF IRRIGATED FORAGE PALM CULTIVARS UNDER DIFFERENT SALINITY LEVELS IN A SEMI-ARID REGION 2 ABSTRACT The forage palm stands out for being a crop well adapted to the edaphoclimatic conditions of the Brazilian semiarid region, for it presents anatomical, morphophysiological, and chemical characteristics that enable its development. This work aimed to evaluate the effect of different levels of salinity of irrigation water on the growth of forage palm cultivars in the semiarid region. The experimental design was in randomized blocks in a 4 x 3 factorial scheme, with four salt levels (0.2; 2.0; 3.8 and 5.6 dS m-1) and three cultivars (Miúda, Mexican Orelha de Elefante, and IPA-Sertânia), four repetitions. The variables of plant height, plant width, length, width, perimeter and thickness of the primary cladodes were evaluated. The variables were subjected to analysis of variance by the F test at the level of 1 and 5% probability, when significant were subjected to linear and quadratic regression analysis for quantitative variables and Tukey test (p < 0.05) for the qualitative variable. The development of the forage palm irrigated with different saline levels was influenced with increasing salinity, and the best condition for the cultivar Miúda was a salinity of 3.8 dS m-1, and for Baiana and Mexican Elephant's Ear was salinity of 2.0 dS m-1. Keywords: Opuntias, Napolea, Saline Water, Semi-arid.

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Greenberg, Mark, Vitaly Shteiman y Menahem Kaftory. "Topochemically controlled solid-state methyl rearrangement in thiocyanurates". Acta Crystallographica Section B Structural Science 57, n.º 3 (25 de mayo de 2001): 428–34. http://dx.doi.org/10.1107/s0108768101005171.

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4,6-Dimethoxy-3-methyl-1,3,5-triazine-2(3H)-thione crystallizes in two polymorphic forms, needles and plates. In the needle-shaped crystals (9a) the molecules occupy the crystallographic mirror plane, thus the layers are stacked along the b axis. The molecules of the other polymorph [plate-shape crystals, (9b)] are packed in a herringbone packing mode. Upon heating, (9b) undergoes a phase transition to form (9a). At 378 K the needles undergo O → S topochemically controlled methyl transfer in the solid state to produce 1-methyl-4-methoxy-6-methylthio-1,3,5-triazine-2(1H)-one in 75% yield. The enthalpy of the rearrangement is estimated to be −39.1 kJ mol−1. 1-Methyl-6-methoxy-4-methylthio-1,3,5-triazine-2(1H)-thione crystallizes in space group P21 with two crystallographically independent molecules in the asymmetric unit. Compound (9b) undergoes O → S methyl transfer in the solid state at 373 K. The rearrangement is topochemically assisted and the product, 1-methyl-2,4-bismethylthio-1,3,5-triazine-6(1H)-one, is obtained in quantitative yield. The enthalpy of the rearrangement is estimated to be −58.8 kJ mol−1. The crystal structures of the compounds as well as their DSC thermographs are described and discussed. Energy calculation by ab initio methods shows that the driving force for the reactions is the difference between the molecular energies of the pre-rearranged compounds and their products, 54.2 and 59.3 kJ mol−1 in the two cases, respectively.

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