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Gyawali, Chetan, Bhimsen Chaulagain, Sangita Kaduwal, Pankaj Gyawaly, Prakash Paneru, Narayan Khatri, and Prakash Pantha. "Performance of Promising Rice Genotypes as Affected by Different Nitrogen Levels in Central Terai of Nepal." Agronomy Journal of Nepal 7 (July 10, 2023): 111–20. http://dx.doi.org/10.3126/ajn.v7i1.62165.
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Application of appropriate level of nitrogen (N) for rice is a key to increase nitrogen use efficiency thereby yields. Six rice genotypes under six N levels were evaluated in a split plot design with three replications under irrigated conditions in National Rice Research Program, Dhanusha during 2020 with the objective of determining the high yielding variety and the best dose of N for obtaining higher yield. The six rice genotypes were NR 2168, NR 2158, NR 2157-122, NR 2175, NR 2182 and PR 126 while various N levels were 0. 75, 100, 125, 150 and 175 kg N ha-1. The results indicated that NR 2182 recorded the highest grain yield of 5.28 t ha-1 while PR 126 recorded the lowest grain yield 3.98 t ha-1. A linear increase in grain yield was observed with a continuous increase in N level from 0 to 150 kg ha-1 while it decreased thereafter. The grain yield was significantly higher with the application of 150 kg N ha-1 as compared to control. Agronomic N use efficiency for studied rice genotypes varied significantly and ranged from negative to 12.63 kg grain yield per kg of N applied. NR 2182 recorded the highest value of agronomic nitrogen use efficiency for the N level of 150 kg ha-1. It can be concluded that increasing nitrogen levels resulted in significant variations in the response of different varieties, with all varieties consistently recording lower yields at highest N levels. Thus, opting for an intermediate N level appears both economically prudent and environmentally sustainable.
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Fang, Miao-Miao, Hong Yan, Xian-Chen Song, and Yong-Hui Sun. "Effect of (Pr+Ce) Additions on Microstructure and Mechanical Properties of AlSi5Cu1Mg Alloy." Applied Sciences 9, no. 9 (May 6, 2019): 1856. http://dx.doi.org/10.3390/app9091856.
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The microstructure and mechanical properties of AlSi5Cu1Mg alloy with (Pr+Ce) addition were investigated by optical microscopy (OM), energy dispersive spectroscopy (EDS), and scanning electron microscopy (SEM). The results demonstrated that the rare earth (Pr+Ce) addition refined the grain. The long needle-like eutectic Si phases turned to granual. The secondary dendrite arm spacing (SADS) of the primary α-Al phase with the AlSi5Cu1Mg+0.6 wt.% (Pr+Ce) alloy reached the minimum value, which decreased by 50.2%. The mean length and the aspect ratio of the eutectic Si decreased by 78.8% and 67.4%. The ultimate tensile strength (UTS), the microhardness, and the breaking elongation of the AlSi5Cu1Mg+0.6 wt.% (Pr+Ce) alloy reached a maximum, and increased by 21.5%, 21.7%, and 8.0% compared to the AlSi5Cu1Mg alloy. The fracture examinations manifested in cleaved surfaces and brittle fracture areas, which were seen from the AlSi5Cu1Mg+0.6 wt.% (Pr+Ce) alloy. The number of dimples slightly increased.
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Almudallal, Mohammed W., and Norhani Bakri. "Examining the Role of Public Relations Departments in Universities and their Relationships with the Graduates in Palestine." Journal of Business and Social Review in Emerging Economies 3, no. 1 (June 30, 2017): 101–8. http://dx.doi.org/10.26710/jbsee.v3i1.183.
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Purpose: This paper aims to examine the role of public relations departments in universities and how they deal with graduates. Universities in general have PR departments that are created to increase the missions and strengthen the visions. Frequently, the PR department is responsible for enhancing the objectives of the university to improve its image to publics. This study therefore investigates the extent of the PR role as a tool for facilitating the achievement of the objectives of universities. Data for the study was collected from a sample of one hundred and twenty (120) respondents sampled from graduates of the university. Which %78.3 males and %21.7 females from different districts in Gaza Strip in Palestine. Findings from the study showed that the administration of the PR departments reinforces the affiliation of graduates to their universities. Furthermore, the PR departments mainly participate in holding graduation ceremonies and in coordinating with other departments. The PR departments continue with the graduates to assist them find suitable careers in the future. They also communicate with the graduates through various means of social connectivity websites.
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MLIK, Randa, Salim Meddour, Nour Elhouda Mekhadmi, Amar Eddoud, Karim Souttou, and Makhlouf Sekour. "FIRST DATA ON BACTERIAL, FUNGAL AND PARASITIC INFECTIONS OF BLACK RATS (RATTUS RATTUS) FROM THE PALM GROVES OF THE ALGERIAN SAHARA." Journal of microbiology, biotechnology and food sciences 13, no. 5 (January 31, 2024): e10186. http://dx.doi.org/10.55251/jmbfs.10186.
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The present study aimed to detect the parasitic fauna associated with black rats (Rattus rattus) from southeastern Algeria. It showed the presence of seven species of parasitic fungi namely Penicillium sp. (Prevalence Pr=91.3%), Aspergillus niger (Pr=91.3%), Alternaria sp. (Pr=58.7%), Cladosporium sp. (Pr=87%), Microsporum sp. (Pr=19.6%), Trichophyton sp. (Pr=21.7%) and Chrysosporium sp. (Pr=10.9%), noting that saprophytic fungi were the most recorded. On the other hand, according to the richness (S), adults (S = 7) and sub-adults (S = 7) of black rats were the most infested, with leaning for males compared to females, considering all the isolated species as satellites except the Chrysosporium sp. (2.9%) which is presented as a rare species. Concerning parasitic bacteria, aged rats were the most infected followed by adults and sub-adults where total coliforms were present in all individuals of the three classes tested. However, fecal streptococci were noted with a similar infestation rate in all age groups. Unlike this, clostridium sulfite-reducer (CSR) was mostly recorded on aged rats. Concerning the endoparasites found in the intestines of black rats, the pinworms (Syphacia muris, Syphacia obvelata, and Aspiculuris tetraptera) were more abundant than the other species. Hence, the current study allowed us to demonstrate that black rats can be considered an important reservoir of several microorganisms that can hold germs and represent a threat to biomedical and veterinary public health.
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Cesar, Juraci A., Luana P. Marmitt, and Raúl A. Mendoza-Sassi. "Episiotomy in Southern Brazil: prevalence, trend, and associated factors." Revista de Saúde Pública 56 (April 22, 2022): 26. http://dx.doi.org/10.11606/s1518-8787.2022056003908.
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OBJECTIVE To identify and analyze the prevalence, trend, and factors associated with episiotomy in Rio Grande, in the state of Rio Grande do Sul, Southern Brazil. METHODS A single, standardized questionnaire was applied to all pregnant women, residents in the municipality of Rio Grande, who had children in local hospitals between January 1 and December 12 of the years 2007, 2010, 2013, 2016 e 2019. Demographic and socioeconomic characteristics were investigated, as well as the assistance received during pregnancy and delivery. Chi-square test was used to compare proportions and Poisson regression with robust variance adjustment was used for multivariable analysis. Prevalence ratio (PR) was used as effect measure. RESULTS Among the 12,645 births that occurred in the five years, 5,714 (45.2%) were vaginal delivery. Of these mothers, 2,930 (51.3%; 95%CI: 50.0%–52.6%) underwent episiotomy. Over this period, the episiotomy rate decreased from 70.9% (68.4–73.5) in 2007 to 19.4% (17.1–21.7) in 2019. Adjusted analysis showed a high PR of episiotomy occurrence among women who were young (PR = 2.23; 95%CI: 1.89–2.63), had higher education (PR = 1.21; 95%Cl: 1.03–1.42), had a higher family income (PR = 1.25; 95%CI: 1.10–1.41), were primiparous (PR = 3.41; 95%CI: 2.95–3.95), had prenatal care in the private sector (PR = 1.25; 95%CI: 1.07–1.46), had oxytocin-induced labor (PR = 1.18; 95%CI:1.09–1.27), underwent forceps (PR = 1.32; 95%CI: 1.16–1.50), and whose newborn weighed 4,000 g or more (PR = 1.43; 95%CI: 1.14–1.80). CONCLUSION Although the prevalence of episiotomy fell sharply within the studied period, its occurrence is more likely among women at lower risk of birth complications.
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Ernst, Sophie M., Ronald van Marion, Peggy N. Atmodimedjo, Evert de Jonge, Ron H. Mathijssen, Marthe S. Paats, Peter de Bruijn, Ron H. N. van Schaik, Hendrikus J. Dubbink, and Anne-Marie C. Dingemans. "Abstract 2137: Clinical utility of circulating tumor DNA in patients with advanced KRAS G12C-mutated NSCLC treated with sotorasib." Cancer Research 83, no. 7_Supplement (April 4, 2023): 2137. http://dx.doi.org/10.1158/1538-7445.am2023-2137.
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Abstract Introduction: The CodeBreaK 200 trial showed that in patients (pts) with advanced KRAS G12C mutated (KRAS+) NSCLC sotorasib, a KRAS G12C-specific inhibitor, is superior to docetaxel for progression free survival (PFS) (HR 0.66) with a one-year PFS of 25%. We hypothesized that the detection of circulating tumor DNA (ctDNA) in plasma could allow for treatment response prediction and longitudinal monitoring. We analyzed serial plasma samples at baseline and within 3 months of start of sotorasib to evaluate ctDNA changes and correlation with clinical response. Methods: Pts with sotorasib treated KRAS+ NSCLC were prospectively enrolled in our biomarker START-TKI study (NCT05221372) after written informed consent. Plasma samples were collected prior to treatment (T0) and at first response evaluation (T1). The TruSight Oncology 500 ctDNA panel was used for mutation detection in cell-free DNA (cfDNA). cfDNA KRAS/TP53/STK11/KEAP1 status was determined and compared to tumor tissue pathology reports to filter out false positives. Radiological response and PFS was assessed per RECIST 1.1. Results: Between May 2021 and August 2022, 35 pts were included (table 1). Of these, 29 (83%) had detectable ctDNA KRAS G12C at T0, and 24 had both T0 and T1 samples. A decrease in variant allele frequency (VAF) at T1 compared to T0 was observed in 88% (n=21); 42% (n=10) showed complete clearance of ctDNA KRAS G12C. Six-months PFS was 83% in T0 negative pts (n=6) versus 43% in T0 positive pts (n=29); and 65% in pts with complete clearance (n=10) versus 14% in pts with incomplete clearance (n=11). VAF increase was seen in 3 pts, of which 1 had progression at T1. Conclusions: In pts with KRAS+ NSCLC treated with sotorasib, baseline ctDNA and ctDNA clearance within 3 months of treatment correlated with treatment response. Pts with undetectable KRAS ctDNA at baseline, or with complete clearance at first evaluation, had superior PFS. PFS will be updated as follow-up duration extends. Table 1. Patient cohort Liver metastasis KRAS p.G12C ctDNA at T0, median VAF % (range) KRAS p.G12C ctDNA at T1, median VAF % (range) Median change in VAF % (range) TP53/STK11/KEAP1 ctDNA T0 T1 response Reason EOT ꝉ Time on treatment (months) * Negative at T0 (n=6) No = 6 0 NE NE NE 1x PR; 4x SD; 1x PD 2x PD; 4x ongoing >8 months 6 (1 - 11) Positive at T0 (n=29) No = 20; Yes = 9 2.6 (0.1 - 46.7) 0.6 (0.1 - 38.9) -95% (-100 - +39) 4x TP53; 2x STK11; 1x STK11●; 2x KEAP1; 2x KEAP1●; 2x TP53 + KEAP1; 1x TP53 + STK11● 4x PR; 21x SD; 2x PD; 2x NE 19x PD; 3x toxicity; 6x ongoing >4 months; 1x loss to follow up 3 (1 - 15) Complete clearance at T1 (n=10) No = 6; Yes = 4 1.4 (0.1 - 8.4) 0 100% 2x TP53; 1x TP53 + KEAP1; 1x KEAP1; 1x KEAP1● 1x PR; 9x SD 6x PD; 1x toxicity; 2x ongoing >6 months; 1x loss to follow up 5 (1 - 11) Incomplete clearance at T1 (n=11) No = 7; Yes = 4 3.6 (1.3 - 46.7) 0.4 (0.1 - 29.4) -89% (-23 - -99) 2x TP53; 1x STK11; 1x STK11●; 2x TP53 + STK11●; 1x TP53 + STK11 + KEAP1; 1x STK11 + KEAP1 3x PR; 7x SD; 1x PD 8x PD; 2x toxicity; 1x ongoing >4 months 3 (1 - 8) Increase in VAF at T1 (n=3) No = 2; Yes = 1 1.0 (0.5 - 35.2) 1.1 (0.6 - 38.9) +11% (+10 - +39) 1x TP53●; 1x TP53 + KEAP1; 1x STK11● + KEAP1● 1x PD; 2x SD 3x PD 3 (1 - 15) Positive T0, no T1 available (n=5) No = 5 6.2 (0.3 - 24.6) NE NE 1x TP53; 1x TP53●; 1x KEAP1; 1x STK11 + KEAP1 3x SD; 2x NE 2x PD; 3x ongoing >3 months 2 (1 - 3) NE = Not evaluated; ● = Positive cell-free DNA (cfDNA), not tested in tumor tissue; PR = Partial response; SD = Stable disease; PD = Progressive disease; EOT = End of treatment; ꝉ for PFS analysis patients who discontinued treatment due to toxicity were censored at treatment discontinuation, and patients with ongoing sotorasib treatment were censored at data cut off (16-Nov-2022); * = excluding ongoing patients. Citation Format: Sophie M. Ernst, Ronald van Marion, Peggy N. Atmodimedjo, Evert de Jonge, Ron H. Mathijssen, Marthe S. Paats, Peter de Bruijn, Ron H.N. van Schaik, Hendrikus J. Dubbink, Anne-Marie C. Dingemans. Clinical utility of circulating tumor DNA in patients with advanced KRAS G12C-mutated NSCLC treated with sotorasib [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2137.
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Rex, Anne Sofie, Chunsen Wu, Jørn Aagaard, and Jens Fedder. "DNA Fragmentation in Human Spermatozoa and Pregnancy Rates after Intrauterine Insemination. Should the DFI Threshold Be Lowered?" Journal of Clinical Medicine 10, no. 6 (March 22, 2021): 1310. http://dx.doi.org/10.3390/jcm10061310.
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Sperm DNA fragmentation index (DFI) can be analyzed by a flow cytometric assay after treatment with acid and acridine orange. In this prospective, cohort study, the value of DFI was determined in a semen analysis collected before fertility treatment (baselineDFI) in 146 couples and during 1–3 intrauterine inseminations (IUI) in 211 couples (511 cycles). The pregnancy rate (PR)/cycle was 9.9% if baselineDFI was >10 and 21.7% if baselineDFI was ≤10, (p < 0.005). The live birth rate (LBR)/cycle was 5% if baselineDFI was >10 and 14.2% if baselineDFI was ≤10 (p < 0.005). PR/patient was 23.1% if baselineDFI was >10 and 45.5% if baselineDFI was ≤10 (p < 0.005). LBR/patient was 12.4% if baselineDFI was >10 and 34% if baselineDFI was ≤10 (p < 0.005). When isolating non-stimulated IUI cycles and couples with female age < 35, a significant difference in PR and LBR between couples with high DFI and low DFI was seen. Results suggest that DFI > 10 could advice against timed coitus and non-stimulated IUI cycles. Analysis for DFI performed before treatment provides information about PR and LBR after IUI.
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Popkova, Tereza, Ludek Pour, Ivan Spicka, Jakub Radocha, Alexandra Jungova, Jiri Minarik, Tomas Jelinek, et al. "Survival Analysis of Newly Diagnosed Transplant-Eligible Multiple Myeloma Patients in Czech Republic." Blood 138, Supplement 1 (November 5, 2021): 4894. http://dx.doi.org/10.1182/blood-2021-153978.
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Abstract Introduction: Although highly effective agents and novel therapeutic strategies are being developed, high-dose chemotherapy followed by autologous stem cell transplantation (HDT/ASCT) has not been overcome in the first-line treatment for fit patients (pts) with multiple myeloma. The objective of this work is to retrospectively analyze the use of this procedure in newly diagnosed Czech patients. Methods: Data were derived using the Czech Myeloma Group Registry of Monoclonal Gammopathies. By February 2 nd 2021, a total of 2154 newly diagnosed multiple myeloma patients who underwent HDT/ASCT were identified. Results: At the time of multiple myeloma diagnosis, the median age was 59 years; 24%/56%/14%/5%/1% pts were ECOG 0/1/2/3/4; 44%/32%/24% pts were ISS stage I/II/III; 14.5%/17.5%/68% and 84%/16% pts were Durie-Salmon stage I/II/III and subclassification A/B, respectively. The combinations of agents used in the induction regimen were proteasome inhibitor (PI), immunomodulatory drug (IMiD) and glucocorticoid (GC) in 28.5% (613/2154) pts; PI, GC and chemotherapy (CHT) in 24.8% (534/2154) pts; GC and CHT in 22,5% and IMiD, GC and CHT in 16.1% (346/2154). Other combination of drugs was used in 8.2% (177/2154) pts. It was registered that 3.7% (79/2154) induction regimens were switched to a different combination because of toxicity, patient's choice, poor peripheral venous access or other reasons. Single HDT/ASCT was performed in 77.3% (1665/2154) cases whereas tandem HDT/ASCT was given to 11.8% (254/2154) patients. In 10% (215/2154) cases, the transplantation technique was not specified. Nine percent (193/2154) patients were treated within a clinical study. The median progression free survival (mPFS) and the median overall survival (mOS) of the whole cohort was 28.9 and 92.1 months, respectively. Information about response to treatment before and after the high-dose therapy were available for 75.7% (1627/2154) and 92.2% (1987/2154) patients, respectively. Disease status at the time of HDT/ASCT was defined as stringent complete response (sCR) at 2.2% (36/1627), complete response (CR) at 11.9% (194/1627), very good partial response (VGPR) at 38.2% (621/1627), partial response (PR) at 40.9% (666/1627), minimal response (MR) at 3.6%, (58/1627), stable disease (SD) at 2.2% (36/1627), progressive disease (PD) at 1% (16/1627) patients. The overall response rate (ORR) on day 100 was 92.8% (sCR: 10.5% [209/1987], CR: 22.4% [446/1987], VGPR: 35% [696/1987], PR: 24.8% [493/1987], MR: 2.7% [54/1987], SD: 1.4% [27/1987], PD: 3.1% [62/1987]). We also performed a survival analysis of patients progressing up to 18 months after HDT/ASCT (n=1219) versus patients progressing in more than 18 months (n=935). The median OS was 41.5 versus 124.9 months, respectively. An analysis of the role of tandem HDT/ASCT in this real-world cohort will be presented at the conference. Conclusion: Globally as well as in the Czech Republic, HDT/ASCT is an important therapeutic approach in the first-line treatment of multiple myeloma. Our analysis of 2154 newly diagnosed transplant-eligible patients confirms high effectiveness - ORR of 92.8%, mPFS of 28.9 months, and long-term survival reaching mOS of 92.1 months. Disclosures Minarik: Amgen: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Takeda: Consultancy, Honoraria.
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Stevanovic, Lidija, Matthias Choschzick, Linda Moskovszky, and Zsuzsanna Varga. "Variability of predictive markers (hormone receptors, Her2, Ki67) and intrinsic subtypes of breast cancer in four consecutive years 2015–2018." Journal of Cancer Research and Clinical Oncology 145, no. 12 (October 18, 2019): 2983–94. http://dx.doi.org/10.1007/s00432-019-03057-0.
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Abstract Purpose Accurate monitoring of predictive markers is of utmost importance as oncological treatment decisions almost entirely depend on these factors. In this study, we conducted a quality control assessment on hormone receptors, Her2 status, Ki67 Labelling Index (LI) and histological grading in breast cancer over 4 years (2015–2018). Methods Altogether 2214 consecutive breast cancer cases were included. Data on estrogen (ER) and progesterone receptors (PR), Her2 and Ki67, were available in all cases and were tested mostly on preoperative biopsies, in selected cases on postoperative surgical specimens. ER, PR, and Ki67 were assessed with immunohistochemistry (IHC), Her2 status with IHC and fluorescence in situ hybridization. Results ER/PR were positive in 74–79% cases, ER/PR/Her2 negative in 6.16–10.70% and Her2 positive in 11.49–13.88%/year. Ki67 had median values as 15–17.5% in ER/PR-positive cases, 55–60% in triple-negative cases and 30–32.50% in Her2-positive cases. Histological grading distribution for well (G1), moderately (G2) and poorly (G3) differentiated carcinomas was 15.8–19.1% for G1, 54.2–54.8% for G2 and 21.7–23.7% for G3 cases. Variation in yearly distributions was not significant in any of these markers. Conclusions Predictive markers displayed a yearly similar distribution in breast cancer cases independently of grading or of intrinsic subtypes. These results point to a qualitative high performance of predictive marker assessment in breast cancer, corresponding to expected on average positivity rate per marker and per year. It is recommended to monitor positivity rate of ER, PR, Ki67 and Her2 yearly or periodically to comply with quality assurance requirements.
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Sorrentino, Roberto, Gennaro Ruggiero, Bruna Borelli, Alberta Barlattani, and Fernando Zarone. "Dentin Exposure after Tooth Preparation for Laminate Veneers: A Microscopical Analysis to Evaluate the Influence of Operators’ Expertise." Materials 15, no. 5 (February 26, 2022): 1763. http://dx.doi.org/10.3390/ma15051763.
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Background: To assess the quantity of dentin exposure detected by 3 operators with different clinical expertise for 2 designs of tooth preparation for laminate veneers: window (WI) and butt joint (BJ). Methods: 20 intact maxillary central incisors were collected and then prepared for laminate veneers to a depth of 0.6 mm, with a cervical mini-chamfer finish line of 0.3 mm. Each prepared tooth was analyzed by 3 operators with different expertise: undergraduate student (ST), general practitioner (GP), and prosthodontist (PR), at sight under magnification. Besides descriptive statistics (CI 95%), 2-way ANOVA and Games–Howell tests were used to analyze differences among groups (α = 0.05). Results: The means of percentage and area of detected dentin exposure were WI = 30.48%, 21.57 mm2; BJ = 30.99%, 21.97 mm2; ST/WI = 22.82%, 16.44 mm2; GP/WI = 58.05%, 40.64 mm2; PR/WI = 10.55%, 7.63 mm2; ST/BJ = 28.99%, 20.83 mm2; GP/BJ = 40.56%, 28.32 mm2; PR/BJ = 23.42%, 16.75 mm2. Significant differences were found between ST/WI vs. GP/WI (p = 0.005) and GP/WI vs. PR/WI (p < 0.001). Conclusions: There was no difference in detection of exposed dentin among operators with different expertise for BJ preparation, whereas differences were found between the general practitioner and the other 2 operators in WI. Moreover, the quantity of exposed dentin was not related to different tooth preparation designs.
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Win, Aung Zaw, and Carina Mari Aparici. "Carcinoma en Cuirasse from Recurrent Breast Cancer seen on FDG-PET/CT." Journal of Clinical Imaging Science 5 (June 29, 2015): 35. http://dx.doi.org/10.4103/2156-7514.159456.
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Our patient was a 36-year-old female diagnosed with Grade II ER+/PR−/Her-2 − ductal carcinoma in situ (DCIS) in the left breast. She underwent left lumpectomy and received treatment with tamoxifen and radiotherapy. Three years later, she presented with multiple diffused skin nodules on the chest and upper left arm. 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) exam showed widespread metastasis in the chest, upper left arm, left axillary lymph nodes, and left suprascapular muscle. FDG-PET/CT imaging of breast carcinoma en cuirasse is very rare. FDG-PET/CT is useful in detecting recurrent breast cancer.
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Bailey, Jane H. E., John E. Drake, and Maria L. Y. Wong. "Preparation and characterization of a series of bromodiphenyl(N,N-dialkyldithiocarbamato)tellurium(IV) compounds where R=Me, Et, i-Pr, Bu, and of chlorodiphenyl(N,N-dibutyldithiocarbamato)tellurium(IV) and diphenylbis(N,N-dibutyldithiocarbamato)tellurium(IV). Crystal structure of Ph2TeBr[S2CNEt2] and Ph2Te[S2CNBu2]2." Canadian Journal of Chemistry 69, no. 12 (December 1, 1991): 1948–56. http://dx.doi.org/10.1139/v91-280.
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The series Ph2TeBr[S2CNR2], where R = Bu, Pr, i-Pr, Et, and Me, as well as Ph2TeCl[S2CNR2] and Ph2Te[S2CNR2]2, where R=Bu, Pr, have been synthesized and characterized by elemental analysis and vibrational spectroscopy. Comparisons of the effect of changing R groups and halogen atoms can be made based on the two crystal structures determined herein along with earlier work. The geometry about tellurium is consistent with that of a distorted sawhorse structure where the dithiocarbamate groups are monodentate (or anisobidentate). The crystal structures of Ph2TeBr[S2CNEt2], 4, and Ph2Te[S2CNBu2]2, 7, were completed. The cell parameters for 4 are a = 11.204(3) Å, b = 14.106(11) Å, c = 13.867(10) Å, α = 99.62(6)°, β = 102.76(5)°, γ = 87.73(4)°, V = 2107 Å3, Z = 4, R = 0.0448, and Rw = 0.0489 and for 7 are a = 19.392(6) Å, b = 9.622(2) Å, c = 19.089(6) Å, β = 104.70(2)°, V = 3445(2) Å3, Z = 4, R = 0.0397, and Rw = 0.0439. Nuclear magnetic resonance spectra are not simple and indicate that several species are present in solution, as rearrangements and reductive elimination take place. Key words: structure, tellurium, bromo, diphenyl, dialkyldithiocarbamato.
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Qi, Gaoxiu, Xin Zhang, Xiaoying Gai, and Xiong Yan. "Retrospective analysis of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER2), Ki67 changes and their clinical significance between primary breast cancer and metastatic tumors." PeerJ 12 (May 15, 2024): e17377. http://dx.doi.org/10.7717/peerj.17377.
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Objective To explore the relationship between receptor heterogeneity and clinicopathological characteristics in 166 patients with invasive breast cancer during metastasis. Methods We conducted a retrospective analysis of 166 patients diagnosed with metastatic breast cancer through biopsy, who were admitted to our hospital from January 2018 to December 2022. Statistical analysis was employed to assess the heterogeneity of receptors in both primary and metastatic lesions, including estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER2), Ki67, as well as their association with clinicopathological features such as tumor size, lymph node metastasis, treatment regimen, and disease-free survival. Results The discordant expression rates of ER, PR, HER2, Ki-67 and Luminal classification between primary and metastatic lesions were 21.7%, 41.6%, 8.9%, 34.4% and 36.8%, respectively. There is a significant difference in disease-free survival between patients with consistent and inconsistent receptor status of primary and metastatic lesions, which is statistically significant. The median DFS for primary HER2(-) to metastatic HER2(+) was 84 months, which was relatively high. The Cox multivariate regression analysis revealed that the expression differences of ER, PR, HER2, and Ki67 were not influenced by endocrine therapy and chemotherapy. However, a statistically significant difference in HER2 expression was observed with targeted therapy. Tumor size was correlated with ER and Ki67 receptor status (P = 0.019, 0.016). Tumor size was not correlated with PR, and HER2 (P = 0.679, 0.440). Lymph node metastasis was not associated with changes in ER, PR, HER2, and Ki67. The discordant rates of ER, PR, HER2, and Ki-67 in patients with local recurrence were 22%, 23.7%, 5.1%, and 28.8% respectively, whereas those in patients with distant metastasis were 21.5%, 36.4%, 10.3%, and 31.8% respectively. Conclusions The expression levels of ER, PR, HER2, and Ki-67 in primary and metastatic breast cancer exhibit heterogeneity, which is closely associated with the prognosis and treatment outcomes of patients.
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Wong-Ng, W., G. Liu, I. Levin, I. Williamson, P. Ackerman, K. R. Talley, J. Martin, et al. "X-ray diffraction and density functional theory studies of R(Fe0.5Co0.5)O3 (R = Pr, Nd, Sm, Eu, Gd)." Powder Diffraction 31, no. 4 (September 20, 2016): 259–66. http://dx.doi.org/10.1017/s088571561600049x.
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The structure of a series of lanthanide iron cobalt perovskite oxides, R(Fe0.5Co0.5)O3 (R = Pr, Nd, Sm, Eu, and Gd), have been investigated. The space group of these compounds was confirmed to be orthorhombic Pnma (No. 62), Z = 4. From Pr to Gd, the lattice parameter a varies from 5.466 35(13) Å to 5.507 10(13) Å, b from 7.7018(2) to 7.561 75(13) Å, c from 5.443 38(10) to 5.292 00(8) Å, and unit-cell volume V from 229.170(9) Å3 to 220.376(9) Å3, respectively. While the trend of V follows the trend of the lanthanide contraction, the lattice parameter “a” increases as the ionic radius r(R3+) decreases. X-ray diffraction (XRD) and transmission electron microscopy confirm that Fe and Co are disordered over the octahedral sites. The structure distortion of these compounds is evidenced in the tilt angles θ, ϕ, and ω, which represent rotations of an octahedron about the pseudocubic perovskite [110]p, [001]p, and [111]p axes. All three tilt angles increase across the lanthanide series (for R = Pr to R = Gd: θ increases from 12.3° to 15.2°, ϕ from 7.5° to 15.8°, and ω from 14.4° to 21.7°), indicating a greater octahedral distortion as r(R3+) decreases. The bond valence sum for the sixfold (Fe/Co) site and the eightfold R site of R(Fe0.5Co0.5)O3 reveal no significant bond strain. Density Functional Theory calculations for Pr(Fe0.5Co0.5)O3 support the disorder of Fe and Co and suggest that this compound to be a narrow band gap semiconductor. XRD patterns of the R(Fe0.5Co0.5)O3 samples were submitted to the Powder Diffraction File.
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Danilov, Alexey, Michael T. Tees, Krish Patel, William G. Wierda, Manish Patel, Ian W. Flinn, Tahir Latif, et al. "A First-in-Human Phase 1 Trial of NX-2127, a First-in-Class Bruton's Tyrosine Kinase (BTK) Dual-Targeted Protein Degrader with Immunomodulatory Activity, in Patients with Relapsed/Refractory B Cell Malignancies." Blood 142, Supplement 1 (November 28, 2023): 4463. http://dx.doi.org/10.1182/blood-2023-179872.
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Introduction: Although BTK inhibitors (BTKi) are effective therapeutics in the treatment of B cell malignancies, emerging BTK resistance mutations in chronic lymphocytic leukemia (CLL), as well as potential growth-promoting kinase-independent scaffolding function of BTK, present a need for improved or new approaches. Additionally, preclinical and clinical data in non-Hodgkin's lymphoma (NHL) suggest that drugs modulating cereblon may synergize with BTKi to provide a therapeutic effect. NX-2127 is an oral, first-in-class, dual-function small molecule degrader that combines BTK degradation with the immunomodulatory activity of an Ikaros and Aiolos degrader. Preliminary safety of NX-2127 in patients across B cell malignancies and efficacy in patients with CLL have been presented previously [Mato et al. 2022; Danilov et al. 2023]. Here we report further safety and efficacy follow-up in patients with CLL and efficacy data in patients with NHL enrolled to date. Methods: NX-2127-001 (NCT04830137) is a first-in-human, multicenter, open-label, dose-escalation (Phase 1a) and cohort-expansion (Phase 1b) trial evaluating the safety and preliminary efficacy of NX-2127 in adults with relapsed/refractory B cell malignancies, including CLL, diffuse large B cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), and Waldenstrom's macroglobulinemia (WM). NX-2127 is administered orally once daily in 28-day cycles. Results: As of 9 June 2023, 47 patients were enrolled and treated with NX-2127 at once-daily doses of 100 mg (n=28), 200 mg (n=10), and 300 mg (n=9). Patients were predominantly male (66%), with a median age of 74 (range 50-92) years. Twenty-nine patients were treated for CLL/small lymphocytic lymphoma, 5 DLBCL (2 GCB [Germinal-center B-cell-like], 3 non-GCB), 5 MCL, 3 MZL, 3 WM, and 2 FL. Patients enrolled were heavily pretreated with median prior lines of therapy of 4 (range 2-10) in NHL and 5 (range 2-11) in CLL. Prior treatments in patients with CLL comprised: BTKi 100% (including covalent [cBTKi] and non-covalent [ncBTKi] inhibitors); BCL2 inhibitor 76%, with a large proportion of CLL patients exhibiting BTKi resistance mutations at baseline. Prior treatments in patients with NHL included: BTKi 72% (cBTKi and ncBTKi); bispecific antibody 1/18; bispecific antibody and CAR-T 1/18. There were two reported dose-limiting toxicities: one previously reported cognitive disturbance in a patient with CLL treated at 300 mg; and neutropenia in a patient with MZL treated at 300 mg. The most common any grade treatment-emergent adverse events (TEAEs) were fatigue (48.9%), neutropenia (42.6%) and hypertension (36.2%, see Table). The most common grade ≥3 TEAEs were neutropenia (38.3%), hypertension (14.9%) and anemia (12.8%). Contusion was reported in 27.7% of patients (all below grade 3), atrial fibrillation in 12.8% of patients (6.4% grade ≥3). Most common reasons for treatment discontinuation were progressive disease (PD, 25.5%) and AE (21.3%). Median follow-up for the study was 9.5 (range 0.1-24.3) months. NX-2127 exhibited dose-dependent pharmacokinetics (PK) with a mean half-life of 2-4 days across cohorts. Rapid, robust and sustained BTK degradation was observed in all patients, regardless of their absolute BTK starting level, tumor type, or dose level of NX-2127 (Figure). In addition, degradation of the cereblon neo-substrate Ikaros was observed. Among the efficacy evaluable patients with CLL, there were 9 PRs/PR with rebound lymphocytosis; additionally, 11 patients had SD at the time of data cut-off and 4 had PD. Two patients with WM were treated and efficacy evaluable (1 SD, 1 PD). Among the efficacy evaluable patients with NHL, there were 2 CRs and 1 PR; additionally, 3 patients had SD, and 5 had PD. Two CRs are ongoing with 9.2 and 11.8 months of duration. Conclusion: This first-in-human study of NX-2127 is actively enrolling and dose-expansion cohorts in DLBCL and MCL have been initiated at the 300 mg daily dose. Findings include dose-dependent PK accompanied by degradation of BTK and Ikaros. Encouraging and persistent responses were observed in heavily pretreated patients with relapsed/refractory CLL and NHL with a manageable safety profile. These data support the treatment concept of combining immunomodulatory activity and BTK degradation in a single molecule and support further development of NX-2127 in B cell malignancies.
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Opalinska, A., C. Leonelli, W. Lojkowski, R. Pielaszek, E. Grzanka, T. Chudoba, H. Matysiak, T. Wejrzanowski, and K. J. Kurzydlowski. "Effect of Pressure on Synthesis of Pr-Doped Zirconia Powders Produced by Microwave-Driven Hydrothermal Reaction." Journal of Nanomaterials 2006 (2006): 1–8. http://dx.doi.org/10.1155/jnm/2006/98769.
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A high-pressure microwave reactor was used to study the hydrothermal synthesis of zirconia powders doped with 1 mol%Pr. The synthesis was performed in the pressure range from 2 to 8 MPa corresponding to a temperature range from 215C∘to 305C∘. This technology permits a synthesis of nanopowders in short time not limited by thermal inertia of the vessel. Microwave heating permits to avoid contact of the reactants with heating elements, and is thus particularly well suited for synthesis of doped nanopowders in high purity conditions. A mixture ofZrO2particles with tetragonal and monoclinic crystalline phases, about 15 nm in size, was obtained. The p/T threshold of about 5-6 MPa/265–280C∘was necessary to obtain good quality of zirconia powder. A new method for quantitative description of grain-size distribution was applied, which is based on analysis of the fine structure of the X-ray diffraction line profiles. It permitted to follow separately the effect of synthesis conditions on the grain-size distribution of the monoclinic and tetragonal phases.
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Kaplan, Muhammet Ali, Ülkü Yalçintas Arslan, Abdurrahman Isikdogan, Berna Oksuzoglu, Mevlude Inanc, Tulay Akman, Ali Inal, et al. "Biologic subtypes and first relapse pattern in curative surgery performed breast cancer patients: Study of Anatolian Society of Medical Oncology." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): e11559-e11559. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.e11559.
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e11559 Background: Relapse is one of the most important risk factors in overall survival, and distant recurrence is related to a complex biologic interaction of seed and soil factors. The aim of the study was to investigate the association between the molecular subtypes and patterns of relapse in patients with curative surgery performed breast cancer. Methods: We retrospectively evaluated clinical data from 1126 breast cancer patients with relapses after their curative surgery between 1998 and 2012 from referral centers of Turkey. Study population was divided into four biological subtypes according to their hormone receptor status and HER2 expression.Patients were divided into four biological subtypes according to IHC: triple negative (ER negative, PR negative, and HER2 negative), HER2 overexpressing (ER negative, PR negative, and HER2 positive), luminal B (ER and/or PR positive, HER2 positive), and luminal A (ER and/or PR positive, HER2 negative). Results: The proportion of patients with luminal A, Luminal B, HER2-overexpressing, and triple negative breast cancer was 42.0% (n=473), 23.0% (n=259), 13.3% (n=150), and 21,7% (n=244), respectively. Median time to relapse was 26.6 months. 22.5% of the patients (n=253) had multiple relapse sites. The incidence of first distant recurrence site was significantly different among the subtypes. Liver (31.8% vs. 22.4%, p=0.008), bone (42.2% vs 37.0%, p<0.001), and lung metastases (30.9% vs. 22.2%, p=0.019) were increased in HER2 overexpressing, luminal A and triple negative group as first relapse site compared with other groups, respectively. Brain metastasis was increased in HER2 overexpressing and triple negative groups (17.7%), compared with Luminal A and B groups (8.0%, p<0.001). Conclusions: Organ-specific metastasis may depend on the molecular subtype of breast cancer. Tailored strategies against distant metastasis concerning the molecular subtypes in breast cancer may be considered.
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Sharmin, Samira, Farida Yasmin, Debabrata Ghosh, Afroza Naznin, Azmal Kabir Sarker, Jamiul Hossain, Hosne Ara Rahman, Md Monir Uddin, and Syed Muhammad Baqui Billah. "Influence of Age, Estrogen receptor (ER),Progesterone receptor (PR) and Epidermal growth factor -2 (HER-2) in Breast Carcinoma Patient in correlation with Radionuclide Bone Scan – Single Institute Based Experience." Bangladesh Journal of Nuclear Medicine 22, no. 2 (February 1, 2021): 114–18. http://dx.doi.org/10.3329/bjnm.v22i2.51761.
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Background: Breast carcinoma is a common type of malignancy in women worldwide. Radionuclide bone scintigraphy is recognized choice of investigation for the detection of bone metastases both in asymptomatic and symptomatic patients. Biomarkers like Estrogen Receptor (ER), Progesterone Receptor (PR), Human Epidermal growth factor -2 (HER-2) also play important role in the management and prognosis of breast cancer. The study was aimed to find out the relationship between the MDP bone scan findingsand hormone receptor and HER-2 status of breast carcinoma patients referred to the Institute of Nuclear Medicine and Allied Sciences (INMAS), Mitford, Dhaka.
Patients and Methods: This cross sectional study was conducted among 301 breast carcinoma patients between January 2018 and December 2019. Planar bone scan and SPECT (if needed) was done to all the patients after intravenous injection of 99mTc-MDP. Receptor status (ER, PR and HER-2) were documented from the patient’s medical records. Breast tumors were classified as (a) Triple positive- HER2-, ER-, and PR-positive) (b) Triple negative- HER2-, ER-, and PR-negative (c) Hormonereceptor (HR) positive (ER+/PR+) with HER-2 negative and d) HR negative (ER-/PR-) with HER-2 positive.Patients were broadly grouped according to age as A. less than 50 years (n = 59) and B. more than 50 (n = 260 ) years.
Results: The mean age of the patients enrolled for this study was 59.02±9.3 with range of 32 to 81 years. Out of the 301 patients, positive bone scans were found in 105 (34.8%) and negative bone scan were found 196 (66.2%). Patients of group A (<50years) with triple negative and HR+/HER-status had no bone or bone with visceral metastases. Triple positive subtype had 2 bone metastases, and HR-/HER-2+ subtype had 2 bone metastases and 1 had bone with visceral metastases. Group B (> 50years) patients having HR+/HER2- receptor status showed 16% solitary metastases, 53.2% multiple metastases, 33.3% extensive bony metastases, 13.6% bone with visceral metastases. Triple negative subtype showed 36.0 % solitary metastases, 19.1% bone with visceral metastases. Triple positive subtype group had 40.0% solitary metastases, 34.0 % multiple metastases, 66.7% extensive bony metastases, and 13.6% bone with visceral metastases. HR-/HER-2+ subtype group had 8% solitary metastases, 12.8% multiple metastases, and 18.2 % bone metastases with visceral involvement Overall relationship between bone scan and hormone receptor subtype, showed that most of the patients had HR+/ HER-2-(35.2%) subtype and 25.6% patient had triple positive, 23.3% patient had triple negative and 15.9% patient had HR-/HER-2 – receptor subtype. This study showed the visceral involvement with bone metastases (13 % in HR+/HER-2- 52.2 % in triple negative, 13 % in triple positive, 21.7 % in HR-/HER-2+subtype). Highest bone only metastases (35) in triple positive and HR+/HER-2-(31) subtype. Most of the patiens who had bone metastases with visceral involvement belong to triple negative (52.2%) and HER-2 subtypes -HR-/HER-2+ (21.7%). The result was significant (P<0.001).
Conclusion: It is observed from this study that triple positive and HR+/HER-2- were more likely to develop bone metastases than triple negative and HR-/HER-2-. Patients with bone scan negative and HR-/HER-2- or triple negative receptor status most likely develop visceral metastases
Bangladesh J. Nuclear Med. 22(2): 114-118, Jul 2019
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Cheng, Xiangdong, Zhiyuan Xu, Yian Du, Ping Hu, Guofa Yu, and Conggang Hu. "Phase II study of conversion therapy using S1/paclitaxel chemotherapy plus apatinib in unresectable gastric cancer (Ahead-G325 trial)." Journal of Clinical Oncology 35, no. 4_suppl (February 1, 2017): 53. http://dx.doi.org/10.1200/jco.2017.35.4_suppl.53.
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53 Background: Occasionally, an initially unresectable gastric cancer (GC) can be converted to a resectable one by chemotherapy. Combination with inhibitors against VEGFR-2 can lead to a clinical improvement. We aimed to investigate the efficacy and safety of S1/paclitaxel chemotherapy plus apatinib, a novel inhibitor of VEGFR-2, in the conversion therapy of unresectable GC. Methods: This was a multicentre, single-arm, open-label, phase II design. Eligible patients (pts) were aged 20-70 years and had histologically proven unresectable, HER-2 negative, advanced GC with a single non-curable factor confined to either the liver (H1), peritoneum (P1), or para-aortic lymph nodes (16a1/b2). The ECOG performance status was 0-2. No prior radiotherapy, chemotherapy, target therapy or immunotherapy was allowed. Patients received 2 cycles of S1/paclitaxel chemotherapy (S1: 60 mg, oral, bid for 2 weeks followed by a drug-free interval of 1 week; paclitaxel: 150 mg/m2, iv, 3h, on day 1) plus apatinib (500 mg, oral, qd) and 1 cycle of S1/paclitaxel chemotherapy prior to radical surgery. Three cycles of adjuvant chemotherapy (S1 and apatinib) were given 4-6 weeks after surgery. Primary endpoint was R0 resection rate. Thirty-three pts were enrolled. Results: Among the 28 pts eligible for preoperative efficacy evaluation, 21 achieved partial response (PR), 5 had stable disease (SD), and 2 had progressive disease (PD), resulting in an overall response rate of 75.0% and a disease control rate of 92.9%. Of the 21 pts with PR, 3 refused consents for surgery and 18 achieved R0 resection. The incidence of adverse events (AEs) was 73.9%. The common hematologic AEs were neutropenia (60.9%), leukopenia (52.2%) and hemoglobin decrease (47.8%), and nonhematologic AEs included hyperbilirubinemia (56.5%), hand-foot syndrome (34.8%), oral mucositis (30.4%), fatigue (30.4%), proteinuria (21.7%) and hypocalcemia (21.7%). There was no severe surgery-related complication. Conclusions: Combination of apatinib with S1/paclitaxel chemotherapy shows clinical benefits in unresectable GC, with acceptable safety profile. Clinical trial information: NCT02529878.
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Ткачев, Андрей Владимирович, Наталья Анатольевна Вишневская, and Елена Игоревна Чесалова. "Специализация месторождений редких земель по элементному составу их руд." Вестник ВГУ. Серия: Геология, no. 2 (August 10, 2023): 57–72. http://dx.doi.org/10.17308/geology/1609-0691/2023/2/57-72.
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Введение: Масштабы использования редкоземельных элементов (РЗЭ) промышленностью в XXI в. увеличиваются высокими темпами. Однако потребность в отдельных РЗЭ растет неравномерно: для части элементов рост спроса очень большой, для других он менее значительный или отсутствует. Из-за диспропорций между возможностями используемой в настоящее время ресурсной базы и потреблением отдельных РЗЭ цены на дефицитные празеодим (Pr), неодим (Nd) и тяжелые лантаноиды (LnY) на 1–2 порядка выше, чем на остальные РЗЭ. Важность этих элементов как для традиционных, так и инновационных отраслей современной промышленности делает их не просто дефицитными, а критичными. Поэтому геологоразведочные компании во всем мире рассматривают выявление месторождений с повышенной долей дефицитных РЗЭ в качестве большого бонуса. При этом на начальном этапе работы часто ведутся без предварительной стратегии, т.к. в научной и методической литературе отсутствуют эмпирически обоснованные данные о возможных вариациях колебаний соотношений между дефицитными и недефицитными РЗЭ в месторождениях разных типов. Наше исследование имеет целью исправить такое положение вещей. Данные и методика анализа: Собраны и впервые сопоставлены данные о распределении РЗЭ в рудах 127 месторождений РЗЭ со всего мира. Месторождения представляют девять металлогенических типов, к которым проявлялся интерес со стороны геологоразведочных или добывающих компаний в последние десятилетия. Результаты и обсуждение: Были установлены возможные диапазоны значений для относительных долей (%) дефицитных групп РЗЭ (Pr+Nd min–max/mean; LnY min–max/mean) в рудах месторождений следующих металлогенических типов: карбонатитовом (11.2–35.0/19.4; 0.4–7.6/2.2), гипергенном в карбонатитах (15.2–28.9/21.4; 0.6–7.7/3.4), фоидном (14.0–25.6/18.1; 1.2–17.6/8.1), сиенитовом (16.1–20.9/18.9; 3.1–16.3/8.7), щелочногранитном (0.2–20.7/11.5; 7.8–34.0/21.7), субщелочногранитном (13.5–23.4/17.7; 0.1–13.3/3.5), ионно-адсорбционном (4.2–36.8/22.3; 4.5–34.2/16.3), россыпном (18.8–25.3/21.7; 1.6–11.9/5.4) и внутриразломном (4.6–10.5/7.6; 19.7–28.2/23.9). Для некоторых типов месторождений установлены минералогические или геологические особенности, влияющие на увеличение доли дефицитных РЗЭ в рудах. Заключение: Полученные данные количественно маркируют границы специализации разных типов месторождений РЗЭ на наиболее востребованные группы РЗЭ. Такая информация дает возможность специалистам более целенаправленно проводить региональное прогнозирование и геологоразведочные работы ранних стадий для выявления месторождений с желаемым соотношением разных групп РЗЭ.
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Chiang, Nai-Jung, Jen-Shi Chen, Ming-Huang Chen, Shih-Hung Yang, Chiun Hsu, Chia-Jui Yen, Hsiao-Hui Tsou, Shan Yanshen, and Li-Tzong Chen. "A phase II trial of modified gemcitabine plus S-1 combination as the first-line treatment in patients with advanced biliary tract cancer." Journal of Clinical Oncology 35, no. 4_suppl (February 1, 2017): 417. http://dx.doi.org/10.1200/jco.2017.35.4_suppl.417.
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417 Background: Gemcitabine plus platinum, notably cisplatin, is conceived as the standard regimen for advanced biliary tract cancer (ABTC) nowadays. Recent randomized phase II study (JCOG0805) showed that gemcitabine plus S-1 was more promising than S-1 alone in ABTC, and a randomized phase III, UMIN 000001685, is currently ongoing to compare the efficacy of gemcitabine plus either S-1 (GS) or cisplatin (GC) in ABTC. Herein, we report the results of a single arm phase II of modified GS in Taiwanese ABTC patients, NCT02425137. Methods: Patients with chemonaïve ABTC were eligible to receive 800mg/m2 gemcitabine with 10 mg/m2/min infusion, on day 1 plus daily 80/100/120 mg of S-1 (based on BSA) days 1-10, in a 2-week cycle. With Optimal Simon’s two-stage design and (p0= 0.4, p1= 0.6) for 12-week disease control rate (proportion of patients with complete or partial response [CR/PR] or stable disease ≥ 12 weeks [SD≥ 12weeks]) and given error probabilities (alpha = 0.05, beta = 0.2), the null hypothesis (p0) would be rejected if 24 or more patients with CR/PR/SD≥ 12weeks were observed among 46 accruals. Tumor response was assessed by CT/MRI every 6 weeks according to RECIST v1.1. Results: Between May 2015 and April 2016, totally 46 evaluable patients were enrolled to receive a median of 9.5 cycles (range: 3-31) of modified GS. After a median of 8.7 months (95% CI, 6.7-9.1) follow-up, 10 (21.7%) patients achieved PR and additional 23 (50%) had SD>12weeks. The median progression-free survival and overall survival was 5.6 (95% CI, 4.4-7.2) and 10.8 (95% CI, 7.6-not reached) months, respectively. All grade 3 treatment-related AEs were < 5%. The dose intensity of S-1 and gemcitabine were both more than 95%. Conclusions: By the observation of 33 patients with PR/SD≥ 12weeks, the null hypothesis was rejected. Modified GS is an active regimen with excellent safety profiles and deserves further investigation for the management of Asian ABTC patients. Clinical trial information: NCT 02425137.
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Camacho, Juan C., Nima Kokabi, David M. Schuster, and Hyun Sik Kim. "PERCIST criteria to predict survival at 3 months following intra-arterial resin-based yttrium-90 (Y-90) radioembolization therapy of unresectable intrahepatic cholangiocarcinoma refractory to standard chemotherapy: A proof of concept study." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): e15141-e15141. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.e15141.
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e15141 Background: To investigate the prognostic value of PET Response Criteria in Solid Tumors (PERCIST) on predicting survival in patients with unresectable intrahepatic cholangiocarcinoma (ICC) after resin-basedYttrium-90 (Y-90) radioembolization. Methods: IRB approved prospective correlative study in ICC patients refractory to standard chemotherapy who had 18F-FDG PET-CT before and after Y-90 therapy. Measurable tumor was defined as a lesion ≥ 1 cm in diameter and maximum standardized uptake ((max) SUV) ≥ 2.5. (Max) SUV was measured in targeted and non-targeted lesions after local therapy (overall response). PERCIST criteria defined complete response (CR) as no FDG uptake within target lesion, and partial response (PR) as reduction of 30% in FDG (max) SUV peak in measurable lesions. Objective response included PR/CR. PET imaging was acquired pre-treatment, 1-3-and-6 months following Y90. Survival analyses were carried out with Kaplan–Meier and Log-Rank proportional models using SPSS software v20 (IBM, Armonk, NY) with significance set at <0.05. Results: 9 consecutive patients were enrolled (56% men, mean age 58). Median overall survival from Y90 was 21.7 months. Average max SUV pretreatment was 10.02 and after Y90, 6.03. At 1-month after Y90, target PERCIST criteria showed CR= 1 (11.1%), PR=1 (11.1%), SD=7 (33.3%) and PD=0 (0.0%). Following 3-month after Y90, target response was CR= 2 (22.2%), PR=3 (33.3%), SD=3 (33.3%) and PD=1 (11.1%). No correlation between survival and either target or overall PERCIST criteria response on 1-month follow-up scan was seen(p=0.260). Statistically significant prolonged overall survival was observed for patients with objective targeted response based on PERCIST criteria at 3-month scan (P=0.022). In addition, objective overall PERCIST response at 3-month showed significant correlation with overall survival (p= 0.011). Conclusions: In patients with unresectable ICC refractory to standard chemotherapy, PERCIST criteria at 3-months following Y-90 therapy predict overall survival.
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Sabbaghizadeh, Rahim, Mansor Hashim, and Sasan Moraddeh. "Dependence of microstructure and magnetic properties of (Nd,Pr)-(Fe,Ti,C)-B melt-spun ribbon on quenching wheel speed." Electronic Materials Letters 9, no. 3 (May 2013): 337–40. http://dx.doi.org/10.1007/s13391-012-2153-4.
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Deodhar, A., A. Ostor, A. Maniccia, F. Ganz, T. Gao, A. Chu, and D. Poddubnyy. "POS0905 ACHIEVEMENT OF PARTIAL REMISSION AND INACTIVE DISEASE IN UPADACITINIB-TREATED PATIENTS WITH ANKYLOSING SPONDYLITIS." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 710.2–711. http://dx.doi.org/10.1136/annrheumdis-2021-eular.566.
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Background:Assessment of SpondyloArthritis international Society (ASAS) response criteria and AS Disease Activity Score (ASDAS) are both commonly used, rigorous composite indices consisting of components with relevance to patients. Clinically meaningful thresholds for these measures have been defined to reflect partial remission (PR), inactive disease (ID), and low disease activity (LDA).Objectives:To study the association of ASAS PR and ordinal ASDAS disease categories (including ASDAS ID, which is the most stringent category of this composite score) in upadacitinib (UPA)-treated patients with AS.Methods:In the SELECT-AXIS 1 (NCT03178487) study, biologic DMARD naïve-patients (pts; ≥18 y) with active AS and intolerance/contraindication or inadequate response to ≥2 NSAIDs were randomized 1:1 to UPA 15 mg once daily (QD) or placebo (PBO).1 At wk 14, pts entered an open-label extension (OLE) of UPA 15 mg QD; pts randomized to PBO were switched to UPA. This post hoc analysis assessed the responsiveness of individual ASAS and ASDAS core components among pts who achieved ASAS PR. The association of ASAS PR with achievement of ASDAS ID (ASDAS <1.3), ASDAS LDA (ASDAS <2.1 but ≥1.3) or ASDAS high disease activity (HDA)/very HDA (VHDA) (ASDAS ≥2.1 for HDA/VHDA) was also assessed by measures including Youden index, distance to perfect point, and sensitivity/specificity equality. These evaluations were performed in pts randomized to UPA from baseline (BL; continuous UPA, assessed at wk 14) and those who were randomized to PBO and switched to UPA upon entry in the OLE (PBO to UPA; re-baselined at wk 14 and assessed at wk 32, representing 18 wks of UPA exposure).Results:At wk 14, for the continuous UPA group, 16 pts (19%) achieved ASAS PR. At wk 32, following 18 wks of UPA exposure for the PBO-to-UPA group, 28 pts (33%) achieved ASAS PR. Among both groups (continuous UPA and PBO-to-UPA), improvements were seen across all core components (Figure 1). Of the 44 total pts who achieved ASAS PR, 91% achieved either ASDAS ID or LDA. The majority of patients who achieved ASAS PR achieved ASDAS ID in the continuous UPA and PBO-to-UPA groups: 11/16 (69%) and 16/28 (57%), respectively. For the continuous UPA group, the remaining 5 pts who achieved ASAS PR also achieved ASDAS LDA (Table 1). ASAS PR was associated with ASDAS categories in the following manner: the highest rate of ASAS PR was achieved for ASDAS ID followed by ASDAS LDA followed by ASDAS HDA/VHDA. The cutoff of 1.3 (the upper threshold for ASDAS ID) was a better discrimination threshold for ASAS PR than the cutoff of 2.1 (the upper threshold for ASDAS LDA).Conclusion:Nineteen percent of pts receiving UPA from BL achieved ASAS PR after 14 wks of treatment, with similar results seen in pts who were originally randomized to PBO and switched to UPA at wk 14. A consistent improvement was seen across all core components of ASAS among those who achieved ASAS PR with UPA treatment. The achievement of ASAS PR was most closely associated with the achievement of ASDAS ID, providing further clarity on the reduction of disease activity in AS pts treated with UPA.References:[1]van der Heijde, et al. Lancet. 2019;394(10214):2108-2117.Table 1.Association Between ASAS PR and ASDAS Clinical Thresholds (ID/LDA/HDA or VHDA)ASDAS ID(<1.3)ASDAS LDA(1.3 to <2.1)ASDAS HDA or VHDA(≥2.1)Continuous UPA Groupn=15n=31n=39 ASAS PR Responders (n=16)1150 ASAS PR Non-responders (n=69)42639PBO to UPA Groupn=25n=35n=25 ASAS PR Responders (n=28)1684 ASAS PR Non-responders (n=57)92721P<0.001 for association of ASAS PR with the ordered ASDAS categories of ID-LDA-HDA, for both Continuous UPA Group and PBO to UPA Group. P-value calculated from Cochran-Armitage trend test for association of ordinal categories.ASAS, Assessment of SpondyloArthritis international Society response criteria; ASDAS, AS Disease Activity Score; HDA, high disease activity; ID, inactive disease; LDA, low disease activity; PBO, placebo; PR, partial remission; UPA, upadacitinib; VHDA, very high disease activity.Acknowledgements:AbbVie funded this study and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of the publication. All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship. Medical writing support was provided by J Urbanik of AbbVie and M Hovenden and J Matsuura of Complete Publication Solutions, LLC (funded by AbbVie).Disclosure of Interests:Atul Deodhar Speakers bureau: Novartis and Pfizer, Consultant of: Novartis, Pfizer, AbbVie, Eli Lilly, UCB Pharma, GlaxoSmithKline, Galapagos, Janssen, Boehringer Ingelheim and Celgene, Amgen., Grant/research support from: AbbVie, Eli Lilly, UCB Pharma, GlaxoSmithKline, Andrew Ostor Consultant of: AbbVie, BMS, Roche, Janssen, Lilly, Novartis, Pfizer, UCB, Gilead, and Paradigm, anna maniccia Shareholder of: AbbVie, Employee of: AbbVie, Fabiana Ganz Shareholder of: AbbVie, Employee of: AbbVie, Tianming Gao Shareholder of: AbbVie, Employee of: AbbVie, Alvina Chu Shareholder of: AbbVie, Employee of: AbbVie, Denis Poddubnyy Speakers bureau: AbbVie, BMS, Lilly, MSD, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Biocad, Gilead, GSK, Lilly, MSD, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Lilly, MSD, Novartis, and Pfizer
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Gafita, Andrei, Isabel Rauscher, Manuel Weber, Boris A. Hadaschik, Hui Wang, Wesley R. Armstrong, Robert Tauber, et al. "Novel framework for treatment response evaluation using PSMA-PET/CT in patients with metastatic castration-resistant prostate cancer (RECIP): An international multicenter study." Journal of Clinical Oncology 40, no. 6_suppl (February 20, 2022): 42. http://dx.doi.org/10.1200/jco.2022.40.6_suppl.042.
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42 Background: We aimed to develop a novel framework for Response Evaluation Criteria In PSMA-PET/CT (RECIP) 1.0 and a composite response classification which combines responses by PSA measurements and by RECIP 1.0 (PSA+RECIP). Methods: This was an international, multicenter, retrospective study. 124 men with mCRPC who underwent 177Lu-PSMA therapy and received PSMA-PET/CT at baseline (bPET) and at interim at 12 weeks (iPET) were included. Pairs of bPET and iPET were interpreted by consensus among three blinded readers for appearance of new lesions. Tumor lesions were segmented and total PSMA-positive tumor volume (PSMA-VOL) was obtained. Appearance of new lesions and changes in PSMA-VOL were combined to develop RECIP 1.0, which was defined as: complete response (RECIP-CR: absence of any PSMA-ligand uptake on iPET), partial response (PSMA-PR: decline ≥30% in PSMA-VOL and no appearance of new lesions), progressive disease (RECIP-PD: increase ≥20% in PSMA-VOL and appearance of new lesions), stable disease (RECIP-SD: any condition but RECIP-PR or RECIP-PD). Changes in PSA levels at 12 weeks by PCWG3 were recorded. Responses by PSA+RECIP were defined as: response (PSA decline ≥50% or RECIP-PR/CR) and progression (PSA increase ≥25% or RECIP-PD). Study's primary outcome measure was the prognostic value of RECIP 1.0 for overall survival (OS). Secondary outcome measure was the prognostic accuracy (C-index) of PSA+RECIP vs PSA responses. Results: Patients with progressive disease (RECIP-PD; n=39; 8.3 mo) had shorter OS compared to patients with stable disease (RECIP-SD; n=47; 13.1 mo; p<0.001) and to those with partial response (RECIP-PR; n=38; 21.7 mo; p<0.001). PSA+RECIP had superior C-indices in identifying responders and progressors compared to PSA only: 0.65 vs 0.62 (p=0.028) and 0.66 vs 0.63 (p=0.044), respectively. Conclusions: PSMA-PET/CT by RECIP 1.0 is prognostic for OS and can be used as a response biomarker to monitor efficacy of 177Lu-PSMA in men with mCRPC. PSA+RECIP may be used as a novel composite endpoint in mCRPC clinical trial design.
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Favero, Andrea Cecília Mercaldi, Sônia Regina Pinheiro, Silvio Arruda Vasconcellos, Zenáide Maria Morais, Fernando Ferreira, and José Soares Ferreira Neto. "Sorovares de leptospiras predominantes em exames sorológicos de bubalinos, ovinos, caprinos, eqüinos, suínos e cães de diversos estados brasileiros." Ciência Rural 32, no. 4 (August 2002): 613–19. http://dx.doi.org/10.1590/s0103-84782002000400011.
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Em estudo retrospectivo abrangendo os anos de 1984 a 1997, foram realizados 15.558 exames sorológicos para leptospirose (SAM, com coleção de 24 sorovares), que incluíram: 284 ovinos, 879 bubalinos, 983 cães, 1.941 caprinos, 2.903 eqüinos e 8.568 suínos, distribuídos percentualmente por estado da seguinte forma: ovinos - SP (100%); bubalinos - SP (100%); cães - SP (80,7%), RS (0,10%), SC (0,10%) e PI (19,0%); caprinos - SP (33,1%), PB (63,7%) e CE (3,2%); eqüinos - SP (79,3%), RS (9,98%), SC (0,62%), PR (2,5%), RJ (0,17%), MG (1,96%), MT (3,99%), PB (1,3%) e PI (0,03%); suínos - SP (61,91%), RS (0,3%), SC (5,95%), PR (3,67%), RJ (0,88%), MG (24,38%), GO (1,12%), SE (0,2%), PE (0,90%), CE (0,34%) e MA (0,1%). A distribuição temporal dos animais examinados incluiu: para a espécie ovina - 54,5% referentes aos anos 1996 e 97, 33,3% referentes a 89 e 90 e 12,2% aos outros anos; espécie bubalina - 21,7% no intervalo de 1984 a 95 e 78,83% entre 96 e 97; espécie canina - 16,91% entre 1984 e 92 e 83,09% entre 1993 e 97; caprinos - 6,97% entre 1984 e 91 e 93,09% entre 1992 e 97, sendo que 49% das amostras foram referentes ao ano de 1992; eqüinos - 18,1% no intervalo de 84 a 90 e 81,9% de1991 a 97; suínos - 61,16% referentes aos anos 90, 91, 95 e 96. As médias de animais reatores e variantes mais freqüentes por espécie foram: ovinos - 0,70% de soropositividade e reações mais freqüentes para a variante icterohaemorrhagiae; bubalinos - 43,7% de positivos e variantes hardjo seguida de pomona; cães - soropositividade de 17,7% e reações para as variantes copenhageni e icterohaemorrhagiae no estado de SP e pyrogenes no PI; caprinos - 4,17% de positividade e variantes icterohaemorrhagiae e grippotyphosa no CE, icterohaemorrhagiae na PB e pyrogenes em SP; eqüinos - 29% de soros positivos e variantes icterohaemorrhagiae no PR, SC, SP, RJ e MG, grippotyphosa no MT, pyrogenes na PB e patoc no RS; suínos - soropositividade de 24,46% e grippotyphosa seguida de icterohaemorrhagiae em MG, pomona no RS, pomona e icterohaemorrhagiae em PE e RJ, autumnalis no CE e icterohaemorrhagiae em GO, PR, SC e SP.
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Watanabe, Fumiaki, Koichi Suzuki, and Toshiki Rikiyama. "Early molecular assessment to predict prognosis in patients who respond to chemotherapy on initial imaging in pancreatic cancer." Journal of Clinical Oncology 42, no. 3_suppl (January 20, 2024): 683. http://dx.doi.org/10.1200/jco.2024.42.3_suppl.683.
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683 Background: It is helpful to predict early the response to anticancer drugs in non-resectable solid tumors. The purpose of this study is to evaluate whether circulating tumor DNA (ctDNA) helps predict prognosis in patients with non-resectable pancreatic cancer who have received first-line FFX or GnP therapy and have responded to treatment (CR, PR, SD groups) on initial imaging. Methods: A total of 61 patients with non-resectable pancreatic cancer treated with FFX (N=22) and GnP (N=39) as first-line therapy were included in the study. Before and after chemotherapy treatment (median 42 days, after two courses), KRAS-mutated ctDNA was measured using droplet digital PCR with CA19-9. We defined the Responder group as those with CR, PR, or SD other than PD on initial imaging and the molecular assessment as the change in KRAS-mutated ctDNA before and after treatment. (1) No appearance of KRAS-mutated ctDNA before and after treatment was defined as molecular negative (mNT); (2) disappearance of KRAS-mutated ctDNA or decrease in copy number after treatment was defined as molecular response (mR); (3) new appearance of KRAS-mutated ctDNA or increase in copy number after treatment was defined as molecular progressive disease (mPD). We investigated whether the increase or decrease of CA19-9 before and after treatment (Increase group, decrease group) and the molecular assessment were useful as prognostic factors in the Responder group. Results: Male: female = twenty-nine: thirty-two. There were fourteen patients in the locally advanced group and forty-seven patients in the distant metastatic group, both of whom were considered non-resectable. Thirty-eight patients received any second-line treatment. The prognosis of fourteen patients with PD on initial imaging was significantly worse than that of the Responder group (N=47) (Responder: PD=18.4: 9.2 months, p=0.000108). The molecular assessment in the responder group showed 30 patients in mNT group, 10 patients in mR group, and 7 patients in mPD group. The MST was 21.7, 13.2, and 13.2 months. In univariate analysis, increased CA19-9 (Increase group) and mPD were associated with worse prognosis (Increase: Decrease=13.6: 18.4 months, p=0.0487), (mPD: mNT+mR=13.2: 21.7 months, p=0.0194) and the only independent prognostic factor in multivariate analysis was mPD (Hazard ratio=3.005, p=0.0361). Conclusions: The prognosis of patients with molecular negative or molecular response after chemotherapy is relatively good (MST; 21.7 months), and efforts should be made to continue GnP and FFX. In contrast, the prognosis of patients with molecular progressive disease in the responder group is worse. Therefore, strict follow-up and change of anticancer drugs, including palliation, should be considered.
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Corimayhua-Silva, Andrés A., Carlos Elías-Peñafiel, Tatiana Rojas-Ayerve, Américo Guevara-Pérez, Lucero Farfán-Rodríguez, and Christian R. Encina-Zelada. "Red Dragon Fruit Peels: Effect of Two Species Ratio and Particle Size on Fibre Quality and Its Application in Reduced-Fat Alpaca-Based Sausages." Foods 13, no. 3 (January 24, 2024): 386. http://dx.doi.org/10.3390/foods13030386.
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This research aimed to assess the influence of red dragon fruit peels ratio (RDF-PR) from two species, Hylocereus hybridum (HH) and Hylocereus undatus (HU), and particle size (PS) on quality parameters of red dragon fruit peel powder (RDF-PP) and its further application in emulsified alpaca-based sausages as partial substitutes of pork-back fat. A three-level full factorial design (nine treatments) was employed to evaluate the effect of RDF-PR (HH(0%):HU(100%), HH(50%):HU(50%), and HH(100%):HU(0%)) and PS (499–297, 296–177, and <177 µm) on the dependent variables: L*, a*, b*, C, h°, water-holding capacity, oil-holding capacity, swelling capacity, pectin yield, degree of esterification (analysed through FT-IR), and crude fibre content. The data analysed through a response surface methodology showed that treatment one (T1) is the best with the optimised conditions at 100% HU RDF-PR and PS of <177 µm. The statistical validation of T1 exhibited the highest water-holding capacity (32.1 g/g peel), oil-holding capacity (2.20 g oil/g peel), and pectin yield (27.1%). A completely randomised design (four formulations) was then used to assess the effect of partial replacement of pork-back fat by T1 in emulsified alpaca-based sausages on the colourimetric, physicochemical, and texture properties (hardness, chewiness, cohesiveness, springiness, adhesiveness, and adhesive force). Likewise, a sensory hedonic scale was employed to evaluate the appearance, colour, odour, flavour, texture, and overall acceptability of sausages. The results revealed that 65.7% of pork-back fat content was successfully replaced compared with a control formulation. Additionally, F3 showed significantly (p < 0.05) better colourimetric, physicochemical, and textural characteristics, such as lower hardness (34.8 N) and chewiness (21.7 N) and higher redness (a* = 19.3) and C (22.9), compared to a control formulation. This research presents RDF-PP as a promising fat substitute for developing healthier, reduced-fat meat products using fibre-rich agroindustry by-products.
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Fangusaro, Jason, Arzu Onar-Thomas, Tina Young Poussaint, Shelly Lensing, Azra H. Ligon, Neal Lindeman, Anuradha Banerjee, et al. "LGG-05. REPORT ON PEDIATRIC BRAIN TUMOR CONSORTIUM (PBTC)-029B, A PROSPECTIVE PHASE 2 CLINICAL TRIAL OF SELUMETINIB IN TREATING YOUNG PATIENTS WITH RECURRENT/PROGRESSIVE LOW-GRADE GLIOMA: NEW RESULTS ON STRATA 2, 5, AND 6 WITH UPDATED LONG-TERM SURVIVAL OUTCOMES ON STRATA 1, 3, AND 4." Neuro-Oncology 26, Supplement_4 (June 18, 2024): 0. http://dx.doi.org/10.1093/neuonc/noae064.398.
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Abstract BACKGROUND PBTC-029B was a phase 2 trial evaluating efficacy of selumetinib (up to 26 courses) in children with recurrent/progressive low-grade glioma. We report new results on strata 2, 5, and 6 as well as update long-term survival outcomes on strata 1, 3, and 4. METHODS Stratum 2 enrolled children with pilocytic astrocytoma (PA) whose tumor screened negative for the BRAF-KIAA1549 fusion and the BRAFV600E mutation. Stratum 5 enrolled children with non-PA whose tumor screened positive for one of these two BRAF aberrations. Stratum 6 enrolled children who consented to tissue screening, but there was an assay failure. Responses were based on T2/FLAIR. RESULTS Stratum 2: among 14 patients, there was 1 partial response (PR), 7 stable disease (SD) and 6 progressive disease (PD) with overall response rate (ORR) of 7.1%. Two-year progression-free survival (PFS)/overall survival (OS) were 57.1/100%, respectively. Stratum 5: among 23 patients, there was 1 complete response, 4 PR, 12 SD and 6 PD with ORR of 21.7%. Two-year PFS/OS were 74.8%/100%, respectively. Stratum 6: among 26 patients, there were 7 PR, 14 SD and 5 PD with ORR of 26.9%. Two-year PFS/OS were 72.0%/100%, respectively. Long-term outcomes have now been evaluated in strata 1, 3, and 4. Stratum 1 enrolled patients with PA whose tumor screened positive for one of the two BRAF aberrations; stratum 3 enrolled patients with neurofibromatosis type-1 (NF1) associated pLGG; and stratum 4 enrolled non-NF1 optic pathway/hypothalamic tumors. Among strata 1, 3, and 4, the current median follow-up for patients without events are 60.4, 60.4, and 58.1 months, respectively. Five-year PFS/OS are 30.8%/88.9%, 54.2%/100%, and 51.0%/100%, respectively. CONCLUSIONS These data demonstrate that selumetinib provides tumor stability and responses among diverse pLGG tumors as well as show that many patients will achieve long-term disease control even several years after stopping treatment.
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Silva, Bruna Lira, and Sandra Mara Silvério Lopes. "Implementação das práticas integrativas complementares - Acupuntura, nas unidades básicas de saúde da 12a regional de saúde de Umuarama (Paraná)." Revista Brasileira de Terapias e Saúde 11, no. 2 (October 22, 2020): 1–6. http://dx.doi.org/10.7436/rbts-2020.11.02.01.
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Contextualização: As Práticas Integrativas Complementares em Saúde (PICS), em especial a acupuntura, tem despertado interesse por parte da população e gestores de saúde pública, porém a comunidade científica e gestora desconhece dados de sua implantação como recurso de saúde pública. Objetivo: Verificar a implantação da acupuntura pelas secretarias de saúde municipais dos municípios pertencentes a 12a Regional de Saúde de Umuarama-PR. Métodos: Foi elaborado um questionário e aplicado ao responsável pela secretaria municipal de saúde de cada município. Resultados: 21 (vinte e um) municípios correspondentes a região, onde 56,1% (151.946) da população tem acesso a acupuntura pelo SUS, 22,6% (61.408) não tem acesso a acupuntura e 21,7% (57.356) correspondem a soma do número de municípios que não responderam a pesquisa. Conclusão: Apesar da acupuntura uma das PICS estar presente em sua oferta pelo SUS em um maior percentual nas cidades da região pesquisada ainda considera-se incipiente a incorporação das mesmas.
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Qiu, Lina, Jiandi Li, Weiwei Zhang, Aijun Gong, Xiaotao Yuan, and Yang Liu. "Extraction and Back-Extraction Behaviors of La(III), Ce(III), Pr(III), and Nd(III) Single Rare Earth and Mixed Rare Earth by TODGA." Sensors 21, no. 24 (December 12, 2021): 8316. http://dx.doi.org/10.3390/s21248316.
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N,N,N′,N′-Tetraoctyl diglycolamide (TODGA), as a new extraction agent, is effective for its excellent performance and low environmental hazard, and it is very welcome for the rare earth separation process. In this paper, by controlling the extraction time, diluent type, acid type and its concentration, rare earth concentration, etc., the optimum extraction and back-extraction effects of TODGA on La(III), Ce(III), Pr(III), and Nd(III) and mixed rare earths were obtained. The experiment showed that 0.10 mol·L−1 TODGA had the best extraction effect on single rare earth under the conditions of using petroleum ether as diluent, 5 mol·L−1 nitric acid, 20 min extraction time, and 0.01 mol·L−1 rare earth. In the mixed rare earth extraction, the percentage concentrations of La(III), Ce(III), Pr(III), and Nd(III) could be achieved from 21.7%, 19.9%, 30.8%, and 22.2% at the initial stage to 90.5%, 37%, 51%, and 62% after extraction, respectively, by controlling the number of back-extraction cycles and the concentrations of hydrochloric acid and nitric acid in the back-extraction system. The TODGA–rare earth carrier system showed the best back-extraction effect when the hydrochloric acid concentration was 1 mol·L−1 and the back-extraction time was 20 min. At the same time, the mixed rare earth liquid system with low initial concentration was selected for extraction and separation of mixed rare earth. The separation effect was better, and the recovery rate was higher than that of mixed rare earth liquid system with a high initial concentration.
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Chae, Young Kwang, Christopher W. Ryan, Naing Aung, William R. Robinson, Megan Othus, Elad Sharon, David M. O'Malley, et al. "Abstract CT162: A phase II basket trial of dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART) SWOG S1609: the clear cell ovarian, endometrial, cervical cancer cohorts." Cancer Research 83, no. 8_Supplement (April 14, 2023): CT162. http://dx.doi.org/10.1158/1538-7445.am2023-ct162.
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Abstract Background: Dual checkpoint inhibition with anti-PD-1 and anti-CTLA4 checkpoint inhibitors have proven to be efficacious in numerous malignancies. This study presents the first results of ipilimumab and nivolumab in the clear cell gynecologic cancer cohorts of the SWOG S1609 Dual Anti-CTLA-4 & Anti-PD-1 blockade in Rare Tumors (DART) trial. Methods: DART is a prospective, open-label, multicenter/multi-cohort phase 2 clinical trial of ipilimumab (1mg/kg IV every 6wk) plus nivolumab (240mg IV every 2wk). The primary endpoint was objective response rate (ORR) (RECIST v1.1) (confirmed CR and PR); progression-free survival (PFS), overall survival (OS), stable disease (SD) >6 months, and toxicity are secondary endpoints. Results: Evaluable patients were as follows: clear cell ovarian cancer (N=19); clear cell endometrial cancer (N=8); clear cell cervical (N=5) (median ages, 53, 66, and 59 years; cohorts 46, 45, and 42, respectively) In the clear cell ovarian cancer cohort, ORR was 21.1% [CR, 15.8%, n=3; PR, 5.3%, n=1]; clinical benefit rate (CBR) (includes stable disease ≥6 months) was 31.6% (6/19 patients). Among three patients with confirmed CR, two patients showed 100% regression (with ongoing response at 36+ months and 37+ months respectively), and the other patient showed 67% regression (due to lymph node < 1.0cm), but eventually progressed after 722 days. One confirmed PR patient achieved 75% regression (ongoing response at 53+ months). Of note, three patients achieved unconfirmed PR; one showed 34% regression (5 months); another, 38% (51.5+ months); and another, 58% regression (5 months). The ORR when including unconfirmed PR is 36.8% (7/19). Median PFS was 3.7 months (95% confidence interval (CI); 1.7-∞). Median OS was 21.7 months (6.4-∞). In the clear cell endometrial cancer cohort, ORR was 0%; CBR, 25% (2/8 patients). Of note, one patient achieved unconfirmed PR with 69% regression (4 months). The ORR when including unconfirmed PR is 12.5% (1/8). Median PFS was 2.0 months (95% confidence interval; 1.8-na). Median OS was 4.3 months (4.2-na). In the clear cell cervical cancer cohort, ORR was 0%; CBR, 20.0% (1/5 patients). Median PFS was 2.2 months (95% CI; 1.9-na). Median OS was 23.6 months (95% CI; 15.3-na). The most common adverse events, in the three cohorts combined, were nausea (37.5%, n=12), fatigue (34.4%, n=11), anorexia (31.2%, n=10), hypothyroidism (31.2%, n=10), and pruritus (28.1%, n=9). Grade 3-4 adverse events were reported in 17 cases (53.1%) with no grade 5 adverse events. Conclusion: Ipilimumab plus nivolumab in 19 clear cell ovarian cancer patients resulted in an ORR of 21.1% and CBR of 31.6%, with two durable CRs ongoing at 3+ years; CBR was 25% and 20%, respectively, in clear cell endometrial and cervical cohorts, with no objective responses, albeit with only 8 and 5 patients per cohort. Correlative studies to determine response/resistance markers are ongoing. Further prospective studies in rare gynecologic malignancies are warranted. Citation Format: Young Kwang Chae, Christopher W. Ryan, Naing Aung, William R. Robinson, Megan Othus, Elad Sharon, David M. O'Malley, Floortje J. Backes, Charles D. Blanke, Ramez N. Eskander, Razelle Kurzrock. A phase II basket trial of dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART) SWOG S1609: the clear cell ovarian, endometrial, cervical cancer cohorts [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT162.
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Kumar, Tapsi, Yiyun Lin, Yun Yan, Shanshan Bai, Jianzhuo Li, Tuan Tran, Min Hu, et al. "Abstract 2147: Decoding the natural biology of triple-negative breast cancer and response to chemotherapy by single-cell transcriptomics." Cancer Research 83, no. 7_Supplement (April 4, 2023): 2147. http://dx.doi.org/10.1158/1538-7445.am2023-2147.
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Abstract Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that lacks the expression of estrogen receptor (ER), progesterone receptor (PR) and HER2 and therefore have limited hormonal treatment options. Neoadjuvant chemotherapy (NAC) is backbone of treatment for TNBC, and about 50% of patients respond well leading to pathological complete response (pCR). However, the remaining patients develop resistance to NAC and progress to metastatic disease and poor survival in 1-2 years after the initial treatment. Previous studies have performed bulk RNA expression profiling of TNBC patients and identified 5-6 subgroups of patients, however these studies could not resolve expression programs at single cell resolution to distinguish between the tumor cells and different components of the tumor microenvironment (TME). Here we performed scRNA-seq of pre-treatment fresh core biopsy tissue samples from TNBC patients in the ARTEMIS clinical trial and compared these data between pCR and non-pCR patients to identify programs associated with response to NAC. We also compared these data to scRNA-seq data from patients with disease-free breast tissue to understand the basic biology of TNBC and identify cell types that are reprogrammed in malignant disease. Using the single cell tumor cell data, we identified 4 archetypes of TNBC which represent patient-level intertumor expression programs: luminal secretory-like (LS), basal/luminal-like (BL), immunoregulatory (IM), and luminal androgen receptor (LAR). Notably, the archetype BL was associated with non-pCR, while IM was associated with pCR. We further identified 13 metatraits, which are unique intratumoral expression programs that are shared across patients. Across the cancer cells, we identified 13 metatraits such as cell cycling, stress, hypoxia, interferon response, HLA, partial epithelial-mesenchymal transition, and endoplasmic reticulum stress, many of which corresponded to NAC response. In the immune compartment, we found 15 myeloid cell states, 14 T/NK cell states, and 6 B cell states, several of which corresponded to pCR/non-pCR. Similarly, in the stromal compartment, there were 4 fibroblast cell states, 4 pericyte cell states, and 7 endothelial cell subtypes, of which several cell states were associated with NAC response. Overall, these data report the natural biology of TNBC patients and malignant cell states that are reprogrammed in malignant disease, as well as their correspondence to NAC response, providing new data to predict which TNBC patients are likely to respond to chemotherapy. Citation Format: Tapsi Kumar, Yiyun Lin, Yun Yan, Shanshan Bai, Jianzhuo Li, Tuan Tran, Min Hu, Elizabeth Ravenberg, Maia Rauch, Alyson Clayborn, Alastair Thompson, Lei Huo, Stacy Moulder, Clinton Yam, Nicholas Navin. Decoding the natural biology of triple-negative breast cancer and response to chemotherapy by single-cell transcriptomics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2147.
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Knijff, Marthe, Airin Roshita, Julia Suryantan, Doddy Izwardy, and Jee Hyun Rah. "Frequent Consumption of Micronutrient-Rich Foods Is Associated With Reduced Risk of Anemia Among Adolescent Girls and Boys in Indonesia: A Cross-Sectional Study." Food and Nutrition Bulletin 42, no. 1_suppl (June 2021): S59—S71. http://dx.doi.org/10.1177/0379572120977455.
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Background: Anemia is a global public health concern. Its devastating consequences include impaired cognitive and motor development, reduced work productivity, and adverse birth outcomes, all of which apply to adolescents, as well as adults and children. Objective: This study aimed to examine the determinants of anemia in Indonesian adolescent girls and boys from Klaten and Lombok Barat districts. Methods: A total of 2150 adolescents who participated in a cross-sectional household survey were included in the analysis. The dietary intake of adolescents was assessed using a 7-day food frequency questionnaire. The relationship between anemia status, dietary intake, and other hypothesized determinants was assessed for adolescent girls and boys on a separate basis, using complex samples Cox regression analysis. Variables were selected for inclusion in multivariate models if they were significantly associated with the dependent variable in univariate models ( P < .05). Results: The prevalence of anemia among adolescent girls and boys was 19% and 5%, respectively. In multivariate analyses, frequent consumption of animal-based iron-rich foods was significantly associated with a lower risk of anemia (prevalence ratio [PR]: 0.59; 95% CI: 0.36-0.97) among adolescent girls, whereas a higher intake of vitamin A-rich fruits and vegetables was associated with a reduced risk of anemia (PR: 0.41; 95% CI: 0.20-0.85) among adolescent boys, after adjustment for all potential confounders. Conclusions: Increased consumption of iron- and vitamin A-rich foods through the implementation of gender-responsive Social Behaviour Change Communication (SBCC) interventions is warranted. This should be coupled with improved coverage and quality of iron and folic acid supplementation programs in adolescents.
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Bae, Soo Youn, Ji Eun Lee, Woo-Chan Park, Chang Ik Yoon, Dooreh Kim, Kabsoo Shin, and Youngjoo Lee. "Clinical subtypes and survival outcomes in invasive breast cancer with Paget’s disease: A SEER population-based study." Journal of Clinical Oncology 41, no. 16_suppl (June 1, 2023): e12564-e12564. http://dx.doi.org/10.1200/jco.2023.41.16_suppl.e12564.
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e12564 Background: The objective of this study was to investigate the clinicopathological characteristics, especially subtypes and survival outcomes of Invasive breast cancer with Paget's disease. Methods: 4930 patients were identified using the histopathology codes from the International Classification of Disease for Oncology third edition (ICD-O-3), from 2000 to 2019 in the Surveillance, Epidemiology, and End Results (SEER) database. Excluding 787 patients whose ICD-O-3 and TNM stages did not match, there were 663 patients with '8540/3, Paget disease, mammary', 976 patients with ‘8543/3, Paget disease and intraductal carcinoma(DCIS)’ and 2540 patients with ‘8541/3, and ‘8541/3, Paget disease and infiltrating ductal carcinoma (IDC) of breast’. ER and PR status have been available since 1990, and HER2 status since 2010. Results: Among patients with IDC and Paget's disease, 24.6% were under the age of 50 and 2.7% were male, which was higher than the other two groups. Expressions of ER and PR were higher than both groups, and HER2 expression was lower. The ratio of HR-/HER2+ subtype was also lower than the other two groups at 29.6%. ER+, Paget 43.7%, DCIS with Paget 36.4%, IDC with Paget 53.6%. PR+ Paget 21.6%, DCIS with Paget 21.7%, IDC with Paget 40.1%. HER2+ Paget 69.2%, DCIS with Paget 83.1 %, IDC with Paget 58.3%. HR-/HER2+subtype, Paget 40.7%, DCIS with Paget 49.2%, IDC with Paget 29.6%. As a result of survival analysis in patients with IDC and Paget's disease, the HR-/HER2+ subtype had shown the best prognosis in Overall Survival (OS) analysis (5year OS, HR+/HER2- 70.8%, HR+/HER2+ 74.9%, HR-/HER2- 63.7%, HR-/HER2+ 80.7% P=0.010) In the BCSS analysis, the 5-year BCSS was the best at 87.0% in the HR-HER2+ subtype, but there was no statistically significant difference. Conclusions: In IDC with Paget's disease, the distribution of subtypes is different from that of DCIS with Paget's, and HER2 expression can be considered as a favor prognostic factor. It is considered necessary to study the relationship between the loss of HER2 overexpression and invasion/progression in invasive breast cancer with Paget's disease.
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Pegoraro, Adhemar, Anselmo Chaves Neto, Sonia Maria Noemberg Lazzari, Débora Cristina Pereira Barros da Costa, and Sandra Regina Nunes Rodrigues. "FORRAGEAMENTO DE APIS MELLIFERA L. EM INFLORESCÊNCIA DE SYMPLOCOS TENUIFOLIA BRAND." Revista Acadêmica Ciência Animal 10, no. 4 (October 15, 2012): 327. http://dx.doi.org/10.7213/academica.7738.
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Tornou-se relevante conhecer o potencial das plantas apícolas visando ao melhoramento da florada em áreas de Reserva Legal. Este trabalho objetivou avaliar a concentração de sólidos solúveis (açúcares) no néctar do Symplocos tenuifolia; avaliar o percentual médio de operárias portadoras de néctar, pólen e ambos sobre as inflorescências desta planta; correlacionar a concentração de açúcares no néctar à temperatura atmosférica, à umidade relativa do ar e à luminosidade. O experimento foi realizado em Mandirituba (PR) utilizando-se 1.050 operárias para calcular a percentagem média de alimentos que elas portavam. Os valores médios percentuais dos recursos alimentares foram: néctar 21,7%, pólen 15,3%, ambos 31,7%. Nas operárias que portavam néctar foi medida a concentração de açúcares com refratômetro de mão. Entre as horas do dia existiu diferença significativa na concentração de açúcares no néctar variando de 22,8 a 30,1%. A temperatura apresentou correlação positiva significativa em relação à concentração de açúcares no néctar e a umidade relativa no ar apresentou correlação moderada e inversa. S. tenuifolia pode ser utilizada para melhorar o pasto apícola, visto que a espécie disponibiliza alimento no fim da primavera.
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Xu, Yongkang, Shumin Fu, Ye Mao, Fengming Yi, Weiming Jiang, Long Feng, and Jianbing Wu. "Efficacy and safety of hepatic arterial infusion chemotherapy combined with lenvatinib and tislelizumab for unresectable hepatocellular carcinoma: A single-arm, phase II study." Journal of Clinical Oncology 42, no. 3_suppl (January 20, 2024): 500. http://dx.doi.org/10.1200/jco.2024.42.3_suppl.500.
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500 Background: Unresectable hepatocellular carcinoma (uHCC) patients (pts) had high unmet medical needs in practice. Retrospective studies suggested a potent antitumor effect and long-term survival benefit of hepatic arterial infusion chemotherapy (HAIC) plus programmed death-1 inhibitor and lenvatinib. This prospective phase II study aimed to evaluate the efficacy and safety of HAIC combined with lenvatinib and tislelizumab in uHCC pts. Methods: Eligible pts were aged ≥18 years and had histologically confirmed uHCC, ECOG PS ≤1, Child-Pugh (C-P) A/B, and ≥1 measurable lesion per RECIST 1.1. Pts received HAIC of modified FOLFOX (oxaliplatin, 85 mg/m2; leucovorin, 400 mg/m2; 5-fluorouracil bolus, 400 mg/m2 on day 1; 5-fluorouracil infusion, 2400 mg/m2 for 46 h), lenvatinib (8 or 12 mg once daily for body weight <60 or ≥60 kg), and tislelizumab (200 mg every 3 weeks). HAIC was allowed to repeat on demands. Primary endpoint was objective response rate (ORR) per RECIST 1.1. Secondary endpoints included ORR per mRECIST, disease control rate (DCR), surgical conversion rate, progression-free survival (PFS), overall survival (OS), and adverse events (AEs). Results: Between June 2021 and January 2023, 46 pts were enrolled. The median age of pts was 51-year-old, most were male 42 (91.3%), ECOG PS 0 33 (71.7%), C-P A 44 (95.7%), tumor diameter ≥10 cm 31 (67.4%), multiple tumors 33 (71.7%), vascular invasion 38 (82.6%), extrahepatic metastasis 7 (15.2%). As of August 15, 2023, . All pts entered efficacy and safety analysis, ORR was 52.2% (0 complete response [CR], 24 partial response [PR]) per RECIST 1.1; ORR was 84.8% per mRECIST, with 5 CR and 34 PR. DCR was 95.6% per either RECIST 1.1 or mRECIST. Surgical conversion rate was 21.7% (10/46). Median PFS was 10.9 (95% CI, 8.0-13.8) months; 12-month OS rate was 41.3%. COX analysis revealed that ECOG PS 1 (HR, 3.17; 95% CI, 1.43-7.03; p=0.005), multiple tumors (HR, 3.68; 95% CI, 1.22-11.14; p=0.021), and extrahepatic metastasis (HR, 4.04; 95% CI, 1.57-10.40; p=0.004) were independently associated with poor PFS. Any-grade AEs occurred in 43 (93.5%) pts, the most common were proteinuria (43.4%), aspartate aminotransferase (AST) increased (35.8%), and alanine aminotransferase (ALT) increased (32.1%). Grades ≥3 AEs occurred in 10 (21.7%) pts and mainly included AST increased (7.5%), hypertension (3.8%), and hyperbilirubinemia (3.8%). Conclusions: HAIC combined with lenvatinib and tislelizumab showed meaningful clinical benefits and acceptable safety in uHCC pts. The study is ongoing, OS will be reported later. Clinical trial information: ChiCTR2200064384 .
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Maloney, D. G., A. J. Grillo-López, D. J. Bodkin, C. A. White, T. M. Liles, I. Royston, C. Varns, J. Rosenberg, and R. Levy. "IDEC-C2B8: results of a phase I multiple-dose trial in patients with relapsed non-Hodgkin's lymphoma." Journal of Clinical Oncology 15, no. 10 (October 1997): 3266–74. http://dx.doi.org/10.1200/jco.1997.15.10.3266.
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PURPOSE To evaluate the safety, pharmacokinetics, and biologic effect of multiple doses of the chimeric anti-CD20 monoclonal antibody (mAb) IDEC-C2B8 in patients with relapsed B-cell lymphoma. PATIENTS AND METHODS Twenty patients with relapsed low-grade (n = 15) or intermediate-/high-grade (n = 5) lymphoma received weekly infusions times four of 125 mg/m2 (n = 3), 250 mg/m2 (n = 7), or 375 mg/m2 (n = 10) of IDEC-C2B8. RESULTS Infusional side effects during the initial infusion were mainly grade I/II fever, asthenia, chills, nausea, rash, and urticaria. More serious events were rare. Peripheral-blood B cells were rapidly depleted and slowly recovered over 3 to 6 months. There was no change in mean immunoglobulin (Ig) levels. Antibody serum half-life (and maximum concentration [Cmax]) generally increased between the first and fourth infusions (33.2 hours v 76.6 hours, respectively) following the 375-mg/m2 doses. Six of 18 assessable patients had a partial remission (PR), with a median time to disease progression of 6.4 months (range, 3 to 21.7). Minor responses (MRs) were observed in five patients and progressive disease (PD) in seven. Tumor responses occurred in peripheral blood, bone marrow (BM), spleen, bulky lymph nodes, and extranodal sites, and in patients who had relapsed following high-dose myeloablative chemotherapy. Six of 14 patients (40%) with a low-grade histology responded. Four of six with bulky disease had a PR. CONCLUSION IDEC-C2B8 chimeric anti-CD20 mAb therapy is well tolerated and has clinical activity in patients with relapsed B-cell lymphoma. The 375-mg/m2 dose has been selected for a phase II trial in patients with relapsed low-grade or follicular B-cell lymphoma.
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Raut, Manoj Kumar. "Socio-demographic determinants of vitamin A supplementation in Bangladesh: evidence from two rounds of Bangladesh demographic and health surveys, 2007 and 2011." International Journal Of Community Medicine And Public Health 5, no. 3 (February 24, 2018): 1149. http://dx.doi.org/10.18203/2394-6040.ijcmph20180775.
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Background: Vitamin A supplementation reduces night blindness, child morbidity and mortality. In Bangladesh, Vitamin A deficiency among children 6-59 months has remained just about stagnant at 20.5 per cent as per the latest Bangladesh National Micronutrient Status Survey 2011-12 declining by a meagre 1.2 per cent from 21.7 per cent in 1997 (IPHN/HKI, 1997). Alarmingly, there is an absolute decline of 24 percentage points in VAS supplementation from 2007 to 2011 according to the Bangladesh Demographic & Health Surveys (BDHS). The current status of vitamin A supplementation raises concern because the Ministry of Health and Family Welfare (MoHFW)’s Health, Population and Nutrition Sector Development Program (HPNSDP) 2011-2016 target of 90 per cent needs to be achieved by 2016.Methods: This paper tries to explore the socio-demographic causes of receipt of Vitamin A in Bangladesh by analysing the data of the demographic and health surveys for 2007 and 2011 using SAS software. A log binomial regression was conducted to explore the effect of education and exposure to mass media on receipt of vitamin A supplementation.Results: After adjusting for related socio-economic and demographic factors, parent’s education and among mass media channels, television seems to play an important role in predicting receipt of Vitamin A, (Prevalence Ratio [PR]: 1.0973, 95% Confidence Interval [CI] 1.0499-1.1469) in BDHS 2011. Similarly, also those who watched television were more likely to have received vitamin A (Prevalence Ratio [PR]: 1.0542, 95% Confidence Interval [CI] 1.0304-1.0784).Conclusions: It can be concluded that mass media seems to be working well in making the mothers aware about the vitamin A campaign, especially, the exposure to television. Though mother’s education was not associated in the 2007 survey, but it was significantly associated with the receipt of vitamin A in the 2011 survey.
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Nogueira, Lorena Slusarz, Manoelito Ferreira Silva Junior, and Erildo Vicente Müller. "Perfil sociodemográfico e fatores de atração e saída dos médicos atuantes na estratégia saúde da família no município de Ponta Grossa, Paraná, Brasil." Revista Brasileira de Medicina de Família e Comunidade 16, no. 43 (September 26, 2021): 2159. http://dx.doi.org/10.5712/rbmfc16(43)2159.
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Introdução: Diversos estudos destacam a alta rotatividade e a dificuldade de fixação dos profissionais nas equipes, especialmente médicos, como um dos grandes desafios para a consolidação da estratégia saúde da família (ESF) no Brasil. A rotatividade prejudica a longitudinalidade do cuidado, a formação do vínculo com a equipe e a qualidade da assistência prestada. Objetivo: Descrever o perfil sociodemográfico e os fatores de atração e saída de médicos inseridos na ESF. Métodos: Estudo transversal com abordagem quantitativa, realizado entre março e abril de 2019, do município de Ponta Grossa-PR, Brasil, por meio de questionário semiestruturado e autoaplicado desenvolvido no estudo. A análise descritiva foi realizada por frequências relativas (%) e absolutas (n). Resultados: Participaram 61 médicos. Houve predomínio de profissionais mulheres (57,4%), com menos de 30 anos (49,2%), formou-se após 2015 (60,7%) e não é natural do município (82%). Apenas 1,6% possuía residência em medicina de família e comunidade e 9,8% especialização em saúde da família. Foi alto o percentual de médicos contratados pelo “Programa Mais Médicos” (82%) e que trabalha na ESF há menos de 6 meses (59%). A identificação com o trabalho foi apontada como o principal fator que levou à inserção na ESF, enquanto o excesso de demanda e de processos burocráticos foi mencionado como importante fator de desmotivação. O principal motivo de saída dos profissionais foi a realização de residência médica. Conclusão: Houve predomínio de profissionais com baixo tempo de trabalho na ESF do município oriundos do “Programa Mais Médicos”, em contratos temporários e relações trabalhistas precárias. A rotatividade médica é um assunto complexo, mas estratégias de valorização da carreira na atenção primária à saúde e a oferta de melhores condições de trabalho podem contribuir para sua resolução.
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Qu, Jian-Hang, Wen-Wen Ma, Jia Zhou, Xi-Feng Wang, Wen-Lan Lu, Ling-Bo Qu, and Lin-Feng Wang. "Gemmobacter caeruleus sp. nov., a novel species originating from lake sediment." International Journal of Systematic and Evolutionary Microbiology 70, no. 3 (March 1, 2020): 1987–92. http://dx.doi.org/10.1099/ijsem.0.004007.
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An aerobic, Gram-stain-negative, non-spore-forming and rod-shaped bacterial strain, designated N8T, was isolated from the interfacial sediment of Taihu Lake in PR China. The strain formed white to blue colonies on R2A agar. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain N8T represented a member of the genus Gemmobacter and was most closely related to Gemmobacter aquaticus A1-9T (97.97 %). The average nucleotide identity and digital DNA–DNAhybridization values between strain N8T and G. aquaticus A1-9T based on their whole genomes were 78.8 and 21.7 %, respectively. Q-10 was the main predominant ubiquinone. The major fatty acids were summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c), C18 : 0 and C16 : 0. The G+C content of the genomic DNA was 66.1 mol%. The polar lipids comprised phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine, one unidentified phospholipid, two unidentified glycolipids and two unidentified lipids. Based on its physiological, biochemical and chemotaxonomic characteristics, strain N8T represents a novel species of the genus Gemmobacter , for which the name Gemmobacter caeruleus sp. nov. is proposed. The type strain is N8T=(KACC 21307T=MCCC 1K04036T).
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Van Den Eynde, Marc, Nicolas Huyghe, Astrid De Cuyper, Isabelle Sinapi, Marie Ferrier, Mélanie Gilet, Aline Van Maanen, Marie-Laure Castella, Jerome Galon, and Javier Carrasco. "Interim analysis of the AVETUXIRI Trial: Avelumab combined with cetuximab and irinotecan for treatment of refractory microsatellite stable (MSS) metastatic colorectal cancer (mCRC)—A proof of concept, open-label, nonrandomized phase IIa study." Journal of Clinical Oncology 39, no. 3_suppl (January 20, 2021): 80. http://dx.doi.org/10.1200/jco.2021.39.3_suppl.80.
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80 Background: Immune checkpoint inhibitors have demonstrated poor efficacy in MSS mCRC. Previous research indicate that cetuximab (anti-EGFR chimeric monoclonal antibody) could initiate, independently from RAS mutation, an immunogenic tumor cell death and mediate antitumor immune response. In this trial, we aim to explore the clinical efficacy and safety of anti-PDL1 avelumab (AVE) combined with cetuximab (CET) and irinotecan (IRI) for treatment refractory MSS mCRC. Methods: AVETUXIRI (NCT03608046) is a multicenter academic study recruiting MSS, BRAFV600E wt, mCRC patients (pts) refractory to standard treatment (fluoropyrimidine, oxaliplatin, irinotecan and anti-EGFR treatment if RAS wt tumor) in 2 cohorts (cohort A: RAS wt – cohort B: RAS mut). In both cohorts, patients receive CET (400 mg/m2 W1, 250 mg/m2 W2, 500 mg/m2/2 weeks from W3), IRI (180 - 150 mg/m2/2 weeks from W1) and AVE (10 mg/kg/2 weeks starting from W3). Primary endpoints are overall response rate (ORR), defined as partial or complete response (PR or CR) according (i)RECIST1.1, and safety. Secondary endpoints include disease control rate (DCR), PFS and OS. Based on a Simon 2-stage design for ORR in each cohort (cohort A: P0=0.15, P1=0.33 / cohort B: P0=0.09, P1=0.25 / α = 0.1, β = 0.2 in both cohorts), 10 and 13 patients are required in the first stage of cohort A and B respectively. At least 2 pts have to reach PR or CR in each cohort to allow the continuation of the trial in the 2nd stage. Results: Between Oct 2018 and Jan 2020, 23 patients (median age 62 y-old, 86.9% male 78.3% left-sided, 91.3% synchronous mCRC) have been included in the first stage of the trial. No major or unexpected safety events were observed. 21.7% (5/23) of pts presented grade 3 diarrhea, all related to IRI, with complete resolution after IRI dose reduction or interruption. A reduced starting dose of IRI (150 mg/m2) was amended (09/2019) for the last included 8 pts without any grade 3-4 diarrhea occurrence. Grade 1-2 hypothyroidism was the only immune-related side effect. 3 PR were observed in cohort A and none in cohort B. DCR was 60.0% (6/10) and 61.5% (8/13) in cohort A and B respectively. Median PFS and OS were respectively 4.2 and 12.7 months (cohort A) and 3.8 and 14.0 months (cohort B). 6 months-PFS rate was 40.0% and 38.5% in cohort A and B. 12 months-OS rate was 53.3% and 57.7% in cohort A and B. The median follow-up of patients was 9.2 months. Conclusions: The AVETUXIRI trial met its primary efficacy endpoint for RAS wt mCRC pts justifying the study continuation in cohort A (2nd stage). No PR was observed in RAS-mut cohort. Nevertheless, encouraging data of DCR, PFS and OS observed in RAS mut cohort allow the opening of a new cohort for RAS-mut mCRC (cohort C) with PFS as primary endpoint. Clinical trial information: NCT03608046.
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Badreldin, Waleed, Simon Chowdhury, Stephen John Harland, Danish Mazhar, Thomas Powles, Peter Wilson, and Jonathan Shamash. "The efficacy of irinotecan, paclitaxel, and oxaliplatin (IPO) in relapsed germ cell tumours: A non-cisplatin-based regimen." Journal of Clinical Oncology 30, no. 15_suppl (May 20, 2012): 4529. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.4529.
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4529 Background: Cisplatin-based chemotherapy with or without high dose chemotherapy remains the standard approach in managing relapsed germ cell tumors (GCT). The feasibility of IPO was first described in 2006.Non cisplatin-based therapies offer the advantage of differing side effect profiles which may be useful to certain patients.Here we describe the outcome of an expanded cohort of these patients. Methods: The results of 72 consecutive patients were reviewed (18% had metastatic mediastinal GCTs). IPO was used either as 2nd line treatment (n=29) of which 20 had HDCT or 3rd line (n=43) of which 32 had HDCT. IPO consisted of oxaliplatin 100mg/m2, irinotecan 200mg/m2 and weekly pac litaxel 80mg/m2 ( IPO) every 3 weeks for 3-4 cycles with the intention of high dose carboplatin , thiotepa and topotecan as consolidation (HDCT). Results: The 2 year PFS and 3 year OS for the whole cohort was 28.4% (95%CI 17.3-40.5%) and 31.6% (95%CI: 20.1-43.8 %) respectively. The overall response was as follows; CR – 3%, m-ve PR 41%, m+ve PR 18%, SD 17%, PD 20%. In the second line setting, the 2 year PFS was 41.8% (95%CI: 21.7-60.8%) and 3y OS 45.8% (95%CI: 24.2-65.1%). The 2 year PFS according to the IGCCCG2 prognostic score was Intermediate = 34%, High risk =50% and very high risk = 30%. In the 3rd line setting the 2 year PFS was 20.9% (95%CI 9.5-35.4%) and 3 year OS was 23.8% (95%CI 11.7-38.2). For HDCT the 2 y PFS was good risk= 52%, Intermediate =29% and poor risk= 0%. There were 2 treatment related deaths from IPO, and 4 from HDCT. Grade 3 or 4 toxicities were as follows (>5%): neutropenia 35%, thrombocytopenia 18%, infection 15%, diarrhea 11%, lethargy 8%. Conclusions: IPO is a safe, non-nephrotoxic day care regimen which produces encouraging responses particularly in high risk cases. Where cisplatin is contra-indicated this is may be a useful alternative.
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Qiu, Ying, Ruidong Zhao, Mark M. Yun, Xia Han, Feiyu Yun, Bingchun Liu, Erxia Zhou, Xiaohui Ouyang, and Sheng Yun. "Immunity Enhancement in Immunocompromised Gastrointestinal Cancer Patients with Allogeneic Umbilical Cord Blood Mononuclear Cell Transfusion." BioMed Research International 2017 (2017): 1–8. http://dx.doi.org/10.1155/2017/5945190.
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Objectives. In order to enhance the immunity of cancer patients to prevent relapse or to prolong survival time, umbilical cord blood mononuclear cells (UCMCs) were transplanted to cancer patients. Patients and Methods. UCMCs were transfused to 63 immunocompromised gastrointestinal cancer patients with nonmyeloablative (NMA) conditioning regimen. Results. The clinical study showed that the number of both T and B cells increased much more rapidly after transfusion of UCMCs than that of the control group without transplantation (p<0.01). Proinflammation cytokines IFNγ and TNFα in serum increased to or above the normal range in 80.9% of patients at 12 weeks after UCMC transfusion. However, they recovered to the normal range in 21.7% of patients at the same time point in the control group only. In addition, the clinical investigation also showed that the transfusion of UCMC increased stable disease (SD) and reduced progressive disease (PD) significantly (p<0.01); however, it did not have significant effects on complete response (CR), partial response (PR), or mortality rates compared with the control group (p>0.05). Conclusions. UCMCs have powerful repairing effects on damaged cells and tissues and may reconstruct the impaired immunity. Transfusion of UCMCs could reconstruct the immunity of cancer patients with immunosuppression.
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Desai, Ami Vijay, Andrew Gilman, Mehmet Fevzi Ozkaynak, Arlene Naranjo, Wendy B. London, Sheena Cretella Tenney, Malcolm Smith, et al. "Outcomes and toxicities in patients (pts) non-randomly assigned to immunotherapy Children’s Oncology Group (COG) ANBL0032." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): 10523. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.10523.
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10523 Background: Immunotherapy with the anti-GD2 antibody dinutuximab plus sargramostim (GM-CSF), aldesleukin (IL-2) and isotretinoin following consolidation therapy improved outcome for high-risk neuroblastoma (HRNBL) pts enrolled on COG ANBL0032. Randomization was halted in 2009; subsequent pts were non-randomly assigned to immunotherapy. Toxicities and survival were evaluated. Methods: HRNBL pts < 31 years old with a pre-autologous stem cell transplant (ASCT) response of ≥ partial response (PR) were eligible. Demographics, INSS stage, tumor biology, 1993 INRC pre-ASCT response and toxicities were summarized using descriptive statistics. Five-year (yr) EFS and OS from time of study enrollment were estimated. Results: From 2009-2015, 1,183 pts were non-randomly assigned to immunotherapy. 96.7% (n = 1,144) were ≥18 months old and 83.1% (n = 765/921) had stage 4 disease. 45.1% (n = 363/805) of tumors with known biology were MYCN amplified, 94.5% (n = 749/793) had unfavorable histology, and 54.9% (n = 397/723) were diploid. Pre-ASCT, 352 (29.8%) pts had complete response (CR), 418 (35.3%) had very good partial response (VGPR), and 413 (34.9%) had PR. 1,042 (88.1%) pts underwent a single and 141 (11.9%) underwent tandem ASCT. For the entire cohort, 5-yr EFS was 61.1±1.9% and 5-yr OS was 71.9±1.7%. 5-yr EFS and OS for pts ≥18 months of age with stage 4 disease (n = 746) were 58.4±2.3% and 71.0±2.1%. 5-yr EFS and OS were 82.3±4.8% and 86.7±4.2% among pts with stage 3 disease (n = 110). EFS but not OS was superior for those with a CR/VGPR pre-ASCT vs. PR (5-yr EFS: 64.2±2.2% vs. 55.4±3.2%, p = 0.0133; OS: 72.7±2.1% vs. 70.5±2.9%, p = 0.3811). There was a trend toward improved OS for those treated with tandem vs. single transplant (5-yr EFS: 65.9±4.3% vs. 60.4±2.1%, p = 0.1282; OS: 76.5±3.8% vs. 71.2±1.9%, p = 0.0704). Grade ≥3 toxicities ( > 10% of pts) during GM-CSF and IL-2-containing cycles, respectively, included pain (15.6/11.4%), fever (15.1/32.7%), anemia (18.9/21.7%), thrombocytopenia (13.9/17.4%), lymphopenia (12.3/16.0%), and hypokalemia (13.3/25.2%). Additional Grade ≥3 toxicities ( > 10% of pts) included hypoxia (10.1%) during GM-CSF-containing cycles, and anaphylaxis (12.0%), neutropenia (16.1%), hyponatremia (16.5%), and hypotension (13.8%) during IL-2-containing cycles. Conclusions: In this large cohort of HRNBL pts treated with immunotherapy, 5-yr EFS was 61.1%. Superior EFS was observed for pts with stage 3 disease and for those with CR/VGPR pre-ASCT. IL-2-containing cycles were associated with increased toxicity. Clinical trial information: NCT00026312.
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Hu, Yang, Junha Shin, Sushmita Roy, and Mark E. Burkard. "Abstract P4-07-05: Tumor mutational profiles of extreme long-term survivors with metastatic breast cancer." Cancer Research 82, no. 4_Supplement (February 15, 2022): P4–07–05—P4–07–05. http://dx.doi.org/10.1158/1538-7445.sabcs21-p4-07-05.
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Abstract Background: Extreme population sampling can discover genomic characteristics with a high likelihood of functional significance. Here, we focus on people who live for many years or decades with metastatic breast cancer (MBC). Identification of genetic markers characteristic of this population may allow long-term survival to be predicted and enable de-escalation of treatment and improved care for this subgroup of breast cancer patients. . Methods: We identified women who have MBC and have lived greater than 10 years (HR+ breast cancer) or greater than 5 years (HR- breast cancer) from initial diagnosis. A total of 14 had archived FFPE metastatic tumor specimens and matched blood available for analysis. We performed whole-exome sequencing (WES) on FFPE tumor specimens (somatic) and blood samples (germline) pairs of 14 long term survivor patients. We used Illumina DRAGEN pipeline for the read alignment and base quality calibration and GATK MuTect2 pipeline for the somatic short variant identification. Common variants were filtered using 1000 Genomes Project, Exome Sequencing Project and gnomAD and annotated using Funcotator of the GATK pipeline. Results: A cohort of 53 patients, who met criteria, with biopsy proven MBC and long survival were identified in our institution. Among them, 14 patients had sufficient archived tumor for analysis, consisting of 7 HR+/HER2-, 5 HR+/HER2+, 1 HR+/HER2- and 1 TNBC specimens. Histological type was ductal in 9 patients and lobular in 4 patients. The median age of MBC diagnosis was 53 years with 11 patients diagnosed between ages 35-64 and 3 patients diagnosed after age 65. At the time of study, 13 of these 14 patients are still living. Median time to metastasis after diagnosis was 10.2 years with metastasis occurring in less than 1 year in 2 patients, less than 5 years in 10 patients and greater than 5 years in 2 patients. Metastases to bone were present in 9 patients, to visceral organs in 8 patients and to local and regional lymph nodes in 8 patients. The most common somatic variants identified were in PIK3CA, ARID1A, and TP53. When compared with prior analyses of MBC (INSERM, MBC Project), we found that ARID1A mutations were more commonly found, whereas PTEN and ESR1 mutations were never identified, suggesting a somatic mutational profile characteristic of extreme survivors. ARID1A mutations (2 nonsense - p.R1505* and p.Q944*, 1 missense - p.L1496V, 1 frameshift - p.P729fs) occurred in 4 patients, all with ER/PR+ and all HER2- breast cancer. Median survival to date since diagnosis was 30.1 years (range 21.4-39.0). Median survival to date after metastasis was 14.9 years (range 2.7-35.0). PIK3CA mutations (5 missense - p.H1047R x2, E545K, H1047L, E545K) occurred in 5 patients, all with ER/PR+ and 2 with HER2+ breast cancer. Median survival to date since diagnosis was 23.5 years (range 20.1-39.0). Median survival to date after metastasis was 15.97 years (range 3.4-35.0). TP53 mutations (1 nonsense - p.E285*, 1 missense - p.E285K, 1 frameshift - p.N200fs) occurred in 3 patients, all with ER/PR+ and 2 with HER2+ breast cancer. Median survival to date since diagnosis was 21.7 years (range 21.7-36.2). Median survival after metastasis was 16.0 years (range 2.7-21.4). Conclusions: ARID1A mutations are overrepresented and PTEN and ESR1 are underrepresented in metastatic tumors in extreme long-term survivors with MBC. Further analyses will determine if ARID1A mutations are present at tumor inception or are acquired in metastases in this cohort with indolent disease. Additionally, it is possible that germline genomic profiles may be relevant to long-term survival. Given the variability in this cohort, a larger sample of extreme survivors will be necessary to identify characteristic genetic profiles. Citation Format: Yang Hu, Junha Shin, Sushmita Roy, Mark E Burkard. Tumor mutational profiles of extreme long-term survivors with metastatic breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-07-05.
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Kim, Youn, Sean Whittaker, Marie France Demierre, Alain H. Rook, Adam Lerner, Madeleine Duvic, Sunil Reddy, et al. "Clinically Significant Responses Achieved with Romidepsin in Treatment-Refractory Cutaneous T-Cell Lymphoma: Final Results from a Phase 2B, International, Multicenter, Registration Study." Blood 112, no. 11 (November 16, 2008): 263. http://dx.doi.org/10.1182/blood.v112.11.263.263.
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Abstract Background: Responses to romidepsin, a novel pan-HDAC inhibitor, have been observed in patients (pts) with cutaneous T-cell Lymphoma (CTCL). This Phase 2B, singlearm, open-label registration study enrolled pts with CTCL (Stages IB–IVA) at 33 European and US sites. Pts with histologically confirmed CTCL who failed ≥1 prior systemic therapy, had adequate organ function, and ECOG PS 0 or 1 were eligible. Exclusions included significant cardiovascular abnormality or treatment with QTc-prolonging or CYP3A4-inhibiting drugs. Pts received romidepsin 14 mg/m2 as a 4-hr IV infusion on days 1, 8, and 15 every 28 days for up to 6 cycles (extended for stable disease or response). Aim: The primary endpoint was the response rate among evaluable pts, measured by a combination of a weighted scoring instrument to determine skin involvement (SWAT), imaging, and circulating Sézary cells (as applicable). Results: 96 pts were enrolled and received romidepsin (as-treated); 72 (75%) were evaluable (≥2 cycles) for efficacy. Enrollment is complete, 4 pts with confirmed PR continue to receive romidepsin on extended treatment, 5 pts off-treatment are being followed. Mean age of all pts was 57±12 yrs, and median time since diagnosis was 3 yrs (range <1–26). 68 pts (71%) had disease stage ≥IIB. Median number of prior systemic therapies was 2 (range 1–8). Response (assessed by investigators) and pruritus relief (assessed by visual analog scale [VAS]) data are in the table. Objective disease response rate (ORR) was not lower in pts with advanced-stage disease; 23 (47.9%) of 48 pts with stage IIB-IVA and 7 (29%) of 24 pts with stage IB-IIA achieved OR. With a median follow-up of 5.3 months (mo), median duration of response has not been reached. 50% of responders (evaluable pts) have maintained a response for ≥5 mo and 30% for ≥8 mo. The maximum duration of response was 19.8 mo. 24 (80%) of the 30 pts with a response had not progressed as of the last assessment. Most pts (48/52; 92%) with pruritus at baseline (≥30 mm on VAS) had some relief, including most of those with severe pruritus. Adverse events (AEs) occurred in 93 pts (97%). AEs reported in ≥20% of pts were nausea (56%), asthenia (52%), vomiting (29%), anorexia (23%), hypomagnesemia (21%), and pyrexia (20%). AEs ≥ grade 3 occurred in 32 pts (33%), most commonly fatigue (7%), disease progression (4%), and pyrexia (4%). 21 pts (22%) had a serious AE; the most frequently reported serious AEs were disease progression (6%), pyrexia (3%), sepsis (2%), tumor lysis syndrome (2%), and hypotension (2%). 20 pts (21%) withdrew because of AEs, including fatigue (4%), pyrexia (2%), prolonged QT (2%), and CTCL progression (2%). 6 pts (6%) died, 1 possibly related to treatment. Mean QTcF change from baseline to 2 hrs post-dose was 4.6 msec using baseline assessments before any anti-emetics and 1.3 msec using baseline assessment after anti-emetics. No pts had QTcF values >500 msec. Conclusions: This study shows clinical benefit associated with romidepsin use in treatment-refractory CTCL, with pts achieving durable response and relief from pruritus. Toxicities associated with romidepsin were tolerable and manageable. Evaluable Pts N=72 As-treated Pts N=96 a stable disease for ≥90 days b relief = ≥ 30mm decrease on 100mm VAS or score of 0 for 2 consecutive cycles Confirmed ORR 42% 34% PR, n (%) 24 (33%) 27 (28%) CCR, n (%) 6 (8%) 6 (6%) SD90a, n (%) 26 (36%) 28 (29%) Overall disease control (CCR+PR+SD90) 56 (78%) 61 (64%) Median time (mo) to response (range) 1.9 (0.9–4.8) 1.9 (0.9–4.8) Median time (mo) to disease progression (range) 9.0 (2.7–21.7) 8.3 (0–21.7) Confirmed OR in stage ≥ IIB, n (%) 23/48 (48%) 26/68 (38%) Relief of pruritusb, n (%) 25/52 (48%) NA Relief of severe pruritus, n (%) 16/29 (55%) NA
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Gaudeau, Albane, Coralie Clua Provost, Thierry Dorval, Andrew Walsh, Michael Hannus, Franck Perez, Jacques Camonis, Elaine Del Nery, and Jean-Philippe Stephan. "Cell-based siRNA screens highlight triple-negative breast cancer cell epigenetic vulnerability." International Journal of Scientific Reports 7, no. 4 (March 22, 2021): 196. http://dx.doi.org/10.18203/issn.2454-2156.intjscirep20211035.
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<p><strong>Background:</strong> Triple-negative breast cancer (TNBC) is a heterogeneous disease defined by ER-, PR- and HER2-negative phenotype and in most cases, a relatively aggressive clinical behaviour. The lack of specific targeted therapies and low efficiency of currently available chemotherapies spurred several clinical trials in the last few years. Despite encouraging results, TNBC still remains a major unmet medical need that prompted us to explore the role of 863 epigenetic modulators in TNBC cell survival.</p><p><strong>Methods:</strong> A comprehensive siRNA library was screened to explore the role of known epigenetic modulators in TNBC cell viability and growth. The knock-down effect was evaluated for 863 epigenetic genes using 4 siRNAs/gene in two TNBC and a non-TNBC cell lines using ATP-based luminescence and nuclei count image-based assays. Considering siRNA off-target effects, four analysis methods including a classical threshold-based analysis and three ranking methods were applied to determine on-target hits for each screen readout. Hit genes common to both phenotypic readouts highlighted strong epigenetic players involved in TNBC cell survival.</p><p><strong>Results:</strong> Overall, knock-down of many epigenetic modulator genes mitigates cell survival in TNBC and a non-TNBC cell lines depicted from both phenotypic readouts. Interestingly, ranking-based analysis confirmed hit genes identified in threshold-based analysis and also revealed additional hits enabling us to confirm CDK1 and KMT5A as important regulators in TNBC cell viability and growth. Surprisingly, CHAF1A appeared as a new candidate gene involved in TNBC cell survival.</p><p><strong>Conclusions:</strong> Taken together, siRNA epigenetic screening results identified CHAF1A as a novel regulator of TNBC cell survival.</p>
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Yang, Yichen, Qin Zhang, Caihong He, Jing Chen, Danfeng Deng, Wenwen Lu, and Yuming Wang. "Prevalence of sarcopenia was higher in women than in men: a cross-sectional study from a rural area in eastern China." PeerJ 10 (August 2, 2022): e13678. http://dx.doi.org/10.7717/peerj.13678.
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Background There were limited studies specifically evaluating whether the difference of the prevalence of sarcopenia exists in men and women in older adults from rural areas in China. The aim of this study was to compare the prevalence of sarcopenia between men and women in a rural area in eastern China and to explore the underlying causes. Methods This study included 1,105 participants aged 60-89 years. Muscle mass was measured by bio-electrical impedance analysis. Hand grip strength was measured by Jamar Hydraulic Hand Dynamometer. Sarcopenia was diagnosed according to the Asian Working Group for Sarcopenia-2019 Consensus. Data were analyzed using log-binomial and linear regression. Results The prevalence of sarcopenia was 21.7% in women and 12.9% in men among the study cohort. After adjusting for age, education level, number of diseases, income level, smoking, drinking, and eating habits, proportion of people with sarcopenia was 1.49-fold greater in women than in men (PR = 1.49, 95% CI [1.01–2.26], P = 0.055). Conclusions The prevalence of sarcopenia in elderly women in this rural area of eastern China is higher than in men, suggesting that women in rural areas in China seem to be more vulnerable for sarcopenia, thus early screening and prevention need to be provided for them to address such gender disparity in health.
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Mancuso, A., P. Saletti, S. Sacchetta, E. Romagnani, F. Cavalli, and C. N. Sternberg. "Treatment outcomes with first and second line chemotherapy in advanced and metastatic pancreatic cancer patients." Journal of Clinical Oncology 24, no. 18_suppl (June 20, 2006): 14107. http://dx.doi.org/10.1200/jco.2006.24.18_suppl.14107.
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14107 Background: Recent advances in the treatment of pancreatic cancer might influence the management of locally advanced and metastatic disease, nonetheless prognosis remains dismal (1-year survival rates: 24%). The impact on survival of palliative second-line therapy is hotly debated. Methods: We retrospectively reviewed the clinical records of 103 pancreatic cancer patients admitted to San Camillo/Forlanini Hospital (Rome, Italy) and the Oncology Institute of Southern Switzerland during the period June, 1997 to August, 2005 [60 males, 43 females, median age 65 years (range 43–80); median ECOG performance status (PS): 1]. All patients received Gemcitabine as single agent (90%) or in combination with Oxaliplatin (10%) as upfront therapy. A total of 12 fluoropyrimidine-based salvage regimens were administered to 46 patients in the second line setting. Best supportive care was selected in 57 patients after failing first line therapy. Results: Of 103 evaluable patients, first line chemotherapy produced overall tumor growth control of partial response (PR) and stable disease(SD) by RECIST criteria of 52.4% with a median progression free survival (PFS) of 4.6 months. Multivariate analysis revealed that the most important prognostic factor for PFS was the patient’s PS, as patients with PS of 1–2 at diagnosis had significantly worse results than patients with PS = 0 (First line PFS: 110 days vs 193 days, p<0.05). Baseline CA19–9 and number of metastatic sites were not independent prognostic factors for better first-line PFS. PR was observed in 8/46 patients (17.3%) who received second line chemotherapy, SD in 10 (21.7%), and 28 patients progressed (61%). Median overall second line PFS was 3.2 months. Patients who had responded to first-line Gemcitabine were more likely to respond or attain stable disease with second-line treatment, with a PFS of 5.6 vs 2.85 months (p<0.05). The overall survival for all evaluable patients was 8.4 months. 1-year survival was 52% for patients treated with second line therapy. Conclusions: These results are consistent with historical studies and suggest that fluoropyrimidine-based salvage regimens have marginal but definite activity and should be considered in patients who have responded to first line chemotherapy with an optimal PS. No significant financial relationships to disclose.