bluuebunny/crossref_metadata_2025_split huggingface dataset:
Parameter-dependent transmission dynamics and optimal control of foot and mouth disease in a contaminated environment
Authors: Mugabi Francis , Mugisha Joseph , Nannyonga Betty , Kasumba Henry , Tusiime Margaret 
Published: March 2020

AbstractThe problem of foot and mouth disease (FMD) is of serious concern to the livestock sector in most nations, especially in developing countries. This paper presents the formulation and analysis of a deterministic model for the transmission dynamics of FMD through a contaminated environment. It is shown that the key parameters that drive the transmission of FMD in a contaminated environment are the shedding, transmission, and decay rates of the virus. Using numerical results, it is depicted that the host-to-host route is more severe than the environmental-to-host route. The model is then transformed into an optimal control problem. Using the Pontryagin’s Maximum Principle, the optimality system is determined. Utilizing a gradient type algorithm with projection, the optimality system is solved for three control strategies: optimal use of vaccination, environmental decontamination, and a combination of vaccination and environmental decontamination. Results show that a combination of vaccination and environmental decontamination is the most optimal strategy. These results indicate that if vaccination and environmental decontamination are used optimally during an outbreak, then FMD transmission can be controlled. Future studies focusing on the control measures for the transmission of FMD in a contaminated environment should aim at reducing the transmission and the shedding rates, while increasing the decay rate.
On conformally doubly warped product Finsler manifold
Authors: Soleiman A. , Abdelsalam A.M. 
Published: March 2020

AbstractThe aim of the present paper is to introduce the notion of conformally doubly warped product Finsler manifold (CDWPF). For such a Finsler manifold, the coefficients of Barthel connection and its curvature tensor are investigated. The coefficients of Cartan, Berwald, Hashiguchi and Chern (Rund) connections of CDWPF are calculated. Some special Finsler spaces are studied.
Coupled coincidence point technique and its application for solving nonlinear integral equations in RPOCbML spaces
Authors: Hammad Hasanen A. , Albaqeri Dhekra M. , Rashwan Rashwan A. 
Published: March 2020

AbstractThe aim of this paper is to obtain some new important consequences related to coupled coincidence points via C-class functions in the context of a regular partial ordered complete b-metric-like space (for short, RPOCbML space); this space arises from combining the results of b-metric-like space with partial metric space and adding the regularity condition. Finally, we support our theoretical results by some examples and an application about finding an analytical solution for nonlinear integral equations.
Hall and ion slip effects on Unsteady MHD Convective Rotating flow of Nanofluids—Application in Biomedical Engineering
Authors: Krishna M. Veera , Chamkha Ali J. 
Published: March 2020

AbstractThere is an intense worldwide activity in the development of instrumentation for medical diagnosis and bioscreening based on biological labeling and detection of nanoparticles. Based on this profound observation, Hall and ion slip effects on magnetohydrodynamic (MHD) free convective rotating flow of nanofluids in a porous medium past a moving vertical semi-infinite flat plate are investigated. The equations for governing flow are solved analytically by perturbation approximation. The effects of various parameters on the flow are discussed through graphs and tables. The velocity increases with Hall and ion slip parameters. An increase in the convective parameter led to amplify the thermal boundary layer thickness, but when the heat generation parameter is taken into consideration, an opposite effect occurs. The skin friction coefficient increases with an increase in nanoparticle volume fraction and it reduces with increase in Hall and ion slip parameters. Outcomes disclose that the impact of thermal convection of nanoparticles has increased the temperature distribution, which helps in destroying the cancer cells during the drug delivery process.
Activity of Vincristine and Irinotecan in Diffuse Anaplastic Wilms Tumor and Therapy Outcomes of Stage II to IV Disease: Results of the Children’s Oncology Group AREN0321 Study
Authors: Daw Najat C. , Chi Yueh-Yun , Kalapurakal John A. , Kim Yeonil , Hoffer Fredric A. , Geller James I. , Perlman Elizabeth J. , Ehrlich Peter F. , Mullen Elizabeth A. , Warwick Anne B. , Grundy Paul E. , Paulino Arnold C. , Gratias Eric , Ward Deborah , Anderson James R. , Khanna Geetika , Tornwall Brett , Fernandez Conrad V. , Dome Jeffrey S. ,   on behalf of the AREN0321 Study Committee
Published: March 2020

PURPOSE AREN0321 evaluated the activity of vincristine and irinotecan (VI) in patients with newly diagnosed diffuse anaplastic Wilms tumor (DAWT) and whether a regimen containing carboplatin (regimen UH1) in addition to regimen I agents used in the National Wilms Tumor Study 5 (NWTS-5; vincristine, doxorubicin, cyclophosphamide, and etoposide plus radiotherapy) would improve patient outcomes. PATIENTS AND METHODS Patients with stage II to IV DAWT without measurable disease received regimen UH1. Patients with stage IV measurable disease were eligible to receive VI (vincristine, 1.5 mg/m2 per day intravenously on days 1 and 8; irinotecan, 20 mg/m2 per day intravenously on days 1-5 and 8-12 of a 21-day cycle) in an upfront window; those with complete (CR) or partial response (PR) had VI incorporated into regimen UH1 (regimen UH2). The study was designed to detect improvement in outcomes of patients with stage II to IV DAWT compared with historical controls treated with regimen I. RESULTS Sixty-six eligible patients were enrolled. Of 14 patients with stage IV measurable disease who received VI, 11 (79%) achieved CR (n = 1) or PR (n = 10) after 2 cycles. Doses of doxorubicin, cyclophosphamide, and etoposide were reduced midstudy because of nonhematologic toxicity. Four patients (6%) died as a result of toxicity. Four-year event-free survival, relapse-free survival, and overall survival rates were 67.7% (95% CI, 55.9% to 79.4%), 72.9% (95% CI, 61.5% to 84.4%), and 73.7% (95% CI, 62.7% to 84.8%), respectively, compared with 57.5% (95% CI, 47.6% to 67.4%; P = .26), 57.5% (95% CI, 47.6% to 67.4%; P = .048), and 59.2% (95% CI, 49.4% to 69.0%; P = .08), respectively, in NWTS-5. CONCLUSION VI produced a high response rate in patients with metastatic DAWT. AREN0321 treatment seemed to improve outcomes for patients with stage II to IV DAWT compared with NWTS-5, but with increased toxicity. The UH2 regimen warrants further investigation with modifications to reduce toxicity.
Characteristics of a single-centre series of familial testicular germ cell tumours
Authors: Coffey J. , Huddart R. A. , Norman A. R. , Dudakia D. , Stratton M. R. , Rapley E. A. 
Published: March 2020

10039 Background: Testicular germ cell tumors (TGCTs) account for 1% of all male cancers with increasing incidence rates documented. A family history of TGCT occurs in 2% of patients, conferring relative risks of 8–10 for brothers and 4–6 for fathers or sons of patients. These risks are high in comparison to other solid cancers and suggest that the risk of developing TGCT may be, at least in part, inherited rather than acquired. Methods: Pedigrees with >1 male family member with TGCT were identified from a tumor database and systematically collected from 1992. Patients donated samples and medical details with full informed consent and under ethical review board approval. Pedigree and medical data were obtained by interview, mail and telephone contact. Results: This series examines 78 pedigrees, containing 160 cases and 170 TGCTs. In the period 1994–2003 6% of all cases had a family history of TGCT. It includes 35 sib-pairs, 12 father-son pairs, 11 uncle-nephew pairs, 10 cousin pairs and 4 pedigrees with ≥ 3 cases of TGCT. The dataset contains 66 seminomas, 56 non-seminomas, 17 mixed histology, 1 CIS and 30 tumors of unconfirmed histology. The median age at diagnosis was 33 (range 17 to 87). The median difference in age at diagnosis between the cases in each pedigree was 6 years (0–58). Histology was concordant between family members in 22 of the 53 (41.5%) 2-case pedigrees. 11 pedigrees contained a case with bilateral TGCTs (6.9% of all cases, compared to 1.1% in the sporadic patient population, p<0.001) with 50% histological concordance. The median age at diagnosis of bilateral tumors was 32 (21–42) for the first tumor and 35 (26–49) for second tumors. 24 TGCT cases (15%, compared to an expected rate of 10%, p=0.045) reported a history of UDT. 9/162 (5.5%) of TGCT cases also developed non-TGCT cancers, including penile, bladder, colorectal, hepatic and pancreatic tumors. Conclusions: When systematic collection is undertaken the incidence of familial TGCT may be higher than previously reported. Familial cases have a higher incidence of UDT and bilateral disease. The majority of this set has been used in an international genome-wide linkage analysis to identify TGCT susceptibility genes. No significant financial relationships to disclose.
Heat shock protein 70 vaccines activate NK cells through NKG2D
Authors: Liu B. , Qaio Y. , Li Z. 
Published: March 2020

10044 Background: We have previously reported that vaccination with heat shock protein 70 (HSP70) induced natural killer (NK) cell activity in patients with chronic myelogenous leukemia (CML). The underlying mechanism is unclear. Methods: HSP70 was purified from the peripheral blood mononuclear cells. CD56+ NK cells were enriched by magnetic sorting after staining PBMCs with anti-CD56 monoclonal antibody. Dendritic cells (DCs) were derived from peripheral blood monocytes after culture in the presence of IL-4 and GM-CSF. NK activation was measured by the IFNgamma ELISPOT assay. Results: Unexpectedly, HSP70 of autologous, allogeneic as well as xenogeneic origin was found to stimulate IFNgamma production from peripheral blood mononuclear cells of CML patients as well as normal subjects. Further studies demonstrated that the activity of HSP70 was dependent on both NK cells and DCs. HSP70 did not induce significant IFNgamma production from either NK cells or DCs alone. Mechanistically, we found that HSP70-mediated DC-NK cell crosstalk required cell-cell contact, which could be inhibited completely by neutralizing antibody against NK activating receptor NKG2D. The significance of NKG2D was further corroborated by the finding that HSP70 induced the expression of an NKG2D ligand, the MHC class I chain-related protein A (MICA), on DCs; HSP70-augmented IFNgamma release was abrogated by antibody against MICA. Conclusions: Thus HSP70 may serve as a critical link between NK and DCs in mounting immune responses against infections, cancers and self-antigens. Our novel findings support further studies in the development of HSP70-based vaccines against human malignancies. Acknowledgement: Z.L. is a clinical scholar of the Leukemia and Lymphoma Society. No significant financial relationships to disclose.
Endothelial progenitor marker CD133 mRNA expression in peripheral blood mononuclear cells predicts outcome of cancer patients
Authors: Mehra N. , Penning M. , Maas J. , Van Daal N. , Voest E. 
Published: March 2020

10087 Background: We examined whether expression of CD133, a surface molecule expressed on progenitors of hematopoietic and endothelial lineages, is increased in the peripheral blood mononuclear cells (PBMC’s) of cancer patients. Furthermore we correlated CD133 mRNA expression with tumor prognostication factors and overall survival. Methods: PBMC’s were isolated from the blood of 130 advanced cancer patients (43 renal cell carcinoma, 27 colorectal cancer, 34 prostate cancer, 27 head and neck cancer). Clinicopathological parameters were obtained. Median follow-up time was 16 months after inclusion (range 3–33 months). For the quantification of CD133 mRNA we used a real-time detection and quantification method based on nucleic acid sequence-based amplification (NASBA). Also U1A DNA was quantified as internal control for input and isolation. CD133 mRNA copy numbers were expressed as copies per 10.000 cells, as determined by U1A DNA. Results: Patients with metastasized disease have a significant increase in CD133 mRNA as compared to patients without metastasis. This increase is strongest in patients with bone metastasis. Subgroup analysis in patients with bone involvement show that CD133 mRNA also correlates with PSA (n=34)and inversely with hemoglobin (n=50). CD133 mRNA expression is an independent predictor for overall survival in Cox’s multivariate analysis (variables in the model included age, hemoglobin, metastasis, previous treatment and CD133 as categorical variable). A CD133 mRNA cut-off value was established by Receiver Operating Characteristic analysis of CD133 expression in relationship to survival (sensitivity 64% and specificity 71%). Cancer patients with more than 200 copies of CD133 mRNA, demonstrate a decreased survival compared to patients with lower CD133 expression (median survival 8 and 15.4 months, respectively). In patients with bone metastasis the median survival of high and low expressers is 6.3 months and 21.9 months, respectively. Conclusions: mRNA expression of stem-cell marker CD133 is increased in cancer patients with metastasized disease and an independent prognostic factor for overall survival. Increased CD133 mRNA expression may reflect an activated angiogenic state in these cancer patients. [Table: see text]
Efficacy of zoledronic acid versus placebo on biochemical markers of bone metabolism in patients with breast cancer metastatic to bone
Authors: Kohno N. , Aogi K. , Minami H. , Takashima S. 
Published: March 2020

10559 Background: Zoledronic acid reduces the levels of bone markers and the risk of skeletal complications in patients with bone metastases. Recently, a correlation between the levels of biochemical markers of bone metabolism and the risk of clinical complications (ie, skeletal complications, disease progression, and death) in patients with bone metastases has been reported. The effect of zoledronic acid on bone marker levels was assessed in patients with bone metastases from breast cancer in a multicenter randomized trial conducted in Japan. Methods: Women with bone metastases secondary to breast cancer (N = 228) were randomized to 4 mg zoledronic acid (n = 114) or placebo (n = 114) every 4 weeks for 1 year. Levels of urinary N-telopeptide (NTX), a sensitive marker of bone resorption, were measured at baseline and regularly throughout the study. Results: The table shows that zoledronic acid reduced NTX levels in patients compared with placebo. Patients treated with zoledronic acid had a mean decrease of 61% from baseline NTX levels at week 2. This decrease was maintained throughout the study in this treatment group and was 54% at week 52. In contrast, patients in the placebo group had a mean increase of 27% from baseline NTX levels at week 2, and levels of NTX continued to increase during the study, reaching 146% above baseline at week 52. Conclusions: This analysis shows that treatment with zoledronic acid reduced NTX levels in patients with bone metastases from breast cancer compared with placebo. These results are consistent with published reports in patients with prostate or lung cancer and are consistent with the significant reduction in skeletal morbidity observed in this trial in breast cancer patients. Zoledronic acid demonstrated a 39% reduction in skeletal morbidity in this patient population. [Table: see text] No significant financial relationships to disclose.
Fulvestrant (F) in metastatic breast cancer: Standard dose (Std) vs loading dose (Ld)—A retrospective study
Authors: Moussallem C. D. , Lopez A. , Gauthier A. , Moore S. , Johnson M. , Murray J. L. , Ibrahim N. K. 
Published: March 2020

10575 Background: Fulvestrant is shown to be an effective hormonal agent in menopausal hormone-receptor positive metastatic breast cancer (MBC) patients. This study aimed at showing if Ld of fulvestrant will improve its efficacy over the FDA approved Std schedule. Methods: We retrospectively reviewed our pharmacy electronic database over a period of two years to identify MBC patients who were treated with fulvestrant. Patients received either Std of 250 mg IM on day (d) 1 and repeated Q28d or Ld of 500 mg IM d1 and 15 and Std on d28 which was repeated every 28 days until evidence of progression. All medical records were reviewed and responses were recorded as improved disease (ID), stable disease (SD), or progressive (PD) as documented by the treating oncologist. Time to response (TTR) (the interval from first injection until response) as well the duration of response (DR), was determined. Results: Medical records of 157 consecutive, evaluable patients who received F for their MBC were identified and reviewed. Group 1 (Gp1) received std (N = 122) and Group 2 (Gp2) received loading dose (N = 35). There were no significant differences between the two groups in relation to age, pathology, grade, Her-2, ER and PR status or number of prior chemotherapy regimens (p > 0.05). Gp2 had statistically significant more prior hormone therapies (p = 0.0159). Median number of doses for Gp2 was 5 (R: 1–18) compared to 3 (R: 1–25) for Gp1 (p = 0.0169). Responses (ID) 14% for Gp1 and 18% for Gp2; clinical benefits (ID + SD) were 37.7% and 38%, respectively, NSS (p = 0.9550). TTR was 10 (R: 6–32) wks for Gp1 and 8 (R: 4–20) wks for Gp2; the DR was 15.5 (R: 4- 84) weeks for Gp1, and 12 (R: 2- 96) for Gp2. No statistical significance was detected between the 2 groups. Conclusions: This study showed there is no significant difference between the 2 dose schedules, either in the response rate or its duration. Prospective studies are needed to prove the equivalence of the Std and Ld of F. No significant financial relationships to disclose.
Phase II trial of gemcitabine and carboplatin, plus trastuzumab in HER2+ patients as first line therapy in metastatic breast cancer
Authors: Yardley D. A. , Peacock N. W. , Shipley D. , Waterhouse D. , Landgdon R. , Simons L. , Thomas S. , Hainsworth J. D. , Spigel D. R. , Burris H. A. 
Published: March 2020

10590 Background: Gemcitabine (G) and carboplatin (C) demonstrate significant preclinical synergy together as well as in combination with trastuzumab (H) in metastatic breast cancer (MBC) pts. This multicenter phase II trial evaluates the efficacy and safety of G + C with trastuzumab in HER2 + pts as 1st line therapy in MBC. Methods: Eligibility requirements: females > 18 with no prior regimens for MBC, ECOG 0–2, RECIST bidimensional disease, and adequate organ function. FISH HER2 + pts received H with GC. Treatment: G 1,000 mg/m2 D1& 8 with C AUC 5 D1 in the first 20 pts. Following a toxicity assessment revealing significant myelosuppression, C was administered in subsequent pts at AUC 4. 14 HER2+ pts received H 8 mg/kg loading dose followed by 6 mg/kg q21 days. Pts were evaluated for response after 9 weeks; treatment continued until progression or toxicity except in HER2+ pts who received up to 6 cycles GCH followed by single agent H. Results: Between 11/03 & 11/05, 45 pts have been treated: median age 55 for GC, 65 for GCH, ECOG 0/1 22/23. 19 pts were chemonaive. 26 pts received prior adjuvant chemotherapy: 20 pts adjuvant anthracyclines (A) & taxanes (T), 3 only prior A and 3 prior T. 73% had 2 or more metastatic sites of disease. 31 pts received GC & 14 pts received GCH. 18 of 41 evaluable pts (44%) had objective responses (PR 16, CR 2) with 17 pts (42%) exhibiting SD & 6 pts PD (15%). 91% of AT pretreated pts demonstrated SD or better. 9 remain on study. 6 went off study due to heme related toxicities and 9 due to MD discretion [4 max benefit, 3 XRT]. Median # of cycles was 5. Combined G3/4 hematologic toxicity was notable for 66% neutropenia (only 1 FN), 55% thrombocytopenia, and 32% anemia, predominately occurring at the carboplatin AUC 5 dose level. Transfusions of PRBCs and plts were administered in 14 and 8 pts respectively. Nonhematologic toxicity was minimal and remarkable for G3/4 fatigue in 20%. Conclusions: In FISH HER2+ pts, the addition of trastuzumab to GC yielded a 50% RR, with no evident cardiotoxicity. The combination of gemcitabine with carboplatin AUC 4 is active, albeit with moderate hematologic toxicity, warranting further exploration of alternate GC ± H schedules in breast cancer. [Table: see text]
Every-other week capecitabine (C7) combinations: An active and well tolerated treatment in heavily pretreated patients (p) with advanced solid tumours
Authors: Chacon J. , López L. , Quintanar T. , Rubio G. , Blanca M. , Andrade J. , Carbonero I. , G Esteban C. , Cruz M. A. 
Published: March 2020

10649 Background: Standard C schedule is 14 days every 3 w (C14). However, data have shown that C7 schedule is as effective as and significantly less toxic than C14. The objective is to evaluate retrospectively the response rate and toxicity of C7 as single agent or in combination in heavily pretreated p with advanced solid tumours. Methods: p with advanced solid tumour, age ≤ 75 years, ECOG PS <2 and adequate bone marrow, renal and hepatic functions were analyzed. p received C7: 1250 mg/m2/12 h x 7 days every-other week. The combination drugs doses were adjusted to be used days 1 and 15. Cycles every 28 days. Response was evaluated every 3 cycles according to RECIST criteria Results: 20 p received C7. Cancer type: 11 breast (BC), 7 colo-rectal (CRC), 1 H&N and 1 gastric (GC). Median age 56 y (33–75). M/F: 8p/12p. ECOG 0/1: 39%/61%. 19 p stage IV and 1 (H&N) stage III. The most frequent metastatic site was liver 42.2%. 90% p had been heavily pretreated with chemotherapy (CT): 55% p had received ≥ 2 CT lines. 15% p had been treated with taxanes, 45% p taxanes + anthracyclines, 10% p 5-FU, 15% p oxaliplatin (Oxa) and/or raltritexed. 2 BC p had also received herceptin (Her) and 2 p (1BC/1CRC) had been previously treated with C14. Median nº cycles: 6 (1–19). C7 combinations were: 5/7 CRC p Oxa or CPT-11 and 11/11 BC p docetaxel (1p) or gemcitabine (1 p) or carboplatin (9 p) ± Her. 4 p received C7 alone. Toxicity (20 p). Grade I/II: HFS 55%, diarrhoea 25%, nausea/vomiting 15%, mucositis 5%, skin 5% and parestesias 5%. Grade III/IV: diarrhoea in 2 p (1CRC and 1 BC). Response (20 p): 2 CR (10%) both CRC p; 6 PR (30%) 5 BC p and 1 CRC p; 4 SD (20%) and 8 PD (40%). 40% ORR rate and 60% TGC. Median response duration: 37 w (22–44 w). 2 p who achieved CR received C7 combined with CPT-11. C7 combination in p with PR were Oxa (1 CRC p) and carboplatin ± Her (5 BC p). Conclusions: C7 schedule is an active regimen in patients with advanced CRC and BC heavily pretreated with CT and it shows a very favourable toxicity profile. These results warrant a phase II trial of carboplatin-C7 in MBC as front line therapy that will by lauched by Feb-2006. No significant financial relationships to disclose.