Correlation of diaphragm surgical findings with preoperative CT scans in ovarian cancer

Correlation of diaphragm surgical findings in ovarian cancer patients with and without diaphragm metastases with pre-operative CT diaphragm findings to assess sensitivity and specificity for diaphragm disease. Material and Methods: A retrospective study of 120 ovarian cancer patients (60 with and 60 without diaphragm metastases at surgery), FIGO Stage IIIC or IV, undergoing cytoreductive surgery at Mayo Clinic, Arizona, between January 2000 and October 2014. All patients had preoperative imaging with CT scan of abdomen and pelvis including the lower lung fields. CTs were not reviewed retrospectively. Results: Among 60 patients with diaphragm metastases, preoperative CTs were positive for diaphragm disease in 17 patients, with a sensitivity rate of 28% (CI 95%: 0.17-0.41). All 60 patients with no diaphragm metastases had negative CTs, with a specificity of 100% (CI 95%: 94.0%-100%). When analyzed by lesion size, CTs were negative in 66.7-80% of patients with diaphragm lesions ranging from 1-15 mm. There was a trend towards increased detection rate with increasing size of lesions, but it did not reach significance (p = 0.529). CT detection rate for single metastatic lesion was 18.2% (6/33) and for multiple lesions it was 25.9% (7/27). There was no difference for CT identification of right, left, or bilateral metastases (p = 0.399). The sensitivity and specificity of CT for pleural effusion was 100% (CI 95%: 72.2%-100%) and 88% (CI 95%: 76.2%- 94.4%), respectively. The area under the receiver operating characteristic (ROC) curve was 0.680 (CI 95%: 55.3%-72.2%) for CT detection of diaphragm metastases and 0.957 (CI 95%: 79.9%-95.3%) for pleural effusions. Conclusion: CT has a low sensitivity and a high specificity for the prediction of diaphragm metastases in ovarian cancer. The size, location, and number of diaphragm lesions do not significantly improve CT detection rat

Pegylated interferon alfa-2a for polycythemia vera or essential thrombocythemia resistant or intolerant to hydroxyurea

Prior studies have reported high response rates with recombinant interferon-a (rIFN-a) therapy in patients with essential thrombocythemia (ET) and polycythemia vera (PV). To further define the role of rIFN-a,we investigated the outcomes of pegylated-rIFN-a2a (PEG) therapy in ET and PV patients previously treated with hydroxyurea (HU). The Myeloproliferative Disorders Research Consortium (MPD-RC)-111 study was an investigator-initiated, international, multicenter, phase 2 trial evaluating the ability of PEG therapy to induce complete (CR) and partial (PR) hematologic responses in patients with high-risk ET or PVwho were either refractory or intolerant to HU. The study included 65 patients with ET and 50 patients with PV. The overall response rates (ORRs; CR/PR) at 12 monthswere 69.2%(43.1% and 26.2%) in ET patients and 60% (22% and 38%) in PV patients. CR rates were higher in CALR-mutated ET patients (56.5% vs 28.0%; P 5 .01), compared with those in subjects lacking a CALR mutation. The median absolute reduction in JAK2V617F variant allele fraction was 26% (range, 284%to 47%) in patients achieving a CR vs 14%(range, 218% to 56%) in patients with PR or nonresponse (NR). Therapy was associated with a significant rate of adverse events (AEs); most were manageable, and PEG discontinuation related to AEs occurred in only 13.9% of subjects. We conclude that PEG is an effective therapy for patients with ET or PV who were previously refractory and/or intolerant of HU

Selektivno određivanje Fe(III) u uzorcima Fe(II) UV-spektrofotometrijom pomoću kvercetina i morina

Selective UV-spectrophotometric methods for determination of iron(III) in iron(II) samples have been developed. The methods are based on the interaction of Fe(III) with quercetin and morin, compounds of the flavonoid group. Redox reactions occurring between Fe(III) ions and the reagents used make the basis for the detection. Iron(II) does not react with quercetin and morin under the conditions applied [aqueous-methanolic (3 : 2) solutions, 0.3 mol L1 HCl, and 1.2 × 10-4 mol L1 quercetin (morin)] and does not interfere with the determination of Fe(III). Iron(III) can be determined up to 15 μg mL1 using both the examined systems. The detection limits are 0.06 and 0.38 μg mL1 when using quercetin or morin, respectively. The method with quercetin was applied to the determination of Fe(III) (ca. 0.2%) in a Fe(II) pharmaceutical product.U radu je opisan razvoj selektivnih UV-spektrofotometrijskih metoda za određivanje željeza(III) u uzorku željeza(II). Metode se temelje na redoks reakciji Fe(III) sa spojevima iz skupine flavonoida kvercetinom i morinom u reakcijskim uvjetima u kojima željezo(II) ne reagira (vodeno/metanolna otopina 3:2, 0,3 mol L1 HCl, 1,2 x 104 mol L1 kvercetin ili morin). Najniža koncentracija željeza(III) koja se može odrediti je 15 μg mL1 u oba ispitivana sustava. Granice detekcije su 0,06 i 0,38 μg mL1 ako se koristi kvercetin, odnosno morfin. Metoda s kvercetinom primijenjena je za određivanje Fe(III (približno 0,2%) u farmaceutskom produktu Fe(II)

Synergistic combination of cytotoxic chemotherapy and cyclin-dependent kinase 4/6 inhibitors in biliary tract cancers

Background and aims: Biliary tract cancers (BTCs) are uncommon, but highly lethal, gastrointestinal malignancies. Gemcitabine/cisplatin is a standard-of-care systemic therapy, but has a modest impact on survival and harbors toxicities, including myelosuppression, nephropathy, neuropathy, and ototoxicity. Whereas BTCs are characterized by aberrations activating the cyclinD1/cyclin-dependent kinase (CDK)4/6/CDK inhibitor 2a/retinoblastoma pathway, clinical use of CDK4/6 inhibitors as monotherapy is limited by lack of validated biomarkers, diffident preclinical efficacy, and development of acquired drug resistance. Emerging studies have explored therapeutic strategies to enhance the antitumor efficacy of CDK4/6 inhibitors by the combination with chemotherapy regimens, but their mechanism of action remains elusive.Approach and results: Here, we report in vitro and in vivo synergy in BTC models, showing enhanced efficacy, reduced toxicity, and better survival with a combination comprising gemcitabine/cisplatin and CDK4/6 inhibitors. Furthermore, we demonstrated that abemaciclib monotherapy had only modest efficacy attributable to autophagy-induced resistance. Notably, triplet therapy was able to potentiate efficacy through elimination of the autophagic flux. Correspondingly, abemaciclib potentiated ribonucleotide reductase catalytic subunit M1 reduction, resulting in sensitization to gemcitabine.Conclusions: As such, these data provide robust preclinical mechanistic evidence of synergy between gemcitabine/cisplatin and CDK4/6 inhibitors and delineate a path forward for translation of these findings to preliminary clinical studies in advanced BTC patients.</p

Safe Optimization of Steel Manufacturing with Reinforcement Learning

Steel production is a complex problem, and little has been done to improve it with the usage of Reinforcement Learning techniques. Most studies focus on decomposing it into sub-problems, instead of tacking it as a whole. Research has shown promising results in the area of safe policy improvement on toy problems. These algorithms are not only computationally tractable but also do not compromise the agent's safety concerns during learning. This thesis investigates how they perform on the real-world problem of improving steel production logistics. We take a simulation of a steel plant that uses hand-crafted heuristics for scheduling tasks and model it as a Markov Decision Process. We experiment with safe policy improvement algorithms by using different baseline policies. Given problem suffers from the known ''Curse of dimensionality''. Hence, the algorithms are adjusted to cope with the fast-expanding complexity. The methods prove to learn with fewer amount of samples than exploration methods. The results are especially promising with a highly stochastic baseline policy, as then the agent has a better understanding of the large environment. The next focus is on the factored representation, which has the advantage of better utilizing the problem. However, in our setting, the algorithms become too computationally expensive.Computer Science | Data Science and Technolog

Antioxidant properties of high quality black teas available on the e-commerce market

Celem publikacji było oznaczenie aktywności przeciwutleniającej wysokogatunkowych herbat czarnych pochodzących z wyselekcjonowanych upraw w Indiach, Nepalu, Ruandzie oraz Turcji, zakupionych na rynku e-commerce. Oznaczono również parametry barwy mierzonej w systemie CIEL*a*b*. Podjęto próbę określenia statystycznych zależności pomiędzy barwą a zawartością związków polifenolowych. Dodatkowo, wykorzystując wyniki analizy głównych składowych, podjęto próbę klasyfikacji jakościowej badanych herbat. Badane herbaty pod względem analizowanych parametrów można zaliczyć do herbat wysokogatunkowych, gdyż charakteryzowały się dużą zawartością związków polifenolowych, w zakresie od 335,32 do 534,57 mg GAE/100 ml naparu. Herbaty pochodzące z Ruandy cechowała statystycznie istotnie wyższa zawartość związków polifenolowych w stosunku do pozostałych, szczególnie tych z Nepalu i Indii, które zgodnie z oznaczeniami powinny być najlepszej jakości. Mimo umiarkowanego stopnia skorelowania badanych parametrów nie udało się ustalić liniowego związku pomiędzy tymi zmiennymi.The aim of the publication was to determine the antioxidant activity of high-quality black teas from selected crops in India, Nepal, Rwanda and Turkey purchased on the e-commerce market. The color parameters were also marked in the CIE L*a*b* system and compared to the total polyphenols content. In addition, using the results of principal components, an attempt was made to qualitatively classify analyzed teas. Regarding the parameters, the studied samples of tea could be classified as high-quality teas as an average content of polyphenols in all of the infusions ranged from 335,32 mg GAE/100 ml to 534,57 mg GAE/100 ml. The highest content of polyphenols was determined in samples of tea from Rwanda and it was significantly higher in relation to others, particularly those from India and Nepal that were described as the highest quality products. Despite the moderate degree of the linear correlation between studied parameters, the linear relationship could not be determined with the statistically significant accuracy between these variables