A Self-Organized ECM-Mimetic Model Based on an Amphiphilic Multiblock Silk-Elastin-Like co-Recombinamer with a Concomitant Dual Physical Gelation Process

Although significant progress has been made in the area of injectable hydrogels for biomedical applications and model cell niches, further improvements are still needed, especially in terms of mechanical performance, stability, and biomimicry of the native fibrillar architecture found in the extracellular matrix (ECM). This work focuses on the design and production of a silk-elastin-based injectable multiblock corecombinamer that spontaneously forms a stable physical nanofibrillar hydrogel under physiological conditions. That differs from previously reported silk-elastin-like polymers on a major content and predominance of the elastin-like part, as well as a more complex structure and behavior of such a part of the molecule, which is aimed to obtain well-defined hydrogels. Rheological and DSC experiments showed that this system displays a coordinated and concomitant dual gelation mechanism. In a first stage, a rapid, thermally driven gelation of the corecombinamer solution takes place once the system reaches body temperature due to the thermal responsiveness of the elastin-like (EL) parts and the amphiphilic multiblock design of the corecombinamer. A bridged micellar structure is the dominant microscopic feature of this stage, as demonstrated by AFM and TEM. Completion of the initial stage triggers the second, which is comprised of a stabilization, reinforcement, and microstructuring of the gel. FTIR analysis shows that these events involve the formation of β-sheets around the silk motifs. The emergence of such β-sheet structures leads to the spontaneous self-organization of the gel into the final fibrous structure. Despite the absence of biological cues, here we set the basis of the minimal structure that is able to display such a set of physical properties and undergo microscopic transformation from a solution to a fibrous hydrogel. The results point to the potential of this system as a basis for the development of injectable fibrillar biomaterial platforms toward a fully functional, biomimetic, artificial extracellular matrix, and cell niches.Este trabajo forma parte de Proyectos de Investigación financiados por la Comisión Europea a través del Fondo Europeo de Desarrollo Regional (ERDF), por el del MINECO (MAT2013-41723-R, MAT2013- 42473-R, PRI-PIBAR-2011-1403 y MAT2012-38043), la Junta de Castilla y León (VA049A11, VA152A12 y VA155A12) y el Instituto de Salud Carlos III bajo el Centro en Red de Medicina Regenerativa y Terapia Celular de Castilla y León

Prediction of overall survival for patients with metastatic castration-resistant prostate cancer : development of a prognostic model through a crowdsourced challenge with open clinical trial data

Background Improvements to prognostic models in metastatic castration-resistant prostate cancer have the potential to augment clinical trial design and guide treatment strategies. In partnership with Project Data Sphere, a not-for-profit initiative allowing data from cancer clinical trials to be shared broadly with researchers, we designed an open-data, crowdsourced, DREAM (Dialogue for Reverse Engineering Assessments and Methods) challenge to not only identify a better prognostic model for prediction of survival in patients with metastatic castration-resistant prostate cancer but also engage a community of international data scientists to study this disease. Methods Data from the comparator arms of four phase 3 clinical trials in first-line metastatic castration-resistant prostate cancer were obtained from Project Data Sphere, comprising 476 patients treated with docetaxel and prednisone from the ASCENT2 trial, 526 patients treated with docetaxel, prednisone, and placebo in the MAINSAIL trial, 598 patients treated with docetaxel, prednisone or prednisolone, and placebo in the VENICE trial, and 470 patients treated with docetaxel and placebo in the ENTHUSE 33 trial. Datasets consisting of more than 150 clinical variables were curated centrally, including demographics, laboratory values, medical history, lesion sites, and previous treatments. Data from ASCENT2, MAINSAIL, and VENICE were released publicly to be used as training data to predict the outcome of interest-namely, overall survival. Clinical data were also released for ENTHUSE 33, but data for outcome variables (overall survival and event status) were hidden from the challenge participants so that ENTHUSE 33 could be used for independent validation. Methods were evaluated using the integrated time-dependent area under the curve (iAUC). The reference model, based on eight clinical variables and a penalised Cox proportional-hazards model, was used to compare method performance. Further validation was done using data from a fifth trial-ENTHUSE M1-in which 266 patients with metastatic castration-resistant prostate cancer were treated with placebo alone. Findings 50 independent methods were developed to predict overall survival and were evaluated through the DREAM challenge. The top performer was based on an ensemble of penalised Cox regression models (ePCR), which uniquely identified predictive interaction effects with immune biomarkers and markers of hepatic and renal function. Overall, ePCR outperformed all other methods (iAUC 0.791; Bayes factor >5) and surpassed the reference model (iAUC 0.743; Bayes factor >20). Both the ePCR model and reference models stratified patients in the ENTHUSE 33 trial into high-risk and low-risk groups with significantly different overall survival (ePCR: hazard ratio 3.32, 95% CI 2.39-4.62, p Interpretation Novel prognostic factors were delineated, and the assessment of 50 methods developed by independent international teams establishes a benchmark for development of methods in the future. The results of this effort show that data-sharing, when combined with a crowdsourced challenge, is a robust and powerful framework to develop new prognostic models in advanced prostate cancer.Peer reviewe

Changes in the concentration of grass pollen in the atmosphere of Poznan

The aim of the study was to determine the concentrations of grass pollen during the vegetation season in the atmosphere of Poznań against the background of the content of pollen of other plants and mould fungi. Observations were conducted in 1997. Concentrations of pollen grains and spores of mould fungi in the atmosphere were assessed by the volumetric method. For this purpose, the Burkard apparatus (Seven-Day Recording Volumetric Spore Trap) was set up on the roof of the 8-storey high building of the Maximum College of the Agricultural University in Poznań. The continuous, 24-hour work of the apparatus made possible to monitor concentrations of allergenic pollen throughout the experiment. The tape was glued to a microscopic glass and evaluated under the light microscope. The number of pollen grains and mould spores on individual sections (2 mm per hour) of the tape allowed determining their concentration per 1 m3 of air. Microscopic evaluation was conducted every 24 hours, collecting analytical material from the trap at 10 a.m. in which pollen and spores were determined. From among many wind pollinated taksons of plants, species from the grass family - because of their long period of pollination and clinical significance - play an important role in the structure of allergenic pollen in the atmosphere of Poznań. The highest concentration of grass pollen was recorded during the period from the end of May to the end of the first decade of July. From then on, the concentration of grass pollen in the air dropped rapidly and remained on a low level, not exceeding 7.5 pollen grains calculated per 1 m3 air per 24 hours. The higher concentration of grass pollen was recorded on June 29th - 360.4 grains · m-3. In terms of 24-hour period, the highest concentrations of the pollen grains in the air on a day without rain occurred between 9 and 11 a.m., whereas the lowest - at night.Celem badań było określenie stężenia w okresie wegetacji pyłku traw w atmos- ferze Poznania na tle zawartości pyłku alergogennego innych roślin oraz grzybów pleśniowych.Badania przeprowadzono w 1997 roku. Do oceny stężenia ziaren pyłku i za- rodników grzybów pleśniowych w atmosferze wykorzystano metodę objętościową. W tym celu na dachu 8-piętrowego budynku Collegium Maximum Akademii Rolni- czej w Poznaniu zainstalowano aparat Burkarda (Seven-Day Recording Volumetric Spore Trap). Ciągła, przez 24 godziny na dobę, praca aparatu umożliwiła monitoring dobowego stężenia pyłku alergennego w czasokresie prowadzenia badań. Taśma była przyklejana na szkiełko mikroskopowe i oceniana w mikroskopie świetlnym. Ilość ziaren pyłku i zarodników pleśni w poszczególnych odcinkach (2 mm na godzinę) taśmy umożliwiło określenie ich stężenia w odniesieniu do 1 m3 powietrza. Badania mikroskopowe prowadzono co 24 godziny pobierając materiał analityczny z aparatu o godz. 10.00. Spośród wielu wiatropylnych taksonów roślin, gatunki z rodziny traw ze wzglę- du na długi okres pylenia i znaczenie kliniczne odgrywają istotną rolę w strukturze pyłku alergogennego w atmosferze Poznania. Największe nasilenie pylenia traw od- notowano w okresie od końca maja do końca pierwszej dekady lipca. W kolejnych dniach stężenie pyłku traw w powietrzu gwałtownie spadło i utrzymywało się na niskim poziomie, nie przekraczającym 7,5 ziaren pyłku w przeliczeniu na 1 m3 powietrza w ciągu doby. Największą koncentrację ziaren pyłku traw stwierdzono 29. czerw- ca na poziomie 360,4 szt · m3. W ujęciu analizy dobowego stężenia pyłku traw w powietrzu największe wartości w czasie dni bez opadów deszczu odnotowano po- między godziną 9.00 a 11.00, natomiast najmniejsze w nocy

Investigations on seed retention strength in spikelets of Lolium multiflorum

Investigations were carried out in 2008–2009 to assess the seed retention strength in spikelets of various Lolium multiflorum genotypes depending on their growth stages. The cultivars (Turtetra and Mitos), breeding strains (SZD 1021, SZD 1022, SZD 1023, SZD 216 and SZD 228) and ecotypes were used. With the aid of a special testing machine, retention strength of successive flowers/kernels in spikelets as well as strength required to rachilla breaking of selected spikelets were determined. It was found that the examined Lolium multiflorum genotypes were characterised by specificity regarding seed retention strength in spikelets. This biological feature was smaller for top flowers/kernels and increased with the movement down the spikelet. It was found that in the examined genotypes of Italian ryegrass the seed retention strength in spikelets in the analysed consecutive growth stages was smallest in spikelets situated in the upper part of the inflorescence and the highest in the lower part