Spray drying of emulsions: Influence of the emulsifier system on changes in oil droplet size during the drying step

The goal of this study was to investigate the influence of the emulsifier system on the changes in oil droplet size occurring during the drying step of spray drying of emulsions. Atomization and spray drying experiments were performed with emulsions stabilized with whey protein isolate (WPI) alone or in combination with low molecular weight emulsifiers (lecithin, mono- and diglycerides (MoDi), and citrem). Oil droplet coalescence was observed for the systems WPI/Citrem and WPI/MoDi, as the d$_{90,0}$ increased from 0.86 ± 0.16 and 1.67 ± 0.35 µm after atomization to 1.83 ± 0.24 and 1.90 ± 0.17 µm after drying, respectively. Oil droplets stabilized with WPI or WPI/Lecithin remained stable during drying. Measurements of dilatational rheology of the interfacial film showed that phase angle values increase in the order WPI/Lecithin < WPI < WPI/Citrem = WPI/MoDi. Therefore, in the studied system oil droplet coalescence during drying increases when the elastic behavior of the interfacial film decreases

Optical Microscopy in the Nano-World

Scanning near-field optical microscopy (SNOM) is an optical microscopy whose resolution is not bound to the diffraction limit. It provides chemical information based upon spectral, polarization and/or fluorescence contrast images. Details as small as 20 nm can be recognized. Photophysical and photochemical effects can be studied with SNOM on a similar scale. This article reviews a good deal of the experimental and theoretical work on SNOM in Switzerland

Hostile Takeover by Plasmodium: Reorganization of Parasite and Host Cell Membranes during Liver Stage Egress

The protozoan parasite Plasmodium is transmitted by female Anopheles mosquitoes and undergoes obligatory development within a parasitophorous vacuole in hepatocytes before it is released into the bloodstream. The transition to the blood stage was previously shown to involve the packaging of exoerythrocytic merozoites into membrane-surrounded vesicles, called merosomes, which are delivered directly into liver sinusoids. However, it was unclear whether the membrane of these merosomes was derived from the parasite membrane, the parasitophorous vacuole membrane or the host cell membrane. This knowledge is required to determine how phagocytes will be directed against merosomes. Here, we fluorescently label the candidate membranes and use live cell imaging to show that the merosome membrane derives from the host cell membrane. We also demonstrate that proteins in the host cell membrane are lost during merozoite liberation from the parasitophorous vacuole. Immediately after the breakdown of the parasitophorous vacuole membrane, the host cell mitochondria begin to degenerate and protein biosynthesis arrests. The intact host cell plasma membrane surrounding merosomes allows Plasmodium to mask itself from the host immune system and bypass the numerous Kupffer cells on its way into the bloodstream. This represents an effective strategy for evading host defenses before establishing a blood stage infection

Population dynamics and genetic connectivity in recent chimpanzee history

The European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement no. 864203) (to T.M.-B.). BFU2017-86471-P (MINECO/FEDER, UE) (to T.M.-B.). “Unidad de Excelencia María de Maeztu”, funded by the AEI (CEX2018-000792-M) (to T.M.-B.). Howard Hughes International Early Career (to T.M.-B.). NIH 1R01HG010898-01A1 (to T.M.-B.). Secretaria d’Universitats i Recerca and CERCA Program del Departament d’Economia i Coneixement de la Generalitat de Catalunya (GRC 2017 SGR 880) (to T.M.-B.). UCL’s Wellcome Trust ISSF3 award 204841/Z/16/Z (to A.M.A. and J.M.S.). Generalitat de Catalunya (2017 SGR-1040) (to M. Llorente). Wellcome Trust Investigator Award 202802/Z/16/Z (to D.A.H.). The Pan African Program: The Cultured Chimpanzee (PanAf) is generously funded by the Max Planck Society, the Max Planck Society Innovation Fund, and the Heinz L. Krekeler Foundation.Knowledge on the population history of endangered species is critical for conservation, but whole-genome data on chimpanzees (Pan troglodytes) is geographically sparse. Here, we produced the first non-invasive geolocalized catalog of genomic diversity by capturing chromosome 21 from 828 non-invasive samples collected at 48 sampling sites across Africa. The four recognized subspecies show clear genetic differentiation correlating with known barriers, while previously undescribed genetic exchange suggests that these have been permeable on a local scale. We obtained a detailed reconstruction of population stratification and fine-scale patterns of isolation, migration, and connectivity, including a comprehensive picture of admixture with bonobos (Pan paniscus). Unlike humans, chimpanzees did not experience extended episodes of long-distance migrations, which might have limited cultural transmission. Finally, based on local rare variation, we implement a fine-grained geolocalization approach demonstrating improved precision in determining the origin of confiscated chimpanzees.Publisher PDFPeer reviewe

Clinical Calculator for Early Mortality in Metastatic Colorectal Cancer: An Analysis of Patients From 28 Clinical Trials in the Aide et Recherche en Cancérologie Digestive Database

Purpose: Factors contributing to early mortality after initiation of treatment of metastatic colorectal cancer are poorly understood. Materials and Methods: Data from 22,654 patients enrolled in 28 randomized phase III trials contained in the ARCAD (Aide et Recherche en Cancérologie Digestive) database were pooled. Multivariable logistic regression models for 30-, 60-, and 90-day mortality were constructed, including clinically and statistically significant patient and disease factors and interaction terms. A calculator (nomogram) for 90-day mortality was developed and validated internally using bootstrapping methods and externally using a 10% random holdout sample from each trial. The impact of early progression on the likelihood of survival to 90 days was examined with time-dependent Cox proportional hazards models. Results: Mortality rates were 1.4% at 30 days, 3.4% at 60 days, and 5.5% at 90 days. Among baseline factors, advanced age, lower body mass index, poorer performance status, increased number of metastatic sites, BRAF mutant status, and several laboratory parameters were associated with increased likelihood of early mortality. A multivariable model for 90-day mortality showed strong internal discrimination (C-index, 0.77) and good calibration across risk groups as well as accurate predictions in the external validation set, both overall and within patient subgroups. Conclusion: A validated clinical nomogram has been developed to quantify the risk of early death for individual patients during initial treatment of metastatic colorectal cancer. This tool may be used for patient eligibility assessment or risk stratification in future clinical trials and to identify patients requiring more or less aggressive therapy and additional supportive measures during and after treatment

Impact of geography on prognostic outcomes of 21,509 patients with metastatic colorectal cancer enrolled in clinical trials: an ARCAD database analysis

Impact of geography on prognostic outcomes of 21,509 patients with metastatic colorectal cancer enrolled in clinical trials: an ARCAD database analysis Show less Jun Yin*, Shaheenah Dawood*, Romain Cohen, Jeff Meyers, John Zalcberg, Takayuki Yoshino, Matthew Seymour, Tim Maughan, Leonard Saltz, Eric Van Cutsem, Alan Venook, Hans-Joachim Schmoll, Richard Goldberg, Paulo Hoff, J. Randolph Hecht, Herbert Hurwitz, Cornelis Punt, Eduard Diaz Rubio, Miriam Koopman, Chiara Cremolini, Volker Heinemann, Christophe Tournigard, Carsten Bokemeyer, Charles Fuchs, Niall Tebbutt, John Souglakos, Jean-Yves Doulliard, Fairooz Kabbinavar, Benoist Chibaudel, Aimery de Gramont, Qian Shi, Axel Grothey, Richard AdamsFirst Published June 30, 2021 Research Article https://doi.org/10.1177/17588359211020547 Article information Article has an altmetric score of 7 Open AccessCreative Commons Attribution, Non Commercial 4.0 License Article Information Volume: 13 Article first published online: June 30, 2021; Issue published: January 1, 2021 Received: December 29, 2020; Accepted: May 05, 2021 Jun Yin* Department of Health Sciences Research, Mayo Clinic, 200 First Street, SW Rochester, MN 55905, USA Shaheenah Dawood* Mediclinic City Hospital: North Wing, Dubai Health Care City, Dubai UAE Romain Cohen Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA Jeff Meyers Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA John Zalcberg School of Public Health and Preventative Medicine, Monash University, Melbourne, Australia Takayuki Yoshino Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Chiba, Japan Matthew Seymour NIHR Clinical Research Network, Leeds, UK Tim Maughan CRUK/MRC Oxford Institute for Radiation Oncology, Oxford, UK Leonard Saltz Memory Sloan Kettering Cancer Center, New York, NY, USA Eric Van Cutsem Digestive Oncology, University Hospitals Gasthuisberg Leuven and KU Leuven, Leuven, Belgium Alan Venook Department of Medicine, The University of California San Francisco, San Francisco, CA, USA Hans-Joachim Schmoll Klinik fur Innere Med IV, University Clinic Halle, Saale, Germany Richard Goldberg Department of Oncology, West Virginia University, Morgantown, WV, USA Paulo Hoff Centro de Oncologia de Brasilia do Sirio Libanes: Unidade Lago Sul, Siro Libanes, Brazil J. Randolph Hecht Ronald Reagan UCLA Medical Center, UCLS Medical Center, Santa Monica, CA, USA Herbert Hurwitz Duke Cancer Institute, Duke University, Durham, NC, USA Cornelis Punt Department of Medical Oncology, University of Amsterdam, Amsterdam, The Netherlands Eduard Diaz Rubio Department Oncology, Hospital Clínico San Carlos, Madrid, Spain Miriam Koopman Department of Medical Oncology, University Medical Center Utrecht, University of Utrecht, Utrecht, The Netherlands Chiara Cremolini Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy Volker Heinemann Department of Medical Oncology and Comprehensive Cancer Center, University of Munich, Munich, Germany Christophe Tournigard Hopital Henri Mondor, Creteil, France Carsten Bokemeyer Department of Oncology, Hematology and Bone Marrow Transplantation with Section of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany Charles Fuchs Director of Yale Cancer Center, Boston, MA, USA Niall Tebbutt Sydney Medical School, University of Sydney, Sydney, Australia John Souglakos University of Crete, Heraklion, Greece Jean-Yves Doulliard University of Nantes Medical School, Nantes, France Fairooz Kabbinavar UCLA Medical Center, Santa Monica, CA, USA Benoist Chibaudel Department of Medical Oncology, Franco-British Institute, Levallois-Perret, France Aimery de Gramont Department of Medical Oncology, Franco-British Institute, Levallois-Perret, France Qian Shi Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA Axel Grothey West Cancer Center, Germantown, TN, USA Richard Adams Cardiff University and Velindre Cancer Center, Cardiff, UK Corresponding Author: [email protected] *Co-first authors. https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (https://us.sagepub.com/en-us/nam/open-access-at-sage). Abstract Background: Benchmarking international cancer survival differences is necessary to evaluate and improve healthcare systems. Our aim was to assess the potential regional differences in outcomes among patients with metastatic colorectal cancer (mCRC) participating in international randomized clinical trials (RCTs). Design: Countries were grouped into 11 regions according to the World Health Organization and the EUROCARE model. Meta-analyses based on individual patient data were used to synthesize data across studies and regions and to conduct comparisons for outcomes in a two-stage random-effects model after adjusting for age, sex, performance status, and time period. We used mCRC patients enrolled in the first-line RCTs from the ARCAD database, which provided enrolling country information. There were 21,509 patients in 27 RCTs included across the 11 regions. Results: Main outcomes were overall survival (OS) and progression-free survival (PFS). Compared with other regions, patients from the United Kingdom (UK) and Ireland were proportionaly over-represented, older, with higher performance status, more frequently male, and more commonly not treated with biological therapies. Cohorts from central Europe and the United States (USA) had significantly longer OS compared with those from UK and Ireland (p = 0.0034 and p < 0.001, respectively), with median difference of 3–4 months. The survival deficits in the UK and Ireland cohorts were, at most, 15% at 1 year. No evidence of a regional disparity was observed for PFS. Among those treated without biological therapies, patients from the UK and Ireland had shorter OS than central Europe patients (p < 0.001). Conclusions: Significant international disparities in the OS of cohorts of mCRC patients enrolled in RCTs were found. Survival of mCRC patients included in RCTs was consistently lower in the UK and Ireland regions than in central Europe, southern Europe, and the USA, potentially attributed to greater overall population representation, delayed diagnosis, and reduced availability of therapies

Formation of Protoanemonin from 2-Chloro-cis,cis-Muconate by the Combined Action of Muconate Cycloisomerase and Muconolactone Isomerase

Muconate cycloisomerases are known to catalyze the reversible conversion of 2-chloro-cis,cis-muconate by 1,4- and 3,6-cycloisomerization into (4S)-(+)-2-chloro- and (4R/5S)-(+)-5-chloromuconolactone. 2-Chloromuconolactone is transformed by muconolactone isomerase with concomitant dechlorination and decarboxylation into the antibiotic protoanemonin. The low k(cat) for this compound compared to that for 5-chloromuconolactone suggests that protoanemonin formation is of minor importance. However, since 2-chloromuconolactone is the initially predominant product of 2-chloromuconate cycloisomerization, significant amounts of protoanemonin were formed in reaction mixtures containing large amounts of muconolactone isomerase and small amounts of muconate cycloisomerase. Such enzyme ratios resemble those observed in cell extracts of benzoate-grown cells of Ralstonia eutropha JMP134. In contrast, cis-dienelactone was the predominant product formed by enzyme preparations, in which muconolactone isomerase was in vitro rate limiting. In reaction mixtures containing chloromuconate cycloisomerase and muconolactone isomerase, only minute amounts of protoanemonin were detected, indicating that only small amounts of 2-chloromuconolactone were formed by cycloisomerization and that chloromuconate cycloisomerase actually preferentially catalyzes a 3,6-cycloisomerization