729 research outputs found

    “One more chance to survive”:the experiences of patients with advanced melanoma and their partners with tumor-infiltrating lymphocyte therapy—a qualitative study and recommendations for future care

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    Purpose: Patients with advanced melanoma refractory to first-line treatment have a need for effective second-line treatment options. A recent phase 3 trial showed promising results for adoptive cell therapy with tumor-infiltrating lymphocytes (TILs) as second-line therapy in patients with advanced melanoma. However, it remains unknown how patients and their partners experience TIL therapy, which is key to evaluate and improve the quality of care. Methods: Semi-structured interviews about the experience of TIL therapy were conducted with patients with advanced melanoma and their partners 2–4 weeks post-treatment (short term) and &gt;6 months after treatment (long term). Results: In total, 25 interviews were conducted with advanced melanoma patients treated with TIL (n=13) and their partners (n=12), with the majority being short-term interviews (n=17). Overall, patients and partners experienced TIL therapy as intense (uncertainty of successful TIL culture, multiple treatment-related toxicities, and extensive hospitalization). Patients and partners with young children or other caregiving responsibilities encountered the most challenges during TIL therapy. All patients, however, reported a recovery of all treatment-related toxicities within 2–4 weeks (except fatigue). Conclusion: Clinical data justify the role of TIL therapy in the treatment of advanced melanoma. With the distinct nature of TIL therapy compared to the current standard of care, we have provided patient-centered recommendations that will further enhance the quality of TIL therapy. Implications for Cancer Survivors: As more patients with advanced melanoma are expected to receive TIL therapy in the future, our findings could be incorporated into survivorship care plans for this novel group of advanced melanoma survivors treated with TIL.</p

    Diversity of colacosome-interacting mycoparasites expands the understanding of the evolution and ecology of Microbotryomycetes

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    Mycoparasites in Basidiomycota comprise a diverse group of fungi, both morphologically and phylogenetically. They interact with their hosts through either fusion-interaction or colacosome-interaction. Colacosomes are subcellular structures formed by the mycoparasite at the host–parasite interface, which penetrate the parasite and host cell walls. Previously, these structures were detected in 19 fungal species, usually by means of transmission electron microscopy. Most colacosome-forming species have been assigned to Microbotryomycetes (Pucciniomycotina, Basidiomycota), a highly diverse class, comprising saprobic yeasts, mycoparasites, and phytoparasites. In general, these myco- and phytoparasites are dimorphic organisms, with a parasitic filamentous morph and saprobic yeast morph. We investigated colacosome-forming mycoparasites based on fungarium material, freshly collected specimens, and cultures of yeast morphs. We characterised the micromorphology of filamentous morphs, the physiological characteristics of yeast morphs, and inferred phylogenetic relationships based on DNA sequence data from seven loci. We outline and employ an epifluorescence-based microscopic method to assess the presence and organisation of colacosomes. We describe five new species in the genus Colacogloea, the novel dimorphic mycoparasite Mycogloiocolax gerardii, and provide the first report of a sexual, mycoparasitic morph in Colacogloea philyla and in the genus Slooffia. We detected colacosomes in eight fungal species, which brings the total number of known colacosome-forming fungi to 27. Finally, we revealed three distinct types of colacosome organisation in Microbotryomycetes

    Fungal Planet description sheets: 1182-1283

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    Novel species of fungi described in this study include those from various countries as follows: Algeria, Phaeoacremonium adelophialidum from Vitis vinifera. Antarctica, Comoclathris antarctica from soil. Australia, Coniochaeta salicifolia as endophyte from healthy leaves of Geijera salicifolia, Eremothecium peggii in fruit of Citrus australis, Microdochium ratticaudae from stem of Sporobolus natalensis, Neocelosporium corymbiae on stems of Corymbia variegata, Phytophthora kelmanii from rhizosphere soil of Ptilotus pyramidatus, Pseudosydowia backhousiae on living leaves of Backhousia citriodora, Pseudosydowia indoor oopillyensis, Pseudosydowia louisecottisiae and Pseudosydowia queenslandica on living leaves of Eucalyptus sp. Brazil, Absidia montepascoalis from soil. Chile, Ilyonectria zarorii from soil under Maytenus boaria. Costa Rica, Colletotrichum filicis from an unidentified fern. Croatia, Mollisia endogranulata on deteriorated hardwood. Czech Republic, Arcopilus navicularis from tea bag with fruit tea, Neosetophoma buxi as endophyte from Buxus sempervirens, Xerochrysium bohemicum on surface of biscuits with chocolate glaze and filled with jam. France, Entoloma cyaneobasale on basic to calcareous soil, Fusarium aconidiale from Triticum aestivum, Fusarium juglandicola from buds of Juglans regia. Germany, Tetraploa endophytica as endophyte from Microthlaspi perfoliatum roots. India, Castanediella ambae on leaves of Mangifera indica, Lactifluus kanadii on soil under Castanopsis sp., Penicillium uttarakhandense from soil. Italy, Penicillium ferraniaense from compost. Namibia, Bezerromyces gobabebensis on leaves of unidentified succulent, Cladosporium stipagrostidicola on leaves of Stipagrostis sp., Cymostachys euphorbiae on leaves of Euphorbia sp., Deniquelata hypolithi from hypolith under a rock, Hysterobrevium walvisbayicola on leaves of unidentified tree, Knufia hypolithi and Knufia walvisbayicola from hypolith under a rock, Lapidomyces stipagrostidicola on leaves of Stipagrostis sp., Nothophaeotheca mirabibensis (incl. Nothophaeotheca gen. nov.) on persistent inflorescence remains of Blepharis obmitrata, Paramyrothecium salvadorae on twigs of Salvadora persica, Preussia procaviicola on dung of Procavia sp., Sordaria equicola on zebra dung, Volutella salvadorae on stems of Salvadora persica. Netherlands, Entoloma ammophilum on sandy soil, Entoloma pseudocruentatum on nutrient poor(acid)soil, Entoloma pudens on plant debris, amongst grasses. [...]Leslie W.S. de Freitas and colleagues express their gratitude to Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) for scholarships provided to Leslie Freitas and for the research grant provided to André Luiz Santiago; their contribution was financed by the projects ‘Diversity of Mucoromycotina in the different ecosystems of the Atlantic Rainforest of Pernambuco’ (FACEPE–First Projects Program PPP/ FACEPE/CNPq–APQ–0842-2.12/14) and ‘Biology of conservation of fungi s.l. in areas of Atlantic Forest of Northeast Brazil’ (CNPq/ICMBio 421241/ 2017-9) H.B. Lee was supported by the Graduate Program for the Undiscovered Taxa of Korea (NIBR202130202). The study of O.V. Morozova, E.F. Malysheva, V.F. Malysheva, I.V. Zmitrovich, and L.B. Kalinina was carried out within the framework of a research project of the Komarov Botanical Institute RAS (АААА-А19-119020890079-6) using equipment of its Core Facility Centre ‘Cell and Molecular Technologies in Plant Science’. The work of O. V. Morozova, L.B. Kalinina, T. Yu. Svetasheva, and E.A. Zvyagina was financially supported by Russian Foundation for Basic Research project no. 20-04-00349. E.A. Zvyagina and T.Yu. Svetasheva are grateful to A.V. Alexandrova, A.E. Kovalenko, A.S. Baykalova for the loan of specimens, T.Y. James, E.F. Malysheva and V.F. Malysheva for sequencing. J.D. Reyes acknowledges B. Dima for comparing the holotype sequence of Cortinarius bonachei with the sequences in his database. A. Mateos and J.D. Reyes acknowledge L. Quijada for reviewing the phylogeny and S. de la Peña- Lastra and P. Alvarado for their support and help. Vladimir I. Kapitonov and colleagues are grateful to Brigitta Kiss for help with their molecular studies. This study was conducted under research projects of the Tobolsk Complex Scientific Station of the Ural Branch of the Russian Academy of Sciences (N АААА-А19-119011190112-5). E. Larsson acknowledges the Swedish Taxonomy Initiative, SLU Artdatabanken, Uppsala (dha.2019.4.3-13). The study of D.B. Raudabaugh and colleagues was supported by the Schmidt Science Fellows, in partnership with the Rhodes Trust. Gregorio Delgado is grateful to Michael Manning and Kamash Pillai (Eurofins EMLab P&K) for provision of laboratory facilities. Jose G. Maciá-Vicente acknowledges support from the German Research Foundation under grant MA7171/1-1, and from the Landes-Offensive zur Entwicklung Wissenschaftlich-ökonomischer Exzellenz (LOEWE) of the state of Hesse within the framework of the Cluster for Integrative Fungal Research (IPF). Thanks are also due to the authorities of the Cabañeros National Park and Los Alcornocales Natural Park for granting the collection permit and for support during field work. The study of Alina V. Alexandrova was carried out as part of the Scientific Project of the State Order of the Government of Russian Federation to Lomonosov Moscow State University No. 121032300081-7. Michał Gorczak was financially supported by the Ministry of Science and Higher Education through the Faculty of Biology, University of Warsaw intramural grant DSM 0117600- 13. M. Gorczak acknowledges M. Klemens for sharing a photo of the Białowieża Forest logging site and M. Senderowicz for help with preparing the illustration. Ivona Kautmanová and D. Szabóová were funded by the Operational Program of Research and Development and co-financed with the European Fund for Regional Development (EFRD). ITMS 26230120004: ‘Building of research and development infrastructure for investigation of genetic biodiversity of organisms and joining IBOL initiative’. Ishika Bera, Aniket Ghosh, Jorinde Nuytinck and Annemieke Verbeken are grateful to the Director, Botanical Survey of India (Kolkata), Head of the Department of Botany & Microbiology & USIC Dept. HNB Garhwal University, Srinagar, Garhwal for providing research facilities. Ishika Bera and Aniket Ghosh acknowledge the staff of the forest department of Arunachal Pradesh for facilitating the macrofungal surveys to the restricted areas. Sergey Volobuev was supported by the Russian Science Foundation (RSF project N 19-77- 00085). Aleksey V. Kachalkin and colleagues were supported by the Russian Science Foundation (grant No. 19-74-10002). The study of Anna M. Glushakova was carried out as part of the Scientific Project of the State Order of the Government of Russian Federation to Lomonosov Moscow State University No. 121040800174-6. Tracey V. Steinrucken and colleagues were supported by AgriFutures Australia (Rural Industries Research and Development Corporation), through funding from the Australian Government Department of Agriculture, Water and the Environment, as part of its Rural Research and Development for Profit program (PRJ-010527). Neven Matočec and colleagues thank the Croatian Science Foundation for their financial support under the project grant HRZZ-IP-2018-01-1736 (ForFungiDNA). Ana Pošta thanks the Croatian Science Foundation for their support under the grant HRZZ-2018-09-7081. The research of Milan Spetik and co-authors was supported by Internal Grant of Mendel University in Brno No. IGAZF/ 2021-SI1003. K.C. Rajeshkumar thanks SERB, the Department of Science and Technology, Government of India for providing financial support under the project CRG/2020/000668 and the Director, Agharkar Research Institute for providing research facilities. Nikhil Ashtekar thanks CSIR-HRDG, INDIA, for financial support under the SRF fellowship (09/670(0090)/2020-EMRI), and acknowledges the support of the DIC Microscopy Facility, established by Dr Karthick Balasubramanian, B&P (Plants) Group, ARI, Pune. The research of Alla Eddine Mahamedi and co-authors was supported by project No. CZ.02.1.01/0.0/0.0/16_017/0002334, Czech Republic. Tereza Tejklová is thanked for providing useful literature. A. Polhorský and colleagues were supported by the Operational Program of Research and Development and co-financed with the European fund for Regional Development (EFRD), ITMS 26230120004: Building of research and development infrastructure for investigation of genetic biodiversity of organisms and joining IBOL initiative. Yu Pei Tan and colleagues thank R. Chen for her technical support. Ernest Lacey thanks the Cooperative Research Centres Projects scheme (CRCPFIVE000119) for its support. Suchada Mongkolsamrit and colleagues were financially supported by the Platform Technology Management Section, National Center for Genetic Engineering and Biotechnology (BIOTEC), Project Grant No. P19-50231. Dilnora Gouliamova and colleagues were supported by a grant from the Bulgarian Science Fund (KP-06-H31/19). The research of Timofey A. Pankratov was supported by the Russian Foundation for Basic Research (grant No. 19-04-00297a). Gabriel Moreno and colleagues wish to express their gratitude to L. Monje and A. Pueblas of the Department of Drawing and Scientific Photography at the University of Alcalá for their help in the digital preparation of the photographs, and to J. Rejos, curator of the AH herbarium, for his assistance with the specimens examined in the present study. Vit Hubka was supported by the Charles University Research Centre program No. 204069. Alena Kubátová was supported by The National Programme on Conservation and Utilization of Microbial Genetic Resources Important for Agriculture (Ministry of Agriculture of the Czech Republic). The Kits van Waveren Foundation (Rijksherbariumfonds Dr E. Kits van Waveren, Leiden, Netherlands) contributed substantially to the costs of sequencing and travelling expenses for M. Noordeloos. The work of B. Dima was supported by the ÚNKP-20-4 New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research, Development and Innovation Fund, and by the ELTE Thematic Excellence Programme 2020 supported by the National Research, Development and Innovation Office of Hungary (TKP2020-IKA-05). The Norwegian Entoloma studies received funding from the Norwegian Biodiversity Information Centre (NBIC), and the material was partly sequenced through NorBOL. Gunnhild Marthinsen and Katriina Bendiksen (Natural History Museum, University of Oslo, Norway) are acknowledged for performing the main parts of the Entoloma barcoding work. Asunción Morte is grateful to AEI/FEDER, UE (CGL2016-78946-R) and Fundación Séneca - Agencia de Ciencia y Tecnología de la Región de Murcia (20866/PI/18) for financial support. Vladimír Ostrý was supported by the Ministry of Health, Czech Republic - conceptual development of research organization (National Institute of Public Health – NIPH, IN 75010330). Konstanze Bensch (Westerdijk Fungal Biodiversity Institute, Utrecht) is thanked for correcting the spelling of various Latin epithets.Peer reviewe

    The Evolution of Illicit Flows. Displacement and Convergence among Transnational Crime

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    This book focuses on the displacement and convergence of transnational crimes in North Africa and in the area of the Mediterranean Sea, providing empirical analysis of human smuggling and of drug trafficking. It discusses the displacement of crime due to the exploitation of asymmetries in legislation, law enforcement, and other vulnerabilities. Using an innovative multimethodology, this volume describes the evolution of illicit flows related to human smuggling and trafficking of illicit goods. This approach helps to provide critical information such as traffickers’ modi operandi, most exploited paths, and trafficked goods, that would not be achievable through more traditional methods. The Evolution of Illicit Flows will be a valuable resource for scholars and researchers of criminology and migration studies, as well as for policymakers and law enforcement working in transnational crimes and trafficking

    A dynamic portal for a community-driven, continuously updated classification of Fungi and fungus-like organisms: outlineoffungi.org

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    The website http://outlineoffungi.org, is launched to provide a continuous up-to-date classification of the kingdom Fungi (including fossil fungi) and fungus-like taxa. This is based on recent publications and on the outline of fungi and fungus-like taxa published recently (Mycosphere 11, 1060-1456, Doi: 10.5943/mycosphere/11/1/8). The website is continuously updated according to latest classification schemes, and will present an important platform for researchers, industries, government officials and other users. Users can provide input about missing genera, new genera, and new data. They will also have the opportunity to express their opinions on classifications with notes published in the 'Notes' section of the webpage following review and editing by the curators and independent experts. The website will provide a system to stay abreast of the continuous changes in fungal classification and provide a general consensus on the systematics of fungi

    Fusarium: more than a node or a foot-shaped basal cell

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    Recent publications have argued that there are potentially serious consequences for researchers in recognising distinct genera in the terminal fusarioid clade of the family Nectriaceae. Thus, an alternate hypothesis, namely a very broad concept of the genus Fusarium was proposed. In doing so, however, a significant body of data that supports distinct genera in Nectriaceae based on morphology, biology, and phylogeny is disregarded. A DNA phylogeny based on 19 orthologous protein-coding genes was presented to support a very broad concept of Fusarium at the F1 node in Nectriaceae. Here, we demonstrate that re-analyses of this dataset show that all 19 genes support the F3 node that represents Fusarium sensu stricto as defined by F. sambucinum (sexual morph synonym Gibberella pulicaris). The backbone of the phylogeny is resolved by the concatenated alignment, but only six of the 19 genes fully support the F1 node, representing the broad circumscription of Fusarium. Furthermore, a re-analysis of the concatenated dataset revealed alternate topologies in different phylogenetic algorithms, highlighting the deep divergence and unresolved placement of various Nectriaceae lineages proposed as members of Fusarium. Species of Fusarium s. str. are characterised by Gibberella sexual morphs, asexual morphs with thin- or thick-walled macroconidia that have variously shaped apical and basal cells, and trichothecene mycotoxin production, which separates them from other fusarioid genera. Here we show that the Wollenweber concept of Fusarium presently accounts for 20 segregate genera with clear-cut synapomorphic traits, and that fusarioid macroconidia represent a character that has been gained or lost multiple times throughout Nectriaceae. Thus, the very broad circumscription of Fusarium is blurry and without apparent synapomorphies, and does not include all genera with fusarium-like macroconidia, which are spread throughout Nectriaceae (e.g., Cosmosporella, Macroconia, Microcera). In this study four new genera are introduced, along with 18 new species and 16 new combinations. These names convey information about relationships, morphology, and ecological preference that would otherwise be lost in a broader definition of Fusarium. To assist users to correctly identify fusarioid genera and species, we introduce a new online identification database, Fusarioid-ID, accessible at www.fusarium.org. The database comprises partial sequences from multiple genes commonly used to identify fusarioid taxa (act1, CaM, his3, rpb1, rpb2, tef1, tub2, ITS, and LSU). In this paper, we also present a nomenclator of names that have been introduced in Fusarium up to January 2021 as well as their current status, types, and diagnostic DNA barcode data. In this study, researchers from 46 countries, representing taxonomists, plant pathologists, medical mycologists, quarantine officials, regulatory agencies, and students, strongly support the application and use of a more precisely delimited Fusarium (= Gibberella) concept to accommodate taxa from the robust monophyletic node F3 on the basis of a well-defined and unique combination of morphological and biochemical features. This F3 node includes, among others, species of the F. fujikuroi, F. incarnatum-equiseti, F. oxysporum, and F. sambucinum species complexes, but not species of Bisifusarium [F. dimerum species complex (SC)], Cyanonectria (F. buxicola SC), Geejayessia (F. staphyleae SC), Neocosmospora (F. solani SC) or Rectifusarium (F. ventricosum SC). The present study represents the first step to generating a new online monograph of Fusarium and allied fusarioid genera (www.fusarium.org)

    Phosphoproteomic Analysis of FLCN Inactivation Highlights Differential Kinase Pathways and Regulatory TFEB Phosphoserines

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    In Birt–Hogg–Dubé (BHD) syndrome, germline loss-of-function mutations in the Folliculin (FLCN) gene lead to an increased risk of renal cancer. To address how FLCN inactivation affects cellular kinase signaling pathways, we analyzed comprehensive phosphoproteomic profiles of FLCNPOS and FLCNNEG human renal tubular epithelial cells (RPTEC/TERT1). In total, 15,744 phosphorylated peptides were identified from 4329 phosphorylated proteins. INKA analysis revealed that FLCN loss alters the activity of numerous kinases, including tyrosine kinases EGFR, MET, and the Ephrin receptor subfamily (EPHA2 and EPHB1), as well their downstream targets MAPK1/3. Validation experiments in the BHD renal tumor cell line UOK257 confirmed that FLCN loss contributes to enhanced MAPK1/3 and downstream RPS6K1/3 signaling. The clinically available MAPK inhibitor Ulixertinib showed enhanced toxicity in FLCNNEG cells. Interestingly, FLCN inactivation induced the phosphorylation of PIK3CD (Tyr524) without altering the phosphorylation of canonical Akt1/Akt2/mTOR/EIF4EBP1 phosphosites. Also, we identified that FLCN inactivation resulted in dephosphorylation of TFEB Ser109, Ser114, and Ser122, which may be linked to increased oxidative stress levels in FLCNNEG cells. Together, our study highlights differential phosphorylation of specific kinases and substrates in FLCNNEG renal cells. This provides insight into BHD-associated renal tumorigenesis and may point to several novel candidates for targeted therapies

    Serum Potassium and Mortality Risk in Hemodialysis Patients: A Cohort Study

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    Rationale & Objective: Both hypo- and hyperkalemia can cause fatal cardiac arrhythmias. Although predialysis serum potassium level is a known modifiable risk factor for death in patients receiving hemodialysis, especially for hypokalemia, this risk may be underestimated. Therefore, we investigated the relationship between predialysis serum potassium level and death in incident hemodialysis patients and whether there is an optimum level. Study Design: Prospective multicenter cohort study. Setting & Participants: 1,117 incident hemodialysis patients (aged >18 years) from the Netherlands Cooperative Study on the Adequacy of Dialysis-2 study were included and followed from their first hemodialysis treatment until death, transplantation, switch to peritoneal dialysis, or a maximum of 10 years. Exposure: Predialysis serum potassium levels were obtained every 6 months and divided into 6 categories: ≤4.0 mmol/L, >4.0 mmol/L to ≤4.5 mmol/L, >4.5 mmol/L to ≤5.0 mmol/L, >5.0 mmol/L to ≤5.5 mmol/L (reference), >5.5 mmol/L to ≤6.0 mmol/L, and >6.0 mmol/L. Outcomes: 6-month all-cause mortality. Analytical Approach: Cox proportional hazards and restricted cubic spline analyses with time-dependent predialysis serum potassium levels were used to calculate the adjusted HRs for death. Results: At baseline, the mean age of the patients was 63 years (standard deviation, 14 years), 58% were men, 26% smoked, 24% had diabetes, 32% had cardiovascular disease, the mean serum potassium level was 5.0 mmol/L (standard deviation, 0.8 mmol/L), 7% had a low subjective global assessment score, and the median residual kidney function was 3.5 mL/min/1.73 m2 (IQR, 1.4-4.8 mL/min/1.73 m2). During the 10-year follow-up, 555 (50%) deaths were observed. Multivariable adjusted HRs for death according to the 6 potassium categories were as follows: 1.42 (95% CI, 1.01-1.99), 1.09 (95% CI, 0.82-1.45), 1.21 (95% CI, 0.94-1.56), 1 (reference), 0.95 (95% CI, 0.71-1.28), and 1.32 (95% CI, 0.97-1.81). Limitations: Shorter intervals between potassium measurements would have allowed for more precise mortality risk estimations. Conclusions: We found a U-shaped relationship between serum potassium level and death in incident hemodialysis patients. A low predialysis serum potassium level was associated with a 1.4-fold stronger risk of death than the optimal level of approximately 5.1 mmol/L. These results may imply the cautious use of potassium-lowering therapy and a potassium-restricted diet in patients receiving hemodialysis
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