TY - JOUR A1 - Tamihardja, Jörg A1 - Lutyj, Paul A1 - Kraft, Johannes A1 - Lisowski, Dominik A1 - Weick, Stefan A1 - Flentje, Michael A1 - Polat, Bülent T1 - Two-Weekly High-Dose-Rate Brachytherapy Boost After External Beam Radiotherapy for Localized Prostate Cancer: Long-Term Outcome and Toxicity Analysis JF - Frontiers in Oncology N2 - Purpose Evaluation of clinical outcome of two-weekly high-dose-rate brachytherapy boost after external beam radiotherapy (EBRT) for localized prostate cancer. Methods 338 patients with localized prostate cancer receiving definitive EBRT followed by a two-weekly high-dose-rate brachytherapy boost (HDR-BT boost) in the period of 2002 to 2019 were analyzed. EBRT, delivered in 46 Gy (DMean) in conventional fractionation, was followed by two fractions HDR-BT boost with 9 Gy (D90%) two and four weeks after EBRT. Androgen deprivation therapy (ADT) was added in 176 (52.1%) patients. Genitourinary (GU)/gastrointestinal (GI) toxicity was evaluated utilizing the Common Toxicity Criteria for Adverse Events (version 5.0) and biochemical failure was defined according to the Phoenix definition. Results Median follow-up was 101.8 months. 15 (4.4%)/115 (34.0%)/208 (61.5%) patients had low-/intermediate-/high-risk cancer according to the D`Amico risk classification. Estimated 5-year and 10-year biochemical relapse-free survival (bRFS) was 84.7% and 75.9% for all patients. The estimated 5-year bRFS was 93.3%, 93.4% and 79.5% for low-, intermediate- and high-risk disease, respectively. The estimated 10-year freedom from distant metastasis (FFM) and overall survival (OS) rates were 86.5% and 70.0%. Cumulative 5-year late GU toxicity and late GI toxicity grade ≥ 2 was observed in 19.3% and 5.0% of the patients, respectively. Cumulative 5-year late grade 3 GU/GI toxicity occurred in 3.6%/0.3%. Conclusions Two-weekly HDR-BT boost after EBRT for localized prostate cancer showed an excellent toxicity profile with low GU/GI toxicity rates and effective long-term biochemical control. KW - prostate cancer KW - high-dose-rate (HDR) brachytherapy KW - radiotherapy KW - long-term outcome KW - toxicity KW - external beam radiotherapy (EBRT) KW - biochemical relapse free survival Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-250992 SN - 2234-943X VL - 11 ER - TY - JOUR A1 - Strilciuc, Stefan A1 - Vécsei, László A1 - Boering, Dana A1 - Pražnikar, Aleš A1 - Kaut, Oliver A1 - Riederer, Peter A1 - Battistin, Leontino T1 - Safety of Cerebrolysin for neurorecovery after acute ischemic stroke: a systematic review and meta-analysis of twelve randomized-controlled trials JF - Pharmaceuticals N2 - We performed a systematic search and meta-analysis of available literature to determine the safety profile of Cerebrolysin in acute ischemic stroke, filling existing safety information gaps and inconsistent results. We searched EMBASE, PubMed, and Cochrane Databases of Systematic Reviews and Clinical Trials up to the end of February 2021. Data collection and analysis were conducted using methods described in the Cochrane Handbook for Systematic Reviews of Interventions. All safety outcomes were analyzed based on risk ratios (RR) and their 95% confidence intervals. The meta-analysis pooled 2202 patients from twelve randomized clinical trials, registering non-statistically significant (p > 0.05) differences between Cerebrolysin and placebo throughout main and subgroup analyses. The lowest rate of Serious Adverse Events (SAE), as compared to placebo, was observed for the highest dose of Cerebrolysin (50 mL), highlighting a moderate reduction (RR = 0.6). We observed a tendency of superiority of Cerebrolysin regarding SAE in high dose treatment courses for moderate-severe ischemic stroke, suggesting some effect of the agent against adverse events. This comprehensive safety meta-analysis confirms the safety profile for patients treated with Cerebrolysin after acute ischemic stroke, as compared to placebo. KW - ischemic stroke KW - safety KW - Cerebrolysin KW - neurorehabilitation Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-252403 SN - 1424-8247 VL - 14 IS - 12 ER - TY - JOUR A1 - Nguemeni, Carine A1 - Hiew, Shawn A1 - Kögler, Stefanie A1 - Homola, György A. A1 - Volkmann, Jens A1 - Zeller, Daniel T1 - Split-belt training but not cerebellar anodal tDCS improves stability control and reduces risk of fall in patients with multiple sclerosis JF - Brain Sciences N2 - The objective of this study was to examine the therapeutic potential of multiple sessions of training on a split-belt treadmill (SBT) combined with cerebellar anodal transcranial direct current stimulation (tDCS) on gait and balance in People with Multiple Sclerosis (PwMS). Twenty-two PwMS received six sessions of anodal (PwMS\(_{real}\), n = 12) or sham (PwMS\(_{sham}\), n = 10) tDCS to the cerebellum prior to performing the locomotor adaptation task on the SBT. To evaluate the effect of the intervention, functional gait assessment (FGA) scores and distance walked in 2 min (2MWT) were measured at the baseline (T0), day 6 (T5), and at the 4-week follow up (T6). Locomotor performance and changes of motor outcomes were similar in PwMS\(_{real}\) and PwMS\(_{sham}\) independently from tDCS mode applied to the cerebellum (anodal vs. sham, on FGA, p = 0.23; and 2MWT, p = 0.49). When the data were pooled across the groups to investigate the effects of multiple sessions of SBT training alone, significant improvement of gait and balance was found on T5 and T6, respectively, relative to baseline (FGA, p < 0.001 for both time points). The FGA change at T6 was significantly higher than at T5 (p = 0.01) underlining a long-lasting improvement. An improvement of the distance walked during the 2MWT was also observed on T5 and T6 relative to T0 (p = 0.002). Multiple sessions of SBT training resulted in a lasting improvement of gait stability and endurance, thus potentially reducing the risk of fall as measured by FGA and 2MWT. Application of cerebellar tDCS during SBT walking had no additional effect on locomotor outcomes. KW - multiple sclerosis KW - split-belt treadmill KW - cerebellar tDCS KW - gait KW - balance KW - risk of fall Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-252179 SN - 2076-3425 VL - 12 IS - 1 ER - TY - JOUR A1 - Khare, Siddhartha A1 - Deslauriers, Annie A1 - Morin, Hubert A1 - Latifi, Hooman A1 - Rossi, Sergio T1 - Comparing time-lapse PhenoCams with satellite observations across the boreal forest of Quebec, Canada JF - Remote Sensing N2 - Intercomparison of satellite-derived vegetation phenology is scarce in remote locations because of the limited coverage area and low temporal resolution of field observations. By their reliable near-ground observations and high-frequency data collection, PhenoCams can be a robust tool for intercomparison of land surface phenology derived from satellites. This study aims to investigate the transition dates of black spruce (Picea mariana (Mill.) B.S.P.) phenology by comparing fortnightly the MODIS normalized difference vegetation index (NDVI) and the enhanced vegetation index (EVI) extracted using the Google Earth Engine (GEE) platform with the daily PhenoCam-based green chromatic coordinate (GCC) index. Data were collected from 2016 to 2019 by PhenoCams installed in six mature stands along a latitudinal gradient of the boreal forests of Quebec, Canada. All time series were fitted by double-logistic functions, and the estimated parameters were compared between NDVI, EVI, and GCC. The onset of GCC occurred in the second week of May, whereas the ending of GCC occurred in the last week of September. We demonstrated that GCC was more correlated with EVI (R\(^2\) from 0.66 to 0.85) than NDVI (R\(^2\) from 0.52 to 0.68). In addition, the onset and ending of phenology were shown to differ by 3.5 and 5.4 days between EVI and GCC, respectively. Larger differences were detected between NDVI and GCC, 17.05 and 26.89 days for the onset and ending, respectively. EVI showed better estimations of the phenological dates than NDVI. This better performance is explained by the higher spectral sensitivity of EVI for multiple canopy leaf layers due to the presence of an additional blue band and an optimized soil factor value. Our study demonstrates that the phenological observations derived from PhenoCam are comparable with the EVI index. We conclude that EVI is more suitable than NDVI to assess phenology in evergreen species of the northern boreal region, where PhenoCam data are not available. The EVI index could be used as a reliable proxy of GCC for monitoring evergreen species phenology in areas with reduced access, or where repeated data collection from remote areas are logistically difficult due to the extreme weather. KW - PhenoCam KW - GCC KW - NDVI KW - EVI KW - Google Earth Engine KW - coniferous species KW - Picea mariana Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-252213 SN - 2072-4292 VL - 14 IS - 1 ER - TY - JOUR A1 - Dosoo, Korshi T1 - Healing traditions in Coptic magical texts JF - Trends in Classics N2 - Within the ‘market of healing’ of Christian Egypt (here broadly considered as the fourth through twelfth centuries CE), ‘magical’ practitioners represent an elusive yet recurrent category. This article explores the evidence for magical healing from three perspectives – first, literary texts which situate ‘magicians’ in competition with medical and ecclesiastical healing; second, the papyrological evidence of Coptic-language magical texts, which provide evidence for concepts of disease, wellness, and their mediation; and finally confronting the question of how these healing traditions might be understood within the methodologically materialistic framework of academic history, using the concepts of placebo and healing as a performance. KW - Placebo KW - healing KW - Coptic KW - magic KW - ritual Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-251219 SN - 1866-7473 SN - 1866-7481 N1 - This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively. VL - 13 IS - 1 SP - 44 EP - 94 ER - TY - JOUR A1 - Schmidt, Karsten A1 - Jakubietz, Michael Georg A1 - Gilbert, Fabian A1 - Fenwick, Annabel A1 - Meffert, Reiner Heribert A1 - Jakubietz, Rafael Gregor T1 - Muscle cuff in distal pedicled adipofascial sural artery flaps: a retrospective case control study JF - PRS Global Open N2 - Background: Amputation after open tibial fracture occurs in 3% of cases. The rate increases when flap reconstruction is required. The standard care involves microsurgical tissue transfer although the pedicled reverse sural artery adipofascial flap (PRSAF) is a local alternative in patients endangered by a prolonged operative time. Incorporation of a gastrocnemius muscle cuff in this flap can be used to fill dead space and increase healing potential. Literature shows superior survival rates for both PRSAF and inclusion of a muscle cuff in comparison with the cutaneous version. The aim of the study was to compare the outcome of the PRSAF and the musculoadipofascial version (PRSMAF). We hypothesize that the PRSMAF provides similar lap viability and flap-related complication rates as does the adipofascial version. The muscle component may reduce the long-term osteomyelitis rate. Methods: Patients were evaluated retrospectively after reconstruction with either PRSAF or PRSMAF. Preoperative osteomyelitis, flap survival, complications and osteomyelitis clearance were analyzed. Results: The study shows preliminary results supporting the potential use of the PRSMAF. We compare either 23 PRSMAF or 20 PRSAF flaps. We found no statistically significant differences in flap survival or in complication rate. Conclusions: Although the anatomical situation may sometimes dictate the use of a free flap, a technically less-complicated option may in some cases offer a viable alternative. This study shows that the PRSMAF can serve as an alternative for complex bone defects in the limb, though it does not provide statistical improvement to the PRSAF. KW - muscle cuff Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-259875 VL - 9 IS - 3 ER - TY - JOUR A1 - Hojsgaard, Diego A1 - Schartl, Manfred T1 - Skipping sex: A nonrecombinant genomic assemblage of complementary reproductive modules JF - BioEssays N2 - The unusual occurrence and developmental diversity of asexual eukaryotes remain a puzzle. De novo formation of a functioning asexual genome requires a unique assembly of sets of genes or gene states to disrupt cellular mechanisms of meiosis and gametogenesis, and to affect discrete components of sexuality and produce clonal or hemiclonal offspring. We highlight two usually overlooked but essential conditions to understand the molecular nature of clonal organisms, that is, a nonrecombinant genomic assemblage retaining modifiers of the sexual program, and a complementation between altered reproductive components. These subtle conditions are the basis for physiologically viable and genetically balanced transitions between generations. Genomic and developmental evidence from asexual animals and plants indicates the lack of complementation of molecular changes in the sexual reproductive program is likely the main cause of asexuals' rarity, and can provide an explanatory frame for the developmental diversity and lability of developmental patterns in some asexuals as well as for the discordant time to extinction estimations. KW - amphimixis KW - apomixis KW - automixis KW - gynogenesis KW - hybridogenesis KW - parthenogenesis Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-225818 VL - 43 IS - 1 ER - TY - JOUR A1 - Bousquet, Jean A1 - Anto, Josep M. A1 - Bachert, Claus A1 - Haahtela, Tari A1 - Zuberbier, Torsten A1 - Czarlewski, Wienczyslawa A1 - Bedbrook, Anna A1 - Bosnic‐Anticevich, Sinthia A1 - Walter Canonica, G. A1 - Cardona, Victoria A1 - Costa, Elisio A1 - Cruz, Alvaro A. A1 - Erhola, Marina A1 - Fokkens, Wytske J. A1 - Fonseca, Joao A. A1 - Illario, Maddalena A1 - Ivancevich, Juan‐Carlos A1 - Jutel, Marek A1 - Klimek, Ludger A1 - Kuna, Piotr A1 - Kvedariene, Violeta A1 - Le, LTT A1 - Larenas‐Linnemann, Désirée E. A1 - Laune, Daniel A1 - Lourenço, Olga M. A1 - Melén, Erik A1 - Mullol, Joaquim A1 - Niedoszytko, Marek A1 - Odemyr, Mikaëla A1 - Okamoto, Yoshitaka A1 - Papadopoulos, Nikos G. A1 - Patella, Vincenzo A1 - Pfaar, Oliver A1 - Pham‐Thi, Nhân A1 - Rolland, Christine A1 - Samolinski, Boleslaw A1 - Sheikh, Aziz A1 - Sofiev, Mikhail A1 - Suppli Ulrik, Charlotte A1 - Todo‐Bom, Ana A1 - Tomazic, Peter‐Valentin A1 - Toppila‐Salmi, Sanna A1 - Tsiligianni, Ioanna A1 - Valiulis, Arunas A1 - Valovirta, Erkka A1 - Ventura, Maria‐Teresa A1 - Walker, Samantha A1 - Williams, Sian A1 - Yorgancioglu, Arzu A1 - Agache, Ioana A1 - Akdis, Cezmi A. A1 - Almeida, Rute A1 - Ansotegui, Ignacio J. A1 - Annesi‐Maesano, Isabella A1 - Arnavielhe, Sylvie A1 - Basagaña, Xavier A1 - D. Bateman, Eric A1 - Bédard, Annabelle A1 - Bedolla‐Barajas, Martin A1 - Becker, Sven A1 - Bennoor, Kazi S. A1 - Benveniste, Samuel A1 - Bergmann, Karl C. A1 - Bewick, Michael A1 - Bialek, Slawomir A1 - E. Billo, Nils A1 - Bindslev‐Jensen, Carsten A1 - Bjermer, Leif A1 - Blain, Hubert A1 - Bonini, Matteo A1 - Bonniaud, Philippe A1 - Bosse, Isabelle A1 - Bouchard, Jacques A1 - Boulet, Louis‐Philippe A1 - Bourret, Rodolphe A1 - Boussery, Koen A1 - Braido, Fluvio A1 - Briedis, Vitalis A1 - Briggs, Andrew A1 - Brightling, Christopher E. A1 - Brozek, Jan A1 - Brusselle, Guy A1 - Brussino, Luisa A1 - Buhl, Roland A1 - Buonaiuto, Roland A1 - Calderon, Moises A. A1 - Camargos, Paulo A1 - Camuzat, Thierry A1 - Caraballo, Luis A1 - Carriazo, Ana‐Maria A1 - Carr, Warner A1 - Cartier, Christine A1 - Casale, Thomas A1 - Cecchi, Lorenzo A1 - Cepeda Sarabia, Alfonso M. A1 - H. Chavannes, Niels A1 - Chkhartishvili, Ekaterine A1 - Chu, Derek K. A1 - Cingi, Cemal A1 - Correia de Sousa, Jaime A1 - Costa, David J. A1 - Courbis, Anne‐Lise A1 - Custovic, Adnan A1 - Cvetkosvki, Biljana A1 - D'Amato, Gennaro A1 - da Silva, Jane A1 - Dantas, Carina A1 - Dokic, Dejan A1 - Dauvilliers, Yves A1 - De Feo, Giulia A1 - De Vries, Govert A1 - Devillier, Philippe A1 - Di Capua, Stefania A1 - Dray, Gerard A1 - Dubakiene, Ruta A1 - Durham, Stephen R. A1 - Dykewicz, Mark A1 - Ebisawa, Motohiro A1 - Gaga, Mina A1 - El‐Gamal, Yehia A1 - Heffler, Enrico A1 - Emuzyte, Regina A1 - Farrell, John A1 - Fauquert, Jean‐Luc A1 - Fiocchi, Alessandro A1 - Fink‐Wagner, Antje A1 - Fontaine, Jean‐François A1 - Fuentes Perez, José M. A1 - Gemicioğlu, Bilun A1 - Gamkrelidze, Amiran A1 - Garcia‐Aymerich, Judith A1 - Gevaert, Philippe A1 - Gomez, René Maximiliano A1 - González Diaz, Sandra A1 - Gotua, Maia A1 - Guldemond, Nick A. A1 - Guzmán, Maria‐Antonieta A1 - Hajjam, Jawad A1 - Huerta Villalobos, Yunuen R. A1 - Humbert, Marc A1 - Iaccarino, Guido A1 - Ierodiakonou, Despo A1 - Iinuma, Tomohisa A1 - Jassem, Ewa A1 - Joos, Guy A1 - Jung, Ki‐Suck A1 - Kaidashev, Igor A1 - Kalayci, Omer A1 - Kardas, Przemyslaw A1 - Keil, Thomas A1 - Khaitov, Musa A1 - Khaltaev, Nikolai A1 - Kleine‐Tebbe, Jorg A1 - Kouznetsov, Rostislav A1 - Kowalski, Marek L. A1 - Kritikos, Vicky A1 - Kull, Inger A1 - La Grutta, Stefania A1 - Leonardini, Lisa A1 - Ljungberg, Henrik A1 - Lieberman, Philip A1 - Lipworth, Brian A1 - Lodrup Carlsen, Karin C. A1 - Lopes‐Pereira, Catarina A1 - Loureiro, Claudia C. A1 - Louis, Renaud A1 - Mair, Alpana A1 - Mahboub, Bassam A1 - Makris, Michaël A1 - Malva, Joao A1 - Manning, Patrick A1 - Marshall, Gailen D. A1 - Masjedi, Mohamed R. A1 - Maspero, Jorge F. A1 - Carreiro‐Martins, Pedro A1 - Makela, Mika A1 - Mathieu‐Dupas, Eve A1 - Maurer, Marcus A1 - De Manuel Keenoy, Esteban A1 - Melo‐Gomes, Elisabete A1 - Meltzer, Eli O. A1 - Menditto, Enrica A1 - Mercier, Jacques A1 - Micheli, Yann A1 - Miculinic, Neven A1 - Mihaltan, Florin A1 - Milenkovic, Branislava A1 - Mitsias, Dimitirios I. A1 - Moda, Giuliana A1 - Mogica‐Martinez, Maria‐Dolores A1 - Mohammad, Yousser A1 - Montefort, Steve A1 - Monti, Ricardo A1 - Morais‐Almeida, Mario A1 - Mösges, Ralph A1 - Münter, Lars A1 - Muraro, Antonella A1 - Murray, Ruth A1 - Naclerio, Robert A1 - Napoli, Luigi A1 - Namazova‐Baranova, Leyla A1 - Neffen, Hugo A1 - Nekam, Kristoff A1 - Neou, Angelo A1 - Nordlund, Björn A1 - Novellino, Ettore A1 - Nyembue, Dieudonné A1 - O'Hehir, Robyn A1 - Ohta, Ken A1 - Okubo, Kimi A1 - Onorato, Gabrielle L. A1 - Orlando, Valentina A1 - Ouedraogo, Solange A1 - Palamarchuk, Julia A1 - Pali‐Schöll, Isabella A1 - Panzner, Peter A1 - Park, Hae‐Sim A1 - Passalacqua, Gianni A1 - Pépin, Jean‐Louis A1 - Paulino, Ema A1 - Pawankar, Ruby A1 - Phillips, Jim A1 - Picard, Robert A1 - Pinnock, Hilary A1 - Plavec, Davor A1 - Popov, Todor A. A1 - Portejoie, Fabienne A1 - Price, David A1 - Prokopakis, Emmanuel P. A1 - Psarros, Fotis A1 - Pugin, Benoit A1 - Puggioni, Francesca A1 - Quinones‐Delgado, Pablo A1 - Raciborski, Filip A1 - Rajabian‐Söderlund, Rojin A1 - Regateiro, Frederico S. A1 - Reitsma, Sietze A1 - Rivero‐Yeverino, Daniela A1 - Roberts, Graham A1 - Roche, Nicolas A1 - Rodriguez‐Zagal, Erendira A1 - Rolland, Christine A1 - Roller‐Wirnsberger, Regina E. A1 - Rosario, Nelson A1 - Romano, Antonino A1 - Rottem, Menachem A1 - Ryan, Dermot A1 - Salimäki, Johanna A1 - Sanchez‐Borges, Mario M. A1 - Sastre, Joaquin A1 - Scadding, Glenis K. A1 - Scheire, Sophie A1 - Schmid‐Grendelmeier, Peter A1 - Schünemann, Holger J. A1 - Sarquis Serpa, Faradiba A1 - Shamji, Mohamed A1 - Sisul, Juan‐Carlos A1 - Sofiev, Mikhail A1 - Solé, Dirceu A1 - Somekh, David A1 - Sooronbaev, Talant A1 - Sova, Milan A1 - Spertini, François A1 - Spranger, Otto A1 - Stellato, Cristiana A1 - Stelmach, Rafael A1 - Thibaudon, Michel A1 - To, Teresa A1 - Toumi, Mondher A1 - Usmani, Omar A1 - Valero, Antonio A. A1 - Valenta, Rudolph A1 - Valentin‐Rostan, Marylin A1 - Pereira, Marilyn Urrutia A1 - van der Kleij, Rianne A1 - Van Eerd, Michiel A1 - Vandenplas, Olivier A1 - Vasankari, Tuula A1 - Vaz Carneiro, Antonio A1 - Vezzani, Giorgio A1 - Viart, Frédéric A1 - Viegi, Giovanni A1 - Wallace, Dana A1 - Wagenmann, Martin A1 - Wang, De Yun A1 - Waserman, Susan A1 - Wickman, Magnus A1 - Williams, Dennis M. A1 - Wong, Gary A1 - Wroczynski, Piotr A1 - Yiallouros, Panayiotis K. A1 - Yusuf, Osman M. A1 - Zar, Heather J. A1 - Zeng, Stéphane A1 - Zernotti, Mario E. A1 - Zhang, Luo A1 - Shan Zhong, Nan A1 - Zidarn, Mihaela T1 - ARIA digital anamorphosis: Digital transformation of health and care in airway diseases from research to practice JF - Allergy N2 - Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed. KW - ARIA KW - asthma KW - CARAT KW - digital transformation of health and care KW - MASK KW - rhinitis Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-228339 VL - 76 IS - 1 SP - 168 EP - 190 ER - TY - JOUR A1 - Dohrn, Maike F. A1 - Ihne, Sandra A1 - Hegenbart, Ute A1 - Medina, Jessica A1 - Züchner, Stephan L. A1 - Coelho, Teresa A1 - Hahn, Katrin T1 - Targeting transthyretin ‐ Mechanism‐based treatment approaches and future perspectives in hereditary amyloidosis JF - Journal of Neurochemistry N2 - The liver‐derived, circulating transport protein transthyretin (TTR) is the cause of systemic hereditary (ATTRv) and wild‐type (ATTRwt) amyloidosis. TTR stabilization and knockdown are approved therapies to mitigate the otherwise lethal disease course. To date, the variety in phenotypic penetrance is not fully understood. This systematic review summarizes the current literature on TTR pathophysiology with its therapeutic implications. Tetramer dissociation is the rate‐limiting step of amyloidogenesis. Besides destabilizing TTR mutations, other genetic (RBP4, APCS, AR, ATX2, C1q, C3) and external (extracellular matrix, Schwann cell interaction) factors influence the type of onset and organ tropism. The approved small molecule tafamidis stabilizes the tetramer and significantly decelerates the clinical course. By sequence‐specific mRNA knockdown, the approved small interfering RNA (siRNA) patisiran and antisense oligonucleotide (ASO) inotersen both significantly reduce plasma TTR levels and improve neuropathy and quality of life compared to placebo. With enhanced hepatic targeting capabilities, GalNac‐conjugated siRNA and ASOs have recently entered phase III clinical trials. Bivalent TTR stabilizers occupy both binding groves in vitro, but have not been tested in trials so far. Tolcapone is another stabilizer with the potential to cross the blood–brain barrier, but its half‐life is short and liver failure a potential side effect. Amyloid‐directed antibodies and substances like doxycycline aim at reducing the amyloid load, however, none of the yet developed antibodies has successfully passed clinical trials. ATTR‐amyloidosis has become a model disease for pathophysiology‐based treatment. Further understanding of disease mechanisms will help to overcome the remaining limitations, including application burden, side effects, and blood–brain barrier permeability. KW - amyloid‐directed antibodies KW - ATTRv amyloidosis KW - familial amyloid polyneuropathy (FAP) KW - transthyretin KW - TTR knockdown KW - TTR stabilization Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-224481 VL - 156 IS - 6 SP - 802 EP - 818 ER - TY - JOUR A1 - Flentje, Michael A1 - Richter, Jürgen T1 - Professor Dr. Werner Bohndorf gestorben JF - Strahlentherapie und Onkologie N2 - Kein Abstract verfügbar. KW - Werner Bohndorf KW - Nachruf Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-264838 SN - 1439-099X VL - 197 IS - 7 ER - TY - JOUR A1 - Linsenmann, Thomas A1 - Cattaneo, Andrea A1 - März, Alexander A1 - Weiland, Judith A1 - Stetter, Christian A1 - Nickl, Robert A1 - Westermaier, Thomas T1 - Combined frameless stereotactical biopsy and intraoperative cerebral angiography by 3D-rotational fluoroscopy with intravenous contrast administration: a feasibility study JF - BMC Medical Imaging N2 - Background Mobile 3-dimensional fluoroscopes are an integral part of modern neurosurgical operating theatres and can also be used in combination with free available image post processing to depict cerebral vessels. In preparation of stereotactic surgery, preoperative Computed Tomography (CT) may be required for image fusion. Contrast CT may be of further advantage for image fusion as it regards the vessel anatomy in trajectory planning. Time-consuming in-hospital transports are necessary for this purpose. Mobile 3D-fluoroscopes may be used to generate a CT equal preoperative data set without an in-hospital transport. This study was performed to determine the feasibility and image quality of intraoperative 3-dimensional fluoroscopy with intravenous contrast administration in combination with stereotactical procedures. Methods 6 patients were included in this feasibility study. After fixation in a radiolucent Mayfield clamp a rotational fluoroscopy scan was performed with 50 mL iodine contrast agent. The image data sets were merged with the existing MRI images at a planning station and visually evaluated by two observer. The operation times were compared between the frame-based and frameless systems (“skin-to-skin” and “OR entry to exit”). Results The procedure proves to be safe. The entire procedure from fluoroscope positioning to the transfer to the planning station took 5–6 min with an image acquisition time of 24 s. In 5 of 6 cases, the fused imaging was able to reproduce the vascular anatomy accurately and in good quality. Both time end-points were significantly shorter compared to frame-based interventions. Conclusion The images could easily be transferred to the planning and navigation system and were successfully merged with the MRI data set. The procedure can be completely integrated into the surgical workflow. Preoperative CT imaging or transport under anaesthesia may even be replaced by this technique in the future. Furthermore, hemorrhages can be successfully visualized intraoperatively and might prevent time delays in emergencies. KW - 3 D rotational fluoroscopy KW - neurosurgery KW - stereotaxy KW - frameless systems KW - intraoperative imaging Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-270370 VL - 21 ER - TY - JOUR A1 - Kann, Simone A1 - Blessmann, Joerg A1 - Winkelmann, Yvonne A1 - Hansen, Jessica A1 - Maya Amaya, Leonardo J. A1 - Rivera Salcedo, Gadith E. A1 - Halas, Hussein El A1 - Schmidt‐Chanasit, Jonas A1 - Keoviengkhone, Latdamone A1 - Sopraseuth, Vatsana A1 - Deschermeier, Christina A1 - Mika, Angela T1 - Dengue virus detection in Lao PDR and Colombia: Comparative evaluation of PCR tests JF - Tropical Medicine & International Health N2 - Objectives Dengue virus (DENV) detection by polymerase chain reaction (PCR) facilitates diagnosis of dengue fever, which is the most frequent arboviral disease globally. Two studies were performed in countries with high dengue incidence, to assess the diagnostic performance of different PCR techniques. Methods/Results Two hundred and seventy‐nine acute phase blood samples from febrile patients were analyzed for DENV by the RealStar Dengue RT‐PCR kit (Altona Diagnostics) as gold standard in comparison with the Tropical Fever Core multiplex PCR (Fast Track Diagnostics). In total, 102 samples collected in Savannakhet Province (Lao PDR, Southeast Asia) in 2013 and 35 samples from Valledupar (Colombia, South America) tested positive for DENV by RealStar RT‐PCR. In comparison, the Tropical Fever Core multiplex PCR detected 65.0% (65/102) and 68.6% (24/35) of these samples as positive for DENV in Savannakhet and Valledupar, respectively. Diagnostic sensitivity of the multiplex PCR strongly correlated with viral load. A subset of DENV PCR‐confirmed samples was additionally tested by BNITM in house Dengue Type RT‐PCR in comparison with two commercial test kits (RealStar Dengue Type RT‐PCR [Altona Diagnostics], Dengue differentiation PCR [Fast Track Diagnostics]). The leading dengue serotype in Savannakhet was DENV‐3 (58% [29/50]), while DENV‐1 (53.8% [14/26]) was the predominant serotype found in samples collected in Valledupar by BNITM‐type PCR. However, three DENV serotypes were circulating in Valledupar and in Savannakhet. In 2015, additional studies found predominantly DENV‐4 (71% [12/17]) in Savannakhet. Conclusions Both studies emphasized that routine diagnostics in both regions will benefit from an expanded use of highly sensitive pan‐dengue PCRs. KW - Colombia KW - dengue infections KW - dengue serotypes KW - Lao PDR KW - PCR diagnostics Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-262703 VL - 26 IS - 10 SP - 1296 EP - 1302 ER - TY - JOUR A1 - Freitag‐Wolf, Sandra A1 - Munz, Matthias A1 - Junge, Olaf A1 - Graetz, Christian A1 - Jockel‐Schneider, Yvonne A1 - Staufenbiel, Ingmar A1 - Bruckmann, Corinna A1 - Lieb, Wolfgang A1 - Franke, Andre A1 - Loos, Bruno G. A1 - Jepsen, Søren A1 - Dommisch, Henrik A1 - Schaefer, Arne S. T1 - Sex‐specific genetic factors affect the risk of early‐onset periodontitis in Europeans JF - Journal of Clinical Periodontology N2 - Aims Various studies have reported that young European women are more likely to develop early‐onset periodontitis compared to men. A potential explanation for the observed variations in sex and age of disease onset is the natural genetic variation within the autosomal genomes. We hypothesized that genotype‐by‐sex (G × S) interactions contribute to the increased prevalence and severity. Materials and methods Using the case‐only design, we tested for differences in genetic effects between men and women in 896 North‐West European early‐onset cases, using imputed genotypes from the OmniExpress genotyping array. Population‐representative 6823 controls were used to verify that the interacting variables G and S were uncorrelated in the general population. Results In total, 20 loci indicated G × S associations (P < 0.0005), 3 of which were previously suggested as risk genes for periodontitis (ABLIM2, CDH13, and NELL1). We also found independent G × S interactions of the related gene paralogs MACROD1/FLRT1 (chr11) and MACROD2/FLRT3 (chr20). G × S‐associated SNPs at CPEB4, CDH13, MACROD1, and MECOM were genome‐wide‐associated with heel bone mineral density (CPEB4, MECOM), waist‐to‐hip ratio (CPEB4, MACROD1), and blood pressure (CPEB4, CDH13). Conclusions Our results indicate that natural genetic variation affects the different heritability of periodontitis among sexes and suggest genes that contribute to inter‐sex phenotypic variation in early‐onset periodontitis. KW - alveolar bone loss KW - gene × sex interaction KW - genetic risk KW - heritability KW - inflammation Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-262445 VL - 48 IS - 11 SP - 1404 EP - 1413 ER - TY - JOUR A1 - Karimi, Sohail M. A1 - Freund, Matthias A1 - Wager, Brittney M. A1 - Knoblauch, Michael A1 - Fromm, Jörg A1 - M. Mueller, Heike A1 - Ache, Peter A1 - Krischke, Markus A1 - Mueller, Martin J. A1 - Müller, Tobias A1 - Dittrich, Marcus A1 - Geilfus, Christoph-Martin A1 - Alfaran, Ahmed H. A1 - Hedrich, Rainer A1 - Deeken, Rosalia T1 - Under salt stress guard cells rewire ion transport and abscisic acid signaling JF - New Phytologist N2 - Soil salinity is an increasingly global problem which hampers plant growth and crop yield. Plant productivity depends on optimal water-use efficiency and photosynthetic capacity balanced by stomatal conductance. Whether and how stomatal behavior contributes to salt sensitivity or tolerance is currently unknown. This work identifies guard cell-specific signaling networks exerted by a salt-sensitive and salt-tolerant plant under ionic and osmotic stress conditions accompanied by increasing NaCl loads. We challenged soil-grown Arabidopsis thaliana and Thellungiella salsuginea plants with short- and long-term salinity stress and monitored genome-wide gene expression and signals of guard cells that determine their function. Arabidopsis plants suffered from both salt regimes and showed reduced stomatal conductance while Thellungiella displayed no obvious stress symptoms. The salt-dependent gene expression changes of guard cells supported the ability of the halophyte to maintain high potassium to sodium ratios and to attenuate the abscisic acid (ABA) signaling pathway which the glycophyte kept activated despite fading ABA concentrations. Our study shows that salinity stress and even the different tolerances are manifested on a single cell level. Halophytic guard cells are less sensitive than glycophytic guard cells, providing opportunities to manipulate stomatal behavior and improve plant productivity. KW - soil KW - stomata KW - abscisic acid (ABA) KW - glycophyte Arabidopsis KW - guard cell KW - halophyte Thellungiella/Eutrema KW - ion transport KW - salt stress Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-259635 VL - 231 IS - 3 ER - TY - JOUR A1 - Lemm, Lukas T1 - Is there a decline of democracy in the EU between 2004 and 2016? The relevance of data selection: a replication study of Smolka (2021) and comparison of democracy measures JF - Zeitschrift für Vergleichende Politikwissenschaft N2 - Is there a Decline of Democracy? Democracy measurement provides the basis for answering this question. However, there are different measurement tools based on different meanings of democracy that have been shown to vary in their concept validity. Therefore, it is relevant to examine whether the results of the different measurement tools converge or diverge with respect to a potential decline of democracy. Smolka (2021) finds a decline of democracy for new and old EU states based on standardized data from the Democracy Barometer. A re-analysis using the original data of the Democracy Barometer and the Democracy Matrix can hardly replicate these results. A comparison of further measurements shows that the instruments diverge rather than converge. I therefore conclude with some thoughts on overcoming the selection problem that arises in light of these contrasts. KW - EU member states KW - quality of democracy KW - decline of democracy KW - replication studies KW - robustness checks KW - measuring democracy Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-270107 SN - 1865-2654 VL - 15 IS - 3 ER - TY - JOUR A1 - Schmitt, T. A1 - Egu, D.T. A1 - Walter, E. A1 - Sigmund, A.M. A1 - Eichkorn, R. A1 - Yazdi, A. A1 - Schmidt, E. A1 - Sárdy, M. A1 - Eming, R. A1 - Goebeler, M. A1 - Waschke, J. T1 - Ca\(^{2+}\) signalling is critical for autoantibody‐induced blistering of human epidermis in pemphigus JF - British Journal of Dermatology N2 - Background Pemphigus is a severe bullous autoimmune skin disease. Pemphigus foliaceus (PF) is characterized by antidesmoglein (Dsg) 1 IgG causing epidermal blistering; mucosal pemphigus vulgaris (mPV) by anti‐Dsg3 IgG inducing erosions in the mucosa; and mucocutaneous pemphigus vulgaris (PV) by affecting both, with autoantibodies targeting Dsg1 and Dsg3. Objectives To characterize the Ca\(^{2+}\) flux pathway and delineate its importance in pemphigus pathogenesis and clinical phenotypes caused by different antibody profiles. Methods Immunoprecipitation, Ca\(^{2+}\) flux analysis, Western blotting, immunofluorescence staining, dissociation assays and a human skin ex vivo model were used. Results PV IgG and PF IgG, but neither Dsg3‐specific monoclonal antibody (AK23) nor mPV IgG, caused Ca\(^{2+}\) influx in primary human keratinocytes. Phosphatidylinositol 4‐kinase α interacts with Dsg1 but not with Dsg3. Its downstream target – phospholipase‐C‐γ1 (PLC) – was activated by PV IgG and PF IgG but not AK23 or mPV IgG. PLC releases inositol 1,4,5‐trisphosphate (IP3) causing IP3 receptor (IP3R) activation and Ca2+ flux from the endoplasmic reticulum into the cytosol, which stimulates Ca2+ release‐activated channels (CRAC)‐mediated Ca\(^{2+}\) influx. Inhibitors against PLC, IP3R and CRAC effectively blocked PV IgG and PF IgG‐induced Ca\(^{2+}\) influx; ameliorated alterations of Dsg1 and Dsg3 localization, and reorganization of keratin and actin filaments; and inhibited loss of cell adhesion in vitro. Finally, inhibiting PLC or IP3R was protective against PV IgG‐induced blister formation and redistribution of Dsg1 and Dsg3 in human skin ex vivo. Conclusions Ca2+‐mediated signalling is important for epidermal blistering and dependent on the autoantibody profile, which indicates different roles for signalling complexes organized by Dsg1 and Dsg3. Interfering with PLC and Ca\(^{2+}\) signalling may be a promising approach to treat epidermal manifestations of pemphigus. KW - pemphigus KW - epidermis KW - Ca\(^{2+}\) signalling Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-262810 VL - 185 IS - 3 SP - 595 EP - 604 ER - TY - JOUR A1 - Dittmann, Lara A. T1 - Sprach- und Kommunikationsnuancen in literarischen Interspeziesbegegnungen – Juan Ramón Jiménezʼ Platero y yo (1914/1917) und Thomas Manns Herr und Hund (1919) JF - promptus - Würzburger Beiträge zur Romanistik N2 - The encounter with non-human animals has always been a major preoccupation in the (philosophical) quest of understanding the human (condition). Of course, they are not only present in literary texts, but also in other media such as music and art. We consider ourselves aware of their selves, natures and skills as well as their sensory perceptions. Indeed, the ways we interact with non-human animals in everyday life and in the fictional world, how we perceive, think and talk about them as well as how we communicate with them are often related to our own self-perceptions in the social collective and in social-historical discourse. If we take a closer look at literary interspecies relations, we can detect clear shades in language and communication. Based on the approaches of Human-Animal Studies, this article deals with those nuances regarding animal-human encounters in Juan Ramón Jiménez’ Platero y yo (1914/1917) and Thomas Mann's Herr und Hund (1919) in a comparative perspective. In addition to this, a special focus is placed on the effect these elements can have on (inter)acting literary subjects as well as on extra-textual recipients. KW - Human-Animal Studies KW - interspecies encounters KW - Platero y yo KW - Herr und Hund KW - animal-human relations Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-305658 SN - 2364-6705 VL - 7 ER - TY - JOUR A1 - Henk, Lars Thorben T1 - «We’re on the road to nowhere» – Felwine Sarrs narrativer Weg in die Afrotopie JF - promptus - Würzburger Beiträge zur Romanistik N2 - According to the Senegalesian scholar Felwine Sarr who conceives an African utopia in his programmatic essay Afrotopia (2016), this Afrotopos has already germinated in contemporary African literature. However, it still needs to be enquired to what extent the narrated topos of the street in Sarr’s own anthology 105 Rue Carnot (2011) has already realized the Afrotopos. In order to respond to this question, we would like to mobilise Michel Foucault’s concept of heterotopia, which elaborates on the interactions between truth production/knowledge, power and space, and permits us to conceive of «les lieux utopiques» (Foucault 2005: 40) as actually locatable on the map and real other places outside of all places (cf. Foucault 1994: 755). Thus, in the street, a different relationship between global North and South is founded, which becomes legible as an African «utopie localisée» (Foucault 2005: 41) that Sarr calls for in Afrotopia (2016). KW - utopia KW - heterotopia KW - street KW - space KW - power Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-305662 SN - 2364-6705 VL - 7 ER - TY - JOUR A1 - Kneifel, Malte T1 - Futur-Formen und ihre Funktionen im Português Arcaico JF - promptus - Würzburger Beiträge zur Romanistik N2 - This article aims to trace the development of different verb forms that express future tense of Old Portuguese from the 13th to the 15th century by analyzing a historical text corpus. During this period, Portuguese future tense could be expressed through one synthetical as well as two analytical morphological verb constructions. Adapting an analytic model formerly employed by the Mexican researcher Concepción Company Company for an investigation of similar future tense forms in Old Spanish, this article seeks to point out that the use of the different verb forms in Portuguese followed distinct functions regarding aspects of both information structure as well as modality. KW - historical linguistics KW - Portuguese future tense KW - Old Portuguese KW - modality KW - information structure Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-305673 SN - 2364-6705 VL - 7 ER - TY - JOUR A1 - Klamp, Yannic T1 - Alma und ánima in spanisch-zapotekischen Evangelisierungswerken: die Translation des Konzepts Seele im kolonialen Missionskontext (Neu-Spanien, 16.-18. Jh.) JF - promptus - Würzburger Beiträge zur Romanistik N2 - The arrival of the Spanish in present-day Oaxaca, Mexico, led to manifold communicative challenges and was the origin of the first written documents in the local indigenous languages. This paper focuses on Spanish-Zapotec translations produced by Christian missionaries during the colonial period. In this context, it aims to investigate the expression of the concept of soul in their catechisms and confesionarios by analyzing chronologically how different authors apply the Spanish synonyms alma and ánima. On the one hand, we can observe some similar tendencies in central Mexican documents for the early colonial period so that we can assume that the corpus was influenced by Nahuatl translations. On the other hand, there is an independent development in Spanish-Zapotec translations not only regarding the target text but also the source text. KW - colonial Mexico KW - Spanish-Zapotec translations KW - missionary texts KW - catechisms KW - loanwords Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-305681 SN - 2364-6705 VL - 7 ER -