TY - JOUR A1 - Kölligan, Daniel T1 - A note on Vedic cīti- JF - Indogermanische Forschungen N2 - Vedic cīti-, attested in the Atharvaveda, is argued to be related to Av. ṣ̌āitī-, OP šiyāti- ‘happiness’ built to PIE *kʷi̯eh₁- ‘to (come to) rest’. KW - Vedic KW - Atharvaveda KW - disease KW - healing KW - etymology Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-250986 SN - 1613-0405 SN - 0019-7262 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 - 126 IS - 1 SP - 135 EP - 140 ER - 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 -