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Jhang, Genie ; Estee, Justin ; Barney, Jonathan ; Cerizza, Giordano ; Kaneko, Masanori ; Lee, Jung Woo ; Lynch, William G. ; Isobe, Tadaaki ; Kurata-Nishimura, Mizuki ; Murakami, Tetsuya ; Tsang, Chun Yuen ; Tsang, Betty ; Wang, Rensheng ; Ahn, Deuk Soon ; Atar, Leyla ; Aumann, Thomas ; Baba, Hidetada ; Boretzky, Konstanze ; Brzychczyk, Janusz ; Chiga, Nobuyuki ; Fukuda, Naoki ; Gašparić, Igor ; Hong, Byungsik ; Horvat, Andrea ; Ieki, Kazuo ; Inabe, Naohito ; Kim, Y.J. ; Kobayashi, Taizo ; Kondo, Yosuke ; Lasko, Pawel ; Lee, H.S. ; Leifels, Yvonne ; Łukasik, Jerzy ; Manfredi, Juan ; McIntosh, Alan B. ; Morfouace, Pierre ; Nakamura, Takashi ; Nakatsuka, N. ; Nishimura, Shunji ; Olsen, Robert ; Otsu, Hideaki ; Pawłowski, Piotr ; Pelczar, Krzysztof ; Rossi, Dominic M. ; Sakurai, Hiroyoshi ; Santamaria, Clementine ; Sato, Hiromi ; Scheit, Heiko ; Shane, Rebecca ; Shimizu, Yohei ; Simon, Haik ; Snoch, Aleksandra ; Sochocka, Anna ; Sosin, Zbigniew ; Sumikama, Toshiyuki ; Suzuki, Hiroshi ; Suzuki, Daisuke ; Takeda, Hiroshi ; Tangwancharoen, Suwat ; Törnqvist, Hans Toshihide ; Togano, Yasuhiro ; Xiao, Zhi-Gang ; Yennello, Sherry J. ; Yurkon, John ; Zhang, Youhong ; Colonna, Maria ; Cozma, Dan ; Danielewicz, Paweł ; Elfner, Hannah ; Ikeno, Natsumi ; Ko, Che Ming ; Mohs, Justin ; Oliinychenko, Dmytro ; Ono, Akira ; Su, Jun ; Jia Wang, Yong ; Wolter, Hermann ; Xu, Jun ; Zhang, Ying-Xun ; Zhang, Zhen
In the past two decades, pions created in the high density regions of heavy ion collisions have been predicted to be sensitive at high densities to the symmetry energy term in the nuclear equation of state, a property that is key to our understanding of neutron stars. In a new experiment designed to study the symmetry energy, the multiplicities of negatively and positively charged pions have been measured with high accuracy for central 132Sn+124Sn, 112Sn+124Sn, and 108Sn+112Sn collisions at E/A = 270 MeV with the SπRIT Time Projection Chamber. While individual pion multiplicities are measured to 4% accuracy, those of the charged pion multiplicity ratios are measured to 2% accuracy. We compare these data to predictions from seven major transport models. The calculations reproduce qualitatively the dependence of the multiplicities and their ratios on the total neutron and proton number in the colliding systems. However, the predictions of the transport models from different codes differ too much to allow extraction of reliable constraints on the symmetry energy from the data. This finding may explain previous contradictory conclusions on symmetry energy constraints obtained from pion data in Au+Au system. These new results call for still better understanding of the differences among transport codes, and new observables that are more sensitive to the density dependence of the symmetry energy.
Zhang, Ying ; Gazyakan, Emre ; Hundeshagen, Gabriel ; Fischer, Sebastian ; Bigdeli, Amir Khosrow ; Will-Marks, Patrick ; Knese, Ulrich ; Hirche, Christoph
Background: Compound flaps offer the advantage of one stage defect reconstruction respecting all relevant tissues and early functional recovery by optimal vascularity of all components. Due to its specific vascular anatomy and the three-dimensional donor site, compound flaps with bone components may result in higher complication rates compared to soft tissue compound flaps. The meta-analysis summarizes the available evidence and evaluates whether bone components are a risk factor for periprocedural complications in upper extremity multidimensional defect reconstruction. Method: PubMed and Embase were searched for all publications addressing compound free flaps for upper extremity defect reconstruction with bone or soft tissue components published between January 1988 and May 2018. The methodological quality was assessed with the American Society of Plastic Surgeons Evidence Rating Scale for Therapeutic Studies. Flap loss, thrombosis rate, early infection, hematoma, seroma, as well as donor site complications were extracted and analyzed. Results: Twelve out of 1157 potentially eligible studies (evidence-III) comprising 159 patients were finally included with publication bias for all summarized complication rates. Complication rates for flaps with/ without bone components were: total flap loss 5%, 95% CI = 3%–10% (6%/5%); partial flap loss 8%, 95% CI = 5%–15%, (9%/8%); arterial/venous thrombosis 7%, 95% CI = 4%–12%, (8%/5%)/14%, 95% CI = 9%–21% (16%/6%, P < .05) with higher risk for flaps with bone components; infection 6%, 95% CI = 3%–12% (6%/6%); hematoma 6%, 95% CI = 3%–11% (6%/5%); seroma 5%, 95% CI = 3%–10% (5%/5%); dehiscence 10%, 95% CI = 6%–17% (11%/9%). Conclusion: Compound flaps for upper extremity defect reconstruction including bone components have a higher venous thrombosis rate compared to compound soft-tissue flaps.
Rosenow, Felix ; Brandt, Christian ; Bozorg, Ali ; Dimova, Svetlana ; Steiniger‐Brach, Björn ; Zhang, Ying ; Ferrò, Bruno ; Holmes, Gregory L. ; Kälviäinen, Reetta
Objectives: To assess tolerability and efficacy of lacosamide in adults with cerebrovascular epilepsy etiology (CVEE).
Materials and methods: Exploratory post hoc analyses of a double‐blind, initial monotherapy trial of lacosamide vs carbamazepine‐controlled release (carbamazepine‐CR) (SP0993; NCT01243177); a double‐blind conversion to lacosamide monotherapy trial (SP0902; NCT00520741); and an observational study of adjunctive lacosamide added to one antiepileptic drug (SP0973 VITOBA; NCT01098162). Patients with CVEE were identified based on epilepsy etiology recorded at baseline.
Results: In the initial monotherapy trial, 61 patients had CVEE (lacosamide: 27; carbamazepine‐CR: 34). 20 (74.1%) patients on lacosamide (27 [79.4%] on carbamazepine‐CR) reported treatment‐emergent adverse events (TEAEs), most commonly (≥10%) headache, dizziness, and fatigue (carbamazepine‐CR: headache, dizziness). A numerically higher proportion of patients on lacosamide than carbamazepine‐CR completed 6 months (22 [81.5%]; 20 [58.8%]) and 12 months (18 [66.7%]; 17 [50.0%]) treatment without seizure at last evaluated dose. In the conversion to monotherapy trial, 26/30 (86.7%) patients with CVEE reported TEAEs, most commonly (≥4 patients) dizziness, convulsion, fatigue, headache, somnolence, and cognitive disorder. During lacosamide monotherapy, 17 (56.7%) patients were 50% responders and six (20.0%) were seizure‐free. In the observational study, 36/83 (43.4%) patients with CVEE reported TEAEs, most commonly (≥5%) fatigue and dizziness. Effectiveness was assessed for 75 patients. During the last 3 months, 60 (80%) were 50% responders and 42 (56.0%) were seizure‐free.
Conclusions: These exploratory post hoc analyses suggested lacosamide was generally well tolerated and effective in patients with CVEE, with data from the initial monotherapy trial suggesting numerically better efficacy than carbamazepine‐CR.
Eight species of the genus Notosemus Förster, 1869 (Hymenoptera: Ichneumonidae) are reported, three of which are new to science: N. albimaculatus Sheng & Sun, sp. nov. and N. planus Sheng & Sun, sp. nov., both collected from Xizang Autonomous Region, SW China, and N. wugongicus Sheng & Sun, sp. nov., collected from Jiangxi Province, S China. One new record for China, N. bohemani (Wesmael, 1855), was reared from Zeiraphera griseana (Hübner, 1789) (Lepidoptera, Tortricidae), a leaf pest of Larix principis-rupprechtii Mayr. (Pinaceae) in Ningxia Hui Autonomous Region, NW China. A key to the species of the genus Notosemus is provided.
Ri, Keiken ; Weng, Tsai-Hsuan ; Claveras Cabezudo, Ainara ; Jösting, Wiebke ; Yu, Zhang ; Bazzone, Andre ; Leong, Nancy C. P. ; Welsch, Sonja ; Doty, Raymond T. ; Gursu, Gonca ; Lim, Tiffany Jia Ying ; Luise Schmidt, Sarah ; Abkowitz, Janis L. ; Hummer, Gerhard ; Wu, Di ; Nguyen, Long N. ; Safarian, Schara
Human feline leukemia virus subgroup C receptor-related proteins 1 and 2 (FLVCR1 and 2) are members of the major facilitator superfamily1. Their dysfunction is linked to several clinical disorders, including PCARP, HSAN, and Fowler syndrome2–7. Earlier studies concluded that FLVCR1 may function as a putative heme exporter8–12, while FLVCR2 was suggested to act as a heme importer13, yet conclusive biochemical and detailed molecular evidence remained elusive for the function of both transporters14–17. Here, we show that FLVCR1 and FLVCR2 facilitate the transport of choline and ethanolamine across human plasma membranes, utilizing a concentration-driven substrate translocation process. Through structural and computational analyses, we have identified distinct conformational states of FLVCRs and unraveled the coordination chemistry underlying their substrate interactions. Within the binding pocket of both transporters, we identify fully conserved tryptophan and tyrosine residues holding a central role in the formation of cation-π interactions, essential for choline and ethanolamine selectivity. Our findings not only clarify the mechanisms of choline and ethanolamine transport by FLVCR1 and FLVCR2, enhancing our comprehension of disease-associated mutations that interfere with these vital processes, but also shed light on the conformational dynamics of these MFS-type proteins during the transport cycle.
Ri, Keiken ; Weng, Tsai-Hsuan ; Claveras Cabezudo, Ainara ; Jösting, Wiebke ; Zhang, Yu ; Bazzone, Andre ; Leong, Nancy C. P. ; Welsch, Sonja ; Doty, Raymond T. ; Gursu, Gonca ; Lim, Tiffany Jia Ying ; Schmidt, Sarah Luise ; Abkowitz, Janis L. ; Hummer, Gerhard ; Wu, Di ; Nguyen, Long N. ; Safarian, Schara
Human feline leukaemia virus subgroup C receptor-related proteins 1 and 2 (FLVCR1 and FLVCR2) are members of the major facilitator superfamily1. Their dysfunction is linked to several clinical disorders, including PCARP, HSAN and Fowler syndrome2,3,4,5,6,7. Earlier studies concluded that FLVCR1 may function as a haem exporter8,9,10,11,12, whereas FLVCR2 was suggested to act as a haem importer13, yet conclusive biochemical and detailed molecular evidence remained elusive for the function of both transporters14,15,16. Here, we show that FLVCR1 and FLVCR2 facilitate the transport of choline and ethanolamine across the plasma membrane, using a concentration-driven substrate translocation process. Through structural and computational analyses, we have identified distinct conformational states of FLVCRs and unravelled the coordination chemistry underlying their substrate interactions. Fully conserved tryptophan and tyrosine residues form the binding pocket of both transporters and confer selectivity for choline and ethanolamine through cation–π interactions. Our findings clarify the mechanisms of choline and ethanolamine transport by FLVCR1 and FLVCR2, enhance our comprehension of disease-associated mutations that interfere with these vital processes and shed light on the conformational dynamics of these major facilitator superfamily proteins during the transport cycle.