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1. Iron rescues glucose-mediated photosynthesis repression during lipid accumulation in the green alga Chromochloris zofingiensis

Author: Tim L. Jeffers, Samuel O. Purvine, Carrie D. Nicora, Ryan McCombs, Shivani Upadhyaya, Adrien Stroumza, Ken Whang, Sean D. Gallaher, Alice Dohnalkova, Sabeeha S. Merchant, Mary Lipton, Krishna K. Niyogi, and Melissa S. Roth
Subjects: Science
Abstract: Abstract Energy status and nutrients regulate photosynthetic protein expression. The unicellular green alga Chromochloris zofingiensis switches off photosynthesis in the presence of exogenous glucose (+Glc) in a process that depends on hexokinase (HXK1). Here, we show that this response requires that cells lack sufficient iron (−Fe). Cells grown in −Fe+Glc accumulate triacylglycerol (TAG) while losing photosynthesis and thylakoid membranes. However, cells with an iron supplement (+Fe+Glc) maintain photosynthesis and thylakoids while still accumulating TAG. Proteomic analysis shows that known photosynthetic proteins are most depleted in heterotrophy, alongside hundreds of uncharacterized, conserved proteins. Photosynthesis repression is associated with enzyme and transporter regulation that redirects iron resources to (a) respiratory instead of photosynthetic complexes and (b) a ferredoxin-dependent desaturase pathway supporting TAG accumulation rather than thylakoid lipid synthesis. Combining insights from diverse organisms from green algae to vascular plants, we show how iron and trophic constraints on metabolism aid gene discovery for photosynthesis and biofuel production.
Published: 2024
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2. Green microalga Chromochloris zofingiensis conserves substrate uptake pattern but changes their metabolic uses across trophic transition

Author: Yuntao Hu, Nakian Kim, Melissa S. Roth, Katherine B. Louie, Suzanne M. Kosina, Shivani Upadhyaya, Tim L. Jeffers, Jacob S. Jordan, Benjamin P. Bowen, Krishna K. Niyogi, and Trent R. Northen
Subjects: microalgae, Chromochloris zofingiensis, arginine, purine, metabolomics, orotic acid, Microbiology, QR1-502
Abstract: The terrestrial green alga Chromochloris zofingiensis is an emerging model species with potential applications including production of triacylglycerol or astaxanthin. How C. zofingiensis interacts with the diverse substrates during trophic transitions is unknown. To characterize its substrate utilization and secretion dynamics, we cultivated the alga in a soil-based defined medium in transition between conditions with and without glucose supplementation. Then, we examined its exometabolite and endometabolite profiles. This analysis revealed that regardless of trophic modes, C. zofingiensis preferentially uptakes exogenous lysine, arginine, and purines, while secreting orotic acid. Here, we obtained metabolomic evidences that C. zofingiensis may use arginine for putrescine synthesis when in transition to heterotrophy, and for the TCA cycle during transition to photoautotrophy. We also report that glucose and fructose most effectively inhibited photosynthesis among thirteen different sugars. The utilized or secreted metabolites identified in this study provide important information to improve C. zofingiensis cultivation, and to expand its potential industrial and pharmaceutical applications.
Published: 2024
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3. The Potential of Neural Radiance Fields and 3D Gaussian Splatting for 3D Reconstruction from Aerial Imagery

Author: D. Haitz, M. Hermann, A. S. Roth, and M. Weinmann
Subjects: Technology, Engineering (General). Civil engineering (General), TA1-2040, Applied optics. Photonics, TA1501-1820
Abstract: In this paper, we focus on investigating the potential of advanced Neural Radiance Fields (NeRFs) and 3D Gaussian Splatting for 3D scene reconstruction from aerial imagery obtained via sensor platforms with an almost nadir-looking camera. Such a setting for image acquisition is convenient for capturing large-scale urban scenes, yet it poses particular challenges arising from imagery with large overlap, very short baselines, similar viewing direction and almost the same but large distance to the scene, and it therefore differs from the usual object-centric scene capture. We apply a traditional approach for image-based 3D reconstruction (COLMAP), a modern NeRF-based approach (Nerfacto) and a representative for the recently introduced 3D Gaussian Splatting approaches (Splatfacto), where the latter two are provided in the Nerfstudio framework. We analyze results achieved on the recently released UseGeo dataset both quantitatively and qualitatively. The achieved results reveal that the traditional COLMAP approach still outperforms Nerfacto and Splatfacto approaches for various scene characteristics, such as less-textured areas, areas with high vegetation, shadowed areas and areas observed from only very few views.
Published: 2024
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4. No immediate attentional bias towards or choice bias for male secondary sexual characteristics in Bornean orang-utans (Pongo pygmaeus)

Author: Tom S. Roth, Iliana Samara, Juan Olvido Perea-Garcia, and Mariska E. Kret
Subjects: Medicine, Science
Abstract: Abstract Primate faces provide information about a range of variant and invariant traits, including some that are relevant for mate choice. For example, faces of males may convey information about their health or genetic quality through symmetry or facial masculinity. Because perceiving and processing such information may have bearing on the reproductive success of an individual, cognitive systems are expected to be sensitive to facial cues of mate quality. However, few studies have investigated this topic in non-human primate species. Orang-utans are an interesting species to test mate-relevant cognitive biases, because they are characterised by male bimaturism: some adult males are fully developed and bear conspicuous flanges on the side of their face, while other males look relatively similar to females. Here, we describe two non-invasive computerised experiments with Bornean orang-utans (Pongo pygmaeus), testing (i) immediate attention towards large flanges and symmetrical faces using a dot-probe task (N = 3 individuals; 2F) and (ii) choice bias for pictures of flanged males over unflanged males using a preference test (N = 6 individuals; 4F). In contrast with our expectations, we found no immediate attentional bias towards either large flanges or symmetrical faces. In addition, individuals did not show a choice bias for stimuli of flanged males. We did find exploratory evidence for a colour bias and energy efficiency trade-offs in the preference task. We discuss our null results and exploratory results in the context of the evolutionary history of Bornean orang-utans, and provide suggestions for a more biocentric approach to the study of orang-utan cognition.
Published: 2024
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5. N-Butyl-2-Cyanoacrylate Adhesive Versus Absorbable Tacks in Laparoscopic Groin Hernia Repair: A Multicenter Randomized Clinical Trial

Author: Clayton C. Petro, MD, Benjamin K. Poulose, MD, Michael J. Rosen, MD, Alfredo M. Carbonell, II, DO, Adel G. El-Ghazzawy, MD, Jeremy A. Warren, MD, Emanuele Lo Menzo, MD, Ajita S. Prabhu, MD, David M. Krpata, MD, Samuel Szomstein, MD, Vimal Narula, MD, Crystal F. Totten, MD, Kelly R. Haisley, MD, Andrew C. Bernard, MD, Henrik O. Berdel, MD, Jessica K. Reynolds, MD, Zachary D. Warriner, MD, and John S. Roth, MD
Subjects: Surgery, RD1-811
Abstract: Objective:. We aimed to determine whether n-butyl-2-cyanoacrylate (NB2C) adhesive is a safe and effective mechanism for nonpenetrating mesh and peritoneal fixation during laparoscopic groin hernia repair. Background:. Chronic pain after laparoscopic groin hernia repair has been associated with penetrating fixation, but there had been no US Food and Drug Administration–approved devices for nonpenetrating fixation in this context. Methods:. Patients undergoing laparoscopic transabdominal preperitoneal (TAP) or totally extraperitoneal (TEP) groin hernia repair with mesh at 1 of 5 academic medical centers were randomized to mesh (TAP/TEP) and peritoneal (TAP) fixation with NB2C adhesive or absorbable tacks. The primary outcome was improvement in pain (visual analog scale [VAS]) at 6 months. The noninferiority margin was 0.9 (α = 0.025; β = 80%). Recurrence, successful use of the device, quality of life, and rates of adverse events (AEs) were secondary outcomes. Results:. From 2019 to 2021, 284 patients were randomized to either NB2C adhesive or absorbable tacks (n = 142/142). Patient and hernia characteristics were comparable, and 65% were repaired using a TAP approach. The difference in VAS improvement at 6 months with NB2C adhesive was not inferior to absorbable tacks in intention-to-treat and per-protocol analyses, respectively (0.25 [95% CI, −0.33 to 0.82]; P = 0.013; 0.22 [95% CI, −0.36 to 0.80], noninferiority P = 0.011). There were no differences in secondary outcomes including recurrence, successful use of each device to fixate the mesh and peritoneum, quality of life, and additional VAS pain scores. Rates of adverse and serious AEs were also comparable. Conclusions:. NB2C adhesive is safe and effective for mesh fixation and peritoneal closure during laparoscopic groin hernia repair.
Published: 2024
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6. Editorial: Women in coevolution 2022

Author: Laura Núñez-Pons, Vera Tai, and Melissa S. Roth
Subjects: coevolution, symbiosis, mutualism, underrepresentation, women in science, Evolution, QH359-425, Ecology, QH540-549.5
Published: 2024
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7. Effect of solution ions on the charge and performance of nanofiltration membranes

Author: Rebecca S. Roth, Liat Birnhack, Mor Avidar, Elizabeth A. Hjelvik, Anthony P. Straub, and Razi Epsztein
Subjects: Water supply for domestic and industrial purposes, TD201-500
Abstract: Abstract Considering growing efforts to understand and improve the solute-specific selectivity of nanofiltration (NF) membranes, we explored the ion-specific effects that govern the charge and performance of a loose polyamide NF membrane that is commonly used for solute-solute separations. Specifically, we systematically evaluated the zeta potential of the membrane under different conditions of pH, salinity, and ionic composition, and correlated the obtained data with membrane performance tested under similar conditions. Our results identify the pK a of both carboxylic and amine groups bonded to the membrane surface and suggest that the highly polarizable chloride anions in the solution adsorb to the polyamide, increasing its negative charge. We also show that monovalent cations of different “stickiness” can neutralize the negative membrane charge to different extents due to their varying tendency to sorb to the polymer matrix or screen the fixed carboxyl groups on the membrane surface. Notably, our correlation between zeta potential measurements and permeability experiments indicates the substantial contribution of solution ions to Donnan exclusion in NF membranes.
Published: 2024
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8. Cytoskeleton remodeling induced by SMYD2 methyltransferase drives breast cancer metastasis

Author: Alexandre G. Casanova, Gael S. Roth, Simone Hausmann, Xiaoyin Lu, Ludivine J. M. Bischoff, Emilie M. Froeliger, Lucid Belmudes, Ekaterina Bourova-Flin, Natasha M. Flores, Ana Morales Benitez, Tourkian Chasan, Marcello Caporicci, Jessica Vayr, Sandrine Blanchet, Francesco Ielasi, Sophie Rousseaux, Pierre Hainaut, Or Gozani, Muriel Le Romancer, Yohann Couté, Andres Palencia, Pawel K. Mazur, and Nicolas Reynoird
Subjects: Cytology, QH573-671
Abstract: Abstract Malignant forms of breast cancer refractory to existing therapies remain a major unmet health issue, primarily due to metastatic spread. A better understanding of the mechanisms at play will provide better insights for alternative treatments to prevent breast cancer cell dispersion. Here, we identify the lysine methyltransferase SMYD2 as a clinically actionable master regulator of breast cancer metastasis. While SMYD2 is overexpressed in aggressive breast cancers, we notice that it is not required for primary tumor growth. However, mammary-epithelium specific SMYD2 ablation increases mouse overall survival by blocking the primary tumor cell ability to metastasize. Mechanistically, we identify BCAR3 as a genuine physiological substrate of SMYD2 in breast cancer cells. BCAR3 monomethylated at lysine K334 (K334me1) is recognized by a novel methyl-binding domain present in FMNLs proteins. These actin cytoskeleton regulators are recruited at the cell edges by the SMYD2 methylation signaling and modulate lamellipodia properties. Breast cancer cells with impaired BCAR3 methylation lose migration and invasiveness capacity in vitro and are ineffective in promoting metastases in vivo. Remarkably, SMYD2 pharmacologic inhibition efficiently impairs the metastatic spread of breast cancer cells, PDX and aggressive mammary tumors from genetically engineered mice. This study provides a rationale for innovative therapeutic prevention of malignant breast cancer metastatic progression by targeting the SMYD2-BCAR3-FMNL axis.
Published: 2024
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9. Author Correction: Cytoskeleton remodeling induced by SMYD2 methyltransferase drives breast cancer metastasis

Author: Alexandre G. Casanova, Gael S. Roth, Simone Hausmann, Xiaoyin Lu, Ludivine J. M. Bischoff, Emilie M. Froeliger, Lucid Belmudes, Ekaterina Bourova-Flin, Natasha M. Flores, Ana Morales Benitez, Tourkian Chasan, Marcello Caporicci, Jessica Vayr, Sandrine Blanchet, Francesco Ielasi, Sophie Rousseaux, Pierre Hainaut, Or Gozani, Muriel Le Romancer, Yohann Couté, Andres Palencia, Pawel K. Mazur, and Nicolas Reynoird
Subjects: Cytology, QH573-671
Published: 2024
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10. Measurements of neutrino oscillation parameters from the T2K experiment using $$3.6\times 10^{21}$$ 3.6 × 10 21 protons on target

Author: K. Abe, N. Akhlaq, R. Akutsu, A. Ali, S. Alonso Monsalve, C. Alt, C. Andreopoulos, M. Antonova, S. Aoki, T. Arihara, Y. Asada, Y. Ashida, E. T. Atkin, M. Barbi, G. J. Barker, G. Barr, D. Barrow, M. Batkiewicz-Kwasniak, F. Bench, V. Berardi, L. Berns, S. Bhadra, A. Blanchet, A. Blondel, S. Bolognesi, T. Bonus, S. Bordoni, S. B. Boyd, A. Bravar, C. Bronner, S. Bron, A. Bubak, M. Buizza Avanzini, J. A. Caballero, N. F. Calabria, S. Cao, D. Carabadjac, A. J. Carter, S. L. Cartwright, M. G. Catanesi, A. Cervera, J. Chakrani, D. Cherdack, P. S. Chong, G. Christodoulou, A. Chvirova, M. Cicerchia, J. Coleman, G. Collazuol, L. Cook, A. Cudd, C. Dalmazzone, T. Daret, Yu. I. Davydov, A. De Roeck, G. De Rosa, T. Dealtry, C. C. Delogu, C. Densham, A. Dergacheva, F. Di Lodovico, S. Dolan, D. Douqa, T. A. Doyle, O. Drapier, J. Dumarchez, P. Dunne, K. Dygnarowicz, A. Eguchi, S. Emery-Schrenk, G. Erofeev, A. Ershova, G. Eurin, D. Fedorova, S. Fedotov, M. Feltre, A. J. Finch, G. A. Fiorentini Aguirre, G. Fiorillo, M. D. Fitton, J. M. Franco Patiño, M. Friend, Y. Fujii, Y. Fukuda, K. Fusshoeller, L. Giannessi, C. Giganti, V. Glagolev, M. Gonin, J. González Rosa, E. A. G. Goodman, A. Gorin, M. Grassi, M. Guigue, D. R. Hadley, J. T. Haigh, P. Hamacher-Baumann, D. A. Harris, M. Hartz, T. Hasegawa, S. Hassani, N. C. Hastings, Y. Hayato, D. Henaff, A. Hiramoto, M. Hogan, J. Holeczek, A. Holin, T. Holvey, N. T. Hong Van, T. Honjo, F. Iacob, A. K. Ichikawa, M. Ikeda, T. Ishida, M. Ishitsuka, H. T. Israel, K. Iwamoto, A. Izmaylov, N. Izumi, M. Jakkapu, B. Jamieson, S. J. Jenkins, C. Jesús-Valls, J. J. Jiang, P. Jonsson, S. Joshi, C. K. Jung, P. B. Jurj, M. Kabirnezhad, A. C. Kaboth, T. Kajita, H. Kakuno, J. Kameda, S. P. Kasetti, Y. Kataoka, Y. Katayama, T. Katori, M. Kawaue, E. Kearns, M. Khabibullin, A. Khotjantsev, T. Kikawa, H. Kikutani, S. King, V. Kiseeva, J. Kisiel, T. Kobata, H. Kobayashi, T. Kobayashi, L. Koch, S. Kodama, A. Konaka, L. L. Kormos, Y. Koshio, A. Kostin, T. Koto, K. Kowalik, Y. Kudenko, Y. Kudo, S. Kuribayashi, R. Kurjata, T. Kutter, M. Kuze, M. La Commara, L. Labarga, K. Lachner, J. Lagoda, S. M. Lakshmi, M. Lamers James, M. Lamoureux, A. Langella, J.-F. Laporte, D. Last, N. Latham, M. Laveder, L. Lavitola, M. Lawe, Y. Lee, C. Lin, S.-K. Lin, R. P. Litchfield, S. L. Liu, W. Li, A. Longhin, K. R. Long, A. Lopez Moreno, L. Ludovici, X. Lu, T. Lux, L. N. Machado, L. Magaletti, K. Mahn, M. Malek, M. Mandal, S. Manly, A. D. Marino, L. Marti-Magro, D. G. R. Martin, M. Martini, J. F. Martin, T. Maruyama, T. Matsubara, V. Matveev, C. Mauger, K. Mavrokoridis, E. Mazzucato, N. McCauley, J. McElwee, K. S. McFarland, C. McGrew, J. McKean, A. Mefodiev, G. D. Megias, P. Mehta, L. Mellet, C. Metelko, M. Mezzetto, E. Miller, A. Minamino, O. Mineev, S. Mine, M. Miura, L. Molina Bueno, S. Moriyama, P. Morrison, Th. A. Mueller, D. Munford, L. Munteanu, K. Nagai, Y. Nagai, T. Nakadaira, K. Nakagiri, M. Nakahata, Y. Nakajima, A. Nakamura, H. Nakamura, K. Nakamura, K. D. Nakamura, Y. Nakano, S. Nakayama, T. Nakaya, K. Nakayoshi, C. E. R. Naseby, T. V. Ngoc, V. Q. Nguyen, K. Niewczas, S. Nishimori, Y. Nishimura, K. Nishizaki, T. Nosek, F. Nova, P. Novella, J. C. Nugent, H. M. O’Keeffe, L. O’Sullivan, T. Odagawa, T. Ogawa, R. Okada, W. Okinaga, K. Okumura, T. Okusawa, N. Ospina, R. A. Owen, Y. Oyama, V. Palladino, V. Paolone, M. Pari, J. Parlone, S. Parsa, J. Pasternak, M. Pavin, D. Payne, G. C. Penn, D. Pershey, L. Pickering, C. Pidcott, G. Pintaudi, C. Pistillo, B. Popov, K. Porwit, M. Posiadala-Zezula, Y. S. Prabhu, F. Pupilli, B. Quilain, T. Radermacher, E. Radicioni, B. Radics, M. A. Ramírez, P. N. Ratoff, M. Reh, C. Riccio, E. Rondio, S. Roth, N. Roy, A. Rubbia, A. C. Ruggeri, C. A. Ruggles, A. Rychter, K. Sakashita, F. Sánchez, G. Santucci, C. M. Schloesser, K. Scholberg, M. Scott, Y. Seiya, T. Sekiguchi, H. Sekiya, D. Sgalaberna, A. Shaikhiev, F. Shaker, A. Shaykina, M. Shiozawa, W. Shorrock, A. Shvartsman, N. Skrobova, K. Skwarczynski, D. Smyczek, M. Smy, J. T. Sobczyk, H. Sobel, F. J. P. Soler, Y. Sonoda, A. J. Speers, R. Spina, I. A. Suslov, S. Suvorov, A. Suzuki, S. Y. Suzuki, Y. Suzuki, A. A. Sztuc, M. Tada, S. Tairafune, S. Takayasu, A. Takeda, Y. Takeuchi, K. Takifuji, H. K. Tanaka, Y. Tanihara, M. Tani, A. Teklu, V. V. Tereshchenko, N. Teshima, N. Thamm, L. F. Thompson, W. Toki, C. Touramanis, T. Towstego, K. M. Tsui, T. Tsukamoto, M. Tzanov, Y. Uchida, M. Vagins, D. Vargas, M. Varghese, G. Vasseur, C. Vilela, E. Villa, W. G. S. Vinning, U. Virginet, T. Vladisavljevic, T. Wachala, J. G. Walsh, Y. Wang, L. Wan, D. Wark, M. O. Wascko, A. Weber, R. Wendell, M. J. Wilking, C. Wilkinson, J. R. Wilson, K. Wood, C. Wret, J. Xia, Y.-H. Xu, K. Yamamoto, T. Yamamoto, C. Yanagisawa, G. Yang, T. Yano, K. Yasutome, N. Yershov, U. Yevarouskaya, M. Yokoyama, Y. Yoshimoto, N. Yoshimura, M. Yu, R. Zaki, A. Zalewska, J. Zalipska, K. Zaremba, G. Zarnecki, X. Zhao, T. Zhu, M. Ziembicki, E. D. Zimmerman, M. Zito, S. Zsoldos, and T2K Collaboration
Subjects: Astrophysics, QB460-466, Nuclear and particle physics. Atomic energy. Radioactivity, QC770-798
Abstract: Abstract The T2K experiment presents new measurements of neutrino oscillation parameters using $$19.7(16.3)\times 10^{20}$$ 19.7 ( 16.3 ) × 10 20 protons on target (POT) in (anti-)neutrino mode at the far detector (FD). Compared to the previous analysis, an additional $$4.7\times 10^{20}$$ 4.7 × 10 20 POT neutrino data was collected at the FD. Significant improvements were made to the analysis methodology, with the near-detector analysis introducing new selections and using more than double the data. Additionally, this is the first T2K oscillation analysis to use NA61/SHINE data on a replica of the T2K target to tune the neutrino flux model, and the neutrino interaction model was improved to include new nuclear effects and calculations. Frequentist and Bayesian analyses are presented, including results on $$\sin ^2\theta _{13}$$ sin 2 θ 13 and the impact of priors on the $$\delta _{\textrm{CP}}$$ δ CP measurement. Both analyses prefer the normal mass ordering and upper octant of $$\sin ^2\theta _{23}$$ sin 2 θ 23 with a nearly maximally CP-violating phase. Assuming the normal ordering and using the constraint on $$\sin ^2\theta _{13}$$ sin 2 θ 13 from reactors, $$\sin ^2\theta _{23}=0.561^{+0.021}_{-0.032}$$ sin 2 θ 23 = 0 . 561 - 0.032 + 0.021 using Feldman–Cousins corrected intervals, and $$\varDelta {}m^2_{32}=2.494_{-0.058}^{+0.041}\times 10^{-3}~\text {eV}^2$$ Δ m 32 2 = 2 . 494 - 0.058 + 0.041 × 10 - 3 eV 2 using constant $$\varDelta \chi ^{2}$$ Δ χ 2 intervals. The CP-violating phase is constrained to $$\delta _{\textrm{CP}}=-1.97_{-0.70}^{+0.97}$$ δ CP = - 1 . 97 - 0.70 + 0.97 using Feldman–Cousins corrected intervals, and $$\delta _{\textrm{CP}}=0,\pi $$ δ CP = 0 , π is excluded at more than 90% confidence level. A Jarlskog invariant of zero is excluded at more than $$2\sigma $$ 2 σ credible level using a flat prior in $$\delta _{\textrm{CP}},$$ δ CP , and just below $$2\sigma $$ 2 σ using a flat prior in $$\sin \delta _{\textrm{CP}}.$$ sin δ CP . When the external constraint on $$\sin ^2\theta _{13}$$ sin 2 θ 13 is removed, $$\sin ^2\theta _{13}=28.0^{+2.8}_{-6.5}\times 10^{-3},$$ sin 2 θ 13 = 28 . 0 - 6.5 + 2.8 × 10 - 3 , in agreement with measurements from reactor experiments. These results are consistent with previous T2K analyses.
Published: 2023
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11. Sex as a risk factor regarding presbyopia in the rhesus monkey.

Author: Mary Ann Croft, Jared P Mcdonald, Julie Kiland, Julie A Mattison, George S Roth, Don Ingram, and Paul L Kaufman
Subjects: Medicine, Science
Abstract: PurposeTo determine the effect of sex as a risk factor regarding presbyopia.MethodsMaximum accommodation was pharmacologically induced (40% cabachol corneal iontophoresis) in 97 rhesus monkeys (49 males and 48 females) ranging in age from 8 to 36 years old. Accommodation was measured by Hartinger coincidence refractometry.ResultsAccommodative amplitude measured refractometrically decreased with age, and the rate of change was not different between males and females (p = 0.827).ConclusionsPresbyopia is essentially sex neutral, and no one is spared. There may be modest variations between different populations for various reasons, but essentially it is monotonously predictable. At present there is no biological therapeutic.
Published: 2024
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12. Radiological diagnosis of hepatocellular carcinoma does not preclude biopsy before treatment

Author: Bleuenn Brusset, Marion Jacquemin, Yann Teyssier, Gaël S. Roth, Nathalie Sturm, Matthieu Roustit, Alexandre Bône, Julien Ghelfi, Charlotte E. Costentin, and Thomas Decaens
Subjects: Hepatocellular carcinoma, Diagnostic performance, LI-RADS V2018, American Association for the study of Liver Diseases 2011, Biopsy, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract: Background & Aims: The diagnosis of hepatocellular carcinoma (HCC) in patients with cirrhosis relies on non-invasive criteria based on international guidelines. The advent of systemic therapies warrants reconsideration of the role of biopsy specimens in the diagnosis of HCC. Accordingly, we investigated the diagnostic performance of the LI-RADS 2018 and the AASLD 2011 criteria. Methods: Consecutive patients with cirrhosis who underwent a biopsy for suspected HCC between 2015 and 2020 were included. The available imaging studies (computed tomography and/or magnetic resonance imaging) were blindly reviewed by two independent radiologists. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were assessed for LI-RADS, AASLD, and biopsies. Results: In total, 167 patients underwent both available biopsy and imaging. Of the 137 relevant biopsies, 114 patients had HCC (83.2%), 12 (9%) had non-HCC malignant lesions, and 11 (8%) had benign nodules. The PPV and NPV of the biopsies were 100% and 62%, respectively; 30 biopsies were non-contributive. The PPV and NPV of the LI-RADS categories were 89% and 32.8% for LR-5 and 85.5% and 54.5% for LR-4 + 5 + TIV, respectively. The PPV and NPV of the 2011 AASLD criteria were 93.2% and 35.6%, respectively. The interobserver kappa (k = 0.380) for the LR-5 categories was reasonable. Of 100 LR-5 nodules, 11 were misclassified, in particular one case was a colorectal metastasis, and two cases were cholangiocarcinomas, of which nine were identified through biopsy, whereas six were correctly classified according to LI-RADS (LR-M or LR-TIV). Fifty percent of macrotrabecular HCC and 48.4% of poorly differentiated HCC (Edmonson 3 and 4) were not classified as LR-5. Conclusions: LI-RADS 2018 did not outperform the AASLD 2011 score as a non-invasive diagnosis of HCC. Tumor biopsy allowed restoration of an accurate diagnosis in 11% of LR-5 cases. A combined radiological and histological diagnosis should be considered mandatory for good treatment assessment. Impact and Implications: Although biopsy is not required for hepatocellular carcinoma diagnosis when the LI-RADS criteria are met according to current guidelines, our study underscores the limits of radiology and the need for biopsy when hepatocellular carcinoma is suspected. Histological findings could change therapeutics of liver tumors even if only for a small proportion of patients. Histological proof of the type of cancer is a standard in oncology.
Published: 2024
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13. Preclinical characterization of an mRNA-encoded anti-Claudin 18.2 antibody

Author: Hayat Bähr-Mahmud, Ursula Ellinghaus, Christiane R. Stadler, Leyla Fischer, Claudia Lindemann, Anuhar Chaturvedi, Jan Diekmann, Stefan Wöll, Imke Biermann, Bernhard Hebich, Caroline Scharf, Manuela Siefke, Alexandra S. Roth, Martin Rao, Kerstin Brettschneider, Eva-Maria Ewen, Uğur Şahin, and Özlem Türeci
Subjects: ADCC, BNT141, human CLDN18.2, IMAB362, immunotherapy, RiboMab, Immunologic diseases. Allergy, RC581-607, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: ABSTRACTIMAB362/Zolbetuximab, a first-in-class IgG1 antibody directed against the cancer-associated gastric-lineage marker CLDN18.2, has recently been reported to have met its primary endpoint in two phase 3 trials as a first-line treatment in combination with standard of care chemotherapy in CLDN18.2-positive Her2 negative advanced gastric cancer. Here we characterize the preclinical pharmacology of BNT141, a nucleoside-modified RNA therapeutic encoding the sequence of IMAB362/Zolbetuximab, formulated in lipid nanoparticles (LNP) for liver uptake. We show that the mRNA-encoded antibody displays a stable pharmacokinetic profile in preclinical animal models, mediates CLDN18.2-restricted cytotoxicity comparable to IMAB362 recombinant protein and inhibits human tumor xenograft growth in immunocompromised mice. BNT141 administration did not perpetrate mortality, clinical signs of toxicity, or gastric pathology in animal studies. A phase 1/2 clinical trial with BNT141 mRNA-LNP has been initiated in advanced CLDN18.2-expressing solid cancers (NCT04683939).
Published: 2023
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14. Agreement between Patient-reported Pain Medication Use and Electronic Medical Record Data in Surgical Amputation Patients

Author: Carrie A. Kubiak, MD, Jennifer C. Lee, MD, Jennifer B. Hamill, MPH, H. Myra Kim, PhD, Randy S. Roth, PhD, Paul S. Cederna, MD, Michael E. Geisser, PhD, Theodore A. Kung, MD, and Stephen W. P. Kemp, PhD
Subjects: Surgery, RD1-811
Abstract: Background:. Opioid misuse after surgery remains a public health crisis in the United States. Recent efforts have focused on tracking pain medication use in surgical populations. However, accurate interpretations of medication use remain quite challenging given inconsistent usage of different datasets. The purpose of this study was to investigate the agreement between electronic medical records (EMR) versus patient self-reported use of pain medications in a surgical amputation population. Methods:. Patients undergoing major lower extremity amputation or amputation-related procedures were included in this study. Both self-reported and EMR data for pain medication intake were obtained for each patient at three time points (preoperatively, 4 months postoperatively, and 12 months postoperatively). Percentage agreement and the kappa statistic were calculated for both usage (yes/no) and dose categories. Results:. Forty-five patients were included in this study, resulting in 108 pairs of self-reported and EMR datasets. Substantial levels of agreement (>70% agreement, kappa >0.61) for opioid use was seen at preoperative and 12 months postoperative. However, agreement dropped at 4 months postoperatively. Anticonvulsant medication showed high levels, whereas acetaminophen showed lower levels of agreements at all time points. Conclusions:. Either self-reported or EMR data may be used in research and clinical settings for preoperative or 12-month postoperative patients with little concern for discrepancies. However, at time points immediately following the expected end of acute surgical pain, self-reported data may be needed for more accurate medication reporting. With these findings in mind, usage of datasets should be driven by study objectives and the dataset’s strength (eg, accuracy, ease, lack of bias).
Published: 2023
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15. Individual attractiveness preferences differentially modulate immediate and voluntary attention

Author: Tom S. Roth, Iliana Samara, Juan Olvido Perea-Garcia, and Mariska E. Kret
Subjects: Medicine, Science
Abstract: Abstract Physical attractiveness plays a crucial role in mate choice for both men and women. This is reflected in visual attention: people immediately attend towards and look longer at attractive faces, especially when they are motivated to find a partner. However, previous studies did not incorporate real-life dating decisions. Here, we aimed to combine attentional tasks with individual attractiveness ratings and a real-life mate choice context, namely a speed-dating paradigm. We investigated whether heterosexual non-committed young adults showed biases in immediate and voluntary attention towards attractive faces and preferred dating partners. In line with previous research, we found considerable individual differences in individual attractiveness preferences. Furthermore, our results showed that men had a bias towards attractive faces and preferred dating partners in the immediate attention task, while results for women were mixed. In the voluntary attention task, however, both men and women had an attentional bias towards attractive faces and preferred dating partners. Our results suggest that individual attractiveness preferences are good predictors of especially voluntary attention. We discuss these findings from an evolutionary perspective and suggest directions for future research.
Published: 2023
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16. Do Traits Travel? Multiple-Herbicide-Resistant A. tuberculatus, an Alien Weed Species in Israel

Author: Idan S. Roth, Aviv Singer, Inon Yadid, Moshe Sibony, Zvi Peleg, and Baruch Rubin
Subjects: waterhemp, glyphosate, acetolactate synthase (ALS), protoporphyrinogen oxidase (PPO), gene transfer, seed-mediated gene flow, Botany, QK1-989
Abstract: Amaranthus tuberculatus is the most common weed in soybean and corn in the USA and Canada. In Israel, it has been a minor riverbank weed. However, in recent years, growing densities of this plant have been observed in field crops, orchards, and roadsides. Between 2017 and 2022, we surveyed the distribution of A. tuberculatus and collected seeds for further study. We identified three main distribution zones in Israel: the Jezreel Valley, Hula Valley, and Coastal Plain. Most of the populations were found near water sources, fishponds, barns, dairies, or bird-feeding sites, suggesting the involvement of imported grain in introducing A. tuberculatus to Israel. Populations were screened for their responses to various post-emergence herbicides (i.e., ALS, EPSPS, PPO, HPPD, and PSII inhibitors). Several populations from the Jezreel Valley were found to be putatively resistant to ALS, EPSPS, and PPO inhibitors. The responses of those populations to trifloxysulfuron, glyphosate, and carfentrazone-ethyl were also studied. A single ALS-, EPSPS- and PPO-resistant plant was vegetatively propagated to create a clonal population, which was treated with foramsulfuron, glyphosate, and carfentrazone-ethyl. No resistance to PSII or HPPD inhibitors was observed, but resistance to herbicides that inhibit ALS, EPSPS, and PPO was observed. A clonal propagation assay revealed the existence of a population that was resistant to ALS, EPSPS, and PPO inhibitors. Since the local A. tuberculatus populations have not been exposed to herbicide selection pressure, these traits probably reached Israel through seed-mediated gene flow via imported grain.
Published: 2023
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17. Characterization and tissue localization of zebrafish homologs of the human ABCB1 multidrug transporter

Author: Robert W. Robey, Andrea N. Robinson, Fatima Ali-Rahmani, Lyn M. Huff, Sabrina Lusvarghi, Shahrooz Vahedi, Jordan M. Hotz, Andrew C. Warner, Donna Butcher, Jennifer Matta, Elijah F. Edmondson, Tobie D. Lee, Jacob S. Roth, Olivia W. Lee, Min Shen, Kandice Tanner, Matthew D. Hall, Suresh V. Ambudkar, and Michael M. Gottesman
Subjects: Medicine, Science
Abstract: Abstract Capillary endothelial cells of the human blood–brain barrier (BBB) express high levels of P-glycoprotein (P-gp, encoded by ABCB1) and ABCG2 (encoded by ABCG2). However, little information is available regarding ATP-binding cassette transporters expressed at the zebrafish BBB, which has emerged as a potential model system. We report the characterization and tissue localization of two genes that are similar to ABCB1, zebrafish abcb4 and abcb5. When stably expressed in HEK293 cells, both Abcb4 and Abcb5 conferred resistance to P-gp substrates; however, Abcb5 poorly transported doxorubicin and mitoxantrone compared to zebrafish Abcb4. Additionally, Abcb5 did not transport the fluorescent P-gp probes BODIPY-ethylenediamine or LDS 751, while they were transported by Abcb4. High-throughput screening of 90 human P-gp substrates confirmed that Abcb4 has an overlapping substrate specificity profile with P-gp. In the brain vasculature, RNAscope probes for abcb4 colocalized with staining by the P-gp antibody C219, while abcb5 was not detected. The abcb4 probe also colocalized with claudin-5 in brain endothelial cells. Abcb4 and Abcb5 had different tissue localizations in multiple zebrafish tissues, potentially indicating different functions. The data suggest that zebrafish Abcb4 functionally phenocopies P-gp and that the zebrafish may serve as a model to study the role of P-gp at the BBB.
Published: 2021
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18. Twelve-month observational study of children with cancer in 41 countries during the COVID-19 pandemic

Author: Md Hasanuzzaman, Mohamed Ahmed, Ahmed Samir, Charlotte Smith, Lubna Samad, Vaishnavi Govind, Fakher Rahim, Ahmed Moussa, Adesoji O Ademuyiwa, Bobby John, Augusto Zani, Vivek Singh, Muhammad Arshad, Sadaf Altaf, Chan Hon Chui, Pooja Kumari, Thomas Smith, Ayesha Saleem, Matthew HV Byrne, Madhivanan Karthigeyan, Pravin Salunke, Darica Au, Kate Cross, Kokila Lakhoo, Vishal Kumar, Anna Maria Testi, Robyn Brown, Noel Peter, Georgios Tsoulfas, Francesco Pata, Adesoji Ademuyiwa, Tahmina Banu, Bruce Bvulani, Milind Chitnis, Maryam Ghavami Adel, Vrisha Madhuri, Pierfrancesco Lapolla, Andrea Mingoli, Hamidah Alias, Simone de Campos Vieira Abib, Ibukunolu Olufemi Ogundele, Felix M Alakaloko, Emmanuel A Ameh, Laila Hessissen, Kareem O Musa, Georgios Karagiannidis, Manoj Gupta, Maricarmen Olivos, Daniel Rhee, Maryam Khan, Christine Nitschke, Alexandra Valetopoulou, Ashrarur Rahman Mitul, Sabbir Karim, Mahmoud M Saad, Francis Abantanga, Gaetano Gallo, Mohamedraed Elshami, Mahmoud Elfiky, Soham Bandyopadhyay, Muath Alser, Elliott H Taylor, Duha Jasim, Somy Charuvila, Nazmul Islam, William B Lo, Uttam Kumar Nath, Robin Simpson, Zarina Abdul Latiff, Bruno Cirillo, Gioia Brachini, Megan Murphy, Zineb Bentounsi, Anette S Jacobsen, Anna Casey, Mohammed Alhendy, Taiwo Akeem Lawal, Samson Olori, Michael Boettcher, Muhammed Elhadi, Shaun Wilson, Dragana Janić, Amit Sehrawat, Patricia Shinondo, Shireen Anne Nah, Alhassan Abdul-Mumin, Karl-Heinz Frosch, Poorvaprabha Patil, Sarah Muma, Md Asaduzzaman, Athanasios Tragiannidis, Vijayendra Kumar, Mahan Salehi, Sara Ali, Renu Madan, Hafeez Abdelhafeez, Max Pachl, Benjamin Martin, Sonal Nagras, Mihir Sheth, Catherine Dominic, Suraj Gandhi, Divya Parwani, Rhea Raj, Diella Munezero, Rohini Dutta, Nsimire Mulanga Roseline, Kellie McClafferty, Armin Nazari, Smrithi Sriram, Sai Pillarisetti, King-David Nweze, Aishwarya Ashwinee, Gul Kalra, Priyansh Nathani, Khushman Kaur Bhullar, Nehal Rahim, Shweta Madhusudanan, Joshua Erhabor, Manasi Shirke, Aishah Mughal, Sravani Royyuru, Syeda Namayah Fatima Hussain, Daniel Robinson, Mehdi Khan, Alexandre Dukundane, Kwizera Festus, Rohan Pancharatnam, Lorraine Ochieng, Hritik Nautiyal, Leanne Gentle, Ehab Hanafy, Catherine Yang, Gideon Karplus, John Mathew, Olumide Abiodun Elebute, Oluwaseun Ladipo-Ajayi, Okechukwu Hyginus Ekwunife, Sherief Ghozy, Emily Hamilton, Dhruva Ghosh, Ahmed Sherif, Hajar Moujtahid, Ariana Axiaq, Amir Labib, Eman Abdulwahed, Kemal Tolga Saracoglu, Yasin Kara, Ahmed Y Azzam, Omar Elmandouh, Manjul Tripathi, Abdelrahman Azzam, Anfel Bouderbala, Aouabed Nesrine, Ammar Ayman, Mohamed Bonna, Safia Lorabi, Hira Zuberi, Iyad Sultan, Reto M Baertschiger, Kefas John Bwala, AM Umar, Abdurahaman Aremu, Dauda E Suleiman, Tybat Aliyu, Kashaf Turk, Oluseyi Oyebode Ogunsua, Tunde Talib Sholadoye, Musliu Adetola Tolani, Yakubu Alfa, Keffi Mubarak Musa, Ken Muma, Mitchelle Obat, Youssef Sameh Badran, Abdulrahman Ghassan Qasem, Faris Ayasra, Reema Alnajjar, Mohamed Abdel-Maboud, Abdelrahman Bahaa, Ayat M Saadeldin, Mohamed Adwi, Mahmoud Adly, Abdallah Elshenawy, Amer Harky, Kirstie Wright, Jessica Luyt, Olivia White, Nathan Thompson, Imogen Harrison, Sara Kader Alsaeiti, Fatma Saleh Benkhial, Hend Mohammed Masoud, Mabroukah Saeid Alshamikh, Fatma Mohammed Masoud, Nyararai Togarepi, Elaine Carrolan, Ahmed Saleh, Mahmoud Bassiony, Mostafa Qatora, Mohamed Bahaaeldin, Shady Fadel, Yasmine El Chazli, Kamel Hamizi, Mehdi Anouar Zekkour, Rima Rahmoun, Boutheyna Drid, Salma Naje Abu Teir, Mohamed Yazid Kadir, Yassine Zerizer, Nacer Khernane, Brahim Saada, Imane Ammouze, Yahya Elkaoune, Ghita Chaoui, Hajar Benaouda, Meryem Gounni, Narjiss Aji, Joana Mafalda Monteiro, Susana Nunes, Maria do Bom-Sucesso, Kerri Becktell, Md Afruzul Alam, Orindom Shing Pulock, Tasmiah Tahera Aziz, Rosanda Ilic, Danica Grujicic, Tijana Nastasovic, Igor Lazic, Mihailo Milicevic, Vladimir Bascarevic, Radovan Mijalcic, Vuk Scepanovic, Aleksandar Stanimirovic, Aleksandra Paunovic, Ivan Bogdanovic, Shahnoor Islam, AKM Amirul Morshed, Mehnaz Akter, Zannat Ara, Mohammed Tanvir Ahammed, Tania Akter, Kamrun Nahar, Fatema Sayed, Ashfaque Nabi, Elif Akova, Evren Aydogmus, Bekir Can Kendirlioglu, Tufan Hicdonmez, Asim Noor Rana, Mohammed A Azab, Alzhraa Salah Abbas, Olanrewaju Moses, Ibiyeye Taiye Taibat, Taiwo Jones, Kalu Ukoha, Olagundoye Goke, Okorie Ikechukwu, Abiodun Idowu Okunlola, Helga Nauhaus, Danelle Erwee, Agata Chylinska, Prasanna Gomes, Elvercio Pereira de Oliveira Junior, Fabiola Leonelli Diz, Mohamed El Kassas, Usama Eldaly, Ahmed Tawheed, Mohamed Abdelwahab, Oudrhiri Mohammed Yassaad, Bechri Hajar, El Ouahabi Abdessamad, Arkha Yasser, Hessissen Laila, Farah Sameer Yahya, Maria Teresa Peña Gallardo, Jacqueline Elizabeth Montoya Vásquez, Juan Luis García León, Sebastián Shu Yip, Mariam Lami, Harmit Ghattaura, Eric W Etchill, Stacy Cooper, Kevin Crow, Morgan Drucker, Benjamin Shou, Alan Siegel, Gül Nihal Özdemir, Ehab El Refaee, John George Massoud, Ayah Bassam Ibrahim, Ruaa Bassam Ibrahim, Faris Abu Za'nouneh, Toqa Fahmawee, Ghazwani Salman, Ehab Alameer, Al-Mudeer Ali, Ghazwani Yahia, Khozairi Waleed, Khalil Ghandour, Shaima' Al-Dabaibeh, Ammar Al-Basiti, Hazim Ababneh, Omaima El-Qurneh, Yousef Alalawi, Ahmad Al Ayed, Naif Al Bolowi, Heidi Barola, Aubrey L Pagaduan, Jingdan Fan, Olufemi Oni, Janita Zarrish, Ramsha Saleem, Soha Zahid, Atiqa Amirali, Ahsan Nadeem, Sameer Saleem Tebha, Zonaira Qayyum, Sana Tahir, Anneqa Tahir, Rabbey Raza Khan, Ayesha Mehmood, Taimur Iftikhar Qureshi, Victor Calvagna, Nathalie Galea, Matthew R Schuelke, Kirk David Wyatt, Agnes Vojcek, Seham M Ragab, Abdallah R Allam, Eman Ibrahim Hager, Kıvılcım Karadeniz Cerit, Adnan Dağçınar, Tümay Umuroğlu, Ayten Saraçoğlu, Mustafa Sakar, Can Kıvrak, Gül Çakmak, Ibrahim Sallam, Gamal Amira, Mohamed Sherief, Arissa Ikeda, Licia Portela, Marianne Monteiro Garrigo, Fernanda Lobo, Sima Ester Ferman, Andrew Nwankwo Osuigwe, Chisom Adaobi Nri-Ezedi, Eric Okechukwu Umeh, Abiodun Folashade Adekanmbi, Olubunmi Motunrayo Fatungase, Olubunmi Obafemi Obadaini, Sarah Al-Furais, Humaida Hemlae, Sreylis Nay, Fabianne Altruda de Moraes Costa Carlesse, Denis Cozzi, Paolo Musiu, Paolo Sapienza, Martina Zambon, Simona Meneghini, Pierfranco Cicerchia, Abdulrahman Omar Taha, Bouaoud Souad, Mebarki Malika, Bioud Belkacem, Fayza Haider, Halwani Yaninga Fuseini, Peter Gyamfi Kwarteng, Abubakari Bawa Abdulai, Sheba Mary Pognaa Kunfah, Stephanie Ajinkpang, Mary Joan Kpiniong, Kingsley Aseye Hattor, Kingsley Appiah Bimpong, Mohamed Elbahnasawy, Sherief Abdelsalam, Amanpreet Brar, Andreea C Matei, Hira Khalid Zuberi, Kishwer Nadeem, Naema Khayyam, Fatima Ambreen Imran, Nida Zia, Sadia Muhammad, Muhammad Rafie Raza, Muhammad Rahil Khan, Alaa Hamdan, Abdeljawad Mazloum, Ali Abodest, Nisreen Ali, Ammar Omran, Alaa Ahmed, Munawar Hraib, Victor Khoury, Abdulrahman Almjersah, Mohammad Ali Deeb, Akram Ahmed, Ahmad Bouhuwaish, Alqasim Abdulkarim, Marwa Biala, Reem Ghamgh, Amani Alamre, Marwa Shelft, Hoda Tawel, Emmanuel Hatzipantelis, Eleni Tsotridou, Assimina Galli-Tsinopoulou, C-Khai Loh, Doris Lau, Kelvin Ifeanyichukwu Egbuchulem, Olakayode Olaolu Ogundoyin, Isaac Dare Olulana, Oluwasegun Joshua Afolaranmi, AbdulBasit Fehintola, Annika Heuer, Matthias Priemel, Lennart Viezens, Martin Stangenberg, Marc Dreimann, Alonja Reiter, Jasmin Meyer, Leon Köpke, Uduak Offiong, Philip Mari Mshelbwala, Fashie Andrew Patrick, Aminu Muhammed Umar, N Otene ThankGod, Yuki Julius Ng, Syukri Ahmad Zubaidi, Murad Almasri, Rasaq Olaosebikan, Akila Muthukumar, Amon Ngongola, Azad Patel, Abdullahi Nuhu-Koko, Baba Jibrin, Gabriela Guillén, Sergio López, José Andrés Molino, Pablo Velasco, Omar Hamam, Rim Elmandouh, Nensi Melissa Ruzgar, Rachel Levinson, Shashwat Kala, Sarah Ullrich, Emily Christison-Lagay, Janice Hui Ling Wong, Reto Baertschiger, Essam Elhalaby, Guido Seitz, Judith Lindbert, Asimina Galli-Tsinopoulou, Calogero Virgone, Eric Mwangi Irungu, Outani Oumaima, Lily Saldana, Jan Godzinsky, Abdelbasit Ali, Mohamed Bella Jalloh, Nellie Bell, Annette Jacobsen, Israel Fernandez Pineda, Lucas Krauel, Waha Rahama, Hazim Elfatih, Arda Isik, Andrea Hayes-Jordan, Roshni Dasgupta, Krishna Kumar Govindarajan, Marta deAndres Crespo, Nitin James Peters, Santosh Kumar Mahalik, Rajat Piplani, Enono Yhoshu, K S Rajkumar, Sadi A Abukhalaf, Mohammed Miftah Faraj Almihashhish, Eman Salem Muftah Burzeiza, Raja Mari Mohammed Nasef, Benjamin J O'Sullivan, Mohamed Hassanin, Dave R Lal, Brian T Craig, Vishal Michael, M Joseph John, William Bhatti, Swati Daniel, Jyoti Dhiman, Hunar Mahal, Atul Suroy, Shruti Kakkar, Shaina Kamboj, Suraj Singh, AKM Khairul Basher, SM Rezanur Rahman, Md Asif Iqbal, Md Masud Rana, Monica Dobs, Mohamed Atef Mohamed Ghamry, Joana Monteiro, Marco Aurelio Ciriaco Padilha, Lucas Garschagen deCarvalho, Sandip Kumar Rahul, Digamber Chaubey, Rejin Kebudi, Sema Bay Buyukkapu, Kumaravel Sambandan, Smita Kayal, Gunaseelan Karunanithi, Bikash Kumar Naredi, Bibekanand Jindal, Ranya M Baddourah, Ayah Al Shraideh, Ahmad Ozair, Ankur Bajaj, Bal Krishna Ojha, Kaushal Kishor Singh, Atique Anwar, Vinay Suresh, Mohamad K Abou Chaar, Christopher O Bode, Justina O Seyi-Olajide, George C Ihediwa, Edamisan O Temiye, Adeseye M Akinsete, Iqra Effendi, Khaled Mamdouh, Mohamed Atef, Mohamed Faried, Jake A Kloeber, Robert L Owen, Alexander S Roth, J Hudson Barnett, Lucien P Jay, Paul J Galardy, Bernard Mbwele, Irene Nguma, Moshi Moshi Shabani, Amani Twaha, Bilal Matola, Mahmoud Maher Abdelnaby Alrahawy, Simone deOliveira Coelho, Ricardo Vianna deCarvalho, FernandaFerreira daSilva Lima, Moawia Mohammed AliElhassan, Nada Osman Yousif Elhaj, Hytham KS Hamid, Vincent E Nwatah, Adewumi B Oyesakin, RM Jeffri Ismail, Simone deCamposVieira Abib, Mayara Caroline Amorim Fanelli, Fernanda Kelly Marques de Souza, Sandeep Mohindra, Ninad R Patil, Richa Jain, Gopal Nambi, Norehan Johari, Anas Shikha, Win SabaiPhyu Han, Zahidah Ahmad, Yen Yan Lim, Roserahayu Idros, Noorainun Mohd Yusof, David Nelson Jaisingh, Fatema Naser AlFayez, Elana Kleinman, Taylor Ibelli, Rochelle Fayngor, Tzvi Najman, Etai Adam, Daniella Melamed, Cecilia Paasche, Farman Ali Laghari, Zainab Al Balushi, Abdulhakim Awadh SalimAl-Rawas, Ali Al Sharqi, Ammar Saif AlShabibi, Ismail Al Bulushi, Muna Alshahri, Abdulrahman AlMirza, Ola Al Hamadani, Jawaher Al Sharqi, Anisa Al Shamsi, Bashar Dawud, Sareya Al Sibai, Gilbert B Bonsaana, Edmund M Der, Francis A Abantanga, Bardisan Gawrieh, Hassan Salloum, Mohammad Ahmad Almahmod Alkhalil, Waseem Shater, Ali Farid Alelayan, Alaa Guzlan, Asmaa AM Albanna, Dayang AnitaAbdul Aziz, Azrina Syarizad Khutubul Zaman, Biobele J Brown, Ajiboye L Olalekan, Christopher S Lukong, Ezekiel I Ajayi, Luca Pio, Nitin James Peter, Ravi Kishore, Mohammad K Abou Chaar, Dayang Anita Abdul Aziz, Dhruva Nath Ghosh, and Raphael N Vuille-dit-Bille
Subjects: Medicine (General), R5-920, Infectious and parasitic diseases, RC109-216
Abstract: Introduction Childhood cancer is a leading cause of death. It is unclear whether the COVID-19 pandemic has impacted childhood cancer mortality. In this study, we aimed to establish all-cause mortality rates for childhood cancers during the COVID-19 pandemic and determine the factors associated with mortality.Methods Prospective cohort study in 109 institutions in 41 countries. Inclusion criteria: children
Published: 2022
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19. DEEPLIO: DEEP LIDAR INERTIAL SENSOR FUSION FOR ODOMETRY ESTIMATION

Author: A. Javanmard-Gh., D. Iwaszczuk, and S. Roth
Subjects: Technology, Engineering (General). Civil engineering (General), TA1-2040, Applied optics. Photonics, TA1501-1820
Abstract: Having a good estimate of the position and orientation of a mobile agent is essential for many application domains such as robotics, autonomous driving, and virtual and augmented reality. In particular, when using LiDAR and IMU sensors as the inputs, most existing methods still use classical filter-based fusion methods to achieve this task. In this work, we propose DeepLIO, a modular, end-to-end learning-based fusion framework for odometry estimation using LiDAR and IMU sensors. For this task, our network learns an appropriate fusion function by considering different modalities of its input latent feature vectors. We also formulate a loss function, where we combine both global and local pose information over an input sequence to improve the accuracy of the network predictions. Furthermore, we design three sub-networks with different modules and architectures derived from DeepLIO to analyze the effect of each sensory input on the task of odometry estimation. Experiments on the benchmark dataset demonstrate that DeepLIO outperforms existing learning-based and model-based methods regarding orientation estimation and shows a marginal position accuracy difference.
Published: 2021
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20. Hidden bulk and surface effects in the spin polarization of the nodal-line semimetal ZrSiTe

Author: G. Gatti, D. Gosálbez-Martínez, S. Roth, M. Fanciulli, M. Zacchigna, M. Kalläne, K. Rossnagel, C. Jozwiak, A. Bostwick, E. Rotenberg, A. Magrez, H. Berger, I. Vobornik, J. Fujii, O. V. Yazyev, M. Grioni, and A. Crepaldi
Subjects: Astrophysics, QB460-466, Physics, QC1-999
Abstract: Local inversion symmetry breaking in centrosymmetric materials can lead to large spin polarization of the electronic band structure in separate sectors of the unit cell. Here, the authors reveal such hidden spin polarisation in ZrSiTe using spin and angle resolved photoemission spectroscopy in combination with ab initio band structure calculations and investigate the resultant spin polarised bulk and surface properties
Published: 2021
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21. Impact of the COVID-19 pandemic on patients with paediatric cancer in low-income, middle-income and high-income countries: a multicentre, international, observational cohort study

Author: Mohamed Ahmed, Ahmad Mansour, Ahmed Samir, Charlotte Smith, Lubna Samad, Vaishnavi Govind, Fakher Rahim, Augusto Zani, Muhammad Arshad, Sadaf Altaf, Chan Hon Chui, Pooja Kumari, Thomas Smith, Ayesha Saleem, Darica Au, Kate Cross, Kokila Lakhoo, Anna Maria Testi, Robyn Brown, Noel Peter, Francesco Pata, Adesoji Ademuyiwa, Tahmina Banu, Bruce Bvulani, Milind Chitnis, Maryam Ghavami Adel, Matthew H V Byrne, Pierfrancesco Lapolla, Andrea Mingoli, Lucy Davies, Dennis Mazingi, Hamidah Alias, Simone de Campos Vieira Abib, Ibukunolu Olufemi Ogundele, Laila Hessissen, Mohammad Ahmad, Maricarmen Olivos, Daniel Rhee, Maryam Khan, Christine Nitschke, Alexandra Valetopoulou, Ashrarur Rahman Mitul, Sabbir Karim, Gaetano Gallo, Mohamedraed Elshami, Mahmoud Elfiky, Soham Bandyopadhyay, Muath Alser, Elliott H Taylor, Duha Jasim, Somy Charuvila, Nazmul Islam, William B Lo, Robin Simpson, Zarina Abdul Latiff, Bruno Cirillo, Gioia Brachini, Megan Murphy, Zineb Bentounsi, Anette S Jacobsen, Anna Casey, Abdulrasheed A Nasir, Taiwo Akeem Lawal, Samson Olori, Michael Boettcher, Muhammed Elhadi, Shaun Wilson, Dragana Janić, Patricia Shinondo, Shireen Anne Nah, Alhassan Abdul-Mumin, Dayang Anita Abdul Aziz, J Benjamin, Karl-Heinz Frosch, Poorvaprabha Patil, Sarah Muma, Emmanuel Uwiringiyimana, Athanasios Tragiannidis, Mahan Salehi, Sara Ali, Hafeez Abdelhafeez, Max Pachl, Benjamin Martin, Sonal Nagras, Mihir Sheth, Catherine Dominic, Suraj Gandhi, Divya Parwani, Rhea Raj, Diella Munezero, Rohini Dutta, Nsimire Mulanga Roseline, Kellie McClafferty, Armin Nazari, Smrithi Sriram, Sai Pillarisetti, Aishwarya Ashwinee, Gul Kalra, Priyansh Nathani, Khushman Kaur Bhullar, Nehal Rahim, Shweta Madhusudanan, Joshua Erhabor, Manasi Shirke, Aishah Mughal, Sravani Royyuru, Daniel Robinson, Mehdi Khan, Alexandre Dukundane, Kwizera Festus, Rohan Pancharatnam, Lorraine Ochieng, Hritik Nautiyal, Leanne Gentle, Ehab Hanafy, Catherine Yang, John Mathew, Olumide Abiodun Elebute, Oluwaseun Ladipo-Ajayi, Okechukwu Hyginus Ekwunife, Sherief Ghozy, Aya Zazo, Salah Eddine Oussama Kacimi, Ahmed Sherif, Krithi Ravi, Nermin Badwi, Hajar Moujtahid, Ariana Axiaq, Eman Abdulwahed, Kemal Tolga Saracoglu, Yasin Kara, Ahmed Y Azzam, Omar Elmandouh, KingDavid Nweze, Syeda Namayah Fatima Hussain, Marta de Andres Crespo, Fatumata Jalloh, Shahnur Shah, Rohini Rajpal, Masooma Rana, Muskaan Abdul Qadir, Abdelrahman Azzam, Mayara Fanelli, Gustavo Mendonça Ataíde Gomes, Igor Lima Buarque, Isadora Schwaab Guerini, Anfel Bouderbala, Sarah Alfurais, Mohamed Gamal, Yara Hijazi, Shatha Tailakh, Hamza AlNaggar, Zain Douba, Sewar Elejla, Abdullah Eldaly, Ekram Sharashi, Tamara Elyan, Aouabed Nesrine, Ammar Ayman, Mohamed Bonna, Safia Lorabi, Hassan Alalami, Rawan Yasser Emam, Mohamad K Abou Chaar, Hira Zuberi, Iyad Sultan, Dhruv Nath Ghosh, Nitin James Peters, Reto M Baertschiger, Kefas John Bwala, AM Umar, Abdurahaman Aremu, Dauda E Suleiman, Tybat Aliyu, Kashaf Turk, Oluseyi Oyebode Ogunsua, Tunde Talib Sholadoye, Musliu Adetola Tolani, Yakubu Alfa, Keffi Mubarak Musa, Mwangi Irungu, Ken Muma, Mitchelle Obat, Youssef Sameh Badran, Abdulrahman Ghassan Qasem, Faris Ayasra, Reema Alnajjar, Mohamed Abdel-Maboud, Abdelrahman Bahaa, Ayat M Saadeldin, Mohamed Adwi, Mahmoud Adly, Abdallah Elshenawy, Amer Harky, Kirstie Wright, Jessica Luyt, Olivia White, Nathan Thompson, Imogen Harrison, Sara Kader Alsaeiti, Fatma Saleh Benkhial, Mohammed Miftah Faraj Almihashhish, Eman Salem Muftah Burzeiza, Raja Mari Mohammed Nasef, Hend Mohammed Masoud, Mabroukah Saeid Alshamikh, Fatma Mohammed Masoud, Nyararai Togarepi, Elaine Carrolan, Mohamed Hassanin O'Sullivan, Ahmed Saleh, Mahmoud Bassiony, Mostafa Qatora, Mohamed Bahaaeldin, Shady Fadel, Yasmine El Chazli, Kamel Hamizi, Mehdi Anouar Zekkour, Rima Rahmoun, Boutheyna Drid, Salma Naje Abu Teir, Mohamed Yazid Kadir, Yassine Zerizer, Nacer Khernane, Brahim Saada, Imane Ammouze, Yahya Elkaoune, Ghita Chaoui, Hajar Benaouda, Meryem Gounni, Narjiss Aji, Joana Mafalda Monteiro, Susana Nunes, Maria do Bom-Sucesso, Dave R. Lal, Brian T. Craig, Kerri Becktell, Md Afruzul Alam, Orindom Shing Pulock, Tasmiah Tahera Aziz, Rosanda Ilic, Danica Grujicic, Tijana Nastasovic, Igor Lazic, Mihailo Milicevic, Vladimir Bascarevic, Radovan Mijalcic, Vuk Scepanovic, Aleksandar Stanimirovic, Aleksandra Paunovic, Ivan Bogdanovic, Shahnoor Islam, AKM Amirul Morshed, A. K. M. Khairul Basher, Mehnaz Akter, S. M. Rezanur Rahman, Zannat Ara, Mohammed Tanvir Ahammed, Tania Akter, Kamrun Nahar, Fatema Sayed, Ashfaque Nabi, Md. Asif Iqbal, Md. Masud Rana, Md. Asaduzzaman, Md. Hasanuzzaman, Elif Akova, Evren Aydogmus, Bekir Can Kendirlioglu, Tufan Hicdonmez, Arshiya Adhnon, Asim Noor Rana, Hani Humad, Anjan Madasu, Mohammed A Azab, Alzhraa Salah Abbas, Olanrewaju Moses, Ibiyeye Taiye Taibat, Taiwo Jones, Kalu Ukoha, Olagundoye Goke, Okorie Ikechukwu, Abiodun Idowu Okunlola, Helga Nauhaus, Danelle Erwee, Agata Chylinska, Prasanna Gomes, Marco Aurelio Ciriaco Padilha, Elvercio Pereira de Oliveira Junior, Lucas Garschagen de Carvalho, Fabiola Leonelli Diz, Mohamed El Kassas, Usama Eldaly, Ahmed Tawheed, Mohamed Abdelwahab, Oudrhiri Mohammed Yassaad, Bechri Hajar, El Ouahabi Abdessamad, Arkha Yasser, Hessissen Laila, Farah Sameer Yahya, Yasir Al-Agele, Maria Teresa Peña Gallardo, Jacqueline Elizabeth Montoya Vásquez, Juan Luis García León, Sebastián Shu Yip, Mariam Lami, Harmit Ghattaura, Eric W Etchill, Stacy Cooper, Kevin Crow, Morgan Drucker, Benjamin Shou, Alan Siegel, Gül Nihal Özdemir, Ehab El Refaee, John George Massoud, Ayah Bassam Ibrahim, Ruaa Bassam Ibrahim, Faris Abu Za'nouneh, Ranya M. Baddourah, Toqa Fahmawee, Ayah Al_Shraideh, Ghazwani Salman, Ehab Alameer, Al-Mudeer Ali, Ghazwani Yahia, Khozairi Waleed, Mohamad K. Abou Chaar, Khalil Ghandour, Shaima' Al-Dabaibeh, Ammar Al-Basiti, Hazim Ababneh, Omaima El-Qurneh, Yousef Alalawi, Ahmad Al Ayed, Naif Al Bolowi, Amos HP Loh, Heidi Barola, Aubrey L Pagaduan, Jingdan Fan, Adesoji O. Ademuyiwa, Christopher O. Bode, Justina O. Seyi-Olajide, Felix M. Alakaloko, George C. Ihediwa, Kareem O. Musa, Edamisan O. Temiye, Olufemi Oni, Adeseye M. Akinsete, Janita Zarrish, Ramsha Saleem, Soha Zahid, Atiqa Amirali, Ahsan Nadeem, Sameer Saleem Tebha, Zonaira Qayyum, Sana Tahir, Anneqa Tahir, Rabbey Raza Khan, Ayesha Mehmood, Taimur Iftikhar Qureshi, Victor Calvagna, Nathalie Galea, Matthew R Schuelke, Jake A. Kloebe, Robert L. Owen, Alexander S. Roth, J. Hudson Barnett, Lucien P. Jay, Kirk David Wyatt, Paul J. Galardy, Agnes Vojcek, Mahmoud Maher Abdelnaby Alrahawy, Seham M Ragab, Abdallah R Allam, Eman Ibrahim Hager, Kıvılcım Karadeniz Cerit, Adnan Dağçınar, Tümay Umuroğlu, Ayten Saraçoğlu, Mustafa Sakar, Can Kıvrak, Gül Çakmak, Ibrahim Sallam, Gamal Amira, Mohamed Sherief, Simone de Oliveira Coelho, Arissa Ikeda, Licia Portela, Marianne Monteiro Garrigo, Ricardo Vianna de Carvalho, Fernanda Lobo, Sima Ester Ferman, Fernanda Ferreira da Silva Lima, Moawia Mohammed Ali Elhassan, Nada Osman Yousif Elhaj, Hytham K. S. Hamid, Emmanuel A. Ameh, Vincent E. Nwatah, Adewumi B. Oyesakin, Andrew Nwankwo Osuigwe, Chisom Adaobi Nri-Ezedi, Eric Okechukwu Umeh, Nellie Patiala, Abiodun Folashade Adekanmbi, Olubunmi Motunrayo Fatungase, Olubunmi Obafemi Obadaini, Sarah Al-Furais, Humaida Hemlae, Sreylis Nay, R M Jeffri Ismail, Simonede Campos Vieira Abib, Fabianne Altruda de Moraes Costa Carlesse, Mayara Caroline Amorim Fanelli, Fernanda Kelly Marques de Souza, Denis Cozzi, Paolo Musiu, Paolo Sapienza, Martina Zambon, Simona Meneghini, Pierfranco Cicerchia, Abdulrahman Omar Taha, Bouaoud Souad, Mebarki Malika, Bioud Belkacem, Ayman Meelad, Hajier Salim Alrashed, Fayza Haider, Fatema Naser Al Fayez, Halwani Yaninga Fuseini, Peter Gyamfi Kwarteng, Abubakari Bawa Abdulai, Sheba Mary Pognaa Kunfah, Gilbert B. Bonsaana, Stephanie Ajinkpang, Edmund M. Der, Francis A. Abantanga, Mary Joan Kpiniong, Kingsley Aseye Hattor, Kingsley Appiah Bimpong, Mohamed Elbahnasawy, Sherief Abdelsalam, Reto M. Baertschiger, Amanpreet Brar, Andreea C Matei, Hira Khalid Zuberi, Kishwer Nadeem, Naema Khayyam, Fatima Ambreen Imran, Nida Zia, Sadia Muhammad, Muhammad Rafie Raza, Muhammad Rahil Khan, Alaa Hamdan, Abdeljawad Mazloum, Ali Abodest, Nisreen Ali, Bardisan Gawarieh, Ammar Omran, Almed Moussa, Alaa Ahmed, Munawar Hraib, Victor Khoury, Abdulrahman Almjersah, Mohammad Ali Deeb, Almahmod Alkhalil, Akram Ahmed, Ali Alelayan, Ali Hammed, Wassem Shater, Ahmad Bouhuwaish, Alqasim Abdulkarim, Marwa Biala, Reem Ghamgh, Amani Alamre, Marwa Shelft, Asmaa A. M. Albanna, Hoda Tawel, Emmanuel Hatzipantelis, Eleni Tsotridou, Assimina Galli-Tsinopoulou, C-Khai Loh, Doris Lau, Azrina Syarizad Khutubul, Raphael N. Vuille-dit-Bille, Stefan G. Holland-Cunz, Nima Allafi, Kelvin Ifeanyichukwu Egbuchulem, Olakayode Olaolu Ogundoyin, Isaac Dare Olulana, Biobele J. Brown, Oluwasegun Joshua Afolaranmi, AbdulBasit Fehintola, Annika Heuer, Matthias Priemel, Lennart Viezens, Martin Stangenberg, Marc Dreimann, Alonja Reiter, Jasmin Meyer, Leon Köpke, Uduak Offiong, Philip Mari Mshelbwala, Fashie Andrew Patrick, Aminu Muhammed Umar, N Otene ThankGod, Kazeem O. O. Ibrahim, Dupe S. Ademola-Popoola, Olayinka T. Sayomi, Alege Abdurrzzaq, Ademola A. Adeyeye, Khadijah O. Omokanye, Lukman O Abdur-Rahman, Olubisi Olutosin Bamidele, Shakirullah AbdulAzeez, Aminat Akinoso, Michael O. Adegboye, Yuki Julius Ng, Syukri Ahmad Zubaidi, Murad Almasri, Rasaq Olaosebikan, Akila Muthukumar, Amon Ngongola, Azad Patel, Abdullahi Nuhu-Koko, Baba Jibrin, Ajiboye L. Olalekan, Christopher S. Lukong, Ezekiel I. Ajayi, Gabriela Guillén, Sergio López, José Andrés Molino, Pablo Velasco, Omar Hamam, Rim Elmandouh, Nensi Melissa Ruzgar, Rachel Levinson, Shashwat Kala, Sarah Ullrich, Emily Christison-Lagay, Aya Sabry Mortada, Mahmoud Ahmed Ebada, Eman Seif Alnaser Solimam, Khaled Abualkher, Amr Mohammed Elsayed Yousf, Mohamed Mohamed Holail, Reem Mohamed Almowafy, Janice Hui Ling Wong, Reto Baertschiger, Essam Elhalaby, Mahmoud M. Saad, Guido Seitz, Judith Lindbert, Francis Abantanga Georgios Tsoulfas, Asimina Galli-Tsinopoulou, Calogero Virgone, Mohammad K. Abou Chaar, Eric Mwangi Irungu, Outani Oumaima, Lily Saldana, Jan Godzinsky, Abdelbasit Ali, Mohamed Bella Jalloh, Nellie Bell, Annette Jacobsen, Israel Fernandez Pineda, Lucas Krauel, Waha Rahama, Hazim Elfatih, Arda Isik, Andrea Hayes-Jordan, and Roshni Dasgupta
Subjects: Medicine
Abstract: Objectives Paediatric cancer is a leading cause of death for children. Children in low-income and middle-income countries (LMICs) were four times more likely to die than children in high-income countries (HICs). This study aimed to test the hypothesis that the COVID-19 pandemic had affected the delivery of healthcare services worldwide, and exacerbated the disparity in paediatric cancer outcomes between LMICs and HICs.Design A multicentre, international, collaborative cohort study.Setting 91 hospitals and cancer centres in 39 countries providing cancer treatment to paediatric patients between March and December 2020.Participants Patients were included if they were under the age of 18 years, and newly diagnosed with or undergoing active cancer treatment for Acute lymphoblastic leukaemia, non-Hodgkin’s lymphoma, Hodgkin lymphoma, Wilms’ tumour, sarcoma, retinoblastoma, gliomas, medulloblastomas or neuroblastomas, in keeping with the WHO Global Initiative for Childhood Cancer.Main outcome measure All-cause mortality at 30 days and 90 days.Results 1660 patients were recruited. 219 children had changes to their treatment due to the pandemic. Patients in LMICs were primarily affected (n=182/219, 83.1%). Relative to patients with paediatric cancer in HICs, patients with paediatric cancer in LMICs had 12.1 (95% CI 2.93 to 50.3) and 7.9 (95% CI 3.2 to 19.7) times the odds of death at 30 days and 90 days, respectively, after presentation during the COVID-19 pandemic (p
Published: 2022
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22. Social Vigilance of Friends and Foes in Western Lowland Gorillas (Gorilla gorilla gorilla)

Author: Tom S. Roth and Elisabeth H. M. Sterck
Subjects: social attention, despotism, good relationships, friendship, apes, social complexity, Zoology, QL1-991
Abstract: In social species, such as many primate species, conspecifics can pose a threat and individuals that are socially vigilant can prevent harassment. Many previous studies have focused on the role of agonistic interactions on social vigilance. In a variety of primate species, individuals are more vigilant for aggressive or dominant group members. In contrast, only few studies have investigated whether affiliative relationships also affect social vigilance. These studies revealed that individuals with an affiliative relationship showed lower levels of vigilance towards each other. Here, we tested the differential effects of both dyadic agonism and affiliation on the level of social vigilance of group-living western lowland gorillas (Gorilla gorilla gorilla) at Apenheul Primate Park, The Netherlands. We made continuous focal observations of agonistic and affiliative interactions and we scored level of vigilance during neutral approaches of conspecifics. We found that dyads with many affiliative interactions showed lower levels of vigilance towards each other. The opposite pattern was found for agonistic experiences, but this effect was not statistically robust. In addition, the adult male and adolescent males received higher levels of social vigilance than individuals from other age-sex classes. Our results indicate that level of social vigilance was linked to affiliative and, to a lesser extent, agonistic relationships in western lowland gorillas. We suggest that future studies in both egalitarian and despotic species should investigate whether, next to aggression, affiliation also influences social vigilance.
Published: 2020
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23. Measurement of the charged-current electron (anti-)neutrino inclusive cross-sections at the T2K off-axis near detector ND280

Author: The T2K collaboration, K. Abe, N. Akhlaq, R. Akutsu, A. Ali, C. Alt, C. Andreopoulos, L. Anthony, M. Antonova, S. Aoki, A. Ariga, T. Arihara, Y. Asada, Y. Ashida, E. T. Atkin, Y. Awataguchi, S. Ban, M. Barbi, G. J. Barker, G. Barr, D. Barrow, C. Barry, M. Batkiewicz-Kwasniak, A. Beloshapkin, F. Bench, V. Berardi, L. Berns, S. Bhadra, S. Bienstock, A. Blondel, S. Bolognesi, T. Bonus, B. Bourguille, S. B. Boyd, D. Brailsford, A. Bravar, D. Bravo Berguño, C. Bronner, S. Bron, A. Bubak, M. Buizza Avanzini, J. Calcutt, T. Campbell, S. Cao, S. L. Cartwright, M. G. Catanesi, A. Cervera, A. Chappell, C. Checchia, D. Cherdack, N. Chikuma, G. Christodoulou, M. Cicerchia, J. Coleman, G. Collazuol, L. Cook, D. Coplowe, A. Cudd, A. Dabrowska, G. De Rosa, T. Dealtry, P. F. Denner, S. R. Dennis, C. Densham, F. Di Lodovico, N. Dokania, S. Dolan, T. A. Doyle, O. Drapier, J. Dumarchez, P. Dunne, A. Eguchi, L. Eklund, S. Emery-Schrenk, A. Ereditato, P. Fernandez, T. Feusels, A. J. Finch, G. A. Fiorentini, G. Fiorillo, C. Francois, M. Friend, Y. Fujii, R. Fujita, D. Fukuda, R. Fukuda, Y. Fukuda, K. Fusshoeller, C. Giganti, T. Golan, M. Gonin, A. Gorin, M. Guigue, D. R. Hadley, J. T. Haigh, P. Hamacher-Baumann, M. Hartz, T. Hasegawa, S. Hassani, N. C. Hastings, T. Hayashino, Y. Hayato, A. Hiramoto, M. Hogan, J. Holeczek, N. T. Hong Van, T. Honjo, F. Iacob, A. K. Ichikawa, M. Ikeda, T. Ishida, T. Ishii, M. Ishitsuka, K. Iwamoto, A. Izmaylov, N. Izumi, M. Jakkapu, B. Jamieson, S. J. Jenkins, C. Jesús-Valls, M. Jiang, S. Johnson, P. Jonsson, C. K. Jung, X. Junjie, P. B. Jurj, M. Kabirnezhad, A. C. Kaboth, T. Kajita, H. Kakuno, J. Kameda, D. Karlen, S. P. Kasetti, Y. Kataoka, Y. Katayama, T. Katori, Y. Kato, E. Kearns, M. Khabibullin, A. Khotjantsev, T. Kikawa, H. Kikutani, H. Kim, S. King, J. Kisiel, A. Knight, A. Knox, T. Kobata, T. Kobayashi, L. Koch, T. Koga, A. Konaka, L. L. Kormos, Y. Koshio, A. Kostin, K. Kowalik, H. Kubo, Y. Kudenko, N. Kukita, S. Kuribayashi, R. Kurjata, T. Kutter, M. Kuze, L. Labarga, J. Lagoda, M. Lamoureux, D. Last, M. Laveder, M. Lawe, M. Licciardi, T. Lindner, R. P. Litchfield, S. L. Liu, X. Li, A. Longhin, L. Ludovici, X. Lu, T. Lux, L. N. Machado, L. Magaletti, K. Mahn, M. Malek, S. Manly, L. Maret, A. D. Marino, L. Marti-Magro, J. F. Martin, T. Maruyama, T. Matsubara, K. Matsushita, V. Matveev, C. Mauger, K. Mavrokoridis, E. Mazzucato, M. McCarthy, N. McCauley, J. McElwee, K. S. McFarland, C. McGrew, A. Mefodiev, C. Metelko, M. Mezzetto, A. Minamino, O. Mineev, S. Mine, M. Miura, L. Molina Bueno, S. Moriyama, J. Morrison, Th. A. Mueller, L. Munteanu, S. Murphy, Y. Nagai, T. Nakadaira, M. Nakahata, Y. Nakajima, A. Nakamura, K. G. Nakamura, K. Nakamura, Y. Nakano, S. Nakayama, T. Nakaya, K. Nakayoshi, C. Nantais, C. E. R. Naseby, T. V. Ngoc, K. Niewczas, K. Nishikawa, Y. Nishimura, E. Noah, T. S. Nonnenmacher, F. Nova, P. Novella, J. Nowak, J. C. Nugent, H. M. O’Keeffe, L. O’Sullivan, T. Odagawa, T. Ogawa, R. Okada, K. Okumura, T. Okusawa, S. M. Oser, R. A. Owen, Y. Oyama, V. Palladino, J. L. Palomino, V. Paolone, M. Pari, W. C. Parker, S. Parsa, J. Pasternak, P. Paudyal, M. Pavin, D. Payne, G. C. Penn, L. Pickering, C. Pidcott, G. Pintaudi, E. S. Pinzon Guerra, C. Pistillo, B. Popov, K. Porwit, M. Posiadala-Zezula, A. Pritchard, B. Quilain, T. Radermacher, E. Radicioni, B. Radics, P. N. Ratoff, E. Reinherz-Aronis, C. Riccio, E. Rondio, S. Roth, A. Rubbia, A. C. Ruggeri, C. A. Ruggles, A. Rychter, K. Sakashita, F. Sánchez, G. Santucci, C. M. Schloesser, K. Scholberg, J. Schwehr, M. Scott, Y. Seiya, T. Sekiguchi, H. Sekiya, D. Sgalaberna, R. Shah, A. Shaikhiev, F. Shaker, A. Shaykina, M. Shiozawa, W. Shorrock, A. Shvartsman, A. Smirnov, M. Smy, J. T. Sobczyk, H. Sobel, F. J. P. Soler, Y. Sonoda, J. Steinmann, S. Suvorov, A. Suzuki, S. Y. Suzuki, Y. Suzuki, A. A. Sztuc, M. Tada, M. Tajima, A. Takeda, Y. Takeuchi, H. K. Tanaka, H. A. Tanaka, S. Tanaka, Y. Tanihara, M. Tani, N. Teshima, L. F. Thompson, W. Toki, C. Touramanis, T. Towstego, K. M. Tsui, T. Tsukamoto, M. Tzanov, Y. Uchida, M. Vagins, S. Valder, Z. Vallari, D. Vargas, G. Vasseur, C. Vilela, W. G. S. Vinning, T. Vladisavljevic, V. V. Volkov, T. Wachala, J. Walker, J. G. Walsh, Y. Wang, D. Wark, M. O. Wascko, A. Weber, R. Wendell, M. J. Wilking, C. Wilkinson, J. R. Wilson, R. J. Wilson, K. Wood, C. Wret, Y. Yamada, K. Yamamoto, C. Yanagisawa, G. Yang, T. Yano, K. Yasutome, S. Yen, N. Yershov, M. Yokoyama, T. Yoshida, M. Yu, A. Zalewska, J. Zalipska, K. Zaremba, G. Zarnecki, M. Ziembicki, E. D. Zimmerman, M. Zito, S. Zsoldos, and A. Zykova
Subjects: Other experiments, Nuclear and particle physics. Atomic energy. Radioactivity, QC770-798
Abstract: Abstract The electron (anti-)neutrino component of the T2K neutrino beam constitutes the largest background in the measurement of electron (anti-)neutrino appearance at the far detector. The electron neutrino scattering is measured directly with the T2K off-axis near detector, ND280. The selection of the electron (anti-)neutrino events in the plastic scintillator target from both neutrino and anti-neutrino mode beams is discussed in this paper. The flux integrated single differential charged-current inclusive electron (anti-)neutrino cross-sections, dσ/dp and dσ/d cos(θ), and the total cross-sections in a limited phase-space in momentum and scattering angle (p > 300 MeV/c and θ ≤ 45°) are measured using a binned maximum likelihood fit and compared to the neutrino Monte Carlo generator predictions, resulting in good agreement.
Published: 2020
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24. LR-CNN: LOCAL-AWARE REGION CNN FOR VEHICLE DETECTION IN AERIAL IMAGERY

Author: W. Liao, X. Chen, J. Yang, S. Roth, M. Goesele, M. Y. Yang, and B. Rosenhahn
Subjects: Technology, Engineering (General). Civil engineering (General), TA1-2040, Applied optics. Photonics, TA1501-1820
Abstract: State-of-the-art object detection approaches such as Fast/Faster R-CNN, SSD, or YOLO have difficulties detecting dense, small targets with arbitrary orientation in large aerial images. The main reason is that using interpolation to align RoI features can result in a lack of accuracy or even loss of location information. We present the Local-aware Region Convolutional Neural Network (LR-CNN), a novel two-stage approach for vehicle detection in aerial imagery. We enhance translation invariance to detect dense vehicles and address the boundary quantization issue amongst dense vehicles by aggregating the high-precision RoIs’ features. Moreover, we resample high-level semantic pooled features, making them regain location information from the features of a shallower convolutional block. This strengthens the local feature invariance for the resampled features and enables detecting vehicles in an arbitrary orientation. The local feature invariance enhances the learning ability of the focal loss function, and the focal loss further helps to focus on the hard examples. Taken together, our method better addresses the challenges of aerial imagery. We evaluate our approach on several challenging datasets (VEDAI, DOTA), demonstrating a significant improvement over state-of-the-art methods. We demonstrate the good generalization ability of our approach on the DLR 3K dataset.
Published: 2020
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25. Remdesivir: A Review of Its Discovery and Development Leading to Emergency Use Authorization for Treatment of COVID-19

Author: Richard T. Eastman, Jacob S. Roth, Kyle R. Brimacombe, Anton Simeonov, Min Shen, Samarjit Patnaik, and Matthew D. Hall
Subjects: Chemistry, QD1-999
Published: 2020
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26. Fecal incontinence after total mesorectal excision for rectal cancer—impact of potential risk factors and pelvic intraoperative neuromonitoring

Author: Daniel W. Kauff, Yvonne D. S. Roth, Rika S. Bettzieche, and Werner Kneist
Subjects: Rectal cancer, Autonomic nervous system, Neoadjuvant therapy, Fecal incontinence, Intraoperative monitoring, Surgery, RD1-811, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Abstract Background Fecal incontinence frequently occurs after total mesorectal excision for rectal cancer. This prospective study analyzed predictive factors and the impact of pelvic intraoperative neuromonitoring at different follow-up intervals. Methods Fifty-two patients were included undergoing total mesorectal excision for rectal cancer, and 29 under control of pelvic intraoperative neuromonitoring. Fecal incontinence was assessed using the Wexner Score at 3 and 6 months after stoma closure (follow-ups 1 and 2) as well as 1 and 2 years after surgery (follow-ups 3 and 4). Risk factors were identified by means of logistic regression. Results New onset of fecal incontinence was significantly lower in the neuromonitoring group at each follow-up (follow-up 1: 2 of 29 patients (7%) vs. 8 of 23 (35%), (p = 0.014); follow-up 2: 3 of 29 (10%) vs. 9 of 23 (39%), (p = 0.017); follow-up 3: 5 of 29 (17%) vs. 11 of 23 (48%), p = 0.019; follow-up 4: 6 of 28 (21%) vs. 11 of 22 (50%), p = 0.035). Non-performance of neuromonitoring was found to be an independent predictor for fecal incontinence throughout the survey. Neoadjuvant chemoradiotherapy was an independent predictor in the further course 1 and 2 years after surgery. Conclusions Performance of pelvic intraoperative neuromonitoring is associated with significantly lower rates of fecal incontinence. Neoadjuvant chemoradiotherapy was found to have negative late effects. This became evident 1 year after surgery.
Published: 2020
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27. Development and efficacy testing of a portable negative pressure enclosure for airborne infection containment

Author: Benjamin S. Roth, Phillip Moschella, Ehsan S. Mousavi, Amanda S. LeMatty, Robert J. Falconer, Noah D. Ashley, Ali Mohammadi Nafchi, Chris Gaafary, and John D. DesJardins
Subjects: clinical engineering, COVID‐19, medical device design, negative pressure isolation, negative pressure pods, personal protective equipment, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Objectives To overcome the shortage of personal protective equipment and airborne infection isolation rooms (AIIRs) in the COVID‐19 pandemic, a collaborative team of research engineers and clinical physicians worked to build a novel negative pressure environment in the hopes of improving healthcare worker and patient safety. The team then sought to test the device's efficacy in generating and maintaining negative pressure. The goal proved prescient as the US Food and Drug Administration (FDA) later recommended that all barrier devices use negative pressure. Methods Initially, engineers observed simulations of various aerosol‐ and droplet‐generating procedures using hospital beds and stretchers to determine the optimal working dimensions of the containment device. Several prototypes were made based on these dimensions which were combined with filters and various flow‐generating devices. Then, the airflow generated and the pressure differential within the device during simulated patient care were measured, specifically assessing its ability to create a negative pressure environment consistent with standards published by the Centers for Disease Control and Prevention (CDC). Results The portable fans were unable to generate any airflow and were dropped from further testing. The vacuums tested were all able to generate a negative pressure environment with the magnitude of pressure differential increasing with the vacuum horsepower. Only the 3.5‐horsepower Shop‐Vac, however, generated a −3.0 pascal (Pa) pressure gradient, exceeding the CDC‐recommended minimum of −2.5 Pa for AIIRs. Conclusion A collaborative team of physicians and engineers demonstrated the efficacy of a prototype portable negative pressure environment, surpassing the negative pressure differential recommended by the CDC.
Published: 2022
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28. Grand Challenges in Coevolution

Author: Mónica Medina, David M. Baker, David A. Baltrus, Gordon M. Bennett, Ulisse Cardini, Adrienne M. S. Correa, Sandie M. Degnan, Gregor Christa, Eunsoo Kim, Jingchun Li, David R. Nash, Ezequiel Marzinelli, Michele Nishiguchi, Carlos Prada, Melissa S. Roth, Mahasweta Saha, Christopher I. Smith, Kevin R. Theis, and Jesse Zaneveld
Subjects: microbiome, symbiosis, network, holobiont, coevolution, Evolution, QH359-425, Ecology, QH540-549.5
Published: 2022
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29. Type I and II PRMTs inversely regulate post-transcriptional intron detention through Sm and CHTOP methylation

Author: Maxim I Maron, Alyssa D Casill, Varun Gupta, Jacob S Roth, Simone Sidoli, Charles C Query, Matthew J Gamble, and David Shechter
Subjects: PRMT5, PRMT1, retained detained introns, RNA processing, snRNP, A549, Medicine, Science, Biology (General), QH301-705.5
Abstract: Protein arginine methyltransferases (PRMTs) are required for the regulation of RNA processing factors. Type I PRMT enzymes catalyze mono- and asymmetric dimethylation; Type II enzymes catalyze mono- and symmetric dimethylation. To understand the specific mechanisms of PRMT activity in splicing regulation, we inhibited Type I and II PRMTs and probed their transcriptomic consequences. Using the newly developed Splicing Kinetics and Transcript Elongation Rates by Sequencing (SKaTER-seq) method, analysis of co-transcriptional splicing demonstrated that PRMT inhibition resulted in altered splicing rates. Surprisingly, co-transcriptional splicing kinetics did not correlate with final changes in splicing of polyadenylated RNA. This was particularly true for retained introns (RI). By using actinomycin D to inhibit ongoing transcription, we determined that PRMTs post-transcriptionally regulate RI. Subsequent proteomic analysis of both PRMT-inhibited chromatin and chromatin-associated polyadenylated RNA identified altered binding of many proteins, including the Type I substrate, CHTOP, and the Type II substrate, SmB. Targeted mutagenesis of all methylarginine sites in SmD3, SmB, and SmD1 recapitulated splicing changes seen with Type II PRMT inhibition, without disrupting snRNP assembly. Similarly, mutagenesis of all methylarginine sites in CHTOP recapitulated the splicing changes seen with Type I PRMT inhibition. Examination of subcellular fractions further revealed that RI were enriched in the nucleoplasm and chromatin. Taken together, these data demonstrate that, through Sm and CHTOP arginine methylation, PRMTs regulate the post-transcriptional processing of nuclear, detained introns.
Published: 2022
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30. Residual Entropy as a Diagnostic and Stopping Metric for CLEAN

Author: D. C. Homan, J. S. Roth, and A. B. Pushkarev
Subjects: Interferometry, Deconvolution, Radio astronomy, Astronomy, QB1-991
Abstract: We propose the use of entropy, measured from the spatial and flux distribution of pixels in the residual image, as a potential diagnostic and stopping metric for the CLEAN algorithm. Despite its broad success as the standard deconvolution approach in radio interferometry, finding the optimum stopping point for the iterative CLEAN algorithm is still a challenge. We show that the entropy of the residual image, measured during the final stages of CLEAN, can be computed without prior knowledge of the source structure or expected noise levels, and that finding the point of maximum entropy as a measure of randomness in the residual image serves as a robust stopping criterion. We also find that, when compared to the expected thermal noise in the image, the maximum entropy of the residuals is a useful diagnostic that can reveal the presence of data editing, calibration, or deconvolution issues that may limit the fidelity of the final CLEAN map.
Published: 2023
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31. 54. ONE YEAR OUTCOMES AFTER REGENERATIVE PERIPHERAL NERVE INTERFACE SURGERY FOR POSTAMPUTATION PAIN: RESULTS OF A PROSPECTIVE CLINICAL TRIAL

Author: Nishant Ganesh Kumar, MD, Carrie A. Kubiak, MD, Jennifer Hamill, MPH, Hyungjin M. Kim, Sc D, Melissa J. Tinney, MD, Randy S. Roth, PhD, Michael E. Geisser, PhD, Paul Cederna, MD, Stephen W.P. Kemp, PhD, and Theodore A. Kung, MD
Subjects: Surgery, RD1-811
Published: 2022
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32. An outreach activity to enhance biochemistry pedagogy

Author: Karl S. Roth, Tammy Bannerman, and Venkat Gopalan
Subjects: Molecular Biology, Biochemistry
Published: 2023
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33. Arthroscopic Single-Row Superior Capsular Reconstruction for Irreparable Rotator Cuff Tears

Author: Travis S. Roth, M.D., M.S., Matthew L. Welsh, M.D., Daryl C. Osbahr, M.D., and Amit Varma, M.D.
Subjects: Orthopedic surgery, RD701-811
Abstract: Massive, irreparable rotator cuff tears are challenging to manage. Often, these tears are not amenable to primary repair and necessitate additional treatment options. This is especially true in patients with absent glenohumeral arthritis in the setting of a massive, irreparable rotator cuff tear. Superior capsular reconstruction (SCR), originally described by Mihata using a fascia lata autograft, has grown in popularity for the treatment of irreparable rotator cuff tears as a salvage option with good clinical outcomes. More recently, SCR techniques have been described using dermal allograft. Biomechanical studies and reported clinical series show promising results, with favorable postoperative clinical outcomes. The procedure, however, may be technically challenging, especially when performed using an all-arthroscopic technique. This article describes an all-arthroscopic technique using a predetermined graft size, unique medial fixation to ease graft passage, and knotless single-row lateral fixation to optimize suture management and efficiency.
Published: 2020
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34. Canvass: A Crowd-Sourced, Natural-Product Screening Library for Exploring Biological Space

Author: Sara E. Kearney, Gergely Zahoránszky-Kőhalmi, Kyle R. Brimacombe, Mark J. Henderson, Caitlin Lynch, Tongan Zhao, Kanny K. Wan, Zina Itkin, Christopher Dillon, Min Shen, Dorian M. Cheff, Tobie D. Lee, Danielle Bougie, Ken Cheng, Nathan P. Coussens, Dorjbal Dorjsuren, Richard T. Eastman, Ruili Huang, Michael J. Iannotti, Surendra Karavadhi, Carleen Klumpp-Thomas, Jacob S. Roth, Srilatha Sakamuru, Wei Sun, Steven A. Titus, Adam Yasgar, Ya-Qin Zhang, Jinghua Zhao, Rodrigo B. Andrade, M. Kevin Brown, Noah Z. Burns, Jin K. Cha, Emily E. Mevers, Jon Clardy, Jason A. Clement, Peter A. Crooks, Gregory D. Cuny, Jake Ganor, Jesus Moreno, Lucas A. Morrill, Elias Picazo, Robert B. Susick, Neil K. Garg, Brian C. Goess, Robert B. Grossman, Chambers C. Hughes, Jeffrey N. Johnston, Madeleine M. Joullie, A. Douglas Kinghorn, David G.I. Kingston, Michael J. Krische, Ohyun Kwon, Thomas J. Maimone, Susruta Majumdar, Katherine N. Maloney, Enas Mohamed, Brian T. Murphy, Pavel Nagorny, David E. Olson, Larry E. Overman, Lauren E. Brown, John K. Snyder, John A. Porco, Fatima Rivas, Samir A. Ross, Richmond Sarpong, Indrajeet Sharma, Jared T. Shaw, Zhengren Xu, Ben Shen, Wei Shi, Corey R.J. Stephenson, Alyssa L. Verano, Derek S. Tan, Yi Tang, Richard E. Taylor, Regan J. Thomson, David A. Vosburg, Jimmy Wu, William M. Wuest, Armen Zakarian, Yufeng Zhang, Tianjing Ren, Zhong Zuo, James Inglese, Sam Michael, Anton Simeonov, Wei Zheng, Paul Shinn, Ajit Jadhav, Matthew B. Boxer, Matthew D. Hall, Menghang Xia, Rajarshi Guha, and Jason M. Rohde
Subjects: Chemistry, QD1-999
Published: 2018
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35. The Combination of Trametinib and Ganitumab is Effective in RAS-Mutated PAX-Fusion Negative Rhabdomyosarcoma Models

Author: Katie E. Hebron, Xiaolin Wan, Jacob S. Roth, David J. Liewehr, Nancy E. Sealover, William J.E. Frye, Angela Kim, Stacey Stauffer, Olivia L. Perkins, Wenyue Sun, Kristine A. Isanogle, Christina M. Robinson, Amy James, Parirokh Awasthi, Priya Shankarappa, Xiaoling Luo, Haiyan Lei, Donna Butcher, Roberta Smith, Elijah F. Edmondson, Jin-Qiu Chen, Noemi Kedei, Cody J. Peer, Jack F. Shern, W. Douglas Figg, Lu Chen, Matthew D. Hall, Simone Difilippantonio, Frederic G. Barr, Robert L. Kortum, Robert W. Robey, Angelina V. Vaseva, Javed Khan, and Marielle E. Yohe
Subjects: Cancer Research, Oncology
Abstract: Purpose: PAX-fusion negative rhabdomyosarcoma (FN RMS) is driven by alterations in the RAS/MAP kinase pathway and is partially responsive to MEK inhibition. Overexpression of IGF1R and its ligands is also observed in FN RMS. Preclinical and clinical studies have suggested that IGF1R is itself an important target in FN RMS. Our previous studies revealed preclinical efficacy of the MEK1/2 inhibitor, trametinib, and an IGF1R inhibitor, BMS-754807, but this combination was not pursued clinically due to intolerability in preclinical murine models. Here, we sought to identify a combination of an MEK1/2 inhibitor and IGF1R inhibitor, which would be tolerated in murine models and effective in both cell line and patient-derived xenograft models of RAS-mutant FN RMS. Experimental Design: Using proliferation and apoptosis assays, we studied the factorial effects of trametinib and ganitumab (AMG 479), a mAb with specificity for human and murine IGF1R, in a panel of RAS-mutant FN RMS cell lines. The molecular mechanism of the observed synergy was determined using conventional and capillary immunoassays. The efficacy and tolerability of trametinib/ganitumab was assessed using a panel of RAS-mutated cell-line and patient-derived RMS xenograft models. Results: Treatment with trametinib and ganitumab resulted in synergistic cellular growth inhibition in all cell lines tested and inhibition of tumor growth in four of six models of RAS-mutant RMS. The combination had little effect on body weight and did not produce thrombocytopenia, neutropenia, or hyperinsulinemia in tumor-bearing SCID beige mice. Mechanistically, ganitumab treatment prevented the phosphorylation of AKT induced by MEK inhibition alone. Therapeutic response to the combination was observed in models without a mutation in the PI3K/PTEN axis. Conclusions: We demonstrate that combined trametinib and ganitumab is effective in a genomically diverse panel of RAS-mutated FN RMS preclinical models. Our data also show that the trametinib/ganitumab combination likely has a favorable tolerability profile. These data support testing this combination in a phase I/II clinical trial for pediatric patients with relapsed or refractory RAS-mutated FN RMS.
Published: 2022
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36. Factors associated with acute postoperative pain following breast reconstruction

Author: Anita R. Kulkarni, Andrea L. Pusic, Jennifer B. Hamill, Hyungjin M. Kim, Ji Qi, Edwin G. Wilkins, and Randy S. Roth
Subjects: Postoperative pain, Breast reconstruction, Depression, Anxiety, Mastectomy, Chronic postsurgical pain, Surgery, RD1-811
Abstract: Introduction: Postmastectomy breast reconstruction has become an increasingly important component of breast cancer treatment. Unfortunately, some patients experience severe postoperative pain, placing them at risk for increased clinical morbidity and the development of disabling chronic pain. To identify patients at risk, we prospectively evaluated patient characteristics and medical/surgical variables associated with more severe acute post-reconstruction pain. Methods: Women (N = 2207; 1-week 82.8% response rate) undergoing breast reconstruction were assessed for pain experience, anxiety, depression, and sociodemographic characteristics before surgery. Pain assessments were made preoperatively and postoperatively at 1 week using validated survey instruments including the McGill Pain Questionnaire-Short Form (MPQ-SF), Numerical Pain Rating Scale (NPRS), and BREAST-Q Chest and Upper Body scale. Depressive symptoms and anxiety severity were assessed by the Patient Health Questionnaire and Generalized Anxiety Disorders Scale, respectively. Mixed-effects regression modeling was used to examine the relationships between patient characteristics and medical/surgical variables and 1-week postoperative pain. Results: Younger age; bilateral reconstruction; and severity of preoperative pain, anxiety, and depression were associated with more severe acute postoperative pain on all the pain measures and BREAST-Q. Surgical procedure type indicated less severe postoperative pain for PTRAM, DIEP, and SIEA reconstructive surgery when compared with tissue expander/implant reconstruction. Conclusions: This study identifies patients at risk for severe acute postoperative pain following breast reconstruction. These findings will allow plastic surgeons to better tailor postoperative care to improve patient comfort, reduce clinical morbidity, and enhance patient satisfaction with their surgical outcome.
Published: 2017
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37. The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project

Author: Lawrence N. Hudson, Tim Newbold, Sara Contu, Samantha L. L. Hill, Igor Lysenko, Adriana De Palma, Helen R. P. Phillips, Tamera I. Alhusseini, Felicity E. Bedford, Dominic J. Bennett, Hollie Booth, Victoria J. Burton, Charlotte W. T. Chng, Argyrios Choimes, David L. P. Correia, Julie Day, Susy Echeverría‐Londoño, Susan R. Emerson, Di Gao, Morgan Garon, Michelle L. K. Harrison, Daniel J. Ingram, Martin Jung, Victoria Kemp, Lucinda Kirkpatrick, Callum D. Martin, Yuan Pan, Gwilym D. Pask‐Hale, Edwin L. Pynegar, Alexandra N. Robinson, Katia Sanchez‐Ortiz, Rebecca A. Senior, Benno I. Simmons, Hannah J. White, Hanbin Zhang, Job Aben, Stefan Abrahamczyk, Gilbert B. Adum, Virginia Aguilar‐Barquero, Marcelo A. Aizen, Belén Albertos, E. L. Alcala, Maria delMar Alguacil, Audrey Alignier, Marc Ancrenaz, Alan N. Andersen, Enrique Arbeláez‐Cortés, Inge Armbrecht, Víctor Arroyo‐Rodríguez, Tom Aumann, Jan C. Axmacher, Badrul Azhar, Adrián B. Azpiroz, Lander Baeten, Adama Bakayoko, András Báldi, John E. Banks, Sharad K. Baral, Jos Barlow, Barbara I. P. Barratt, Lurdes Barrico, Paola Bartolommei, Diane M. Barton, Yves Basset, Péter Batáry, Adam J. Bates, Bruno Baur, Erin M. Bayne, Pedro Beja, Suzan Benedick, Åke Berg, Henry Bernard, Nicholas J. Berry, Dinesh Bhatt, Jake E. Bicknell, Jochen H. Bihn, Robin J. Blake, Kadiri S. Bobo, Roberto Bóçon, Teun Boekhout, Katrin Böhning‐Gaese, Kevin J. Bonham, Paulo A. V. Borges, Sérgio H. Borges, Céline Boutin, Jérémy Bouyer, Cibele Bragagnolo, Jodi S. Brandt, Francis Q. Brearley, Isabel Brito, Vicenç Bros, Jörg Brunet, Grzegorz Buczkowski, Christopher M. Buddle, Rob Bugter, Erika Buscardo, Jörn Buse, Jimmy Cabra‐García, Nilton C. Cáceres, Nicolette L. Cagle, María Calviño‐Cancela, Sydney A. Cameron, Eliana M. Cancello, Rut Caparrós, Pedro Cardoso, Dan Carpenter, Tiago F. Carrijo, Anelena L. Carvalho, Camila R. Cassano, Helena Castro, Alejandro A. Castro‐Luna, Cerda B. Rolando, Alexis Cerezo, Kim Alan Chapman, Matthieu Chauvat, Morten Christensen, Francis M. Clarke, Daniel F.R. Cleary, Giorgio Colombo, Stuart P. Connop, Michael D. Craig, Leopoldo Cruz‐López, Saul A. Cunningham, Biagio D'Aniello, Neil D'Cruze, Pedro Giovâni daSilva, Martin Dallimer, Emmanuel Danquah, Ben Darvill, Jens Dauber, Adrian L. V. Davis, Jeff Dawson, Claudio deSassi, Benoit deThoisy, Olivier Deheuvels, Alain Dejean, Jean‐Louis Devineau, Tim Diekötter, Jignasu V. Dolia, Erwin Domínguez, Yamileth Dominguez‐Haydar, Silvia Dorn, Isabel Draper, Niels Dreber, Bertrand Dumont, Simon G. Dures, Mats Dynesius, Lars Edenius, Paul Eggleton, Felix Eigenbrod, Zoltán Elek, Martin H. Entling, Karen J. Esler, Ricardo F. deLima, Aisyah Faruk, Nina Farwig, Tom M. Fayle, Antonio Felicioli, Annika M. Felton, Roderick J. Fensham, Ignacio C. Fernandez, Catarina C. Ferreira, Gentile F. Ficetola, Cristina Fiera, Bruno K. C. Filgueiras, Hüseyin K. Fırıncıoğlu, David Flaspohler, Andreas Floren, Steven J. Fonte, Anne Fournier, Robert E. Fowler, Markus Franzén, Lauchlan H. Fraser, Gabriella M. Fredriksson, Geraldo B. Freire Jr, Tiago L. M. Frizzo, Daisuke Fukuda, Dario Furlani, René Gaigher, Jörg U. Ganzhorn, Karla P. García, Juan C. Garcia‐R, Jenni G. Garden, Ricardo Garilleti, Bao‐Ming Ge, Benoit Gendreau‐Berthiaume, Philippa J. Gerard, Carla Gheler‐Costa, Benjamin Gilbert, Paolo Giordani, Simonetta Giordano, Carly Golodets, Laurens G. L. Gomes, Rachelle K. Gould, Dave Goulson, Aaron D. Gove, Laurent Granjon, Ingo Grass, Claudia L. Gray, James Grogan, Weibin Gu, Moisès Guardiola, Nihara R. Gunawardene, Alvaro G. Gutierrez, Doris L. Gutiérrez‐Lamus, Daniela H. Haarmeyer, Mick E. Hanley, Thor Hanson, Nor R. Hashim, Shombe N. Hassan, Richard G. Hatfield, Joseph E. Hawes, Matt W. Hayward, Christian Hébert, Alvin J. Helden, John‐André Henden, Philipp Henschel, Lionel Hernández, James P. Herrera, Farina Herrmann, Felix Herzog, Diego Higuera‐Diaz, Branko Hilje, Hubert Höfer, Anke Hoffmann, Finbarr G. Horgan, Elisabeth Hornung, Roland Horváth, Kristoffer Hylander, Paola Isaacs‐Cubides, Hiroaki Ishida, Masahiro Ishitani, Carmen T. Jacobs, Víctor J. Jaramillo, Birgit Jauker, F. Jiménez Hernández, McKenzie F. Johnson, Virat Jolli, Mats Jonsell, S. Nur Juliani, Thomas S. Jung, Vena Kapoor, Heike Kappes, Vassiliki Kati, Eric Katovai, Klaus Kellner, Michael Kessler, Kathryn R. Kirby, Andrew M. Kittle, Mairi E. Knight, Eva Knop, Florian Kohler, Matti Koivula, Annette Kolb, Mouhamadou Kone, Ádám Kőrösi, Jochen Krauss, Ajith Kumar, Raman Kumar, David J. Kurz, Alex S. Kutt, Thibault Lachat, Victoria Lantschner, Francisco Lara, Jesse R. Lasky, Steven C. Latta, William F. Laurance, Patrick Lavelle, Violette Le Féon, Gretchen LeBuhn, Jean‐Philippe Légaré, Valérie Lehouck, María V. Lencinas, Pia E. Lentini, Susan G. Letcher, Qi Li, Simon A. Litchwark, Nick A. Littlewood, Yunhui Liu, Nancy Lo‐Man‐Hung, Carlos A. López‐Quintero, Mounir Louhaichi, Gabor L. Lövei, Manuel Esteban Lucas‐Borja, Victor H. Luja, Matthew S. Luskin, M Cristina MacSwiney G, Kaoru Maeto, Tibor Magura, Neil Aldrin Mallari, Louise A. Malone, Patrick K. Malonza, Jagoba Malumbres‐Olarte, Salvador Mandujano, Inger E. Måren, Erika Marin‐Spiotta, Charles J. Marsh, E. J. P. Marshall, Eliana Martínez, Guillermo Martínez Pastur, David Moreno Mateos, Margaret M. Mayfield, Vicente Mazimpaka, Jennifer L. McCarthy, Kyle P. McCarthy, Quinn S. McFrederick, Sean McNamara, Nagore G. Medina, Rafael Medina, Jose L. Mena, Estefania Mico, Grzegorz Mikusinski, Jeffrey C. Milder, James R. Miller, Daniel R. Miranda‐Esquivel, Melinda L. Moir, Carolina L. Morales, Mary N. Muchane, Muchai Muchane, Sonja Mudri‐Stojnic, A. Nur Munira, Antonio Muoñz‐Alonso, B. F. Munyekenye, Robin Naidoo, A. Naithani, Michiko Nakagawa, Akihiro Nakamura, Yoshihiro Nakashima, Shoji Naoe, Guiomar Nates‐Parra, Dario A. Navarrete Gutierrez, Luis Navarro‐Iriarte, Paul K. Ndang'ang'a, Eike L. Neuschulz, Jacqueline T. Ngai, Violaine Nicolas, Sven G. Nilsson, Norbertas Noreika, Olivia Norfolk, Jorge Ari Noriega, David A. Norton, Nicole M. Nöske, A. Justin Nowakowski, Catherine Numa, Niall O'Dea, Patrick J. O'Farrell, William Oduro, Sabine Oertli, Caleb Ofori‐Boateng, Christopher Omamoke Oke, Vicencio Oostra, Lynne M. Osgathorpe, Samuel Eduardo Otavo, Navendu V. Page, Juan Paritsis, Alejandro Parra‐H, Luke Parry, Guy Pe'er, Peter B. Pearman, Nicolás Pelegrin, Raphaël Pélissier, Carlos A. Peres, Pablo L. Peri, Anna S. Persson, Theodora Petanidou, Marcell K. Peters, Rohan S. Pethiyagoda, Ben Phalan, T. Keith Philips, Finn C. Pillsbury, Jimmy Pincheira‐Ulbrich, Eduardo Pineda, Joan Pino, Jaime Pizarro‐Araya, A. J. Plumptre, Santiago L. Poggio, Natalia Politi, Pere Pons, Katja Poveda, Eileen F. Power, Steven J. Presley, Vânia Proença, Marino Quaranta, Carolina Quintero, Romina Rader, B. R. Ramesh, Martha P. Ramirez‐Pinilla, Jai Ranganathan, Claus Rasmussen, Nicola A. Redpath‐Downing, J. Leighton Reid, Yana T. Reis, José M. Rey Benayas, Juan Carlos Rey‐Velasco, Chevonne Reynolds, Danilo Bandini Ribeiro, Miriam H. Richards, Barbara A. Richardson, Michael J. Richardson, Rodrigo Macip Ríos, Richard Robinson, Carolina A. Robles, Jörg Römbke, Luz Piedad Romero‐Duque, Matthias Rös, Loreta Rosselli, Stephen J. Rossiter, Dana S. Roth, T'ai H. Roulston, Laurent Rousseau, André V. Rubio, Jean‐Claude Ruel, Jonathan P. Sadler, Szabolcs Sáfián, Romeo A. Saldaña‐Vázquez, Katerina Sam, Ulrika Samnegård, Joana Santana, Xavier Santos, Jade Savage, Nancy A. Schellhorn, Menno Schilthuizen, Ute Schmiedel, Christine B. Schmitt, Nicole L. Schon, Christof Schüepp, Katharina Schumann, Oliver Schweiger, Dawn M. Scott, Kenneth A. Scott, Jodi L. Sedlock, Steven S. Seefeldt, Ghazala Shahabuddin, Graeme Shannon, Douglas Sheil, Frederick H. Sheldon, Eyal Shochat, Stefan J. Siebert, Fernando A. B. Silva, Javier A. Simonetti, Eleanor M. Slade, Jo Smith, Allan H. Smith‐Pardo, Navjot S. Sodhi, Eduardo J. Somarriba, Ramón A. Sosa, Grimaldo Soto Quiroga, Martin‐Hugues St‐Laurent, Brian M. Starzomski, Constanti Stefanescu, Ingolf Steffan‐Dewenter, Philip C. Stouffer, Jane C. Stout, Ayron M. Strauch, Matthew J. Struebig, Zhimin Su, Marcela Suarez‐Rubio, Shinji Sugiura, Keith S. Summerville, Yik‐Hei Sung, Hari Sutrisno, Jens‐Christian Svenning, Tiit Teder, Caragh G. Threlfall, Anu Tiitsaar, Jacqui H. Todd, Rebecca K. Tonietto, Ignasi Torre, Béla Tóthmérész, Teja Tscharntke, Edgar C. Turner, Jason M. Tylianakis, Marcio Uehara‐Prado, Nicolas Urbina‐Cardona, Denis Vallan, Adam J. Vanbergen, Heraldo L. Vasconcelos, Kiril Vassilev, Hans A. F. Verboven, Maria João Verdasca, José R. Verdú, Carlos H. Vergara, Pablo M. Vergara, Jort Verhulst, Massimiliano Virgilio, Lien Van Vu, Edward M. Waite, Tony R. Walker, Hua‐Feng Wang, Yanping Wang, James I. Watling, Britta Weller, Konstans Wells, Catrin Westphal, Edward D. Wiafe, Christopher D. Williams, Michael R. Willig, John C. Z. Woinarski, Jan H. D. Wolf, Volkmar Wolters, Ben A. Woodcock, Jihua Wu, Joseph M. Wunderle Jr, Yuichi Yamaura, Satoko Yoshikura, Douglas W. Yu, Andrey S. Zaitsev, Juliane Zeidler, Fasheng Zou, Ben Collen, Rob M. Ewers, Georgina M. Mace, Drew W. Purves, Jörn P. W. Scharlemann, and Andy Purvis
Subjects: data sharing, global biodiversity modeling, global change, habitat destruction, land use, Ecology, QH540-549.5
Abstract: Abstract The PREDICTS project—Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (https://www.nhm.ac.uk/our-science/our-work/biodiversity/predicts.html)—has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
Published: 2017
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38. Caloric restriction improves health and survival of rhesus monkeys

Author: Julie A. Mattison, Ricki J. Colman, T. Mark Beasley, David B. Allison, Joseph W. Kemnitz, George S. Roth, Donald K. Ingram, Richard Weindruch, Rafael de Cabo, and Rozalyn M. Anderson
Subjects: Science
Abstract: Caloric restriction (CR) delays ageing of model organisms, but whether it works in nonhuman primates has been controversial. Here, the authors pool and reanalyse data from two long-running CR primate studies, concluding that moderate CR indeed improves health and survival of rhesus monkeys.
Published: 2017
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39. Bedeutung von intraoperativer Gefrierschnittanalyse und histopathologischen Ergebnissen von Wächterlymphknotenbiopsien: Vergleich von Z0011-Studie-geeigneten mit ungeeigneten Brustkrebspatientinnen

Author: Florian Reinhardt, Anna Fiedler, Felix Borgmeier, Petra Reinecke, Irene Esposito, Katalin Mattes-György, Mardjan Dabir, Verena Friebe, Natalia Krawczyk, Thomas Kaleta, Jürgen Hoffmann, Eugen Ruckhäberle, Tanja Fehm, Katrin S. Roth, and Svjetlana Mohrmann
Subjects: General Medicine
Abstract: Zusammenfassung Hintergrund Nach der Veröffentlichung der American College of Surgeons Oncology Group Z0011-Studie (ACOSOG Z0011) ist die Analyse der intraoperativen Gefrierschnitte von Wächterlymphknoten zurückgegangen. Aber für Patientinnen, welche die ACOSOG Z0011-Kriterien nicht erfüllen, bleibt die Gefrierschnittanalyse ein wichtiges Instrument für die intraoperative Entscheidungsfindung im Hinblick auf eine Axilladissektion. Ziel dieser Studie war es, eine retrospektive Evaluierung der Vorteile und der diagnostischen Genauigkeit von Gefrierschnittanalysen bei Brustkrebspatientinnen durchzuführen, welche die Kriterien der Z0011-Studie erfüllten oder nicht erfüllten, und dabei mögliche prädiktive Faktoren für falsch negative Ergebnisse festzustellen. Methoden Zwischen 2008 und 2013 wurde eine intraoperative Gefrierschnittanalyse der Wächterlymphknoten bei 522 cT1-T3-Brustkrebspatientinnen durchgeführt. Die klinisch-pathologischen Merkmale wurden retrospektiv mithilfe der Krankenakten evaluiert. Ergebnisse Insgesamt betrug die Sensitivität und Spezifität für alle Gefrierschnittanalysen 67,8 % bzw. 100 %. Generell war die Sensitivität für Makrometastasen höher als für Mikrometastasen. Bei der Gruppe, welche die Kriterien der Z0011-Studie erfüllte, betrugen die Sensitivität und Spezifität 72,7 % bzw. 100 %, verglichen mit 62,1 % bzw. 100 % für die Gruppe, welche die Z0011-Kriterien nicht erfüllte. In der Gruppe, welche die Z0011-Kriterien erfüllte, wurde eine Untergruppenanalyse durchgeführt, und die Ergebnisse für ≤ 2 positiven Wächterlymphknoten wurden mit den Ergebnissen für > 2 verglichen. Bei beiden Untergruppen betrugen Spezifität und Sensitivität jeweils 100 %. In der Patientinnengruppe, welche die Z0011-Kriterien nicht erfüllte, waren mehrere klinisch-pathologische Faktoren mit einer höheren Rate an falsch positiven Ergebnissen assoziiert. Im Hinblick auf die intraoperative Entscheidungsfindung für eine Axilladissektion brachte die Durchführung einer intraoperativen Gefrierschnittanalyse Vorteile für 22,2 % der Patientinnen, welche die Z0011-Kriterien nicht erfüllten, aber nur für 0,6 % der Patientinnen, welche die Z0011-Kriterien erfüllten. Schlussfolgerungen Die Gefrierschnittanalyse ist besonders für die intraoperative Evaluierung von Wächterlymphknoten bei Patientinnen, welche die Z0011-Kriterien nicht erfüllen, vorteilhaft, da dadurch eine Zweitoperation zur Axilladissektion vermieden werden kann. Obwohl die Sensitivität der Gefrierschnittanalyse in der Gruppe, welche die Z0011-Kriterien erfüllte, insgesamt niedriger war, hat die Gefrierschnittanalyse in beiden Gruppen eine vergleichbar hohe Sensitivität und diagnostische Genauigkeit für Makrometastasen.
Published: 2022
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40. Warming and grazing independently and interactively impact plant defenses and palatability

Author: Jamila S. Roth, Todd Z. Osborne, and Laura K. Reynolds
Subjects: Ecology, Evolution, Behavior and Systematics
Published: 2023
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41. Comparative long-term effectiveness between ventral hernia repairs with biosynthetic and synthetic mesh

Author: Benjamin G. Morrison, Kiah Gledhill, Margaret A. Plymale, Daniel L. Davenport, and John S. Roth
Subjects: Surgery
Published: 2023
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42. Supplementary Data from SMYD3 Impedes Small Cell Lung Cancer Sensitivity to Alkylation Damage through RNF113A Methylation–Phosphorylation Cross-talk

Author: Nicolas Reynoird, Nima Mosammaparast, Pawel K. Mazur, Pierre Hainaut, Michiel Vermeulen, Yohann Couté, Pascal W.T.C. Jansen, Marianne Tardif, Rebecca Rodell, Jessica Vayr, Ana Morales Benitez, Florent Chuffart, Alexandre G. Casanova, Joshua R. Brickner, Ning Tsao, Tanveer Ahmad, Clement Oyeniran, Gael S. Roth, Simone Hausmann, and Valentina Lukinović
Abstract: Supplementary Data from SMYD3 Impedes Small Cell Lung Cancer Sensitivity to Alkylation Damage through RNF113A Methylation–Phosphorylation Cross-talk
Published: 2023
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43. Supplementary Table from SMYD3 Impedes Small Cell Lung Cancer Sensitivity to Alkylation Damage through RNF113A Methylation–Phosphorylation Cross-talk

Author: Nicolas Reynoird, Nima Mosammaparast, Pawel K. Mazur, Pierre Hainaut, Michiel Vermeulen, Yohann Couté, Pascal W.T.C. Jansen, Marianne Tardif, Rebecca Rodell, Jessica Vayr, Ana Morales Benitez, Florent Chuffart, Alexandre G. Casanova, Joshua R. Brickner, Ning Tsao, Tanveer Ahmad, Clement Oyeniran, Gael S. Roth, Simone Hausmann, and Valentina Lukinović
Abstract: Supplementary Table from SMYD3 Impedes Small Cell Lung Cancer Sensitivity to Alkylation Damage through RNF113A Methylation–Phosphorylation Cross-talk
Published: 2023
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44. Data from SMYD3 Impedes Small Cell Lung Cancer Sensitivity to Alkylation Damage through RNF113A Methylation–Phosphorylation Cross-talk

Author: Nicolas Reynoird, Nima Mosammaparast, Pawel K. Mazur, Pierre Hainaut, Michiel Vermeulen, Yohann Couté, Pascal W.T.C. Jansen, Marianne Tardif, Rebecca Rodell, Jessica Vayr, Ana Morales Benitez, Florent Chuffart, Alexandre G. Casanova, Joshua R. Brickner, Ning Tsao, Tanveer Ahmad, Clement Oyeniran, Gael S. Roth, Simone Hausmann, and Valentina Lukinović
Abstract: Small cell lung cancer (SCLC) is the most fatal form of lung cancer, with dismal survival, limited therapeutic options, and rapid development of chemoresistance. We identified the lysine methyltransferase SMYD3 as a major regulator of SCLC sensitivity to alkylation-based chemotherapy. RNF113A methylation by SMYD3 impairs its interaction with the phosphatase PP4, controlling its phosphorylation levels. This cross-talk between posttranslational modifications acts as a key switch in promoting and maintaining RNF113A E3 ligase activity, essential for its role in alkylation damage response. In turn, SMYD3 inhibition restores SCLC vulnerability to alkylating chemotherapy. Our study sheds light on a novel role of SMYD3 in cancer, uncovering this enzyme as a mediator of alkylation damage sensitivity and providing a rationale for small-molecule SMYD3 inhibition to improve responses to established chemotherapy.Significance:SCLC rapidly becomes resistant to conventional chemotherapy, leaving patients with no alternative treatment options. Our data demonstrate that SMYD3 upregulation and RNF113A methylation in SCLC are key mechanisms that control the alkylation damage response. Notably, SMYD3 inhibition sensitizes cells to alkylating agents and promotes sustained SCLC response to chemotherapy.This article is highlighted in the In This Issue feature, p. 2007
Published: 2023
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45. Supplementary Table S2 from PRC2 Inhibitors Overcome Glucocorticoid Resistance Driven by NSD2 Mutation in Pediatric Acute Lymphoblastic Leukemia

Author: Jonathan D. Licht, Richard B. Lock, Matthew D. Hall, Adolfo A. Ferrando, Richard L. Bennett, Alberto Riva, Min Shen, Christine M. Will, Jon A. Oyer, Marta Kulis, Alok Swaroop, Catalina Troche, Heidi L. Casellas Román, Duohui Jing, Jacob S. Roth, Daphne Dupéré-Richér, Crissandra Piper, Jonathan H. Shrimp, Julia Hlavka-Zhang, and Jianping Li
Abstract: ALL patients with NSD2 mutations
Published: 2023
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46. Figure S2 from Efficacy of AKT Inhibitor ARQ 092 Compared with Sorafenib in a Cirrhotic Rat Model with Hepatocellular Carcinoma

Author: Thomas Decaens, Vincent Leroy, Patrice N. Marche, Benoit Busser, Yi Yu, Giovanni Abbadessa, Séyédéh Tayébéh Ahmad Pour, Keerthi Kurma, Ayca Zeybek Kuyucu, Zuzana Macek Jilkova, and Gaël S. Roth
Abstract: Migration
Published: 2023
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47. Supplementary Material and Method, Supplementary Tables 1-2, and Figure Legends from Efficacy of AKT Inhibitor ARQ 092 Compared with Sorafenib in a Cirrhotic Rat Model with Hepatocellular Carcinoma

Author: Thomas Decaens, Vincent Leroy, Patrice N. Marche, Benoit Busser, Yi Yu, Giovanni Abbadessa, Séyédéh Tayébéh Ahmad Pour, Keerthi Kurma, Ayca Zeybek Kuyucu, Zuzana Macek Jilkova, and Gaël S. Roth
Abstract: Supplementary Table 1: IC20 and IC50 values of ARQ 092 and sorafenib in Hep3B, Huh-7, HepG2, PLC/PRF/5 and HR4 cell lines after 48h of exposure; Supplementary Table 2: List of significantly different phospho-kinases from ARQ 092 treated rats compared to control group.
Published: 2023
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48. Supplementary Methods and Figures from PRC2 Inhibitors Overcome Glucocorticoid Resistance Driven by NSD2 Mutation in Pediatric Acute Lymphoblastic Leukemia

Author: Jonathan D. Licht, Richard B. Lock, Matthew D. Hall, Adolfo A. Ferrando, Richard L. Bennett, Alberto Riva, Min Shen, Christine M. Will, Jon A. Oyer, Marta Kulis, Alok Swaroop, Catalina Troche, Heidi L. Casellas Román, Duohui Jing, Jacob S. Roth, Daphne Dupéré-Richér, Crissandra Piper, Jonathan H. Shrimp, Julia Hlavka-Zhang, and Jianping Li
Abstract: Supplementary Methods and Figures
Published: 2023
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49. Data from PRC2 Inhibitors Overcome Glucocorticoid Resistance Driven by NSD2 Mutation in Pediatric Acute Lymphoblastic Leukemia

Author: Jonathan D. Licht, Richard B. Lock, Matthew D. Hall, Adolfo A. Ferrando, Richard L. Bennett, Alberto Riva, Min Shen, Christine M. Will, Jon A. Oyer, Marta Kulis, Alok Swaroop, Catalina Troche, Heidi L. Casellas Román, Duohui Jing, Jacob S. Roth, Daphne Dupéré-Richér, Crissandra Piper, Jonathan H. Shrimp, Julia Hlavka-Zhang, and Jianping Li
Abstract: Mutations in epigenetic regulators are common in relapsed pediatric acute lymphoblastic leukemia (ALL). Here, we uncovered the mechanism underlying the relapse of ALL driven by an activating mutation of the NSD2 histone methyltransferase (p.E1099K). Using high-throughput drug screening, we found that NSD2-mutant cells were specifically resistant to glucocorticoids. Correction of this mutation restored glucocorticoid sensitivity. The transcriptional response to glucocorticoids was blocked in NSD2-mutant cells due to depressed glucocorticoid receptor (GR) levels and the failure of glucocorticoids to autoactivate GR expression. Although H3K27me3 was globally decreased by NSD2 p.E1099K, H3K27me3 accumulated at the NR3C1 (GR) promoter. Pretreatment of NSD2 p.E1099K cell lines and patient-derived xenograft samples with PRC2 inhibitors reversed glucocorticoid resistance in vitro and in vivo. PRC2 inhibitors restored NR3C1 autoactivation by glucocorticoids, increasing GR levels and allowing GR binding and activation of proapoptotic genes. These findings suggest a new therapeutic approach to relapsed ALL associated with NSD2 mutation.Significance:NSD2 histone methyltransferase mutations observed in relapsed pediatric ALL drove glucocorticoid resistance by repression of the GR and abrogation of GR gene autoactivation due to accumulation of K3K27me3 at its promoter. Pretreatment with PRC2 inhibitors reversed resistance, suggesting a new therapeutic approach to these patients with ALL.This article is highlighted in the In This Issue feature, p. 1
Published: 2023
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50. Supplementary Information and Data from The Combination of Vemurafenib and Procaspase-3 Activation Is Synergistic in Mutant BRAF Melanomas

Author: Paul J. Hergenrother, Howard S. Roth, Kathryn L. Wycislo, Timothy M. Fan, and Jessie Peh
Abstract: The supplementary information file contains details about primers used for this work, supplementary Figures S1-S8, supplementary Table S1, and results from cell line authentication and from mycoplasma testing.
Published: 2023
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