Therapeutic benefit of the dual ALK/FAK inhibitor ESK440 in ALK-driven neuroblastoma by Seema Chugh, Jean C. Tien, Jennifer Hon, Carson Kenum, Rahul Mannan, Yunhui Cheng, Chi Chiang Li, Zainab I. Taher, Andrew D. Delekta, Pushpinder Singh Bawa, Ingrid J. Apel, Stephanie J. Miner, Xuhong Cao, Rohit Mehra, Saravana M. Dhanasekaran, Yuanyuan Qiao, Rajen Mody, Arul M. Chinnaiyan

“…In addition, a proportion of high-risk patients harbor amplification or activating mutations in anaplastic lymphoma kinase (ALK), and co-occurrence of ALK mutations and MYCN amplification have been associated with aggressive disease. In this study, we analyzed the efficacy of a Phase Ia-cleared, orally bioavailable dual ALK and focal adhesion kinase (FAK) inhibitor, ESK440, in multiple preclinical NB models. …”
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Impact of bedroom light exposure on glucose metabolic markers and the role of circadian-dependent meal timing: A population-based cross-sectional study by Qi Li, Yu-xiang Xu, Xiu-zhen Lu, Yu-ting Shen, Yu-hui Wan, Pu-yu Su, Fang-biao Tao, Xin Chen, Ying Sun

“…However, little is known about the effects of bedroom LAN exposure on glucose metabolism markers. We aimed to explore the association between intensity and duration of bedroom LAN exposure with glucose metabolism markers, and the role of circadian-dependent meal timing in these associations. …”
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A humanized anti-MSLN×4-1BB bispecific antibody exhibits potent antitumour activity through 4-1BB signaling activation and fc function without systemic toxicity by Da-yan Zhang, Zhi-hua Zhang, Wen-ting Liu, Wei-ming Zhou, Peng-fei Zhou, Juan-juan Wei, Xue-jing Dai, Xiao-li Zeng, Yu-qiong Zhou, Han-wang Li, Heng Zhang, Ao-lin Shen, Lian-sheng Cheng, Guo-dong Shen, Yi-fu He

“…In vivo antitumour activity was assessed by establishing humanized mice bearing human MSLN-expressing MC38 (MC38/hMSLN) or CT26 (CT26/hMSLN) cells, and safety was further evaluated in cynomolgus monkeys. Results We generated two humanized anti-MSLN×4-1BB bsAbs (HK013-G1/G4) by fusing an anti-4-1BB scFv to the C-terminus of an anti-MSLN VHH with an intact Fc fragment from human IgG1 or IgG4. …”
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Neoadjuvant apatinib addition to sintilimab and carboplatin-taxane based chemotherapy in patients with early triple-negative breast cancer: the phase 2 NeoSAC trial by Guoshuang Shen, Zhilin Liu, Miaozhou Wang, Yi Zhao, Xinlan Liu, Yujin Hou, Wenbiao Ma, Jingqi Han, Xiaofeng Zhou, Dengfeng Ren, Fuxing Zhao, Zitao Li, Shifen Huang, Yongzhi Chen, Yingjian He, Yan Liu, Zijun Zhu, Yongxin Li, Jinming Li, Mengting Da, Hongnan Mo, Feng Du, Liang Cui, Jing Bai, Zhen Liu, Fei Ma, Jiuda Zhao

“…Abstract We aimed to evaluate the efficacy and safety of adding apatinib, to sintilimab and chemotherapy in the neoadjuvant treatment of early triple-negative breast cancer (TNBC). …”
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Neurotropic Tick-Borne Flavivirus in Alpine Chamois (<i>Rupicapra rupicapra rupicapra</i>), Austria, 2017, Italy, 2023 by Norbert Nowotny, Maria Lucia Mandola, Isabella Monne, Zoltán Bagó, Chiara Nogarol, Alice Fusaro, Katharina Dimmel, Barbara Moroni, Lisa Guardone, Jolanta Kolodziejek, Elisa Palumbo, Gabriela Stanclova, Adi Steinrigl, Gabriele Fidler, Cristina Bertasio, Irene Bertoletti, Alessandro Bianchi, Mattia Calzolari, Paola Prati, Nadia Vicari, Angela Salomoni, Maria Francesca Priore, Federica Gobbo, Aitor Garcia-Vozmediano, Tom Loney, Ahmad Abou Tayoun, Alawi Alsheikh-Ali, Paola De Benedictis, Jeremy V. Camp, Zdenek Hubalek, Ivo Rudolf, Davide Lelli, Ana Moreno

“…The European subtype of tick-borne encephalitis virus (TBEV-Eur; species <i>Orthoflavivirus encephalitidis</i>, family <i>Flaviviridae</i>) was the only tick-borne flavivirus present in central Europe known to cause neurologic disease in humans and several animal species. Here, we report a tick-borne flavivirus isolated from Alpine chamois (<i>Rupicapra rupicapra rupicapra</i>) with encephalitis and attached ticks, present over a wide area in the Alps. …”
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Biomarkers of pembrolizumab efficacy in advanced anal squamous cell carcinoma: analysis of a phase II clinical trial and a cohort of long-term responders by Jeffrey A Meyerhardt, Sunil Kumar, Jessica A Zerillo, Aparna Parikh, James M Cleary, Scott Rodig, Benjamin Schlechter, Kimmie Ng, Stephanie K Dougan, Nora Horick, Glenn J Hanna, Andrew L Coveler, Anuj K Patel, Nadine J McCleary, Douglas A Rubinson, Jeffrey W Clark, Kent Mouw, Kathleen Pfaff, Thomas A Abrams, Matthew B Yurgelun, Eliezer M Van Allen, S Jennifer Wang, Leah H Biller, Harshabad Singh, Emma L Welsh, Brandon M Huffman, Lestat R Ali, Megan T Hoffman, Katherine A Metayer, Shayla Murray, Alexandra Bird, Jennifer A Chan, Wolfram Goessling, Jeffrey S Wisch, Brendan Reardon, Robert J Mayer, Catherine Del Vecchio Fitz, Charlotte Kuperwasser

“…To characterize the clinical features of long-term responders, we combined data from our prospective trial with a retrospective cohort of patients with anal cancer treated with anti-PD-1 immunotherapy (n=18).Results In the phase II study, the ORR to pembrolizumab monotherapy was 9.4% and the median progression-free survival was 2.2 months. …”
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Quantifying the spatial patterns of retinal ganglion cell loss and progression in optic neuropathy by applying a deep learning variational autoencoder approach to optical coherence... by Jui-Kai Wang, Jui-Kai Wang, Brett A. Johnson, Zhi Chen, Zhi Chen, Honghai Zhang, Honghai Zhang, David Szanto, Brian Woods, Brian Woods, Michael Wall, Young H. Kwon, Young H. Kwon, Edward F. Linton, Edward F. Linton, Andrew Pouw, Mark J. Kupersmith, Mark J. Kupersmith, Mark J. Kupersmith, Mona K. Garvin, Mona K. Garvin, Mona K. Garvin, Mona K. Garvin, Randy H. Kardon, Randy H. Kardon

“…IntroductionGlaucoma, optic neuritis (ON), and non-arteritic anterior ischemic optic neuropathy (NAION) produce distinct patterns of retinal ganglion cell (RGC) damage. We propose a booster Variational Autoencoder (bVAE) to capture spatial variations in RGC loss and generate latent space (LS) montage maps that visualize different degrees and spatial patterns of optic nerve bundle injury. …”
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Risk of aortic aneurysm or dissection following use of fluoroquinolones: a retrospective multinational network cohort studyResearch in context by Jack L. Janetzki, Jung Ho Kim, Evan Minty, Jung Ah Lee, Daniel R. Morales, Rohan Khera, Chungsoo Kim, Thamir M. Alshammari, Scott L. DuVall, Michael E. Matheny, Thomas Falconer, Seonji Kim, Thanh-Phuc Phan, Phung-Anh Nguyen, Min-Huei Hsu, Jason C. Hsu, Rae Woong Park, Kenneth K.C. Man, Sarah Seager, Mui Van Zandt, James P. Gilbert, Patrick B. Ryan, Martijn J. Schuemie, Marc A. Suchard, George Hripcsak, Nicole Pratt, Seng Chan You

“…There was no increased risk of AA/AD associated with FQ compared to TMP or CPH in patients treated for UTI in the outpatient setting. As we only examined FQ used to treat UTIs in the outpatient setting, the results may not be generalisable to other indications with different severity. …”
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Oligodendrocytes drive neuroinflammation and neurodegeneration in Parkinson’s disease via the prosaposin-GPR37-IL-6 axis by Qiang Ma, Jin-Lan Tian, Yao Lou, Ran Guo, Xiao-Ru Ma, Jian-Bin Wu, Jing Yang, Bing-Jie Tang, Shun Li, Mengsheng Qiu, Shumin Duan, Jing-Wei Zhao, Jing Zhang, Zhen-Zhong Xu

“…Recent studies have identified a striking association between oligodendrocytes and PD progression, yet how oligodendrocytes regulate the pathogenesis of PD is still unknown. Here, we show that G-protein-coupled receptor 37 (GPR37) is upregulated in oligodendrocytes of the substantia nigra and that prosaposin (PSAP) secretion is increased in parkinsonian mice. …”
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Climate change rivals fertilizer use in driving soil nitrous oxide emissions in the northern high latitudes: Insights from terrestrial biosphere models by Naiqing Pan, Hanqin Tian, Hao Shi, Shufen Pan, Josep G. Canadell, Jinfeng Chang, Philippe Ciais, Eric A. Davidson, Gustaf Hugelius, Akihiko Ito, Robert B. Jackson, Fortunat Joos, Sebastian Lienert, Dylan B. Millet, Stefan Olin, Prabir K. Patra, Rona L. Thompson, Nicolas Vuichard, Kelley C. Wells, Chris Wilson, Yongfa You, Sönke Zaehle

“…Critically, contributions from soils in the Northern High Latitudes (NHL, >50°N) remain poorly quantified despite their exposure to rapid rates of regional warming and changing hydrology due to climate change. In this study, we used an ensemble of six process-based terrestrial biosphere models (TBMs) from the Global Nitrogen/Nitrous Oxide Model Intercomparison Project (NMIP) to quantify soil N2​O emissions across the NHL during 1861–2016. …”
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Studying the Oncolytic Activity of <i>Streptococcus pyogenes</i> Strains Against Hepatoma, Glioma, and Pancreatic Cancer <i>In Vitro</i> and <i>In Vivo</i> by Anna N. Tsapieva, Alexander N. Chernov, Nadezhda V. Duplik, Anastasiya O. Morozova, Tatiana A. Filatenkova, Mariia A. Suvorova, Elena Egidarova, Elvira S. Galimova, Kseniya Bogatireva, Alexander N. Suvorov

“…Additionally, the <i>S. pyogenes</i> GURSA1 strain did not exhibit cytotoxic activity against healthy skin fibroblast cells (cell viability 104.2 ± 1.3%, <i>p =</i> 0.2542). We demonstrated that tumor treatment with <i>S. pyogenes</i> GURSA1 significantly increased the lifespan of C57BL/6 mice with hepatoma (34 days, <i>p =</i> 0.040) and pancreatic cancer (32 days, <i>p =</i> 0.039) relative to the control groups (24 and 28 days, respectively). …”
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Differentiating the Acceleration Mechanisms in the Slow and Alfvénic Slow Solar Wind by Yeimy J. Rivera, Samuel T. Badman, J. L. Verniero, Tania Varesano, Michael L. Stevens, Julia E. Stawarz, Katharine K. Reeves, Jim M. Raines, John C. Raymond, Christopher J. Owen, Stefano A. Livi, Susan T. Lepri, Enrico Landi, Jasper. S. Halekas, Tamar Ervin, Ryan M. Dewey, Rossana De Marco, Raffaella D’Amicis, Jean-Baptiste Dakeyo, Stuart D. Bale, B. L. Alterman

“…Through a well-timed conjunction between Solar Orbiter and Parker Solar Probe (PSP), we trace the energetics of slow wind to compare with a neighboring Alfvénic slow solar wind stream. …”
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Targeting protein kinase C-α prolongs survival and restores liver function in sepsis: Evidence from preclinical models by Ling Xiong, Dustin Beyer, Na Liu, Tina Lehmann, Sophie Neugebauer, Sascha Schaeuble, Oliver Sommerfeld, Philipp Ernst, Carl-Magnus Svensson, Sandor Nietzsche, Sebastian Scholl, Tony Bruns, Nikolaus Gaßler, Markus H. Gräler, Marc Thilo Figge, Gianni Panagiotou, Michael Bauer, Adrian T. Press

“…Using a preclinical murine sepsis model, we found that both PKCα knockout and the use of a PKCα-inhibitor midostaurin successfully restored liver function without hindering the host’s response or ability to clear the pathogen, highlighting PKCα’s vital role in excretory liver failure. …”
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Synergistical effect of CoIn alloy and oxygen vacancies over Co-In-Zr ternary catalysts boosting CO2 hydrogenation to methanol by Xueyang Jiang, Xiaoshen Li, Shaohui Xiong, Wei Liu, Jiayan Yan, Xiang Duan, Song Song, Qingpeng Cheng, Ye Tian, Xingang Li

“…Unfortunately, how to obtain both high activity and methanol selectivity is still a trade-off challenge for catalyst development. Herein, we synthesize Co-In-Zr ternary metal oxide precursors via a simple hydrothermal method for hydrogenation of CO2 to methanol. …”
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First-in-human dose escalation trial to evaluate the clinical safety and efficacy of an anti-MAGEA1 autologous TCR-transgenic T cell therapy in relapsed and refractory solid tumors by Ignacio I Wistuba, Mamta Kalra, Linus Backert, Martin Wermke, Edwin R Parra, Jason John Luke, Apostolia M Tsimberidou, Sebastian Bunk, Mohammad B Hossain, Andrea Mayer-Mokler, Arun Satelli, Norbert Hilf, Steffen Walter, Cedrik M Britten, Van K Morris, Tobias A W Holderried, Winfried H Alsdorf, Katrin Wetzko, Borje S Andersson, Sandra Grund-Gröschke, Katrin Aslan, Anantha Marisetty, Swapna Satam, Jens Hukelmann, M Alper Kursunel, Karine Pozo, Andreas Acs, Melissa Baumeister, Claudia Wagner, Oliver Schoor, Ali S Mohamed, Delfi Krishna

“…Rationale of the trial Although the use of engineered T cells in cancer immunotherapy has greatly advanced the treatment of hematological malignancies, reaching meaningful clinical responses in the treatment of solid tumors is still challenging. We investigated the safety and tolerability of IMA202 in a first-in-human, dose escalation basket trial in human leucocyte antigen A*02:01 positive patients with melanoma-associated antigen A1 (MAGEA1)-positive advanced solid tumors.Trial design The 2+2 trial design was an algorithmic design based on a maximally acceptable dose-limiting toxicity (DLT) rate of 25% and the sample size was driven by the algorithmic design with a maximum of 16 patients. …”
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Changing Treatment and Metastatic Disease Patterns in Patients with EGFR Mutated NSCLC: An Academic Thoracic Medical Investigator’s Consortium Registry Analysis by Margaret Stalker, MD, Connor B. Grady, MPH, Alex Watts, MS, Wei-Ting Hwang, PhD, Krishna Chandrasekhara, MS, Fangdi Sun, MD, Geoffrey Liu, MD, Devalben Patel, MD, Jorge Nieva, MD, Amanda Herrmann, MD, Kristen Marrone, MD, Vincent K. Lam, MD, Vamsidhar Velcheti, MD, Stephen V. Liu, MD, Gabriela Liliana Bravo Montenegro, MD, William Tompkins, MD, Tejas Patil, MD, Jared Weiss, MD, Kelsey Leigh Miller, MD, William Schwartzman, MD, Jonathan E. Dowell, MD, Khvaramze Shaverdashvili, MD, PhD, Liza Villaruz, MD, Amanda Cass, PharmD, Wade Iams, MD, Dara Aisner, MD, PhD, Charu Aggarwal, MD, MD, D. Ross Camidge, MD, PhD, Lova Sun, MD, Melina E. Marmarelis, MD

“…Introduction: Osimertinib is now a standard first-line (1L) therapy for EGFR-mutated (EGFRm) advanced NSCLC. We aimed to characterize patterns of therapy and longitudinal risk of brain and liver metastasis in a cohort of EGFRm NSCLC. …”
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Type III procollagen peptide level can indicate liver dysfunction associated with volume overload in acute heart failure by Akihiro Shirakabe, Hirotake Okazaki, Masato Matsushita, Yusaku Shibata, Shota Shigihara, Suguru Nishigoori, Tomofumi Sawatani, Nozomi Sasamoto, Kazutaka Kiuchi, Masanori Atsukawa, Norio Itokawa, Taeang Arai, Nobuaki Kobayashi, Kuniya Asai

“…Abstract Aim The role of serum type III procollagen peptide (P3P) level in the acute phase of acute heart failure (AHF) requires clarification. We hypothesized that serum P3P level is temporarily higher during the acute phase, reflecting liver dysfunction due to congestion. …”
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<i>Vismia guianensis</i> Improves Survival of <i>Tenebrio molitor</i> and Mice During Lethal Infection with <i>Candida albicans</i> by Arthur André Castro Costa, Elizangela Pestana Motta, Aluísio Silva Oliveira, Pamela Gomes Santos, Josivan Regis Farias, Danielle Cristine Gomes Franco, Mayara Cristina Pinto Silva, Nicolle Teixeira Barbosa, Simone Batista Muniz, Luís Douglas Miranda. Silva, Lucilene Amorim Silva, Claudia Quintino Rocha, Flavia Raquel Fernandes Nascimento, Rosane Nassar Meireles Guerra

“…To evaluate toxicity, the uninfected larvae were treated with EHVG or anthraquinone. We considered the following groups: the controls received PBS; ANFO B received amphotericin B (600 mg/mL); EHVG received the extract; and ANTQ received anthraquinone. …”
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Exploring the physiological and biochemical mechanisms underlying growth rate variability in Hong Kong oyster (Crassostrea hongkongensis) by Na Hu, Wenhong Li, Pingping He, Pinyuan Wei, Ke Bai, Junliang Guan, Li Zhang, Yongxian Chen, Wei Li, Yusi Zheng, Qingsong He, Longcheng Liu, Xingzhi Zhang, Jinxia Peng

“…The Hong Kong oyster (Crassostrea hongkongensis), a key aquaculture species in southern China, has significant potential for enhancing profitability through increased growth rate. In this study, we examined the physiological and biochemical characteristics of the large-size (SL) and small-size (SS) from the selected strain, as well as the large-size (CL) and small-size (CS) from the wild population. …”
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Distinct clinical outcomes based on multiple serum cytokine and chemokine profiles rather than autoantibody profiles and ultrasound findings in rheumatoid arthritis: a prospective... by Yukitaka Ueki, Tom W J Huizinga, René E M Toes, Shoichi Fukui, Tomoki Origuchi, Takahiro Maeda, Atsushi Kawakami, Tomohiro Koga, Naoki Matsuoka, Toshihiko Hidaka, Naoki Iwamoto, Mami Tamai, Shin-ya Kawashiri, Akitomo Okada, Ayako Nishino, Tamami Yoshitama, Takahisa Suzuki, Toshimasa Shimizu, Shimpei Morimoto, Tomomi Tsuru, Karin A J van Schie, Masahiro Ayano, Remi Sumiyoshi, Yushiro Endo, Tohru Michitsuji, Kaori Furukawa, Masataka Umeda, Nobutaka Eiraku, Hiroaki Hamada

“…Objectives To evaluate the potential of clinical factors, ultrasound findings, serum autoantibodies, and serum cytokine and chemokine profiles as predictors of clinical outcomes in rheumatoid arthritis (RA).Patients and methods We included 200 patients with RA treated with biological and targeted synthetic disease-modifying antirheumatic drugs in a prospective multicentre ultrasound cohort study. …”
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