Identification of Quorum-Sensing Inhibitors Disrupting Signaling between Rgg and Short Hydrophobic Peptides in Streptococci by Chaitanya Aggarwal, Juan Cristobal Jimenez, Hyun Lee, George E. Chlipala, Kiira Ratia, Michael J. Federle

“…The best hits were found to bind Rgg3 in vitro with submicromolar affinities, to specifically abolish transcription of Rgg2/3-controlled genes, and to prevent biofilm development in S. pyogenes without affecting bacterial growth. Furthermore, the top hit, cyclosporine A, as well as its nonimmunosuppressive analog, valspodar, inhibited Rgg-SHP pathways in multiple species of Streptococcus. …”
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Flubendazole inhibits PD-1 and suppresses melanoma growth in immunocompetent mice by Yue Li, Ben Wu, Md Jakir Hossain, Lily Quagliata, Connor O’Meara, Marc R. Wilkins, Susan Corley, Levon M. Khachigian

“…KEGG pathway analysis showed FLU up-regulated genes over-represented in multiple pathways (p < 0.01), the top hit being amoebiasis. FLU also affected the expression of genes in cancer-associated pathways, both through down-regulation and up-regulation. …”
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A Genome-Wide CRISPR/Cas9 Screen Reveals the Requirement of Host Sphingomyelin Synthase 1 for Infection with Pseudorabies Virus Mutant gD^–Pass by Julia E. Hölper, Finn Grey, John Kenneth Baillie, Tim Regan, Nicholas J. Parkinson, Dirk Höper, Thiprampai Thamamongood, Martin Schwemmle, Katrin Pannhorst, Lisa Wendt, Thomas C. Mettenleiter, Barbara G. Klupp

“…In these cells, sphingomyelin synthase 1 (SMS1) was identified as the top hit candidate. Infection efficiency was reduced by up to 90% for PrV-gD^–Pass in rabbit RK13-sgms1_KO cells compared to wildtype cells accompanied by lower viral progeny titers. …”
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Integrative analysis of therapy resistance and transcriptomic profiling data in glioblastoma cells identifies sensitization vulnerabilities for combined modality radiochemotherapy by Leon Emanuel Schnöller, Valerie Albrecht, Nikko Brix, Alexander Edward Nieto, Daniel Felix Fleischmann, Maximilian Niyazi, Julia Hess, Claus Belka, Kristian Unger, Kirsten Lauber, Michael Orth

“…Resistance scores were extracted by dimensionality reduction and subjected to correlation analyses with the mRNA expression data. Top-hit candidates with positive correlation coefficients were validated by pharmacological inhibition in clonogenic survival assays and DNA repair analyses via residual γH2AX/53BP1-foci staining. …”
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FRMD8 is a novel regulator of iRhom-dependent ADAM17 activity by Künzel, U

“…</p> <p>I developed a mass spectrometry-based screen to identify new binding partners of human iRhoms using co-immunoprecipitation. The top hit of the screen was the poorly characterised FERM domain-containing protein 8 (FRMD8), which binds to both iRhom1 and iRhom2. …”

High-Throughput RNA Sequencing Analysis of Plasma Samples Reveals Circulating microRNA Signatures with Biomarker Potential in Dengue Disease Progression by Jaya Saini, Bhaswati Bandyopadhyay, Abhay Deep Pandey, V. G. Ramachandran, Shukla Das, Vikas Sood, Arup Banerjee, Sudhanshu Vrati

“…To understand the abundance and specificity of the DEMs in the context of dengue infection and disease progression, eight top-hit DEMs were further validated in the dengue virus-infected cell lines as well as in the patient’s plasma and peripheral blood mononuclear cells (PBMCs) using the quantitative reverse transcription-PCR (qRT‐PCR) method. …”
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Comparative Loss-of-Function Screens Reveal ABCE1 as an Essential Cellular Host Factor for Efficient Translation of <italic toggle="yes">Paramyxoviridae</italic> and <italic toggle... by Danielle E. Anderson, Kristin Pfeffermann, So Young Kim, Bevan Sawatsky, James Pearson, Mikhail Kovtun, David L. Corcoran, Yvonne Krebs, Kristmundur Sigmundsson, Sharon F. Jamison, Zhen Zhen Joanna Yeo, Linda J. Rennick, Lin-Fa Wang, Pierre J. Talbot, W. Paul Duprex, Mariano A. Garcia-Blanco, Veronika von Messling

“…In comparative genome-scale siRNA screens with wild-type-derived measles, mumps, and respiratory syncytial viruses in A549 cells, a human lung adenocarcinoma cell line, we identified vesicular transport, RNA processing pathways, and translation as the top pathways required by all three viruses. As the top hit in the translation pathway, ABCE1, a member of the ATP-binding cassette transporters, was chosen for further study. …”
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In silico identification of potential PvFKBP35 inhibitors from Entadrophragma angolense Limonoids extracts as antimalarial agents by Latif Adams, Abdul Rashid Issahaku, Clement Agoni, Michael Afiadenyo, Kwadwo Asamoah Kusi, Siobhan Moane, Dorcas Obiri -Yeboah, Michelle McKeon-Bennett

“…Sixteen [16] Limonoids extracted from the bark of the stem of Entadrophragma angolense were virtually screened against PvFKPB35. The top hit compounds were subjected to 500 ns Molecular Dynamics simulation and Molecular Mechanics – Poisson Boltzmann Surface Area calculations to examine their stability and free binding energy. …”
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PPARG dysregulation as a potential molecular target in adrenal Cushing's syndrome by Sharmilee Vetrivel, Mariangela Tamburello, Mariangela Tamburello, Andrea Oßwald, Ru Zhang, Ali Khan, Sara Jung, Jessica E. Baker, William E. Rainey, Elisabeth Nowak, Barbara Altieri, Mario Detomas, Deepika Watts, Tracy Ann Williams, Ben Wielockx, Felix Beuschlein, Felix Beuschlein, Martin Reincke, Silviu Sbiera, Anna Riester

“…In vivo findings were further characterized using three adrenocortical cell-lines (NCI-H295R, CU-ACC2, MUC1).ResultsPathway mapping based on significant expression patterns identified PPARG (peroxisome proliferator-activated receptor gamma) pathway as the top hit. Quantitative PCR (QPCR) confirmed that PPARG (l2fc&lt;-1.5) and related genes – FABP4 (l2fc&lt;-5.5), PLIN1 (l2fc&lt;-4.1) and ADIPOQ (l2fc&lt;-3.3) – were significantly downregulated (p&lt;0.005) in PBMAH. …”
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A microRNA panel that regulates proinflammatory cytokines as diagnostic and prognosis biomarkers in colon cancer by Antonio Martínez-Gutierrez, Berenice Carbajal-Lopez, Triet M. Bui, Monica Mendoza-Rodriguez, Alma D. Campos-Parra, Germán Calderillo-Ruiz, David Cantú-De Leon, Eduardo-Osiris Madrigal-Santillán, Ronen Sumagin, Carlos Pérez-Plasencia, Eloy-Andrés Pérez-Yépez

“…An inflammation associated-miRNA panel composed of 11-miRNAs was found to be overexpressed in CC but not in inflamed or normal tissues (miR-21-5p, miR-304-5p, miR-577, miR-335-5p, miR-21-3p, miR-27b-5p, miR-335-3p, miR-215-5p, miR-30b-5p, miR-192-5p, miR-3065-5p). The association of top hit miRNAs, miR-3065-5p and miR-30b-5p expression with overall survival of CC patients was demonstrated using Kaplan-Meier tests. …”
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Imaging-Based Screen Identifies Laminin 411 as a Physiologically Relevant Niche Factor with Importance for i-Hep Applications by John Ong, Maria Paola Serra, Joe Segal, Ana-Maria Cujba, Soon Seng Ng, Richard Butler, Val Millar, Stephanie Hatch, Salman Zimri, Hiroyuki Koike, Karen Chan, Andrew Bonham, Michelle Walk, Ty Voss, Nigel Heaton, Ragai Mitry, Anil Dhawan, Daniel Ebner, Davide Danovi, Hiromitsu Nakauchi, S. Tamir Rashid

“…The HLI was then applied in a targeted screen of extracellular niche factors to identify substrates driving i-Heps closer to the standard. Laminin 411, the top hit, was validated in two additional induced pluripotent stem cell (iPSC) lines, primary tissue, and an in vitro model of α1-antitrypsin deficiency. …”
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Sulfatase modifying factor 1 (SUMF1) is associated with Chronic Obstructive Pulmonary Disease by Julie Weidner, Linnea Jarenbäck, Kim de Jong, Judith M. Vonk, Maarten van den Berge, Corry-Anke Brandsma, H. Marike Boezen, Don Sin, Yohan Bossé, David Nickle, Jaro Ankerst, Leif Bjermer, Dirkje S. Postma, Alen Faiz, Ellen Tufvesson

“…We found alterations in mRNA expression in sputum cells and lung fibroblasts associated with SNP rs11915920 (top hit in eQTL), which validated the results of the lung tissue eQTL analysis. …”
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Anti‐Coronaviral Nanocluster Restrain Infections of SARS‐CoV‐2 and Associated Mutants through Virucidal Inhibition and 3CL Protease Inactivation by Hao Tang, Hongbo Qin, Shiting He, Qizhen Li, Huan Xu, Mengsi Sun, Jiaan Li, Shanshan Lu, Shengdong Luo, Panyong Mao, Pengjun Han, Lihua Song, Yigang Tong, Huahao Fan, Xingyu Jiang

“…Thus, a library of nanomaterials on GX_P2V, a SARS‐CoV‐2‐like coronavirus of pangolin origin, is screened and a surface‐functionalized gold nanocluster (TMA‐GNC) is identified as the top hit. TMA‐GNC inhibits transcription‐ and replication‐competent SARS‐CoV‐2 virus‐like particles and all tested pseudoviruses of SARS‐CoV‐2 variants. …”
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MassGenie: A Transformer-Based Deep Learning Method for Identifying Small Molecules from Their Mass Spectra by Aditya Divyakant Shrivastava, Neil Swainston, Soumitra Samanta, Ivayla Roberts, Marina Wright Muelas, Douglas B. Kell

“…We also use VAE-Sim, a previously published variational autoencoder, to generate candidate molecules that are ‘similar’ to the top hit. In addition to using the ‘top hits’ directly, we can produce a rank order of these by ‘round-tripping’ candidate molecules and comparing them with the true molecules, where known. …”
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Deciphering Genetic Susceptibility to Tuberculous Meningitis by Haiko Schurz, Brigitte Glanzmann, Brigitte Glanzmann, Nicholas Bowker, Ronald van Toorn, Regan Solomons, Johan Schoeman, Paul D. van Helden, Craig J. Kinnear, Craig J. Kinnear, Eileen G. Hoal, Marlo Möller, Marlo Möller

“…In addition, several top-hit genes ascribed to the development of the central nervous system (CNS) and innate immune system regulation were identified. …”
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Signature of miRNAs derived from the circulating exosomes of patients with amyotrophic lateral sclerosis by Yang-Fan Cheng, Yang-Fan Cheng, Xiao-Jing Gu, Xiao-Jing Gu, Tian-Mi Yang, Qian-Qian Wei, Bei Cao, Yang Zhang, Hui-Fang Shang, Hui-Fang Shang, Yong-Ping Chen, Yong-Ping Chen

“…Of these, 11 overlapping dysregulated miRNAs were identified in both groups. Among the 14 top-hit candidate miRNAs validated by RT-qPCR, hsa-miR-34a-3p was specifically downregulated in patients with SOD1-mutated ALS, while hsa-miR-1306-3p was downregulated in ALS patients with both SOD1 and C9orf72 mutations. …”
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Terminology versus action (Editorial) by Lindsay Glynn

“…A final search for evidence based information had this journal as the top hit. Being a busy librarian with a lot of work to do, I stopped right there. …”
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UGDH promotes tumor-initiating cells and a fibroinflammatory tumor microenvironment in ovarian cancer by Brittney S. Harrington, Rahul Kamdar, Franklin Ning, Soumya Korrapati, Michael W. Caminear, Lidia F. Hernandez, Donna Butcher, Elijah F. Edmondson, Nadia Traficante, Joy Hendley, Australian Ovarian Cancer Study, Madeline Gough, Rebecca Rogers, Rohan Lourie, Jyoti Shetty, Bao Tran, Fathi Elloumi, Abdalla Abdelmaksoud, Madhu Lal Nag, Krystyna Mazan-Mamczarz, Carrie D. House, John D. Hooper, Christina M. Annunziata

“…To target TICs to prevent recurrence, we identified genes critical for TIC viability from a whole genome siRNA screen. A top hit was the cancer-associated, proteoglycan subunit synthesis enzyme UDP-glucose dehydrogenase (UGDH). …”
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In-silico studies to recognize repurposing therapeutics toward arginase-I inhibitors as a potential onco-immunomodulators by Magdi E. A. Zaki, Sami A. Al-Hussain, Aamal A. Al-Mutairi, Abdul Samad, Arabinda Ghosh, Somdatta Chaudhari, Pravin N. Khatale, Prashant Ajmire, Rahul D. Jawarkar

“…As shown in the Williams plot, the top hit molecule, ZINC000252286875, has a low leverage value of HAT i/i h* = 0.140, placing it towards the boundary of the usable range. …”
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Chlorambucil targets BRCA1/2‐deficient tumours and counteracts PARP inhibitor resistance by Eliana MC Tacconi, Sophie Badie, Giuliana De Gregoriis, Timo Reisländer, Xianning Lai, Manuela Porru, Cecilia Folio, John Moore, Arnaud Kopp, Júlia Baguña Torres, Deborah Sneddon, Marcus Green, Simon Dedic, Jonathan W Lee, Ankita Sati Batra, Oscar M Rueda, Alejandra Bruna, Carlo Leonetti, Carlos Caldas, Bart Cornelissen, Laurent Brino, Anderson Ryan, Annamaria Biroccio, Madalena Tarsounas

“…To identify drugs that target specifically BRCA2‐deficient cells, we screened a chemical library containing compounds in clinical use. The top hit was chlorambucil, a bifunctional alkylating agent used for the treatment of chronic lymphocytic leukaemia (CLL). …”
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