Clinical and molecular outcomes from the 5-Year natural history study of SSADH Deficiency, a model metabolic neurodevelopmental disorder by Itay Tokatly Latzer, Jean-Baptiste Roullet, Wardiya Afshar-Saber, Henry H. C. Lee, Mariarita Bertoldi, Gabrielle E. McGinty, Melissa L. DiBacco, Erland Arning, Melissa Tsuboyama, Alexander Rotenberg, Thomas Opladen, Kathrin Jeltsch, Àngels García-Cazorla, Natalia Juliá-Palacios, K. Michael Gibson, Mustafa Sahin, Phillip L. Pearl

“…Autism, epilepsy, movement disorders, sleep disturbances, and various psychiatric behaviors constituted the core of the disorder’s clinical phenotype. Lower clinical severity scores, indicating worst severity, coincided with older age (R= -0.302, p = 0.03), as well as age-adjusted lower values of plasma γ-aminobutyrate (GABA) (R = 0.337, p = 0.02) and γ-hydroxybutyrate (GHB) (R = 0.360, p = 0.05). …”
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Impact of Ketogenic and Mediterranean Diets on Gut Microbiota Profile and Clinical Outcomes in Drug-Naïve Patients with Diabesity: A 12-Month Pilot Study by Vanessa Palmas, Andrea Deledda, Vitor Heidrich, Giuseppina Sanna, Giulia Cambarau, Michele Fosci, Lorenzo Puglia, Enrico Antonio Cappai, Alessio Lai, Andrea Loviselli, Aldo Manzin, Fernanda Velluzzi

“…The VLCKD-MD had a more beneficial impact than the MD on the GM phenotype. A substantial positive modulatory effect was observed especially up to the sixth month of the NI in KETO due to the progressive increase in bacterial markers of human health. …”
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RECQL4 affects MHC class II‐mediated signalling and favours an immune‐evasive signature that limits response to immune checkpoint inhibitor therapy in patients with malignant melan... by Sara Egea‐Rodriguez, Renáta Váraljai, Thierry M. Nordmann, Restuan Lubis, Manuel Philip, Florian Rambow, Alexander Roesch, Michael Flaig, Susanne Horn, Raphael Stoll, Fang Zhao, Annette Paschen, Bert Klebl, Ian D. Hickson, Dirk Schadendorf, Matthias Mann, Iris Helfrich

“…RECQL4 favours an immune‐evasive phenotype by downregulating major histocompatibility complex class II molecules.…”
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First-in-human phase I trial of the bispecific CD47 inhibitor and CD40 agonist Fc-fusion protein, SL-172154 in patients with platinum-resistant ovarian cancer by Lini Pandite, Simon Metenou, Debra L Richardson, Erika Hamilton, Linda Van Le, Bo Ma, Fatima Rangwala, Nehal J Lakhani, Justin Call, Daphne Stewart, Lauren E Dockery, Guanfang Wang, Jade Huguet, Elliot Offman

“…Paired tumor biopsies demonstrated a shift in macrophages from an M2- to an M1-dominant phenotype and increased infiltration of CD8 T cells. …”
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Epidemiological evidence for a hereditary contribution to myasthenia gravis: a retrospective cohort study of patients from North America by Joel Oger, Joshua D Green, Bryan J Traynor, Richard J Barohn, Michael Benatar, Emanuela Bartoccion, Derrick Blackmore, Vinay Chaudhry, Manisha Chopra, Andrea Corse, Mazen M Dimachkie, Amelia Evoli, Julaine Florence, Miriam Freimer, James F Howard, Theresa Jiwa, Henry J Kaminski, John T Kissel, Wilma J Koopman, Bernadette Lipscomb, Michelanglo Maestri, Mariapaola Marino, Janice M Massey, April McVey, Michelle M Mezei, Srikanth Muppidi, Michael W Nicolle, Robert M Pascuzzi, Mamatha Pasnoor, Alan Pestronk, Carlo Provenzano, Roberta Ricciardi, David P Richman, Julie Rowin, Donald B Sanders, Zaeem Siddiqi, Aimee Soloway, Gil I Wolfe, Charlie Wulf, Daniel B Drachman

“…Objectives To approximate the rate of familial myasthenia gravis and the coexistence of other autoimmune disorders in the patients and their families.Design Retrospective cohort study.Setting Clinics across North America.Participants The study included 1032 patients diagnosed with acetylcholine receptor antibody (AChR)-positive myasthenia gravis.Methods Phenotype information of 1032 patients diagnosed with AChR-positive myasthenia gravis was obtained from clinics at 14 centres across North America between January 2010 and January 2011. …”
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Revealing the biological features of the axolotl pancreas as a new research model by Hui Ma, Hui Ma, Hui Ma, Guangcong Peng, Yan Hu, Binbin Lu, Binbin Lu, Yiying Zheng, Yingxian Wu, Weimin Feng, Yu Shi, Xiangyu Pan, Li Song, Ina Stützer, Yanmei Liu, Jifeng Fei, Jifeng Fei, Jifeng Fei

“…The mutation of Pdx1 resulted in hyperglycemia and a significant reduction in pancreatic cell mass, including a complete loss of endocrine cells, although it did not lead to a lethal phenotype.DiscussionThis study examines the axolotl pancreas, highlighting the conservation of pancreatic development. …”
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A genomic duplication spanning multiple P450s contributes to insecticide resistance in the dengue mosquito Aedes aegypti by Bacot, Tiphaine, Haberkorn, Chloe, Guilliet, Joseph, Cattel, Julien, Kefi, Mary, Nadalin, Louis, Filee, Jonathan, Boyer, Frederic, Gaude, Thierry, Laporte, Frederic, Tutagata, Jordan, Vontas, John, Dusfour, Isabelle, Bonneville, Jean-Marc, David, Jean-Philippe

“…The involvement of this P450 duplication in deltamethrin survival was supported by a significant phenotypic response to the P450 inhibitor piperonyl butoxide together with genotype-phenotype association and RNA interference. …”
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Molecular assessment of splicing variants in a cohort of patients with inborn errors of immunity: methodological approach and interpretation remarks by Laura Miguel Berenguel, Carla Gianelli, Carla Gianelli, Carla Gianelli, Elisabet Matas Pérez, Teresa del Rosal, Ana Méndez Echevarría, Ángel Robles Marhuenda, Marta Feito Rodríguez, Maria Teresa Caballero Molina, Maria Teresa Caballero Molina, Lorena Magallares García, Brenda Sánchez Garrido, Samantha Hita Díaz, Luis Allende Martínez, Luis Allende Martínez, Pilar Nozal Aranda, Pilar Nozal Aranda, Pilar Nozal Aranda, Carmen Cámara Hijón, Carmen Cámara Hijón, Carmen Cámara Hijón, Eduardo López Granados, Eduardo López Granados, Eduardo López Granados, Rebeca Rodríguez Pena, Rebeca Rodríguez Pena, Rebeca Rodríguez Pena, María Bravo García-Morato, María Bravo García-Morato, María Bravo García-Morato

“…Molecular validation was required only in the cases of genes of uncertain significance (GUS), high homology pseudogenes or incompatible clinical phenotype. Seven patients showed variants outside canonical positions. …”
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MSCs Contribute to the Conversion of Ly6Chigh Monocytes into Ly6Clow Subsets under AMI by Wenbin Lu, Genshan Ma, Zulong Sheng, Qingjie Wang, Lijuan Chen, Junhua Qi, Ronghui Shi, Jingjing Ji, Zhenjun Ji, Qiming Dai

“…NR4A1 is a novel target for modulating the inflammatory phenotype of monocytes during atherogenesis. Objectives. …”
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Brief Report: Clinical Characteristics and Outcomes of Patients With Thoracic SMARCA4-Deficient Undifferentiated Tumors by Alissa J. Cooper, MD, Andrea Arfe, PhD, Biagio Ricciuti, MD, Andréanne Gagné, MD, PhD, Lynette M. Sholl, MD, Alessandro Di Federico, MD, Mark M. Awad, MD, PhD, Mihaela Aldea, MD, PhD, Maria Rosa Ghigna, MD, Miruna Grecea, MD, Phoebe Clark, MS, Jamie E. Chaft, MD, Mark G. Kris, MD, Gregory J. Riely, MD, Charles M. Rudin, MD, PhD, Ibiayi Dagogo-Jack, MD, Mari Mino-Kenudson, MD, Lingzhi Hong, MD, PhD, Neda Kalhor, MD, Natalie Vokes, MD, Anita Bowman, MS, Soo-Ryum Yang, MD, Natasha Rekhtman, MD, PhD, Adam J. Schoenfeld, MD

“…Methods: We collected clinical, pathologic, and demographic variables from five institutions for patients whose tumors met criteria for SMARCA4-UTs (undifferentiated phenotype and loss of SMARCA4 (BRG1) by immunohistochemistry). …”
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Retinoblastoma-binding Protein 9 Suppresses Intestinal Inflammation and Inflammation-induced Tumorigenesis in MiceSummary by Kensuke Hamada, Yuki Nakanishi, Yu Muta, Mayuki Omatsu, Kosuke Iwane, Munehiro Ikeda, Jiayu Chen, Yoko Masui, Naoki Aoyama, Nobukazu Agatsuma, Go Yamakawa, Takahiro Utsumi, Hiroki Kitamoto, Makoto Okabe, Yoshiro Itatani, Takumi Adachi, Koubun Yasuda, Shuji Yamamoto, Akihisa Fukuda, Etsushi Kuroda, Masaki Ohmuraya, Kazutaka Obama, Seiichi Hirota, Hiroki Ikeuchi, Kenji Nakanishi, Hiroshi Seno

“…RNA sequencing was analyzed to identify the phenotype alternation upon Rbbp9 deletion. In addition, genetic and pharmacological inhibition of the Janus kinase (JAK)/signal transducer and activator of transcription 1 (STAT1) pathway was performed. …”
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Image Segmentation Method of Chinese Yam Leaves in Complex Background Based on Improved ENet by LU Bibo, LIANG Di, YANG Jie, SONG Aiqing, HUANGFU Shangwei

“…[Conclusions]The improved algorithm can accurately and quickly segment Chinese yam leaves, providing not only a more accurate means for determining Chinese yam phenotype data, but also a new method and approach for embedded research of Chinese yam. …”
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Dynamic conditioning of porcine kidney grafts with extracellular vesicles derived from urine progenitor cells: A proof‐of‐concept study by Perrine Burdeyron, Sébastien Giraud, Maryne Lepoittevin, Nina Jordan, Sonia Brishoual, Maïté Jacquard, Virginie Ameteau, Nadège Boildieu, Estelle Lemarie, Jonathan Daniel, Frédéric Martins, Nicolas Mélis, Marine Coué, Raphaël Thuillier, Henri Leuvenink, Luc Pellerin, Thierry Hauet, Clara Steichen

“…Porcine UPCs were successfully isolated from urine and fully characterized as well as their EVs which were found of expected size/phenotype. EVs injection during HMP alone, NMP alone, or both was feasible and safe and did not impact perfusion parameters. …”
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Single cell profiling of circulating autoreactive CD4 T cells from patients with autoimmune liver diseases suggests tissue imprinting by Anaïs Cardon, Thomas Guinebretière, Chuang Dong, Laurine Gil, Sakina Ado, Pierre-jean Gavlovsky, Martin Braud, Richard Danger, Christoph Schultheiß, Aurélie Doméné, Perrine Paul-Gilloteaux, Caroline Chevalier, Laura Bernier, Jean-Paul Judor, Cynthia Fourgeux, Astrid Imbert, Marion Khaldi, Edouard Bardou-Jacquet, Laure Elkrief, Adrien Lannes, Christine Silvain, Matthieu Schnee, Florence Tanne, Fabienne Vavasseur, Lucas Brusselle, Sophie Brouard, William W. Kwok, Jean-François Mosnier, Ansgar W. Lohse, Jeremie Poschmann, Mascha Binder, Jérôme Gournay, Sophie Conchon, Pierre Milpied, Amédée Renand

“…Using a mouse model, we demonstrate that, following antigen recognition in the liver, CD4 T cells acquire an exhausted phenotype, play a crucial role in liver damage, and are controlled by immune checkpoint pathways. …”
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Podophyllotoxin mediates hepatic toxicity via the C5a/C5aR/ROS/NLRP3 and cGMP/PKG/mTOR axis in rats based on toxicological evidence chain (TEC) concept by phosphoproteomic analysis by Chuanxin Liu, Xiaobin Huang, Jiao Kong, Xuejiao Li, Yuming Wang, Fangfang Zhang, Jiajia Duan

“…This approach involves a tiered search for evidence of Harmful Ingredients Evidence (HIE), Injury Phenotype Evidence (IPE), Adverse Outcomes Evidence (AOE), and Toxic Events Evidence (TEE) during the development of PPT-induced hepatotoxicity, thereby constructing a guiding toxicology evidence chain. …”
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Genome data based deep learning identified new genes predicting pharmacological treatment response of attention deficit hyperactivity disorder by Yilu Zhao, Zhao Fu, Eric J. Barnett, Ning Wang, Kangfuxi Zhang, Xuping Gao, Xiangyu Zheng, Junbin Tian, Hui Zhang, XueTong Ding, Shaoxian Li, Shuyu Li, Qingjiu Cao, Suhua Chang, Yufeng Wang, Stephen V. Faraone, Li Yang

“…Based on genotype data of medication-naïve patients with ADHD who received pharmacological treatments for 12 weeks, the current study performed GWAS using the percentage changes in ADHD-RS score as phenotype. Then, DL models were constructed to predict percentage changes in symptom scores using genetic variants selected based on four different genome-wide P thresholds (E-02, E-03, E-04, E-05) as inputs. …”
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Paracrine role of endothelial IGF-1 receptor in depot-specific adipose tissue adaptation in male mice by Cheukyau Luk, Katherine I. Bridge, Nele Warmke, Katie J. Simmons, Michael Drozd, Amy Moran, Amanda D. V. MacCannell, Chew W. Cheng, Sam Straw, Jason L. Scragg, Jessica Smith, Claire H. Ozber, Chloe G. Wilkinson, Anna Skromna, Natallia Makava, Hiran A. Prag, T. Simon Futers, Oliver I. Brown, Alexander-Francisco Bruns, Andrew MN Walker, Nicole T. Watt, Romana Mughal, Kathryn J. Griffin, Nadira Y. Yuldasheva, Sunti Limumpornpetch, Hema Viswambharan, Piruthivi Sukumar, David J. Beech, Antonio Vidal-Puig, Klaus K. Witte, Michael P. Murphy, Richard C. Hartley, Stephen B. Wheatcroft, Richard M. Cubbon, Lee D. Roberts, Mark T. Kearney, Natalie J. Haywood

“…We explore the role of endothelial insulin-like growth factor-1 receptor (IGF-1R), as a paracrine modulator of white adipose phenotype. We show that a reduction in endothelial IGF-1R expression in the presence of high-fat feeding in male mice leads to depot-specific beneficial white adipose tissue remodelling, increases whole-body energy expenditure and enhances insulin sensitivity via a non-cell-autonomous paracrine mechanism. …”
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Molecular underpinnings of exceptional response in primary malignant melanoma of the esophagus to anti-PD-1 monotherapy by Yu Chen, Xuan Wang, Jie Dai, Li Zhou, Xuefeng Xia, Jun Guo, Xue Bai, Lu Si, Bixia Tang, Chuanliang Cui, Xiaoting Wei, Xinan Sheng, Siming Li, Zhihong Chi, Lili Mao, Bin Lian, Xieqiao Yan, Yan Kong, Caili Li, Xuan Gao, Lirui Tang, Linzi Sun, Zhonghui Qi, Zelong Xu

“…The multiplex immunohistochemical analysis also demonstrated higher CD8+ T-cell infiltration in PMME than in NEMM.Conclusions PMME is an outlier of mucosal melanoma showing a malicious phenotype but a particularly high response rate to ICB because of its distinct molecular characteristics. …”
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Genomic deletions on 16p11.2 associated with severe obesity in Brazil by Izadora Sthephanie da Silva Assis, Izadora Sthephanie da Silva Assis, Kaio Cezar Rodrigues Salum, Kaio Cezar Rodrigues Salum, Kaio Cezar Rodrigues Salum, Rafaela de Freitas Martins Felício, Lohanna Palhinha, Gabriella de Medeiros Abreu, Gabriella de Medeiros Abreu, Tamara Silva, Fernanda Cristina Carvalho Mattos, Eliane Lopes Rosado, Verônica Marques Zembrzuski, Mario Campos Junior, Clarissa Menezes Maya-Monteiro, Pedro Hernán Cabello, João Regis Ivar Carneiro, Patrícia Torres Bozza, Ana Carolina Proença da Fonseca, Ana Carolina Proença da Fonseca, Ana Carolina Proença da Fonseca, Ana Carolina Proença da Fonseca

“…Thus, this study aimed to identify deleterious copy number variations (CNVs) linked to obesity and explore the clinical phenotypes.MethodThe sample comprised 195 adults with severe obesity (BMI≥35kg/m2) who developed this phenotype during childhood or adolescence. …”
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SECTM1 acts as an immune-related biomarker of poor prognosis and promotes cancer progression by modulating M2 macrophage polarization in esophageal squamous cell carcinoma by Pengzhou Kong, Pengzhou Kong, Pengzhou Kong, Ye Jiao, Ye Jiao, Meng Sun, Meng Sun, Zhinan Zhou, Zhinan Zhou, Yingying Zhang, Yingying Zhang, Xin Yang, Xin Yang, Jing Ren, Jing Ren, Mengyuan Yang, Mengyuan Yang, Yanyan Dong, Yanyan Dong, Yanyan Dong, Bin Song

“…Furthermore, its overexpression promoted macrophage polarization towards the M2-like phenotype and promoted the migration of M2-like macrophage cells and C-C Motif Chemokine Ligand 5 (CCL5) was the key mediator in the pro-cancer effect of SECTM1. …”
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