journal
https://read.qxmd.com/read/38760587/prediction-of-dna-methylation-based-tumor-types-from-histopathology-in-central-nervous-system-tumors-with-deep-learning
#21
JOURNAL ARTICLE
Danh-Tai Hoang, Eldad D Shulman, Rust Turakulov, Zied Abdullaev, Omkar Singh, Emma M Campagnolo, H Lalchungnunga, Eric A Stone, MacLean P Nasrallah, Eytan Ruppin, Kenneth Aldape
Precision in the diagnosis of diverse central nervous system (CNS) tumor types is crucial for optimal treatment. DNA methylation profiles, which capture the methylation status of thousands of individual CpG sites, are state-of-the-art data-driven means to enhance diagnostic accuracy but are also time consuming and not widely available. Here, to address these limitations, we developed Deep lEarning from histoPathoLOgy and methYlation (DEPLOY), a deep learning model that classifies CNS tumors to ten major categories from histopathology...
May 17, 2024: Nature Medicine
https://read.qxmd.com/read/38760586/integrative-multi-omics-profiling-in-human-decedents-receiving-pig-heart-xenografts
#22
JOURNAL ARTICLE
Eloi Schmauch, Brian Piening, Maedeh Mohebnasab, Bo Xia, Chenchen Zhu, Jeffrey Stern, Weimin Zhang, Alexa K Dowdell, Jacqueline I Kim, David Andrijevic, Karen Khalil, Ian S Jaffe, Bao-Li Loza, Loren Gragert, Brendan R Camellato, Michelli F Oliveira, Darragh P O'Brien, Han M Chen, Elaina Weldon, Hui Gao, Divya Gandla, Andrew Chang, Riyana Bhatt, Sarah Gao, Xiangping Lin, Kriyana P Reddy, Larisa Kagermazova, Alawi H Habara, Sophie Widawsky, Feng-Xia Liang, Joseph Sall, Alexandre Loupy, Adriana Heguy, Sarah E B Taylor, Yinan Zhu, Basil Michael, Lihua Jiang, Ruiqi Jian, Anita S Chong, Robert L Fairchild, Suvi Linna-Kuosmanen, Minna U Kaikkonen, Vasishta Tatapudi, Marc Lorber, David Ayares, Massimo Mangiola, Navneet Narula, Nader Moazami, Harvey Pass, Ramin S Herati, Adam Griesemer, Manolis Kellis, Michael P Snyder, Robert A Montgomery, Jef D Boeke, Brendan J Keating
In a previous study, heart xenografts from 10-gene-edited pigs transplanted into two human decedents did not show evidence of acute-onset cellular- or antibody-mediated rejection. Here, to better understand the detailed molecular landscape following xenotransplantation, we carried out bulk and single-cell transcriptomics, lipidomics, proteomics and metabolomics on blood samples obtained from the transplanted decedents every 6 h, as well as histological and transcriptomic tissue profiling. We observed substantial early immune responses in peripheral blood mononuclear cells and xenograft tissue obtained from decedent 1 (male), associated with downstream T cell and natural killer cell activity...
May 17, 2024: Nature Medicine
https://read.qxmd.com/read/38760585/a-prognostic-neural-epigenetic-signature-in-high-grade-glioma
#23
JOURNAL ARTICLE
Richard Drexler, Robin Khatri, Thomas Sauvigny, Malte Mohme, Cecile L Maire, Alice Ryba, Yahya Zghaibeh, Lasse Dührsen, Amanda Salviano-Silva, Katrin Lamszus, Manfred Westphal, Jens Gempt, Annika K Wefers, Julia E Neumann, Helena Bode, Fabian Hausmann, Tobias B Huber, Stefan Bonn, Kerstin Jütten, Daniel Delev, Katharina J Weber, Patrick N Harter, Julia Onken, Peter Vajkoczy, David Capper, Benedikt Wiestler, Michael Weller, Berend Snijder, Alicia Buck, Tobias Weiss, Pauline C Göller, Felix Sahm, Joelle Aline Menstel, David Niklas Zimmer, Michael B Keough, Lijun Ni, Michelle Monje, Dana Silverbush, Volker Hovestadt, Mario L Suvà, Saritha Krishna, Shawn L Hervey-Jumper, Ulrich Schüller, Dieter H Heiland, Sonja Hänzelmann, Franz L Ricklefs
Neural-tumor interactions drive glioma growth as evidenced in preclinical models, but clinical validation is limited. We present an epigenetically defined neural signature of glioblastoma that independently predicts patients' survival. We use reference signatures of neural cells to deconvolve tumor DNA and classify samples into low- or high-neural tumors. High-neural glioblastomas exhibit hypomethylated CpG sites and upregulation of genes associated with synaptic integration. Single-cell transcriptomic analysis reveals a high abundance of malignant stemcell-like cells in high-neural glioblastoma, primarily of the neural lineage...
May 17, 2024: Nature Medicine
https://read.qxmd.com/read/38760584/dual-energy-lattice-tip-ablation-system-for-persistent-atrial-fibrillation-a-randomized-trial
#24
JOURNAL ARTICLE
Elad Anter, Moussa Mansour, Devi G Nair, Dinesh Sharma, Tyler L Taigen, Petr Neuzil, Erich L Kiehl, Josef Kautzner, Jose Osorio, Stavros Mountantonakis, Andrea Natale, John D Hummel, Anish K Amin, Usman R Siddiqui, Doron Harlev, Paul Hultz, Shufeng Liu, Birce Onal, Khaldoun G Tarakji, Vivek Y Reddy
Clinical outcomes of catheter ablation for atrial fibrillation (AF) are suboptimal due, in part, to challenges in achieving durable lesions. Although focal point-by-point ablation allows for the creation of any required lesion set, this strategy necessitates the generation of contiguous lesions without gaps. A large-tip catheter, capable of creating wide-footprint ablation lesions, may increase ablation effectiveness and efficiency. In a randomized, single-blind, non-inferiority trial, 420 patients with persistent AF underwent ablation using a large-tip catheter with dual pulsed field and radiofrequency energies versus ablation using a conventional radiofrequency ablation system...
May 17, 2024: Nature Medicine
https://read.qxmd.com/read/38750352/the-evolution-of-personalized-nutrition
#25
JOURNAL ARTICLE
Josef Neu
No abstract text is available yet for this article.
May 15, 2024: Nature Medicine
https://read.qxmd.com/read/38750351/senaparib-as-first-line-maintenance-therapy-in-advanced-ovarian-cancer-a-randomized-phase-3-trial
#26
JOURNAL ARTICLE
Xiaohua Wu, Jihong Liu, Jing Wang, Li Wang, Zhongqiu Lin, Xiaobin Wang, Jianqing Zhu, Beihua Kong, Junwei Fei, Ying Tang, Bairong Xia, Zhiqing Liang, Ke Wang, Yi Huang, Hong Zheng, An Lin, Kui Jiang, Wei Wang, Xin Wang, Ge Lou, Hongming Pan, Shuzhong Yao, Guiling Li, Min Hao, Yunlang Cai, Xuejun Chen, Zhijun Yang, Youguo Chen, Hongwu Wen, Pengpeng Qu, Cong Xu, Chih-Yi Hsieh
Poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors as maintenance therapy after first-line chemotherapy have improved progression-free survival in women with advanced ovarian cancer; however, not all PARP inhibitors can provide benefit for a biomarker-unselected population. Senaparib is a PARP inhibitor that demonstrated antitumor activity in patients with solid tumors, including ovarian cancer, in phase 1 studies. The multicenter, double-blind, phase 3 trial FLAMES randomized (2:1) 404 females with advanced ovarian cancer (International Federation of Gynecology and Obstetrics stage III-IV) and response to first-line platinum-based chemotherapy to senaparib 100 mg (n = 271) or placebo (n = 133) orally once daily for up to 2 years...
May 15, 2024: Nature Medicine
https://read.qxmd.com/read/38750350/heat-exposure-induced-risks-of-preterm-birth-mediated-by-maternal-hypertension
#27
JOURNAL ARTICLE
Liyun Wang, Jiangli Di, Qiong Wang, Huanhuan Zhang, Wei Zhao, Xiaoming Shi, Qian Di, John S Ji, Wannian Liang, Cunrui Huang
Heat exposure is associated with an increased risk of preterm birth (PTB), with previous work suggesting that maternal blood pressure may play a role in these associations. Here we conducted a cohort study of 197,080 singleton live births across 8 provinces in China from 2015 to 2018. The study first estimated the associations between heat exposure, maternal hypertension and clinical subtypes of PTB, and then quantified the role of maternal hypertension in heat and PTB using mediation analyses. We show that heat exposure (>85th, 90th and 95th percentiles of local temperature distributions) spanning from conception to the 20th gestational week was associated with a 15-21% increase in PTB, and a 20-22% increase in medically indicated PTB...
May 15, 2024: Nature Medicine
https://read.qxmd.com/read/38749475/effectiveness-of-bariatric-metabolic-surgery-versus-glucagon-like-peptide-1-receptor-agonists-for-prevention-of-congestive-heart-failure
#28
JOURNAL ARTICLE
Yael Wolff Sagy, Gil Lavie, Noga Ramot, Erez Battat, Ronen Arbel, Orna Reges, Dror Dicker
Comparative evidence for the effects of bariatric metabolic surgery (BMS) and glucagon-like peptide-1 receptor agonists (GLP1-RA) on cardiovascular outcomes is limited. Here, in an observational, retrospective cohort study, we compared the incidence of Congestive Heart Failure (CHF) in adults living with obesity and diabetes without history of CHF (primary CHF) treated with BMS versus GLP-1RA. The population cohort comprised members of Clalit Health Services with no prior history of ischemic heart disease, ischemic stroke, or CHF...
May 15, 2024: Nature Medicine
https://read.qxmd.com/read/38745012/author-correction-axicabtagene-ciloleucel-as-second-line-therapy-in-large-b-cell-lymphoma-ineligible-for-autologous-stem-cell-transplantation-a-phase-2-trial
#29
Roch Houot, Emmanuel Bachy, Guillaume Cartron, François-Xavier Gros, Franck Morschhauser, Lucie Oberic, Thomas Gastinne, Pierre Feugier, Rémy Duléry, Catherine Thieblemont, Magalie Joris, Fabrice Jardin, Sylvain Choquet, Olivier Casasnovas, Gabriel Brisou, Morgane Cheminant, Jacques-Olivier Bay, Francisco Llamas Gutierrez, Cédric Menard, Karin Tarte, Marie-Hélène Delfau, Cédric Portugues, Emmanuel Itti, Xavier Palard-Novello, Paul Blanc-Durand, Yassine Al Tabaa, Clément Bailly, Camille Laurent, François Lemonnier
No abstract text is available yet for this article.
May 14, 2024: Nature Medicine
https://read.qxmd.com/read/38745011/progranulin-aav-gene-therapy-for-frontotemporal-dementia-translational-studies-and-phase-1-2-trial-interim-results
#30
JOURNAL ARTICLE
Jeffrey Sevigny, Olga Uspenskaya, Laura Dean Heckman, Li Chin Wong, Daniel A Hatch, Ambika Tewari, Rik Vandenberghe, David J Irwin, Dario Saracino, Isabelle Le Ber, Rebekah Ahmed, Jonathan D Rohrer, Adam L Boxer, Sebastian Boland, Patricia Sheehan, Alissa Brandes, Suzanne R Burstein, Benjamin M Shykind, Sitharthan Kamalakaran, Carter W Daniels, E David Litwack, Erin Mahoney, Jenny Velaga, Ilan McNamara, Patricia Sondergaard, Syed A Sajjad, Yvonne M Kobayashi, Asa Abeliovich, Franz Hefti
GRN mutations cause progranulin haploinsufficiency, which eventually leads to frontotemporal dementia (FTD-GRN). PR006 is an investigational gene therapy delivering the granulin gene (GRN) using an adeno-associated virus serotype 9 (AAV9) vector. In non-clinical studies, PR006 transduced neurons derived from induced pluripotent stem cells of patients with FTD-GRN, resulted in progranulin expression and improvement of lipofuscin, lysosomal and neuroinflammation pathologies in Grn-knockout mice, and was well tolerated except for minimal, asymptomatic dorsal root ganglionopathy in non-human primates...
May 14, 2024: Nature Medicine
https://read.qxmd.com/read/38745010/dynamics-of-cognitive-variability-with-age-and-its-genetic-underpinning-in-nihr-bioresource-genes-and-cognition-cohort-participants
#31
JOURNAL ARTICLE
Md Shafiqur Rahman, Emma Harrison, Heather Biggs, Chloe Seikus, Paul Elliott, Gerome Breen, Nathalie Kingston, John R Bradley, Steven M Hill, Brian D M Tom, Patrick F Chinnery
A leading explanation for translational failure in neurodegenerative disease is that new drugs are evaluated late in the disease course when clinical features have become irreversible. Here, to address this gap, we cognitively profiled 21,051 people aged 17-85 years as part of the Genes and Cognition cohort within the National Institute for Health and Care Research BioResource across England. We describe the cohort, present cognitive trajectories and show the potential utility. Surprisingly, when studied at scale, the APOE genotype had negligible impact on cognitive performance...
May 14, 2024: Nature Medicine
https://read.qxmd.com/read/38745009/trastuzumab-deruxtecan-in-her2-positive-advanced-gastric-cancer-exploratory-biomarker-analysis-of-the-randomized-phase-2-destiny-gastric01-trial
#32
JOURNAL ARTICLE
Kohei Shitara, Yung-Jue Bang, Satoru Iwasa, Naotoshi Sugimoto, Min-Hee Ryu, Daisuke Sakai, Hyun Cheol Chung, Hisato Kawakami, Hiroshi Yabusaki, Yasuhiro Sakamoto, Tomohiro Nishina, Koichiro Inaki, Yusuke Kuwahara, Naoya Wada, Fumitaka Suto, Takeo Arita, Masahiro Sugihara, Zenta Tsuchihashi, Kaku Saito, Akihito Kojima, Kensei Yamaguchi
Trastuzumab deruxtecan (T-DXd) showed statistically significant clinical improvement in patients with human epidermal growth factor receptor 2-positive (HER2+ ) gastric cancer in the DESTINY-Gastric01 trial. Exploratory results from DESTINY-Gastric01 suggested a potential benefit in patients with HER2-low gastric cancer. Spatial and temporal heterogeneity in HER2 expression or gene alteration, an inherent characteristic of gastric cancer tumors, presents a challenge in identifying patients who may respond to T-DXd...
May 14, 2024: Nature Medicine
https://read.qxmd.com/read/38745008/prevalence-of-comorbidities-in-individuals-with-neurodevelopmental-disorders-from-the-aggregated-phenomics-data-of-51-227-pediatric-individuals
#33
JOURNAL ARTICLE
Alexander J M Dingemans, Sandra Jansen, Jeroen van Reeuwijk, Nicole de Leeuw, Rolph Pfundt, Janneke Schuurs-Hoeijmakers, Bregje W van Bon, Carlo Marcelis, Charlotte W Ockeloen, Marjolein Willemsen, Pleuntje J van der Sluijs, Gijs W E Santen, R Frank Kooy, Anneke T Vulto-van Silfhout, Tjitske Kleefstra, David A Koolen, Lisenka E L M Vissers, Bert B A de Vries
The prevalence of comorbidities in individuals with neurodevelopmental disorders (NDDs) is not well understood, yet these are important for accurate diagnosis and prognosis in routine care and for characterizing the clinical spectrum of NDD syndromes. We thus developed PhenomAD-NDD, an aggregated database containing the comorbid phenotypic data of 51,227 individuals with NDD, all harmonized into Human Phenotype Ontology (HPO), with in total 3,054 unique HPO terms. We demonstrate that almost all congenital anomalies are more prevalent in the NDD population than in the general population, and the NDD baseline prevalence allows for an approximation of the enrichment of symptoms...
May 14, 2024: Nature Medicine
https://read.qxmd.com/read/38741000/gut-bacteria-switch-a-and-b-blood-types-to-universal
#34
Karen O'Leary
No abstract text is available yet for this article.
May 13, 2024: Nature Medicine
https://read.qxmd.com/read/38740999/the-efficacy-of-dapagliflozin-in-a-hierarchical-kidney-outcome-in-heart-failure
#35
JOURNAL ARTICLE
(no author information available yet)
No abstract text is available yet for this article.
May 13, 2024: Nature Medicine
https://read.qxmd.com/read/38740998/artificial-intelligence-in-surgery
#36
REVIEW
Chris Varghese, Ewen M Harrison, Greg O'Grady, Eric J Topol
Artificial intelligence (AI) is rapidly emerging in healthcare, yet applications in surgery remain relatively nascent. Here we review the integration of AI in the field of surgery, centering our discussion on multifaceted improvements in surgical care in the preoperative, intraoperative and postoperative space. The emergence of foundation model architectures, wearable technologies and improving surgical data infrastructures is enabling rapid advances in AI interventions and utility. We discuss how maturing AI methods hold the potential to improve patient outcomes, facilitate surgical education and optimize surgical care...
May 13, 2024: Nature Medicine
https://read.qxmd.com/read/38740997/high-resolution-african-hla-resource-uncovers-hla-drb1-expression-effects-underlying-vaccine-response
#37
JOURNAL ARTICLE
Alexander J Mentzer, Alexander T Dilthey, Martin Pollard, Deepti Gurdasani, Emre Karakoc, Tommy Carstensen, Allan Muhwezi, Clare Cutland, Amidou Diarra, Ricardo da Silva Antunes, Sinu Paul, Gaby Smits, Susan Wareing, HwaRan Kim, Cristina Pomilla, Amanda Y Chong, Debora Y C Brandt, Rasmus Nielsen, Samuel Neaves, Nicolas Timpson, Austin Crinklaw, Cecilia S Lindestam Arlehamn, Anna Rautanen, Dennison Kizito, Tom Parks, Kathryn Auckland, Kate E Elliott, Tara Mills, Katie Ewer, Nick Edwards, Segun Fatumo, Emily Webb, Sarah Peacock, Katie Jeffery, Fiona R M van der Klis, Pontiano Kaleebu, Pandurangan Vijayanand, Bjorn Peters, Alessandro Sette, Nezih Cereb, Sodiomon Sirima, Shabir A Madhi, Alison M Elliott, Gil McVean, Adrian V S Hill, Manjinder S Sandhu
How human genetic variation contributes to vaccine effectiveness in infants is unclear, and data are limited on these relationships in populations with African ancestries. We undertook genetic analyses of vaccine antibody responses in infants from Uganda (n = 1391), Burkina Faso (n = 353) and South Africa (n = 755), identifying associations between human leukocyte antigen (HLA) and antibody response for five of eight tested antigens spanning pertussis, diphtheria and hepatitis B vaccines...
May 13, 2024: Nature Medicine
https://read.qxmd.com/read/38740996/screening-and-diagnosis-of-cardiovascular-disease-using-artificial-intelligence-enabled-cardiac-magnetic-resonance-imaging
#38
JOURNAL ARTICLE
Yan-Ran Joyce Wang, Kai Yang, Yi Wen, Pengcheng Wang, Yuepeng Hu, Yongfan Lai, Yufeng Wang, Kankan Zhao, Siyi Tang, Angela Zhang, Huayi Zhan, Minjie Lu, Xiuyu Chen, Shujuan Yang, Zhixiang Dong, Yining Wang, Hui Liu, Lei Zhao, Lu Huang, Yunling Li, Lianming Wu, Zixian Chen, Yi Luo, Dongbo Liu, Pengbo Zhao, Keldon Lin, Joseph C Wu, Shihua Zhao
Cardiac magnetic resonance imaging (CMR) is the gold standard for cardiac function assessment and plays a crucial role in diagnosing cardiovascular disease (CVD). However, its widespread application has been limited by the heavy resource burden of CMR interpretation. Here, to address this challenge, we developed and validated computerized CMR interpretation for screening and diagnosis of 11 types of CVD in 9,719 patients. We propose a two-stage paradigm consisting of noninvasive cine-based CVD screening followed by cine and late gadolinium enhancement-based diagnosis...
May 13, 2024: Nature Medicine
https://read.qxmd.com/read/38740995/refining-neoadjuvant-immunotherapy-for-resectable-lung-cancer
#39
JOURNAL ARTICLE
Misty D Shields, Christine M Lovly
No abstract text is available yet for this article.
May 13, 2024: Nature Medicine
https://read.qxmd.com/read/38740994/association-between-pretreatment-emotional-distress-and-immune-checkpoint-inhibitor-response-in-non-small-cell-lung-cancer
#40
JOURNAL ARTICLE
Yue Zeng, Chun-Hong Hu, Yi-Zheng Li, Jian-Song Zhou, Shu-Xing Wang, Meng-Dong Liu, Zhen-Hua Qiu, Chao Deng, Fang Ma, Chun-Fang Xia, Fei Liang, Yu-Rong Peng, Ao-Xi Liang, Sheng-Hao Shi, Shi-Jiao Yao, Jun-Qi Liu, Wen-Jie Xiao, Xiao-Qiao Lin, Xin-Yu Tian, Ying-Zhe Zhang, Zhuo-Ying Tian, Ji-An Zou, Yun-Shu Li, Chao-Yue Xiao, Tian Xu, Xiao-Jie Zhang, Xiao-Ping Wang, Xian-Ling Liu, Fang Wu
Emotional distress (ED), commonly characterized by symptoms of depression and/or anxiety, is prevalent in patients with cancer. Preclinical studies suggest that ED can impair antitumor immune responses, but few clinical studies have explored its relationship with response to immune checkpoint inhibitors (ICIs). Here we report results from cohort 1 of the prospective observational STRESS-LUNG study, which investigated the association between ED and clinical efficacy of first-line treatment of ICIs in patients with advanced non-small-cell lung cancer...
May 13, 2024: Nature Medicine
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