32 Works

Data from: Age- and diet-associated metabolome remodeling characterizes the aging process driven by damage accumulation

Andrei S. Avanesov, Vadim N. Gladyshev, Clary B. Clish, Byung Cheon Lee, Kerry A. Pierce, Sun Hee Yim & Siming Ma
Aging is thought to be associated with increased molecular damage, but representative markers vary across conditions and organisms, making it difficult to assess properties of cumulative damage throughout lifespan. We used nontargeted metabolite profiling to follow age-associated trajectories of >15,000 metabolites in Drosophila subjected to control and lifespan-extending diets. We find that aging is associated with increased metabolite diversity and low-abundance molecules, suggesting they include cumulative damage. Remarkably, the number of detected compounds leveled-off in...

Data from: Ranking and characterization of established BMI and lipid associated loci as candidates for gene-environment interactions

Dmitry Shungin, Wei Q. Deng, Tibor V. Varga, Jian'an Luan, Evelin Mihailov, Andres Metspalu, Andrew P. Morris, Nita G. Forouhi, Cecilia Lindgren, Patrik K. E. Magnusson, Nancy L. Pedersen, Göran Hallmans, Audrey Y. Chu, Anne E. Justice, Mariaelisa Graff, Thomas W. Winkler, Lynda M. Rose, Claudia Langenberg, L. Adrienne Cupples, Paul M. Ridker, Nicholas J. Wareham, Ken K. Ong, Ruth J. F. Loos, Daniel I. Chasman, Erik Ingelsson … & Paul W. Franks
Phenotypic variance heterogeneity across genotypes at a single nucleotide polymorphism (SNP) may reflect underlying gene-environment (G·E) or gene-gene interactions. We modeled variance heterogeneity for blood lipids and BMI in up to 44,211 participants and investigated relationships between variance effects (Pv), G·E interaction effects (with smoking and physical activity), and marginal genetic effects (Pm). Correlations between Pv and Pm were stronger for SNPs with established marginal effects (Spearman's ρ=0.401 for triglycerides, and ρ=0.236 for BMI) compared...

The structural determinants of PH domain-mediated regulation of Akt revealed by segmental labeling

Nam Chu, Thibault Viennet, Philip Cole, Haribabu Arthanari, Antonieta Salguero, Hwan Bae & Andras Boeszoermenyi
Akt is a critical protein kinase that governs cancer cell growth and metabolism. Akt appears to be autoinhibited by an intramolecular interaction between its N-terminal pleckstrin homology (PH) domain and kinase domain, which is relieved by C-tail phosphorylation, but the precise molecular mechanisms remain elusive. Here we use a combination of protein semisynthesis, NMR, and enzymological analysis to characterize structural features of the PH domain in its autoinhibited and activated states. We find that Akt...

Plasma glycated CD59 predicts early gestational diabetes and large for gestational age newborns

Jose Halperin
Gestational diabetes mellitus (GDM) diagnosed in early pregnancy is a health care challenge because it increases the risk of adverse outcomes. Plasma glycated CD59 (pGCD59) is an emerging biomarker for diabetes and GDM. The aim of this study was to assess the performance of pGCD59 as a biomarker of early GDM and its association with delivering a large for gestational age (LGA) infant. Study: Blood levels of pGCD59 were measured in samples from 693 women...

Neurology Rounding Study (NEURONS): A Randomized Study of Bedside versus Hallway Rounding

Jacqueline Solomon, Shamik Bhattacharyya, Ahya Ali, Liam Cleary, Sarah Dibari, Robert Boxer, Brian Healy & Tracey Milligan
Objective: To compare bedside rounding with hallway rounding on an academic neurology inpatient service and assess efficiency, educational, and patient care outcomes. Methods: We conducted a single-center, crossover, randomized study of bedside versus hallway rounding on new inpatient neurology admissions over one-week blocks. The bedside team presented patients at the bedside, while the hallway team presented patients outside of the patient’s room. We evaluated the two approaches with time-motion analysis, which investigated the rounding style’s...

Stepwise-edited, human melanoma models reveal mutations’ effect on tumor and microenvironment

Eran Hodis & Elena Torlai Triglia
Establishing causal relationships between genetic alterations of human cancers and the specific phenotypes of malignancy remains a challenge. We sequentially introduced mutations into healthy human melanocytes in up to five genes spanning six commonly disrupted melanoma pathways forming nine genetically distinct cellular models of melanoma. We connected mutant melanocyte genotypes to malignant cell expression programs in vitro and in vivo, replicative immortality, malignancy, rapid tumor growth, pigmentation, metastasis, and histopathology. Mutations in malignant cells also...

NREM sleep EEG and wake ERP summary: The first wave of the Global Research Initiative on the neurophysiology of schizophrenia (GRINS)

Nataliia Kozhemiako, Jun Wang, Chenguang Jiang, Lei A Wang, Guanchen Gai, Kai Zou, Zhe Wang, Xiaoman Yu, Zhenglin Guo, Hailiang Huang, Zhenhe Zhou, Wei Zhu, Mei-Hua Hall, Shaun M. Purcell & Jen Q. Pan
Motivated by the potential of objective neurophysiological markers to index thalamocortical function in patients with severe psychiatric illnesses, we comprehensively characterized key NREM sleep parameters across multiple domains, their interdependencies, and their relationship to waking event-related potentials and symptom severity. In 72 schizophrenia (SCZ) patients and 58 controls, we confirmed a marked reduction in sleep spindle density in SCZ and extended these findings to show that fast and slow spindle properties were largely uncorrelated. We...

Data from: Use of anisotropy, 3D segmented atlas, and computational analysis to identify gray matter subcortical lesions common to concussive injury from different sites on the cortex

Praveen Kulkarni, William Kenkel, Seth P. Finklestine, Thomas M. Barchet, JingMei Ren, Mathew Davenport, Martha E. Shenton, Zora Kikinis, Mark Nedelman & Craig F. Ferris
Traumatic brain injury (TBI) can occur anywhere along the cortical mantel. While the cortical contusions may be random and disparate in their locations, the clinical outcomes are often similar and difficult to explain. Thus a question that arises is, do concussions at different sites on the cortex affect similar subcortical brain regions? To address this question we used a fluid percussion model to concuss the right caudal or rostral cortices in rats. Five days later,...

Data from: Effect of IV glyburide on adjudicated edema endpoints in the GAMES-RP Trial

W. Taylor Kimberly, Matthew B. Bevers, Rüdiger Von Kummer, Andrew M. Demchuk, Javier M. Romero, Jordan J. Elm, Holly E. Hinson, Bradley J. Molyneaux, J. Marc Simard & Kevin Navin Sheth
Objective: In this secondary analysis of the GAMES-RP trial, we report the effect of IV glyburide on adjudicated, edema-related endpoints. Methods: Blinded adjudicators assigned designations for hemorrhagic transformation, neurological deterioration, malignant edema and edema-related death to patients from the GAMES-RP Phase II randomized controlled trial of IV glyburide for large hemispheric infarct. Rates of these endpoints were compared between treatment arms in the per-protocol sample. In those participants with malignant edema, the effects of treatment...

Data from: Akt-mTORC1 signaling regulates Acly to integrate metabolic input to control of macrophage activation

Anthony J. Covarrubias, Halil Ibrahim Aksoylar, Jiujiu Yu, Nathaniel W. Snyder, Andrew J. Worth, Shankar S. Iyer, Jiawei Wang, Issam Ben-Sahra, Vanessa Byles, Tiffany Polynne-Stapornkul, Erika C. Espinosa, Dudley Lamming, Brendan D. Manning, Yijing Zhang, Ian A. Blair & Tiffany Horng
Macrophage activation/polarization to distinct functional states is critically supported by metabolic shifts. How polarizing signals coordinate metabolic and functional reprogramming, and the potential implications for control of macrophage activation, remains poorly understood. Here we show that IL-4 signaling co-opts the Akt-mTORC1 pathway to regulate Acly, a key enzyme in Ac-CoA synthesis, leading to increased histone acetylation and M2 gene induction. Only a subset of M2 genes is controlled in this way, including those regulating cellular...

Skeletal Muscle and Peripheral Nerve Histopathology in COVID-19

Joome Suh, Shibani Mukerji, Sarah Collens, Robert Padera, Geraldine Pinkus, Anthony Amato & Isaac Solomon
To explore the spectrum of skeletal muscle and nerve pathology of patients who died following SARS-CoV-2 infection and assess for direct viral invasion of these tissues. Psoas muscle and femoral nerve were sampled from 35 consecutive autopsies of patients who died following SARS-CoV-2 infection and 10 SARS-CoV-2-negative controls were examined under light microscopy. Clinical and laboratory data were obtained by chart review. In SARS-CoV-2-positive patients, mean age at death was 67.8 years (range 43-90 years)...

Data from: Automatic segmentation of multiple cardiovascular structures from cardiac computed tomography angiography images using deep learning

Lohendran Baskaran, Subhi J. Al’Aref, Gabriel Maliakal, Benjamin C. Lee, Zhuoran Xu, Jeong W. Choi, Sang-Eun Lee, Ji Min Sung, Fay Y. Lin, Simon Dunham, Bobak Mosadegh, Yong-Jin Kim, Ilan Gottlieb, Byoung Kwon Lee, Eun Ju Chun, Filippo Cademartiri, Erica Maffei, Hugo Marques, Sanghoon Shin, Jung Hyun Choi, Kavitha Chinnaiyan, Martin Hadamitzky, Edoardo Conte, Daniele Andreini, Gianluca Pontone … & Leslee J. Shaw
Objectives: To develop, demonstrate and evaluate an automated deep learning method for multiple cardiovascular structure segmentation. Background: Segmentation of cardiovascular images is resource-intensive. We design an automated deep learning method for the segmentation of multiple structures from Coronary Computed Tomography Angiography (CCTA) images. Methods: Images from a multicenter registry of patients that underwent clinically-indicated CCTA were used. The proximal ascending and descending aorta (PAA, DA), superior and inferior vena cavae (SVC, IVC), pulmonary artery (PA),...

Deep-sequence phylogenetics to quantify patterns of HIV transmission in the context of a universal testing and treatment trial – BCPP/ Ya Tsie trial

Lerato Magosi, Yinfeng Zhang, Tanya Golubchik, Victor DeGruttola, Eric Tchetgen Tchetgen, Vladimir Novitsky, Janet Moore, Pam Bachanas, Tebogo Segolodi, Refeletswe Lebelonyane, Molly Pretorius Holme, Sikhulile Moyo, Joseph Makhema, Shahin Lockman, Christophe Fraser, Myron Essex & Marc Lipsitch
Background: Mathematical models predict that community-wide access to HIV testing-and-treatment can rapidly and substantially reduce new HIV infections. Yet several large universal test-and-treat HIV prevention trials in high-prevalence epidemics demonstrated variable reduction in population-level incidence. Methods: To elucidate patterns of HIV spread in universal test-and-treat trials we quantified the contribution of geographic-location, gender, age and randomized-HIV-intervention to HIV transmissions in the 30-community Ya Tsie trial in Botswana (estimated trial population: 175,664). Results: Deep-sequence phylogenetic analysis...

Appendix: Association between hemostatic profile and migraine: a Mendelian randomization analysis

Yanjun Guo, Pamela Rist, Maria Sabater-Lleal, Paul De Vries, Nicholas Smith, Paul Ridker, Tobias Kurth & Daniel Chasman
Objective: To assess support for a causal relationship between hemostatic measures and migraine susceptibility using genetic instrumental analysis. Methods: Two-sample Mendelian randomization (MR) instrumental leveraging available genome-wide association study (GWAS) summary statistics was applied to hemostatic measures as potential causal for migraine and its subtypes, migraine with aura (MA) and migraine without aura (MO). Twelve blood-based measures of hemostasis were examined, including plasma level or activity of eight hemostatic factors and two fibrinopeptides together with...

Data from: Effectiveness and meaningful use of paediatric surgical safety checklists and their implementation strategies: a systematic review with narrative synthesis

Janaka Lagoo, Steven R. Lopushinsky, Alex B. Haynes, Paul Bain, Helene Flageole, Erik D. Skarsgard & Mary E. Brindle
ObjectiveTo examine the effectiveness and meaningful use of pediatric surgical safety checklists (SSCs) and their implementation strategies through a systematic review with narrative synthesis. Summary Background Data Since the launch of the World Health Organization SSC, checklists have been integrated into surgical systems worldwide. Information is sparse on how SSCs have been integrated into the pediatric surgical environment. Methods A broad search strategy was created using Pubmed, Embase, CINAHL, Cochrane Central, Web of Science, Science...

Data from: Association between aspirin dose and subarachnoid hemorrhage from saccular aneurysms: a case-control study

Anil Can, Robert F. Rudy, Victor M. Castro, Sheng Yu, Dmitriy Dligach, Sean Finan, Vivian Gainer, Nancy A. Shadick, Guergana Savova, Shawn Murphy, Tianxi Cai, Scott T. Weiss & Rose Du
Objective: We aimed to determine the association between ruptured saccular aneurysms and aspirin use/aspirin dose. Methods: 4,701 patients who were diagnosed at the Massachusetts General Hospital and Brigham and Women’s Hospital between 1990 and 2016 with 6,411 unruptured and ruptured saccular intracranial aneurysms were evaluated. Univariable and multivariable logistic regression analyses were performed to determine the association between aSAH and aspirin use, including aspirin dose. Inverse probability weighting using propensity scores was used to adjust...

Data from: Assessment of plasma proteomics biomarker’s ability to distinguish benign from malignant lung nodules

Gerard A. Silvestri, Nichole T. Tanner, Paul Kearney, Anil Vachani, Pierre P. Massion, Alexander Porter, Steven C. Springmeyer, Kenneth C. Fang, David Midthun, Peter J. Mazzone, D. Madtes, J. Landis, A. Levesque, K. Rothe, M. Balaan, B. Dimitt, B. Fortin, N. Ettinger, A. Pierre, L. Yarmus, K. Oakjones-Burgess, N. Desai, Z. Hammoud, A. Sorenson, R. Murali … & F. Allison
Background: Lung nodules are a diagnostic challenge, with an estimated yearly incidence of 1.6 million in the United States. This study evaluated the accuracy of an integrated proteomic classifier in identifying benign nodules in patients with a pretest probability of cancer (pCA) ≤ 50%. Methods: A prospective, multicenter observational trial of 685 patients with 8- to 30-mm lung nodules was conducted. Multiple reaction monitoring mass spectrometry was used to measure the relative abundance of two...

Data from: Anemia and related nutrient deficiencies after Roux-en-Y gastric bypass surgery: a systematic review and meta-analysis

Ting-Chia Weng, Chia-Hsuin Chang, Yaa-Hui Dong, Yi-Cheng Chang & Lee-Ming Chuang
Objective: To obtain a pooled risk estimate on the long-term impact of anaemia and related nutritional deficiencies in patients receiving Roux-en-Y gastric bypass (RYGB) surgery. Design: Systematic review and meta-analysis. Data sources: MEDLINE, EMBASE and Cochrane databases were searched to identify English reports published before 16 May 2014. Eligibility criteria: Articles with case numbers >100, follow-up period >12 months, and complete data from both before and after surgery were selected. Outcomes of interest were changes...

Data from: Diverse nucleosome site-selectivity among histone deacetylase complexes

Zhipeng Wang, Christopher Millard, Chia-Liang Lin, Jennifer Gurnett, Mingxuan Wu, Kwangwoon Lee, Louise Fairall, John Schwabe & Philip Cole
Histone acetylation regulates chromatin structure and gene expression and is removed by histone deacetylases (HDACs). HDACs are commonly found in various protein complexes to confer distinct cellular functions, but how the multi-subunit complexes influence deacetylase activities and site-selectivities in chromatin is poorly understood. Recent studies on the HDAC1 containing CoREST complex and acetylated nucleosome substrates revealed a notable preference for deacetylation of histone H3 acetyl-Lys9 vs. acetyl-Lys14 (M. Wu et al, 2018). Here we analyze...

Supplement to: Sex and race differences in the risk of ischemic stroke associated with fasting blood glucose in REGARDS

Tracy Madsen, D. Leann Long, April P. Carson, George Howard, Dawn O. Kleindorfer, Karen L. Furie, JoAnn E. Manson, Simin Liu & Virginia J. Howard
Background: To investigate sex and race differences in the association between fasting blood glucose (FBG) and risk of ischemic stroke (IS). Methods: This prospective longitudinal cohort study included adults age ≥45 years at baseline in the Reasons for Geographic And Racial Differences in Stroke Study, followed for a median of 11.4 years. The exposure was baseline FBG (mg/dL); suspected IS events were ascertained by phone every 6 months and were physician-adjudicated. Cox proportional hazards were...

Fine particulate matter and neuroanatomic risk for Alzheimer’s disease in older women

Diana Younan, Xinhui Wang, Ramon Casanova, Ryan Barnard, Sarah Gaussoin, Santiago Saldana, Andrew Petkus, Daniel Beavers, Susan Resnick, JoAnn Manson, Marc Serre, William Vizuete, Victor Henderson, Bonnie Sachs, Joel Salinas, Margaret Gatz, Mark Espeland, Helena Chui, Sally Shumaker, Stephen Rapp & Jiu-Chiuan Chen
Objective: To examine whether late-life exposure to PM2.5 (particulate matter with aerodynamic diameters <2.5-µm) contributes to progressive brain atrophy predictive of Alzheimer’s disease (AD) using a community-dwelling cohort of women (aged 71-89) with up to two brain MRI scans (MRI-1: 2005-6; MRI-2: 2010-11). Methods: AD pattern similarity (AD-PS) scores, developed by supervised machine learning and validated with MRI data from the AD Neuroimaging Initiative, was used to capture high-dimensional gray matter atrophy in brain areas...

Data from: Origins of lymphatic and distant metastases in human colorectal cancer

Kamila Naxerova, Johannes G. Reiter, Elena Brachtel, Jochen K. Lennerz, Marc Van De Wetering, Andrew Rowan, Tianxi Cai, Hans Clevers, Charles Swanton, Martin A. Nowak, Stephen J. Elledge & Rakesh K. Jain
The spread of cancer cells from primary tumors to regional lymph nodes is often associated with reduced survival. One prevailing model to explain this association posits that fatal, distant metastases are seeded by lymph node metastases. This view provides a mechanistic basis for the TNM staging system and is the rationale for surgical resection of tumor-draining lymph nodes. Here we examine the evolutionary relationship between primary tumor, lymph node, and distant metastases in human colorectal...

Large mitochondrial DNA deletions in HIV sensory neuropathy

Ricardo Roda, David Bargiela, Weiran Chen, Ken Perry, Ronald J. Ellis, David B. Clifford, Ajay Bharti, Asha Kallianpur, Michelli F Oliveira, Monica M. Diaz, Leah H. Rubin, Christina Gavegnano, Justin C. McArthur, Ahmet Hoke & Michael Polydefkis
Objective: The primary objective of this study was to evaluate the correlation of large mitochondrial DNA deletions in skin samples of people with HIV with measure of neuropathy and prior exposure to therapy. We hypothesized that deletions would be associated with the presence of neuropathy. As secondary objectives we determined the correlation of deletion burden with demographic data and neuropathy measures. Methods: In this retrospective cohort study we measured the accumulation of large mtDNA deletions...

Safety and efficacy of remote ischemic postconditioning after thrombolysis in patients with stroke

Guoliang Li, Jia-Qi An, Ya-Wen Cheng, Yi-Chen Guo, Meng Wei, Min-Jie Gong, Yong-Lan Tang, Xing-Yun Yuan, Wen-Feng Song, Chunying Mu, Ai-Feng Zhang, Ardan Saguner & Guo-Gang Luo
Objective: To determine the effect of remote ischemic post-conditioning (RIPC) on acute ischemic stroke (AIS) patients undergoing intravenous thrombolysis (IVT). Methods: A single-center, randomized controlled trial was performed with AIS patients receiving IVT. Patients in the RIPC group were administered RIPC treatment (after IVT) during hospitalization. The primary endpoint was a score of 0 or 1 on the modified Rankin scale (mRS) at day 90. The safety, tolerability and neuroprotection biomarkers associated with RIPC were...

Data from: Clinical presentation and management of SMART syndrome

Sebastian F. Winter, Joshua P. Klein, Eugene J. Vaios, Philipp Karschnia, Eudocia Q. Lee, Helen A. Shih, Franziska Loebel & Jorg Dietrich
Stroke-like migraine attacks after radiation therapy (SMART) syndrome represents a rare but serious condition manifesting years after cranial radiation therapy (RT). Characterized by migraine-type headaches, stroke-like deficits and/or seizures and MR imaging abnormalities, including cortical gyriform enhancement in irradiated brain regions, SMART remains diagnostically and therapeutically challenging. Distinction from tumor progression is difficult and treatment options are limited. Although frequently reversible, SMART episodes can recur and effectuate persistent neurologic and/or imaging sequelae.

Registration Year

  • 2022
  • 2021
  • 2020
  • 2019
  • 2018
  • 2017
  • 2016
  • 2015
  • 2014

Resource Types

  • Dataset
  • Image
  • Output Management Plan


  • Brigham and Women's Hospital
  • Massachusetts General Hospital
  • Harvard University
  • University of Pennsylvania
  • Broad Institute
  • Emory University School of Medicine
  • Charité
  • University of Washington
  • Stanford University
  • University of North Carolina