tbuckley/cabot-search huggingface dataset:
A call for standardised age-disaggregated health data
Authors: Theresa Diaz, Kathleen L Strong, Bochen Cao, Regina Guthold, Allisyn C Moran, Ann-Beth Moller, Jennifer Requejo, Ritu Sadana, Jotheeswaran Amuthavalli Thiyagarajan, Emmanuel Adebayo, Elsie Akwara, Agbessi Amouzou, John J Aponte Varon, Peter S Azzopardi, Cynthia Boschi-Pinto, Liliana Carvajal, Venkatraman Chandra-Mouli, Sarah Crofts, Saeed Dastgiri, Jeremiah S Dery, Shatha Elnakib, Lucy Fagan, B Jane Ferguson, Julia Fitzner, Howard S Friedman, Ann Hagell, Eduard Jongstra, Laura Kann, Somnath Chatterji, Mike English, Philippe Glaziou, Claudia Hanson, Ahmad R Hosseinpoor, Andrew Marsh, Alison P Morgan, Melinda K Munos, Abdisalan Noor, Boris I Pavlin, Rich Pereira, Tyler A Porth, Joanna Schellenberg, Rizwana Siddique, Danzhen You, Lara M E Vaz, Anshu Banerjee
Journal: The Lancet Healthy Longevity (2021)

The 2030 Sustainable Development Goals agenda calls for health data to be disaggregated by age. However, age groupings used to record and report health data vary greatly, hindering the harmonisation, comparability, and usefulness of these data, within and across countries. This variability has become especially evident during the COVID-19 pandemic, when there was an urgent need for rapid cross-country analyses of epidemiological patterns by age to direct public health action, but such analyses were limited by the lack of standard age categories. In this Personal View, we propose a recommended set of age groupings to address this issue. These groupings are informed by age-specific patterns of morbidity, mortality, and health risks, and by opportunities for prevention and disease intervention. We recommend age groupings of 5 years for all health data, except for those younger than 5 years, during which time there are rapid biological and physiological changes that justify a finer disaggregation. Although the focus of this Personal View is on the standardisation of the analysis and display of age groups, we also outline the challenges faced in collecting data on exact age, especially for health facilities and surveillance data. The proposed age disaggregation should facilitate targeted, age-specific policies and actions for health care and disease management.
Corrigendum to: Eighteen Coral Genomes Reveal the Evolutionary Origin of Acropora Strategies to Accommodate Environmental Changes
Authors: Chuya Shinzato, Konstantin Khalturin, Jun Inoue, Yuna Zayasu, Miyuki Kanda, Mayumi Kawamitsu, Yuki Yoshioka, Hiroshi Yamashita, Go Suzuki, Noriyuki Satoh
Journal: Molecular Biology and Evolution (2021)
Fc Receptor for Immunoglobulin May Play Functional Role in Endothelium-dependent Vascular Relaxation and Production of Superoxide in Hypercholesterolemic Mice.
Authors: Sumiyoshi Katsuhiko, Mokuno Hiroshi, Iesaki Takafumi, Shimada Kazunori, Miyazaki Tetsuro, Kume Atsumi, Kuremoto Kenichi, Watanabe Yoshiro, Tada Nobuhiro, Daida Hiroyuki
Journal: Circulation (2006)
Abstract 129: Transient Activation of AMPK Prior to Cardiac Pressure Overload Alleviates Fibrotic Accumulation and Functional Decline
Authors: Erin L Reineke, George E Taffet, Jason T Kaelber, Heinrich Taegtmeyer, Mark L Entman, Bert W O'Malley
Journal: Circulation Research (2016)

The multiple adaptive pathways activated during cardiac stress must communicate with each other for an efficient response; however, little is known about the molecular mechanisms underlying this coordination. During left ventricular pressure overload induced by transverse aortic constriction (TAC), an increase in metabolic flux to meet the ATP demand is the first molecular change observed in the heart. Following initial metabolic changes, there is genetic remodeling of the metabolic machinery and activation of other acute and long-term adaptive pathways to control hypertrophy, fibrosis, and contraction. In order to better understand how the early metabolic changes affect the activation and magnitude of the downstream pathways, we treated mice with the AMPK activator AICAR for 6 days prior to TAC and then monitored effects on the cardiac stress response for 4 weeks. This treatment was performed in both WT mice and in mice lacking cardiomyocyte expression of steroid receptor coactivator-2 (SRC-2 CKO), a model we have previously shown to be genetically similar to a stressed mouse and whose function declines rapidly in response to TAC. Interestingly, we found that this small transient treatment with AICAR is sufficient to blunt hypertrophy (20% reduction) and fibrotic accumulation (56% reduction) and prevent left ventricular dilation and pleural edema. Furthermore, AICAR treatment in the SRC-2 CKO animals was able to rescue the functional decline observed post-TAC. We are currently investigating the molecular pathways underlying these changes. Our results strongly suggest that there are very early events during cardiac stress that are key determinants in the ability of the heart to adapt and maintain function under stress, even in late stages post-stress. Disruption of these determinants can lead to rapid failure, whereas their promotion could hold a key for therapeutic intervention.
Copy number alteration profiling facilitates differential diagnosis between ossifying fibroma and fibrous dysplasia of the jaws
Authors: Ming Ma, Lu Liu, Ruirui Shi, Jianyun Zhang, Xiaotian Li, Xuefen Li, Jiaying Bai, Jianbin Wang, Yanyi Huang, Tiejun Li
Journal: International Journal of Oral Science (2021)

Abstract Ossifying fibroma (OF) and fibrous dysplasia (FD) are two fibro-osseous lesions with overlapping clinicopathological features, making diagnosis challenging. In this study, we applied a whole-genome shallow sequencing approach to facilitate differential diagnosis via precise profiling of copy number alterations (CNAs) using minute amounts of DNA extracted from morphologically correlated microdissected tissue samples. Freshly frozen tissue specimens from OF ( n = 29) and FD ( n = 28) patients were obtained for analysis. Lesion fibrous tissues and surrounding normal tissues were obtained by laser capture microdissection (LCM), with ~30–50 cells (5 000–10 000 µm 2 ) per sample. We found that the rate of recurrent CNAs in OF cases was much higher (44.8%, 13 of 29) than that in FD cases (3.6%, 1 of 28). Sixty-nine percent (9 of 13) of the CNA-containing OF cases involved segmental amplifications and deletions on Chrs 7 and 12. We also identified eight CNA-associated genes (HILPDA, CALD1, C1GALT1, MICALL2, PHF14, AIMP2, MDM2, and CDK4) with amplified expression, which was consistent with the copy number changes. We further confirmed a jaw lesion with a previous uncertain diagnosis due to its ambiguous morphological features and the absence of GNAS mutation as OF based on the typical Chr 12 amplification pattern in its CNA profile. Moreover, analysis of a set of longitudinal samples collected from an individual with a cellular lesion in suspicion of OF at the first surgery, recurrence and the latest malignant transformation revealed identical CNA patterns at the three time points, suggesting that copy number profiling can be used as an important tool to identify borderline lesions or lesions with malignant potential. Overall, CNA profiling of fibro-osseous lesions can greatly improve differential diagnosis between OF and FD and help predict disease progression.
Paired box 6 programs essential exocytotic genes in the regulation of glucose-stimulated insulin secretion and glucose homeostasis
Authors: Wing Yan So, Wai Nam Liu, Adrian Kee Keong Teo, Guy A. Rutter, Weiping Han
Journal: Science Translational Medicine (2021)

The paired box 6 (PAX6) transcription factor is crucial for normal pancreatic islet development and function. Heterozygous mutations of PAX6 are associated with impaired insulin secretion and early-onset diabetes mellitus in humans. However, the molecular mechanism of PAX6 in controlling insulin secretion in human beta cells and its pathophysiological role in type 2 diabetes (T2D) remain ambiguous. We investigated the molecular pathway of PAX6 in the regulation of insulin secretion and the potential therapeutic value of PAX6 in T2D by using human pancreatic beta cell line EndoC-βH1, the db/db mouse model, and primary human pancreatic islets. Through loss- and gain-of-function approaches, we uncovered a mechanism by which PAX6 modulates glucose-stimulated insulin secretion (GSIS) through a cAMP response element-binding protein (CREB)/Munc18-1/2 pathway. Moreover, under diabetic conditions, beta cells and pancreatic islets displayed dampened PAX6/CREB/Munc18-1/2 pathway activity and impaired GSIS, which were reversed by PAX6 replenishment. Adeno-associated virus-mediated PAX6 overexpression in db/db mouse pancreatic beta cells led to a sustained amelioration of glycemic perturbation in vivo but did not affect insulin resistance. Our study highlights the pathophysiological role of PAX6 in T2D-associated beta cell dysfunction in humans and suggests the potential of PAX6 gene transfer in preserving and restoring beta cell function.
Passive transfer of fibromyalgia symptoms from patients to mice
Authors: Andreas Goebel, Emerson Krock, Clive Gentry, Mathilde R. Israel, Alexandra Jurczak, Carlos Morado Urbina, Katalin Sandor, Nisha Vastani, Margot Maurer, Ulku Cuhadar, Serena Sensi, Yuki Nomura, Joana Menezes, Azar Baharpoor, Louisa Brieskorn, Angelica Sandström, Jeanette Tour, Diana Kadetoff, Lisbet Haglund, Eva Kosek, Stuart Bevan, Camilla I. Svensson, David A. Andersson
Journal: Journal of Clinical Investigation (2021)

Fibromyalgia syndrome (FMS) is characterized by widespread pain and tenderness, and patients typically experience fatigue and emotional distress. The etiology and pathophysiology of fibromyalgia are not fully explained and there are no effective drug treatments. Here we show that IgG from FMS patients produced sensory hypersensitivity by sensitizing nociceptive neurons. Mice treated with IgG from FMS patients displayed increased sensitivity to noxious mechanical and cold stimulation, and nociceptive fibers in skin-nerve preparations from mice treated with FMS IgG displayed an increased responsiveness to cold and mechanical stimulation. These mice also displayed reduced locomotor activity, reduced paw grip strength, and a loss of intraepidermal innervation. In contrast, transfer of IgG-depleted serum from FMS patients or IgG from healthy control subjects had no effect. Patient IgG did not activate naive sensory neurons directly. IgG from FMS patients labeled satellite glial cells and neurons in vivo and in vitro, as well as myelinated fiber tracts and a small number of macrophages and endothelial cells in mouse dorsal root ganglia (DRG), but no cells in the spinal cord. Furthermore, FMS IgG bound to human DRG. Our results demonstrate that IgG from FMS patients produces painful sensory hypersensitivities by sensitizing peripheral nociceptive afferents and suggest that therapies reducing patient IgG titers may be effective for fibromyalgia.
Predictors for single-agent resistance in FIGO score 5 or 6 gestational trophoblastic neoplasia: a multicentre, retrospective, cohort study
Authors: Antonio Braga, Gabriela Paiva, Ehsan Ghorani, Fernanda Freitas, Luis Guillermo Coca Velarde, Baljeet Kaur, Nick Unsworth, Jingky Lozano-Kuehne, Ana Paula Vieira dos Santos Esteves, Jorge Rezende Filho, Joffre Amim, Xianne Aguiar, Naveed Sarwar, Kevin M Elias, Neil S Horowitz, Ross S Berkowitz, Michael J Seckl
Journal: The Lancet Oncology (2021)
Follicular lymphoma triggers phenotypic and functional remodeling of the human lymphoid stromal cell landscape
Authors: Frédéric Mourcin, Léa Verdière, David Roulois, Rada Amin, Claire Lamaison, Vonick Sibut, Brice Thamphya, Céline Pangault, Céline Monvoisin, Sarah Huet, Marine Seffals, Sylvain Baulande, Fatima Mechta-Grigoriou, Patricia Legoix, Delphine Rossille, Marion Guirriec, Simon Léonard, Guillaume Cartron, Gilles Salles, Thierry Fest, Karin Tarte
Journal: Immunity (2021)
Quality and Safety in Healthcare, Part LXXXIX
Authors: Jay A. Harolds
Journal: Clinical Nuclear Medicine (2021)

A major priority of the Toyota Production System is to satisfy the customers by providing high value. The use of continuous flow, pull systems, the Andon system, standard work, visual controls, the 5S system, and reliable technology are critically important. Optimizing one's workforce is also very important by developing leaders and teams, using consensus in decision making, and becoming a learning organization. To fully understand the problems, it is also important that leaders go to the workplace to talk to workers and see what is going on.
Prenatal Lead (Pb) Exposure and Peripheral Blood DNA Methylation (5mC) and Hydroxymethylation (5hmC) in Mexican Adolescents from the ELEMENT Birth Cohort
Authors: Christine A. Rygiel, Jaclyn M. Goodrich, Maritsa Solano-González, Adriana Mercado-García, Howard Hu, Martha M. Téllez-Rojo, Karen E. Peterson, Dana C. Dolinoy
Journal: Environmental Health Perspectives (2021)

Gestational lead (Pb) exposure can adversely affect offspring health through multiple mechanisms, including epigenomic alterations via DNA methylation (5mC) and hydroxymethylation (5hmC), an intermediate in oxidative demethylation. Most current methods do not distinguish between 5mC and 5hmC, limiting insights into their individual roles.Our study sought to identify the association of trimester-specific (T1, T2, T3) prenatal Pb exposure with 5mC and 5hmC levels at multiple cytosine-phosphate-guanine sites within gene regions previously associated with prenatal Pb (HCN2, NINJ2, RAB5A, TPPP) in whole blood leukocytes of children ages 11-18 years of age.Participants from the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) birth cohorts were selected (n=144) for pyrosequencing analysis following oxidative or standard sodium bisulfite treatment. This workflow directly quantifies total methylation (5mC+5hmC) and 5mC only; 5hmC is estimated by subtraction.Participants were 51% male, and mean maternal blood lead levels (BLL) were 6.43±5.16μg/dL in Trimester 1 (T1), 5.66±5.21μg/dL in Trimester 2 (T2), and 5.86±4.34μg/dL in Trimester 3 (T3). In addition, 5hmC levels were calculated for HCN2 (mean±standard deviation(SD), 2.08±4.18%), NINJ2 (G/C: 2.01±5.95; GG: 0.90±3.97), RAB5A (0.66±0.80%), and TPPP (1.11±6.67%). Furthermore, 5mC levels were measured in HCN2 (81.3±9.63%), NINJ2 (heterozygotes: 38.6±7.39%; GG homozygotes: 67.3±9.83%), RAB5A (1.41±1.21%), and TPPP (92.5±8.03%). Several significant associations between BLLs and 5mC/5hmC were identified: T1 BLLs with 5mC in HCN2 (β=-0.37, p=0.03) and 5hmC in NINJ2 (β=0.49, p=0.003); T2 BLLs with 5mC in HCN2 (β=0.37, p=0.03) and 5hmC in NINJ2 (β=0.27, p=0.008); and T3 BLLs with 5mC in HCN2 (β=0.50, p=0.01) and NINJ2 (β=-0.35, p=0.004) and 5hmC in NINJ2 (β=0.45, p<0.001). NINJ2 5mC was negatively correlated with gene expression (Pearson r=-0.5, p-value=0.005), whereas 5hmC was positively correlated (r=0.4, p-value=0.04).These findings suggest there is variable 5hmC in human whole blood and that prenatal Pb exposure is associated with gene-specific 5mC and 5hmC levels at adolescence, providing evidence to consider 5hmC as a regulatory mechanism that is responsive to environmental exposures. https://doi.org/10.1289/EHP8507.
Abstract SY07-02: Gaining biologic insights into glioblastoma using proteomics
Authors: Jill S. Barnholtz-Sloan
Journal: Cancer Research (2021)

Abstract Glioblastoma (GBM) is the most common type of primary malignant tumor in adults and contributes disproportionately to cancer morbidity and mortality. Understanding its molecular pathogenesis is crucial for improving diagnosis and treatment. Integrated analysis of genomic, proteomic, post-translational modification and metabolomics data on 99-treatment naïve GBMs provided insights to GBM biology. Multiple key findings emerged that were not known from traditional genomic analyses: (1) Analysis of protein phosphorylation identified key signaling intermediates in the RTK/RAS path-way common to multiple RTK genomic alterations (PTPN11 and PLCG1), potentially offering common therapeutic targets for different oncogenic drivers in GBM. (2) Phosphoproteomics also identified potential druggable targets based on kinase-substrate pathway analysis, as well as novel phosphoprotein targets associated with the regulation of telomere length by ATRX in IDH mutants. (3) TP53 protein abundance in GBM is regulated by protein/phosphoprotein effectors (4) Four immune GBM subtypes exist, characterized by distinct immune cell population differences – Immune High and Immune Low phenotypes in GBM were driven by tumor-associated macrophage markers, and associated with distinct epigenetic modifications and histone acetylation patterns. (5) The mesenchymal subtype displays EMT signatures specific in tumor cells, distinct from infiltrating immune cells. (6) Histone H2B acetylation and immune-low GBM was driven largely by BRDs, CREBBP, and EP300. (7) Identification of key metabolic changes in IDH mutants facilitating the accumulation of onco-metabolite 2-HG were also associated with lipidomic changes. This work identifies additional therapeutic channels for GBM and novel information useful for more accurate stratification patients for effective treatment. Citation Format: Jill S. Barnholtz-Sloan. Gaining biologic insights into glioblastoma using proteomics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr SY07-02.
Overuse of Levothyroxine in Patients With Subclinical Hypothyroidism
Authors: William K. Silverstein, Deborah Grady
Journal: JAMA Internal Medicine (2021)

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How to fix India’s depleted rural workforce
Authors: Kamala Thiagarajan
Journal: BMJ (2021)

As India continues to struggle with covid-19, the pandemic has laid bare many of the severe vulnerabilities in its healthcare.Particularly concerning are the areas bereft of specialised health services, blood banks, and critical care-so called "medical deserts," which are mostly in rural areas.More than half of the world's population lives in a rural area, according to the United Nations Department of Economic and Social Affairs.Projections suggest that by 2050, that will increase to 68%-one in three people globally.In India, 70% of its 1.3 billion population lives in a rural area.However, around 80% of the country's 1.14 million registered doctors work in cities. 1 India also has a nationwide shortage of doctors, with one for every 11 082 of the population; the World Health Organization recommended ratio is 1:1000. 2he country is estimated to be missing around 600 000 doctors and two million nurses to meet WHO levels, 3 and the problem is particularly acute in less attractive rural areas.Primary healthcare centres are considered the backbone of India's rural health systems-they cater for 20 000 to 30 000 people each and carry most of the patient load in rural areas.However, Gagandeep Kang, professor of gastrointestinal sciences at the Christian Medical College, Vellore, says primary healthcare centres are not adequately equipped to provide critical care during emergencies, such as snake bite, poisoning, or other trauma.Larger, community health centres are fewer, but as 30 bed hospitals they are designed to provide some specialist care.(India also has a hospital bed shortage, and rural India has roughly three government hospital beds per 10 000 people, 4 compared with nearly 12 in urban India 5 ).Each community health centre is supposed to be staffed by a surgeon, a physician, an obstetrician or gynaecologist, and a paediatrician.
Abstract 44: TAK1 Regulates Caspase 8 Activation and Necroptotic Signaling via Multiple Cell Death Checkpoints
Authors: Xaioyun Guo, Haifeng Yin, Yi Chen, Lei Li, Jing Li, Qinghang Liu
Journal: Circulation Research (2016)

Necroptosis has emerged as a new form of programmed cell death implicated in a number of pathological conditions such as ischemic injury, neurodegenerative disease, and viral infection. Recent studies indicate that TGFβ-activated kinase 1 (TAK1) is nodal regulator of necroptotic cell death, but the underlying molecular regulatory mechanisms remain elusive. Here we reported that TAK1 regulates necroptotic signaling as well as caspase 8 activation through both NFκB-dependent and -independent mechanisms. Inhibition of TAK1 promoted TNFα-induced necroptosis through the induction of RIP1 phosphorylation/activation and necrosome formation, in the presence of ongoing caspase activation. Further, inhibition of TAK1 triggered two caspase 8 activation pathways through the induction of RIP1-FADD-caspase 8 complex as well as FLIP cleavage/degradation. Mechanistically, our data uncovered an essential role of the adaptor protein TRADD in caspase 8 activation and necrosome formation triggered by TAK1 inhibition. Moreover, ablation of the deubiqutinase CYLD prevented both apoptotic and necroptotic signaling induced by TAK1 inhibition, whereas deletion of the E3 ubiquitin ligase TRAF2 had the opposite effect. Finally, blocking the ubiquitin-proteasome pathway prevented the degradation of key necroptotic signaling proteins and necrosome formation. Thus we identified novel regulatory mechanisms underling the critical role of TAK1 in necroptotic signaling through regulation of multiple cell death checkpoints. Targeting key components of the necroptotic pathway (e.g., TRADD and CYLD) and the ubiquitin-proteasome pathway may represent novel therapeutic strategies for pathological conditions driven by necroptosis.
Efficacy and Safety of First-Line Therapy with Chlorambucil, Rituximab and Individualized Dose Lenalidomide in FCR-Unfit Patients with Advanced Chronic Lymphocytic Leukemia (CLL): A Phase I/II HOVON Trial
Authors: Arnon P. Kater, Marinus H.J. H.J. Van Oers, Yvette Norden, Roberto D. Liu, Martin R. Schipperus, Martine Chamuleau, Marcel Nijland, Jeanette K. Doorduijn, Michel van Gelder, Mels Hoogendoorn, Fransien Croon-de Boer, Shulamit Wittebol, Martijn Kerst, Willem Marijt, Ward Posthuma, Reinier Raymakers, Ron Schaafsma, Johan Dobber, Sabina Kersting, Mark-David Levin
Journal: Blood (2017)
P-230 Is stereotactic microwave ablation of resectable colorectal liver metastasis an alternative for liver resection in the Covid-19 pandemic?
Authors: T. Chapelle, B. Op de Beeck, B. Bracke, M. Niekel, G. Roeyen, V. Hartman, M. Spinhoven, D. Ysebaert
Journal: Annals of Oncology (2021)