tbuckley/cabot-search huggingface dataset:
Impact of broad regulatory regions on Gdf5 expression and function in knee development and susceptibility to osteoarthritis
Authors: Steven K Pregizer, Ata M Kiapour, Mariel Young, Hao Chen, Michael Schoor, Zun Liu, Jiaxue Cao, Vicki Rosen, Terence D Capellini
Journal: Annals of the Rheumatic Diseases (2018)

Given the role of growth and differentiation factor 5 (GDF5) in knee development and osteoarthritis risk, we sought to characterise knee defects resulting from Gdf5 loss of function and how its regulatory regions control knee formation and morphology.The brachypodism (bp) mouse line, which harbours an inactivating mutation in Gdf5, was used to survey how Gdf5 loss of function impacts knee morphology, while two transgenic Gdf5 reporter bacterial artificial chromosome mouse lines were used to assess the spatiotemporal activity and function of Gdf5 regulatory sequences in the context of clinically relevant knee anatomical features.Knees from homozygous bp mice (bp/bp) exhibit underdeveloped femoral condyles and tibial plateaus, no cruciate ligaments, and poorly developed menisci. Secondary ossification is also delayed in the distal femur and proximal tibia. bp/bp mice have significantly narrower femoral condyles, femoral notches and tibial plateaus, and curvier medial femoral condyles, shallower trochlea, steeper lateral tibial slopes and smaller tibial spines. Regulatory sequences upstream from Gdf5 were weakly active in the prenatal knee, while downstream regulatory sequences were active throughout life. Importantly, downstream but not upstream Gdf5 regulatory sequences fully restored all the key morphological features disrupted in the bp/bp mice.Knee morphology is profoundly affected by Gdf5 absence, and downstream regulatory sequences mediate its effects by controlling Gdf5 expression in knee tissues. This downstream region contains numerous enhancers harbouring human variants that span the osteoarthritis association interval. We posit that subtle alterations to morphology driven by changes in downstream regulatory sequence underlie this locus' role in osteoarthritis risk.
Precision Medicine in Type 2 Diabetes: Clinical Markers of Insulin Resistance Are Associated With Altered Short- and Long-term Glycemic Response to DPP-4 Inhibitor Therapy
Authors: John M. Dennis, Beverley M. Shields, Anita V. Hill, Bridget A. Knight, Timothy J. McDonald, Lauren R. Rodgers, Michael N. Weedon, William E. Henley, Naveed Sattar, Rury R. Holman, Ewan R. Pearson, Andrew T. Hattersley, Angus G. Jones
Journal: Diabetes Care (2018)

OBJECTIVE A precision approach to type 2 diabetes therapy would aim to target treatment according to patient characteristics. We examined if measures of insulin resistance and secretion were associated with glycemic response to dipeptidyl peptidase 4 (DPP-4) inhibitor therapy. RESEARCH DESIGN AND METHODS We evaluated whether markers of insulin resistance and insulin secretion were associated with 6-month glycemic response in a prospective study of noninsulin-treated participants starting DPP-4 inhibitor therapy (Predicting Response to Incretin Based Agents [PRIBA] study; n = 254), with replication for routinely available markers in U.K. electronic health care records (Clinical Practice Research Datalink [CPRD]; n = 23,001). In CPRD, we evaluated associations between baseline markers and 3-year durability of response. To test the specificity of findings, we repeated analyses for glucagon-like peptide 1 (GLP-1) receptor agonists (PRIBA, n = 339; CPRD, n = 4,464). RESULTS In PRIBA, markers of higher insulin resistance (higher fasting C-peptide [P = 0.03], HOMA2 insulin resistance [P = 0.01], and triglycerides [P &amp;lt; 0.01]) were associated with reduced 6-month HbA1c response to DPP-4 inhibitors. In CPRD, higher triglycerides and BMI were associated with reduced HbA1c response (both P &amp;lt; 0.01). A subgroup defined by obesity (BMI ≥30 kg/m2) and high triglycerides (≥2.3 mmol/L) had reduced 6-month response in both data sets (PRIBA HbA1c reduction 5.3 [95% CI 1.8, 8.6] mmol/mol [0.5%] [obese and high triglycerides] vs. 11.3 [8.4, 14.1] mmol/mol [1.0%] [nonobese and normal triglycerides]; P = 0.01). In CPRD, the obese, high- triglycerides subgroup also had less durable response (hazard ratio 1.28 [1.16, 1.41]; P &amp;lt; 0.001). There was no association between markers of insulin resistance and response to GLP-1 receptor agonists. CONCLUSIONS Markers of higher insulin resistance are consistently associated with reduced glycemic response to DPP-4 inhibitors. This finding provides a starting point for the application of a precision diabetes approach to DPP-4 inhibitor therapy.
Effectiveness of combination therapy versus monotherapy with a third-generation cephalosporin in bacteraemic pneumococcal pneumonia: A propensity score analysis
Authors: C. De la Calle, H.G. Ternavasio-de la Vega, L. Morata, F. Marco, C. Cardozo, C. García-Vidal, A. Del Rio, C. Cilloniz, A. Torres, J.A. Martínez, J. Mensa, A. Soriano
Journal: Journal of Infection (2018)
Efficacy and safety of varenicline for smoking cessation in people living with HIV in France (ANRS 144 Inter-ACTIV): a randomised controlled phase 3 clinical trial
Authors: Patrick Mercié, Julie Arsandaux, Christine Katlama, Samuel Ferret, Aurélie Beuscart, Christian Spadone, Claudine Duvivier, Jacques Reynes, Nathalie Wirth, Laetitia Moinot, Antoine Bénard, David Zucman, Xavier Duval, Jean-Michel Molina, Bruno Spire, Catherine Fagard, Geneviève Chêne, Hélène Allaguy-Salachy, Julie Arsandaux, Henri-Jean Aubin, Antoine Bénard, Claudine Bernard-Henry, Aurélie Beuscart, Claude Beuscart, Anne Borgne, Olivier Bouchaud, Charles Brahmy, Dominique Breilh, André Cabié, Claude Cateland, Geneviève Chêne, Antoine Cheret, Sandrine Couffin-Cadiergues, Marie-Dominique Dautzenberg, Pierre Dellamonica, Pascale Denis-Kandel, Christine Denis-Vatant, Michel Detilleux, Michel Dupon, Xavier Duval, Claudine Duvivier, Brigitte El Harrar, Catherine Fagard, Marie Christine Fagnen Sylvaire, Samuel Ferret, Simone Guillermet, Christine Jacomet, Vincent Jeantils, Christine Katlama, Marek Korzek, Estibaliz Lazaro, Béatrice Le Maitre, Frédéric Lucht, Marianne Maquet, Audrey Mathieu, Thierry May, Patrick Mercié, Sonia Merigeaud, Laetitia Moinot, Jean-Michel Molina, Philippe Morlat, Alissa Naqvi, Didier Neau, Jean Perriot, Sandrine Pierre-François, Isabelle Poizot-Martin, Elisabeth Quoix, Matthieu Rebillard, Jacques Reynes, Caroline Roussillon, Eric Rosenthal, Thierry Sainte-Marie, Dominique Salmon-Céron, Luminita Schneider, Anne Simon, Malika Soussi, Albert Sotto, Christian Spadone, Bruno Spire, Anne-Marie Taburet, Elina Teicher, Monique Termote, Valery Trosini-Desert, Renaud Verdon, Jean-Paul Viard, Daniel Vittecoq, Muriel Vray, Nathalie Wirth, David Youssi, David Zucman
Journal: The Lancet HIV (2018)
Correlation between Count and Ratio of Nasal eosinophil in Children with Nasal symptoms
Authors: Woo ri Bae, Beom joon Kim, Kyunghoon KIM, Hyejin Lee, Eun Ae Yang, Hwan Soo Kim, Yoon Hong Chun, Jong-seo Yoon, Hyun Hee Kim, Jin Tack Kim
Journal: Journal of Allergy and Clinical Immunology (2018)
Saving Office Practice
Authors: Peter Basch
Journal: Annals of Internal Medicine (2004)

Letters18 May 2004Saving Office PracticePeter Basch, MDPeter Basch, MDFrom MedStar Health, Washington, DC 20003.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-140-10-200405180-00026 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:In his recent editorial (1), Dr. Sox calls attention to the decline of interest in office practice and the potential to help reverse this disturbing trend by improving operational efficiency through the use of information technology. This use of information technology, making practice less burdensome and costly, holds the keys to physician adoption and revitalization of interest in office practice and will help to pave the way for quantum improvements in quality.Development of clinical information technology has been primarily focused on the lofty goals of increasing quality and safety. While laudable, this tact has failed to ...References1. Sox HC. Saving office practice [Editorial]. Ann Intern Med. 2003;139:227-8. [PMID: 12899590] LinkGoogle Scholar2. Johnston D, Pan E, Middleton B, Walker J, Bates DW. The value of computerized physician order entry in ambulatory settings. Center for Information Technology Leadership. 15 June 2003. Accessed at citl.org/research/ACPOE_Executive_Preview.pdf on 31 March 2004. Google Scholar Author, Article, and Disclosure InformationAffiliations: From MedStar Health, Washington, DC 20003. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoSaving Office Practice Harold C. Sox Saving Office Practice Harold C. Sox Saving Office Practice Alan R. Ertle Saving Office Practice Scott Matthew Bolhack Metrics 18 May 2004Volume 140, Issue 10Page: 845KeywordsDiagnostic medicineHealth careHealth care qualityHealth information technologyInformation technologySafety ePublished: 18 May 2004 Issue Published: 18 May 2004 CopyrightCopyright © 2004 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Analysis of criteria for treatment initiation in patients with progressive chronic lymphocytic leukemia
Authors: Pablo Mozas, Alfredo Rivas-Delgado, Tycho Baumann, Neus Villamor, Valentín Ortiz-Maldonado, Marta Aymerich, Dolors Costa, Alba Navarro, Eva Giné, Armando López-Guillermo, Emili Montserrat, Julio Delgado
Journal: Blood Cancer Journal (2018)
Health-related quality of life in adolescents with psoriasis: an interview-based study
Authors: H. Randa, J.J. Lomholt, L. Skov, R. Zachariae
Journal: British Journal of Dermatology (2018)

Psoriasis is a common skin disease affecting the physical, psychological and social well‐being of patients and their families. Most research so far has been limited to adults, and little is known about the qualitative experiences of young people with psoriasis. To provide an in‐depth understanding of the impact of psoriasis on adolescents' health‐related quality of life (HRQoL). Patients and their parents were recruited from a dermatology outpatient clinic, the Danish National Birth Cohort and the Danish Psoriasis Association. Thirty‐six semistructured interviews were conducted with adolescents with psoriasis aged 12–17 years (n = 18), their parents (n = 14) and health professionals working with psoriasis (n = 4). Interviews were digitally recorded, transcribed verbatim and analysed using inductive thematic analysis. The participants reported psoriasis‐related HRQoL challenges within six main themes: physical symptoms, feeling different, psoriasis‐related worry about the future, increased attention, attempts to conceal skin, and treatment‐related frustrations and worry. Taken together, a broad range of the reported difficulties appeared to arise from appearance‐related concerns. The impact of psoriasis and its treatment on the adolescents' daily lives varied considerably. This first in‐depth, qualitative study of HRQoL in adolescents with psoriasis provides a conceptual framework for understanding the impact of psoriasis and its treatment on the physical, psychological and social aspects of their daily lives.
Lessons From the Opioid Epidemic to Reinvigorate Tobacco Control Initiatives
Authors: Ilana Richman, Harlan M. Krumholz
Journal: JAMA (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Encouraging Early Results from the First in-Human Clinical Trial of ADCT-402 (Loncastuximab Tesirine), a Novel Pyrrolobenzodiazepine-Based Antibody Drug Conjugate, in Relapsed/Refractory B-Cell Lineage Non-Hodgkin Lymphoma
Authors: Brad S Kahl, Mehdi Hamadani, Paolo Caimi, Carmelo Carlo-Stella, Erin Reid, Jay Feingold, Kirit M Ardeshna, John Radford, Melhem M Solh, Ki-Young Chung, Leonard Heffner, Shui He, Joseph Boni, Owen Anthony O'Connor
Journal: Blood (2017)
Prevention of tuberculosis in rhesus macaques by a cytomegalovirus-based vaccine
Authors: Scott G Hansen, Daniel E Zak, Guangwu Xu, Julia C Ford, Emily E Marshall, Daniel Malouli, Roxanne M Gilbride, Colette M Hughes, Abigail B Ventura, Emily Ainslie, Kurt T Randall, Andrea N Selseth, Parker Rundstrom, Lauren Herlache, Matthew S Lewis, Haesun Park, Shannon L Planer, John M Turner, Miranda Fischer, Christina Armstrong, Robert C Zweig, Joseph Valvo, Jackie M Braun, Smitha Shankar, Lenette Lu, Andrew W Sylwester, Alfred W Legasse, Martin Messerle, Michael A Jarvis, Lynn M Amon, Alan Aderem, Galit Alter, Dominick J Laddy, Michele Stone, Aurelio Bonavia, Thomas G Evans, Michael K Axthelm, Klaus Früh, Paul T Edlefsen, Louis J Picker
Journal: Nature Medicine (2018)
Meta-analysis of the association of serum vitamin D with pulmonary function
Authors: J Xu, TM Bartz, G Chittoor, G Eiriksdottir, AC Frazier-Wood, Lies Lahousse, J Latourelle, AW Manichaikul, F Sun, Natalie Terzikhan, RG Barr, Guy Brusselle, J Dupuis, SA Gharib, S London, KE North, B Psaty, A Smith, DB Hancock, PA Cassano
Journal: American Journal of Respiratory and Critical Care Medicine (2016)
Risk for Arterial and Venous Thrombosis in Patients With Myeloproliferative Neoplasms
Authors: Malin Hultcrantz, Magnus Björkholm, Paul W. Dickman, Ola Landgren, Åsa R. Derolf, Sigurdur Y. Kristinsson, Therese M.L. Andersson
Journal: Annals of Internal Medicine (2018)

Background: Patients with myeloproliferative neoplasms (MPNs) are reported to be at increased risk for thrombotic events. However, no population-based study has estimated this excess risk compared with matched control participants. Objective: To assess risk for arterial and venous thrombosis in patients with MPNs compared with matched control participants. Design: Matched cohort study. Setting: Population-based setting in Sweden from 1987 to 2009, with follow-up to 2010. Patients: 9429 patients with MPNs and 35 820 matched control participants. Measurements: The primary outcomes were rates of arterial and venous thrombosis. Flexible parametric models were used to calculate hazard ratios (HRs) and cumulative incidence with 95% CIs. Results: The HRs for arterial thrombosis among patients with MPNs compared with control participants at 3 months, 1 year, and 5 years were 3.0 (95% CI, 2.7 to 3.4), 2.0 (CI, 1.8 to 2.2), and 1.5 (CI, 1.4 to 1.6), respectively. The corresponding HRs for venous thrombosis were 9.7 (CI, 7.8 to 12.0), 4.7 (CI, 4.0 to 5.4), and 3.2 (CI, 2.9 to 3.6). The rate was significantly elevated across all age groups and was similar among MPN subtypes. The 5-year cumulative incidence of thrombosis in patients with MPNs showed an initial rapid increase followed by gentler increases during follow-up. The HR for venous thrombosis decreased during more recent calendar periods. Limitation: No information on individual laboratory results or treatment. Conclusion: Patients with MPNs across all age groups have a significantly increased rate of arterial and venous thrombosis compared with matched control participants, with the highest rates at and shortly after diagnosis. Decreases in the rate of venous thrombosis over time likely reflect advances in clinical management. Primary Funding Source: The Cancer Research Foundations of Radiumhemmet, Blodcancerfonden, the Swedish Research Council, the regional agreement on medical training and clinical research between Stockholm County Council and Karolinska Institutet, the Adolf H. Lundin Charitable Foundation, and Memorial Sloan Kettering Cancer Center.
Long-Term Outcomes after Protocolized Sedation versus Usual Care in Ventilated Pediatric Patients
Authors: R. Scott Watson, Lisa A. Asaro, James H. Hertzog, Lauren R. Sorce, Alicia G. Kachmar, Leslie A. Dervan, Derek C. Angus, David Wypij, Martha A. Q. Curley
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Rationale: Whether a nurse-implemented goal-directed sedation protocol resulting in more awake yet calm intubated children affects postdischarge functional status, health-related quality of life, or risk for post-traumatic stress disorder is unknown.Objectives: To compare postdischarge outcomes in children with acute respiratory failure cluster-randomized to a sedation protocol or usual care.Methods: A stratified random sample of 1,360 patients from 31 centers in the RESTORE (Randomized Evaluation of Sedation Titration for Respiratory Failure) trial was assessed by mail, electronically, and/or telephone 6 months after ICU discharge. In treatment group comparisons, we controlled for age, baseline functional status, and severity of illness.Measurements and Main Results: We used the Pediatric Overall Performance Category and the Pediatric Cerebral Performance Category to characterize functional status, the Infant and Toddler Quality of Life Questionnaire (97-item full-length version) (<2 yr old) or Pediatric Quality of Life Inventory (≥2 yr old), and the Child Post-traumatic Stress Disorder Symptom Scale (≥8 yr old and developmentally able). Functional status worsened from baseline to follow-up in 20%. Decline in functional status did not differ by treatment arm and was more common among those with baseline impairment than those with baseline normal function (27 vs. 18%; P < 0.001). There were no significant differences in health-related quality of life total scores by treatment arm. Scores indicating risk of post-traumatic stress disorder occurred in 30%, with no difference between treatment arms.Conclusions: A sedation strategy that allows patients to be more awake and exposes them to fewer sedative and analgesic medications produces no long-term harm. However, postdischarge morbidity after acute respiratory failure is common.Clinical trial registered with www.clinicaltrials.gov (NCT00814099).
The Adiponectin Receptor Agonist AdipoRon Ameliorates Diabetic Nephropathy in a Model of Type 2 Diabetes
Authors: Yaeni Kim, Ji Hee Lim, Min Young Kim, Eun Nim Kim, Hye Eun Yoon, Seok Joon Shin, Bum Soon Choi, Yong-Soo Kim, Yoon Sik Chang, Cheol Whee Park
Journal: Journal of the American Society of Nephrology (2018)

Adiponectin exerts renoprotective effects against diabetic nephropathy (DN) by activating the AMP-activated protein kinase (AMPK)/peroxisome proliferative-activated receptor– α (PPAR α ) pathway through adiponectin receptors (AdipoRs). AdipoRon is an orally active synthetic adiponectin receptor agonist. We investigated the expression of AdipoRs and the associated intracellular pathways in 27 patients with type 2 diabetes and examined the effects of AdipoRon on DN development in male C57BLKS/J db/db mice, glomerular endothelial cells (GECs), and podocytes. The extent of glomerulosclerosis and tubulointerstitial fibrosis correlated with renal function deterioration in human kidneys. Expression of AdipoR1, AdipoR2, and Ca 2+ /calmodulin-dependent protein kinase kinase– β (CaMKK β ) and numbers of phosphorylated liver kinase B1 (LKB1)– and AMPK-positive cells significantly decreased in the glomeruli of early stage human DN. AdipoRon treatment restored diabetes-induced renal alterations in db/db mice. AdipoRon exerted renoprotective effects by directly activating intrarenal AdipoR1 and AdipoR2, which increased CaMKK β , phosphorylated Ser 431 LKB1, phosphorylated Thr 172 AMPK, and PPAR α expression independently of the systemic effects of adiponectin. AdipoRon-induced improvement in diabetes-induced oxidative stress and inhibition of apoptosis in the kidneys ameliorated relevant intracellular pathways associated with lipid accumulation and endothelial dysfunction. In high-glucose–treated human GECs and murine podocytes, AdipoRon increased intracellular Ca 2+ levels that activated a CaMKK β /phosphorylated Ser 431 LKB1/phosphorylated Thr 172 AMPK/PPAR α pathway and downstream signaling, thus decreasing high-glucose–induced oxidative stress and apoptosis and improving endothelial dysfunction. AdipoRon further produced cardioprotective effects through the same pathway demonstrated in the kidney. Our results show that AdipoRon ameliorates GEC and podocyte injury by activating the intracellular Ca 2+ /LKB1-AMPK/PPAR α pathway, suggesting its efficacy for treating type 2 diabetes–associated DN.
Cold contact urticaria: association of positive ice cube test and autoimmunity
Authors: Rebeca M. Brugnolli, Pamella Diogo Salles, Larissa P. Cau, Raisa B. Castro, Jorge Elias Kalil Filho, Antonio Abilio Motta, Rosana C. Agondi
Journal: Journal of Allergy and Clinical Immunology (2018)
Tamibarotene As Maintenance Therapy for Acute Promyelocytic Leukemia Improved Long Term Relapse-Free Survival: 7-Year Results from a Randomized Controlled Trial, JALSG-APL204
Authors: Akihiro Takeshita, Norio Asou, Masamitsu Yanada, Toru Sakura, Yasunori Ueda, Masashi Sawa, Nobuaki Dobashi, Makoto Onizuka, Yasuhiro Taniguchi, Masaru Nakagawa, Shigehisa Tamaki, Maki Hagihara, Katsumichi Fujimaki, Hiroaki Furumaki, Hiroyuki Fujita, Noriko Usui, Yukio Kobayashi, Hitoshi Kiyoi, Shigeki Ohtake, Yoshiko Atsuta, Itaru Matsumura, Tomoki Naoe, Yasushi Miyazaki
Journal: Blood (2017)
Environmental Determinants of Breast Cancer
Authors: Robert A. Hiatt, Julia Green Brody
Journal: Annual Review of Public Health (2018)

In the United States, breast cancer is the most common invasive malignancy and the second most common cause of death from cancer in women. Reproductive factors, estrogen, and progesterone have major causal roles, but concerns about other potential causes in the external environment continue to drive research inquiries and stimulate calls for action at the policy level. The environment is defined as anything that is not genetic and includes social, built, and chemical toxicant aspects. This review covers the scope of known and suspected environmental factors that have been associated with breast cancer and illustrates how epidemiology, toxicology, and mechanistic studies work together to create the full picture of environmental effects on this malignancy. Newer approaches to risk-related evaluations may allow this field to move forward and more clearly delineate actionable environmental causes of this most common of cancers in women.