tbuckley/cabot-search huggingface dataset:
Implementing Health Reform: Improved Data Collection and the Monitoring of Health Disparities
Authors: Rashida Dorsey, Garth Graham, Sherry Glied, David Meyers, Carolyn Clancy, Howard Koh
Journal: Annual Review of Public Health (2013)

The relative lack of standards for collecting data on population subgroups has not only limited our understanding of health disparities, but also impaired our ability to develop policies to eliminate them. This article provides background about past challenges to collecting data by race/ethnicity, primary language, sex, and disability status. It then discusses how passage of the Affordable Care Act has provided new opportunities to improve data-collection standards for the demographic variables of interest and, as such, a better understanding of the characteristics of populations served by the U.S. Department of Health and Human Services (HHS). The new standards have been formally adopted by the Secretary of HHS for application in all HHS-sponsored population health surveys involving self-reporting. The new data-collection standards will not only promote the uniform collection and utilization of demographic data, but also help the country shape future programs and policies to advance public health and to reduce disparities.
Knock-in Mutation of the Distal Four Tyrosines of Linker for Activation of T Cells Blocks Murine T Cell Development
Authors: Connie L. Sommers, Rashmi K. Menon, Alexander Grinberg, Weiguo Zhang, Lawrence E. Samelson, Paul E. Love
Journal: The Journal of Experimental Medicine (2001)

The integral membrane adapter protein linker for activation of T cells (LAT) performs a critical function in T cell antigen receptor (TCR) signal transduction by coupling the TCR to downstream signaling pathways. After TCR engagement, LAT is tyrosine phosphorylated by ZAP-70 creating docking sites for multiple src homology 2-containing effector proteins. In the Jurkat T cell line, the distal four tyrosines of LAT bind PLCgamma-1, Grb2, and Gads. Mutation of these four tyrosine residues to phenylalanine (4YF) blocked TCR-mediated calcium mobilization, Erk activation, and nuclear factor (NF)-AT activation. In this study, we examined whether these four tyrosine residues were essential for T cell development by generating LAT "knock-in" mutant mice that express the 4YF mutant protein under the control of endogenous LAT regulatory sequences. Significantly, the phenotype of 4YF knock-in mice was identical to LAT(-/)- (null) mice; thymocyte development was arrested at the immature CD4(-)CD8(-) stage and no mature T cells were present. Knock-in mice expressing wild-type LAT protein, generated by a similar strategy, displayed a normal T cell developmental profile. These results demonstrate that the distal four tyrosine residues of LAT are essential for preTCR signaling and T cell development in vivo.
Multivalent Integrin-Specific Ligands Enhance Tissue Healing and Biomaterial Integration
Authors: Timothy A. Petrie, Jenny E. Raynor, David W. Dumbauld, Ted T. Lee, Subodh Jagtap, Kellie L. Templeman, David M. Collard, Andrés J. García
Journal: Science Translational Medicine (2010)

Titanium implants coated with nanoclustered ligands for integrin adhesion receptors are tightly integrated into bone for orthopedic applications.
BLOODLESS OPERATION FOR HAEMORRHOIDS AND PROLAPSUS ANI
Authors: F. M. Bell
Journal: BMJ (1916)

were no enlarged glands.Professor Walk-er Hall in-vestigated the nature of the lesion, and has been good enough to allow me to publish his report, which is as follows:The mass consists of carcinomatous tissues.The submucous, muscular, and subperitoneal tissues are inva(led by glandular cells arranged atypically.In places the infiltration is so marked that individual blundles of muscle flbres are separated by masses of cancer cells.The cells thlemselves show colloid degeneration, and this process is general throughout the specimen.There is evidence of spread by lymphatic vessels.
Advanced Heart Failure Treated with Continuous-Flow Left Ventricular Assist Device
Authors: Mark S. Slaughter, Joseph G. Rogers, Carmelo A. Milano, Stuart D. Russell, John V. Conte, David Feldman, Benjamin Sun, Antone J. Tatooles, Reynolds M. Delgado, James W. Long, Thomas C. Wozniak, Waqas Ghumman, David J. Farrar, O. Howard Frazier
Journal: New England Journal of Medicine (2009)

Patients with advanced heart failure have improved survival rates and quality of life when treated with implanted pulsatile-flow left ventricular assist devices as compared with medical therapy. New continuous-flow devices are smaller and may be more durable than the pulsatile-flow devices.In this randomized trial, we enrolled patients with advanced heart failure who were ineligible for transplantation, in a 2:1 ratio, to undergo implantation of a continuous-flow device (134 patients) or the currently approved pulsatile-flow device (66 patients). The primary composite end point was, at 2 years, survival free from disabling stroke and reoperation to repair or replace the device. Secondary end points included survival, frequency of adverse events, the quality of life, and functional capacity.Preoperative characteristics were similar in the two treatment groups, with a median age of 64 years (range, 26 to 81), a mean left ventricular ejection fraction of 17%, and nearly 80% of patients receiving intravenous inotropic agents. The primary composite end point was achieved in more patients with continuous-flow devices than with pulsatile-flow devices (62 of 134 [46%] vs. 7 of 66 [11%]; P<0.001; hazard ratio, 0.38; 95% confidence interval, 0.27 to 0.54; P<0.001), and patients with continuous-flow devices had superior actuarial survival rates at 2 years (58% vs. 24%, P=0.008). Adverse events and device replacements were less frequent in patients with the continuous-flow device. The quality of life and functional capacity improved significantly in both groups.Treatment with a continuous-flow left ventricular assist device in patients with advanced heart failure significantly improved the probability of survival free from stroke and device failure at 2 years as compared with a pulsatile device. Both devices significantly improved the quality of life and functional capacity. (ClinicalTrials.gov number, NCT00121485.)
Lymphocyte cytotoxicity in systemic sclerosis: no increase on short-term culture with established human cell lines.
Authors: J K Wright, P Hughes, N R Rowell
Journal: Annals of the Rheumatic Diseases (1982)

Lymphocyte cytotoxicity towards 4 established human epithelial and fibroblast cell lines was investigated in 18 patients with systemic sclerosis by means of both whole blood and peripheral blood mononuclear cells in short term (18 h) Cr-release assays. No difference in the levels of cytotoxicity was found in patients compared with 25 normal controls, even when allowance was made for the severity of the disease and the sex of patients and controls. It is suggested that long-term (3-6 days) culture may be necessary to demonstrate the increased lymphocyte cytotoxicity originally described in the disorder.
Abnormal HDL Apolipoprotein A-I and A-II Kinetics in Hemodialysis Patients
Authors: Keiko Okubo, Katsunori Ikewaki, Soichi Sakai, Norio Tada, Yoshindo Kawaguchi, Seibu Mochizuki
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. Low levels of HDL cholesterol and its major apoprotein constituents apoA-I and apoA-II are common in patients who have ESRD and are undergoing hemodialysis (HD), but the metabolic basis for the low HDL is poorly understood. This study aimed to investigate <i>in vivo</i> metabolism of apoA-I and apoA-II in five normotriglyceridemic ESRD-HD patients and compared it with five control subjects using endogenous stable isotope labeling methods coupled with a multicompartmental modeling. HDL cholesterol, apoA-I, and apoA-II levels were markedly decreased in the ESRD-HD patients by 39, 30, and 44%, respectively, in comparison with the control subjects. Fractional catabolic rate of apoA-I was found to be significantly increased by 59% to 0.360 ± 0.084/d in ESRD-HD patients as compared with control subjects of 0.227 ± 0.076/d (<i>P</i> = 0.028), whereas the production rates remained unchanged. Conversely, the apoA-II production rate significantly decreased by 31% to 1.50 ± 0.61 mg/kg per d in the ESRD-HD patients in comparison with control subjects of 2.17 ± 0.40 mg/kg per d (<i>P</i> = 0.047) with apoA-II fractional catabolic rate unchanged. These results revealed that the decreased levels of apoA-I are due solely to the increased rate of catabolism, whereas the reduced apoA-II levels are due primarily to the decreased rate of production in ESRD-HD patients. This differential regulation of apoA-I and apoA-II further supports the concept that apoA-I and apoA-II have distinct metabolic pathways.
Acute Onset of Decreased Vision and Hearing Traced to Hemodialysis Treatment With Aged Dialyzers
Authors: J C Hutter, M J Kuehnert, R R Wallis, A D Lucas, S Sen, W R Jarvis
Journal: JAMA (2000)

A recent event in which 7 patients at 1 hospital developed decreased vision and hearing, conjunctivitis, headache, and other severe neurologic symptoms 7 to 24 hours after hemodialysis drew attention to the issue of the long-term integrity of dialysis machines and materials.To determine the cause of the adverse reactions that occurred during this event.Retrospective cohort study of all 9 patients who received hemodialysis at hospital A on September 18, 1996, the day of the outbreak. A case-patient was defined as any hospital A patient with acute onset of decreased vision and hearing and conjunctivitis after dialysis on that day. Non-case-patients were all others who underwent dialysis at hospital A on that day but did not develop adverse reactions. In an attempt to reproduce the conditions of the event, cellulose acetate dialysis membranes of various ages were retrieved from other sources and tested for physical and chemical degradation, and degradation products were identified, characterized, and injected intravenously into rabbits.Clinical signs and symptoms, time to resolution of symptoms, mortality, and dialyzer type and age, for case- vs non-case-patients.Seven of the 9 patients met the case definition. In addition to diminished vision and hearing, conjunctivitis, and headache, some case-patients had blood leak alarm activation (n=6), confusion/lethargy (n=5), corneal opacification (n=4), cardiac arrest (n=2), or other neurologic signs and symptoms. One case-patient died during hospitalization after the event; 5 of 7 case-patients died within 13 months. Resolution of signs and symptoms varied but persisted more than 3 years or until death in 3 of the 6 patients who survived hospitalization. All case-patients but no non-case-patients were exposed to 11.5-year-old cellulose acetate dialyzers (all of these dialyzers were discarded by the hospital before our investigation). Laboratory investigation of field-retrieved 0- to 13.6-year-old dialyzers of similar type indicated significant chemical degradation in the older membranes. In vivo injection of extracts of membrane degradation products produced iritis and hemorrhages in rabbits' eyes.Severe patient injury was associated with exposure to aged cellulose acetate membranes of dialyzers, allowing cellulose acetate degradation products to enter the blood. Clinicians should be aware that aged cellulose acetate membranes may cause severe adverse reactions.
Secondary amyloidosis affecting the skin in arthropathic psoriasis
Authors: S. C. SHARMA, G. MORTIMER, S. KENNEDY, J. THOMSON
Journal: British Journal of Dermatology (1983)

A case of secondary systemic amyloidosis associated with arthropathic psoriasis is reported. Amyloid A protein was demonstrated in the kidneys, gastrointestinal tract and liver, and also in psoriatic and clinically uninvolved skin.
Identification of mutations in the coding sequence of the proto-oncogene c-kit in a human mast cell leukemia cell line causing ligand-independent activation of c-kit product.
Authors: T Furitsu, T Tsujimura, T Tono, H Ikeda, H Kitayama, U Koshimizu, H Sugahara, J H Butterfield, L K Ashman, Y Kanayama
Journal: Journal of Clinical Investigation (1993)

The c-kit proto-oncogene encodes a receptor tyrosine kinase. Binding of c-kit ligand, stem cell factor (SCF) to c-kit receptor (c-kitR) is known to activate c-kitR tyrosine kinase, thereby leading to autophosphorylation of c-kitR on tyrosine and to association of c-kitR with substrates such as phosphatidylinositol 3-kinase (PI3K). In a human mast cell leukemia cell line HMC-1, c-kitR was found to be constitutively phosphorylated on tyrosine, activated, and associated with PI3K without the addition of SCF. The expression of SCF mRNA transcript in HMC-1 cells was not detectable by means of PCR after reverse transcription (RT-PCR) analysis, suggesting that the constitutive activation of c-kitR was ligand independent. Sequencing of whole coding region of c-kit cDNA revealed that c-kit genes of HMC-1 cells were composed of a normal, wild-type allele and a mutant allele with two point mutations resulting in intracellular amino acid substitutions of Gly-560 for Val and Val-816 for Asp. Amino acid sequences in the regions of the two mutations are completely conserved in all of mouse, rat, and human c-kit. In order to determine the causal role of these mutations in the constitutive activation, murine c-kit mutants encoding Gly-559 and/or Val-814, corresponding to human Gly-560 and/or Val-816, were constructed by site-directed mutagenesis and expressed in a human embryonic kidney cell line, 293T cells. In the transfected cells, both c-kitR (Gly-559, Val-814) and c-kitR (Val-814) were abundantly phosphorylated on tyrosine and activated in immune complex kinase reaction in the absence of SCF, whereas tyrosine phosphorylation and activation of c-kitR (Gly-559) or wild-type c-kitR was modest or little, respectively. These results suggest that conversion of Asp-816 to Val in human c-kitR may be an activating mutation and responsible for the constitutive activation of c-kitR in HMC-1 cells.
Anisocoria From Scopolamine Patches
Authors: Bruce H. Price
Journal: JAMA (1985)

<h3>To the Editor.—Report of a Case.—</h3> I was confronted with an unexpected situation while on an expedition in the Galapagos Islands off Ecuador. A 25-year-old woman was noted to have an enlarged left pupil. She complained of drowsiness and diarrhea of one day's duration. My examination revealed a lethargic woman with an 8-mm left pupil fixed to light and convergence. Her remaining neurological examination results were normal. The patient adamantly denied the use of ophthalmic solutions or ointments in the left eye. Her medical history was unremarkable. The grave differential diagnosis of intracranial neoplasm, subdural hematoma, and aneurysm came to mind. After discussing the urgent situation with our ship's captain, I reexamined her and found a scopolamine patch behind her left ear. Her physician in the United States had prescribed it in advance of the trip, and she had prophylactically applied it the previous day before we boarded the yacht.
A misplaced lncRNA causes brachydactyly in humans
Authors: Philipp G. Maass, Andreas Rump, Herbert Schulz, Sigmar Stricker, Lisanne Schulze, Konrad Platzer, Atakan Aydin, Sigrid Tinschert, Mary B. Goldring, Friedrich C. Luft, Sylvia Bähring
Journal: Journal of Clinical Investigation (2012)

Translocations are chromosomal rearrangements that are frequently associated with a variety of disease states and developmental disorders. We identified 2 families with brachydactyly type E (BDE) resulting from different translocations affecting chromosome 12p. Both translocations caused downregulation of the parathyroid hormone-like hormone (PTHLH) gene by disrupting the cis-regulatory landscape. Using chromosome conformation capturing, we identified a regulator on chromosome 12q that interacts in cis with PTHLH over a 24.4-megabase distance and in trans with the sex-determining region Y-box 9 (SOX9) gene on chromosome 17q. The element also harbored a long noncoding RNA (lncRNA). Silencing of the lncRNA, PTHLH, or SOX9 revealed a feedback mechanism involving an expression-dependent network in humans. In the BDE patients, the human lncRNA was upregulated by the disrupted chromosomal association. Moreover, the lncRNA occupancy at the PTHLH locus was reduced. Our results document what we believe to be a novel in cis- and in trans-acting DNA and lncRNA regulatory feedback element that is reciprocally regulated by coding genes. Furthermore, our findings provide a systematic and combinatorial view of how enhancers encoding lncRNAs may affect gene expression in normal development.
Goal-Directed Resuscitation for Patients with Early Septic Shock
Journal: New England Journal of Medicine (2014)

Early goal-directed therapy (EGDT) has been endorsed in the guidelines of the Surviving Sepsis Campaign as a key strategy to decrease mortality among patients presenting to the emergency department with septic shock. However, its effectiveness is uncertain.In this trial conducted at 51 centers (mostly in Australia or New Zealand), we randomly assigned patients presenting to the emergency department with early septic shock to receive either EGDT or usual care. The primary outcome was all-cause mortality within 90 days after randomization.Of the 1600 enrolled patients, 796 were assigned to the EGDT group and 804 to the usual-care group. Primary outcome data were available for more than 99% of the patients. Patients in the EGDT group received a larger mean (±SD) volume of intravenous fluids in the first 6 hours after randomization than did those in the usual-care group (1964±1415 ml vs. 1713±1401 ml) and were more likely to receive vasopressor infusions (66.6% vs. 57.8%), red-cell transfusions (13.6% vs. 7.0%), and dobutamine (15.4% vs. 2.6%) (P<0.001 for all comparisons). At 90 days after randomization, 147 deaths had occurred in the EGDT group and 150 had occurred in the usual-care group, for rates of death of 18.6% and 18.8%, respectively (absolute risk difference with EGDT vs. usual care, -0.3 percentage points; 95% confidence interval, -4.1 to 3.6; P=0.90). There was no significant difference in survival time, in-hospital mortality, duration of organ support, or length of hospital stay.In critically ill patients presenting to the emergency department with early septic shock, EGDT did not reduce all-cause mortality at 90 days. (Funded by the National Health and Medical Research Council of Australia and the Alfred Foundation; ARISE ClinicalTrials.gov number, NCT00975793.).
Calorie Restriction-like Effects of 30 Days of Resveratrol Supplementation on Energy Metabolism and Metabolic Profile in Obese Humans
Authors: Silvie Timmers, Ellen Konings, Lena Bilet, Riekelt H. Houtkooper, Tineke van de Weijer, Gijs H. Goossens, Joris Hoeks, Sophie van der Krieken, Dongryeol Ryu, Sander Kersten, Esther Moonen-Kornips, Matthijs K.C. Hesselink, Iris Kunz, Vera B. Schrauwen-Hinderling, Ellen E. Blaak, Johan Auwerx, Patrick Schrauwen
Journal: Cell Metabolism (2011)
Evolution of Abnormal Plasma Glucagon Responses to Mixed-Meal Feedings in Youth With Type 1 Diabetes During the First 2 Years After Diagnosis
Authors: Jennifer Sherr, Eva Tsalikian, Larry Fox, Bruce Buckingham, Stuart Weinzimer, William V. Tamborlane, Neil H. White, Ana Maria Arbelaez, Craig Kollman, Katrina J. Ruedy, Peiyao Cheng, Roy W. Beck
Journal: Diabetes Care (2014)

To examine the evolution of the dysregulated glucagon responses to mixed-meal tolerance tests (MMTTs) in youth with recent-onset type 1 diabetes (T1D).MMTTs were performed in 25 youth (9-18 years of age) with 1.5-12 months disease duration (year 1); 22 subjects were restudied 1 year later (year 2). Twenty nondiabetic (ND) control children were also studied.In T1D children, MMTT-stimulated increases in glucagon were significantly greater than that in ND children (median increments: year 1, 21 pg/mL [16-30]; year 2, 25 pg/mL [16-30]; ND, 9 pg/mL [5-16]; P = 0.001 and P < 0.001, respectively).In comparison with ND control children, exaggerated plasma glucagon responses to mixed-meal feedings are observed in youth with T1D within the first 2 years of diagnosis. Further studies to determine whether suppression of these abnormal responses may help to improve glycemic control are warranted.
Off-the-shelf in-shoe heel inserts: does cost matter?
Authors: A K Ramanathan, M C John, G P Arnold, L A Cochrane, R J Abboud
Journal: British Journal of Sports Medicine (2007)

A growing exercise culture has lead to an increase in the use of off-the-shelf heel inserts. While there are a variety of designs in a spectrum of cost ranges, probably the ease of availability and cost would mainly determine the choice of purchase. This study was designed to determine whether expensive designs provide better pressure attenuation under the heel than their less expensive counterparts.Six brands of off-the-shelf heel inserts were tested. Selection of these was based purely on their availability in all sizes. Cost per pair ranged from 6 pounds sterling to 30 pounds sterling. Thirty-five asymptomatic subjects walked on a 10 m walkway, once with no inserts and once with each pair of inserts. The Pedar in-shoe system recorded a range of parameters under the heel.Institute of Motion Analysis and Research, Ninewells Hospital and Medical School, University of Dundee.Evaluation of plantar pressure parameters under the heel.All inserts reduced peak pressure under the heel. Maximum force and pressure-time integral also decreased. Contact time generally increased with the use of inserts. Values of contact area with and without inserts were comparable.No significant differences were observed under the heel between the pressure attenuation properties of the lowest-priced and the most expensive designs, and hence the less expensive inserts can be considered as good as the expensive brands. However, the endurance power of these inserts may differ and this should be evaluated.
A role for 12R-lipoxygenase in MUC5AC expression by respiratory epithelial cells
Authors: Ignacio Garcia-Verdugo, Fatima BenMohamed, Sonja Tattermusch, Dominique Leduc, Gilles Charpigny, Michel Chignard, Mario Ollero, Lhousseine Touqui
Journal: European Respiratory Journal (2012)

Eicosanoids are metabolites of arachidonic acid produced by cyclooxygenases (COXs) or lipoxygenases (LOXs). They mediate inflammation and mucus secretion in chronic pulmonary inflammatory diseases. The gel-forming mucin MUC5AC is over-expressed in the airways of patients with these diseases. MUC5AC expression is mediated by an extracellular signal-regulated kinase (ERK)/Sp1 dependent mechanism. Our aim was to study the role of eicosanoids and their signalling pathways in MUC5AC expression. Inhibitors of 12-LOX, but not those of COX, 5-LOX or 15-LOX, reduce MUC5AC expression induced by phorbol myristate acetate (PMA) in the bronchial epithelial cell line NCI-H292. These inhibitors also abrogate the production of whole mucus by cell monolayers. Two forms of 12-LOX (R and S) exist in mammals. Using siRNAs we show that 12R-LOX but not 12S-LOX is involved in MUC5AC expression induced by PMA, lipopolysaccharide or transforming growth factor-α. 12R-LOX also participates in MUC2 and MUC5B expression, although to a lesser extent than for MUC5AC. Contrarily, 12R-LOX silencing does not modify interleukin-8 production. 12-LOX inhibitors reduce ERK activation and Sp1 translocation induced by PMA. Moreover, the 12R-LOX product 12(R)-hydroxyeicosatetraenoic acid, induces MUC5AC expression, ERK activation and Sp1 translocation. 12R-LOX is involved in MUC5AC expression. This occurs <i>via</i> ERK- and Sp1-signalling pathways.
Initial Diagnosis of Leprosy in Patients Treated by an Ophthalmologist and Confirmation by Conventional Analysis and Polymerase Chain Reaction
Authors: Imtiaz A. Chaudhry, Farrukh A. Shamsi, Elsanusi Elzaridi, Abdulaziz Awad, Hamad Al-Fraikh, Mohammed Al-Amry, Hassan Al-Dhibi, Fenwick C. Riley
Journal: Ophthalmology (2007)