tbuckley/cabot-search huggingface dataset:
Albuminuria Is a Target for Renoprotective Therapy Independent from Blood Pressure in Patients with Type 2 Diabetic Nephropathy
Authors: Wouter B.A. Eijkelkamp, Zhongxin Zhang, Giuseppe Remuzzi, Hans-Henrik Parving, Mark E. Cooper, William F. Keane, Shahnaz Shahinfar, Gilbert W. Gleim, Matthew R. Weir, Barry M. Brenner, Dick de Zeeuw
Journal: Journal of the American Society of Nephrology (2007)

Albuminuria reduction could be renoprotective in hypertensive patients with diabetic nephropathy. However, the current use of renin-angiotensin-system intervention is targeted to BP only. Therefore, this study investigated the adequacy of this approach in 1428 patients with hypertension and diabetic nephropathy from the placebo-controlled Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) study. Investigated were the extent of discordance in treatment effects on systolic BP (SBP) and albuminuria and its association with renal outcome in a multivariate Cox model. Among patients with a reduced SBP during treatment, a lack of albuminuria reduction was observed in 37, 26, and 51% (total, losartan, and placebo, respectively) at month 6. SBP or albuminuria reduction was associated with a lower risk for ESRD, whereas combined SBP and albuminuria reduction was associated with the lowest risk for events. Across all categories of SBP change, a progressively lower ESRD hazard ratio was observed with a larger albuminuria reduction. A lower residual level of albuminuria was also associated with lower ESRD risk. In conclusion, changes in albuminuria are not concordant in a substantial proportion of patients when titrated for BP. Meanwhile, the ESRD risk showed a clear dependence on albuminuria reduction. The ESRD risk also showed dependence on the residual level of albuminuria, even in patients who reached the current SBP target. Antihypertensive treatment that is aimed at improving renal outcomes in patients with diabetic nephropathy may therefore require a dual strategy, targeting both SBP and albuminuria reduction.
Implementation of an Evidence-based Extubation Readiness Bundle in 499 Brain-injured Patients. A Before–After Evaluation of a Quality Improvement Project
Authors: Antoine Roquilly, Raphaël Cinotti, Samir Jaber, Mickael Vourc’h, Florence Pengam, Pierre Joachim Mahe, Karim Lakhal, Dominique Demeure Dit Latte, Nelly Rondeau, Olivier Loutrel, Jérôme Paulus, Bertrand Rozec, Yvonnick Blanloeil, Marie-Anne Vibet, Véronique Sebille, Fanny Feuillet, Karim Asehnoune
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Mechanical ventilation is associated with morbidity in patients with brain injury.This study aims to assess the effectiveness of an extubation readiness bundle to decrease ventilator time in patients with brain injury.Before-after design in two intensive care units (ICUs) in one university hospital. Brain-injured patients ventilated more than 24 hours were evaluated during two phases (a 3-yr control phase followed by a 22-mo intervention phase). Bundle components were protective ventilation, early enteral nutrition, standardization of antibiotherapy for hospital-acquired pneumonia, and systematic approach to extubation. The primary endpoint was the duration of mechanical ventilation.A total of 299 and 200 patients, respectively, were analyzed in the control and the intervention phases of this before-after study. The intervention phase was associated with lower tidal volume (P < 0.01), higher positive end-expiratory pressure (P < 0.01), and higher enteral intake in the first 7 days (P = 0.01). The duration of mechanical ventilation was 14.9 ± 11.7 days in the control phase and 12.6 ± 10.3 days in the intervention phase (P = 0.02). The hazard ratio for extubation was 1.28 (95% confidence interval [CI], 1.04-1.57; P = 0.02) in the intervention phase. Adjusted hazard ratio was 1.40 (95% CI, 1.12-1.76; P < 0.01) in multivariate analysis and 1.34 (95% CI, 1.03-1.74; P = 0.02) in propensity score-adjusted analysis. ICU-free days at Day 90 increased from 50 ± 33 in the control phase to 57 ± 29 in the intervention phase (P < 0.01). Mortality at Day 90 was 28.4% in the control phase and 23.5% in the intervention phase (P = 0.22).The implementation of an evidence-based extubation readiness bundle was associated with a reduction in the duration of ventilation in patients with brain injury.
Evidence of Clinical Utility: An Unmet Need in Molecular Diagnostics for Patients with Cancer
Authors: David R. Parkinson, Robert T. McCormack, Susan M. Keating, Steven I. Gutman, Stanley R. Hamilton, Elizabeth A. Mansfield, Margaret A. Piper, Patricia DeVerka, Felix W. Frueh, J. Milburn Jessup, Lisa M. McShane, Sean R. Tunis, Caroline C. Sigman, Gary J. Kelloff
Journal: Clinical Cancer Research (2014)

Abstract This article defines and describes best practices for the academic and business community to generate evidence of clinical utility for cancer molecular diagnostic assays. Beyond analytical and clinical validation, successful demonstration of clinical utility involves developing sufficient evidence to demonstrate that a diagnostic test results in an improvement in patient outcomes. This discussion is complementary to theoretical frameworks described in previously published guidance and literature reports by the U.S. Food and Drug Administration, Centers for Disease Control and Prevention, Institute of Medicine, and Center for Medical Technology Policy, among others. These reports are comprehensive and specifically clarify appropriate clinical use, adoption, and payer reimbursement for assay manufacturers, as well as Clinical Laboratory Improvement Amendments–certified laboratories, including those that develop assays (laboratory developed tests). Practical criteria and steps for establishing clinical utility are crucial to subsequent decisions for reimbursement without which high-performing molecular diagnostics will have limited availability to patients with cancer and fail to translate scientific advances into high-quality and cost-effective cancer care. See all articles in this CCR Focus section, “The Precision Medicine Conundrum: Approaches to Companion Diagnostic Co-development.” Clin Cancer Res; 20(6); 1428–44. ©2014 AACR.
STAPLE: Stable Alginate Gel Prepared by Linkage Exchange from Ionic to Covalent Bonds
Authors: Sang Hyeon Hong, Mikyung Shin, Junhee Lee, Ji Hyun Ryu, Suhee Lee, Jae Wook Yang, Wan Doo Kim, Haeshin Lee
Journal: Advanced Healthcare Materials (2015)

A new Ca2+-alginate hydrogel with improved physical stability is prepared by covalent tethering of catechols. Ionic to covalent bond transition spontaneously occurs in physiological conditions. It is found that the kinetics of leaching out of Ca2+ ions from the chelated carboxylates and oxidative intercatechol cross-linking is similar, successfully maintaining the original physical shapes without conventionally performed treatment of cationic polymers on the surface Ca2+-alginate hydrogels.
NOTES ON THE TREATMENT OF DIPHTHERIA
Authors: T. B. Rhodes
Journal: BMJ (1906)

A healthy, urban-dwelling man presented with lassitude, jaundice without increased liver enzymes or obstructive features on imaging, brief acute kidney injury, leucocytosis with near-normal C reactive protein and markedly increased serum amylase and lipase. Leptospirosis was not considered for 10 days because of the low incidence of the disease in the country, absent animal contact and physicians’ low index of suspicion. Presentation without fever and without the commonly associated abdominal pain, myalgia, headache, thrombocytopaenia or elevated serum creatine kinase added to the diagnostic challenge. Once an infectious cause of acute pancreatitis was contemplated, leptospirosis was immediately sought and diagnosed by PCR of urine and microscopic agglutination test, and he fully recovered on ceftriaxone. Physicians in countries with a low incidence of leptospirosis should be more aware of the possibility of the disease even when several key features such as fever or pain are missing and the patient has a rare infectious acute pancreatitis.
High-Dose Therapy and Autologous Hematopoietic Stem-Cell Transplantation Does Not Increase the Risk of Second Neoplasms for Patients With Hodgkin's Lymphoma: A Comparison of Conventional Therapy Alone Versus Conventional Therapy Followed by Autologous Hematopoietic Stem-Cell Transplantation
Authors: Donna L. Forrest, Donna E. Hogge, Thomas J. Nevill, Stephen H. Nantel, Michael J. Barnett, John D. Shepherd, Heather J. Sutherland, Cynthia L. Toze, Clayton A. Smith, Julye C. Lavoie, Kevin W. Song, Nicholas J. Voss, Randy D. Gascoyne, Joseph M. Connors
Journal: Journal of Clinical Oncology (2005)

To determine the incidence of second malignancies among patients with Hodgkin's lymphoma (HL) treated with autologous hematopoietic stem cell transplantation (AHSCT) compared with patients receiving conventional therapy alone and to identify potential risk factors for their occurrence.We analyzed data on 1,732 consecutive patients with HL treated at the British Columbia Cancer Agency from 1976 to 2001, including 202 patients undergoing AHSCT. The median follow-up duration was 9.8 years for the whole cohort, 9.7 years for those patients treated with conventional therapy, and 7.8 years from AHSCT.The cumulative incidence of developing any second malignancy 15 years after therapy for HL was 9% (risk ratio = 3.5; P < .001); however, the incidence did not differ between those patients receiving conventional therapy alone compared with those undergoing AHSCT (10% and 8%, respectively; P = .48). In multivariate analysis, the only factor significantly associated with an increased risk of developing any second neoplasm or solid tumor was age > or = 35 years (P < .0001). An increased risk of therapy-induced acute myeloid leukemia and therapy-induced myelodysplastic syndrome was seen for patients aged > or = 35 years (P = .03) and stage III/IV (P = .04).Patients with HL are at increased risk of developing a second neoplasm. However, those patients undergoing AHSCT do not seem to be at greater risk compared with those patients receiving conventional therapy alone, at least during the first decade after therapy.
Prevalence of Low Glomerular Filtration Rate in Nondiabetic Americans
Authors: Catherine M. Clase, Amit X. Garg, Bryce A. Kiberd
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. End-stage renal disease is an important and costly health problem. Strategies for its prevention are urgently needed. Knowledge of the population-based prevalence of renal insufficiency in nondiabetic adults would inform such strategies. Black and white nondiabetic adult participants in the Third National Health and Nutrition Examination Survey were analyzed. The analysis was stratified by age, gender, and race, and four clinically applicable methods were used to assess renal function. There were 13,251 complete records for analysis. By the Modification of Diet in Renal Diseases (MDRD) GFR (GFR) prediction Equation 7, 58% (95% confidence interval [CI], 56 to 60%) of the total adult nondiabetic black and white US population had MDRD GFR below 80 ml/min per 1.73m 2 , 13% (95% CI, 11 to 14%) below 60 ml/min per 1.73m 2 , and 0.26% (95% CI, 0.19 to 0.33%) below 30 ml/min per 1.73m 2 . By the Cockcroft-Gault formula, the equivalent figures were 39% (95% CI, 37 to 41%), 14% (95% CI, 12% - 16%), and 0.81% (95% CI, 0.46 to 1.2%), respectively. The findings of an unexpectedly high prevalence of low clearance and the increased prevalence of low clearance with age were consistent across the four clearance estimation methods used and for each race-sex stratum. The absolute magnitude of the prevalence of low clearance was, however, dependent on the clearance method used. Assessed by estimation from serum creatinine, low clearance may be very common, particularly with advancing age. The prognosis (in terms of risk for progression and end-stage renal disease) of low clearance in unreferred populations may differ from that in referred populations and requires further study.
Gene Expression Profiling of Hereditary and Sporadic Ovarian Cancers Reveals Unique BRCA1 and BRCA2 Signatures
Authors: I. A. Hedenfalk
Journal: JNCI Journal of the National Cancer Institute (2002)

The recent completion of the draft human genome sequence (1) presents countless opportunities to investigate genome function and the importance of alterations in the genetic code in both health and disease. Among the most rapidly adopted of the emerging genomic technologies, microarray hybridization permits the parallel determination of the expression of tens of thousands of genes in tissue samples (2). Microarray studies have proven to be of great value in further understanding the basic biology of cancer and have been used successfully to classify tumors into distinct, clinically relevant subgroups based on gene expression profiles and to identify potential biomarkers. Ovarian cancers differ from many other human tumors in displaying considerable disease heterogeneity, a poorly understood progression pathway, and few good tumor markers. In addition, ovarian cancers are usually diagnosed at a late stage, and the survival rate, therefore, is poor. Improved knowledge of the changes in gene expression associated with progression of ovarian cancer and with different forms of the disease, therefore, may lead to greater understanding of the underlying disease mechanisms and the development of possible intervention strategies.
Neuromuscular and biomechanical characteristic changes in high school athletes: a plyometric versus basic resistance program
Authors: S M Lephart, J P Abt, C M Ferris, T C Sell, T Nagai, J B Myers, J J Irrgang
Journal: British Journal of Sports Medicine (2005)

In order to improve neuromuscular and biomechanical characteristic deficits in female athletes, numerous injury prevention programs have been developed and have successfully reduced the number of knee ligament injuries. However, few have investigated the neuromuscular and biomechanical changes following these training programs. It is also largely unknown what type of program is better for improving the landing mechanics of female athletes.To investigate the effects of an 8 week plyometric and basic resistance training program on neuromuscular and biomechanical characteristics in female athletes.Twenty seven high school female athletes participated either in a plyometric or a basic resistance training program. Knee and hip strength, landing mechanics, and muscle activity were recorded before and after the intervention programs. In the jump-landing task, subjects jumped as high as they could and landed on both feet. Electromyography (EMG) peak activation time and integrated EMG of thigh and hip muscles were recorded prior to (preactive) and subsequent to (reactive) foot contact.Both groups improved knee extensor isokinetic strength and increased initial and peak knee and hip flexion, and time to peak knee flexion during the task. The peak preactive EMG of the gluteus medius and integrated EMG for the gluteus medius during the preactive and reactive time periods were significantly greater for both groups.Basic training alone induced favourable neuromuscular and biomechanical changes in high school female athletes. The plyometric program may further be utilised to improve muscular activation patterns.
Sphingosine-1-phosphate as a mediator of high-density lipoprotein effects in cardiovascular protection
Authors: K. Sattler, B. Levkau
Journal: Cardiovascular Research (2008)

Sphingosine-1-phosphate (S1P) has gained special attention in the high-density lipoprotein (HDL) field because HDL is the most prominent plasma carrier of S1P and because the S1P content of HDL may be responsible for many of the pleiotropic functions of HDL. This revelation has come from the evidence that HDL employ S1P receptors and signalling pathways to implement several HDL-ascribed biological effects as diverse as endothelial nitric oxide production, vasodilation, survival, and cardioprotection. This review focuses on HDL effects that are completely or partially mediated by the S1P content of the HDL particle and differentiates them from genuine HDL effects that are S1P-independent. In addition, the functional properties of 'free', HDL-unbound S1P are sometimes different from or even contrary to those of HDL-associated S1P. The nature of the physical interactions between HDL and local and systemic S1P production will be discussed as well as their consequences for organ function. Finally, we will elucidate the potential benefits and limitations of S1P analogues as a new class of functional HDL mimetics for cardiovascular therapy.
ABSTRACT OF INTRODUCTORY ADDRESS, DELIVERED AT THE ANNUAL MEETING OF THE DERMATOLOGICAL SOCIETY OF GREAT BRITAIN AND IRELAND, MAY 20th, 1896
Authors: JOSEPH FRANK PAYNE
Journal: British Journal of Dermatology (1896)

THE most important problem relating to Diseases of the Skin is undoubtedly that of Causation or Btiology.In this department of Pathology immense progress has lately been made, and one result is that many old names of diseases are now quite inadequate.Formerly it was thought enough to give as the diagnosis of an organic disease the name of inflammation, or some word ending in -itis.But it is now felt that this diagnoeis is incomplete unless the cause of the inflammation can be assigned.The term "idiopathic" has no meaning.In diseases of the kin the confusion has never been so
Airway Wall Mechanics
Authors: Roger D. Kamm
Journal: Annual Review of Biomedical Engineering (1999)

▪ Abstract The dimensions, composition, and stiffness of the airway wall are important determinants of airway cross-sectional area during dynamic collapse in a forced expiration or when airway smooth muscle is constricted. Under these circumstances, airway caliber is determined by an interaction between the forces acting to open the airway (parenchymal tension and wall stiffness) and those acting to close it (smooth-muscle force and surface tension at the inner gas-liquid interface). Experimental measurements and theoretical models of the airway tube law (relationship between cross-sectional area and transmural pressure) are presented. Data are presented for the elastic properties of the wall tissue. Simulations of airway constriction in normal and asthmatic airways are discussed. To the extent possible, comparisons are presented between the various models and existing experimental data.
HLA-DR associates with specific stress proteins and is retained in the endoplasmic reticulum in invariant chain negative cells.
Authors: W T Schaiff, K A Hruska, D W McCourt, M Green, B D Schwartz
Journal: The Journal of Experimental Medicine (1992)

The major histocompatibility complex class II molecules are composed of two polymorphic chains which, in cells normally expressing them, transiently associate with a third, nonpolymorphic molecule, the invariant chain (Ii). To determine differences in the biology of class II molecules synthesized in the presence or absence of Ii, a comparative study was performed of BALB/c 3T3 cells that had been transfected with human class II HLA-DR molecules with or without cotransfection with human Ii. It was observed that in the absence of Ii, at least three high molecular weight proteins coimmunoprecipitate with HLA-DR molecules. These proteins did not coimmunoprecipitate with HLA-DR from cells cotransfected with Ii, nor did they coimmunoprecipitate with class I molecules from any of the transfectants. NH2-terminal sequence and/or Western blot analysis revealed the identity of two of the proteins as the endoplasmic reticulum (ER) resident stress proteins GRP94 and ERp72. Neither of these proteins was found to have an increased level of synthesis in the Ii- versus the Ii+ transfectants, indicating that their synthesis was not induced over constitutive levels. Fluorescence microscopy revealed that in the Ii- transfectants, the majority of the HLA-DR molecules were present in the ER, whereas in the Ii+ transfectants, the HLA-DR molecules were found in vesicular structures. We hypothesize that in the absence of Ii, ER resident stress proteins bind to class II molecules and retain them in the ER. This process, in turn, could prevent class II molecules from exiting the ER with endogenous peptides bound in their peptide binding cleft, and therefore could minimize autoimmune responses to endogenously processed self-peptides.
Are Combined Analyses Better Than Single Gene Phylogenies? A Case Study Using SSU rDNA and rbcL Sequence Comparisons in the Zygnematophyceae (Streptophyta)
Authors: A. A. Gontcharov
Journal: Molecular Biology and Evolution (2003)

Although the combination of different genes in phylogenetic analyses is a promising approach, the methodology is not well established and analyses often suffer from inadequate, noncongruent taxon sampling, long-branch attraction, or conflicting evolutionary models of the genes analyzed. Conflicts or congruence between multigene and single-gene phylogenies, as well as the assumed superiority of the multigene approach, are often difficult to assess solely because of incongruent taxon sampling. In the present study, a data set of 43 nuclear-encoded SSU rDNA and plastid-encoded rbcL gene sequences was generated from the same strains of conjugating green algae (Zygnematophyceae, Streptophyta). Phylogenetic analyses used the genes individually and in combination, either as concatenated sequences or with the log-likelihood summation method. Single-gene analyses, although mostly congruent, revealed some conflicting nodes and showed different patterns of statistical support. Combined analyses confidently resolved the conflicts between the single-gene analyses, enhanced phylogenetic resolution, and were better supported by morphological information. Long-branch taxa were not the same for the two genes analyzed, and, thus, their effect on phylogenetic resolution was minimized in the combined analyses.
Surface Cytotoxic T Lymphocyte–associated Antigen 4 Partitions Within Lipid Rafts and Relocates to the Immunological Synapse under Conditions of Inhibition of T Cell Activation
Authors: Peter J. Darlington, Miren L. Baroja, Thu A. Chau, Eric Siu, Vincent Ling, Beatriz M. Carreno, Joaquín Madrenas
Journal: The Journal of Experimental Medicine (2002)

T cell activation through the T cell receptor (TCR) involves partitioning of receptors into discrete membrane compartments known as lipid rafts, and the formation of an immunological synapse (IS) between the T cell and antigen-presenting cell (APC). Compartmentalization of negative regulators of T cell activation such as cytotoxic T lymphocyte–associated antigen-4 (CTLA-4) is unknown. Recent crystal structures of B7-ligated CTLA-4 suggest that it may form lattices within the IS which could explain the mechanism of action of this molecule. Here, we show that after T cell stimulation, CTLA-4 coclusters with the TCR and the lipid raft ganglioside GM1 within the IS. Using subcellular fractionation, we show that most lipid raft-associated CTLA-4 is on the T cell surface. Such compartmentalization is dependent on the cytoplasmic tail of CTLA-4 and can be forced with a glycosylphosphatidylinositol-anchor in CTLA-4. The level of CTLA-4 within lipid rafts increases under conditions of APC-dependent TCR–CTLA-4 coligation and T cell inactivation. However, raft localization, although necessary for inhibition of T cell activation, is not sufficient for CTLA-4–mediated negative signaling. These data demonstrate that CTLA-4 within lipid rafts migrates to the IS where it can potentially form lattice structures and inhibit T cell activation.