tbuckley/cabot-search huggingface dataset:
The case for inspiratory muscle training in COPD
Authors: N. Ambrosino
Journal: European Respiratory Journal (2011)

I speak not to disprove what Brutus spoke, 

But here I am to speak what I do know. 

William Shakespeare. Julius Caesar . Act 3, Scene 2, line 100–101.

Pulmonary rehabilitation is a cornerstone for the management of chronic obstructive pulmonary disease (COPD), since treatments other than smoking cessation and long-term oxygen therapy are merely symptomatic [1]. The current recommendations in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines are that all stages of the disease may benefit from such programmes 1. The most effective component of these programmes is peripheral (preferably lower limbs) muscle exercise training, whereas the role of inspiratory muscle training (IMT) of patients with stable COPD remains controversial 2–5.

The American Thoracic Society/European Respiratory Society statement on pulmonary rehabilitation suggested that “although the data are inconclusive, IMT could be considered as adjunctive therapy in pulmonary rehabilitation, primarily in patients with suspected or proven respiratory muscle weakness” 4. The Joint American College of Chest Physicians/American Association of Cardiovascular and Pulmonary Rehabilitation evidence-based clinical practice guidelines panel 5, (including some of the most respected contributors to the previous statement 4) recommended that “IMT be considered in selected patients with COPD who have decreased inspiratory muscle strength and breathlessness despite receiving optimal medical therapy.” That panel suggested that a large-scale, multicentre randomised controlled trial (RCT) should be performed with appropriate statistical power to more completely examine the role of IMT in treating patients with COPD, concluding that “the scientific evidence does not support the routine use of IMT as an essential component of pulmonary rehabilitation” (grade of recommendation 1B) 5. However, why should “inconclusive data” 4 or “grade of recommendation 1B” 5 be considered synonymous with “ineffective”, or prevent a treatment modality in the individual patient 6? Clinical practice …
Circulating Tumor Cells and Circulating Tumor DNA: Challenges and Opportunities on the Path to Clinical Utility
Authors: Michail Ignatiadis, Mark Lee, Stefanie S. Jeffrey
Journal: Clinical Cancer Research (2015)

Abstract Recent technological advances have enabled the detection and detailed characterization of circulating tumor cells (CTC) and circulating tumor DNA (ctDNA) in blood samples from patients with cancer. Often referred to as a “liquid biopsy,” CTCs and ctDNA are expected to provide real-time monitoring of tumor evolution and therapeutic efficacy, with the potential for improved cancer diagnosis and treatment. In this review, we focus on these opportunities as well as the challenges that should be addressed so that these tools may eventually be implemented into routine clinical care. Clin Cancer Res; 21(21); 4786–800. ©2015 AACR.
Effects of proportional assist ventilation on skeletal muscle reoxygenation after high-intensity exercise in chronic heart failure
Authors: Audrey Borghi-Silva, Claudia Carrascossa, Cristino Oliveira, Adriano Barroco, Danilo Berton, Debora Villaça, Edgar Lira-Filho, Dirceu R. de Almeida, Luis Eduardo Nery, José Alberto Neder
Journal: European Respiratory Journal (2012)

Background : Respiratory muscle unloading can enhance the haemodynamic responses to exercise thereby allowing a closer matching between skeletal muscle O 2  delivery and utilization in patients with chronic heart failure (CHF).  Objective :   To assess whether proportional assist ventilation (PAV), compared to sham ventilation, would improve the dynamic coupling between microvascular O 2  delivery and O 2  uptake (V´O 2 ) during recovery from heavy-intensity exercise in patients with CHF.   Methods  - Twelve patients with CHF (NYHA class II and III and left ventricle ejection fraction= 26±9%) underwent two high-intensity, constant-work rate (80% peak) cycle ergometer tests receiving PAV or sham ventilation. Off-exercise kinetics of the “primary” component of V´O 2 , an index of fractional O 2  extraction by near infrared spectroscopy (∼Δ[deoxy-Hb+Mb]) in the vastus lateralis) and cardiac output (QT) by impedance cardiography were assessed.   Results:   PAV speeded the recovery kinetics of all variables compared to sham ventilation.   Conclusions:  These data indicate that PAV has beneficial effects on recovery of muscle metabolism and central haemodynamics after high-intensity exercise in CHF patients.   Financial Support: FAPESP .
<i>Helicobacter pylori</i>targets cancer-associated apical-junctional constituents in gastroids and gastric epithelial cells
Authors: Lydia E Wroblewski, M Blanca Piazuelo, Rupesh Chaturvedi, Michael Schumacher, Eitaro Aihara, Rui Feng, Jennifer M Noto, Alberto Delgado, Dawn A Israel, Yana Zavros, Marshall H Montrose, Noah Shroyer, Pelayo Correa, Keith T Wilson, Richard M Peek
Journal: Gut (2014)

<h3>Objective</h3> <i>Helicobacter pylori</i> strains that express the oncoprotein CagA augment risk for gastric cancer. However, the precise mechanisms through which <i>cag</i><sup>+</sup> strains heighten cancer risk have not been fully delineated and model systems that recapitulate the gastric niche are critical for understanding pathogenesis. Gastroids are three-dimensional organ-like structures that provide unique opportunities to study host-<i>H. pylori</i> interactions in a preclinical model. We used gastroids to inform and direct in vitro studies to define mechanisms through which <i>H. pylori</i> modulates expression of the cancer-associated tight junction protein claudin-7. <h3>Design</h3> Gastroids were infected by luminal microinjection, and MKN28 gastric epithelial cells were cocultured with <i>H. pylori</i> wild-type <i>cag<sup>+</sup></i> strains or isogenic mutants. β-catenin, claudin-7 and snail localisation was determined by immunocytochemistry. Proliferation was assessed using 5-ethynyl-2′-deoxyuridine, and levels of claudin-7 and snail were determined by western blot and flow cytometry. <h3>Results</h3> Gastroids developed into a self-organising differentiation axis and <i>H. pylori</i> induced mislocalisation of claudin-7 and increased proliferation in a CagA- and β-catenin-dependent manner. In MKN28 cells, <i>H pylori</i>-induced suppression of claudin-7 was regulated by β-catenin and snail. Similarly, snail expression was increased and claudin-7 levels were decreased among <i>H. pylori</i>-infected individuals. <h3>Conclusions</h3> <i>H. pylori</i> increase proliferation in a strain-specific manner in a novel gastroid system. <i>H. pylori</i> also alter expression and localisation of claudin-7 in gastroids and human epithelial cells, which is mediated by β-catenin and snail activation. These data provide new insights into molecular interactions with carcinogenic potential that occur between <i>H. pylori</i> and epithelial cells within the gastric niche.
Antitopoisomerase I monoclonal autoantibodies from scleroderma patients and tight skin mouse interact with similar epitopes.
Authors: T Muryoi, K N Kasturi, M J Kafina, D S Cram, L C Harrison, T Sasaki, C A Bona
Journal: The Journal of Experimental Medicine (1992)

We have generated for the first time monoclonal antibodies (mAbs) specific for topoisomerase I (topo I) from scleroderma patients, and tight skin mice which develop a scleroderma-like syndrome. The epitope specificity of these antibodies has been determined using a series of fusion proteins containing contiguous portions of topo I polypeptide. Western blot analysis demonstrated that both human and mouse mAbs bound strongly to fusion protein C encompassing the NH2-terminal portion of the enzyme, and weakly to fusion proteins F and G containing regions close to the COOH-terminal end of the molecule. This crossreactivity is related to a tripeptide sequence homology in F, G, and C fusion proteins. It is interesting that a pentapeptide sequence homologous to that in fusion protein C was identified in the UL70 protein of cytomegalovirus, suggesting that activation of autoreactive B cell clones by molecular mimicry is possible. Both human and mouse mAbs exhibiting the same antigen specificity, also share an interspecies cross-reactive idiotope. These data suggest that B cell clones producing antitopo autoantibodies present in human and mouse repertoire are conserved during phylogeny, and are activated during the development of scleroderma disease.
Kinetics of in vitro bronchoconstriction in an elastolytic mouse model of emphysema
Authors: M. A. Khan, S. Kianpour, M. R. Stämpfli, L. J. Janssen
Journal: European Respiratory Journal (2007)

Thin-slice videomicroscopy was used to examine the kinetics of constriction in small airways in situ. Balb/C mice inhaled elastase (0-20 IU), and were then left to recover for 14 days before euthanisation and lung removal. Cholinergic responsiveness was assessed in thin lung slices. Magnitude and velocity of narrowing in response to 10(-5) M acetylcholine (ACh), as well as the full concentration-response relationship for ACh (10(-8)-10(-5) M) were assessed. In vivo exposure to elastase was accompanied by statistically significantly decreased magnitudes and velocities of contraction, but no change in the ACh concentration-response relationship. Conversely, overnight, in vitro exposure of slices from control animals to elastase (2.5 microg.mL(-1)) resulted in increased magnitudes and velocities of airway narrowing, with impaired relaxation, as well as marked tearing of the airways from the surrounding parenchyma. These changes are characteristic of decreased tethering forces on the airway wall. Thus, the lung slice technique coupled with videomicroscopic analysis of airway contraction velocities provides a powerful tool to study airway-parenchymal interactions. The elastolytic model of emphysema, which manifests with airspace enlargement and loss of parenchymal attachments, is accompanied by decreased airway contraction kinetics. The mechanism(s) underlying this loss of function remain to be elucidated.
Risk Assessment in Criminal Sentencing
Authors: John Monahan, Jennifer L. Skeem
Journal: Annual Review of Clinical Psychology (2015)

The past several years have seen a surge of interest in using risk assessment in criminal sentencing, both to reduce recidivism by incapacitating or treating high-risk offenders and to reduce prison populations by diverting low-risk offenders from prison. We begin by sketching jurisprudential theories of sentencing, distinguishing those that rely on risk assessment from those that preclude it. We then characterize and illustrate the varying roles that risk assessment may play in the sentencing process. We clarify questions regarding the various meanings of "risk" in sentencing and the appropriate time to assess the risk of convicted offenders. We conclude by addressing four principal problems confronting risk assessment in sentencing: conflating risk and blame, barring individual inferences based on group data, failing adequately to distinguish risk assessment from risk reduction, and ignoring whether, and if so, how, the use of risk assessment in sentencing affects racial and economic disparities in imprisonment.
Immunolocalization of annexins IV, V and VI in the failing and non-failing human heart
Authors: R Matteo
Journal: Cardiovascular Research (2000)

The failing human heart is characterized by changes in the expression and function of proteins involved in intracellular Ca2+ cycling, resulting in altered Ca2+ transients and impaired contractile properties of cardiac muscle. The role of the cardiac annexins in this process remains unclear. Annexins may play a role in the regulation of Ca2+ pumps and exchangers on the sarcolemma, and have been shown to be altered in some cardiac disease states.The goal of this study was to compare the immunolocalization and expression of annexins IV, V and VI in failing and non-failing human hearts.We used immunostaining to identify the subcellular location of annexins IV, V and VI proteins within the myocardial cell, and Western blot analysis to quantify the proteins in the same hearts.Annexin IV showed a cytoplasmic distribution in both failing and non-failing human heart cells. Annexin V was localized at the z-line, around lipofuscin granules, and in the cytosol in the non-failing heart cells. Annexin VI was localized at the sarcolemma and intercalated disc. Protein levels of annexins IV and V were up-regulated in failing human hearts, while the expression of annexin VI was unchanged.Alterations in the intracellular localization of annexins, along with up-regulation of annexins IV and V in the failing human heart cells, suggests differential regulation of these Ca2+ regulatory proteins during heart failure.
On the Sympathetic Control of Ventricular Automaticity
Authors: MARIO VASSALLE, MICHAEL J. LEVINE, JACKSON H. STUCKEY
Journal: Circulation Research (1968)

The effects of stellate ganglion stimulation on idioventricular automaticity were studied in anesthetized dogs. An idioventricular rhythm was obtained in one series of animals by ligating the His bundle and in the other by stimulating the vagus. On isolation of the left stellate ganglion, the idioventricular rate fell by 5 beats/min which is compatible with a rate of "tonic" discharge of about 3 impulses/sec. On stimulation of the stellate ganglia at increasingly higher frequencies, the idioventricular rate accelerated progressively and the frequency-response curve was sigmoid. When the stimulation frequency was increased above 10 to 15 pulses/sec, there was no further enhancement of ventricular automaticity. The ventricular rates attained during sympathetic stimulation rarely exceeded 70/min. The interval between the initiation of sympathetic stimulation and the maximal ventricular acceleration was shorter at higher stimulation frequencies. The effects of right and left stellate stimulation on the rate of idioventricular pacemakers were comparable. Reflex vagal inhibition had little influence on the acceleratory action of the sympathetic nerves on the idioventricular pacemakers since in dogs with atrioventricular block the results before and after vagotomy were similar. Furthermore, the idioventricular rhythm during vagally induced block increased on sympathetic stimulation to values comparable to those obtained in dogs with surgically induced block.
Specific suppression of allograft rejection by trinitrophenyl (TNP)-induced suppressor cells in recipients treated with TNP-haptenated donor alloantigens.
Authors: I V Hutchinson, W H Barber, P J Morris
Journal: The Journal of Experimental Medicine (1985)

Suppressor T cells, activated by injection of trinitrobenzene sulphonic acid in DA rats, prevented rejection of LEW kidney allografts in a donor-specific manner when adoptively transferred into syngeneic recipients along with trinitrophenyl (TNP)-haptenated LEW alloantigen. TNP-haptenated third-party alloantigen was ineffective in this system. The donor-specific suppression was dependent, too, on the haptenic portion of the chemically modified alloantigen. Hence, fluorescein isothiocyanate-donor antigen did not lead to suppression in the presence of TNP-reactive suppressor cells. There is, however, some crossreaction between DNP- and TNP-haptenated alloantigens so that TNP-reactive cells and DNP-donor antigen suppressed rejection whereas DNP-reactive cells and TNP-donor antigen did not prevent graft rejection. The suppressor cells were sensitive to cyclophosphamide and radiation but were resistant to hydrocortisone. They appear to be T cells of the OX8 (suppressor/cytotoxic) phenotype since they are positive for the pan T cell antigen W3/13, are Ig negative, and do not carry the W3/25 (T helper cell) marker. However, these suppressor cells are adherent to nylon wool. They are found mainly in the spleen, are detected there within 2 d of TNBS injection, and can persist for up to 12 wk. We propose that these cells are first-order T suppressor (Ts1) cells that act in the afferent phase of the response to a renal allograft.
Risk and Resilience Markers in Bipolar Disorder: Brain Responses to Emotional Challenge in Bipolar Patients and Their Healthy Siblings
Authors: Stephanie Krüger, Martin Alda, L Trevor Young, Kim Goldapple, Saghar Parikh, Helen S Mayberg
Journal: American Journal of Psychiatry (2006)

The authors previously identified depression-specific differences in brain responses to an emotional challenge in patients with bipolar and unipolar mood disorder. In this study, potential markers of bipolar risk and resilience were examined in a new cohort of lithium-responsive bipolar patients and their healthy siblings.Changes in regional cerebral blood flow (rCBF) were measured with [(15)O]water positron emission tomography after induction of transient sadness in nine euthymic lithium responders and nine healthy siblings. The patterns of change in these groups were compared, and then they were contrasted with previous findings on bipolar responders to valproate.Common to all three groups with induced sadness were rCBF increases in the dorsal/rostral anterior cingulate and anterior insula and decreases in the orbitofrontal and inferior temporal cortices. Distinguishing the groups were decreases in the medial frontal cortex in the patients but an increase in this region in the siblings.Common changes with emotional challenge were identified in bipolar patients and their healthy siblings. These were not seen previously in healthy subjects without a family history of mood disorder, suggesting a potential marker of bipolar risk. The siblings' unique increases in the medial frontal cortex appear to identify a compensatory response in this at-risk group, as this pattern was not seen previously in healthy subjects without depression risk factors. This differential change pattern in patients and their siblings highlights the role of the anterior cingulate and medial frontal regions in mediating resiliency and vulnerability in bipolar disorder families.
Conditioning with targeted busulfan and cyclophosphamide for hemopoietic stem cell transplantation from related and unrelated donors in patients with myelodysplastic syndrome
Authors: H. Joachim Deeg, Barry Storer, John T. Slattery, Claudio Anasetti, Kristine C. Doney, John A. Hansen, Hans-Peter Kiem, Paul J. Martin, Effie Petersdorf, Jerald P. Radich, Jean E. Sanders, Howard M. Shulman, Edus H. Warren, Robert P. Witherspoon, Eileen M. Bryant, Thomas R. Chauncey, Lisa Getzendaner, Rainer Storb, Frederick R. Appelbaum
Journal: Blood (2002)
High Rate of Regression From Micro-Macroalbuminuria to Normoalbuminuria in Children and Adolescents With Type 1 Diabetes Treated or Not With Enalapril
Authors: Silvana Salardi, Claudia Balsamo, Stefano Zucchini, Giulio Maltoni, Mirella Scipione, Alessandra Rollo, Stefano Gualandi, Alessandro Cicognani
Journal: Diabetes Care (2011)

To evaluate the frequency of normalization, the persistence of remission, and the impact on normalization of glycemic control and lipid profile, we analyzed data from a retrospective observational cohort study of type 1 diabetic children and adolescents with abnormal urinary albumin excretion (UAE).All diabetic children and adolescents (n = 41) who had persistent abnormal UAE in the period of 1984 to 2008 and followed up until 2009 (follow-up duration = 13.1 ± 6.2 years) were included in the study. Nine patients progressed to macroalbuminuria; 24 patients were administered ACE inhibitor treatment.The cumulative prevalence of abnormal UAE was 9%. During follow-up, 14 of 17 untreated and 19 of 24 treated patients reverted to normoalbuminuria. In the remission group compared with the nonremission group, A1C levels during follow-up decreased (7.5 ± 1.0 vs. 9.4 ± 1.2%, P < 0.0001) and serum HDL cholesterol increased (52.7 ± 11.3 vs. 42.7 ± 8.6 mg/dL, P < 0.05). The micro-macroalbuminuric patients had lower HDL cholesterol (51.0 ± 11.4 vs. 62.4 ± 13.6 mg/dL, P < 0.0001) than 134 normoalbuminuric diabetic patients.Microalbuminuria and macroalbuminuria were not permanent in most of our diabetic children and adolescents. If abnormal UAE values are high and persist for >1 year, only long-lasting treatment with ACE inhibitors seems able to induce persistent remission, especially when associated with good metabolic control and high HDL cholesterol levels.
Prognostic impact of proliferative index determined by quantitative image analysis and the International Prognostic Index in patients with mantle cell lymphoma
Authors: R. Schaffel, C.V. Hedvat, J. Teruya-Feldstein, D. Persky, J. Maragulia, D. Lin, C.S. Portlock, C.H. Moskowitz, A.D. Zelenetz
Journal: Annals of Oncology (2009)

BackgroundThe proliferative index (PI) is a powerful prognostic factor in mantle cell lymphoma (MCL); however, its utility is hampered by interobserver variability. The mantle cell international prognostic index (MIPI) has been reported to have prognostic importance. In this study, we determined the prognostic value of the PI as determined by quantitative image analysis in MCL.Patients and methodsEighty-eight patients with adequate tissue were included in this analysis. Patients were treated with one of two treatment programs: sequential therapy with high-dose therapy consolidation or radioimmunotherapy followed by combination chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone. Patients were divided into four groups based on PI (<10%, 10%–29.9%, 30%–49.9%, and >50%), and outcomes were analyzed.ResultsThirty percent was identified as the optimal cut-off for PI. By univariate analysis, intensive treatment and a low PI were associated with a superior progression-free survival (PFS); only PI was associated with overall survival. By multivariate analysis, both intensive treatment and PI correlated with PFS. The MIPI had no prognostic impact.ConclusionsPI is the most important prognostic factor in MCL. The cut-off of 30% is clinically meaningful and can be used to tailor the intensity of therapy in future clinical trials.
Malignancies in the rheumatoid arthritis abatacept clinical development programme: an epidemiological assessment
Authors: T A Simon, A L Smitten, J Franklin, J Askling, D Lacaille, F Wolfe, M C Hochberg, K Qi, S Suissa
Journal: Annals of the Rheumatic Diseases (2008)

<h3>Objective:</h3> To provide context for the malignancy experience in the rheumatoid arthritis (RA) abatacept clinical development programme (CDP) by performing comparisons with similar RA patients and the general population. <h3>Methods:</h3> Malignancy outcomes included total malignancy (excluding non-melanoma skin cancer (NMSC)), breast, colorectal, lung cancers and lymphoma. Comparisons were made between the observed incidence in patients within the abatacept CDP and RA patients on disease-modifying antirheumatic drugs (DMARD) identified from five data sources: the population-based British Columbia RA Cohort, the Norfolk Arthritis Register, the National Data Bank for Rheumatic Diseases, the Sweden Early RA Register and the General Practice Research Database. Age and sex-adjusted incidence rates (IR) and standardised incidence ratios (SIR) were used to compare events in the abatacept trials with the RA DMARD cohorts and the general population. <h3>Results:</h3> A total of 4134 RA patients treated with abatacept in seven trials and 41 529 DMARD-treated RA patients in the five observational cohorts was identified for study inclusion. In the abatacept-treated patients, the 51 malignancies (excluding NMSC), seven cases of breast, two cases of colorectal, 13 cases of lung cancer and five cases of lymphoma observed were not greater than the range of expected cases from the five RA cohorts. The SIR comparing RA patients with the general population were consistent with those reported in the literature. <h3>Conclusions:</h3> The IR of total malignancy (excluding NMSC), breast, colorectal, lung cancers and lymphoma in the abatacept CDP were consistent with those in a comparable RA population. These data suggest no new safety signals with respect to malignancies, which will continue to be monitored.