tbuckley/cabot-search huggingface dataset:
Ambient and Unobtrusive Cardiorespiratory Monitoring Techniques
Authors: Christoph Bruser, Christoph Hoog Antink, Tobias Wartzek, Marian Walter, Steffen Leonhardt
Journal: IEEE Reviews in Biomedical Engineering (2015)

Monitoring vital signs through unobtrusive means is a goal which has attracted a lot of attention in the past decade. This review provides a systematic and comprehensive review over the current state of the field of ambient and unobtrusive cardiorespiratory monitoring. To this end, nine different sensing modalities which have been in the focus of current research activities are covered: capacitive electrocardiography, seismo- and ballistocardiography, reflective photoplethysmography (PPG) and PPG imaging, thermography, methods relying on laser or radar for distance-based measurements, video motion analysis, as well as methods using high-frequency electromagnetic fields. Current trends in these subfields are reviewed. Moreover, we systematically analyze similarities and differences between these methods with respect to the physiological and physical effects they sense as well as the resulting implications. Finally, future research trends for the field as a whole are identified.
Detection of the Complement Degradation Product C4d in Renal Allografts
Authors: Volker Nickeleit, Matthias Zeiler, Fred Gudat, Gilbert Thiel, M. J. Mihatsch
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. The immunohistochemical detection of the complement degradation product C4d, a component of the classical complement pathway, offers a new and currently poorly defined tool in the evaluation of renal allograft biopsies. Our retrospective study aims at determining the diagnostic and clinical significance of C4d accumulation in kidney transplants, employing immunofluorescence microscopy. We analyzed 398 diagnostic allograft biopsies (n = 265 patients with 1 to 5 biopsies obtained 7 to 7165 d posttransplantation [tx]) and correlated the detection of C4d with 18 histologic changes, panel-reactive antibody titers, response to treatment, and outcome. One hundred twenty-five native kidney and baseline tx biopsies served as controls. Linear deposition of C4d along peritubular capillaries was only found in a subgroup (30%) of allografts post-tx, mainly during the early time-course (median, 38 d post-tx; range, 7 to 5646 d). There was no significant association with infections. C4d staining could change from negative to positive and vice versa within days to weeks. The accumulation of C4d was most tightly linked to a morphologic subtype of rejection, transplant glomerulitis (P < 0.0001). In addition, tubular MHC class II expression was correlated with C4d deposition (P < 0.0001). Both features are signs of “acute active rejection.” In comparison with C4d-negative controls, 43% of C4d-positive patients showed increased (>10%) panel-reactive antibody titers (versus 19% in the negative group; P = 0.001). C4d positivity was frequently associated with higher serum creatinine levels at time of biopsy (compared with C4d-negative group; P < 0.01). More C4d-positive patients were treated with polyclonal antithymocyte globulins (ATG) or monoclonal anti-CD3 antibodies (OKT3) (P < 0.0001). Outcome did not significantly differ between C4d-positive and C4d-negative groups. In conclusion, the detection of C4d identifies a humoral alloresponse in a subgroup of kidney transplants, which is often associated with signs of cellular rejection, i.e. tx glomerulitis. Allograft dysfunction in C4d-positive rejection episodes is often more pronounced. We provide first evidence that C4d-positive rejection might benefit from intensive therapy, potentially preventing the previously reported high graft failure rate. In addition, we show that a subgroup of C4d-positive cases may not require any immediate therapeutic intervention. The presence of C4d is clinically relevant and should be reported in the histologic diagnosis.
Characterisation of T cell populations in proximal and distal airways
Authors: Rebecca Spruce, Gregory Rankin, Christopher Pickard, Jane Warner
Journal: European Respiratory Journal (2011)

Introduction: CD8+ T cells are known to be involved in the pathogenesis of COPD but less is known about CD4+ T cells. We have characterised T cell populations from the distal and proximal airways of patients with and without airways obstruction.

Method: Macroscopically normal matched proximal and distal airway tissue was obtained from 23 patients (mean age 66±2.7 years, FEV1/FVC=0.66±0.02) undergoing lung resection. Samples were dissected into explants, fixed and processed for GMA immunohistochemistry. Sections were stained for CD3, CD4 and CD8. To examine a larger population of T cells, explants from the same patients were incubated for 24 hours to encourage T cell migration into supernatant. Recovered cells were stained for T cell markers (CD3-FITC, CD8-APC) and analyzed via FACS.

Results: Immunohistochemical analysis revealed relatively few T cells in either proximal or distal airways (median CD3+ cells distal airways =1.6/mm2 compared to 1.4/mm2) in the proximal airways. We found more CD4+ than CD8+ cells in both compartments but numbers of cells counted were low. In order to characterise a larger number of T cells FACS was performed on cells that migrated out of the explants. This confirmed that there were more CD4+ cells than CD8+ cells in the distal airways though this was not seen in the proximal airways. The distribution was not significantly affected by the presence of airways obstruction.

Conclusions: Similar numbers of CD3+ cells were found in the proximal and distal airways. CD4+ cells were predominant in the distal airways while the distribution of CD4 and CD8+ cells was equivalent in the proximal airways. The presence of mild/moderate COPD did not affect T cell number or distribution.
Variation in airways resistance when defined over different ranges of airflows.
Authors: P W Lord, J M Edwards
Journal: Thorax (1978)

In eight normal subjects airways resistance (Raw) was assessed over six ranges of airflow (about zero flow at both minimum and maximum lung volumes) using an automated whole body plethysmograph. The intervals of flow used were 21s-1 and 11s-1 spanning zero flow, and 11s-1 and 0.51s-1 measured up to and from zero flow. The wider intervals gave less variable results, the coefficients of variation being of the order 11%, 15%, and 22% for the 2, 1, and 0.51s-1 intervals respectively. In all subjects, at minimum volume Raw was some 1.5 times greater when measured over the ranges at end-expiration than at start-expiration; at maximum volume Raw was some 1.3 times greater when measured over the ranges at end-inspiration than at start-expiration. A slight increase in the slopes of the oscilloscope traces used to determine Raw was observed at minimum volume compared with those at maximum volume. In view of the substantial differences reported it is essential that the exact range of flow, and the respiratory phase used, is described when reporting measurements of Raw. Least variability is obtained by estimating slopes over a wide interval of flow, such as 1 or 21s-1.
Metformin as an Adjunct Therapy in Adolescents With Type 1 Diabetes and Insulin Resistance
Authors: Jill Hamilton, Elizabeth Cummings, Vera Zdravkovic, Diane Finegood, Denis Daneman
Journal: Diabetes Care (2003)

To evaluate whether, in adolescents with type 1 diabetes, the addition of metformin to insulin and standard diabetes management results in 1) higher insulin sensitivity and 2) lower HbA1c, fasting glucose, insulin dosage (units per kilogram per day) and BMI.This was a randomized, placebo-controlled 3-month trial of metformin therapy in 27 adolescents with type 1 diabetes, high insulin dosage (>1 unit. kg(-1). day(-1)), and HbA1c >8%, with measurements of insulin sensitivity (by frequently sampled intravenous glucose tolerance test [FSIGT]), HbA1c, insulin dosage, and BMI at the onset and end of treatment.At t = 0, HbA1c was 9.2 +/- 0.9%, insulin dosage was 1.2 +/- 0.2 units. kg(-1). day(-1), fasting glucose was 10.6 +/- 2.4 mmol/l, and BMI was 24.2 +/- 3.9 kg/m2 (means +/- SD), with no difference between the metformin and placebo groups. At the end of the study, HbA1c was 0.6% lower in the metformin group than in the placebo group (P < 0.05). This was achieved at lower daily insulin dosages (metformin group -0.14 +/- 0.1 vs. placebo group 0.02 +/- 0.2 units. kg(-1). day(-1); P < 0.05), with no significant change in BMI. Fasting glucose levels improved significantly in the metformin group (P < 0.05). Change in insulin sensitivity, measured by FSIGT, was not significantly different between the two groups at study end. Mild hypoglycemia occurred more frequently in the metformin-treated than in the placebo subjects (1.75 +/- 0.8 vs. 0.9 +/- 0.4 events. patient(-1). week(-1); P = 0.03). There were no differences in frequency of severe hypoglycemic episodes or gastrointestinal complaints between the two groups.Metformin treatment lowered HbA1c and decreased insulin dosage with no weight gain in teens with type 1 diabetes in poor metabolic control. Changes in insulin sensitivity were not documented in this study using the FSIGT. Long-term studies will determine whether these improvements are sustained and whether certain subgroups accrue greater benefit from this therapy.
Recovery of Locomotion After Spinal Cord Injury: Some Facts and Mechanisms
Authors: Serge Rossignol, Alain Frigon
Journal: Annual Review of Neuroscience (2011)

After spinal cord injury (SCI), various sensorimotor functions can recover, ranging from simple spinal reflexes to more elaborate motor patterns, such as locomotion. Locomotor recovery after complete spinalization (complete SCI) must depend on the presence of spinal circuitry capable of generating the complex sequential activation of various leg muscles. This is achieved by an intrinsic spinal circuitry, termed the central pattern generator (CPG), working in conjunction with sensory feedback from the legs. After SCI, different changes in cellular and circuit properties occur spontaneously and can be promoted by pharmacological, electrical, or rehabilitation strategies. After partial SCI, hindlimb locomotor recovery can result from regeneration or sprouting of spared pathways, but also from mechanisms observed after complete SCI, namely changes within the intrinsic spinal circuitry and sensory inputs.
Maximum-Likelihood Divergence Date Estimates Based on rRNA Gene Sequences Suggest Two Scenarios of Trypanosoma cruzi Intraspecific Evolution
Authors: S Y Kawashita, G F Sanson, O Fernandes, B Zingales, M R Briones
Journal: Molecular Biology and Evolution (2001)

The phylogenetic relationships of Trypanosoma cruzi strains were inferred using maximum-likelihood from complete 18S rDNA sequences and D7-24Salpha rDNA regions from 20 representative strains of T. cruzi. For this we sequenced the 18S rDNA of 14 strains and the D7-24Salpha rDNA of four strains and aligned them to previously published sequences. Phylogenies inferred from these data sets identified four groups, named Riboclades 1, 2, 3, and 4, and a basal dichotomy that separated Riboclade 1 from Riboclades 2, 3, and 4. Substitution models and other parameters were optimized by hierarchical likelihood tests, and our analysis of the 18S rDNA molecular clock by the likelihood ratio test suggests that a taxa subset encompassing all 2,150 positions in the alignment supports rate constancy among lineages. The present analysis supports the notion that divergence dates of T. cruzi Riboclades can be estimated from 18S rDNA sequences and therefore, we present alternative evolutionary scenarios based on two different views of T. cruzi intraspecific divergence. The first assumes a faster evolutionary rate, which suggests that the divergence between T. cruzi I and II and the extant strains occurred in the Tertiary period (37-18 MYA). The other, which supports the hypothesis that the divergence between T. cruzi I and II occurred in the Cretaceous period (144-65 MYA) and the divergence of the extant strains occurred in the Tertiary period of the Cenozoic era (65-1.8 MYA), is consistent with our previously proposed hypothesis of divergence by geographical isolation and mammalian host coevolution.
microRNA-146a inhibits G protein-coupled receptor-mediated activation of NF-κB by targeting CARD10 and COPS8 in gastric cancer
Authors: Stephanie Geisler Crone, Anders Jacobsen, Birgitte Federspiel, Linda Bardram, Anders Krogh, Anders H Lund, Lennart Friis-Hansen
Journal: Molecular Cancer (2012)

Abstract Background Gastric cancer is the second most common cause of cancer-related death in the world. Inflammatory signals originating from gastric cancer cells are important for recruiting inflammatory cells and regulation of metastasis of gastric cancer. Several microRNAs (miRNA) have been shown to be involved in development and progression of gastric cancer. miRNA-146a (miR-146a) is a modulator of inflammatory signals, but little is known about its importance in gastric cancer. We therefore wanted to identify targets of miR-146a in gastric cancer and examine its biological roles. Results The expression of miR-146a was evaluated by quantitative PCR (qPCR) and found up-regulated in the gastrin knockout mice, a mouse model of gastric cancer, and in 73% of investigated human gastric adenocarcinomas. Expression of miR-146a by gastric cancer cells was confirmed by in situ hybridization. Global analysis of changes in mRNA levels after miR-146a transfection identified two transcripts, caspase recruitment domain-containing protein 10 (CARD10) and COP9 signalosome complex subunit 8 (COPS8), as new miR-146a targets. qPCR, Western blotting and luciferase assays confirmed these transcripts as direct miR-146a targets. CARD10 and COPS8 were shown to be part of the G protein-coupled receptor (GPCR) pathway of nuclear factor-kappaB (NF-kappaB) activation. Lysophosphatidic acid (LPA) induces NF-kappaB activation via this pathway and over-expression of miR-146a inhibited LPA-induced NF-kappaB activation, reduced LPA-induced expression of tumor-promoting cytokines and growth factors and inhibited monocyte attraction. Conclusions miR-146a expression is up-regulated in a majority of gastric cancers where it targets CARD10 and COPS8, inhibiting GPCR-mediated activation of NF-kappaB, thus reducing expression of NF-kappaB-regulated tumor-promoting cytokines and growth factors. By targeting components of several NF-kappaB-activating pathways, miR-146a is a key component in the regulation of NF-kappaB activity.
High Doses of Antimetabolites Followed by High-Dose Sequential Chemoimmunotherapy and Autologous Stem-Cell Transplantation in Patients With Systemic B-Cell Lymphoma and Secondary CNS Involvement: Final Results of a Multicenter Phase II Trial
Authors: Andrés J.M. Ferreri, Giovanni Donadoni, Maria Giuseppina Cabras, Caterina Patti, Michael Mian, Renato Zambello, Corrado Tarella, Massimo Di Nicola, Alfonso M. D'Arco, Gianluca Doa, Marta Bruno-Ventre, Andrea Assanelli, Marco Foppoli, Giovanni Citterio, Alessandro Fanni, Antonino Mulè, Federico Caligaris-Cappio, Fabio Ciceri
Journal: Journal of Clinical Oncology (2015)

Treatment of secondary CNS dissemination in patients with aggressive lymphomas remains an important, unmet clinical need. Herein, we report the final results of a multicenter phase II trial addressing a new treatment for secondary CNS lymphoma based on encouraging experiences with high doses of antimetabolites in primary CNS lymphoma and with rituximab plus high-dose sequential chemoimmunotherapy (R-HDS) in relapsed aggressive lymphoma.HIV-negative patients with aggressive B-cell lymphoma and secondary CNS involvement at diagnosis or relapse, age 18 to 70 years, and Eastern Cooperative Oncology Group performance status ≤ 3 were enrolled and treated with high-doses of methotrexate and cytarabine, followed by R-HDS (cyclophosphamide, cytarabine, and etoposide) supported by autologous stem-cell transplantation (ASCT). Treatment included eight doses of rituximab and four doses of intrathecal liposomal cytarabine. The primary end point was 2-year event-free survival; the planned accrual was 38 patients.Thirty-eight patients were enrolled; CNS disease was detected at presentation in 16 patients. Toxicity was usually hematologic and manageable, with grade 4 febrile neutropenia in 3% of delivered courses and grade 4 nonhematologic toxicity in 2% of delivered courses. Four patients died because of toxicity. Autologous stem cells were successfully collected in 24 (89%) of 27 patients (median, 10 × 10(6)/kg); 20 patients underwent ASCT. Complete response was achieved in 24 patients (complete response rate, 63%; 95% CI, 48% to 78%). At a median follow-up of 48 months, 17 patients remained relapse free, with a 2-year event-free survival rate of 50% ± 8%. At 5 years, 16 patients were alive, with a 5-year overall survival rate of 41% ± 8% for the whole series and 68% ± 11% for patients who received transplantation. Systemic (extra-CNS) and/or meningeal disease did not affect outcome.The combination of high doses of antimetabolites, R-HDS, and ASCT is feasible and effective in patients age 18 to 70 years old with secondary CNS lymphoma, and we propose it as a new standard therapeutic option.
Selumetinib plus dacarbazine versus placebo plus dacarbazine as first-line treatment for BRAF-mutant metastatic melanoma: a phase 2 double-blind randomised study
Authors: Caroline Robert, Reinhard Dummer, Ralf Gutzmer, Paul Lorigan, Kevin B Kim, Marta Nyakas, Ana Arance, Gabriella Liszkay, Dirk Schadendorf, Mireille Cantarini, Stuart Spencer, Mark R Middleton
Journal: The Lancet Oncology (2013)
Polymorphisms in the novel gene acyloxyacyl hydroxylase (AOAH) are associated with asthma and associated phenotypes
Authors: Kathleen C. Barnes, Audrey Grant, Peisong Gao, Daniela Baltadjieva, Tiina Berg, Peter Chi, Shu Zhang, April Zambelli-Weiner, Eva Ehrlich, Omeed Zardkoohi, Mary E. Brummet, Maria Stockton, Tonya Watkins, Li Gao, Marquita Gittens, Marsha Wills-Karp, Christopher Cheadle, Lisa A. Beck, Terri H. Beaty, Kevin G. Becker, Joe G.N. Garcia, Rasika A. Mathias
Journal: Journal of Allergy and Clinical Immunology (2006)
High Prevalence of Type 2 Diabetes in All Ethnic Groups, Including Europeans, in a British Inner City
Authors: Lisa Riste, Farida Khan, Kennedy Cruickshank
Journal: Diabetes Care (2001)

To compare the prevalence of type 2 diabetes in white Europeans and individuals of African-Caribbean and Pakistani descent.Random sampling of population-based registers in inner-city Manchester, Britain's third most impoverished area. A total of 1,318 people (25-79 years of age) were screened (minimum response 67%); 533 individuals without known diabetes underwent 2-h glucose tolerance testing, classified by 1999 World Health Organization criteria.More than 60% of individuals reported household annual income < pound10,000 ($15,000) per year. Energetic physical activity was rare and obesity was common. Age-standardized (35-79 years) prevalence (mean 95% CI) of known and newly detected diabetes was 20% (17-24%) in Europeans, 22% (18-26%) in African-Caribbeans, and 33% (25-41%) in Pakistanis. Minimum prevalence (assuming all individuals not tested were normoglycemic) was 11% (8-14%), 19% (15-23%), and 32% (24-40%), respectively. Marked changes in prevalence represent only small shifts in glucose distributions. Regression models showed that greater waist girth, lower height, and older age were independently related to plasma glucose levels, as was physical activity. Substituting BMI and waist-to-hip ratio revealed their powerful contribution.A surprisingly high prevalence of diabetes, despite expected increases with new lower criteria, was found in Europeans, as previously established in Caribbeans and Pakistanis. Lower height eliminated ethnic differences in regression models. History and relative poverty, which cosegregate with obesity and physical inactivity, are likely contributors. Whatever the causes, the implications for health services are alarming, although substantial preventive opportunities through small reversals of glucose distributions are the challenge.
Taurine depletion and excitation-contraction coupling in rat myocardium.
Authors: D W Eley, N Lake, H E ter Keurs
Journal: Circulation Research (1994)

Although the sulfur-containing amino acid taurine is found in high concentrations in mammalian myocardium, its involvement in function of the cardiac myocyte remains unclear. To examine the effects of taurine depletion on cardiac mechanical function, rats were treated in vivo with the taurine transport antagonist guanidinoethane sulfonate (GES). After 6 weeks of treatment, myocardial taurine concentrations were decreased to &lt; 40% of control, with no change in tissue DNA content. Right ventricular trabeculas from taurine-depleted rats exhibited significant reductions (P &lt; .05) in isometric twitch force (Ft) at all [Ca2+]o levels and systolic sarcomere lengths examined. Taurine-depleted trabeculas also exhibited increased passive compliance. A slight (P &lt; .05) rightward shift in the Ft-[Ca2+]o relation suggested a decrease in the sensitivity of the taurine-depleted muscles to [Ca2+]o. No changes were observed in the force-interval relation, suggesting that the transsarcolemmal Ca(2+)-handling mechanisms remained unchanged. The fraction of Ca2+ recirculated through the sarcoplasmic reticulum, inferred from the decay of postextrasystolic potentiation, was also not different in the taurine-depleted muscles. When force was expressed relative to the rate of stimulation, length of rest periods, or postextrasystolic potentiation, virtually all curves were super-imposable for control and taurine-depleted muscles, suggesting that the deficit was not dependent on Ca2+ handling. Thus, we conclude that in taurine-depleted muscles the force-generating processes showed the same regulation as in control muscle. Furthermore, the substantial deficit in force development is consistent with a reduced population of force generators on the basis of three pieces of evidence.(ABSTRACT TRUNCATED AT 250 WORDS)
Quartet Puzzling: A Quartet Maximum-Likelihood Method for Reconstructing Tree Topologies
Authors: K. Strimmer, A. von Haeseler
Journal: Molecular Biology and Evolution (1996)

A versatile method, quartet puzzling, is introduced to reconstruct the topology (branching pattern) of a phylogenetic tree based on DNA or amino acid sequence data. This method applies maximum-likelihood tree reconstruction to all possible quartets that can be formed from n sequences. The quartet trees serve as starting points to reconstruct a set of optimal n-taxon trees. The majority rule consensus of these trees defines the quartet puzzling tree and shows groupings that are well supported. Computer simulations show that the performance of quartet puzzling to reconstruct the true tree is always equal to or better than that of neighbor joining. For some cases with high transition/transversion bias quartet puzzling outperforms neighbor joining by a factor of 10. The application of quartet puzzling to mitochondrial RNA and tRNAVd’ sequences from amniotes demonstrates the power of the approach. A PHYLIP-compatible ANSI C program, PUZZLE, for analyzing nucleotide or amino acid sequence data is available.