tbuckley/cabot-search huggingface dataset:
Activation sequence and potential distribution maps demonstrating multicentric atrial impulse origin in dogs.
Authors: J P Boineau, C B Miller, R B Schuessler, W R Roeske, L J Autry, A C Wylds, D A Hill
Journal: Circulation Research (1984)

We examined the onset of atrial epicardial excitation by recording unipolar potentials from 360 electrodes arranged in templates affixed to the superior vena cava and right atrium in dogs. Both activation sequence and potential distribution maps were obtained for the period of impulse origin beginning before the surface P wave and continuing through the first 15-20 msec of atrial depolarization. The activation maps demonstrated impulse origin from multiple widely separated sites, resulting in two to three individual wavefronts that merged to form a single widely disseminated wavefront spread over a 50 X 20 mm area by 10-15 msec. Atrial potential maps obtained for the same time periods revealed multiple sites of primary negativity corresponding to the points of impulse origin in the activation maps. The potential distributions and evolution of these maps also indicated the presence of multiple wavefronts originating from widely separated locations, and suggested an extensively dispersed source of impulse origin. One of these sites at the superior cavo-appendicular junction corresponded to the rostral portion of the sinus node and the site of classical unifocal origin. Additional sites of impulse origin and primary negativity distant to the sinus node were noted either concurrently in the same map or in other maps associated with different patterns of impulse initiation. Classical physiological and pharmacological interventions were used to alter adrenergic and cholinergic input to the atrium, and resulted in coincident changes of both the patterns of impulse origin and heart rate. In addition, we examined spontaneous changes in the patterns of impulse initiation which accompanied beat-to-beat changes in cycle length (sinus arrhythmia). There was close agreement between activation and potential maps over the entire steady state and dynamic range of impulse origin. The data can be explained by the concept of a widely distributed system of functionally differentiated but coordinated atrial pacemakers.
Serum concentration of 7S collagen and prognosis in patients with the adult respiratory distress syndrome.
Authors: M Kawamura, F Yamasawa, A Ishizaka, R Kato, K Kikuchi, K Kobayashi, T Aoki, F Sakamaki, N Hasegawa, T Kawashiro
Journal: Thorax (1994)

BACKGROUND--7S collagen, an N-terminal peptide of type IV collagen, is a primary constituent of the basement membrane. To evaluate whether the serum concentration of 7S collagen reflects the severity of inflammatory lung disease, the serum concentration of 7S collagen was measured in patients with adult respiratory distress syndrome (ARDS) and idiopathic pulmonary fibrosis (IPF). METHODS--A radioimmunoassay was used for the measurement of 7S collagen. Gas exchange abnormality was expressed as the arterial oxygen tension (PaO2) divided by the fractional concentration of inspired oxygen (FiO2). RESULTS--The mean (SD) concentration of 7S collagen was 2.7 (0.9) ng/ml in 10 healthy subjects, 5.0 (1.5) ng/ml in 11 patients with IPF, and 14.8 (9.7) ng/ml in 13 patients with ARDS. Significant differences were observed between the patients with ARDS and both healthy subjects and the patients with IPF. In the patients with ARDS serum concentrations of 7S collagen were strongly related to PaO2/FiO2 (r = -0.61). Moreover, the mean (SD) serum concentration of 7S collagen in the eight patients with ARDS who died (19.5 (10.2) ng/ml) was considerably higher than that of the five who survived (7.1 (2.1) ng/ml). CONCLUSION--These results suggest that serum levels of the 7S fragment of type IV collagen may have some prognostic value in ARDS.
T-cell populations specifically depleted of alloreactive potential cannot be induced to lyse H-2-different virus-infected target cells.
Authors: J R Bennink, P C Doherty
Journal: The Journal of Experimental Medicine (1978)

Mouse lymphocyte populations of one parental H-2 type (A) were specificially depleted of alloreactive potential by filtration through irradiated A X B F1 recipients, and thoracic duct cells were then stimulated with virus in an A X B F1 environment. Experiments using T cells that had previously been exposed to influenza virus in the context of A established that cross-priming for recognition of viral components expressed on H-2-different (B) target cells does not occur. Furthermore, immunologically naive T cells stimulated with vaccinia virus, subsequent to negative selection for reactivity to B, could not be shown to interact with virus-infected cells of type B. Either there is no significant T-cell repertoire for recognition of virus associated with an H-2 determinant not encountered during ontogeny, or such T cells are also alloreactive and are removed during filtration.
A bioabsorbable everolimus-eluting coronary stent system (ABSORB): 2-year outcomes and results from multiple imaging methods
Authors: Patrick W Serruys, John A Ormiston, Yoshinobu Onuma, Evelyn Regar, Nieves Gonzalo, Hector M Garcia-Garcia, Koen Nieman, Nico Bruining, Cécile Dorange, Karine Miquel-Hébert, Susan Veldhof, Mark Webster, Leif Thuesen, Dariusz Dudek
Journal: The Lancet (2009)
The Function of Synaptic Transmitters in the Retina
Authors: N W Daw, W J Brunken, D Parkinson
Journal: Annual Review of Neuroscience (1989)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More
PGC1α Expression Defines a Subset of Human Melanoma Tumors with Increased Mitochondrial Capacity and Resistance to Oxidative Stress
Authors: Francisca Vazquez, Ji-Hong Lim, Helen Chim, Kavita Bhalla, Geoff Girnun, Kerry Pierce, Clary B. Clish, Scott R. Granter, Hans R. Widlund, Bruce M. Spiegelman, Pere Puigserver
Journal: Cancer Cell (2013)
Association of Body Mass Index with Outcomes in Patients with CKD
Authors: Jun Ling Lu, Kamyar Kalantar-Zadeh, Jennie Z. Ma, L. Darryl Quarles, Csaba P. Kovesdy
Journal: Journal of the American Society of Nephrology (2014)

Obesity is associated with higher mortality in the general population, but this association is reversed in patients on dialysis. The nature of the relationship of obesity with adverse clinical outcomes in nondialysis-dependent CKD and the putative interaction of the severity of disease with this association are unclear. We analyzed data from a nationally representative cohort of 453,946 United States veterans with eGFR<60 ml/min per 1.73 m(2). The associations of body mass index categories (<20, 20 to <25, 25 to <30, 30 to <35, 35 to <40, 40 to <45, 45 to <50, and ≥50 kg/m(2)) with all-cause mortality and disease progression (using multiple definitions, including incidence of ESRD, doubling of serum creatinine, and the slopes of eGFR) were examined in Cox proportional hazards models and logistic regression models. Multivariable adjustments were made for age, race, comorbidities and medications, and baseline eGFR. Body mass index showed a relatively consistent U-shaped association with clinical outcomes, with the best outcomes observed in overweight and mildly obese patients. Body mass index levels <25 kg/m(2) were associated with worse outcomes in all patients, independent of severity of CKD. Body mass index levels ≥35 kg/m(2) were associated with worse outcomes in patients with earlier stages of CKD, but this association was attenuated in those patients with eGFR<30 ml/min per 1.73 m(2). Thus, until clinical trials establish the ideal body mass index, a cautious approach to weight management is warranted in this patient population.
Surveillance guidelines after removal of colorectal adenomatous polyps
Authors: W S Atkin, B P Saunders
Journal: Gut (2002)

Most colon cancers are assumed to have a premalignant adenomatous polyp phase, therefore colonoscopic detection and polypectomy provides the opportunity for cancer prevention. Some patients who have undergone colonoscopy and have had adenomas removed are at increased risk of developing colorectal cancer (CRC) in the future, and therefore might benefit from colonoscopic surveillance. However, it is important to appreciate that colonoscopy is an invasive and costly procedure with some associated morbidity. It is also an under-resourced procedure in the UK, with a serious lack of fully trained endoscopists. Around one third of the population will develop an adenoma by age 60. Most adenomas are asymptomatic and remain undiagnosed. If colorectal screening is introduced this situation will change dramatically. There are few data on the benefits of colonoscopic surveillance in preventing colorectal cancer after a baseline clearing colonoscopy. It is therefore important that this practice is applied judiciously, balancing the risks and benefits in each individual case. Using published evidence, this guideline recommends appropriate surveillance after adenoma removal. The decision to perform each follow up colonoscopy should also depend on the patient’s wishes, the presence of comorbidity, the patient’s age, and the presence of other risk factors.

### Risk of colorectal cancer and adenomas with advanced pathology (≥1 cm or severely dysplastic) (see fig 1)



 Figure 1  
Surveillance after adenoma removal.



Risk can be stratified according to findings at baseline and refined at each subsequent surveillance examination. (Recommendation Grade B) 

#### Low risk

Patients with only 1–2, small (<1 cm) adenomas.

Recommendation: no follow up or five yearly until one negative examination .

#### Intermediate risk

Patients with 3–4 small adenomas or at least one >1 cm

Recommendation: three yearly until two consecutive negative examinations .

#### High risk

If either of the following are detected at any single examination (at baseline or follow up):

≥5 adenomas or ≥3 adenomas at least one of which is ≥1 cm.

Recommendation: An extra examination should be undertaken at 12 months before returning …
SOMATIC HYPERMUTATION OF IMMUNOGLOBULIN GENES
Authors: Simon D. Wagner, Michael S. Neuberger
Journal: Annual Review of Immunology (1996)

▪ Abstract The relationship between somatic hypermutation and affinity maturation in the mouse is delineated. Recent work on the anatomical and cellular site of this process is surveyed. The molecular characteristics of somatic hypermutation are described in terms of the region mutated and the distinctive patterns of nucleotide changes that are observed. The results of experiments utilizing transgenic mice to find out the minimum cis-acting sequences required to recruit hypermutation are summarized. The hypothesis that V gene sequences have evolved in order to target mutation to certain sites but not others is discussed. The use that different species make of somatic hypermutation to generate either the primary or secondary B cell repertoire is considered. Possible molecular mechanisms for the hypermutation process and future goals of research are outlined.
Circulating interleukin 6 and interleukin 10 in community acquired pneumonia
Authors: P Glynn, R Coakley, I Kilgallen, N Murphy, S O'Neill
Journal: Thorax (1999)

Inflammatory cytokine concentrations correlate with severity of sepsis. We hypothesised that patients with community acquired pneumonia (CAP) associated with systemic inflammatory response syndrome (SIRS) would have greater interleukin 6 (IL-6) production due to activation of the inflammatory cytokine cascade, matched by a significant anti-inflammatory cytokine response. Interleukin 10 (IL-10) was evaluated as a potential surrogate marker of severity of sepsis in CAP and age related impairment of the cytokine response was studied in elderly patients with CAP.Circulating immunoreactive IL-6 and IL-10 levels were measured in 38 patients with CAP subdivided into a group fulfilling the criteria for SIRS (n = 28) and a non-SIRS group (n = 10) in a variety of age groups and correlated with APACHE II scores.80% had circulating IL-6 levels (median 46.7 pg/ml, range 4.6-27,000) and 60% had circulating IL-10 levels (median 15.5 pg/ml, range 2.5-765). Concentrations of both were significantly increased in patients with SIRS compared with non-SIRS patients. Those with activation of the inflammatory cytokine cascade (IL-6 positive) produced more IL-10 than IL-6 negative patients. Older patients had a similar cytokine response. Both cytokines correlated positively with APACHE II scores.This is the first demonstration of circulating IL-10 in CAP. A greater counter-inflammatory response in patients with SIRS and in IL-6 positive patients suggests a potential immunomodulatory role for IL-10 in controlling the inflammatory cytokine response in CAP. IL-10 concentrations correlate with severity of illness in CAP and may be of prognostic importance. There is no age related impairment in the cytokine response.
First-in-Man Phase I Study of GC33, a Novel Recombinant Humanized Antibody Against Glypican-3, in Patients with Advanced Hepatocellular Carcinoma
Authors: Andrew X. Zhu, Philip J. Gold, Anthony B. El-Khoueiry, Thomas A. Abrams, Hideo Morikawa, Norihisa Ohishi, Toshihiko Ohtomo, Philip A. Philip
Journal: Clinical Cancer Research (2013)

Abstract Purpose: GC33 is a novel recombinant fully humanized monoclonal antibody that binds to human glypican-3 (GPC3). The antitumor activity of GC33 was shown in preclinical models of hepatocellular carcinoma (HCC). This first-in-man clinical trial was conducted to evaluate the safety, pharmacokinetic characteristics, and preliminary efficacy of GC33 in patients with advanced HCC. Experimental Design: Patients with measurable, histologically proven, advanced HCC were enrolled to a dose-escalation study of GC33 (2.5–20 mg/kg) given intravenously weekly. The primary endpoint was to determine the maximum tolerated dose of GC33 for further development. Pharmacokinetic characteristics were measured in serum samples. Immunohistochemistry was conducted on tumor biopsies to evaluate GPC3 expression. Tumor response was assessed every 8 weeks using Response Evaluation Criteria in Solid Tumors criteria. Results: Twenty patients were enrolled and treated with GC33. A maximum tolerated dose was not reached as there were no dose-limiting toxicities (DLT) up to the highest planned dose level. Common adverse events with all grades included fatigue (50%), constipation (35%), headache (35%), and hyponatremia (35%). The incidence of adverse events seemed not to be dose dependent. Trough serum concentrations at steady state were in excess of target concentration at doses of 5 mg/kg or greater. Median time to progression (TTP) was 26.0 weeks in the GPC3 high expression group and 7.1 weeks in the low expression group (P = 0.033). Conclusion: This study shows that GC33 was well tolerated in advanced HCC and provides preliminary evidence that GPC3 expression in HCC may be associated with the clinical benefit to GC33 that warrants prospective evaluation. Clin Cancer Res; 19(4); 920–8. ©2012 AACR.
Osteoclasts degrade endosteal components and promote mobilization of hematopoietic progenitor cells
Authors: Orit Kollet, Ayelet Dar, Shoham Shivtiel, Alexander Kalinkovich, Kfir Lapid, Yejezkel Sztainberg, Melania Tesio, Robert M Samstein, Polina Goichberg, Asaf Spiegel, Ari Elson, Tsvee Lapidot
Journal: Nature Medicine (2006)
THE TREATMENT OF HAEMORRHOIDS BY ELECTROLYSIS
Authors: J. C. Webb
Journal: BMJ (1921)

Group I.(a) Non-apposition of fractured ends from.various causes- for example, interpoitioa of soft; structutes '*over-ktension with weights; loss of bone.(b) Movement between apposed ends. (c) Prolonged severe infection.With reference to Group I: Comparativ-ely little is known about (a), but pituitary-'extract is certainly worth a trial; (b) is an important factor, and everytihing possible should be done to encourage use consistent.withprevention of movements at the site of fracture.It is-here that'"massage Splays an inm'portant part.As regards (c) the blood.supplv. may be' injured originally or Jlatercut off by formatio-n of fibrous tissue, and either of these conditions certainly leads to very delayed union.Under Group II are classed those causes of non-union which may be called lack of opportiinit.'T'he' non-apposition of fractured ends is, I think, by far the greatest cause of non-union, and this is, in the great majority of cases, produced by the interposition of some soft'structure.The practice, as was advocated by Leriche, of wholesale removal of all bony fragments in compound comminuted frac- tures is to be condemned.
Regulation of Ion Channel Expression
Authors: Barbara Rosati, David McKinnon
Journal: Circulation Research (2004)

A potentially important mechanism controlling ion channel expression is homeostatic regulation, which can act to maintain a stable electrophysiological phenotype in cardiac myocytes as well as to provide plasticity in response to genetic, pathological, or pharmacological insults. The capabilities and limitations of the homeostatic regulatory mechanisms that contribute to the control of cardiac ion channel expression are the primary topic of this review.
Hypoxia-Inducible Transcription Factors Stabilization in the Thick Ascending Limb Protects against Ischemic Acute Kidney Injury
Authors: Gunnar Schley, Bernd Klanke, Johannes Schödel, Frauke Forstreuter, Deepa Shukla, Armin Kurtz, Kerstin Amann, Michael S. Wiesener, Seymour Rosen, Kai-Uwe Eckardt, Patrick H. Maxwell, Carsten Willam
Journal: Journal of the American Society of Nephrology (2011)

Hypoxia-inducible transcription factors (HIF) protect cells against oxygen deprivation, and HIF stabilization before ischemia mitigates tissue injury. Because ischemic acute kidney injury (AKI) often involves the thick ascending limb (TAL), modulation of HIF in this segment may be protective. Here, we generated mice with targeted TAL deletion of the von Hippel-Lindau protein (Vhl), which mediates HIF degradation under normoxia, using Tamm-Horsfall protein (Thp)-driven Cre expression. These mice showed strong expression of HIF-1α in TALs but no changes in kidney morphology or function under control conditions. Deficiency of Vhl in the TAL markedly attenuated proximal tubular injury and preserved TAL function following ischemia-reperfusion, which may be partially a result of enhanced expression of glycolytic enzymes and lactate metabolism. These results highlight the importance of the thick ascending limb in the pathogenesis of AKI and suggest that pharmacologically targeting the HIF system may have potential to prevent and mitigate AKI.
Decreased clinical response to adalimumab in ankylosing spondylitis is associated with antibody formation
Authors: M K de Vries, E Brouwer, I E van der Horst-Bruinsma, A Spoorenberg, J C van Denderen, A Jamnitski, M T Nurmohamed, B A C Dijkmans, L A Aarden, G J Wolbink
Journal: Annals of the Rheumatic Diseases (2009)

Treatment with anti-tumour necrosis factor (TNF) is very effective in most patients with ankylosing spondylitis (AS), but inefficacy occurs in about 40% of cases.1 Antibody formation against TNF blocking agents is an increasingly recognised problem;2 however, no data have yet been reported on antibody formation against adalimumab (anti-adalimumab) in AS. Lack of response can be explained in two ways: (1) TNF might not be important for disease activity in certain patients; and (2) TNF inhibition might be insufficient. The latter could be caused by excessive production of TNF, low compliance of the patient, insufficient dosing or an enhanced clearance of adalimumab due to antibody formation. Adalimumab is a fully human monoclonal antibody against TNF but, despite this fact, an immune response …
Uncovering protein interaction in abstracts and text using a novel linear model and word proximity networks
Authors: Alaa Abi-Haidar, Jasleen Kaur, Ana Maguitman, Predrag Radivojac, Andreas Rechtsteiner, Karin Verspoor, Zhiping Wang, Luis M Rocha
Journal: Genome biology (2008)

Abstract Background: We participated in three of the protein-protein interaction subtasks of the Second BioCreative Challenge: classification of abstracts relevant for protein-protein interaction (interaction article subtask [IAS]), discovery of protein pairs (interaction pair subtask [IPS]), and identification of text passages characterizing protein interaction (interaction sentences subtask [ISS]) in full-text documents. We approached the abstract classification task with a novel, lightweight linear model inspired by spam detection techniques, as well as an uncertainty-based integration scheme. We also used a support vector machine and singular value decomposition on the same features for comparison purposes. Our approach to the full-text subtasks (protein pair and passage identification) includes a feature expansion method based on word proximity networks. Results: Our approach to the abstract classification task (IAS) was among the top submissions for this task in terms of measures of performance used in the challenge evaluation (accuracy, F-score, and area under the receiver operating characteristic curve). We also report on a web tool that we produced using our approach: the Protein Interaction Abstract Relevance Evaluator (PIARE). Our approach to the full-text tasks resulted in one of the highest recall rates as well as mean reciprocal rank of correct passages. Conclusion: Our approach to abstract classification shows that a simple linear model, using relatively few features, can generalize and uncover the conceptual nature of protein-protein interactions from the bibliome. Because the novel approach is based on a rather lightweight linear model, it can easily be ported and applied to similar problems. In full-text problems, the expansion of word features with word proximity networks is shown to be useful, although the need for some improvements is discussed.
Viewing cognitive mechanisms in the context of biology
Authors: Linda Hermer-Vazquez
Journal: Behavioral and Brain Sciences (2002)

Cognitive mechanisms are based in organisms’biology, and results from biological studies suggest that there is unlikely to be a single mechanism for reorienting or for combining information across modules or domains. Rather, there are likely to be multiple, partly overlapping systems for accomplishing nearly all cognitive and behavioral goals, as is the case for biological mechanisms more generally.
THE ANAEROBIC BACTERIAL FLORA OF THE MOUSE CECUM
Authors: James H. Gordon, René Dubos
Journal: The Journal of Experimental Medicine (1970)

Refinements of the anaerobic technique such as the utilization of prereduced media and the removal of traces of oxygen from the gases used by passage through a hot copper oven resulted in quantitative and qualitative improvements in the recovery of anaerobic bacteria from the cecum of SPF mice. The commonest morphologic types of bacteria in the mouse cecum were tapered rods. These characteristically gave "speckled" colonies on agar plates. Those identified were species of the genera Fusobacterium, Eubacterium, and Clostridium. Several of the morphologic types seen with phase microscopy still could not be cultivated. The implications of these findings for the study of the intestinal flora are discussed.
Chemotherapy response evaluation with FDG–PET in patients with colorectal cancer
Authors: L.F. de Geus-Oei, H.W.M. van Laarhoven, E.P. Visser, R. Hermsen, B.A. van Hoorn, Y.J.L. Kamm, P.F.M. Krabbe, F.H.M. Corstens, C.J.A. Punt, W.J.G. Oyen
Journal: Annals of Oncology (2007)