tbuckley/cabot-search huggingface dataset:
18F-fluoride positron emission tomography for identification of ruptured and high-risk coronary atherosclerotic plaques: a prospective clinical trial
Authors: Nikhil V Joshi, Alex T Vesey, Michelle C Williams, Anoop S V Shah, Patrick A Calvert, Felicity H M Craighead, Su Ern Yeoh, William Wallace, Donald Salter, Alison M Fletcher, Edwin J R van Beek, Andrew D Flapan, Neal G Uren, Miles W H Behan, Nicholas L M Cruden, Nicholas L Mills, Keith A A Fox, James H F Rudd, Marc R Dweck, David E Newby
Journal: The Lancet (2013)

The use of non-invasive imaging to identify ruptured or high-risk coronary atherosclerotic plaques would represent a major clinical advance for prevention and treatment of coronary artery disease. We used combined PET and CT to identify ruptured and high-risk atherosclerotic plaques using the radioactive tracers (18)F-sodium fluoride ((18)F-NaF) and (18)F-fluorodeoxyglucose ((18)F-FDG).In this prospective clinical trial, patients with myocardial infarction (n=40) and stable angina (n=40) underwent (18)F-NaF and (18)F-FDG PET-CT, and invasive coronary angiography. (18)F-NaF uptake was compared with histology in carotid endarterectomy specimens from patients with symptomatic carotid disease, and with intravascular ultrasound in patients with stable angina. The primary endpoint was the comparison of (18)F-fluoride tissue-to-background ratios of culprit and non-culprit coronary plaques of patients with acute myocardial infarction.In 37 (93%) patients with myocardial infarction, the highest coronary (18)F-NaF uptake was seen in the culprit plaque (median maximum tissue-to-background ratio: culprit 1·66 [IQR 1·40-2·25] vs highest non-culprit 1·24 [1·06-1·38], p<0·0001). By contrast, coronary (18)F-FDG uptake was commonly obscured by myocardial uptake and where discernible, there were no differences between culprit and non-culprit plaques (1·71 [1·40-2·13] vs 1·58 [1·28-2·01], p=0·34). Marked (18)F-NaF uptake occurred at the site of all carotid plaque ruptures and was associated with histological evidence of active calcification, macrophage infiltration, apoptosis, and necrosis. 18 (45%) patients with stable angina had plaques with focal (18)F-NaF uptake (maximum tissue-to-background ratio 1·90 [IQR 1·61-2·17]) that were associated with more high-risk features on intravascular ultrasound than those without uptake: positive remodelling (remodelling index 1·12 [1·09-1·19] vs 1·01 [0·94-1·06]; p=0·0004), microcalcification (73% vs 21%, p=0·002), and necrotic core (25% [21-29] vs 18% [14-22], p=0·001).(18)F-NaF PET-CT is the first non-invasive imaging method to identify and localise ruptured and high-risk coronary plaque. Future studies are needed to establish whether this method can improve the management and treatment of patients with coronary artery disease.Chief Scientist Office Scotland and British Heart Foundation.
Crush Injuries with Impairment of Renal Function
Authors: E. G. L. Bywaters, D. Beall
Journal: BMJ (1941)

Amongst air-raid casualties seen at this hospital have been four cases of crush injury of the limbs which, because of the general similarity of their clinical course, were thought to represent a specic and hitherto unreported syndrome, and one which has been and will be seen elsewhere during .thewar.Suich a condition may have been ob- ' _ ' ing.The haemo- IST DAY 2ND globin, however, CHART ]is raised, and a few hours later, despite vasoconstfttbtS, iiade.-ma-iifest by pallor, coldness, and sweating, 'Thfe blood -pressure falls.This is restored--to pre-shock.level by (often multiple) transfusicns of serum, plasrna,&"_ -casionall'
Targeting the EWSR1-FLI1 Oncogene-Induced Protein Kinase PKC-β Abolishes Ewing Sarcoma Growth
Authors: Didier Surdez, Magdalena Benetkiewicz, Virginie Perrin, Zhi-Yan Han, Gaëlle Pierron, Stelly Ballet, François Lamoureux, Françoise Rédini, Anne-Valérie Decouvelaere, Estelle Daudigeos-Dubus, Birgit Geoerger, Gonzague de Pinieux, Olivier Delattre, Franck Tirode
Journal: Cancer Research (2012)

Abstract Ewing sarcoma is a rare but aggressive disease most common in young adults. This cancer is driven by a unique chimeric fusion oncogene but targeted strategies have been elusive. Here we report the identification of the protein kinase PKC-ß (PRKCB) as a disease-specific druggable target for treatment of Ewing sarcoma. We found that transcriptional activation of PRKCB was directly regulated by the chimeric fusion oncogene EWSR1-FLI1 that drives this cancer. PRKCB phosphorylated histone H3T6 to permit global maintenance of H3K4 trimethylation at a variety of gene promoters. PRKCB loss induced apoptosis in vitro and prevented tumor growth in vivo. Gene expression profiling revealed a strong overlap between genes modulated by EWSR1-FLI1 and PRKCB in regulating crucial signaling pathways. Taken together, our findings offer a preclinical proof-of-concept for PRKCB as a promising therapeutic target in Ewing sarcoma. Cancer Res; 72(17); 4494–503. ©2012 AACR.
TREM2 is associated with increased risk for Alzheimer’s disease in African Americans
Authors: Sheng Chih Jin, Minerva M Carrasquillo, Bruno A Benitez, Tara Skorupa, David Carrell, Dwani Patel, Sarah Lincoln, Siddharth Krishnan, Michaela Kachadoorian, Christiane Reitz, Richard Mayeux, Thomas S Wingo, James J Lah, Allan I Levey, Jill Murrell, Hugh Hendrie, Tatiana Foroud, Neill R Graff-Radford, Alison M Goate, Carlos Cruchaga, Nilüfer Ertekin-Taner
Journal: Molecular Neurodegeneration (2015)

TREM2 encodes for triggering receptor expressed on myeloid cells 2 and has rare, coding variants that associate with risk for late-onset Alzheimer's disease (LOAD) in Caucasians of European and North-American origin. This study evaluated the role of TREM2 in LOAD risk in African-American (AA) subjects. We performed exonic sequencing and validation in two independent cohorts of >800 subjects. We selected six coding variants (p.R47H, p.R62H, p.D87N, p.E151K, p.W191X, and p.L211P) for case-control analyses in a total of 906 LOAD cases vs. 2,487 controls.We identified significant LOAD risk association with p.L211P (p=0.01, OR=1.27, 95%CI=1.05-1.54) and suggestive association with p.W191X (p=0.08, OR=1.35, 95%CI=0.97-1.87). Conditional analysis suggests that p.L211P, which is in linkage disequilibrium with p.W191X, may be the stronger variant of the two, but does not rule out independent contribution of the latter. TREM2 p.L211P resides within the cytoplasmic domain and p.W191X is a stop-gain mutation within the shorter TREM-2V transcript. The coding variants within the extracellular domain of TREM2 previously shown to confer LOAD risk in Caucasians were extremely rare in our AA cohort and did not associate with LOAD risk.Our findings suggest that TREM2 coding variants also confer LOAD risk in AA, but implicate variants within different regions of the gene than those identified for Caucasian subjects. These results underscore the importance of investigating different ethnic populations for disease risk variant discovery, which may uncover allelic heterogeneity with potentially diverse mechanisms of action.
Intervention in growth factor activated signaling pathways by renally targeted kinase inhibitors
Authors: Marjan M. Fretz, M.E. (Emmy) M. Dolman, Marie Lacombe, Jai Prakash, Tri Q. Nguyen, Roel Goldschmeding, Janos Pato, Gert Storm, Wim E. Hennink, Robbert J. Kok
Journal: Journal of Controlled Release (2008)
Localization of the duodenal pacemaker and its role in the organization of duodenal myoelectric activity
Authors: J. Hermon-Taylor, C. F. Code
Journal: Gut (1971)

In two series of conscious healthy dogs, a study of duodenal electric activity was made to locate the pacemaker or site of the greatest intrinsic frequency of the pacesetter potential. In three dogs, an annular myotomy of the duodenum about 1 cm proximal (orad) to the biliary ampulla caused a reduction in the frequency of the pacesetter potential distal (caudad) to the conduction block and demonstrated that the pacemaker was not in the region of the ampulla, as had been suggested previously. Annular myotomy of the duodenum at increasing intervals distal to the pylorus in a second series of eight dogs showed that the pacemaker was present in the proximal 5 to 6 mm of duodenum. The greater frequency of the pacemaker was found to maintain constant distal conduction of the pacesetter potential. Distal conduction of the pacesetter potential was shown on occasion to be associated with the distal propagation of action potentials along the duodenum.
Photopatch testing of 1155 patients: results of the U.K. multicentre photopatch study group
Authors: A.M. Bryden, H. Moseley, S.H. Ibbotson, M.M.U. Chowdhury, M.H. Beck, J. Bourke, J. English, P. Farr, I.S. Foulds, D.J. Gawkrodger, S. George, D.I. Orton, S. Shaw, J. McFadden, P. Norris, P. Podmore, S. Powell, L.E. Rhodes, J. Sansom, M. Wilkinson, H. Van Weelden, J. Ferguson
Journal: British Journal of Dermatology (2006)

Background Photoallergic contact dermatitis can be difficult to diagnose if not appropriately investigated. Currently, the most common U.K. photoallergens appear to be sunscreen chemicals. The investigation of choice is photopatch testing (PPT), which is probably underused. In part, this is due to differences in methodology and results interpretation. Objectives To conduct PPT using a group of sunscreen chemicals, defined indications and a standardized methodology including interpretation and relevance of reactions in patients attending for investigation at 17 centres across the U.K., Ireland and the Netherlands. Methods Patients (n = 1155) who fulfilled the inclusion criteria were investigated with PPT using sunscreen chemicals in addition to suspected topical products. Readings were taken at 24, 48 and 72 h following standardized ultraviolet A irradiation (5 J cm−2). The clinical relevance of any reaction was recorded. Results Of the 1155, 130 had allergic reactions (11·3%). Of these, 51 had photoallergy (PA) (4·4%), 64 had contact allergy (CA) (5·5%), and 15 patients had combined PA and CA (1·3%). Multiple PA was seen in some. The most common photoallergen was benzophenone‐3 (27 reactions; 21%). Most reactions (60%) were clinically relevant. The most common indication for testing in patients found to have PA was a history of reacting to a sunscreen (41%). The other 59% had an exposed‐site dermatitis/skin problem or a photodermatosis. Some centres (n = 8) performed readings after the standard 48‐h reading, and an extra 32 PA and 22 CA reactions were detected, which were not evident at 48 h. A new photoallergen (octyl triazone) was detected in two patients. Conclusions Sunscreen PA and CA are probably equally uncommon. Most reactions, of both reaction types, were relevant clinically. A large proportion of patients (59%) found to have PA was unaware of reacting to a sunscreen chemical, suggesting that PA should be considered as an explanation in any exposed‐site dermatitis. Although this study focused on reactions at 48 h postirradiation, readings performed up to 96 h, while inconvenient, add value by detecting additional relevant responses. A previously unknown photoallergen was found, highlighting the need for awareness of novel photoallergens in the marketplace. A standardized PPT method not only encourages more use of this investigation, but also facilitates comparison of results between centres and so will improve our understanding of PA.
Penicillin and Venereal Disease
Authors: L. G. Duff
Journal: BMJ (1946)

<h3>Objectives</h3> Acute myocardial infarction (AMI) case ascertainment improves for the UK general population using linked health data sets. Because care pathways for people with chronic kidney disease (CKD) change based on disease severity, AMI case ascertainment for these people may differ compared with the general population. We aimed to determine the association between CKD severity and AMI case ascertainment in two secondary care data sets, and the agreement in estimated glomerular filtration rate (eGFR) between the same data sets. <h3>Methods</h3> We used a cohort study design. Primary care records for people with CKD or risk factors for CKD, identified using the National CKD Audit (2015–2017), were linked to the Myocardial Ischaemia National Audit Project (MINAP, 2007–2017) and Hospital Episode Statistics (HES, 2007–2017) secondary care registries. People with an AMI recorded in either MINAP, HES or both were included in the study cohort. CKD status was defined using eGFR, derived from the most recent serum creatinine value recorded in primary care. Moderate–severe CKD was defined as eGFR &lt;60 mL/min/1.73 m<sup>2</sup>, and mild CKD or at risk of CKD was defined as eGFR ≥60 mL/min/1.73 m<sup>2</sup> or eGFR missing. CKD stages were grouped as (1) At risk of CKD and Stages 1–2 (eGFR missing or ≥60 mL/min/1.73 m<sup>2</sup>), (2) Stage 3a (eGFR 45–59 mL/min/1.73 m<sup>2</sup>), (3) Stage 3b (eGFR 30–44 mL/min/1.73 m<sup>2</sup>) and (4) Stages 4–5 (eGFR &lt;30 mL/min/1.73 m<sup>2</sup>). <h3>Results</h3> We identified 6748 AMIs: 23% were recorded in both MINAP and HES, 66% in HES only and 11% in MINAP only. Compared with people at risk of CKD or with mild CKD, AMIs in people with moderate–severe CKD were more likely to be recorded in both MINAP and HES (42% vs 11%, respectively), or MINAP only (22% vs 5%), and less likely to be recorded in HES only (36% vs 84%). People with AMIs recorded in HES only or MINAP only had increased odds of death during hospitalisation compared with those recorded in both (adjusted OR 1.61, 95% CI 1.32 to 1.96 and OR 1.60, 95% CI 1.26 to 2.04, respectively). Agreement between eGFR at AMI admission (MINAP) and in primary care was poor (kappa (K) 0.42, SE 0.012). <h3>Conclusions</h3> AMI case ascertainment is incomplete in both MINAP and HES, and is associated with CKD severity.
Randomized, Double‐Blind, Placebo‐Controlled Trial of the Effect of Vitamin D<sub>3</sub> on the Interferon Signature in Patients With Systemic Lupus Erythematosus
Authors: Cynthia Aranow, Diane L. Kamen, Maria Dall'Era, Elena M. Massarotti, Meggan C. Mackay, Fotios Koumpouras, Andreea Coca, W. Winn Chatham, Megan E. B. Clowse, Lisa G. Criscione‐Schreiber, Sherri Callahan, Ellen A. Goldmuntz, Lynette Keyes‐Elstein, Michaela Oswald, Peter K. Gregersen, Betty Diamond
Journal: Arthritis & Rheumatology (2015)

Vitamin D modulates the immune response and blocks induction of an interferon (IFN) signature by systemic lupus erythematosus (SLE) sera. This study was undertaken to investigate the effects of vitamin D supplementation on the IFN signature in patients with SLE.SLE patients (n = 57) with stable, inactive disease, a serum 25-hydroxyvitamin D (25[OH]D) level ≤20 ng/ml, an elevated anti-double-stranded DNA antibody level, and an IFN signature (as determined by measuring the expression levels of 3 IFN response genes) were randomized into a 12-week double-blind, placebo-controlled trial of vitamin D3 at doses of 2,000 IU or 4,000 IU. An IFN signature response was defined as a 50% reduction in the expression of 1 of the 3 genes or a 25% reduction in the expression of 2 of the 3 genes. Disease activity, adverse events, and endocrine effects were assessed.Baseline characteristics of the patients in the 3 treatment groups (placebo, low-dose vitamin D3 , or high-dose vitamin D3 ) were similar. Repletion of 25(OH)D (i.e., levels ≥30 ng/ml) was not observed in any of the patients who were receiving placebo, while repletion was observed in 16 of 33 patients receiving vitamin D3 . The percentage of patients with an IFN signature response did not differ among the treatment groups. Moreover, there was no difference in the percentage of patients with an IFN signature response between those who remained vitamin D deficient and those who demonstrated repletion of vitamin D. Modular microarray analysis of a subset of patients (n = 40) did not reveal changes from baseline in any modules (including the IFN-inducible module) in any of the treatment groups, and no differences in expression were found between patients who demonstrated vitamin D repletion and patients who were persistently vitamin D deficient. Vitamin D3 was well tolerated, and there were no safety concerns.Vitamin D3 supplementation up to 4,000 IU daily was safe and well-tolerated but failed to diminish the IFN signature in vitamin D-deficient SLE patients. Higher 25(OH)D levels sustained for a longer duration may be required to affect immunologic outcomes.
Prolonged pregnancy: the management debate.
Authors: L Cardozo, J Fysh, J M Pearce
Journal: BMJ (1986)

A prospective trial was conducted to compare the effects of conservative management of prolonged pregnancy (conservative group) with routine induction of labour at 42 weeks9 gestation (active group) in otherwise uncomplicated pregnancies. Of the 402 pregnancies studied, 207 (51%) were allocated to conservative management and 195 (49%) were allocated to have labour induced. The groups were well matched for age, parity, and smoking habits. One hundred and sixty six (80%) of the patients in the conservative group went into spontaneous labour. Of the remainder, two underwent elective caesarean section, 19 had labour induced because of clinical concern, and the remaining 20 had labour induced at the patient9s own request. One hundred and twenty five (64%) of the patients in the planned active group underwent induction of labour. Of the remaining 70, 49 went into spontaneous labour and 21 (11%) asked that they should not have labour induced. Comparison of the two groups showed no difference in the length of the first stage of labour but a trend towards an increased need for intervention for fetal distress (p less than 0.06) in the active group. There were no differences in the length of the second stage, the need for intervention, or the mode of delivery. In terms of Apgar scores the neonatal outcome was not significantly different between the two groups, but a greater proportion of the babies (15% v 8%) in the active group required intubation. Umbilical cord venous pH estimated in the last 183 consecutive deliveries in the study showed a significantly lower mean value in the active group (p less than 0.05). There was no difference in birth weight between the two groups. Two deaths occurred in the study. There was a stillbirth in the conservative group at 292 days after massive abruption, and one neonatal death in the active group owing to multiple congenital abnormalities. The outcome for mother and baby in patients from both groups who went into spontaneous labour was generally good. The outcome for patients for whom conservative management was planned but induction became necessary was no different from that of patients who underwent planned induction at term. Thus from our results we can find no evidence to support the view that women with normal prolonged pregnancy should undergo routine induction of labour at 42 weeks9 gestation.
Open-label, randomized, multi-center study comparing the sequence of high dose Aldesleukin (Proleukin® (HD IL-2) and Ipilimumab Yervoy® ) in patients with metastatic melanoma (proclivity 02)
Authors: Sapna Patel, Mohammed Milhem, Sigrun Hallmeyer, Gregory Daniels, Lee Cranmer, Bret Taback, Lawrence Flaherty, Sandra Aung, James Lowder, William Sharfman
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts To investigate whether the sequence of HD IL-2 and a checkpoint inhibitor, Ipilimumab, will have additive or synergistic efficacy or toxicity when used in rapid sequence. Adult patients with Stage IV or unresectable Stage III metastatic melanoma who are eligible to receive HD IL-
The hands of karate experts. Clinical and radiological findings.
Authors: A C Crosby
Journal: British Journal of Sports Medicine (1985)

The hands and wrists of 22 karate instructors who had practiced the sport for a minimum of five years were reviewed. Radiological evidence of a total of ten fractures was found. There was no evidence that practice of the sport predisposed to the early onset of chronic tenosynovitis or osteoarthritis.
The Key Role of Segmented Filamentous Bacteria in the Coordinated Maturation of Gut Helper T Cell Responses
Authors: Valérie Gaboriau-Routhiau, Sabine Rakotobe, Emelyne Lécuyer, Imke Mulder, Annaïg Lan, Chantal Bridonneau, Violaine Rochet, Annamaria Pisi, Marianne De Paepe, Giovanni Brandi, Gérard Eberl, Johannes Snel, Denise Kelly, Nadine Cerf-Bensussan
Journal: Immunity (2009)
Use of serum leptin levels for determination of nutritional status and the effects of different enteral nutrients on intestinal mucosa after minor surgery: An experimental study
Authors: Mehmet Gurdal Oztekin, Serap Erel, Kemal Kismet, Bulent Kilicoglu, Cem Gencay, Hesna Müzeyyen Astarci, Mehmet Ali Akkus
Journal: International Journal of Surgery (2007)
Risk of Progression to Type 2 Diabetes Based on Relationship Between Postload Plasma Glucose and Fasting Plasma Glucose
Authors: Muhammad A. Abdul-Ghani, Ken Williams, Ralph DeFronzo, Michael Stern
Journal: Diabetes Care (2006)

OBJECTIVE—We sought to assess the risk of progression to type 2 diabetes in normal glucose tolerance (NGT) subjects based on the relationship between the plasma glucose concentration during oral glucose tolerance tests (OGTTs) and the fasting plasma glucose (FPG) concentration. RESEARCH DESIGN AND METHODS—Subjects with NGT (n = 1,282) from the San Antonio Heart Study received an OGTT with measurement of the plasma glucose concentration at 0, 30, 60, and 120 min at baseline and after 7–8 years of follow-up. Subjects were divided into four groups based on the relationship between the plasma glucose concentration during the OGTT and the FPG concentration on the same day as the OGTT. Insulin resistance was calculated by the homeostasis model assessment of insulin resistance (HOMA-IR) and Matsuda index. Early-phase insulin secretion was calculated as the ratio between the incremental plasma insulin and glucose concentrations during the first 30 min of the OGTT (ΔI0–30/ΔG0–30). Total insulin secretion was calculated as the ratio between the incremental areas under the insulin and glucose curves during the OGTT [ΔG(AUC)/ΔI(AUC)]. RESULTS—In 23 subjects (group I), the plasma glucose concentration during the OGTT returned to levels below the FPG concentration at 30 min; in 111 subjects (group II) and in 313 subjects (group III), the plasma glucose concentration during the OGTT returned to levels below the FPG concentration at 60 and 120 min, respectively. In the remaining 835 subjects (group IV), the plasma glucose concentration during the OGTT never fell below the FPG concentration. Insulin resistance, measured by HOMA-IR and the Matsuda index, increased progressively from group I through group IV, while insulin secretion measured by ΔI0–30/ΔG0–30 and ΔG(AUC)/ΔI(AUC) decreased progressively from group I through group IV. The incidence of type 2 diabetes was 0% in group I and progressively increased to 0.9% in group II, 3.2% in group III, and 6.4% in group IV. CONCLUSIONS—Subjects whose postload plasma glucose concentration returned to baseline (i.e., FPG level) more quickly had greater insulin sensitivity, a higher insulinogenic index, and a lower risk of developing type 2 diabetes after 8 years of follow-up compared with subjects whose postload glucose concentration returned to baseline more slowly.