tbuckley/cabot-search huggingface dataset:
Abnormal Cardiac and Skeletal Muscle Energy Metabolism in Patients With Type 2 Diabetes
Authors: Michaela Scheuermann-Freestone, Per L. Madsen, David Manners, Andrew M. Blamire, Robin E. Buckingham, Peter Styles, George K. Radda, Stefan Neubauer, Kieran Clarke
Journal: Circulation (2003)

Background— It is well known that patients with type 2 diabetes have increased risk of cardiovascular disease, but it is not known whether they have underlying abnormalities in cardiac or skeletal muscle high-energy phosphate metabolism. Methods and Results— We studied 21 patients with type 2 diabetes with no evidence of coronary artery disease or impaired cardiac function, as determined by echocardiography, and 15 age-, sex-, and body mass index-matched control subjects. Cardiac high-energy phosphate metabolites were measured at rest using 31 P nuclear magnetic resonance spectroscopy (MRS). Skeletal muscle high-energy phosphate metabolites, intracellular pH, and oxygenation were measured using 31 P MRS and near infrared spectrophotometry, respectively, before, during, and after exercise. Although their cardiac morphology, mass, and function appeared to be normal, the patients with diabetes had significantly lower phosphocreatine (PCr)/ATP ratios, at 1.50±0.11, than the healthy volunteers, at 2.30±0.12. The cardiac PCr/ATP ratios correlated negatively with the fasting plasma free fatty acid concentrations. Although skeletal muscle energetics and pH were normal at rest, PCr loss and pH decrease were significantly faster during exercise in the patients with diabetes, who had lower exercise tolerance. After exercise, PCr recovery was slower in the patients with diabetes and correlated with tissue reoxygenation times. The exercise times correlated negatively with the deoxygenation rates and the hemoglobin (Hb)A 1c levels and the reoxygenation times correlated positively with the HbA 1c levels. Conclusions— Type 2 diabetic patients with apparently normal cardiac function have impaired myocardial and skeletal muscle energy metabolism related to changes in circulating metabolic substrates.
Tethered capsule endomicroscopy enables less invasive imaging of gastrointestinal tract microstructure
Authors: Michalina J Gora, Jenny S Sauk, Robert W Carruth, Kevin A Gallagher, Melissa J Suter, Norman S Nishioka, Lauren E Kava, Mireille Rosenberg, Brett E Bouma, Guillermo J Tearney
Journal: Nature Medicine (2013)
Exercise Thallium Tomography Predicts Future Clinically Manifest Coronary Heart Disease in a High-Risk Asymptomatic Population
Authors: Roger S. Blumenthal, Diane M. Becker, Taryn F. Moy, Josef Coresh, Lora B. Wilder, Lewis C. Becker
Journal: Circulation (1996)

Exercise testing, even when combined with radionuclide perfusion imaging, does not accurately predict future clinical coronary heart disease (CHD) in low-risk asymptomatic populations. We hypothesized that these tests would perform better in a higher-risk population with a high prevalence of occult CHD. Siblings of persons with premature CHD represent such a group in whom it would be advantageous to identify affected individuals before the occurrence of clinically manifest CHD.Exercise thallium scintigraphy was performed in 264 asymptomatic individuals less than 60 years of age who had a sibling with documented CHD before age 60. Despite an average age of only 46 years at the time of screening, 19 of 264 siblings developed clinical CHD (sudden death in 1, myocardial infarction in 10, coronary revascularization in 8) over a mean of 6.2 years (range, 1 to 9 years) of follow-up. Abnormal thallium scans were observed in 29% of men and 9% of women, while abnormal exercise ECGs occurred in 12% and 5% respectively. Of men >/= 45 years of age, 45% had an abnormal exercise ECG, thallium scan, or both. In contrast, only 3% of women < 45 years of age had an abnormal test result. Although abnormal exercise ECGs and thallium scans were both predictive of future clinical CHD, the thallium scan was associated with a higher relative risk. After adjustment for age, sex, and exercise ECG results, the relative risk of developing clinical CHD was 4.7 for an abnormal scan. Siblings with a concordant abnormal exercise ECG and thallium scan had a relative risk of 14.5. These siblings were all men > 45 years of age at the time of screening and had a strikingly high incidence of CHD (6 of 12, 50%).Exercise thallium scintigraphy appears to be useful in the risk assessment of asymptomatic siblings of patients with premature CHD, particularly in male siblings who are 45 years of age or older.
Frequency of Allogeneic Hematopoietic Cell Transplantation Among Patients With High- or Intermediate-Risk Acute Myeloid Leukemia in First Complete Remission
Authors: Raya Mawad, Ted A. Gooley, Vicky Sandhu, Jack Lionberger, Bart Scott, Brenda M. Sandmaier, Paul O'Donnell, Pamela S. Becker, Stephen Petersdorf, Kathleen Shannon Dorcy, Paul Hendrie, Mohamed L. Sorror, Roland B. Walter, H. Joachim Deeg, Frederick R. Appelbaum, Elihu H. Estey, John M. Pagel
Journal: Journal of Clinical Oncology (2013)

To determine the frequency of allogeneic hematopoietic cell transplantation (HCT) for patients with acute myeloid leukemia (AML) in first complete remission (CR1).Between January 1, 2008, and March 1, 2011, 212 newly diagnosed patients with AML received treatment at our center. Ninety-five patients age less than 75 years with intermediate- or high-risk AML achieved a complete remission, and 21 patients achieved a morphologic remission with incomplete blood count recovery.Seventy-eight (67%; 95% CI, 58% to 76%) of 116 patients received HCT at a median of 2.8 months (range, 0.5 to 19 months) from their CR1 date. The median age was 57 years in both the HCT patient group (range, 18 to 75 years) and the non-HCT patient group (range, 24 to 70 years; P = .514). Between the HCT patients and the non-HCT patients, the mean Eastern Cooperative Oncology Group performance status was 1.1 compared with 1.5, respectively (P = .005), and the average HCT comorbidity score within 60 days of CR1 was 1.7 and 2.1, respectively (P = .68). Twenty-nine (76%) of 38 non-HCT patients were HLA typed, and matched donors were found for 13 of these 29 patients (34% of all non-HCT patients). The most common causes for patients not receiving transplantation in CR1 were early relapse (within 6 months) in 12 patients (32%), poor performance status in eight patients (21%), and physician decision in five patients (13%).HCT can be performed in CR1 in the majority of patients with AML for whom it is currently recommended. The main barriers to HCT were early relapse and poor performance status, highlighting the need for improved therapies for patients with AML of all ages.
NOTES OX A CASE OF COLLOID DEGENERATION OF THE SKIN (COLLOID MILIUM)
Authors: J. M. H. MACLEOD, J. E. M. WIGLEY, I. MUENDE
Journal: British Journal of Dermatology (1932)

Journal Article NOTES OX A CASE OF COLLOID DEGENERATION OF THE SKIN (COLLOID MILIUM) Get access J. M. H. MACLEOD, J. M. H. MACLEOD Pathological Laboratory, St. John's Hospital Search for other works by this author on: Oxford Academic Google Scholar J. E. M. WIGLEY, J. E. M. WIGLEY Pathological Laboratory, St. John's Hospital Search for other works by this author on: Oxford Academic Google Scholar I. MUENDE I. MUENDE Pathological Laboratory, St. John's Hospital Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 44, Issue 5, 1 May 1932, Pages 257–259, https://doi.org/10.1111/j.1365-2133.1932.tb09601.x Published: 01 May 1932
Glucagon-Like Peptide 1 Receptor Agonist or Bolus Insulin With Optimized Basal Insulin in Type 2 Diabetes
Authors: Michaela Diamant, Michael A. Nauck, Rimma Shaginian, James K. Malone, Simon Cleall, Matthew Reaney, Danielle de Vries, Byron J. Hoogwerf, Leigh MacConell, Bruce H.R. Wolffenbuttel
Journal: Diabetes Care (2014)

OBJECTIVE Mealtime insulin is commonly added to manage hyperglycemia in type 2 diabetes when basal insulin is insufficient. However, this complex regimen is associated with weight gain and hypoglycemia. This study compared the efficacy and safety of exenatide twice daily or mealtime insulin lispro in patients inadequately controlled by insulin glargine and metformin despite up-titration. RESEARCH DESIGN AND METHODS In this 30-week, open-label, multicenter, randomized, noninferiority trial with 12 weeks prior insulin optimization, 627 patients with insufficient postoptimization glycated hemoglobin A1c (HbA1c) were randomized to exenatide (10–20 µg/day) or thrice-daily mealtime lispro titrated to premeal glucose of 5.6–6.0 mmol/L, both added to insulin glargine (mean 61 units/day at randomization) and metformin (mean 2,000 mg/day). RESULTS Randomization HbA1c and fasting glucose (FG) were 8.3% (67 mmol/mol) and 7.1 mmol/L for exenatide and 8.2% (66 mmol/mol) and 7.1 mmol/L for lispro. At 30 weeks postrandomization, mean HbA1c changes were noninferior for exenatide compared with lispro (–1.13 and –1.10%, respectively); treatment differences were –0.04 (95% CI –0.18, 0.11) in per-protocol (n = 510) and –0.03 (95% CI –0.16, 0.11) in intent-to-treat (n = 627) populations. FG was lower with exenatide than lispro (6.5 vs. 7.2 mmol/L; P = 0.002). Weight decreased with exenatide and increased with lispro (−2.5 vs. +2.1 kg; P &amp;lt; 0.001). More patients reported treatment satisfaction and better quality of life with exenatide than lispro, although a larger proportion of patients with exenatide experienced treatment-emergent adverse events. Exenatide resulted in fewer nonnocturnal hypoglycemic episodes but more gastrointestinal adverse events than lispro. CONCLUSIONS Adding exenatide to titrated glargine with metformin resulted in similar glycemic control as adding lispro and was well tolerated. These findings support exenatide as a noninsulin addition for patients failing basal insulin.
Uncomfortable Arithmetic — Whom to Cover versus What to Cover
Authors: Katherine Baicker, Amitabh Chandra
Journal: New England Journal of Medicine (2009)

Much of the current debate about expanding health insurance coverage avoids addressing an uncomfortable trade-off: with a limited budget, making benefits more generous means being able to cover fewer people. Moreover, designing insurance benefits that are limited to coverage of higher-value care but are extended to more people will generate greater improvements in health than providing unlimited care for fewer people. Policymakers and patient advocates are reluctant to acknowledge that in a world of scarce resources it will not be enough to eliminate waste: we will have to make active choices in our public insurance programs between increasing the number . . .
DEAD-box helicase DP103 defines metastatic potential of human breast cancers
Authors: Eun Myoung Shin, Hui Sin Hay, Moon Hee Lee, Jen Nee Goh, Tuan Zea Tan, Yin Ping Sen, See Wee Lim, Einas M. Yousef, Hooi Tin Ong, Aye Aye Thike, Xiangjun Kong, Zhengsheng Wu, Earnest Mendoz, Wei Sun, Manuel Salto-Tellez, Chwee Teck Lim, Peter E. Lobie, Yoon Pin Lim, Celestial T. Yap, Qi Zeng, Gautam Sethi, Martin B. Lee, Patrick Tan, Boon Cher Goh, Lance D. Miller, Jean Paul Thiery, Tao Zhu, Louis Gaboury, Puay Hoon Tan, Kam Man Hui, George Wai-Cheong Yip, Shigeki Miyamoto, Alan Prem Kumar, Vinay Tergaonkar
Journal: Journal of Clinical Investigation (2014)

Despite advancement in breast cancer treatment, 30% of patients with early breast cancers experience relapse with distant metastasis. It is a challenge to identify patients at risk for relapse; therefore, the identification of markers and therapeutic targets for metastatic breast cancers is imperative. Here, we identified DP103 as a biomarker and metastasis-driving oncogene in human breast cancers and determined that DP103 elevates matrix metallopeptidase 9 (MMP9) levels, which are associated with metastasis and invasion through activation of NF-κB. In turn, NF-κB signaling positively activated DP103 expression. Furthermore, DP103 enhanced TGF-β–activated kinase-1 (TAK1) phosphorylation of NF-κB–activating IκB kinase 2 (IKK2), leading to increased NF-κB activity. Reduction of DP103 expression in invasive breast cancer cells reduced phosphorylation of IKK2, abrogated NF-κB–mediated MMP9 expression, and impeded metastasis in a murine xenograft model. In breast cancer patient tissues, elevated levels of DP103 correlated with enhanced MMP9, reduced overall survival, and reduced survival after relapse. Together, these data indicate that a positive DP103/NF-κB feedback loop promotes constitutive NF-κB activation in invasive breast cancers and activation of this pathway is linked to cancer progression and the acquisition of chemotherapy resistance. Furthermore, our results suggest that DP103 has potential as a therapeutic target for breast cancer treatment.
Bacterial aerosols during colonoscopy: something to be worried about?
Authors: P. van den Broek
Journal: Endoscopy (2010)

The surgeon Joseph Lister (1827 – 1912) was the first to see the role of "minute particles suspended in [the air] which are the germs of various low forms of life," in the origin of wound infections that were frequently seen in compound fractures but not in simple fractures [1]. Pasteur had shown that exposure of a boiled fermentable fluid to air did not cause fermentation as long as no particles from the air could settle in the substances. These famous experiments with the swan-neck flasks brought an end to a long debate about spontaneous generation and showed that particles in the air and not miasmas were responsible for infection [2]. Somewhat later these minute particles or germs were named bacteria. Lister developed the carbol spray and antiseptic surgery to prevent the sedimentation of bacteria in wounds, and as a result he changed the fate of surgical patients dramatically [3] [4].
Relationship between endothelin-1 extraction in the peripheral circulation and systemic vascular resistance in patients with severe congestive heart failure
Authors: Takayoshi Tsutamoto, Atsuyuki Wada, Tomoko Hisanaga, Keiko Maeda, Masato Ohnishi, Naoko Mabuchi, Masahide Sawaki, Masaru Hayashi, Masanori Fujii, Masahiko Kinoshita
Journal: Journal of the American College of Cardiology (1999)
Diagnosing overtraining in athletes using the two-bout exercise protocol
Authors: R Meeusen, E Nederhof, L Buyse, B Roelands, G de Schutter, M F Piacentini
Journal: British Journal of Sports Medicine (2008)

In this work, whether a two-bout exercise protocol can be used to make an objective, immediately available distinction between non-functional over reaching (NFO) and overtraining syndrome (OTS) was studied.Underperforming athletes who were diagnosed with the suspicion of NFO or OTS were included in the study. Recovery of the athletes was monitored by a sports physician to retrospectively distinguish NFO from OTS.Sports medicine laboratoryThe protocol was started and completed by 10 underperforming athletes. NFO was retrospectively diagnosed in five athletes, and OTS was diagnosed in five athletes.A two-bout maximal exercise protocol was used to measure physical performance and stressinduced hormonal reactions.Exercise duration, heart rate and blood lactate concentration were measured at the end of both exercise tests. Venous concentrations cortisol, adrenocorticotrophic hormone (ACTH), prolactin and growth hormone were measured both before and after both exercise tests.Maximal blood lactate concentration was lower in OTS compared with NFO, while resting concentrations of cortisol, ACTH and prolactin concentrations were higher. However, sensitivity of these measures was low. The ACTH and prolactin reactions to the second exercise bout were much higher in NFO athletes compared with OTS and showed the highest sensitivity for making the distinction.NFO might be distinguished from OTS based on ACTH and prolactin reactions to a two-bout exercise protocol. This protocol could be a useful tool for diagnosing NFO and OTS; however, more data should be collected before this test can be used as the gold standard.
Treatment of Recent-Onset Type 1 Diabetic Patients With DiaPep277: Results of a Double-Blind, Placebo-Controlled, Randomized Phase 3 Trial. Diabetes Care 2014;37:1392–1400. DOI: 10.2337/dc13-1391
Authors: Itamar Raz, Anette G. Ziegler, Thomas Linn, Guntram Schernthaner, Francois Bonnici, Larry A. Distiller, Carla Giordano, Francesco Giorgino, Liat de Vries, Didac Mauricio, Vlastimil Procházka, Julio Wainstein, Dana Elias, Ann Avron, Merana Tamir, Rachel Eren, Dana Peled, Shlomo Dagan, Irun R. Cohen, Paolo Pozzilli
Journal: Diabetes Care (2014)

On behalf of the authors identified below, the corresponding author has formally requested to retract the above-cited article. An accompanying article (1) has also been retracted.

The article reports on the DIA-AID 1 trial, which examined the safety and efficacy of DiaPep277 to treat type 1 diabetes. The DIA-AID 1 trial, as noted in the Duality of Interest section, was funded by Andromeda Biotech, Ltd.

On 8 September 2014, Hyperion Therapeutics, Inc., which acquired Andromeda Biotech in June 2014, announced that it had chosen to terminate the DiaPep277 program. As stated in the press release …
Evolutionary Relationships of Conserved Cysteine-Rich Motifs in Adhesive Molecules of Malaria Parasites
Authors: Pascal Michon, Jamie R. Stevens, Osamu Kaneko, John H. Adams
Journal: Molecular Biology and Evolution (2002)

Malaria parasites invade erythrocytes in a process mediated by a series of molecular interactions. Invasion of human erythrocytes by Plasmodium vivax is dependent upon the presence of a single receptor, but P. falciparum, as well as some other species, exhibits the ability to utilize multiple alternative invasion pathways. Conserved cysteine-rich domains play important roles at critical times during this invasion process and at other stages in the life cycle of malaria parasites. Duffy-binding–like (DBL) domains, expressed as a part of the erythrocyte-binding proteins (DBL-EBP), are such essential cysteine-rich ligands that recognize specific host cell surface receptors. DBL-EBP, which are products of the erythrocyte-binding–like (ebl) gene family, act as critical determinants of erythrocyte specificity and are the best-defined ligands from invasive stages of malaria parasites. The ebl genes include the P. falciparum erythrocyte-binding antigen-175 (EBA-175) and P. vivax Duffy-binding protein. DBL domains also mediate cytoadherence as a part of the variant erythrocytic membrane protein-1 (PfEMP-1) antigens expressed from var genes on the surface of P. falciparum-infected erythrocytes. A paralogue of the ebl family is the malarial ligand MAEBL, which has a chimeric structure where the DBL domain is functionally replaced with a distinct cysteine-rich erythrocyte-binding domain with similarity to the apical membrane antigen-1 (AMA-1) ligand domain. The Plasmodium AMA-1 ligand domain, which encompasses the extracellular cysteine domains 1 and 2 and is well conserved in a Toxoplasma gondii AMA-1, has erythrocyte-binding activity distinct from that of MAEBL. These important families of Plasmodium molecules (DBL-EBP, PfEMP-1, MAEBL, AMA-1) are interrelated through the MAEBL. Because MAEBL and the other ebl products have the characteristics expected of homologous ligands involved in equivalent alternative invasion pathways to each other, we sought to better understand their roles during invasion by determining their relative origins in the Plasmodium genome. An analysis of their multiple cysteine-rich domains permitted a unique insight into the evolutionary development of Plasmodium. Our data indicate that maebl,ama-1, and ebl genes have ancient origins which predate Plasmodium speciation. The maebl evolved as a single locus, including its unique chimeric structure, in each Plasmodium species, in parallel with the ama-1 and the ebl genes families. The ancient character of maebl, along with its different expression characteristics suggests that MAEBL is unique and does not play an alternative role in invasion to ebl products such as EBA-175. The multiple P. falciparumebl paralogues that express DBL domains, which have occurred by duplication and diversification, potentially do provide multiple functionally equivalent ligands to EBA-175 for alternative invasion pathways.
Asthma and pregnancy: do they give clues to abnormal antiviral activity?
Authors: William W Busse, James E Gern
Journal: Thorax (2011)

Patients with asthma and pregnancy were found as two groups most at risk for severe respiratory outcomes during the H1N1 epidemic in 2008.1–4 This association raises the question as to what immune dysfunctions may link these two conditions together and lead to an increased susceptibility for viral respiratory infections, and whether both patient populations may have similar defects in antiviral activity. This important and interesting clinical question is the focus of the paper by Forbes et al 5 in Thorax .

In both asthma and pregnancy, there is a loss of the normal Th1/Th2 balance.6 7 In pregnancy, the shift away from a Th1 expression and towards a Th2 dominance during gestation likely reflects an ‘immune necessity’ to prevent the mother from having a ‘graft versus host’ reaction and subsequent loss of the pregnancy.7 In asthma, the immune picture is more complex, but the possible contribution of a Th1/Th2 imbalance with the presence of allergic reactions has been the basis of the hygiene hypothesis and target of new treatments.8 In broad-based terms, allergic sensitisation represents an overexpression of Th2 cytokines, interleukin (IL)-4, IL-5 and IL-13, with the resulting production of IgE antibodies with a capacity to cause allergic inflammation following allergen activation. In asthma, and pregnancy, a shift towards Th2 dominance also means a possible reduction in Th1 cytokines, such as interferons. The consequence of diminished interferon generation could explain the increased risk for respiratory infections in both asthma and pregnancy.

A deficiency in the generation of interferon has been most extensively studied in asthma and has been proposed as a risk …
Evidence of increased flux to n-6 docosapentaenoic acid in phospholipids of pancreas from cftr−/− knockout mice
Authors: Mario Ollero, Michael Laposata, Munir M. Zaman, Paola G Blanco, Charlotte Andersson, John Zeind, Yana Urman, Geraldine Kent, Juan G. Alvarez, Steven D. Freedman
Journal: Metabolism (2006)