tbuckley/cabot-search huggingface dataset:
Different intestinal permeability patterns in relatives and spouses of patients with Crohn’s disease: an inherited defect in mucosal defence?
Authors: J D Söderholm, G Olaison, E Lindberg, U Hannestad, A Vindels, C Tysk, G Järnerot, R Sjödahl
Journal: Gut (1999)

Background A familial defect in intestinal barrier function has been found in Crohn’s disease. Aim To investigate possible genetic and environmental influences on this barrier defect by studying intestinal permeability in both relatives and spouses of patients with Crohn’s disease. Subjects The study included 39 patients with Crohn’s disease, 34 healthy first degree relatives, and 22 spouses. Twenty nine healthy volunteers served as controls. Methods Intestinal permeability was assessed as the lactulose:mannitol ratio in five hour urinary excretion after oral load, both before (baseline) and after ingestion of acetylsalicylic acid. The permeability response represents the difference between the two tests. A ratio above the 95th percentile for controls was classified as abnormal. Results Baseline permeability was higher in patients and spouses than in controls. An abnormal baseline permeability was seen in 36% of the patients, 23% of the spouses, 18% of the relatives, and 3% of the controls. After ingestion of acetylsalicylic acid, permeability increased significantly in all groups. Relatives were similar to patients with regard to permeability after exposure to acetylsalicylic acid, whereas spouses were similar to controls. The proportions with an abnormal permeability response to acetylsalicylic acid were 32% in patients, 14% in spouses, 41% in relatives, and 3% in controls. Conclusion The findings suggest that baseline permeability is determined by environmental factors, whereas permeability provoked by acetylsalicylic acid is a function of the genetically determined state of the mucosal barrier, and support the notion that environmental and hereditary factors interact in the pathogenesis of Crohn’s disease.
Sex differences in the risk of injury in World Cup alpine skiers: a 6-year cohort study
Authors: Tone Bere, Tonje Wåle Flørenes, Lars Nordsletten, Roald Bahr
Journal: British Journal of Sports Medicine (2013)

Background In competitive alpine skiing, there is a controversy regarding the sex-related risk of injury. Objective To compare the risk of injury in female versus male World Cup (WC) alpine skiers. Methods Injuries were recorded through the International Ski Federation Injury Surveillance System for six consecutive winter seasons (2006–2012), based on retrospective interviews with athletes from 10 teams at the end of each season. All acute training and competition injuries which required medical attention were recorded. Race exposure was calculated based on the exact number of runs started in the WC for each of the interviewed athletes each season. Results Men had a higher overall rate of injury (relative risk (RR) 1.24, 95% CI 1.05 to 1.47), as well as a higher rate of time-loss injury (RR 1.23, 95% CI 1.03 to 1.48) than women in training and competitions, expressed as injuries/100 athletes/season. These sex differences were even more pronounced during WC races (RR 1.58, 95% CI 1.22 to 2.04 and RR 1.72, 95% CI 1.29 to 2.31, for overall and time-loss injuries, respectively). There was no sex difference in the risk of knee/anterior cruciate ligament (ACL) injuries. Conclusions No previous studies from competitive skiing have reported a significantly higher risk of injuries in men than women. In contrast to recreational skiing and team sports, there was no sex difference in the risk of knee/ACL injuries and prevention efforts should be directed as much towards male as female competitive skiers.
Acute and long-term outcomes of multivessel stenting in patients aged 80 years
Authors: Yoshio Kobayashi, Roxana Mehran, Makoto Hirose, George Dangas, Alexandra J. Lansky, Gregg W. Stone, Issam Moussa, Gary S. Mintz, Michael B. Collins, Edward Kreps, Jeffrey W. Moses, Martin B. Leon
Journal: Journal of the American College of Cardiology (2003)
High-resolution transcription atlas of the mitotic cell cycle in budding yeast
Authors: Marina V Granovskaia, Lars J Jensen, Matthew E Ritchie, Joern Toedling, Ye Ning, Peer Bork, Wolfgang Huber, Lars M Steinmetz
Journal: Genome biology (2010)

Extensive transcription of non-coding RNAs has been detected in eukaryotic genomes and is thought to constitute an additional layer in the regulation of gene expression. Despite this role, their transcription through the cell cycle has not been studied; genome-wide approaches have only focused on protein-coding genes. To explore the complex transcriptome architecture underlying the budding yeast cell cycle, we used 8 bp tiling arrays to generate a 5 minute-resolution, strand-specific expression atlas of the whole genome.We discovered 523 antisense transcripts, of which 80 cycle or are located opposite periodically expressed mRNAs, 135 unannotated intergenic non-coding RNAs, of which 11 cycle, and 109 cell-cycle-regulated protein-coding genes that had not previously been shown to cycle. We detected periodic expression coupling of sense and antisense transcript pairs, including antisense transcripts opposite of key cell-cycle regulators, like FAR1 and TAF2.Our dataset presents the most comprehensive resource to date on gene expression during the budding yeast cell cycle. It reveals periodic expression of both protein-coding and non-coding RNA and profiles the expression of non-annotated RNAs throughout the cell cycle for the first time. This data enables hypothesis-driven mechanistic studies concerning the functions of non-coding RNAs.
UN Meeting to Address Growing Burden of Noncommunicable Diseases
Authors: N. MacReady
Journal: JNCI Journal of the National Cancer Institute (2011)

The annual worldwide number of new cancer cases will exceed 20 million by 2030. Currently, 7.6 million people die of cancer each year, more than deaths from HIV/AIDS, malaria, and tuberculosis combined. And cancer is just one of the four major noncommunicable diseases (NCDs) identified by the World Health Organization that account for nearly all global morbidity and mortality; the others are diabetes, cardiovascular disease, and chronic lung disease. Collectively, NCDs caused 36 million, or 63%, of the 57 million deaths that occurred in 2008. Nine million of those people were younger than 60 years, and more than 90% were in developing countries. Now the United Nations is turning its attention to the growing problem of NCDs in a high-level meeting on September 19 – 20, as part of the opening of the 66th session of the General Assembly. “A high-level meeting is one in which all heads of state are invited and expected to participate; they can’t send a substitute unless that person is empowered to make a decision,” said John Seffrin, M.D., CEO of the American Cancer Society. Of all the high-level meetings held in the General Assembly’s 65-year history, the only other one to address a health-related issue was for HIV/AIDS in 2001, Seffrin noted. “This is our chance to make sure that the world and policymakers and leaders understand the gravity of the NCD burden in the 21stcentury, especially cancer.” NCDs are increasing in part because populations are aging, said Alan Alwan, M.D., assistant director general of noncommunicable diseases and mental health at the WHO. But their four common risk factors — tobacco use, sedentary living, poor diet, and unhealthy use of alcohol — also refl ect the growing trends of globalization and urbanization. “More and more people are now living in urban areas, and unfortunately, in many countries of the world, this urbanization is not planned, so there are huge numbers of people living in urban slums, with no facilities for physical activity or healthy diets. Smoking rates are high, and so you are at more risk of developing diabetes, heart disease, and cancer,” Alwan said. Poverty and NCDs are linked in a vicious cycle, he continued. “Poverty exposes people to the behavioral risk factors for NCDs, and the resulting NCDs become an important driver of the downward spiral that leads to poverty. We now have clear evidence that the disability, illness, and
Primary Tumor Response to Preoperative Chemoradiation With or Without Oxaliplatin in Locally Advanced Rectal Cancer: Pathologic Results of the STAR-01 Randomized Phase III Trial
Authors: Carlo Aschele, Luca Cionini, Sara Lonardi, Carmine Pinto, Stefano Cordio, Gerardo Rosati, Salvatore Artale, Angiolo Tagliagambe, Giovanni Ambrosini, Paola Rosetti, Andrea Bonetti, Maria Emanuela Negru, Maria Chiara Tronconi, Gabriele Luppi, Giovanni Silvano, Domenico Cristiano Corsi, Anna Maria Bochicchio, Germana Chiaulon, Maurizio Gallo, Luca Boni
Journal: Journal of Clinical Oncology (2011)

To investigate oxaliplatin combined with fluorouracil-based chemoradiotherapy as preoperative treatment for locally advanced rectal cancer.Seven hundred forty-seven patients with resectable, locally advanced (cT3-4 and/or cN1-2) adenocarcinoma of the mid-low rectum were randomly assigned to receive pelvic radiation (50.4 Gy in 28 daily fractions) and concomitant infused fluorouracil (225 mg/m(2)/d) either alone (arm A, n = 379) or combined with oxaliplatin (60 mg/m(2) weekly × 6; arm B, n = 368). Overall survival is the primary end point. A protocol-planned analysis of response to preoperative treatment is reported here.Grade 3 to 4 adverse events during preoperative treatment were more frequent with oxaliplatin plus fluorouracil and radiation than with radiation and fluorouracil alone (24% v 8% of treated patients; P < .001). In arm B, 83% of the patients treated with oxaliplatin had five or more weekly administrations. Ninety-one percent, compared with 97% in the control arm, received ≥ 45 Gy (P < .001). Ninety-six percent versus 95% of patients underwent surgery with similar rates of abdominoperineal resections (20% v 18%, arm A v arm B). The rate of pathologic complete responses was 16% in both arms (odds ratio = 0.98; 95% CI, 0.66 to 1.44; P = .904). Twenty-six percent versus 29% of patients had pathologically positive lymph nodes (arm A v arm B; P = .447), 46% versus 44% had tumor infiltration beyond the muscularis propria (P = .701), and 7% versus 4% had positive circumferential resection margins (P = .239). Intra-abdominal metastases were found at surgery in 2.9% versus 0.5% of patients (arm A v arm B; P = .014).Adding oxaliplatin to fluorouracil-based preoperative chemoradiotherapy significantly increases toxicity without affecting primary tumor response. Longer follow-up is needed to assess the impact on efficacy end points.
Targeted therapy in nuclear medicine—current status and future prospects
Authors: W.J.G. Oyen, L. Bodei, F. Giammarile, H.R. Maecke, J. Tennvall, M. Luster, B. Brans
Journal: Annals of Oncology (2007)

In recent years, a number of new developments in targeted therapies using radiolabeled compounds have emerged. New developments and insights in radioiodine treatment of thyroid cancer, treatment of lymphoma and solid tumors with radiolabeled monoclonal antibodies (mAbs), the developments in the application of radiolabeled small receptor-specific molecules such as meta-iodobenzylguanidine and peptides and the position of locoregional treatment in malignant involvement of the liver are reviewed. The introduction of recombinant human thyroid-stimulating hormone and the possibility to enhance iodine uptake with retinoids has changed the radioiodine treatment protocol of patients with thyroid cancer. Introduction of radiolabeled mAbs has provided additional treatment options in patients with malignant lymphoma, while a similar approach proves to be cumbersome in patients with solid tumors. With radiolabeled small molecules that target specific receptors on tumor cells, high radiation doses can be directed to tumors in patients with disseminated disease. Radiolabeled somatostatin derivatives for the treatment of neuroendocrine tumors are the role model for this approach. Locoregional treatment with radiopharmaceuticals of patients with hepatocellular carcinoma or metastases to the liver may be used in inoperable cases, but may also be of benefit in a neo-adjuvant or adjuvant setting. Significant developments in the application of targeted radionuclide therapy have taken place. New treatment modalities have been introduced in the clinic. The concept of combining therapeutic radiopharmaceuticals with other treatment modalities is more extensively explored.
Purified Eicosapentaenoic Acid Reduces Small Dense LDL, Remnant Lipoprotein Particles, and C-Reactive Protein in Metabolic Syndrome
Authors: Noriko Satoh, Akira Shimatsu, Kazuhiko Kotani, Naoki Sakane, Kazunori Yamada, Takayoshi Suganami, Hideshi Kuzuya, Yoshihiro Ogawa
Journal: Diabetes Care (2006)

Eicosapentaenoic acid (EPA), one representative of n-3 unsaturated fatty acids (n-3 PUFAs), is clinically used for its lipid-lowering effects (1). n-3 PUFAs were shown to exert various physiological functions such as antiplatelet actions (by antagonizing effects of arachidonic acid) and plaque stabilization (2,3). Several epidemiological studies have explored antiatherogenic and cardioprotective effects of n-3 PUFA that are abundantly contained in fish oil (4). Dyslipidemia accompanying the metabolic syndrome is often associated with elevated levels of remnant lipoprotein particles and small dense LDL (sdLDL), which are newly recognized risk factors for cardiovascular disease (CVD) (5). It was reported that fish oil improved lipoprotein subclass profiles in subjects with an atherogenic lipoprotein phenotype (6). Besides EPA, docosahexaenoic acid and cholesterol are present in fish oil (7), but it is not clear whether purified EPA independently affects lipoprotein subclass profiles. Therefore, we used purified EPA ethyl ester and examined effects of EPA on atherogenic sdLDL particles and remnant lipoprotein particles in the metabolic syndrome, a precursor of CVD. Furthermore, sdLDL has been reported to synergistically interact with inflammation in pathophysiologic processes leading to CVD (8). Therefore, we simultaneously measured effects of EPA on C-reactive protein (CRP), a marker of inflammation, and examined how alteration of lipoprotein profiles by EPA affects systemic inflammation.

A total of 44 Japanese obese type 2 diabetic patients were recruited in our clinics (Table 1). All patients satisfied the definition and diagnostic criteria of the metabolic syndrome proposed by the National Metabolic Syndrome Criteria Study Group of Japan in 2005 (9). Accordingly, an individual is diagnosed with metabolic syndrome if he or she has central adiposity plus two or more of the following three factors: 1 ) raised concentration of triglycerides …
Kyphoplasty in the Treatment of Osteolytic Vertebral Compression Fractures as a Result of Multiple Myeloma
Authors: S. Dudeney, I.H. Lieberman, M-K. Reinhardt, M. Hussein
Journal: Journal of Clinical Oncology (2002)

PURPOSE: We prospectively evaluated the safety and efficacy of kyphoplasty in the treatment of osteolytic vertebral compression fractures resulting from multiple myeloma. The principle symptoms in multiple myeloma result from bone destruction, especially the spine. Kyphoplasty is a new technique that involves the introduction of inflatable bone tamps (IBT) into the vertebral body. The purpose of the IBT is to restore the vertebral body back toward its original height, while creating a cavity that can be filled with highly viscous bone cement. PATIENTS AND METHODS: Fifty-five consecutive kyphoplasty procedures were performed in 18 patients with osteolytic vertebral compression fractures resulting from multiple myeloma. Cement leakage and any complications were recorded. Early objective analysis was made by comparing preoperative and latest Short Form 36 Health Survey scores. Height restoration was estimated by measuring vertebral height on lateral radiographs. RESULTS: The mean age of patients was 63.5 years, mean duration of symptoms was 11 months, and mean follow-up was 7.4 months. There were no major complications related directly to use of this technique. On average, 34% of height lost at the time of fracture was restored. Asymptomatic cement leakage occurred at two (4%) of 55 levels. Significant improvement in SF36 scores occurred for Bodily Pain (23.2 to 55.4, P = .0008), Physical Function (21.3 to 50.6, P = .0010), Vitality (31.3 to 47.5, P = .010), and Social Functioning (40.6 to 64.8, P = .014). CONCLUSION: Kyphoplasty was efficacious in the treatment of osteolytic vertebral compression fractures resulting from multiple myeloma. Kyphoplasty is associated with early clinical improvement of pain and function as well as some restoration of vertebral body height.
In vitro stimulation by long-acting thyroid stimulator of thyroid glucose oxidation and 32P incorporation into phospholipids
Authors: James B. Field, Adrienne Remer, Gail Bloom, Joseph P. Kriss
Journal: Journal of Clinical Investigation (1968)

Long-acting thyroid stimulator (LATS) increased glucose oxidation and (32)P incorporation into phospholipids in in vitro experiments with dog thyroid slices. The time course of the response was different from that obtained with thyroid-stimulating hormone (TSH), but was very similar to the delayed effect observed in vivo. During a 45 min incubation, TSH, but not LATS increased glucose oxidation, whereas in longer experiments up to 6 hr, both substances augmented (14)CO(2) production. Amounts of pooled human gamma globulin equivalent to LATS were inactive. Although TSH stimulated (32)P incorporation into phospholipids during a 2 hr incubation, LATS was ineffective. In longer incubations, from 4(1/2) to 8 hr, LATS did increase (32)P incorporation. The stimulatory effect of LATS was not abolished by anti-TSH antibody capable of neutralizing human TSH. Effects of LATS were also obtained with beef and pig thyroid slices. In addition to stimulation of glucose oxidation in dog thyroid slices, LATS occasionally also stimulated glucose oxidation in dog spleen and liver slices. Despite a 54-fold increase in LATS concentration, a satisfactory dose-response curve could not be demonstrated when (14)CO(2) production was measured.
Effects of an Energy-Restrictive Diet With or Without Exercise on Abdominal Fat, Intermuscular Fat, and Metabolic Risk Factors in Obese Women
Authors: Ian Janssen, Anne Fortier, Robert Hudson, Robert Ross
Journal: Diabetes Care (2002)

OBJECTIVE—The primary objective was to examine whether the combination of diet and aerobic exercise (DA) or diet and resistance exercise (DR) is associated with greater improvements in metabolic risk factors by comparison to diet only (DO) in obese women. A second objective considered whether reductions in metabolic risk factors are related to concurrent changes in abdominal and/or intermuscular fat distribution. RESEARCH DESIGN AND METHODS—A total of 38 premenopausal obese women were randomly assigned to one of three 16-week treatments: DO (n=13), DA (n=11), or DR (n=14). Plasma glucose, insulin, and lipid levels were measured in a fasting state and after a 75-g oral glucose challenge (oral glucose tolerance test [OGTT]). Total, abdominal subcutaneous, visceral, and intermuscular fat were measured by magnetic resonance imaging. RESULTS—Significant reductions (P &amp;lt; 0.02) in body weight (∼10 kg or 10%) and in total, abdominal subcutaneous, visceral, and intermuscular fat were observed within each group. Fasting and OGTT insulin, total cholesterol, LDL cholesterol, and apolipoprotein B also decreased within each group (P ≤ 0.02). The changes in the body fat and metabolic variables were not different across treatment (P &amp;gt; 0.05). Visceral fat alone was related to the metabolic risk factors both before and after the treatment. CONCLUSIONS—Weight loss was associated with reductions in metabolic risk factors in obese women. The improvement in the metabolic profile was not enhanced by the addition of aerobic or resistance exercise. The findings reinforce the importance of diminished visceral fat in the treatment of insulin resistance.
An anti-silencer– and SATB1-dependent chromatin hub regulates <i>Rag1</i> and <i>Rag2</i> gene expression during thymocyte development
Authors: Bingtao Hao, Abani Kanta Naik, Akiko Watanabe, Hirokazu Tanaka, Liang Chen, Hunter W. Richards, Motonari Kondo, Ichiro Taniuchi, Yoshinori Kohwi, Terumi Kohwi-Shigematsu, Michael S. Krangel
Journal: The Journal of Experimental Medicine (2015)

Rag1 and Rag2 gene expression in CD4+CD8+ double-positive (DP) thymocytes depends on the activity of a distant anti-silencer element (ASE) that counteracts the activity of an intergenic silencer. However, the mechanistic basis for ASE activity is unknown. Here, we show that the ASE physically interacts with the distant Rag1 and Rag2 gene promoters in DP thymocytes, bringing the two promoters together to form an active chromatin hub. Moreover, we show that the ASE functions as a classical enhancer that can potently activate these promoters in the absence of the silencer or other locus elements. In thymocytes lacking the chromatin organizer SATB1, we identified a partial defect in Tcra gene rearrangement that was associated with reduced expression of Rag1 and Rag2 at the DP stage. SATB1 binds to the ASE and Rag promoters, facilitating inclusion of Rag2 in the chromatin hub and the loading of RNA polymerase II to both the Rag1 and Rag2 promoters. Our results provide a novel framework for understanding ASE function and demonstrate a novel role for SATB1 as a regulator of Rag locus organization and gene expression in DP thymocytes.
Evaluation of a Raman probe for pathological diagnosis at colonoscopy
Authors: J. J. Wood, C. Kendall, J. Hutchings, G. Lloyd, N. Stone, N. Shepherd, J. Day, T. Cook
Journal: Gut (2011)

<h3>Introduction</h3> Numerous techniques for improving lesion detection and classification at colonoscopy are under development. When light is scattered by a substance it may be altered in wavelength. By detection of scattered light this process can be represented as a Raman spectrum where wavelength change is plotted against intensity. Raman spectroscopy of human tissue can provide a molecular ‘fingerprint’ unique to the tissue studied and has potential to classify disease.1 An ‘in-house’ fibreoptic Raman probe has been designed which can fit down the accessory channel of a colonoscope2 (see figure 1). This study evaluated the potential to provide a pathological diagnosis at colonoscopy using Raman spectroscopy. <h3>Methods</h3> Biopsy samples were collected at colonoscopy, placed in a 2 ml Cryovial (BDH Corning Ltd.), immediately snap-frozen in liquid nitrogen and stored at −80°C. Raman spectra with 10s acquisition period were measured with the probe tip in contact with the mucosal surface of thawed specimens. The probe illuminated samples with 830 nm laser light. Scattered light was collected by the probe and returned via fibreoptic cables to a Renishaw system 100 spectrometer. Following measurement, samples were formalin fixed and subjected to routine histopathological processing and review. Preliminary mathematical modelling using principal component analysis and linear discriminant analysis was used to correlate Raman spectra with routine histopathological diagnoses. <h3>Results</h3> 350 Raman spectra were measured from a total of 310 colon biopsies (81, 72, 86 and 71 biopsies of normal colon mucosa, hyperplastic polyps (HP), adenomatous polyps and adenocarcinoma respectively). Overall spectral classification accuracy was 78.8% for normal tissue versus HP, 77.5% for normal tissue vs. adenomas, 80.7% for normal tissue versus adenocarcinoma, 85.5% for HP versus adenomas, 86.1% for HP versus adenocarcinoma, and 83.5% for adenomas versus adenocarcinoma. <h3>Conclusion</h3> Our Raman probe system can distinguish between different colorectal pathologies. It is anticipated that a more advanced analysis of this data will increase the classification accuracy to a level suitable for clinical implementation. Experiments with 1s spectral acquisition times are underway which we anticipate will show Raman probe spectroscopy to be a useful tool that can provide an instant pathological diagnosis at colonoscopy.