tbuckley/cabot-search huggingface dataset:
Periodontal disease and systemic illness: will the evidence ever be enough?
Authors: Mary P. Cullinan, Gregory J. Seymour
Journal: Periodontology 2000 (2013)

The concept of focal infection or systemic disease arising from infection of the teeth was generally accepted until the mid-20th century when it was dismissed because of lack of evidence. Subsequently, a largely silo approach was taken by the dental and medical professions. Over the past 20 years, however, a plethora of epidemiological, mechanistic and treatment studies have highlighted that this silo approach to oral and systemic diseases can no longer be sustained. While a number of systemic diseases have been linked to oral diseases, the weight of evidence from numerous studies conducted over this period, together with several systematic reviews and meta-analyses, supports an association between periodontitis and cardiovascular disease, and between periodontitis and diabetes. The association has also been supported by a number of biologically plausible mechanisms, including direct infection, systemic inflammation and molecular mimicry. Treatment studies have shown that periodontal treatment may have a small, but significant, systemic effect both on endothelial function and on glycemic control. Despite this, however, there is no direct evidence that periodontal treatment affects either cardiovascular or diabetic events. Nevertheless, over the past 20 years we have learnt that the mouth is an integral part of the body and that the medical and dental professions need to work more closely together in the provision of overall health care for all patients.
Revised Bethesda Guidelines for Hereditary Nonpolyposis Colorectal Cancer (Lynch Syndrome) and Microsatellite Instability
Authors: A. Umar, C. R. Boland, J. P. Terdiman, S. Syngal, A. d. l. Chapelle, J. Ruschoff, R. Fishel, N. M. Lindor, L. J. Burgart, R. Hamelin, S. R. Hamilton, R. A. Hiatt, J. Jass, A. Lindblom, H. T. Lynch, P. Peltomaki, S. D. Ramsey, M. A. Rodriguez-Bigas, H. F. A. Vasen, E. T. Hawk, J. C. Barrett, A. N. Freedman, S. Srivastava
Journal: JNCI Journal of the National Cancer Institute (2004)

Hereditary nonpolyposis colorectal cancer (HNPCC), also known as Lynch syndrome, is a common autosomal dominant syndrome characterized by early age at onset, neoplastic lesions, and microsatellite instability (MSI). Because cancers with MSI account for approximately 15% of all colorectal cancers and because of the need for a better understanding of the clinical and histologic manifestations of HNPCC, the National Cancer Institute hosted an international workshop on HNPCC in 1996, which led to the development of the Bethesda Guidelines for the identification of individuals with HNPCC who should be tested for MSI. To consider revision and improvement of the Bethesda Guidelines, another HNPCC workshop was held at the National Cancer Institute in Bethesda, MD, in 2002. In this commentary, we summarize the Workshop presentations on HNPCC and MSI testing; present the issues relating to the performance, sensitivity, and specificity of the Bethesda Guidelines; outline the revised Bethesda Guidelines for identifying individuals at risk for HNPCC; and recommend criteria for MSI testing.
Proposal of a linear definition of the Bath Ankylosing Spondylitis Metrology Index (BASMI) and comparison with the 2-step and 10-step definitions
Authors: D van der Heijde, R Landewé, E Feldtkeller
Journal: Annals of the Rheumatic Diseases (2007)

Background: The Bath Ankylosing Spondylitis Metrology Index (BASMI) characterises the spinal mobility of patients with ankylosing spondylitis. Two versions have been published using categorical scores with either scores 0–2 for each of the five assessments, or scores 0–10. For metric purposes, we recently defined a BASMI version with linear score definitions. Aim: to evaluate agreement between three BASMI definitions and to test sensitivity to change. Patients and methods: The performance of the BASMI 2 (based on the 2-step definition), BASMI 10 (based on the 10-step definition), and BASMI lin (based on the linear definition), are compared in 598 status assessments and 222 follow-up assessments with a 24-week interval after an intervention with either placebo or a tumour necrosis factor (TNF) blocker from various cohorts of patients with ankylosing spondylitis (AS). Descriptive statistics and Bland–Altman plots were applied to compare the pairwise agreement of the three definitions. To assess sensitivity to change, Guyatt effect size using change data from the placebo and actively treated patients were used. Results: Bland–Altman analysis showed that the differences between BASMI 2 scores and scores obtained by either of the two other definitions were highly dependent on the magnitude of the measurement. Guyatt effect sizes were 0.66 for the BASMI 2 , 0.95 for the BASMI 10 , and 1.04 for the BASMI lin , respectively, demonstrating best sensitivity to change for the newly-developed BASMI lin . Conclusions: The BASMI 10 and BASMI lin have clear metric advantages as compared to BASMI 2 , among which are their superior sensitivity to change and feasibility of BASMI lin in computer evaluations. The BASMI 10 and BASMI 2 are not interchangeable.
Are Cancer-Related Decision Aids Effective? A Systematic Review and Meta-Analysis
Authors: Mary Ann O'Brien, Timothy J. Whelan, Miguel Villasis-Keever, Amiram Gafni, Cathy Charles, Robin Roberts, Susan Schiff, Wenjie Cai
Journal: Journal of Clinical Oncology (2009)

Decision aids (DAs) have been developed to improve communication between health professionals and patients, and to involve patients in decisions about their health care. Cancer-related decisions can be difficult due to problems in communicating complex information about prognosis and the modest benefits of available treatments. We conducted a systematic review of cancer-related DAs.Randomized controlled trials (RCTs) of cancer-related DAs about screening, prevention, and treatment decision making were included. We completed a comprehensive literature search and conducted both qualitative and quantitative analyses. We also conducted a meta regression to explore heterogeneity of effect estimates.We identified 34 RCTs of DAs in a screening (n = 22 trials) or preventive/treatment (n = 12 trials) context. DAs significantly improved knowledge about screening options when compared to usual practice (weighted average effect size, 0.50; 95% CI, 0.27 to 0.73; P < .0001). A similar effect on knowledge was also found for preventive/treatment options (weighted average effect size, 0.50; 95% CI, 0.31 to 0.70; P < .0001). Overall, general anxiety was not increased in most trials and was significantly reduced in a screening context. Decisional conflict was reduced overall but not when screening and preventive/treatment studies were analyzed separately. There were few differences between different types of DAs.Cancer-related DAs are effective in increasing patient knowledge compared with usual practice without increasing anxiety particularly in the area of cancer screening. Further research is needed to determine the effectiveness of DAs in the prevention and treatment context.
Suppression of Signal Transducer and Activator of Transcription 3 Activation by Butein Inhibits Growth of Human Hepatocellular Carcinoma <i>In Vivo</i>
Authors: Peramaiyan Rajendran, Tina H. Ong, Luxi Chen, Feng Li, Muthu K. Shanmugam, Shireen Vali, Taher Abbasi, Shweta Kapoor, Ashish Sharma, Alan Prem Kumar, Kam M. Hui, Gautam Sethi
Journal: Clinical Cancer Research (2010)

Abstract Purpose: Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide and the third cause of global cancer mortality. Increasing evidence suggest that STAT3 is a critical mediator of oncogenic signaling in HCC and controls the expression of several genes involved in proliferation, survival, metastasis, and angiogenesis. Thus, the novel agents that can suppress STAT3 activation have potential for both prevention and treatment of HCC. Experimental Design: The effect of butein on STAT3 activation, associated protein kinases, STAT3-regulated gene products, cellular proliferation, and apoptosis was investigated. The in vivo effect of butein on the growth of human HCC xenograft tumors in male athymic nu/nu mice was also examined. Results: We tested an agent, butein, for its ability to suppress STAT3 activation in HCC cells and nude mice model along with prospectively testing the hypothesis of STAT3 inhibition in a virtual predictive functional proteomics tumor pathway technology platform. We found that butein inhibited both constitutive and inducible STAT3 activation in HCC cells. The suppression was mediated through the inhibition of activation of upstream kinases c-Src and Janus-activated kinase 2. Butein inhibited proliferation and significantly potentiated the apoptotic effects of paclitaxel and doxorubicin in HCC cells. When administered intraperitoneally, butein inhibited the growth of human HCC xenograft tumors in male athymic nu/nu mice. Conclusions: Overall, cumulative results from experimental and predictive studies suggest that butein exerts its antiproliferative and proapoptotic effects through suppression of STAT3 signaling in HCC both in vitro and in vivo. Clin Cancer Res; 17(6); 1425–39. ©2010 AACR.
Use of surveillance for hepatocellular carcinoma among patients with cirrhosis in the United States
Authors: Jessica A. Davila, Robert O. Morgan, Peter A. Richardson, Xianglin L. Du, Katherine A. McGlynn, Hashem B. El-Serag
Journal: Hepatology (2010)

Surveillance for hepatocellular carcinoma (HCC) in patients with cirrhosis is recommended but may not be performed. The extent and determinants of HCC surveillance are unknown. We conducted a population-based United States cohort study of patients over 65 years of age to examine use and determinants of prediagnosis surveillance in patients with HCC who were previously diagnosed with cirrhosis. Patients diagnosed with HCC during 1994-2002 were identified from the linked Surveillance, Epidemiology, and End-Results registry–Medicare databases. We identified alpha-fetoprotein (AFP) and ultrasound tests performed for HCC surveillance, and examined factors associated with surveillance. We identified 1,873 HCC patients with a prior diagnosis of cirrhosis. In the 3 years before HCC, 17% received regular surveillance and 38% received inconsistent surveillance. In a subset of 541 patients in whom cirrhosis was recorded for 3 or more years prior to HCC, only 29% received routine surveillance and 33% received inconsistent surveillance. Among all patients who received regular surveillance, approximately 52% received both AFP and ultrasound, 46% received AFP only, and 2% received ultrasound only. Patients receiving regular surveillance were more likely to have lived in urban areas and had higher incomes than those who did not receive surveillance. Before diagnosis, approximately 48% of patients were seen by a gastroenterologist/hepatologist or by a physician with an academic affiliation; they were approximately 4.5-fold and 2.8-fold, respectively, more likely to receive regular surveillance than those seen by a primary care physician only. Geographic variation in surveillance was observed and explained by patient and physician factors. Conclusion: Less than 20% of patients with cirrhosis who developed HCC received regular surveillance. Gastroenterologists/hepatologists or physicians with an academic affiliation are more likely to perform surveillance. Hepatology 2010
New Guidelines Encourage Primary Care for Patients With Early HIV Infection
Authors: Charles Marwick
Journal: JAMA (1994)

ALTHOUGH there is no cure for AIDS, if people who test positive for antibodies to the human immunodeficiency virus (HIV) are identified early and appropriate treatment is begun, overt disease can be delayed, life can be prolonged, and its quality can be improved. But for this to happen, say federal AIDS experts, primary care physicians and other medical care providers must become involved in caring for patients with HIV infection. To help them do so, the Agency for Health Care Policy and Research (AHCPR) issued its newest clinical practice guideline,<i>Evaluation and Management of Early HIV Infection</i>. The guideline gives primary care providers the information they need to offer early, appropriate care to HIV-positive patients. See also p 492. Because of the evolving nature of knowledge about HIV infection and AIDS, each recommendation in the guideline is rated and labeled according to the degree to which it is based on
Estrogen Regulation and Physiopathologic Significance of Alternative Promoters in Breast Cancer
Authors: Martin Dutertre, Lise Gratadou, Etienne Dardenne, Sophie Germann, Samaan Samaan, Rosette Lidereau, Keltouma Driouch, Pierre de la Grange, Didier Auboeuf
Journal: Cancer Research (2010)

Alternative promoters (AP) occur in >30% protein-coding genes and contribute to proteome diversity. However, large-scale analyses of AP regulation are lacking, and little is known about their potential physiopathologic significance. To better understand the transcriptomic effect of estrogens, which play a major role in breast cancer, we analyzed gene and AP regulation by estradiol in MCF7 cells using pan-genomic exon arrays. We thereby identified novel estrogen-regulated genes (ERG) and determined the regulation of AP-encoded transcripts in 150 regulated genes. In <30% cases, APs were regulated in a similar manner by estradiol, whereas in >70% cases, they were regulated differentially. The patterns of AP regulation correlated with the patterns of estrogen receptor alpha (ERalpha) and CCCTC-binding factor (CTCF) binding sites at regulated gene loci. Interestingly, among genes with differentially regulated (DR) APs, we identified cases where estradiol regulated APs in an opposite manner, sometimes without affecting global gene expression levels. This promoter switch was mediated by the DDX5/DDX17 family of ERalpha coregulators. Finally, genes with DR promoters were preferentially involved in specific processes (e.g., cell structure and motility, and cell cycle). We show, in particular, that isoforms encoded by the NET1 gene APs, which are inversely regulated by estradiol, play distinct roles in cell adhesion and cell cycle regulation and that their expression is differentially associated with prognosis in ER(+) breast cancer. Altogether, this study identifies the patterns of AP regulation in ERGs and shows the contribution of AP-encoded isoforms to the estradiol-regulated transcriptome as well as their physiopathologic significance in breast cancer.
Oral steroids enhance epithelial repair in nasal polyposis via upregulation of the AP-1 gene network
Authors: C W Li, W Cheung, Z B Lin, T Y Li, J T Lim, D Y Wang
Journal: Thorax (2009)

<h3>ABSTRACT</h3> Hepatic <i>de novo</i> lipogenesis is influenced by the branched-chain α-keto acid dehydrogenase (BCKDH) kinase (BCKDK). We aimed to determine whether circulating levels of the immediate substrates of BCKDH, the branched-chain α-ketoacids (BCKAs) and hepatic <i>BCKDK</i> expression are associated with the presence and severity of non-alcoholic fatty liver disease (NAFLD).Eighty metabolites (3 BCKA, 14 amino acids, 43 acylcarnitines, 20 ceramides) were quantified in plasma from 288 bariatric surgery patients with severe obesity (BMI &gt; 35 kg/m<sup>2</sup>) with scored liver biopsy samples. Metabolite principal component analysis (PCA) factors, BCKA, branched-chain amino acids (BCAA), and the BCKA:BCAA ratio were tested for associations with steatosis grade and presence of non-alcoholic steatohepatitis (NASH). Of all analytes tested, only the valine-derived BCKA, α-ketoisovalerate, and the BCKA:BCAA ratio were associated with both steatosis grade and NASH. Gene expression analysis in liver samples from two independent bariatric surgery cohorts showed that hepatic <i>BCKDK</i> mRNA expression correlates with steatosis, ballooning, and levels of the lipogenic transcription factor <i>SREBP1</i>. Experiments in AML12 hepatocytes showed that SREBP1 inhibition lowers <i>BCKDK</i> mRNA expression. These findings demonstrate that higher plasma levels of BCKA and hepatic expression of <i>BCKDK</i> are features of human NAFLD/NASH and identify SREBP1 as a transcriptional regulator of <i>BCKDK</i>.
X-linked Alport Syndrome
Authors: JEAN PHILIPPE JAIS, BERTRAND KNEBELMANN, IANNIS GIATRAS, MARIO DE MARCHI, GIANFRANCO RIZZONI, ALESSANDRA RENIERI, MANFRED WEBER, OLIVER GROSS, KAI-OLAF NETZER, FRANCES FLINTER, YVES PIRSON, CHRISTINE VERELLEN, JÖRGEN WIESLANDER, ULF PERSSON, KARL TRYGGVASON, PAULA MARTIN, JENS MICHAEL HERTZ, CORNELIS SCHRÖDER, MAREK SANAK, SARKA KREJCOVA, MARIA FERNANDA CARVALHO, JUAN SAUS, CORINNE ANTIGNAC, HUBERT SMEETS, MARIE CLAIRE GUBLER
Journal: Journal of the American Society of Nephrology (2000)

Abstract. Alport syndrome (AS) is a type IV collagen hereditary disease characterized by the association of progressive hematuric nephritis, hearing loss, and, frequently, ocular changes. Mutations in the COL4A5 collagen gene are responsible for the more common X-linked dominant form of the disease. Considerable allelic heterogeneity has been observed. A “European Community Alport Syndrome Concerted Action” has been established to delineate accurately the AS phenotype and to determine genotype-phenotype correlations in a large number of families. Data concerning 329 families, 250 of them with an X-linked transmission, were collected. Characteristics of the 401 male patients belonging to the 195 families with COL4A5 mutation are presented. All male patients were hematuric, and the rate of progression to end-stage renal failure and deafness was mutation-dependent. Large deletions, nonsense mutations, or small mutations changing the reading frame conferred to affected male patients a 90% probability of developing end-stage renal failure before 30 yr of age, whereas the same risk was of 50 and 70%, respectively, in patients with missense or splice site mutation. The risk of developing hearing loss before 30 yr of age was approximately 60% in patients with missense mutations, contrary to 90% for the other types of mutations. The natural history of X-linked AS and correlations with COL4A5 mutations have been established in a large cohort of male patients. These data could be used for further evaluation of therapeutic approaches.
Major East-West Division Underlies Y Chromosome Stratification across Indonesia
Authors: T. M. Karafet, B. Hallmark, M. P. Cox, H. Sudoyo, S. Downey, J. S. Lansing, M. F. Hammer
Journal: Molecular Biology and Evolution (2010)

The early history of island Southeast Asia is often characterized as the story of two major population dispersals: the initial Paleolithic colonization of Sahul approximately 45 ka ago and the much later Neolithic expansion of Austronesian-speaking farmers approximately 4 ka ago. Here, in the largest survey of Indonesian Y chromosomes to date, we present evidence for multiple genetic strata that likely arose through a series of distinct migratory processes. We genotype an extensive battery of Y chromosome markers, including 85 single-nucleotide polymorphisms/indels and 12 short tandem repeats, in a sample of 1,917 men from 32 communities located across Indonesia. We find that the paternal gene pool is sharply subdivided between western and eastern locations, with a boundary running between the islands of Bali and Flores. Analysis of molecular variance reveals one of the highest levels of between-group variance yet reported for human Y chromosome data (e.g., Phi(ST) = 0.47). Eastern Y chromosome haplogroups are closely related to Melanesian lineages (i.e., within the C, M, and S subclades) and likely reflect the initial wave of colonization of the region, whereas the majority of western Y chromosomes (i.e., O-M119*, O-P203, and O-M95*) are related to haplogroups that may have entered Indonesia during the Paleolithic from mainland Asia. In addition, two novel markers (P201 and P203) provide significantly enhanced phylogenetic resolution of two key haplogroups (O-M122 and O-M119) that are often associated with the Austronesian expansion. This more refined picture leads us to put forward a four-phase colonization model in which Paleolithic migrations of hunter-gatherers shape the primary structure of current Indonesian Y chromosome diversity, and Neolithic incursions make only a minor impact on the paternal gene pool, despite the large cultural impact of the Austronesian expansion.
AN ANALYSIS OF MITOSIS IN LIVER RESTORATION
Authors: Austin M. Brues, Beula B. Marble
Journal: The Journal of Experimental Medicine (1937)

1. Following partial hepatectomy in the rat, there is a latent period of 1 day during which the rapidly growing organ shows no increase in cell number. Mitosis then begins rapidly, following a brief pre-mitotic period of visible nuclear changes. 2. It can be shown that the increase in cell number during the ensuing 48 hours follows a formula of the type dN/dt = ke(-kt.), beyond this time it is retarded more than this simplified formula would predict. The average mitosis rate at 1, 2, and 3 day intervals after operation follows the same formula; from this the duration of each mitosis is calculated to be about 49 minutes. It is not necessary to assume that amitotic division plays an important part, and no such divisions have been seen by the writers. 3. The percentage of cells in mitosis in a single hypertrophying liver varies widely from hour to hour, so that a single mitosis count tells nothing about the growth rate. The fluctuations occur at different times in different livers. It appears that no great number of mitoses begin or end simultaneously. 4. Mitoses are evenly distributed throughout the liver and throughout each lobule; there is no preponderance near the bile duct cells. 5. The mean initial mitosis rate (at 24 hours after operation) is 2.13 per cent, and it diminishes from then on. This rate is very similar to that in early embryo heart and tissue cultures of mesenchyme. In individual specimens the rate can be over 8 per cent. This rapid rate occurs without signs of cell dedifferentiation.
Strategies to prevent injury in adolescent sport: a systematic review
Authors: Liz Abernethy, Chris Bleakley
Journal: British Journal of Sports Medicine (2007)

This systematic review set out to identify randomised controlled trials and controlled intervention studies that evaluated the effectiveness of preventive strategies in adolescent sport and to draw conclusions on the strength of the evidence. A literature search in seven databases (Medline, SportDiscus, EMBASE, CINAHL, PEDro, Cochrane Review and DARE) was carried out using four keywords: adolescent, sport, injury and prevention (expanded to capture any relevant literature). Assessment of 154 papers found 12 studies eligible for inclusion. It can be concluded that injury prevention strategies that focus on preseason conditioning, functional training, education, balance and sport-specific skills, which should be continued throughout the sporting season, are effective. The evidence for the effectiveness of protective equipment in injury prevention is inconclusive and requires further assessment.