tbuckley/cabot-search huggingface dataset:
The Meaning of the U.S. Preventive Services Task Force Grade I Recommendation: Screening for Hepatitis C Virus Infection
Authors: Ned Calonge, Gurvaneet Randhawa
Journal: Annals of Internal Medicine (2004)

The U.S. Preventive Services Task Force (USPSTF) formulates evidence-based recommendations for clinical preventive services. These recommendations are communicated by letter grades that reflect the quality of evidence and the magnitude of net health benefit expected from delivering the preventive service. When the USPSTF finds insufficient evidence to determine the balance of health benefits or harms of delivering a preventive service, because of a lack of studies, poor-quality studies, or good-quality studies with conflicting results, the USPSTF assigns the service an I letter grade. The USPSTF found insufficient evidence to recommend for or against screening for hepatitis C virus infection in high-risk individuals (I letter grade). This recommendation reflects the need for further research that would provide adequate evidence to assess the net health benefit for persons screened for hepatitis C virus infection.
Subfamily relationships and clustering of rabbit C repeats.
Authors: Dan E. Krane, Andrew G. Clark, Jan-Feng Cheng, Ross C. Hardison
Journal: Molecular Biology and Evolution (1991)

C repeats constitute the predominant family of short interspersed repeats (SINEs) in the rabbit genome. Determination of the nucleotide sequence 5' to rabbit zeta-globin genes reveals clusters of C repeats, and analysis of these and other sequenced regions of rabbit chromosomes shows that the C repeats have a strong tendency to insert within or in close proximity to other C repeats. An alignment of 44 members of the C repeat family shows that they are composites of different sequences, including a tRNA-like sequence, a conserved central core, a stretch of repeating CT dinucleotides, and an A-rich tract. Cladograms generated by both parsimony and cluster analysis subdivide the C repeats into at least three distinct subfamilies. Nucleotides at sites diagnostic for subfamilies appear to have changed in a punctuated and progressive manner during evolution, indicating that a limited number of progenitors have given rise to new repeats in waves of dispersion. C repeats that insert into preexisting C repeats belong to subfamilies that are proposed to have been propagated more recently; hence, these data support the model of dispersion in successive waves. The divergence among the oldest group of C repeats is greater than that observed for the analogous Alu repeats in humans, indicating that rabbit C repeats have been propagating longer than human Alu repeats. The improved consensus sequence for these repeats is similar to that of the predominant artiodactyl SINE in both the tRNA-like region and a central region. Because members of different subfamilies cross-hybridize very poorly, hybridization data with representatives of each subfamily provide a new minimal estimate, 234,000, for the copy number of C repeats in the rabbit haploid genome, although it is likely that the actual value is closer to 1 million.
Pandemic H1N1 influenza at the 2009 Hajj: understanding the unexpectedly low H1N1 burden
Authors: Ziad A Memish, Shahul H Ebrahim, Qanta A Ahmed, Michael Deming, Abdulla Assiri
Journal: Journal of the Royal Society of Medicine (2010)

The Kingdom of Saudi Arabia (KSA) administered the 2009 Hajj, the largest annual mass gathering of people from about 160 countries, amid a declared global H1N1 pandemic. The unexpectedly low incidence of H1N1 during the Hajj is of concern.1 The official report for the 2009 Hajj refers to laboratory-confirmed, symptomatic pilgrims who sought clinical care in Hajj-related clinical facilities during the five-day period of Hajj. Because of the short duration of the Hajj rituals (5 days), the commitment of pilgrims to perform the Hajj rituals, and the mild clinical course of 2009 H1N1 pandemic influenza for most infected persons, it is possible that symptomatic pilgrims may have deferred contact with the healthcare system, unless symptoms became severe. This could explain the high case fatality observed during the Hajj despite the low disease burden. Furthermore, illnesses that developed after the strictly defined five-day Hajj rituals are not included in the statistics released on the final day of Hajj.

For the 2009 Hajj, KSA collaborated with the US Centers for Disease Control and Prevention, the World Health Organization Eastern Mediterranean Regional Office, and the US Naval Medical Research Unit #3 based in Cairo on H1N1 surveillance. The activities included clinic-based sentinel laboratory surveillance in Hajj-specific clinics and community-based laboratory surveillance activities at the Jeddah Airport Hajj Terminal during the arrival and departure of pilgrims. Given the one- to four-day incubation period of influenza viruses, the departure survey of about 3000 pilgrims (about 0.01% of an estimated 2.5–3 million pilgrims) conducted during the first five days after the end of Hajj will help assess the burden of influenza infections acquired during the preceding Hajj period. Because the laboratory tests in these surveillance activities covered tests for all influenza viruses, real-time reporting of the test results was not feasible.

Participants in any mass gathering may not all travel in the immediate period before or after the mass gathering event, or may use multiple modes of transportation that limits surveillance data capture. Extended surveillance timeframes implemented at diverse entry and exit points are required to capture indicators of disease spread or amplification. Post-event surveillance should be an integral component of mass gathering surveillance systems to understand the full extent of diseases acquired during an event. Given that 75% of the pilgrims originate from the 40 lower or low-to-middle income countries2 with limited surveillance infrastructure, post-Hajj surveillance in home countries of pilgrims remains a challenge.

Rapid one-time disease surveillance among diverse international populations is feasible during mass gatherings and can greatly enhance and ultimately assure global public health security.3
COPD: current therapeutic interventions and future approaches
Authors: P. J. Barnes, R. A. Stockley
Journal: European Respiratory Journal (2005)

Although long-acting bronchodilators have been an important advance for the management of chronic obstructive pulmonary disease (COPD), these drugs do not deal with the underlying inflammatory process. No currently available treatments reduce the progression of COPD or suppress the inflammation in small airways and lung parenchyma. Several new treatments that target the inflammatory process are now in clinical development. Some therapies, such as chemokine antagonists, are directed against the influx of inflammatory cells into the airways and lung parenchyma that occurs in COPD, whereas others target inflammatory cytokines such as tumour necrosis factor-α. Broad spectrum anti-inflammatory drugs are now in phase III development for COPD, and include phosphodiesterase-4 inhibitors. Other drugs that inhibit cell signalling include inhibitors of p38 mitogen-activated protein kinase, nuclear factor-κB and phosphoinositide-3 kinase-γ. More specific approaches are to give antioxidants, inhibitors of inducible nitric oxide synthase and leukotriene B 4 antagonists. Other treatments have the potential to combat mucus hypersecretion, and there is also a search for serine proteinase and matrix metalloproteinase inhibitors to prevent lung destruction and the development of emphysema. More research is needed to understand the cellular and molecular mechanisms of chronic obstructive pulmonary disease and to develop biomarkers and monitoring techniques to aid the development of new therapies.
Effectiveness of single dose rifampicin in preventing leprosy in close contacts of patients with newly diagnosed leprosy: cluster randomised controlled trial
Authors: F Johannes Moet, David Pahan, Linda Oskam, Jan H Richardus
Journal: BMJ (2008)

<b>Objective</b> To determine the effectiveness of chemoprophylaxis using a single dose of rifampicin to prevent leprosy in close contacts. <b>Design</b> Single centre, double blind, cluster randomised, placebo controlled trial. <b>Setting</b>Leprosy control programme in two districts of northwest Bangladesh with a population of more than four million. <b>Participants</b>28 092 close contacts of 1037 patients with newly diagnosed leprosy. 21 711 contacts fulfilled the study requirements. <b>Interventions</b> A single dose of rifampicin or placebo given to close contacts in the second month of starting the index patient's treatment, with follow-up for four years. <b>Main outcome measure</b> Development of clinical leprosy. <b>Results</b> 18 869 of the 21 711 contacts (86.9%) were followed-up at four years. Ninety one of 9452 contacts in the placebo group and 59 of 9417 in the rifampicin group had developed leprosy. The overall reduction in incidence of leprosy using a single dose of rifampicin in the first two years was 57% (95% confidence interval 33% to 72%). The groups did not differ between two and four years. The overall number needed to treat (NNT) to prevent a single case of leprosy among contacts was 297 (95% confidence interval 176 to 537). Differences were found between subgroups at two years, both in reduction of incidence and in NNT. <b>Conclusion</b>A single dose of rifampicin given to contacts of patients with newly diagnosed leprosy is effective at preventing the development of clinical leprosy at two years. The effect was maintained, but no difference was seen between the placebo and rifampicin groups beyond two years. <b>Trial registration</b> Current Controlled Trials ISRCTN61223447.
Dietary Patterns and Breast Cancer Recurrence and Survival Among Women With Early-Stage Breast Cancer
Authors: Marilyn L. Kwan, Erin Weltzien, Lawrence H. Kushi, Adrienne Castillo, Martha L. Slattery, Bette J. Caan
Journal: Journal of Clinical Oncology (2008)

Purpose To determine the association of dietary patterns with cancer recurrence and mortality of early-stage breast cancer survivors. Patients and Methods Patients included 1,901 Life After Cancer Epidemiology Study participants diagnosed with early-stage breast cancer between 1997 and 2000 and recruited primarily from the Kaiser Permanente Northern California Cancer Registry. Diet was assessed at cohort entry using a food frequency questionnaire. Two dietary patterns were identified: prudent (high intakes of fruits, vegetables, whole grains, and poultry) and Western (high intakes of red and processed meats and refined grains). Two hundred sixty-eight breast cancer recurrences and 226 all-cause deaths (128 attributable to breast cancer) were ascertained. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs. Results Increasing adherence to a prudent dietary pattern was associated with a statistically significant decreasing risk of overall death (P trend = .02; HR for highest quartile = 0.57; 95% CI, 0.36 to 0.90) and death from non–breast cancer causes (P trend = .003; HR for highest quartile = 0.35; 95% CI, 0.17 to 0.73). In contrast, increasing consumption of a Western dietary pattern was related to an increasing risk of overall death (P trend = .05) and death from non–breast cancer causes (P = .02). Neither dietary pattern was associated with risk of breast cancer recurrence or death from breast cancer. These observations were generally not modified by physical activity, being overweight, or smoking. Conclusion Women diagnosed with early-stage breast cancer might improve overall prognosis and survival by adopting more healthful dietary patterns.
Stability and Change in Personality Disorders
Authors: Leslie C. Morey, Christopher J. Hopwood
Journal: Annual Review of Clinical Psychology (2012)

Stability is thought to be one of the major distinguishing features between personality disorders (PDs) and other forms of psychopathology. The development of more reliable PD assessments and the implementation of four major longitudinal studies on PD stability have provided critical data with which to evaluate the stability of PD features. Results from these and other studies reveal significant complexity in the interpretation of PD stability because of several issues that can impact stability estimates. Such estimates will vary as a function of the type of constructs being assessed, the type of stability being considered, the modality and reliability of the assessments being used, and the impacts of sampling. In this article, longitudinal research on PD stability is reviewed in the context of these issues. It is concluded that no single answer can be given to the question, "How stable are PDs?" and that future research and classification need to consider carefully and account for the complexity of this question.
Gastric polypoid lesion after gastrectomy
Authors: H.-L. Chen, M.-J. Bair, I.-T. Lin, C.-H. Wu, Y.-J. Chen
Journal: Gut (2010)

An 87-year-old man presented for endoscopy for investigation of anorexia, abdominal bloating and fullness for the previous 2 months. He had had a subtotal gastrectomy with a Billroth II anastomosis 40 years previously for a gastric ulcer with bleeding. Upper endoscopy revealed a 20 mm diameter, broad-based polypoid lesion with a smooth surface at the greater curvature of the middle body of the stomach (figure 1). Biopsies from the surface mucosa showed mild chronic inflammation and mild foveolar hyperplasia and were negative for Helicobacter pylori infection. Abdominal CT revealed a 2×2 cm protruding smooth nodular lesion in an area in keeping with a submucosal lesion such as a gastrointestinal stromal tumour …
Direct Stenting Versus Direct Stenting Followed by Centered Beta-Radiation With Intravascular Ultrasound-Guided Dosimetry and Long-Term Anti-Platelet Treatment
Authors: Patrick W. Serruys, William Wijns, Georgios Sianos, Ivan de Scheerder, Paul A. van den Heuvel, Wolfgang Rutsch, Helmut D. Glogar, Carlos Macaya, Pierre H. Materne, Susan Veldhof, Heike Vonhausen, Patricia C. Otto-Terlouw, Wim J. van der Giessen
Journal: Journal of the American College of Cardiology (2004)
Disturbed Eating Behavior and Eating Disorders in Preteen and Early Teenage Girls With Type 1 Diabetes
Authors: Patricia Colton, Marion Olmsted, Denis Daneman, Anne Rydall, Gary Rodin
Journal: Diabetes Care (2004)

To compare the prevalence of eating disturbances in preteen and early teenage girls with type 1 diabetes to their nondiabetic peers.A cross-sectional, case-controlled study of 101 girls with type 1 diabetes, ages 9-14 years, and 303 age-matched, female nondiabetic control subjects was conducted. Participants completed a Children's Eating Disorder Examination interview. Socioeconomic status, BMI, and diabetes-related variables were assessed. Groups were compared using chi(2) analyses.Binge eating; the use of intense, excessive exercise for weight control; the combination of two disturbed eating-related behaviors; and subthreshold eating disorders were all more common in girls with type 1 diabetes. Metabolic control was not related to eating behavior in this study population.Eating disturbances, though mostly mild, were significantly more common in preteen and early teenage girls with type 1 diabetes. Screening and prevention programs for this high-risk group should begin in the preteen years.
Deciphering the enigma of rosacea continues…
Authors: J.K.L. Tan
Journal: British Journal of Dermatology (2015)

Journal Article Deciphering the enigma of rosacea continues… Get access J.K.L. Tan J.K.L. Tan Western University Windsor Campus and Private Practice Windsor ON Canada Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 173, Issue 3, 1 September 2015, Pages 637–638, https://doi.org/10.1111/bjd.14093 Published: 01 September 2015
Rates of synonymous substitution do not indicate selective constraints on the codon use of the plant psbA gene
Authors: B. R. Morton
Journal: Molecular Biology and Evolution (1997)

The psbA gene of the flowering plant chloroplast genome has a pattern of codon bias that differs from all other angiosperm chloroplast genes. In psbA, unlike all other chloroplast genes, the third-codon-position composition does not reflect the general genome compositional bias of a high A+T content. Instead, in specific synonymous groups, the codon use of psbA more closely corresponds to the tRNA population available for translation. Since it requires a composition unlike the genome composition bias, this pattern of codon use is likely to be the result of selection. Selective constraints on codon use are expected to result in decreased rates of synonymous substitution, and it has been observed that psbA has the lowest rate of synonymous substitution among plant chloroplast genes. In the present study, this is examined further by testing whether or not those synonymous groups that specifically have an atypical codon use in psbA have correspondingly low rates of silent substitution. An analysis of synonymous substitution rate, performed separately for different degeneracy classes of amino acids, shows that, contrary to the expectation, those sites that are presumed, based on their codon use, to be under selective constraint in psbA do not show low rates of substitution and are not responsible for the overall low rate of synonymous substitution in this gene. Instead, they actually show increased rates of substitution relative to other chloroplast genes. Two hypotheses concerning the role of selection in psbA are advanced to explain the results.
ZNF365 Promotes Stability of Fragile Sites and Telomeres
Authors: Yuqing Zhang, Sandra J. Shin, Debra Liu, Elena Ivanova, Friedrich Foerster, Haoqiang Ying, Hongwu Zheng, Yonghong Xiao, Zhengming Chen, Alexei Protopopov, Ronald A. DePinho, Ji-Hye Paik
Journal: Cancer Discovery (2013)

Critically short telomeres activate cellular senescence or apoptosis, as mediated by the tumor suppressor p53, but in the absence of this checkpoint response, telomere dysfunction engenders chromosomal aberrations and cancer. Here, analysis of p53-regulated genes activated in the setting of telomere dysfunction identified Zfp365 (ZNF365 in humans) as a direct p53 target that promotes genome stability. Germline polymorphisms in the ZNF365 locus are associated with increased cancer risk, including those associated with telomere dysfunction. On the mechanistic level, ZNF365 suppresses expression of a subset of common fragile sites, including telomeres. In the absence of ZNF365, defective telomeres engage in aberrant recombination of telomere ends, leading to increased telomere sister chromatid exchange and formation of anaphase DNA bridges, including ultra-fine DNA bridges, and ultimately increased cytokinesis failure and aneuploidy. Thus, the p53-ZNF365 axis contributes to genomic stability in the setting of telomere dysfunction.
Phase II Trial of the Oral Mammalian Target of Rapamycin Inhibitor Everolimus in Relapsed or Refractory Waldenström Macroglobulinemia
Authors: Irene M. Ghobrial, Morie Gertz, Betsy LaPlant, John Camoriano, Suzanne Hayman, Martha Lacy, Stacey Chuma, Brianna Harris, Renee Leduc, Meghan Rourke, Stephen M. Ansell, Daniel DeAngelo, Angela Dispenzieri, Leif Bergsagel, Craig Reeder, Kenneth C. Anderson, Paul G. Richardson, Steven P. Treon, Thomas E. Witzig
Journal: Journal of Clinical Oncology (2010)

PURPOSE The phosphatidylinositol 3-kinase/mammalian target of rapamycin (mTOR) signal transduction pathway controls cell proliferation and survival. Everolimus is an oral agent targeting raptor mTOR (mTORC1). The trial's goal was to determine the antitumor activity and safety of single-agent everolimus in patients with relapsed/refractory Waldenström macroglobulinemia (WM). PATIENTS AND METHODS Eligible patients had measurable disease (immunoglobulin M monoclonal protein > 1,000 mg/dL with > 10% marrow involvement or nodal masses > 2 cm), a platelet count more than 75,000 x 10(6)/L, a neutrophil count more than 1,000 x 10(6)/L, and a creatinine and bilirubin less than 2 x the laboratory upper limit of normal. Patients received everolimus 10 mg orally daily and were evaluated monthly. Tumor response was assessed after cycles 2 and 6 and then every three cycles until progression. Results Fifty patients were treated. The median age was 63 years (range, 43 to 85 years). The overall response rate (complete response plus partial remission [PR] plus minimal response [MR]) was 70% (95% CI, 55% to 82%), with a PR of 42% and 28% MR. The median duration of response and median progression-free survival (PFS) have not been reached. The estimated PFS at 6 and 12 months is 75% (95% CI, 64% to 89%) and 62% (95% CI, 48% to 80%), respectively. Grade 3 or higher related toxicities were observed in 56% of patients. The most common were hematologic toxicities with cytopenias. Pulmonary toxicity occurred in 10% of patients. Dose reductions due to toxicity occurred in 52% of patients. CONCLUSION Everolimus has high single-agent activity with an overall response rate of 70% and manageable toxicity in patients with relapsed WM and offers a potential new therapeutic strategy for this patient group.
Regulation of DNA methyltransferase 1 transcription in BRCA1-mutated breast cancer: a novel crosstalk between E2F1 motif hypermethylation and loss of histone H3 lysine 9 acetylation
Authors: Da Li, Fang-Fang Bi, Ji-Min Cao, Chen Cao, Bo Liu, Qing Yang
Journal: Molecular Cancer (2014)

DNA methyltransferase 1 (DNMT1) plays a critical role in breast cancer progression. However, the epigenetic mechanism regulating DNMT1 expression remains largely unknown. Epigenetic regulation of DNMT1 was assessed in 85 invasive ductal carcinomas from BRCA1 mutation carriers. Association between clinicopathological features and DNMT1 promoter methylation was determined using Fisher's exact test. Univariate analysis of survival was performed using the Kaplan-Meier method. Multivariate Cox regression analysis was performed to identify the independent prognostic factors for overall survival. Hypermethylated E2F transcription factor 1 (E2F1) motif is a key regulatory element for the DNMT1 gene in BRCA1-mutated breast cancer. Mechanistically, the abnormal E2F1 motif methylation-mediated loss of active histone H3 lysine 9 acetylation (H3K9ac) and transcription factor E2F1 enrichment synergistically inhibited the transcription of DNMT1. Clinicopathological data indicated that the hypermethylated E2F1 motif was associated with histological grade, lymph node, Ki67 and E-cadherin status; univariate survival and multivariate analyses demonstrated that lymph node metastasis was an independent and reliable prognostic factor for BRCA1-mutated breast cancer patients. Our findings imply that genetic (such as BRCA1 mutation) and epigenetic mechanisms (such as DNA methylation, histone modification, transcription factor binding) are jointly involved in the malignant progression of DNMT1-related breast cancer.
Lysosomal Storage Diseases: From Pathophysiology to Therapy
Authors: Giancarlo Parenti, Generoso Andria, Andrea Ballabio
Journal: Annual Review of Medicine (2015)

Lysosomal storage diseases are a group of rare, inborn, metabolic errors characterized by deficiencies in normal lysosomal function and by intralysosomal accumulation of undegraded substrates. The past 25 years have been characterized by remarkable progress in the treatment of these diseases and by the development of multiple therapeutic approaches. These approaches include strategies aimed at increasing the residual activity of a missing enzyme (enzyme replacement therapy, hematopoietic stem cell transplantation, pharmacological chaperone therapy and gene therapy) and approaches based on reducing the flux of substrates to lysosomes. As knowledge has improved about the pathophysiology of lysosomal storage diseases, novel targets for therapy have been identified, and innovative treatment approaches are being developed.