tbuckley/cabot-search huggingface dataset:
Genomes in a bottle: creating standard reference materials for genomic variation - why, what and how?
Authors: Justin M Zook, Marc Salit
Journal: Genome biology (2011)

Broad clinical application of ultra-high-throughput sequencing is imminent. In a few notable cases, actionable information has been discovered from sequencing, and the number of such cases is likely to increase. At present, there are no widely accepted genomic standards or quantitative performance metrics. These are needed to achieve the confidence in measurement results that is expected for sound, reproducible research and regulated applications. The National Institute of Standards and Technology (NIST) has been approached about considering development in this area by several commercial entities and regulatory agencies. There is great enthusiasm for translation of sequencing from the research community to clinical practice, and standards that can be used to inform confidence in measurement results (for instance, through validation studies, proficiency testing and routine quality assurance) may be an enabling factor in that goal.

NIST is currently gathering input from the genomics community about which reference materials and data would be useful. For example, NIST and the Coriell Institute for Medical Research may develop genomic reference material from cell lines from families that have already been characterized by a variety of sequencing methods (for example, the cell line from which NA12878 DNA is derived). In addition, we may build synthetic DNA constructs to test specific questions about measuring different types of variants or combinations of variants in different genomic contexts. For example, we might create pairs of constructs with single nucleotide polymorphisms, indels and/or structural variants in GC- or AT-rich regions or repeat regions. To ensure the design of appropriate standards, we are interested in discussing the design and application of genomic reference materials with any interested parties.
Peginterferon Alfa-2b and Ribavirin for the Treatment of Chronic Hepatitis C in Blacks and Non-Hispanic Whites
Authors: Andrew J. Muir, Jeffrey D. Bornstein, Paul G. Killenberg
Journal: New England Journal of Medicine (2004)

Several small studies have reported a lower response rate to interferon alfa among black patients with chronic hepatitis C infection than among white patients. The increased prevalence of infection with hepatitis C virus (HCV) genotype 1, which has a lower response rate than other genotypes, has been suggested as the cause.We treated 100 black patients and 100 non-Hispanic white patients with chronic hepatitis C with peginterferon alfa-2b and ribavirin for 48 weeks. Enrollment was controlled so that the two groups had similar proportions of patients with genotype 1 infection. The primary end point was a sustained virologic response, which was defined as a negative test for serum HCV RNA six months after the completion of therapy.In both cohorts, 98 percent of patients had genotype 1 infection. The rate of sustained virologic response was higher among non-Hispanic white patients than among black patients (52 percent vs.19 percent, P<0.001). The black patients also had significantly lower rates of virologic response at 12 weeks and at the end of treatment. Multivariable analyses examining sociodemographic and clinical characteristics found that black race was the only variable significantly associated with the difference in response rate.Black patients with chronic hepatitis C have a lower rate of response to treatment with peginterferon alfa-2b and ribavirin than non-Hispanic white patients, a difference that is not explained by differences in the viral genotype.
DOES 6-MINUTE WALK TEST PREDICT CLINICAL EVENTS IN PULMONARY ARTERIAL HYPERTENSION? A META-ANALYSIS OF 22 STUDIES
Authors: Gianluigi Savarese, Stefania Paolillo, Pierluigi Costanzo, Francesca Musella, Fabio Marsico, Pasquale Perrone-Filardi
Journal: Journal of the American College of Cardiology (2012)
Colitis and cancer: a tale of inflammatory cells and their cytokines
Authors: Ezra Burstein, Eric R. Fearon
Journal: Journal of Clinical Investigation (2008)

Chronic inflammatory disorders are often associated with an increased cancer risk. A particularly striking example of the chronic inflammation–cancer link is seen in inflammatory bowel disease, in which chronic colitis or persistent inflammation in the colon is associated with elevated risk of colorectal cancer. Animal models exploring the mechanisms by which inflammation increases the risk of colon cancer have shown that inflammatory cells, through the effects of the cytokines they produce, have a major role in promoting neoplastic transformation. In this issue of the JCI, Popivanova and colleagues demonstrate that TNF-α, through its effects on the immune system, plays a critical role in promoting neoplastic transformation in this setting (see the related article beginning on page 560). Importantly, the study also provides evidence that anti–TNF-α therapies, which are currently in clinical use, may interrupt the process.
Why patients choose paracetamol for self poisoning and their knowledge of its dangers
Authors: K. Hawton, C. Ware, H. Mistry, J. Hewitt, S. Kingsbury, D. Roberts, H. Weitzel
Journal: BMJ (1995)

Some practical problems exist, however, ranging from the provision of extra chairs to the need for a liaison nurse to escort parents to and from the recovery room.Few operating suites have waiting areas for relatives, and ward areas are often inadequate.In summary, parents welcomed the opportunity to come to the recovery room at an early stage, few problems occurred, and there was staff support for continuing the practice.
Managing osteoarthritis of the knee
Authors: Martin Johnson
Journal: BMJ (2005)

Developing primary palliative care Continuity of care is paramount but needs to be tailored individuallyEditor-Riley suggests that completion of a form detailing palliative care management should be mandatory for general practitioners. 1 I have spent a great deal of time promoting palliative medicine in primary care, with variable success.Much depends on the individual practitioner's experience and interest, which probably accounts for the variable success of handover forms to communicate with out of hours services.Making this a compulsory part of general practice might bring all practice to the same level.But the initial answer to the question, "Would I be surprised if my patient died in the next 12 months?"would then make the difference.Cynical practitioners would probably answer no for nearly all of their patients, for the longer you practise the less often you are surprised.But, in truth, for many patients in general practice the answer to this question would be no: many elderly patients who live in nursing or residential homes, nearly all patients with chronic disease, including heart disease, chronic obstructive pulmonary disease, neurological disease, and so on.The workload in handing these patients over to the out of hours service would be huge, more so for the out of hours service than the individual practice.Continuity of care for patients who most need it is paramount, including all those with chronic disease.However, more sophisticated systems are needed to meet patient needs: perhaps different systems for different diseases, possibly different systems for each stage of a disease.Whatever the system, it must meet the needs of the individual patient.This entails dialogue between primary care (including out of hours), secondary care, and tertiary care to thrash out the detail.
Cigarette Smoking Is Not Associated with Specific Histological Features or Severity of Nonalcoholic Fatty Liver Disease
Authors: Lorenzo Azzalini, José Altamirano, Ramón Bataller
Journal: Hepatology (2010)

We thank Dr. Yilmaz et al. for their interest in our recent study published in HEPATOLOGY.1 As the authors described in their letter, our experimental study showing that cigarette smoking exacerbates nonalcoholic fatty liver disease (NAFLD) should be confirmed in human studies. In their letter, Yilmaz et al. show the results from a cross-sectional study including 90 patients with histologically-proven NAFLD. The logistic regression analysis showed that cigarette smoking was not an independent factor associated with the severity of NAFLD, after adjusting for sex, age, BMI and other factors. The authors conclude that cigarette smoking per se does not worsen the severity of NAFLD. Although we acknowledge the effort of the authors to address this issue, we think that their observations are too preliminary to reach such strong conclusion. First, NAFLD is a highly heterogeneous disease that involves many environmental and genetic factors and the series from Yilmaz et al. is clearly underpowered because it only includes 90 patients. Large epidemiological studies including a high number of well-characterized patients are clearly needed to elucidate the role of smoking on NAFLD. And second, the impact of total number of pack-years smoked on the development of severe forms of NAFLD according to Kleiner's classification (i.e., definitive nonalcoholic steatohepatitis) should be specifically investigated. In conclusion, carefully designed clinical studies including large number of patients are required to assess the role of smoking on the clinical course of NAFLD. Lorenzo Azzalini*, José Altamirano*, Ramón Bataller*, * Liver Unit, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain.
Liver damage induced by oxyphenisatin.
Authors: P Kotha, M O Rake, D Willatt
Journal: BMJ (1980)

<h3>Abstract</h3> Transcranial alternating current stimulation (tACS) is a well-established brain stimulation technique to modulate human brain oscillations. However, due to the strong electro-magnetic artifacts induced by the stimulation current, the simultaneous measurement of tACS effects during neurophysiological recordings in humans is challenging. Recently, transcranial temporal interference stimulation (tTIS) has been introduced to stimulate neurons at depth non-invasively. During tTIS, two high-frequency sine waves are applied, that interfere inside the brain, resulting in amplitude modulated waveforms at the target frequency. Given appropriate hardware, we show that neurophysiological data during tTIS may be acquired without stimulation artifacts at low-frequencies. However, data must be inspected carefully for possible low-frequency artifacts. Our results may help to design experimental setups to record brain activity during tTIS, which may foster our understanding of its underlying mechanisms.
Leukemic transformation by the MLL-AF6 fusion oncogene requires the H3K79 methyltransferase Dot1l
Authors: Aniruddha J. Deshpande, Liying Chen, Maurizio Fazio, Amit U. Sinha, Kathrin M. Bernt, Deepti Banka, Stuart Dias, Jenny Chang, Edward J. Olhava, Scott R. Daigle, Victoria M. Richon, Roy M. Pollock, Scott A. Armstrong
Journal: Blood (2013)
Human papillomavirus vaccine trials in India
Authors: Amit Sengupta, Anjali Shenoi, NB Sarojini, Y Madhavi
Journal: The Lancet (2011)

Heidi Larson and colleagues in their Comment,1Larson HJ Brocard P Garnett G The India HPV-vaccine suspension.Lancet. 2010; 376: 572-573Summary Full Text Full Text PDF PubMed Scopus (65) Google Scholar and Mark Feinberg of Merck in his response,2Feinberg M HPV vaccine suspension in India.Lancet. 2010; 376: 1644-1645Summary Full Text Full Text PDF PubMed Scopus (7) Google Scholar call for more effective ways to engage with public advocates who question new health interventions, or studies, particularly for diseases that affect developing countries. We disagree with Larson and Feinberg about the human papillomavirus (HPV) vaccine's public health value and would like to reiterate the importance of transparency in research. We are dismayed by its absence in the Indian HPV projects, particularly after two of us (AS, NBS) found evidence of gross ethical violations on a visit to the project site in Bhadrachalam, Andhra Pradesh (report available from the authors). Feinberg states that the India projects are not clinical trials, but studies to facilitate speedier access to a vaccine in the country. The Drugs Controller General of India (DCGI), in a response to an application under the Right to Information Act has described the project as involving “Phase IV studies as per the Schedule Y of Drugs & Cosmetics Act and rules there under”. The Minister of Health and Family Welfare has also described it “as an epidemiological study which needs to be carried out on a bigger population and a larger number of subjects”.3Parliament Proceedings: Calling attention to a matter of urgent public importance: HPV vaccine programme by PATH in certain states of IndiaRajya Sabha Synopsis of Debate.http://164.100.47.5/newsynopsis1/Englishsessionno/219/Syn_%20Eng_%20Dated%2022_04_2010.pdfDate: April 22, 2010Google Scholar These quotes contradict the claims that these were not clinical research. The DCGI's office has used Section 8(1)(d) of the Right to Information Act, to deny information on the study protocols as a “trade secret and commercial confidence of third party”. The Indian Council of Medical Research has also invoked intellectual property rights to deny this information. It is not clear how information from a study done in collaboration with government organisations can be a trade secret. Research done in the public domain must involve the communities affected, and be based on the country's public health priorities. The focus must be on maximising investment in priority health issues, ensuring safety of health interventions, and following not only the letter but also the spirit of ethical protocols and legal obligations. We declare that we have no conflict of interests.
John Gwilym Howells
Authors: C. Adams, R. Howells
Journal: BMJ (2008)

John Gwilym Howells, MD, FRCPsych, AKC, DFAPA, FLS, was formerly director of the Institute of Family Psychiatry from 1950 to 1985, an institute associated with the University of Cambridge. He instigated family psychiatry in the United Kingdom, having been trained as a child psychiatrist. A progressive, he determinedly lead the movement to establish a Royal College of Psychiatrists. While running a busy clinical service for the people of East Suffolk he researched, developed, and applied his family psychiatry model for 35 years. He was a sought-after lecturer and trainer across the world, particularly in the United States, where he was awarded the distinguished fellowship of the American Psychiatric Association. He was a prolific author—writing or editing 48 books in six languages, as well as many scientific papers—expounding ideas on issues as various as child welfare, history, psychopathology, psychiatry and medicine, and his key focus: the concepts of experiential psychopathology and the creation of a salutiferous society.

John was born and brought up in North Wales. He studied medicine at King’s College, London, and Charing Cross Medical School. While at King’s he also successfully took the AKC qualification in response to a developing interest in philosophy and theology. This may have been very influential during the rest of his life when he sought truth through research. It was at King’s that he also first became interested in psychopathology when he took a course by J A Hadfield. …
Echocardiographic Assessment of Commissural Calcium: A Simple Predictor of Outcome After Percutaneous Mitral Balloon Valvotomy
Authors: Charles R Cannan, Rick A Nishimura, Guy S Reeder, Duane R Ilstrup, Dirk R Larson, David R Holmes, A.Jamil Tajik
Journal: Journal of the American College of Cardiology (1997)
Potent induction of apoptosis in human hepatoma cell lines by targeted cytotoxic somatostatin analogue AN-238
Authors: Malika Lasfer, Nathalie Vadrot, Andrew V. Schally, Attila Nagy, Gabor Halmos, Dominique Pessayre, Gérard Feldmann, Florence J. Reyl-Desmars
Journal: Journal of Hepatology (2004)
Myocardial Revascularization for Acute and Chronic Coronary Heart Disease
Authors: H. J. C. SWAN
Journal: Annals of Internal Medicine (1973)

Myocardial revascularization is ideally indicated for critical obstructive lesions in the proximal portions of the coronary vessel, particularly in the left coronary system, with minimally involved distal vessels. Two conditions indicate a serious deficiency in coronary blood supply: severe, disabling, intractable angina pectoris and unstable angina pectoris. The overall operative mortality rate is 7%, including patients with complications of myocardial ischemia (infarction, ventricular aneurysm); in "uncomplicated" symptomatic cases a rate of 3% should be attained. After successful revascularization of the myocardium, with a functioning vein graft and no postoperative myocardial damage, we have shown improved ventricular function. Patients with enlarged hearts with little or no angina, patients with distal as opposed to proximal obstructive disease, and patients with diffuse or localized myocardial scarring are not accepted for surgery.
High-sensitivity C-reactive protein predicts target organ damage in Chinese patients with metabolic syndrome
Authors: Zhigang Zhao, Hai Nie, Hongbo He, Zhencheng Yan, Daoyan Liu, Zhidan Luo, Liqun Ma, Yinxing Ni, Jin Chen, Jin Jing, Tingbing Cao, Hua Yang, Martin Tepel, Weiguo Zhang, Zhiming Zhu
Journal: Metabolism (2007)
Colorectal polypectomy during insertion and withdrawal or only during withdrawal? A randomized controlled trial
Authors: S. Wildi, A. Schoepfer, S. Vavricka, H. Fruehauf, E. Safroneeva, N. Wiegand, P. Bauerfeind, M. Fried
Journal: Endoscopy (2012)

<b>Background and study aims:</b> Removal of colorectal polyps is routinely performed during withdrawal of the endoscope. However, polyps detected during insertion of the colonoscope may be missed at withdrawal. We aimed to evaluate whether polypectomy during both insertion and withdrawal increases polyp detection and removal rates compared with polypectomy at withdrawal only, and to assess the duration of both approaches. <b>Patients and methods:</b> Patients were included into the study when the first polyp was detected, and randomized into two groups; in group A, polyps ≤ 10 mm in diameter were removed during insertion and withdrawal of the colonoscope, while in group B, these polyps were removed at withdrawal only. Main outcome measures were duration of colonoscopy, number of polyps detected during insertion but not recovered during withdrawal, technical ease, patient discomfort, and complications. <b>Results:</b> 150 patients were randomized to group A and 151 to group B. Mean (± standard deviation [SD]) duration of colonoscopy did not differ between the groups (30.8 ± 15.6 min [A] vs. 28.5 ± 13.8 min [B], <i>P</i> = 0.176). In group A 387 polyps (mean 2.58 per colonoscopy) were detected and removed compared with 389 polyps detected (mean 2.58 per colonoscopy) in group B of which 376 were removed (13 polyps were missed, mean size [SD] 3.2 [1.3] mm; 7.3 % of patients). Patient tolerance was similar in the two groups. <b>Conclusions:</b> Removal of polyps ≤ 10 mm during withdrawal only is associated with a considerable polyp miss rate. We therefore recommend that these polyps are removed during both insertion and withdrawal.
Paracrine signalling events in embryonic stem cell renewal mediated by affinity targeted nanoparticles
Authors: Bruna Corradetti, Paz Freile, Steve Pells, Pierre Bagnaninchi, Jason Park, Tarek M. Fahmy, Paul A. de Sousa
Journal: Biomaterials (2012)

Stem cell growth and differentiation is controlled by intrinsic and extrinsic factors. The latter includes growth factors, which are conventionally supplied in vitro in media exchanged daily. Here, we illustrate the use of affinity targeted biodegradable nanoparticles to mediate paracrine stimulation as an alternative approach to sustain the growth and pluripotency of mouse embryonic stem cells. Leukaemia Inhibitory Factor (LIF) was encapsulated in biodegradable nanoparticles and targeted to the cell surface using an antibody to the oligosaccharide antigen SSEA-1. Sustained release of LIF from nanoparticles composed of a solid Poly(lactide-co-glycolic acid) polyester or a hydrogel-based liposomal system, we term Nanolipogel, replenished once after each cell passage, proved as effective as daily replenishment with soluble LIF for maintenance of pluripotency after 5 passages using 10(4)-fold less LIF. Our study constitutes an alternative paradigm for stem cell culture, providing dynamic microenvironmental control of extrinsic bioactive factors benefiting stem cell manufacturing.
Survey of safety and health care in British medical laboratories.
Authors: J M Harrington, H S Shannon
Journal: BMJ (1977)

A retrospective postal survey of 24 000 medical laboratory workers in England, Wales, and Scotland showed highly variable standards of safety and health care. Pre-employment health screening was offered to two-thirds of employees, the physicians being the least likely to be examined (15%). Scottish laboratories provided better safety control than English and Welsh laboratories, while Public Health Service Laboratories had a better record than National Health Service establishments. Mouth pipetting is still practised in 65% of English and Welsh laboratories, and the use of protective clothing is rarely compulsory. The servicing of safety cabinets is often inadequate. Known and suspected carcinogens are still apparently used in a few laboratories (2-10%). In view of the wide variation in standards among laboratories, urgent consideration should be given to establishing regulations for codes of safe practice rather than relying merely on recommendations as at present.
Linear DNAs Concatemerize in Vivo and Result in Sustained Transgene Expression in Mouse Liver
Authors: Zhi-Ying Chen, Stephen R. Yant, Cheng-Yi He, Leonard Meuse, Shiliang Shen, Mark A. Kay
Journal: Molecular Therapy (2001)

The short duration of transgene expression remains a major obstacle for the implementation of nonviral DNA vectors in clinical gene therapy trials. Here, we demonstrate stable, long-term transgene expression in vivo by transfecting a linear DNA expression cassette (LDNA) into mouse liver. Interestingly, despite similar quantities and cellular distribution of injected DNAs in their livers, mice receiving LDNA encoding human α1-antitrypsin (hAAT) expressed approximately 10- to 100-fold more serum hAAT than mice injected with closed circular (cc) DNA for a period of 9 months (length of study). Furthermore, when a linear human factor IX expression cassette was delivered to factor IX-deficient mice, sustained serum concentrations of more than 4 μg/ml (80% of normal) of the human clotting factor and correction of the bleeding diathesis were obtained. Southern blot analyses indicate that, unlike ccDNA, LDNA rapidly formed large, unintegrated concatemers in vivo, suggesting that transgene persistence from plasmid-based vectors was influenced by the structure of the vector in transfected cells. No differences in transgene expression or DNA molecular structures were observed when AAV ITRs were included to flank the hAAT expression cassette in both ccDNA- and LDNA-treated animals. Linear DNA transfection provides an approach for achieving long-term expression of a transgene in vivo.