tbuckley/cabot-search huggingface dataset:
Measuring sequencer size bias using REcount: a novel method for highly accurate Illumina sequencing-based quantification
Authors: Daryl M. Gohl, Alessandro Magli, John Garbe, Aaron Becker, Darrell M. Johnson, Shea Anderson, Benjamin Auch, Bradley Billstein, Elyse Froehling, Shana L. McDevitt, Kenneth B. Beckman
Journal: Genome biology (2019)

Quantification of DNA sequence tags from engineered constructs such as plasmids, transposons, or other transgenes underlies many functional genomics measurements. Typically, such measurements rely on PCR followed by next-generation sequencing. However, PCR amplification can introduce significant quantitative error. We describe REcount, a novel PCR-free direct counting method. Comparing measurements of defined plasmid pools to droplet digital PCR data demonstrates that REcount is highly accurate and reproducible. We use REcount to provide new insights into clustering biases due to molecule length across different Illumina sequencers and illustrate the impacts on interpretation of next-generation sequencing data and the economics of data generation.
Mitochondrial ClpP-Mediated Proteolysis Induces Selective Cancer Cell Lethality
Authors: Jo Ishizawa, Sarah F. Zarabi, R. Eric Davis, Ondrej Halgas, Takenobu Nii, Yulia Jitkova, Ran Zhao, Jonathan St-Germain, Lauren E. Heese, Grace Egan, Vivian R. Ruvolo, Samir H. Barghout, Yuki Nishida, Rose Hurren, Wencai Ma, Marcela Gronda, Todd Link, Keith Wong, Mark Mabanglo, Kensuke Kojima, Gautam Borthakur, Neil MacLean, Man Chun John Ma, Andrew B. Leber, Mark D. Minden, Walid Houry, Hagop Kantarjian, Martin Stogniew, Brian Raught, Emil F. Pai, Aaron D. Schimmer, Michael Andreeff
Journal: Cancer Cell (2019)

The mitochondrial caseinolytic protease P (ClpP) plays a central role in mitochondrial protein quality control by degrading misfolded proteins. Using genetic and chemical approaches, we showed that hyperactivation of the protease selectively kills cancer cells, independently of p53 status, by selective degradation of its respiratory chain protein substrates and disrupts mitochondrial structure and function, while it does not affect non-malignant cells. We identified imipridones as potent activators of ClpP. Through biochemical studies and crystallography, we show that imipridones bind ClpP non-covalently and induce proteolysis by diverse structural changes. Imipridones are presently in clinical trials. Our findings suggest a general concept of inducing cancer cell lethality through activation of mitochondrial proteolysis.
www.happyneuron.com
Authors: Melpomeni Kountouri
Journal: BMJ (2003)

Did you realise you can train your neurones and challenge yourself with mind twisting games? Or have you ever thought to test your concentration or memory skills? This website is designed in French but you can change the language settings to English. It offers a number of exercises challenging cognitive functions and gives feedback on your score. There is a wide range of exercises; from Split Words to Elephant Memory, stimulating specific functions of the brain such as attention, memory, …
Altered C10 domain in cardiac myosin binding protein-C results in hypertrophic cardiomyopathy
Authors: Diederik W D Kuster, Thomas L Lynch, David Y Barefield, Mayandi Sivaguru, Gina Kuffel, Michael J Zilliox, Kyoung Hwan Lee, Roger Craig, Rajasekaran Namakkal-Soorappan, Sakthivel Sadayappan
Journal: Cardiovascular Research (2019)

Abstract Aims A 25-base pair deletion in the cardiac myosin binding protein-C (cMyBP-C) gene (MYBPC3), proposed to skip exon 33, modifies the C10 domain (cMyBP-CΔC10mut) and is associated with hypertrophic cardiomyopathy (HCM) and heart failure, affecting approximately 100 million South Asians. However, the molecular mechanisms underlying the pathogenicity of cMyBP-CΔC10mutin vivo are unknown. We hypothesized that expression of cMyBP-CΔC10mut exerts a poison polypeptide effect leading to improper assembly of cardiac sarcomeres and the development of HCM. Methods and results To determine whether expression of cMyBP-CΔC10mut is sufficient to cause HCM and contractile dysfunction in vivo, we generated transgenic (TG) mice having cardiac-specific protein expression of cMyBP-CΔC10mut at approximately half the level of endogenous cMyBP-C. At 12 weeks of age, significant hypertrophy was observed in TG mice expressing cMyBP-CΔC10mut (heart weight/body weight ratio: 4.43 ± 0.11 mg/g non-transgenic (NTG) vs. 5.34 ± 0.25 mg/g cMyBP-CΔC10mut, P &lt; 0.05). Furthermore, haematoxylin and eosin, Masson’s trichrome staining, as well as second-harmonic generation imaging revealed the presence of significant fibrosis and a greater relative nuclear area in cMyBP-CΔC10mut hearts compared with NTG controls. M-mode echocardiography analysis revealed hypercontractile hearts (EF: 53.4%±2.9% NTG vs. 66.4% ± 4.7% cMyBP-CΔC10mut; P &lt; 0.05) and early diastolic dysfunction (E/E′: 28.7 ± 3.7 NTG vs. 46.3 ± 8.4 cMyBP-CΔC10mut; P &lt; 0.05), indicating the presence of an HCM phenotype. To assess whether these changes manifested at the myofilament level, contractile function of single skinned cardiomyocytes was measured. Preserved maximum force generation and increased Ca2+-sensitivity of force generation were observed in cardiomyocytes from cMyBP-CΔC10mut mice compared with NTG controls (EC50: 3.6 ± 0.02 µM NTG vs. 2.90 ± 0.01 µM cMyBP-CΔC10mut; P &lt; 0.0001). Conclusion Expression of cMyBP-C protein with a modified C10 domain is sufficient to cause contractile dysfunction and HCM in vivo.
Adolescent care after disasters must address mental health
Authors: Irina Haivas
Journal: BMJ (2003)

Healthcare services after disasters should address anxiety, depression, aggression, and substance misuse of directly affected adolescents and their peer group, says new research in The Lancet (2003;362:691-6).

The researchers interviewed 950 young people who were directly and indirectly involved in a fire that killed 14 youngsters and wounded 250 in a …
UK medical schools may be forced to drop entrance standards
Authors: Rhona MacDonald, Sîan Knight
Journal: BMJ (2001)

Medical schools in the United Kingdom will be forced to drop their entry standards if they want to cope with declining applications and increasing places, according to a report in the Guardian (29 August).

The government plans to increase the number of people receiving medical training, but for the last few years the number of people applying for places has been dropping. The …
Abstract 13224: Minimally Invasive versus Traditional Sternotomy Mitral Valve Surgery: A Cost-Effectiveness Analysis
Authors: Alexander Iribarne, Rachel Easterwood, Mark J Russo, Jonathan Yang, Craig R Smith, Yun-Hsin C Wang, Michael Argenziano
Journal: Circulation (2010)

Purpose: The goal of this study was to compare the cost-effectiveness of mitral valve surgery (MVS) performed through a minimally invasive (MI) vs median sternotomy (ST) approach. Methods: From 1/1...
Radiotherapy enhances responses of lung cancer to CTLA-4 blockade
Authors: Anna Wilkins, Fiona McDonald, Kevin Harrington, Alan Melcher
Journal: Journal for ImmunoTherapy of Cancer (2019)

Formenti et al. have recently reported the clinical outcomes and translational readouts of a trial of the anti-CTLA-4 inhibitor, ipilimumab, in combination with palliative radiotherapy in 39 patients with non-small cell lung cancer. A radiological response was seen in 18% of patients and 31% of patients experienced disease control. These clinical outcomes appear to be superior to historical studies using ipilimumab alone and suggest that radiation may have triggered systemic, so-called abscopal, immune responses in some patients. Induction of interferon-beta (IFN-β) and maximal expansion and contraction of distinct T cell receptor clones were the most significant factors predicting response. Importantly, established predictive biomarkers of response to immunotherapy alone, including the expression of PD-L1 in diagnostic biopsies and tumour mutational burden, did not predict response. The report provides important human qualification of pre-clinical mechanistic insights indicating that abscopal responses can be generated with optimised radiotherapy fractionation schedules and anti-CTLA-4 inhibition. Additionally, an intriguing mechanism by which radiation can be immunogenic is described, namely radiation-induced transcriptional upregulation of neo-antigens.
Minerva: February 2000
Authors: M Mitra, R Dias
Journal: BMJ (2000)

Early one November morning in southeast Queensland, a father found his baby son motionless and covered in vomit. He had puncture marks on the back of his right hand and a large black funnel web spider in his bed clothes (Medical Journal of Australia 1999;171:651-3). Four other people in the area have been poisoned by funnel web spiders since 1992. All recovered, but experts warn local hospitals to be ready for an increased incidence of bites as urban centres grow into the spiders' natural territory. The message is to keep antivenom in stock or know where to find it fast.

The National Lottery recently awarded £166 000 to Bag Books, creators of multisensory story kits for children with severe learning difficulties. The “books,” which are three dimensional, incorporate sound, smell, and texture as well as visual stimuli. The lottery money guarantees production for another three years. For more information, or to order a book, email BagBooks@appleonline.net or telephone 020 7385 4021.

Doctors trying to decide whether it is safe to perform a lumbar puncture should trust their gut feeling, say researchers from the United States who studied the value of computed tomography in over 100 patients needing an urgent lumbar …
Film: The Age of Stupid
Authors: Adam Di Chiara
Journal: BMJ (2009)

The Oscar nominated actor Pete Postlethwaite plays “the archivist,” looking back from his high tech Arctic base in 2055. Climate change has run amok, and this rocky outpost is one of the last habitable places on Earth.

From the devastation of New Orleans, after hurricane Katrina, the shrinking of an alpine glacier near to the Mont Blanc road tunnel, the establishment of India’s first budget …
From medical student to junior doctor : maintaining good health during the “baptism of fire”
Authors: Geoffrey Robinson, Sharmila Bernau, Sarah Aldington, Richard Beasley
Journal: BMJ (2006)

Long working hours, sleep deprivation, and fatigue are just a few examples of the stressors experienced by junior doctors. In the seventh article of our series, <b>Geoffrey Robinson</b> and <b>colleagues</b> give advice on how to overcome these problems
Abstract 12438: Intraoperative Magnesium Reduces Postoperative Arrhythmias in Congenital Heart Surgery Is the Effect Arrhythmia-Specific and Dose-Dependent?
Authors: Dingchao He, Nimisha Aggarwal, Xiangming Fan, Yao I Cheng, Charles I Berul, Robert McCarter, Richard A Jonas, Jeffrey P Moak
Journal: Circulation (2016)

Introduction: Magnesium (MG) has been used to decrease the incidence of postoperative junctional ectopic tachycardia (PO JET); its efficacy on other arrhythmias (A) is less known. We tested the hypotheses that the effect of MG on PO A may be: 1) arrhythmia-specific and 2) dose-dependent. Methods: 1871 out of a total of 2208 congenital heart surgeries (CHS), performed from 2005 to 2013, were reviewed based on selection criteria. 750 cases did not receive MG, 338 cases received 25 mg/kg MG (25 Mg) and 783 cases received 50 mg/kg MG (50 Mg) after aortic cross clamp release. All procedures were classified according to Aristotle Score (1 to 4). The incidence of 5 PO A categories was recorded: JET, accelerated junctional rhythm (AJR), atrial tachycardia (AT), ventricular tachycardia (VT) and 2°and 3° heart block (HB). Pearson chi-square test and logistic model analyses were used to evaluate the effect of MG on arrhythmia. BSA, Aristotle score, cardiopulmonary bypass, aortic cross-clamp and surgery times were controlled in logistic models. Results: 1) PO JET was reduced with MG use (0 Mg 15.3%; Mg 7.2%; p&lt;0.001), but without evidence of a difference by dose (25 Mg 7.1%: 50 Mg 7.3%). 2) AJR was reduced with MG use (0 Mg 4.3%: 25 Mg 2.4%: 50 Mg 2.2%, NS between doses). 3) AT was reduced with MG use (0 Mg 9.1%: 25 Mg 3.6 %: 50 Mg 4.0%, NS between doses). 4) VT was reduced in low dose (0 Mg 5.1%: 25 Mg 2.7%; p =0.02), but not at the higher dose (50 Mg 5.5%). 5) PO HB did not differ by Mg use (0 Mg 4.8 %: 25 Mg 3.3 %: 50 Mg 2.6 %). The reduction of PO JET was significantly greater with increasing surgical complexity. Effect of MG was independent of Aristotle score in other A- categories. Conclusion: In agreement with prior clinical trial results, MG use was preventive of PO arrhythmia; however its effect appeared to be arrhythmia-specific. The occurrence of PO JET, AJR, and AT was reduced with Mg use. The effect of MG on PO VT appeared inversely dose dependent with no effect at higher dose and MG appeared to have no impact on PO HB. In general, higher doses of MG did not enhance PO arrhythmia suppression, but might be proarrhythmic (VT) in patients undergoing CHS. Our results suggest that an intraoperative MG dosage of 25 mg/kg may be optimal.
Doctors in Pakistan protest at killing of colleagues
Authors: Zarar Khan
Journal: BMJ (2002)

More than 50 prominent Karachi doctors staged a six hour hunger strike on Saturday 30 March in protest at the targeted killing of fellow doctors in Pakistan. And the Pakistan Medical Association, angered by the government's apparently uncaring attitude towards the killings, called for a countrywide strike on 8 April.

Doctors have been calling for adequate security for some time. This year, 13 doctors, most of them of the Shiite …
Corrections to “Gastrointestinal stromal tumours: ESMO–EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up”
Authors: P.G. Casali, N. Abecassis, H.T. Aro, S. Bauer, R. Biagini, S. Bielack, S. Bonvalot, I. Boukovinas, J V M G Bovee, T. Brodowicz, J.M. Broto, A. Buonadonna, E. De Álava, A.P. Dei Tos, X.G. Del Muro, P. Dileo, M. Eriksson, A. Fedenko, V. Ferraresi, A. Ferrari, S. Ferrari, A.M. Frezza, S. Gasperoni, H. Gelderblom, T. Gil, G. Grignani, A. Gronchi, R.L. Haas, B. Hassan, P. Hohenberger, R. Issels, H. Joensuu, R.L. Jones, I. Judson, P. Jutte, S. Kaal, B. Kasper, K. Kopeckova, D.A. Krákorová, A. Le Cesne, I. Lugowska, O. Merimsky, M. Montemurro, M.A. Pantaleo, R. Piana, P. Picci, S. Piperno-Neumann, A.L. Pousa, P. Reichardt, M.H. Robinson, P. Rutkowski, A.A. Safwat, P. Schöffski, S. Sleijfer, S. Stacchiotti, K. Sundby Hall, M. Unk, F. Van Coevorden, W.T.A. van der Graaf, J. Whelan, E. Wardelmann, O. Zaikova, J.Y. Blay
Journal: Annals of Oncology (2018)

Ann Oncol 2018; 29: iv68–iv78 (doi:10.1093/annonc/mdy095) The following corrections have been made under authorship: The author R.L. Haas has been added with the corresponding affiliation and author disclosure statement. The author name P. Rutkovski has been replaced with: P. Rutkowski Under authorship, the author name: A. Hannu has been replaced with: H.T. Aro. Under authorship, A. A. Safwat’s affiliation: Finland has been replaced with: Denmark. Under authorship, the author name: W. Van der Graaf has been replaced with: W.T.A. van der Graaf. W.T.A. van der Graaf’s institution: 30 has been replaced with: 30, 33, 51. Gastrointestinal stromal tumours: ESMO–EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-upAnnals of OncologyVol. 29PreviewGastrointestinal stromal tumours (GISTs) are rare tumours, with an estimated unadjusted incidence of around 1/100 000/year [1]. This only covers clinically relevant GISTs, since, if investigated, a much higher number of lesions ≤ 1 cm in diameter (microGISTs) can be found at histopathological examination of stomach tissue in middle-aged and elderly individuals. Full-Text PDF Open Archive
Streamlined training for junior doctors set for 2004
Authors: Samena Chaudhry
Journal: BMJ (2003)

Newly qualified doctors in the United Kingdom will soon undertake a two year foundation course covering core clinical skills, including safety of patients and communication skills.

In a drive to reform junior doctors' training, John Hutton, minister for health, recently announced plans to improve the quality of training for doctors to ensure their training is streamlined for the benefit of themselves, the NHS, and patients.

The proposals have been agreed by the United Kingdom's four health departments and will apply to almost 36 000 doctors in training. Pilot studies will be launched later this year, and …
Proper or Improper Use of the Crossover Design in Clinical Trials in Chronic Sciatica?
Authors: Miguel Leal Rato, Gonçalo S. Duarte, Joaquim J. Ferreira
Journal: JAMA Neurology (2019)

To the Editor Robertson et al1 conducted a crossover randomized clinical trial of gabapentin (GBP) vs pregabalin (PBG) in chronic sciatica (CS). We congratulate the authors for their effort toward improving CS management. However, some methodological issues hinder the conclusions in this trial.
Teaching High-Value Care Through Conscious Ordering of Diagnostic Tests
Authors: Kapil Bhatia, Eric Y. Chang, Temidayo Abe
Journal: JAMA Internal Medicine (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Phase II Study of Blinatumomab in Patients with B-Cell Lineage Acute Lymphocytic Leukemia with Positive Minimal/Measurable Residual Disease
Authors: Iman Aboudalle, Hagop M. Kantarjian, Nicholas J Short, Maria Khouri, Koichi Takahashi, Maro N. Ohanian, Gautam Borthakur, Marina Y. Konopleva, Naval G. Daver, Zeev E. Estrov, Yesid Alvarado, Nitin Jain, Farhad Ravandi, Guillermo Garcia-Manero, Michelle Velasquez, Patrice Nasnas, Susan M. O'Brien, Elias J. Jabbour
Journal: Blood (2018)
General surgery resources for students
Authors: Matas Morkevicius
Journal: BMJ (2004)

Medical students spend lots of money on textbooks. But now the internet contains lots of resources including several surgical textbooks that are available free of charge.

Surgical Treatment: Evidence Based and Problem-Oriented (www.ncbi.nlm.nih.gov/books/bv.fcgi?call=bv.View..ShowTOC&rid=surg.TOC) is probably one of the best online texts which covers the various topics in general surgery. The contents follow the usual format of paper surgery textbooks and classify the chapters according to the diseased organ. At the end of each section, a …
Scientists show thalamus dysfunction in early schizophrenia
Authors: Tracey Maher
Journal: BMJ (2001)

The thalamus, the brain's main sensory filter, is dysfunctional in the earliest stages of schizophrenia. A study published in the American Journal of Psychiatry (2001;158:116-8) shows for the first time that thalamic abnormalities are present close to the onset of psychosis. These findings may explain why people with schizophrenia experience confusion during their illness.

The thalamus, the area where …
Picture Quiz: Falling on an outstretched arm
Authors: Marios Tryfonidis, Charalambos Charalambous
Journal: BMJ (2003)

A 6 year old boy attended the emergency department with an isolated injury to his left elbow after falling on his outstretched left arm. On examination, the left elbow joint was swollen and clinically deformed with diffuse tenderness. The skin was intact and there was no neurovascular deficit in the left upper limb. We x rayed the elbow (figure).



X ray of the boy's elbow



1.  What does the x ray film show?

2.  What should the assessment of such an incident include?

3.  What is the classification of supracondylar fractures of the humerus?

4.  What are the potential complications of supracondylar fractures?

5.  How should this fracture be managed?

1.  The x ray film shows a displaced supracondylar fracture of the left humerus with the distal fragment of the humerus displaced posteriorly.

2.  Assessment should include a quick general evaluation of the patient to ensure that the airways are patent, breathing is …
Minerva - November 2001
Authors: Davis Maxwell, Neil Sulke, Richard Goodwin, Colin Long
Journal: BMJ (2001)

The effects of oral steroids on bone density are well documented, but it now seems that inhaled steroids may also put bones at risk. A three year prospective study of 109 premenopausal women with no known con? ditions that cause bone loss, and who used inhaled steroids for their asthma, has found a small but significant dose related reduction in bone density at the hip and trochanter. Serum and urine markers did not predict the degree of bone loss (New England Journal of Medicine 2001;345:941-7).

Lots of people take statins to lower their cholesterol levels, despite being at relatively low risk of a fatal coronary event. A group of pharmacologists has calculated that the risk of mortality from the drugs alone may be 1% in 10 years of use. This, they suggest, would be sufficiently large to negate the beneficial effect on coronary related mor? tality in people with a risk of less than 13% over 10 years (British Journal of Clinical Pharmacology 2001;52:439-46).

Millions of years ago, an Australian desert tree called Acacia victoriae developed “avicins” to protect itself from predators. These killed by inducing apoptosis or by reducing oxidative stress …
Abstract 15476: Relation of Blood Pressure Indices with Differential Risk for Cardiovascular Events: The Atherosclerosis Risk in Communities Study
Authors: Susan Cheng, Deepak K Gupta, Amil M Shah, A. Richey Sharrett, Hicham Skali, Madoka Takeuchi, Brian Clagett, Hanyi Ni, Scott D Solomon
Journal: Circulation (2012)

BACKGROUND: Distinct components of blood pressure (BP) elevation include measures of pulsatile versus steady state load. The extent to which distinct BP components may be associated with varying risk for different cardiovascular outcomes remains uncertain. METHODS: We studied 10,007 participants (mean age 54±6 years, 56% women, 21% African American) of the Atherosclerosis Risk in Communities Study who were free of cardiovascular disease at baseline. We used Cox proportional hazards models to compare the contributions of systolic (SBP), diastolic (DBP), pulse pressure (PP), and mean arterial pressure (MAP) to risk for coronary heart disease (CHD), heart failure (HF), stroke, and all-cause mortality. A larger -2 log-likelihood difference for a model with a single BP measure removed (compared to a full model with 2 measures being compared) was considered to reflect a greater contribution of that BP measure to risk for the given outcome. RESULTS: A total of 1537 CHD events, 951 HF events, 550 stroke events, a...
The 90/10 divide
Authors: Nathan Ford
Journal: BMJ (2002)

Ninety per cent of the world is at risk from infectious diseases, but only 10% of the world9s research and pharmaceutical resources are spent on them. Drug development for diseases that affect poor people has come to a virtual standstill. <b>Nathan Ford</b> explains how Médecins Sans Frontières is trying to redress the balance with its ‘Access to Medicines’ campaign(also see the review of Secret Agents on p298)