tbuckley/cabot-search huggingface dataset:
Mimotope optimization for GD2 directed anti-neuroblastoma immunotherapy
Authors: Matthias Bleeke, Stefan Fest, Nicole Huebener, Christiane Landgraf, Rudolf Volkmer, Gerhard Gaedicke, Elke Michalsky, Ines Jaeger, Robert Preissner, Holger Lode
Journal: Cancer Research (2007)

5101  The disialoganglioside GD2 is an established target for neuroblastoma immunotherapy. To overcome poor antigenicity of the glycolipid GD2, we changed the nature of the antigen into peptides mimicking the structure of GD2, i.e. GD2 mimotopes. The efficiency of mimotope-based active vaccination strategies inducing protective anti-neuroblastoma immunity was already demonstrated in animal experiments.  In order to also achieve therapeutic success with such a vaccination approach, GD2 mimotopes were improved. First, two peptide mimotope sequences MA and MD identified by phage-display experiments were used for a progression of peptide substitutional analyses. For this purpose each amino acid of the MA and MD sequences was sequentially replaced by all other gene encoded amino acids. The substitutional analyses were prepared as cellulose membrane bound peptide arrays and subsequently tested for anti-GD2 MAB ch14.18 binding. The most promising candidate was chosen for the next substitutional analysis round. The best peptide candidates were synthesized and binding affinities to the anti-GD2-mAb ch14.18 were determined as dissociation constants (KD) by surface plasmon resonance studies. This approach resulted in an improved novel peptide (C3) with a more than five-fold increased affinity to ch14.18, compared to the wild type peptide.  Second, an alternative phage-display library independent approach was developed by the adoption of computer aided docking experiments. The criteria is design of an energetically optimal paratope structure of the anti-idiotypic-mAb 1A7 fitting into the corresponding binding domain of ch14.18. The peptide analysis allowed the construction of a stress reduced 3-dimensional model of the variable domain of ch14.18 and the nominal antigen GD2.  These results demonstrate two promising new approaches for the identification of peptide mimotopes for cancer immunotherapy.  Supported by DFG Lo 635-2 and Fordergesellschaft Kinderkrebs-Neuroblastom-Forschung
Association Between Peripheral Neuropathy and Exposure to Oral Fluoroquinolone or Amoxicillin-Clavulanate Therapy
Authors: Daniel Morales, Alexandra Pacurariu, Jim Slattery, Luis Pinheiro, Patricia McGettigan, Xavier Kurz
Journal: JAMA Neurology (2019)

Peripheral neuropathy has been associated with systemic fluoroquinolone exposure, but risk has been poorly quantified.To calculate relative and absolute risk estimates for the association of fluoroquinolone exposure with peripheral neuropathy and to examine how risk may be affected by timing of fluoroquinolone exposure and by other risk factors.This nested case-control study used anonymized data from all patients routinely registered with general practices in The Health Improvement Network database, a large primary care population database in the United Kingdom, from January 1, 1999, to December 31, 2015. Data analyses were conducted January 8, 2018. The cohort consisted of 1 338 900 adults issued 1 or more prescriptions of fluoroquinolone (34.3%) or amoxicillin-clavulanate (65.7%) antibiotics. Adults with incident peripheral neuropathy were matched (on age, sex, general practice, and calendar time) with up to 4 controls by using incidence density sampling selected from a cohort prescribed oral fluoroquinolone or amoxicillin-clavulanate antibiotics. Incidence rate ratios of peripheral neuropathy were calculated for fluoroquinolone and for amoxicillin-clavulanate exposure and compared with nonexposure among patients without diabetes, with sensitivity analyses testing the consistency of the results. Population mean-adjusted rate differences were then estimated, including the number needed to harm for various durations of fluoroquinolone therapy.Current and cumulative exposure to oral fluoroquinolone or amoxicillin-clavulanate antibiotics.Incident peripheral neuropathy cases recorded in electronic medical records.In total, 5357 patients with incident peripheral neuropathy (mean [SD] age, 65.6 [14.7] years; 2809 women [52.4%]) were matched to 17 285 controls (mean [SD] age, 64.4 [15.2] years; 9485 women [54.9%]) without diabetes. Current oral fluoroquinolone exposure was associated with an increased relative incidence of peripheral neuropathy compared with nonexposure (adjusted incident rate ratio, 1.47; 95% CI, 1.13-1.92). Risk increased by approximately 3% for each additional day of current fluoroquinolone exposure and persisted for up to 180 days following exposure. No significant increased risk was observed with oral amoxicillin-clavulanate exposure. The absolute risk with current oral fluoroquinolone exposure was 2.4 (95% CI, 1.8-3.1) per 10 000 patients per year of current use. The number needed to harm for a 10-day course was 152 083 patients (95% CI, 117 742-202 778) and was greatest among men and among patients older than 60 years.The results of the present study suggested that oral fluoroquinolone therapy was associated with an increased risk of incident peripheral neuropathy that may depend on the timing of the exposure and the cumulative dose. Health care professionals should consider these potential risks when prescribing fluoroquinolone antibiotics.
Public health and HIV/AIDS
Authors: Irina Haivas
Journal: BMJ (2005)

Few subjects in medicine have so many websites dedicated to them as HIV/AIDS, so the daunting task is not findinga website but choosing from the selection.



P VIROT/WHO



On the public health side, one of the umbrella websites is www.unaids.org, the website of the Joint United Nations Programme for HIV/AIDS. This site gives recent overviews of the epidemic; reports from a specific area or country; information on the current global policy; and links to many programmes, organisations, resources, and events. The site also has a useful …
Picture Quiz: Circular shadows in the lung field
Authors: Pratyush Ranjan, R N Das
Journal: BMJ (2006)

A 43 year old farmer, a chronic smoker and an alcoholic, was admitted with blood tinged sputum, dry hacking cough, heaviness in the chest, and breathlessness for more than three years. He had no history of fever, night sweats, weight loss, or anorexia. Upon examination he had 5 cm, non-tender, smooth surfaced, enlarged liver and dullness in the right and left apical and mid-zone of both lungs. The base of the right side was also dull on percussion with bronchial breathing. After admission, all investigations, including haemogram, blood sugar, serum electrolytes, and liver and kidney functions were normal.





Fig 1 
The chest radiograph



Hydatid disease or echinococcosis is the general term for four diseases that are caused by the larval stage of the echinococcus tapeworm, the smallest in the Taeniidae family. It remains one of the most intractable and lethal helminthic diseases. Its distribution is not …
The Constant Gardener
Authors: Aula Abbara
Journal: BMJ (2006)

Despite its lacklustre title, this John le Carre adaptation is a beautifully shot exploration of the workings of big pharmaceutical companies. This is a multilayered film, part romance, part conspiracy theory, and part espionage from the director of City of God . It draws the audience in and leaves them in thoughtful appreciative silence when it ends.

The story is built around the relationship of Justin Quayle (Ralph Fiennes) and his wife Tessa (Rachel Weisz). The first scene is of the couple parting in Kenya, and this is followed soon after by a gruesome scene in which Quayle must identify his dead wife's charred body. Fiennes' mild mannered diplomat is complemented by Weisz's portrayal of Tessa as a fiery political activist whose passion leads her after Quayle to Nairobi. After her death, it becomes apparent that although he loved his wife, he never really knew her, and, paradoxically, he only comes closer to doing so after her death.

The cinematography is beautiful, with chaotic colourful scenes matched with tranquil African landscapes. The film carries a strong anticorporate antiestablishment message and, without preaching, it sends out its message clearly. All …
Stromal Support of Metabolic Function through Mitochondrial Transfer in Multiple Myeloma
Authors: Lawrence H. Boise, Mala Shanmugam
Journal: Cancer Research (2019)

Abstract Marlein and colleagues demonstrate in multiple myeloma, bone marrow stromal cells transfer mitochondria to myeloma cells to increase cellular respiration, resulting in increased proliferation. The intercellular transfer occurs through the formation of tunneling nanotubes that connect the myeloma cell to the stromal cell and is dependent on surface CD38 expression on myeloma cells. CD38 is an important therapeutic target in myeloma, therefore, regulation of myeloma metabolism may play a role in the activity of this therapeutic approach. The study reinforces the importance of intercellular interactions in the tumor microenvironment and sheds new light on the control of metabolism in myeloma. See related article by Marlein et al., p. 2285
Measuring lung function in airways diseases: current and emerging techniques
Authors: Nayia Petousi, Nick P Talbot, Ian Pavord, Peter A Robbins
Journal: Thorax (2019)

Chronic airways diseases, including asthma, COPD and cystic fibrosis, cause significant morbidity and mortality and are associated with high healthcare expenditure, in the UK and worldwide. For patients with these conditions, improvements in clinical outcomes are likely to depend on the application of precision medicine, that is, the matching of the right treatment to the right patient at the right time. In this context, the identification and targeting of ‘treatable traits’ is an important priority in airways disease, both to ensure the appropriate use of existing treatments and to facilitate the development of new disease-modifying therapy. This requires not only better understanding of airway pathophysiology but also an enhanced ability to make physiological measurements of disease activity and lung function and, if we are to impact on the natural history of these diseases, reliable measures in early disease. In this article, we outline some of the key challenges faced by the respiratory community in the management of airways diseases, including early diagnosis, disease stratification and monitoring of therapeutic response. In this context, we review the advantages and limitations of routine physiological measurements of respiratory function including spirometry, body plethysmography and diffusing capacity and discuss less widely used methods such as forced oscillometry, inert gas washout and the multiple inert gas elimination technique. Finally, we highlight emerging technologies including imaging methods such as quantitative CT and hyperpolarised gas MRI as well as quantification of lung inhomogeneity using precise in-airway gas analysis and mathematical modelling. These emerging techniques have the potential to enhance existing measures in the assessment of airways diseases, may be particularly valuable in early disease, and should facilitate the efforts to deliver precision respiratory medicine.
Film review: A Clockwork Orange
Authors: Rachel Hughes, Stephen Ford
Journal: BMJ (2000)

> “Art is dangerous. It is one of the attractions: when it ceases to be dangerous you don't want it.” 
> 
> Anthony Burgess
Burgess's thinking is most evident in his disturbing 1962 novel, drama. tised by the late Stanley Kubrick. Burgess crafted his extraordinary tale of teenage delinquency in the year that he anticipated his death from a brain tumour. (He actually died in 1993.) Inspired by his own experiences - his pregnant wife was attacked by four United States army deserters - and events of the time, such as the …
Surgeon defends decision to amputate healthy legs of patients
Authors: Clare Dyer
Journal: BMJ (2000)

A surgeon in Scotland amputated the legs of two psychologically disturbed men who had nothing physically wrong with them but felt a “desperate” need to be amputees, it emerged this week.

Both men, one from England and one from Germany, had a rare type of body dysmorphic disorder known as apotemnophilia, in which patients are convinced from childhood that they will be normal only once a limb has been removed. The obsession is always with the removal of a specific limb, and each patient had a leg amputated above the knee.

The operations were carried out in September …
Who needs medical students?
Authors: Itai Danovitch
Journal: BMJ (2001)

“bottom dwellers of the academic food chain”



One of the challenges for us as medical students making our way on to the wards is to determine our role. Our agenda is to learn. However, we face many different styles of teaching, and at one point or another we must endure the sensation of standing idly against the wall, looking on to a session of rounds with a mixture of genuine interest and selfconscious alienation. We find ourselves asking, “Do they know we are here?”

This first question leads naturally on to a second, “What difference does it make to anyone that we are here?” We are …
Patient Registries in Idiopathic Pulmonary Fibrosis
Authors: Daniel A. Culver, Jürgen Behr, John A. Belperio, Tamera J. Corte, Joao A. de Andrade, Kevin R. Flaherty, Mridu Gulati, Tristan J. Huie, Lisa H. Lancaster, Jesse Roman, Christopher J. Ryerson, Hyun J. Kim
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

Over the past decade, several large registries of patients with idiopathic pulmonary fibrosis (IPF) have been established. These registries are collecting a wealth of longitudinal data on thousands of patients with this rare disease. The data collected in these registries will be complementary to data collected in clinical trials because the patient populations studied in registries have a broader spectrum of disease severity and comorbidities and can be followed for a longer period of time. Maintaining the quality and completeness of registry databases presents administrative and resourcing challenges, but it is important to ensuring the robustness of the analyses. Data from patient registries have already helped improve understanding of the clinical characteristics of patients with IPF, the impact that the disease has on their quality of life and survival, and current practices in diagnosis and management. In the future, analyses of biospecimens linked to detailed patient profiles will provide the opportunity to identify biomarkers linked to disease progression, facilitating the development of precision medicine approaches for prognosis and therapy in patients with IPF.
Answering questions in clinical scenarios
Authors: Chris Yates
Journal: BMJ (2019)

Five tips for students starting placements One of the most common teaching encounters you will come across in medical school is the clinical scenario, or “viva.” These scenarios usually require you to present a clinical case you have seen and to answer questions that test your understanding of the differential diagnosis, investigation, and management of the case. A viva may take place ad hoc while on a ward attachment, or in small groups after clinical encounters with patients. As a medical student you will face questions from senior clinicians on topics with which you might not be familiar. No one knows all the answers. Senior clinicians are more interested in your ability to take a structured history, perform a thorough examination, formulate a differential diagnosis, and suggest appropriate investigations and management. Importantly, you need to demonstrate a safe approach, and seek appropriate help when you need it. Answering viva style questions in medical school helps you to develop the key abilities to become a competent junior doctor. Medical students might dread the stress of answering a question on the spot, especially if feeling the pressure to impress an examiner or senior colleague. The following five tips will not give you specific answers, but they will help you to structure and frame your answers in high stress situations.
ER:The Game
Authors: Amy Johnstone
Journal: BMJ (2006)

It's 3 am; only two hours of your shift to go and you need to treat five cardiology patients, capture an escaped ninja, and simultaneously maintain your hygiene, composure, and energy. Do you think you could do it? Well, now you can prove your skills in ER: The Game . Test your intern skills while walking through the halls of the infamous Chicago hospital. Fans will be pleased that Carter, Lewis, and Pratt, characters from the well known television series, have lent their voices to the script.



The game is based around you, the intern, …
The Scientific Basis for Health Care
Authors: Victoria K Reeves
Journal: BMJ (1999)

I selected this book on the basis of its title, expecting a diatribe on the dangers of modern health care. What I encountered was the exact opposite: a splendidly written summary of the foundations of health care at the turn of the millennium.

The book covers a vast quantity of information yet presents it in a readable form. It is divided into sections on cell biology, pharmacology, microbiology, immunology, and pathology. Each section contains chapters covering broad topics of medical practice, such as pharmacokinetics, …
Sham surgery may put patients at risk
Authors: Muhunthan Thillai
Journal: BMJ (2000)

Researchers in the United States have sparked off debate by using a controversial form of placebo surgery during clinical trials for patients suffering from Parkinson's disease.

Investigators at the University of South Florida are using “sham surgery” to test the efficacy of implanting fetal brain cells into patients with severe Parkinson's disease. They hope that direct injection of embryonic dopaminergic neurones into the brain will help patients regain motor function in their limbs.

Researchers at the university want to show that any benefits are a result of the treatment and not …
Family support decreases suicide risk
Authors: Negin Shamsian
Journal: BMJ (2001)

Adolescents and teenagers are much less likely to attempt suicide if they have a sense of “connectedness” to parents, family, or other adults, report researchers in a study in Pediatrics (2000;107:485-93).

The study showed that perceived family closeness protected against suicide attempts among black, Hispanic, and white girls and boys. Risk factors included previous suicide attempts, violence victimisation, violence perpetration, alcohol use, marijuana use, and school problems. …
Indian scientists find flatulence cure for bean eaters
Authors: Samena Chaudhry
Journal: BMJ (2002)

Irradiation could reduce the flatulence caused by eating beans. Scientists at the food science laboratory at the Bhabha Atomic Research Centre, Trombay, India, used standard food irradiation technology and discovered that zapping beans reduces the chemicals which cause flatulence.

The researchers tested mung beans, chickpeas, black eyed beans, and red kidney beans. Some samples …
From Malaga to London
Authors: Tiago Villanueva
Journal: BMJ (2006)

<b>Sara Carrillo de Albornoz</b> interrupted her medical studies in her home city in Spain to spend some time in the United Kingdom. What was supposed to be a gap year ended up as six years filled with an eclectic range of study, work, and life experiences. <b>Tiago Villanueva</b> finds out how it all happened
Abstract 18873: Exercise Time in Target Heart Rate Zone and Perceived Benefits and Barriers Mediate the Relationship Between Depressed Mood and Functional Status in Patients Following Cardiac Rehabilitation
Authors: Kelly L Wierenga, Shirley M Moore
Journal: Circulation (2017)

Cardiac rehabilitation improves functional status for patients overall, but debilitating depressive symptoms can undermine efforts. The transience of depressive symptoms makes it difficult for practitioners to identify this modifiable risk factor known to contribute to diminished functional capacity. It is unknown if additional factors may help to explain why some patients with depressive symptoms achieve greater functional capacity (6MWT) than others. We sought to determine: 1) if depressive symptoms at any time in the 12 months following completion of cardiac rehabilitation negatively impact functional status and; 2) if additional factors (exercise, perceived benefits and barriers, self-efficacy, social support, and comorbidity) mediate this relationship. Patients enrolled in a RCT completed measures of depressed mood, perceived benefits and barriers to exercise, exercise self-efficacy, social support, and functional ability (6MWT) at four points of the year following cardiac rehabilitation. Exercise wa...
Abstract 13039: Prostaglandin E1 Facilitates 5-HT4 Serotonergic and Beta-adrenergic Receptor Mediated Inotropic Effects in Failing Human Heart
Authors: Jon Riise, Oivind Orstavik, Eirik Qvigstad, Christen P Dahl, Jan-Bjorn Osnes, Tor Skomedal, Finn O Levy, Kurt A Krobert
Journal: Circulation (2011)

Introduction and hypothesis: Prostaglandins have displayed both beneficial and detrimental effects in clinical studies in patients with severe heart failure. Prostaglandins are known to increase ca...
Understanding personality type: What do type dynamics tell us about life stages and stress reactions?
Authors: Anita Houghton
Journal: BMJ (2005)

In the seventh article of her series, Anita Houghton explains how preferences interact and develop over time In the first article of this series it was claimed that the beauty of psychological type is that it provides a simple framework to describe ways in which people differ, while allowing room for great depth and complexity within it. In this article we start to explore the complexity that is type dynamics. The dynamic nature of type means that for each type there is a hierarchy of preferences and these develop at different stages of our lives. Type dynamics are also important in understanding how different types respond to stress. The two central letters of a type denote the functions—for example, S and T are the functions of the type ESTJ. One of these functions is dominant (in bold), and operates in either the extravert or the introvert mode, depending on that type's preference,1 and the other letter denotes the second, auxiliary function. If the dominant function is extraverted, the auxiliary function will be introverted, and vice versa, thus providing balance and support for the dominant. In the type ESTJ, the dominant function is extraverted T, whereas the auxiliary is introverted S. There is then a tertiary function, which is the opposite of the auxiliary function (so if the auxiliary function is sensing, the tertiary function will be intuition), and finally, there is an inferior function, which is the opposite of the dominant function (see box 1 for example). ### Box 1: Example of type dynamics—ESTJ #### Dominant function Extraverted thinking - What this type does best #### Auxilliary function Introverted sensing … RETURN TO TEXT
“n01se: transforming sensation” at the Wellcome Trust's Two 01 Gallery
Authors: Sripurna Basu
Journal: BMJ (2000)

The self consciously 21st century title of this exhibition puts it into that bracket of corporate sponsored contemporary art occupied by Saatchi's proteges and the contents of London's Millennium Dome. The blurb contained abstruse phrases alluding to the “sounds of colours and the shape of taste.” What's more, it promised to connect art and science. Few exhibitions have managed to meld what is essentially art with the essence of science without …