tbuckley/cabot-search huggingface dataset:
In sickness and in hangover: pitfalls in choosing a clinical partner
Authors: Donald Asprey
Journal: BMJ (2010)

“Do you take this medical student to be your clinical partner, to respect and cherish from this day forward, for better for worse, for smarter for dumber, in sickness and in hangover, till graduation do you part?”

In UK medical schools at the beginning of clinical rotations students partner up to be attached to the same consultants during each block and attend the same clinics and ward rounds. Students in each pair act as study partners and chaperones when examining patients.

Alas this year a record number of medical student partnerships at Warwick have sued for divorce half way through our clinical rotations, with 50 students out of 186 choosing to break their vows, …
Pulsed Field Ablation for Pulmonary Vein Isolation in Atrial Fibrillation
Authors: Vivek Y. Reddy, Petr Neuzil, Jacob S. Koruth, Jan Petru, Moritoshi Funosako, Hubert Cochet, Lucie Sediva, Milan Chovanec, Srinivas R. Dukkipati, Pierre Jais
Journal: Journal of the American College of Cardiology (2019)

Catheter ablation of atrial fibrillation using thermal energies such as radiofrequency or cryothermy is associated with indiscriminate tissue destruction. During pulsed field ablation (PFA), subsecond electric fields create microscopic pores in cell membranes-a process called electroporation. Among cell types, cardiomyocytes have among the lowest thresholds to these fields, potentially permitting preferential myocardial ablation.The purpose of these 2 trials was to determine whether PFA allows durable pulmonary vein (PV) isolation without damage to collateral structures.Two trials were conducted to assess the safety and effectiveness of catheter-based PFA in paroxysmal atrial fibrillation. Ablation was performed using proprietary bipolar PFA waveforms: either monophasic with general anesthesia and paralytics to minimize muscle contraction, or biphasic with sedation because there was minimal muscular stimulation. No esophageal protection strategy was used. Invasive electrophysiological mapping was repeated after 3 months to assess the durability of PV isolation.In 81 patients, all PVs were acutely isolated by monophasic (n = 15) or biphasic (n = 66) PFA with ≤3 min elapsed delivery/patient, skin-to-skin procedure time of 92.2 ± 27.4 min, and fluoroscopy time of 13.1 ± 7.6 min. With successive waveform refinement, durability at 3 months improved from 18% to 100% of patients with all PVs isolated. Beyond 1 procedure-related pericardial tamponade, there were no additional primary adverse events over the 120-day median follow-up, including: stroke, phrenic nerve injury, PV stenosis, and esophageal injury. The 12-month Kaplan-Meier estimate of freedom from arrhythmia was 87.4 ± 5.6%.In first-in-human trials, PFA preferentially affected myocardial tissue, allowing facile ultra-rapid PV isolation with excellent durability and chronic safety. (IMPULSE: A Safety and Feasibility Study of the IOWA Approach Endocardial Ablation System to Treat Atrial Fibrillation; NCT03700385; and PEFCAT: A Safety and Feasibility Study of the FARAPULSE Endocardial Ablation System to Treat Paroxysmal Atrial Fibrillation; NCT03714178).
Longitude Prize—What is the greatest scientific challenge of our time?
Authors: Rhys Davies
Journal: BMJ (2014)

On 19 May the Longitude Prize 2014 was launched at the BBC’s New Broadcasting House, London. Funded by Nesta, a charity dedicated to innovation, the prize offers a £10m (€12m; $17m) reward for solving the greatest scientific challenge of our time. The focus of the challenge is to be decided by public vote and the polls are open until 25 June.

Six shortlisted challenges cover a range …
Abstract P6-10-01: Consumption of sugar-containing beverages and cancer risk: Results from the NutriNet-Santé prospective cohort
Authors: E Chazelas, B Srour, E Desmetz, E Kesse-Guyot, C Julia, N Druesne-Pecollo, P Galan, L Zelek, S Hercberg, P Latino-Martel, M Deschasaux, M Touvier
Journal: Cancer Research (2019)

Abstract OBJECTIVE To assess the associations between the consumption of sugar-containing and artificially sweetened beverages and cancer risk. DESIGN Population based prospective cohort study. SETTING AND PARTICIPANTS Overall, 101 257 participants aged ≥18y (mean age: 42.2±14.4y) from the French NutriNet-Santé cohort (2009-2017) were included. Consumptions of sugar-containing and artificially sweetened beverages were assessed using repeated 24h-dietary records, designed to register participants' usual consumption for 3300 different food and beverage items. MAIN OUTCOME MEASURES Associations between beverage consumption and overall, breast, prostate and colorectal cancer risk were assessed by multivariable Cox Proportional Hazard models adjusted for known risk factors. RESULTS A 100mL increase in the consumption of sugar-containing beverages was significantly associated with an increased risk of overall cancer (HR=1.08, 95% confidence interval 1.04 to 1.12, P&amp;lt;.0001) and breast cancer (HR=1.11, 95% confidence interval 1.04 to 1.19, P&amp;lt;0.002). The consumption of artificially sweetened beverages was not associated with cancer risk. In sub-analyses, a 100 mL increase in the consumption of 100% fruit juice was significantly associated with an increased risk of overall cancers (HR=1.08, 95% confidence interval 1.02 to 1.15, P=0.01). These associations were strongly mediated by the sugar contained in these beverages. In contrast, weight gain during follow-up did not appear as a strong mediator. Besides, results were similar in overweight and non-overweight participants. CONCLUSIONS In this large prospective study, a 100mL increase in the consumption of sugar-containing beverages in the diet was associated with an 8% significant increase in overall cancer risk and an 11% significant increase in breast cancer risk. 100% fruit juices were also associated with an 8% increased risk of overall cancers. Given the massive consumption of sugar-containing beverages in Western countries, these results suggest that they may represent a key modifiable risk factor for cancer prevention. Citation Format: Chazelas E, Srour B, Desmetz E, Kesse-Guyot E, Julia C, Druesne-Pecollo N, Galan P, Zelek L, Hercberg S, Latino-Martel P, Deschasaux M, Touvier M. Consumption of sugar-containing beverages and cancer risk: Results from the NutriNet-Santé prospective cohort [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-10-01.
Living with . . . congenital heart block from birth
Authors: Anna Sayburn
Journal: BMJ (2015)

#### Biography

Liza Morton, from Falkirk, Scotland, is a chartered counselling psychologist and a voluntary campaign manager for the Somerville Foundation, which supports young people and adults born with a heart condition. Liza has congenital heart block and has needed a heart pacemaker since birth. She has one son, who is nine years old.

I was born with complete heart block so I’m completely dependent on a cardiac pacemaker. When I was born I quickly went into congestive heart failure and was fitted with an internal pacemaker. In 1978 this was very experimental, and at 11 days old I was the youngest person in the world at the time to be fitted with one.

Growing up I was quite a poorly child. I was in and out of hospital all the time. Although the doctors said I should be able to function normally, I couldn’t exert myself because the early pacemakers were set at a fixed rate regardless of what I did.

Hospital was as familiar to me as school or home. My cardiologist and his team were like family to me.

By the time I was seven I’d had heart surgery five times. I also had a hole in the heart, an atrial septal defect, corrected by open heart surgery when I was 12. It has been relentless. My first variable rate pacemaker was fitted when I was 12, which helped me …
Inflammatory bowel disease and Parkinson’s disease
Authors: Elsebeth Lynge, Maria Skaalum Petersen, Søren Nymand Lophaven
Journal: Gut (2019)

We read with interest the study by Villumsen et al on the risk of Parkinson’s disease (PD) in patients with IBD.1 This study took advantage of the long series of nation-wide data from 1977 to 2014 in the Danish Population and Patient Registers. For each person ever living in Denmark during this period, the register data include dates of birth, immigration, emigration, death, diagnosis with IBD and diagnosis with PD. This allows for a cohort design with accumulation of person-years and …
Immune-enrichment of non-small cell lung cancer baseline biopsies for multiplex profiling define prognostic immune checkpoint combinations for patient stratification
Authors: Anne Monette, Derek Bergeron, Amira Ben Amor, Liliane Meunier, Christine Caron, Anne-Marie Mes-Masson, Nidhameddine Kchir, Kamel Hamzaoui, Igor Jurisica, Réjean Lapointe
Journal: Journal for ImmunoTherapy of Cancer (2019)

Permanence of front-line management of lung cancer by immunotherapies requires predictive companion diagnostics identifying immune-checkpoints at baseline, challenged by the size and heterogeneity of biopsy specimens. An innovative, tumor heterogeneity reducing, immune-enriched tissue microarray was constructed from baseline biopsies, and multiplex immunofluorescence was used to profile 25 immune-checkpoints and immune-antigens. Multiple immune-checkpoints were ranked, correlated with antigen presenting and cytotoxic effector lymphocyte activity, and were reduced with advancing disease. Immune-checkpoint combinations on TILs were associated with a marked survival advantage. Conserved combinations validated on more than 11,000 lung, breast, gastric and ovarian cancer patients demonstrate the feasibility of pan-cancer companion diagnostics. In this hypothesis-generating study, deepening our understanding of immune-checkpoint biology, comprehensive protein-protein interaction and pathway mapping revealed that redundant immune-checkpoint interactors associate with positive outcomes, providing new avenues for the deciphering of molecular mechanisms behind effects of immunotherapeutic agents targeting immune-checkpoints analyzed.
US obtains first criminal conviction of a pharma CEO over opioid doctor kickbacks
Authors: Owen Dyer
Journal: BMJ (2019)

The leadership of a pharmaceutical company is facing prison for the first time in US history, following the conviction of Insys Therapeutics’ billionaire founder and four senior executives on racketeering and kickback charges.

The decision by a federal jury in a Boston court also represents a milestone in the government’s battle against the opioid epidemic. Four of the five defendants, including Insys founder John Kapoor, were found guilty of illegal distribution of a controlled substance.

The executives were convicted of masterminding and executing a scheme in which the company paid doctors to prescribe its flagship product Subsys, a fentanyl sublingual spray, for a wide range of claimed pain conditions, although it …
Alcohol use: global target to reduce harm is likely to be missed as intake rises
Authors: Elisabeth Mahase
Journal: BMJ (2019)

The World Health Organization’s target to cut the harmful use of alcohol by 10% by 2025 is unlikely to be met, researchers have warned, after finding that the total volume consumed worldwide each year increased by 70% from 1990 to 2017.1

Alcohol intake rose by 0.6 L of pure alcohol per adult per year over that period (up from 5.9 L to 6.5 L), and this is predicted to rise by a further 1.1 L to reach 7.6 L by 2030, in a study reported in the Lancet . Although alcohol consumption in the UK dropped from 12.3 L in 2010 to 11.4 L in 2017, other countries saw increases.

Consumption rose by 34% …
Abstract P4-10-16: Neoadjuvant chemotherapy infusion in the arm ipsilateral to breast cancer increases the risk of lymphedema
Authors: A Bergmann, MA Bello, LC Thuker, MF Andrade, JI Bevilacqua
Journal: Cancer Research (2019)

Abstract Background: Neoadjuvant chemotherapy (NAC) has been administered to clinically axillary positive breast cancer (BC) patients. Current guidelines still recommend axillary lymphadenectomy (AL) in patients with persistent positive axillary lymph node disease. We aimed to evaluate the association of NAC and/or adjuvant chemotherapy (CT) infusion in the ipsilateral upper limb (IA) with AL and the occurrence of lymphedema (LE) secondary to BC treatment. Methods: A prospective cohort study of 683 women subjected to AL and treated with NAC and/or adjuvant CT for BC. The patients were evaluated before treatment, immediate and every 6 months after surgery. Cumulative incidence and population attributable risks of LE were calculated. Results: 8-year cumulative incidence of LE was 33.1%. NAC and CT infusion and infusion of &amp;gt;2 cycles into the IA respectively increased by 1.68, 1.67 and 1.78 times the risk of LE respectively (all P&amp;lt;0.01). LE could be avoided in 9.4% of cases if the CT infusion had not been administered in the IA. Conclusions: 33.1% of women developed LE. The risk of LE was increased among women who received CT in the IA. Avoidance of NAC or adjuvant CT in the IA could prevent 9% of the LE cases observed in this population. Citation Format: Bergmann A, Bello MA, Thuker LC, Andrade MF, Bevilacqua JI. Neoadjuvant chemotherapy infusion in the arm ipsilateral to breast cancer increases the risk of lymphedema [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-10-16.
Abstract P4-12-01: Not presented
Authors: G Werutsky, C Villareal-Garza, HG Moreno, AA Cartagena, S Campos-Gomez, RO Reyes, JJ Lence, P Liedke, T Reinert, M Binotto, V Dybal, J Martinez-Mesa, RD Freitas, PR Nunes Filho, F Zaffaroni, CH Barrios
Journal: Cancer Research (2019)

Abstract This abstract was not presented at the conference. Citation Format: Werutsky G, Villareal-Garza C, Moreno HG, Cartagena AA, Campos-Gomez S, Reyes RO, Lence JJ, Liedke P, Reinert T, Binotto M, Dybal V, Martinez-Mesa J, Freitas RD, Nunes Filho PR, Zaffaroni F, Barrios CH. Not presented [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-12-01.
Abstract P6-17-18: Pathologic complete response (pCR) in locally advanced HER2+ (HER2+) breast cancer (BC) treated with anthracycline-free neoadjuvant therapy
Authors: G Somlo, J Waisman, Y Yuan, L Kruper, P Frankel, V Jones, T Lusi, D Schmolze, J Yim, A Hurria, J Mortimer
Journal: Cancer Research (2019)

Abstract Background: Response to neoadjuvant therapy is a predictor of progression-free and overall survival in HER2+. To decrease treatment associated toxicities in patients with HER2+ breast cancers we utilized a non-anthracycline regimen with pertuzumab (pert), trastuzumab (trast), and nab-paclitaxel (nab). Pre- neoadjuvant therapy biopsies were procured to evaluated possible biological predictors of pathologic complete response (pCR). Methods: Women with locally advanced HER2 positive breast cancers were recruited from our breast cancer clinics. After obtaining informed consent for this IRB-approved trial, patients were treated with 6 cycles of pertuzumab (day 1 every 21 days [d]), and weekly trastuzumab 2 mg/kg with and nab-paclitaxel 100 mg/m2. Formalin fixed paraffin embedded (FFPE) or frozen biopsies pre-NT and post-NT were collected, along with blood samples at pre-treatment, and at the end of study for correlative analysis. Results: Accrual is complete, with 42 of the 45 HER2+ patients assessed for pCR rate (3 too early to evaluate). The median age was 54 yrs (range 31-77 years). 12 patients were stage 3, 26 stage 2, and 1 stage 1 patient. The pCR rate was 64.2% (27/42), with 73.7% (14/19) in ER/PR negative patients and 56.5% (13/23) in ER/PR positive patients. The initial primary tumor size was similar for in those who achieved pCR and non-pCR patients (mean 4.1 cm vs 3.2 cm, respectively). Most patients required dose modifications. Grade 3 AEs reported included 6 patients with hypertension, 3 patients with hematological AEs, 3 patients with elevated LFTs, and 2 patients with diarrhea. Conclusions: This anthracycline-free regimen in HER2+ BC can achieve promising pCR response rates, with toxicities well-managed with dose modifications. Results of correlative analysis will be presented. Citation Format: Somlo G, Waisman J, Yuan Y, Kruper L, Frankel P, Jones V, Lusi T, Schmolze D, Yim J, Hurria A, Mortimer J. Pathologic complete response (pCR) in locally advanced HER2+ (HER2+) breast cancer (BC) treated with anthracycline-free neoadjuvant therapy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-17-18.
Targeted AAVP-based therapy in a mouse model of human glioblastoma: a comparison of cytotoxic versus suicide gene delivery strategies
Authors: Fernanda I Staquicini, Fenny Hui Fen Tang, Tracey L Smith, Juri G Gelovani, Ricardo José Giordano, Steven K Libutti, Richard L Sidman, Webster K Cavenee, Wadih Arap, Renata Pasqualini
Journal: Molecular Therapy (2019)
Abstract P6-18-27: Withdrawn
Authors: D Odom, D Mitra, K Hollis, D Richardson, JA Kaye, L McRoy
Journal: Cancer Research (2019)

Abstract This abstract was withdrawn by the authors. Citation Format: Odom D, Mitra D, Hollis K, Richardson D, Kaye JA, McRoy L. Withdrawn [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-18-27.
A ward round for patients
Authors: Benjamin Gillam
Journal: BMJ (2010)

Although turning a ward round into a fast paced quiz is common among competitive doctors and students, medicine was no longer the only subject on offer. My firm consultant posed questions that I did not expect at a patient’s bedside at 9 am, but answers were expected anyway. Luckily I had seen the news that morning.

“Well?” he repeated in frustration to the four fresh faces desperately trying to formulate a plausible suggestion. “Who is the president of Europe in waiting?” My colleagues fell silent while I responded confidently. Visibly appalled, our senior’s voice echoed around …
Alevin efficiently estimates accurate gene abundances from dscRNA-seq data
Authors: Avi Srivastava, Laraib Malik, Tom Smith, Ian Sudbery, Rob Patro
Journal: Genome biology (2019)

We introduce alevin, a fast end-to-end pipeline to process droplet-based single-cell RNA sequencing data, performing cell barcode detection, read mapping, unique molecular identifier (UMI) deduplication, gene count estimation, and cell barcode whitelisting. Alevin's approach to UMI deduplication considers transcript-level constraints on the molecules from which UMIs may have arisen and accounts for both gene-unique reads and reads that multimap between genes. This addresses the inherent bias in existing tools which discard gene-ambiguous reads and improves the accuracy of gene abundance estimates. Alevin is considerably faster, typically eight times, than existing gene quantification approaches, while also using less memory.
A woman with central chest pain
Authors: Ruairidh Nicoll, Brian O’Rourke
Journal: BMJ (2013)

A 78 year old woman presented to her local hospital with a 90 minute history of severe chest pain, scoring 7/10 in severity, which had started at 9 am that morning. It was central, did not radiate, felt like “indigestion,” and was associated with shortness of breath. She had experienced similar, though milder, pain starting the previous afternoon during an intense argument. She had a history of lumbar spinal stenosis but was otherwise well. She took no regular drugs and had no known allergies. In terms of cardiovascular risk factors she was a current smoker with a 60 pack-year smoking history but she denied any history of hypertension, hyperlipidaemia, diabetes, or a family history of ischaemic heart disease. She cared for her middle aged daughter with Down’s syndrome who lived with her at home. Observations showed she was alert (Glasgow coma scale score 15/15) and afebrile (37.1°C) with a respiratory rate of 14 per minute; SpO2 98% on air; heart rate 90 beats per minute; and blood pressure 183/98 mm Hg. She denied any precordial tenderness, and examination of her respiratory, cardiovascular, and gastrointestinal systems was unremarkable. An electrocardiogram was recorded (fig 1⇓).
Ready, steady, go audience
Authors: Helen Macdonald
Journal: BMJ (2012)

Sir Roger Bannister was not always a knight. In 1954, when he smashed the world record by running a mile in under four minutes, he was a 25 year old medical student studying at St Mary’s Hospital in London. Medical students may take a navel gazing interest in the story of a record smashed by one of their own kind, but Bannister’s mile is a great story for other reasons.

Bannister’s is a story of a scientist. “Here was a heart. Here were muscles. Here were lungs.” He challenged his anatomy and physiology to a self experiment. The research question: “To what extent can this bit of machinery be trained to do a very specific, skilled task?” In the 1950s the sub-four minute mile was thought impossible. Four was …
Abstract 17348: Preconditioning Effect of Obstructive Sleep Apnea on In-Hospital Survival Outcomes After Acute Myocardial Infarction is Lost in the Older-Elderly
Authors: Amina Adil, Rafath Ullah, Vaibhav Gupta, Tadele W Mengesha, Sulaiman Sultan, M. Fuad Jan, Khawaja Afzal Ammar, Suhail Q. Allaqaband, Paul H Werner, Tanvir Bajwa, A. Jamil Tajik, Arshad Jahangir
Journal: Circulation (2017)

Background: Patients with obstructive sleep apnea (OSA) were shown to have better survival outcome compared to matched non-OSA patients suggesting OSA to be an ischemic preconditioning (IPC) equiva...
Limited Evolutionary Conservation of the Phenotypic Effects of Antibiotic Resistance Mutations
Authors: Gábor Apjok, Gábor Boross, Ákos Nyerges, Gergely Fekete, Viktória Lázár, Balázs Papp, Csaba Pál, Bálint Csörgő
Journal: Molecular Biology and Evolution (2019)

Multidrug-resistant clinical isolates are common in certain pathogens, but rare in others. This pattern may be due to the fact that mutations shaping resistance have species-specific effects. To investigate this issue, we transferred a range of resistance-conferring mutations and a full resistance gene into Escherichia coli and closely related bacteria. We found that resistance mutations in one bacterial species frequently provide no resistance, in fact even yielding drug hypersensitivity in close relatives. In depth analysis of a key gene involved in aminoglycoside resistance (trkH) indicated that preexisting mutations in other genes-intergenic epistasis-underlie such extreme differences in mutational effects between species. Finally, reconstruction of adaptive landscapes under multiple antibiotic stresses revealed that mutations frequently provide multidrug resistance or elevated drug susceptibility (i.e., collateral sensitivity) only with certain combinations of other resistance mutations. We conclude that resistance and collateral sensitivity are contingent upon the genetic makeup of the bacterial population, and such contingency could shape the long-term fate of resistant bacteria. These results underlie the importance of species-specific treatment strategies.