tbuckley/cabot-search huggingface dataset:
Emergency and trauma imaging course for trainees
Authors: Muhammad Imran Ul Haq
Journal: BMJ (2009)

The emergency and trauma imaging course emphasises the multifaceted aspects and modern protocols of emergency radiology and aims to fill the vital knowledge gap among trainees, fellows, and junior radiologists. The course concentrates on ultrasound, computed tomography, and emergent vascular and non-vascular interventions, with examples from real time cases displayed on an interactive knowledge sharing platform. Developing an understanding of the basic principles behind different radiological modalities is one of the main focuses of the course. In addition, the course also covers the protocols and policies of the radiology department. The course is held in spring every year by the Radiology Academy at Leeds General Infirmary.

The course is aimed at all trainees who deal with radiology, which means that every trainee should attend this course to gain grass roots knowledge about the rapidly evolving field of radiology. Most of the participants were specialty trainees in radiology from all over the United Kingdom, whereas some participants were radiographers and specialist trainees working in different specialties.

I had completed rotations in surgical specialties and had developed a reasonable understanding of …
Saracatinib impairs maintenance of human T-ALL by targeting the LCK tyrosine kinase in cells displaying high level of lipid rafts
Authors: Anne Buffière, Théo Accogli, Laetitia Saint-Paul, Géraldine Lucchi, Benjamin Uzan, Paola Ballerini, Jean-Noël Bastie, Laurent Delva, Françoise Pflumio, Ronan Quéré
Journal: Leukemia (2018)
SAMD9 and SAMD9L in inherited predisposition to ataxia, pancytopenia, and myeloid malignancies
Authors: Josef Davidsson, Andreas Puschmann, Ulf Tedgård, David Bryder, Lars Nilsson, Jörg Cammenga
Journal: Leukemia (2018)

Germline mutations in the SAMD9 and SAMD9L genes, located in tandem on chromosome 7, are associated with a clinical spectrum of disorders including the MIRAGE syndrome, ataxia–pancytopenia syndrome and myelodysplasia and leukemia syndrome with monosomy 7 syndrome. Germline gain-of-function mutations increase SAMD9 or SAMD9L’s normal antiproliferative effect. This causes pancytopenia and generally restricted growth and/or specific organ hypoplasia in non-hematopoietic tissues. In blood cells, additional somatic aberrations that reverse the germline mutation’s effect, and give rise to the clonal expansion of cells with reduced or no antiproliferative effect of SAMD9 or SAMD9L include complete or partial chromosome 7 loss or loss-of-function mutations in SAMD9 or SAMD9L. Furthermore, the complete or partial loss of chromosome 7q may cause myelodysplastic syndrome in these patients. SAMD9 mutations appear to associate with a more severe disease phenotype, including intrauterine growth restriction, developmental delay and hypoplasia of adrenal glands, testes, ovaries or thymus, and most reported patients died in infancy or early childhood due to infections, anemia and/or hemorrhages. SAMD9L mutations have been reported in a few families with balance problems and nystagmus due to cerebellar atrophy, and may lead to similar hematological disease as seen in SAMD9 mutation carriers, from early childhood to adult years. We review the clinical features of these syndromes, discuss the underlying biology, and interpret the genetic findings in some of the affected family members. We provide expert-based recommendations regarding diagnosis, follow-up, and treatment of mutation carriers.
A present from Delhi⇓
Authors: Nicola Sharp
Journal: BMJ (2004)

“I bought you a present,” said Hubert.

“I'm too busy to be bothered with presents,” said Martha.

“What's the matter?” asked Hubert.

“Douglas is unemployed. He says he doesn't want to be a doctor any more.”

“I might be able to help,” said Hubert. “But why don't you open your present first?”

“It's over between us,” said Martha. “You went to India.”

“Where I spent hours choosing you a present.” Hubert passed Martha a package wrapped in pink tissue paper.

“Beware of the Greeks,” said Martha.

“I'll open it for you.” Hubert tore off the tissue paper and a swathe of gold cloth fell to the floor.

“What would I want with that?” asked Martha.

“It's a sari. It will look wonderful with your hair.” Hubert held it out to Martha.

Martha took it, then dropped it. “It is the colour of urine,” she said.

“I didn't think of that.”

“But you thought about me while you were in Delhi?”

“I hate curry. I thought of nothing but you.”

“You shouldn't have been thinking about me.”

“I did some work as well.”

“You shouldn't have been working, either. You were on holiday with your wife.” Martha marched off.

“I wasn't on …
Contribution of microRNA-200b-3p to radiation therapy resistance in 22RV1 prostate cancer cells.
Authors: John Thoms, Satoko Aoki, Lourdes Pena Castillo
Journal: Journal of Clinical Oncology (2018)

89 Background: Radiation therapy (RT) is a standard treatment option for men with localized prostate cancer. Despite having well-established treatment regimens, such men still fail RT at a rate of up to 30-50%. RT resistant phenotype is a key component leading to treatment failure. MicroRNAs (miRNAs) can influence the response to RT, and the abundance or lack of certain miRNAs can induce a RT resistant phenotype through alteration of survival pathways. We show that altered expression of miR-200b-3p plays an important role in contributing to RT resistance. Methods: RT resistant subline from the parental 22RV1 prostate cancer cell line was generated by exposure to fractionated RT – 22RV1-RT. The global expression level of miRNAs and mRNA was determined, using the Affymetrix GeneChip®: miRNA 4.0 and Human Gene 2.0 ST Arrays. Parental and 22RV1-RT cells were transfected with miR-200b-3p mimics or negative control. The influence of miR-200b-3p on cellular proliferation, morphology, migration, clonogenic survival and response to RT was determined by standard assays. Results: MiR-200b-3p was the only miRNA that was statistically differentially expressed between the two cell lines. There were 39 differentially expressed genes. Of the 65 genes predicted to be regulated by miR-200b-3p as identified from miRTarBase, only Fibronectin 1 (FN1) was in common. FN1 was up-regulated in 22RV1- RT cells. MiR-200b-3p mimics; in comparison to negative control mimics, suppressed cell proliferation in both cell lines. Both cell lines with negative control mimics have fibroblastic-type morphology and display a stretched shape following RT. While, cells transfected with miR-200b-3p mimics demonstrated a round morphology and formed clusters following RT. Over-expression of miR-200b-3p mimics inhibited cell migration synergically with RT and demonstrated a lower degree of clonogenic survival following RT in 22RV1-RT cells compared to negative control mimics. Surprisingly, miR-200b-3p mimics reversed the observed RT resistance and the sensitivity to RT was to the same degree as the parental 22RV1 cells. Conclusions: Together, these data suggest that miR-200b-3p independently contributes to RT resistance in 22RV1 prostate cancer cells.
CAVITATION PHENOMENON CREATING BUBBLES AND THEIR EXPLOSION IN THE CORONARY ARTERIES CAUSED DAMAGE TO THE ENDOTHELIUM AND START THE ATHEROSLEROTIC PROCESS
Authors: Thach N. Nguyen, Nhan Minh Tri Nguyen, Vien Thanh Truong, Viet Minh Vo, Gianluca Rigatelli
Journal: Journal of the American College of Cardiology (2018)
Liver-directed therapy (LDT) for metastatic renal cell carcinoma (mRCC): Single center experience.
Authors: Ruben Raychaudhuri, Kathryn A. Bylow, William Lea, John Byun, Timothy Zellmer, John D. Burfeind, Matthew John Riese, Deepak Kilari
Journal: Journal of Clinical Oncology (2018)

681 Background: Liver metastases arising from RCC are common and signify a poor prognosis. Given the negative impact of liver metastases on overall survival (OS) and quality of life, it is reasonable to to consider therapies directly targeting these lesions in select patients. Little is known about how minimally invasive LDT affects outcomes in patients with mRCC. Methods: Nine patients with mRCC underwent LDT for liver-dominant or liver-only metastatic disease between 2005 and 2015. Retrospective chart review was performed under an IRB protocol to identify patient and disease characteristics, imaging response, and time to next systemic treatment, OS and toxicities. Patients were seen in clinic at one month post-LDT to monitor for toxicities. Imaging was obtained within 2 months prior to treatment and at 3 and 6 months following LDT. Results: Each patient underwent a median of 2.3 procedures. A total of 18 transarterial chemoembolizations (TACE) and 5 yttrium-90 radioembolizations were performed. 2 patients had metastatic disease confined to the liver, and 7 had liver-dominant disease. 7 had multifocal disease involving &lt; 25% of the liver, and 2 had multifocal disease involving &gt; 25% of the liver. 8/9 patients received prior systemic therapies, receiving a median of 3 (0-4) distinct treatments. 4/9 patients were undergoing systemic therapy at the time of LDT, 1 patient declined further treatment, and the median time to initiation of the next systemic therapy in the remaining patients was 3 months (range 2-4 months). Median OS from first line systemic therapy was 39 months, 95% CI [25.9-53.3], and the median OS from the first LDT was 22 months (from 5-45 months). Follow-up imaging post-LDT showed PR or SD in 88% of cases at 3 months and 44% of cases at 6 months. At one month post-procedure, 8/9 patients maintained performance status, and only one patient experienced CTCAE grade 3-4 toxicity. Conclusions: The median OS in RCC patients with liver disease and systemic therapy alone is 14.3 months. The improved median OS of 39 months with LDT in our unmatched and heavily pretreated cohort suggests a role for LDT. LDT is generally well tolerated and should be considered for patients with liver-dominant mRCC with good performance status.
EVALUATION OF GLOBAL AND REGIONAL RIGHT VENTRICULAR FUNCTION USING THREE DIMENSIONAL SPECKLE TRACKING ECHOCARDIOGRAPHY SPECIALIZED FOR RIGHT VENTRICLE
Authors: Konomi Sakata, Yoichiro Uesugi, Aoi Isaka, Junnosuke Ito, Toshinori Minamishima, Mitsufumi Furuya, Touru Satoh, Hideaki Yoshino
Journal: Journal of the American College of Cardiology (2018)
Post-Exercise Oxygen Uptake Recovery Delay
Authors: Cole S. Bailey, Luke T. Wooster, Mary Buswell, Sarvagna Patel, Paul P. Pappagianopoulos, Kristian Bakken, Casey White, Melissa Tanguay, Jasmine B. Blodgett, Aaron L. Baggish, Rajeev Malhotra, Gregory D. Lewis
Journal: JACC Heart Failure (2018)
Real world treatment patterns of first-line combination therapies among BRAF+ metastatic melanoma patients stratified by tumor burden.
Authors: Sameer Ghate, Jackson Tang, Zhiyi Li, Antonio Reis Nakasato
Journal: Journal of Clinical Oncology (2018)

198 Background: For patients (pts) with metastatic melanoma (MM) and BRAF V600 mutation (BRAF+), options for first-line (1L) systemic combination therapy include immunotherapy (IO) or targeted therapy (TT). This study describes real world treatment patterns among BRAF+ MM pts treated with 1L ipilimumab+nivolumab (I+N) or dabrafenib+trametinib (D+T), stratified by tumor burden. Methods: A retrospective observational analysis used Flatiron Health’s electronic health record-derived database from Oct ’15 - Jul ’16. Pts were aged ≥18 years with a MM diagnosis, tested BRAF+ prior to therapy, and treated with ipilimumab+nivolumab (I+N) or dabrafenib+trametinib (D+T) as 1L therapy. Low tumor burden was defined as low/normal LDH (≤ 333 IU/L) and no brain metastasis. High tumor burden was defined as high LDH ( &gt; 333 IU/L) or brain metastasis. Baseline characteristics and treatment patterns were descriptively assessed. Kaplan-Meier (KM) analysis measured time to discontinuation. Results: Among 76 BRAF+ pts, 38% (29) were treated with I+N as 1L, and 62% (47) were treated with D+T as 1L. Of these, 45% (13/29) of I+N vs. 32% (15/47) of D+T had low tumor burden, while 41% (12/29) of I+N vs. 49% (23/47) of D+T had high tumor burden. The two cohorts did not differ by age or gender. Treatment patterns are summarized below. Conclusions: Among pts with low tumor burden, I+N demonstrated shorter time to discontinuation and higher discontinuation rate relative to D+T. Treatment toxicity and progression was the main reason for discontinuation of I+N and D+T, respectively. Among pts with high tumor burden, I+N demonstrated longer time to discontinuation but higher discontinuation rate relative to D+T. Progression was the main reason for discontinuation of both I+N and D+T. [Table: see text]
Foundation trainees on the BBC: fingers on the red button?
Authors: Garry Summers
Journal: BMJ (2012)

The popular show Your Life in Their Hands follows some foundation trainees at work and at home and has been much discussed by colleagues. Having heard negative comments from seniors about the show, I wondered whether exposing yourself to the media when you are very junior is dangerous. What makes good television probably isn’t best for the junior and might not show the rest of us in a great light.

It has become almost impossible for those of us who watch television to avoid the ubiquitous reality show. Our appetite must be insatiable, for they seem to crop up more and more. Between fat clubbing, grand designing, and master chef-ing, you might have thought there was little space on the airwaves for a new band of brave, fresh faced young people armed with stethoscopes. Alas, some newly qualified foundation trainees have found their way on to the BBC in the second series of Your Life in Their Hands , their minds bursting with incorrect drug doses and an eagerness to prescribe them. 

In the days after the initial episodes I was struck by how many colleagues and friends brought the programme up in conversation …
Unexpected Detection of Bone Metastases on Renal Dynamic Scintigraphy
Authors: Yanxia Mi, Jianmin Huang, Yuan Ren, Peng Xie
Journal: Clinical Nuclear Medicine (2018)

Abstract A 57-year-old man with renal mass underwent 99m Tc–diethylenetriaminepentaacetic acid renal dynamic scintigraphy for evaluation of renal function. The blood flow phase images demonstrated a focus of abnormal increased tracer uptake in the region of the right lower quadrant. On the functional phase images, the activity became unimpressive gradually. This focus corresponded to an osteolytic lesion in the right ilium on the CT and MR images, which was a typical pattern of bone metastasis.
Maffucci Syndrome With Extraosseous Chondrosarcoma Imaged With F-18 FDG PET-CT
Authors: William Makis, Marc Hickeson, Robert Lisbona
Journal: Clinical Nuclear Medicine (2009)

Maffucci syndrome is a rare congenital mesodermal dysplasia, characterized by multiple enchondromas and hemangiomas. The syndrome is nonhereditary, and the etiology remains unknown. We present a 42-year-old man with known Maffucci syndrome who had a fluoro-deoxy-glucose positron emission tomography-computed tomography (F-18 FDG PET-CT) scan done for a growing extraosseous mass arising from a known left femoral enchondroma. The PET-CT showed intense FDG uptake in the mass, which was histologically proven to be a myxoid chondrosarcoma. Imaging of patients with Maffucci syndrome with F-18 FDG PET-CT may prove to be useful in detecting malignant transformation of enchondromas in this syndrome.
Radiology, psychiatry, and paediatrics posts are put on national shortage list
Authors: Abi Rimmer
Journal: BMJ (2015)

Consultant clinical radiologists, psychiatry core trainees, and staff grade paediatricians have all been placed on the national shortage occupation list, the government’s Migration Advisory Committee has said in a review of the list.1

The shortage occupation list is an official list of occupations for which there are not enough UK workers to fill vacancies. Employers wanting to recruit someone from outside the European Economic Area (EEA) to fill a vacancy in a job that is on the list can do so without needing to carry out a resident labour market test.

In paediatrics the number of staff, associate specialist, and specialty (SAS) doctors fell …
Circadian Rest-Activity Pattern Changes in Aging and Preclinical Alzheimer Disease
Authors: Erik S. Musiek, Meghana Bhimasani, Margaret A. Zangrilli, John C. Morris, David M. Holtzman, Yo-El S. Ju
Journal: JAMA Neurology (2018)

Circadian rhythm disturbances occur in symptomatic Alzheimer disease (AD) and have been hypothesized to contribute to disease pathogenesis. However, it is unknown whether circadian changes occur during the presymptomatic phase of the disease.To examine the associations between circadian function, aging, and preclinical AD pathology in cognitively normal adults.This cross-sectional study was conducted using community volunteers from the Knight Alzheimer's Disease Research Center at Washington University in St Louis. Cognitively normal participants (n = 205) underwent 7 to 14 days of actigraphy in their home environment between 2010 and 2012, in addition to clinical assessment, amyloid imaging with Pittsburgh Compound B (PiB), and cerebrospinal fluid biomarker collection. Data collected from 3 years before to 6 months after actigraphy were included. Sixteen participants were excluded owing to incomplete data collection.Circadian rhythm analysis was performed on actigraphy data using 3 methods: cosinor, nonparametric, and empirical mode decomposition. Preclinical AD was assessed by longitudinal clinical assessment, amyloid imaging with PiB, and cerebrospinal fluid biomarker collection.Data from 189 participants were included in the analyses. The mean (SD) age was 66.6 (8.3) years, and 121 participants (64%) were women. Older age (β = .247; P = .003) and male sex (β = .170; P = .04), in the absence of amyloid pathology, were associated with a significant increase in intradaily variability, a nonparametric measure of rest-activity rhythm fragmentation, as well as decreased amplitude by several measures. After correction for age and sex, the presence of preclinical amyloid plaque pathology, assessed by positive PiB imaging (mean [SD], 0.804 [0.187] for PiB negative vs 0.875 [0.178] for PiB positive; P = .05) or increasing cerebrospinal fluid phosphorylated-tau to amyloid β 42 ratio (β = .231; P = .008), was associated with increased intradaily variability, indicating rest-activity rhythm fragmentation.Preclinical AD is associated with rest-activity rhythm fragmentation, independent of age or sex. Aging was also associated with circadian dysfunction independently of preclinical AD pathology, particularly in men. The presence of circadian rhythm abnormalities in the preclinical phase of AD suggests that circadian dysfunction could contribute to early disease pathogenesis or serve as a biomarker of preclinical disease.
Characterization of human bladder cancer patient-derived xenograft in vivo and in organoids.
Authors: Hung-Ming Lam, Yuzhen Liu, Funda Vakar-Lopez, Lisha Brown, Robert B. Montgomery, Eva Corey, Andrew Caleb Hsieh, Jonathan L. Wright
Journal: Journal of Clinical Oncology (2018)

479 Background: To establish and molecularly characterize a human bladder cancer patient-derived xenograft (PDX) in vivo and in an organoid system derived from the PDX for preclinical studies. Methods: Two-mm3 bits of urothelial carcinoma originated from muscle invasive disease excised in cystectomy were implanted subcutaneously into male severe combined immunodeficient mice to establish PDXs. Established PDXs (CoCaB 1) were passaged subcutaneously in SCID mice and histopathology of each passage was compared with the originating tumor. Tumor size was measured weekly by caliper to determine the growth rate of PDXs from early (P1/P2) through late passage (P8/P9). Representative early and late passages were collected for organoid establishment. For both early and late passages, proliferation was assessed by Ki67 in PDXs and organoids, and cell cycle analysis and MTS assay specifically in organoids. RNA sequencing was performed to compare the fidelity of PDX and organoids vs. primary tumor. Results: Histologically, 16 of the 16 (100%) PDXs generated from early through late passage (1-2 tumors per passage) were similar to the original high-grade urothelial carcinoma. In vivo, the latency of PDX establishment decreased upon passage (9 weeks to take in early P1/2 vs. 2 weeks to take in late P8/9) and the growth rate increased upon passage. Concordantly, Ki67 proliferation index increased from 40% in P1 to 95% in P8 and was positively correlated with increasing passage (Spearman R=0.804, p=0.001). Similarly, in organoids, late passage demonstrated a shorter growth doubling time, higher Ki67 proliferation index, and faster progression through cell cycle. Transcriptional analysis showed that the PDX contained 81-92% human transcripts, whereas organoids contained &gt;99% human transcripts. Conclusions: Bladder cancer PDXs histologically represented the originating disease. PDX and organoid systems demonstrated concordant increase in proliferation upon serial passages, suggesting clonal selection may take place in this aggressive tumor type. Despite more mouse stromal content in PDX, PDX and organoid represent two independent model systems with highly similar biological responses that allow therapeutic studies.
Opioid use is linked to risk of serious infections
Authors: Jacqui Wise
Journal: BMJ (2018)

Prescription opioid use is associated with a higher risk for serious invasive pneumococcal diseases such as meningitis and pneumonia, a study published in Annals of Internal Medicine has found.1

As opioid use has increased in the United States the safety of prescription opioids has come under scrutiny. But most of the safety concerns have been over the potential for overdose and serious cardiovascular events rather than …