tbuckley/cabot-search huggingface dataset:
Ca2+tapulting HSCs into action
Authors: Amelie V. Guitart, Andrew J. Finch, Kamil R. Kranc
Journal: The Journal of Experimental Medicine (2018)

In this issue of JEM, Umemoto et al. (https://doi.org/10.1084/jem.20180421) demonstrate that calcium influx stimulates mitochondrial metabolism and initiates proliferation in hematopoietic stem cells (HSCs). Extracellular adenosine, sourced from surrounding hematopoietic progenitors, inhibits this calcium influx, thereby suppressing mitochondrial metabolism and promoting HSC quiescence. This is the first demonstration that a calcium–mitochondria pathway regulates HSC division.
IMMUNOHISTOCHEMICAL CLASSIFICATION OF IPMN IN EUS-GUIDED MICROBIOPSIES REVEALS PREDOMINANCE OF THE PANCREATOBILIARY SUBTYPE
Authors: B Kovacevic, C Vestrup Rift, J Gásdal Karstensen, P Klausen, A Toxværd, E Kalaitzakis, JH Storkholm, C Palnæs Hansen, P Vilmann, J Preuss Hasselby
Journal: Endoscopy (2018)

Different histological subtypes of intraductal papillary mucinous neoplasms (IPMN) of the pancreas have unequal potential for malignant transformation, with pancreatobiliary subtype being associated with increased risk of progression to malignancy. However, studies reporting this have almost exclusively examined resected specimens. Recently, endoscopic ultrasound (EUS)-guided microbiopsy from the wall of the cystic lesion has become available, allowing preoperative histopathological diagnosis with further subtyping in case of IPMN. We wanted to examine the prevalence of different subtypes of IPMN in obtained microbiopsies.
Genetic determinants of co-accessible chromatin regions in activated T cells across humans
Authors: Rachel E. Gate, Christine S. Cheng, Aviva P. Aiden, Atsede Siba, Marcin Tabaka, Dmytro Lituiev, Ido Machol, M. Grace Gordon, Meena Subramaniam, Muhammad Shamim, Kendrick L. Hougen, Ivo Wortman, Su-Chen Huang, Neva C. Durand, Ting Feng, Philip L. De Jager, Howard Y. Chang, Erez Lieberman Aiden, Christophe Benoist, Michael A. Beer, Chun J. Ye, Aviv Regev
Journal: Nature Genetics (2018)
Altered Cell-Cycle Control, Inflammation, and Adhesion in High-Risk Persistent Bronchial Dysplasia
Authors: Daniel T. Merrick, Michael G. Edwards, Wilbur A. Franklin, Michio Sugita, Robert L. Keith, York E. Miller, Micah B. Friedman, Lori D. Dwyer-Nield, Meredith A. Tennis, Mary C. O'Keefe, Elizabeth J. Donald, Jessica M. Malloy, Adrie van Bokhoven, Storey Wilson, Peter J. Koch, Charlene O'Shea, Christopher Coldren, David J. Orlicky, Xian Lu, Anna E. Baron, Greg Hickey, Timothy C. Kennedy, Roger Powell, Lynn Heasley, Paul A. Bunn, Mark Geraci, Raphael A. Nemenoff
Journal: Cancer Research (2018)

Persistent bronchial dysplasia is associated with increased risk of developing invasive squamous cell carcinoma (SCC) of the lung. In this study, we hypothesized that differences in gene expression profiles between persistent and regressive bronchial dysplasia would identify cellular processes that underlie progression to SCC. RNA expression arrays comparing baseline biopsies from 32 bronchial sites that persisted/progressed to 31 regressive sites showed 395 differentially expressed genes [ANOVA, FDR ≤ 0.05). Thirty-one pathways showed significantly altered activity between the two groups, many of which were associated with cell-cycle control and proliferation, inflammation, or epithelial differentiation/cell-cell adhesion. Cultured persistent bronchial dysplasia cells exhibited increased expression of Polo-like kinase 1 (PLK1), which was associated with multiple cell-cycle pathways. Treatment with PLK1 inhibitor induced apoptosis and G2-M arrest and decreased proliferation compared with untreated cells; these effects were not seen in normal or regressive bronchial dysplasia cultures. Inflammatory pathway activity was decreased in persistent bronchial dysplasia, and the presence of an inflammatory infiltrate was more common in regressive bronchial dysplasia. Regressive bronchial dysplasia was also associated with trends toward overall increases in macrophages and T lymphocytes and altered polarization of these inflammatory cell subsets. Increased desmoglein 3 and plakoglobin expression was associated with higher grade and persistence of bronchial dysplasia. These results identify alterations in the persistent subset of bronchial dysplasia that are associated with high risk for progression to invasive SCC. These alterations may serve as strong markers of risk and as effective targets for lung cancer prevention.Significance: Gene expression profiling of high-risk persistent bronchial dysplasia reveals changes in cell-cycle control, inflammatory activity, and epithelial differentiation/cell-cell adhesion that may underlie progression to invasive SCC. Cancer Res; 78(17); 4971-83. ©2018 AACR.
Urinary PGDM, a prostaglandin D2 metabolite, is a novel biomarker for objectively detecting allergic reactions of food allergy
Authors: Shinichiro Inagaki, Shingo Maeda, Masami Narita, Tatsuro Nakamura, Tatsuo Shimosawa, Takahisa Murata, Yukihiro Ohya
Journal: Journal of Allergy and Clinical Immunology (2018)
SAFETY AND EFFECTIVENESS OF ENDOSCOPIC TRIMMING OF BILIARY METAL AND PLASTIC STENTS: A SIMPLE ADJUNCT TO ERCP IN SELECTED PATIENTS
Authors: N Mora Cuadrado, A Yaiza Carbajo López, M de Benito Sanz, S Sevilla Ribota, R Sánchez Ocaña, I Peñas Herrero, P Gil Simón, C de la Serna Higuera, M Pérez Miranda
Journal: Endoscopy (2018)

Endoscopic trimming of self-expandable metal stents (SEMS) using argon plasma coagulation (APC) is a valid strategy to manage migration/malposition. However, reported mechanical trimming techniques of plastic stents remain anecdotal. We aimed to describe a novel cautery-based technique for bilio-pancreatic plastic stent trimming and to assess its safety and efficacy during ERCP and related interventions.
Nonclinical and human pharmacology of the potent and selective topical retinoic acid receptor-γ agonist trifarotene
Authors: J. Aubert, D. Piwnica, B. Bertino, S. Blanchet-Réthoré, I. Carlavan, S. Déret, B. Dreno, B. Gamboa, A. Jomard, A.P. Luzy, P. Mauvais, C. Mounier, J. Pascau, I. Pelisson, T. Portal, M. Rivier, P. Rossio, E. Thoreau, E. Vial, J.J. Voegel
Journal: British Journal of Dermatology (2018)

First- and third-generation retinoids are the main treatment for acne. Even though efficacious, they lack full selectivity for retinoic acid receptor (RAR) γ, expressed in the epidermis and infundibulum.To characterize the in vitro metabolism and the pharmacology of the novel retinoid trifarotene.In vitro assays determined efficacy, potency and selectivity on RARs, as well as the activity on the expression of retinoid target genes in human keratinocytes and ex vivo cultured skin. In vivo studies investigated topical comedolytic, anti-inflammatory and depigmenting properties. The trifarotene-induced gene expression profile was investigated in nonlesional skin of patients with acne and compared with ex vivo and in vivo models. Finally, the metabolic stability in human keratinocytes and hepatic microsomes was established.Trifarotene is a selective RARγ agonist with > 20-fold selectivity over RARα and RARβ. Trifarotene is active and stable in keratinocytes but rapidly metabolized by human hepatic microsomes, predicting improved safety. In vivo, trifarotene 0·01% applied topically is highly comedolytic and has anti-inflammatory and antipigmenting properties. Gene expression studies indicated potent activation of known retinoid-modulated processes (epidermal differentiation, proliferation, stress response, retinoic acid metabolism) and novel pathways (proteolysis, transport/skin hydration, cell adhesion) in ex vivo and in vivo models, as well as in human skin after 4 weeks of topical application of trifarotene 0·005% cream.Based on its RARγ selectivity, rapid degradation in human hepatic microsomes and pharmacological properties including potent modulation of epidermal processes, topical treatment with trifarotene could result in good efficacy and may present a favourable safety profile in acne and ichthyotic disorders.
RADIATION DOSE IN MEDICAL STAFF DURING ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY (ERCP) USING OVER COUCH X-RAY TUBE
Authors: BK Son, HC Jung, D Oh
Journal: Endoscopy (2018)

Reducing radiation exposure of medical personnel is an important issue during Endoscopic Retrograde Cholangiopancreatography (ERCP). This study was planned to investigate personnel's radiation doses obtained from ERCP with overcouch X-ray tube.
First report of a secondary aortojejunal fistula diagnosed by double-balloon enteroscopy
Authors: Alberto Murino, Nikolaos Koukias, Andrea Telese, Nikolaos Lazaridis, Edward Despott
Journal: Endoscopy (2019)

Secondary aortoenteric fistula (AEF) can affect up to 1.6 % of patients who undergo abdominal aortic aneurysm (AAA) repair, with the jejunum being involved only in up to 9 % of the cases [1] [2]. Secondary aortojejunal fistula (AJF) is a very rare, life-threatening condition, which may result in catastrophic gastrointestinal (GI) bleeding [3].
Therapeutic vulnerability of multiple myeloma to MIR17PTi, a first-in-class inhibitor of pri-miR-17-92
Authors: Eugenio Morelli, Lavinia Biamonte, Cinzia Federico, Nicola Amodio, Maria Teresa Di Martino, Maria Eugenia Gallo Cantafio, Martina Manzoni, Francesca Scionti, Mehmet Kemal Samur, Annamaria Gullà, Maria Angelica Stamato, Maria Rita Pitari, Daniele Caracciolo, Settimio Sesti, Niels M. Frandsen, Marco Rossi, Antonino Neri, Mariateresa Fulciniti, Nikhil C. Munshi, Pierosandro Tagliaferri, Pierfrancesco Tassone
Journal: Blood (2018)
Low-Flow Aortic Stenosis in Asymptomatic Patients
Authors: Dana Cramariuc, Giovanni Cioffi, Åshild E. Rieck, Richard B. Devereux, Eva M. Staal, Simon Ray, Kristian Wachtell, Eva Gerdts
Journal: JACC. Cardiovascular imaging (2009)

This study sought to assess the impact of valvuloarterial impedance on left ventricular (LV) myocardial systolic function in asymptomatic aortic valve stenosis (AS). In atherosclerotic AS, LV global load consists of combined valvular and arterial resistance to LV ejection. Global load significantly impacts LV ejection fraction (EF) in symptomatic AS, but less is known about its effect on LV myocardial function in asymptomatic AS. Echocardiograms in 1,591 patients with asymptomatic AS (67 ± 10 years, 51% hypertensive) at baseline in the SEAS (Simvastatin Ezetimibe in Aortic Stenosis) study evaluating placebo-controlled combined simvastatin and ezetimibe treatment in AS were used to assess LV global load as valvuloarterial impedance and LV myocardial function as stress-corrected midwall shortening. The study population was divided into tertiles of global load. Stress-corrected midwall shortening was considered low if <87% in men and<90% in women. Low-flow AS was defined as stroke volume index <22 ml/m2.04. Energy loss index decreased (0.85 cm2/m2 vs. 0.77 and 0.75 cm2/m2) and the prevalence of low stress-corrected midwall shortening increased (10% vs. 26% and 63%) with increasing LV global load (all p < 0.001). The EF was low in only 2% of patients. Patients with low-flow AS had higher LV global load and more often low midwall shortening than those with normal-flow AS (9.66 ± 2.23 mm Hg/ml·m2.04 and 77%, vs. 6.38 ± 2.04 mm Hg/ml·m2.04 and 30%, respectively, p < 0.001). In logistic regression analysis, LV global load was a main predictor of low stress-corrected midwall shortening independent of male sex, concentric LV geometry, LV hypertrophy (all p < 0.001), concomitant hypertension, and aortic regurgitation. LV global load impacts LV myocardial function in asymptomatic AS independent of other main covariates of LV systolic function. LV myocardial systolic dysfunction is common in asymptomatic AS in particular in patients with low-flow AS and increased valvuloarterial afterload, whereas EF is generally preserved. (An Investigational Drug on Clinical Outcomes in Patients With Aortic Stenosis [Narrowing of the Major Blood Vessel of the Heart]; NCT00092677)
Pathologic Grading of Malignant Pleural Mesothelioma: An Evidence-Based Proposal
Authors: Giuseppe Pelosi, Mauro Papotti, Luisella Righi, Giulio Rossi, Stefano Ferrero, Silvano Bosari, Fiorella Calabrese, Izidor Kern, Patrick Maisonneuve, Angelica Sonzogni, Adriana Albini, Sergio Harari, Fausto Barbieri, Enrica Capelletto, Anna Maria Catino, Domenica Cavone, Angela De Palma, Nicola Fusco, Francesca Lunardi, Eugenio Maiorano, Andrea Marzullo, Silvia Novello, Nikolaos Papanikolaou, Giulia Pasello, Antonio Pennella, Federica Pezzuto, Alessandra Punzi, Elena Prisciandaro, Federico Rea, Lorenzo Rosso, Anna Scattone, Gabriella Serio
Journal: Journal of Thoracic Oncology (2018)
Adjuvant irradiation for breast cancer
Authors: E. Whipp
Journal: BMJ (2000)

Editor—Kunkler's editorial on adjuvant irradiation for breast cancer addressed an important problem.1 More and more patients of all age groups with potentially highly curable disease are being treated with both adjuvant chemotherapy and radiation. It is therefore most important that the treatment should be given in the safest possible manner while maintaining its therapeutic advantage. Increasingly, people recognise that radiotherapy can improve survival in breast cancer, and practitioners are becoming aware not just of the cardiac morbidity that occurs but also of the cardiac mortality.

To investigate the magnitude of these problems we have undertaken a series of magnetic resonance scans on patients before radiotherapy planning and treatment. The advent of magnetic resonance imaging has allowed us to quantify the accuracy with which radiotherapy treatments are being delivered in breast cancer. The architecture of our magnetic resonance scanner is open and allows patients to be scanned in the treatment position. Magnetic resonance images have the advantage over other imaging techniques in that they clearly show tumour, tumour bed, and lymph nodes.

Because of the limited resource, patients were chosen if they were to have radiotherapy on the left side or if they were to have extensive radiotherapy, including of the nodes, to the right side. We have now scanned 600 patients; preliminary analysis on the first 200 clearly shows that, in at least 30% of cases, conventionally planned treatments would have been suboptimal. As far as the heart is concerned, more than 80% of the left sided treatments would have irradiated a considerable fraction of cardiac tissue, quite often in the territory of the left anterior descending coronary artery.

A finding of potentially greater importance was that the tumour bed was frequently missed. In the first 200 patients more than 30% would have had complete or partial treatment failure. In over 90% of the patients requiring adjacent nodal irradiation the entire cervicoaxillary chain below the clavicle failed to be encompassed.

Despite the lack of precision of conventional treatment planning that we have shown, radiotherapy does improve survival. It is therefore reasonable to expect that if future treatment plans were made with the benefit of adequate anatomical information, its efficacy would be greatly enhanced. In addition, cardiac morbidity and mortality would be reduced.
How often should we go to the dentist?
Authors: M. C Downer, J. Ahlberg, E. J Kay
Journal: BMJ (1999)

Developing world needs access to low cost pharmaceutical information from reliable sourcesEditor-Hafeez and Mirza have assessed how seriously (or not) pharmaceutical companies take their responsibility to provide information on request to prescribers in Pakistan. 1 Two of their conclusions are that "providing information on drugs is not a priority for companies in Pakistan" and that "the decision to respond to a request for more information therefore seems to depend on how favourable it might be to the interests of the company."These conclusions are particularly worrying because the biased information from drug companies is often the only type of information that prescribers have access to.The findings are in one respect an indictment of the pharmaceutical industry's approach in the developing world.But in another respect, the fact that most prescribers in the developing world do not have adequate access to reliable generic information is an indictment of the international health community.We cannot and should not expect the pharmaceutical industry to provide consistently unbiased information.What is needed is universal access to free or low cost information from a reliable source.As a basic source of reliable prescribing information, the British National Formulary is arguably the single most useful formulary for prescribers worldwide and is one of the BMJ Publishing Group's best sellers internationally.We applaud the recent decision to make the eBNF available on line. 2 If this facility is free it will be a benefit to some prescribers in developing countries, although the effort required to get information online will always be a barrier, even to those few who do have access.Low cost, printed formularies with a quality and objectivity parallel to those of the British National Formulary should be made affordable to all prescribers.Their value and use should be vigorously promoted, not just by the BMJ Publishing Group but by the international health community at large.
Traumatic knee pain in a child
Authors: Oliver Beaumont, Robert Miller, Henry Claireaux, Jakob van Oldenrijk
Journal: BMJ (2018)

A 12 year old boy presented to the emergency department with his parents after falling from a motocross bike. The child was unable to describe the precise history of the event or injury mechanism, but he described experiencing immediate and progressive pain in the left knee and was unable to fully extend the knee or bear weight on that side after the injury.

He sustained no other injuries and was haemodynamically stable. On examination, a large effusion in the joint was noticed. Flexion was limited to between 20° and 90°, but the collateral knee ligaments were stable in extension and in 30° of flexion. Anterior drawer and Lachman test suggested grade 1 instability. The pivot shift test was not possible because of patient apprehension. The limb was neurovascularly intact and the boy’s calves were soft and non-tender. Radiographs of the knee were taken (figs 1, 2).



Fig 1 
Anteroposterior plain radiograph of the child’s knee taken shortly after arrival in the emergency department





Fig 2 
Lateral plain radiograph of the left knee





### What is the diagnosis?

The plain radiographs show a fracture of the tibial spine (aka intercondylar eminence) (figs 3, 4). These are bony avulsion fractures of the anterior cruciate ligament (ACL) along with part of its attachment to the intercondylar eminence of the tibia.



Fig 3 
Anteroposterior radiographs of the child’s knee, with arrow pointing …
Effect of 1 month of zopiclone on obstructive sleep apnoea severity and symptoms: a randomised controlled trial
Authors: Sophie G. Carter, Jayne C. Carberry, Garry Cho, Lauren P. Fisher, Charlotte M. Rollo, David J. Stevens, Angela L. D'Rozario, David K. McKenzie, Ronald R. Grunstein, Danny J. Eckert
Journal: European Respiratory Journal (2018)

Hypnotic use in obstructive sleep apnoea (OSA) is contraindicated due to safety concerns. Recent studies indicate that single-night hypnotic use worsens hypoxaemia in some and reduces OSA severity in others depending on differences in pathophysiology. However, longer clinical trial data are lacking. This study aimed to determine the effects of 1 month of zopiclone on OSA severity, sleepiness and alertness in patients with low–moderate respiratory arousal thresholds without major overnight hypoxaemia. 69 participants completed a physiology screening night with an epiglottic catheter to quantify arousal threshold. 30 eligible patients (apnoea–hypopnoea index (AHI) 22±11 events·h −1 ) then completed standard in-laboratory polysomnography (baseline) and returned for two additional overnight sleep studies (nights 1 and 30) after receiving either nightly zopiclone (7.5 mg) or placebo during a 1-month, double-blind, randomised, parallel trial ( ANZCTR identifier ANZCTRN12613001106729). The change in AHI from baseline to night 30 was not different between zopiclone versus placebo groups (−5.9±10.2 versus −2.4±5.5 events·h −1 ; p=0.24). Similarly, hypoxaemia, next-day sleepiness and driving simulator performance were not different. 1 month of zopiclone does not worsen OSA severity, sleepiness or alertness in selected patients without major overnight hypoxaemia. As the first study to assess the effect of a hypnotic on OSA severity and sleepiness beyond single-night studies, these findings provide important safety data and insight into OSA pathophysiology.
Abstract 9739: Impact of Statin Use Before the Onset of Acute Myocardial Infarction on Coronary Plaque Morphology of the Culprit Lesion
Authors: Hiroyuki Hikita, Yuki Oosaka, Naohiko Kawaguchi, Emiko Nakashima, Daiki Akiyama, Tomoyo Sugiyama, Tetsuo Kamiishi, Shigeki Kimura, Atsushi Takahashi, Mitsuaki Isobe
Journal: Circulation (2012)

Statin favorably stabilizes coronary plaque. We evaluated the impact of statin use before the onset of acute ST-elevation myocardial infarction (AMI) on culprit lesion plaque morphology. Methods: Patients (n=127, age 63.3 ± 13.1 year old, mean ± SD) with first AMI (within 12 hours after the onset) were divided into either a statin group (n=31) or a nonstatin group (n=96) based on statin use before the onset of AMI. Coronary plaque morphology of the culprit lesion was evaluated using intravascular ultrasound virtual histology (IVUS-VH) with radiofrequency data analysis before coronary intervention. The IVUS-VH identified 4 types of plaque components: fibrous, fibrofatty, dense calcium, and necrotic core. Values of high-sensitivity CRP (hs-CRP) at admission were measured. Dual SPECT using BMIPP and 201 Tl was performed within 2 weeks after the AMI to measure perfusion-metabolism mismatch score, an indicator of viable myocardium, from each total defect score of Tl/BMIPP using 17-segment model and a semiquantitative visual score (0: normal, to 4: no uptake). Results: The IVUS-VH showed less percentage of necrotic core area (7.6 ± 6.8% vs 25.5 ± 6.8%, statin vs nonstatin, p&lt;0.001), greater percentage of fibrous area (70.0 ± 14.2% vs 59.0 ± 8.2 %, p&lt;0.001), and greater percentage of fibrofatty area (19.3 ± 12.7 % vs 11.6 ± 9.9 %, p&lt;0.001) of the culprit lesion in the statin group than in the nonstatin group. The values of hs-CRP were lower in the statin group than in the nonstatin group (1.2 ± 0.8 mg/L vs 2.1 ± 2.4 mg/L, p&lt;0.05) The values of mismatch score was higher in the statin group than in the nonstatin group (8.0 ± 2.5 vs 5.3 ± 2.7, p&lt;0.001) Conclusions: Statin use before the onset of AMI may have effects on coronary plaque morphology of the AMI culprit lesion with less necrotic core and greater fibrous and fibrofatty component. Reducing necrotic core component of the culprit lesion with statin use before the onset of AMI may be related with lower inflammatory response and greater viable myocardium after AMI.