tbuckley/cabot-search huggingface dataset:
High-resolution MRI demonstrates that more than 90% of small intracranial melanoma metastases develop in close relationship to the leptomeninges
Authors: Arian Lasocki, Chloe Khoo, Peter K H Lau, David L Kok, Grant A Mcarthur
Journal: Neuro-Oncology (2019)

Abstract Background Despite classic teaching that intracranial metastases typically arise at the gray–white matter junction, small intracranial melanoma metastases (IMM) are frequently observed at the interface between the cortex and leptomeninges (ie, “corticomeningeal interface”), suggesting possible leptomeningeal origin. Methods MRI brain examinations of melanoma patients treated at a specialist oncology center from July 2015 to June 2017 were retrospectively reviewed. The MRI examination on which IMM were first visible was identified, utilizing 1 mm volumetric postcontrast imaging prior to local therapy. Individual metastases (up to 10 per patient) were assessed for the presence of leptomeningeal contact, as well as their number, size, and morphology. Lesions ≥10 mm in long axis were excluded, in order to examine early metastatic disease. Results Seventy-five patients had evidence of IMM. Fifteen patients had only lesion(s) measuring ≥10 mm at diagnosis, leaving 60 patients. One hundred ninety-two individual metastases were examined (median 2 per patient; interquartile range, 1–4), 174 (91%) demonstrating leptomeningeal contact. A nodular morphology was observed in 154 of 192 (82%), 32 (17%) were ovoid but elongated along the cortex, and 6 (3%) were linear. Only 3 patients (5%) also exhibited a “classic” linear leptomeningeal disease appearance. Conclusions Most IMM measuring between 2 and 9 mm in diameter are corticomeningeal nodules. These data raise the hypothesis that deeper parenchymal extension of IMM occurs secondarily. If the leptomeninges provide a preferential site for establishment of IMM, further investigation of the underlying biology of this phenomenon may provide opportunities for novel therapeutic strategies for patients with IMM. Key Points 1. Most small IMM develop at the corticomeningeal interface, rather than the gray‒white junction. 2. This suggests that the pia mater provides a preferential site for establishment of IMM. 3. Deeper brain parenchymal extension may occur secondarily.
A regimen to minimize pain during blue light photodynamic therapy of actinic keratoses: Bilaterally controlled, randomized trial of simultaneous versus conventional illumination
Authors: Urvashi Kaw, Muneeb Ilyas, Taylor Bullock, Lisa Rittwage, Margo Riha, Allison Vidimos, Bo Hu, Christine B. Warren, Edward V. Maytin
Journal: Journal of the American Academy of Dermatology (2019)
Lupus Nephritis
Authors: JAMES E. BALOW
Journal: Annals of Internal Medicine (1987)

Nephritis has long been considered one of the most ominous components of systemic lupus erythematosus. Accumulations of immune complexes and lymphoid cells in several locations within the kidney are the best-described elements of lupus nephritis. The extreme diversity of the renal changes indicates that many variables are likely to be involved. Inbred strains of lupus-prone mice have provided homogeneous subjects for study of pathogenesis and response to treatment. Comparable grouping of lupus nephritis in humans according to unique or dominant pathogenetic mechanisms is imprecise and limited by insufficient knowledge of the primary stimulus for the disease. Treatment is also imperfect and, at times, hazardous. Certain regimens incorporating cytotoxic drugs provide a significant therapeutic advantage over corticosteroids alone in the management of this disease.
Microbiota-Gut-Brain Axis: New Therapeutic Opportunities
Authors: Caitríona Long-Smith, Kenneth J. O'Riordan, Gerard Clarke, Catherine Stanton, Timothy G. Dinan, John F. Cryan
Journal: The Annual Review of Pharmacology and Toxicology (2019)

The traditional fields of pharmacology and toxicology are beginning to consider the substantial impact our gut microbiota has on host physiology. The microbiota-gut-brain axis is emerging as a particular area of interest and a potential new therapeutic target for effective treatment of central nervous system disorders, in addition to being a potential cause of drug side effects. Microbiota-gut-brain axis signaling can occur via several pathways, including via the immune system, recruitment of host neurochemical signaling, direct enteric nervous system routes and the vagus nerve, and the production of bacterial metabolites. Altered gut microbial profiles have been described in several psychiatric and neurological disorders. Psychobiotics, live biotherapeutics or substances whose beneficial effects on the brain are bacterially mediated, are currently being investigated as direct and/or adjunctive therapies for psychiatric and neurodevelopmental disorders and possibly for neurodegenerative disease, and they may emerge as new therapeutic options in the clinical management of brain disorders.
A painful shoulder after a fall
Authors: Sarah Abbott, Sukhmeet Grewal, Hassan Mehdi, Michael Rafferty
Journal: BMJ (2019)

A 9 year old boy, right hand dominant, presented to the emergency department after falling onto an outstretched hand while jumping over a vaulting box during a physical education lesson. He had no notable medical or surgical history. He complained of pain over his upper arm.

Deformity, tenderness, and swelling were obvious at the level of the upper third of the right humerus. Range of motion at the shoulder was limited due to pain. There was no tenderness over the right clavicle or scapula and no other bony injury in the …
Noninvasive Diagnostic Approach By per Rectal Portal Scintigraphy for Sinusoidal Obstruction Syndrome after Allogeneic Hematopoietic Cell Transplantation
Authors: Hiroshi Okamura, Hideo Koh, Kentaro Ido, Yosuke Makuuchi, Teruhito Takakuwa, Shoji Ine, Satoru Nanno, Yasuhiro Nakashima, Takahiko Nakane, Atsushi Jogo, Akira Yamamoto, Masao Hamuro, Atsushi Yoshida, Kohei Kotani, Shigeaki Higashiyama, Joji Kawabe, Susumu Shiomi, Masahiko Ohsawa, Masayuki Hino, Hirohisa Nakamae
Journal: Blood (2018)
Inhibition of HSP90β Improves Lipid Disorders by Promoting Mature SREBPs Degradation via the Ubiquitin-proteasome System
Authors: Zu-Guo Zheng, Xin Zhang, Xiao-Xiao Liu, Xiu-Xiu Jin, Lunzhi Dai, Hui-Min Cheng, Dan Jing, Pyone Myat Thu, Mu Zhang, Hongyang Li, Jing Zhu, Chang Liu, Bin Xue, Yu Li, Ligong Chen, Cheng Peng, Weiliang Zhu, Lin Wang, Junli Liu, Hui-Jun Li, Ping Li, Xiaojun Xu
Journal: Theranostics (2019)

Rationale: Heat shock protein 9 (HSP90) are a family of the most highly expressed cellular proteins and attractive drug targets against cancer, neurodegeneration diseases, etc. HSP90 proteins have also been suggested to be linked to lipid metabolism. However, the specific function of HSP90 paralogs, as well as the underlying molecular cascades remains largely unknown. This study aims to unravel the paralog-specific role of HSP90 in lipid metabolism and try to discover paralog-specific HSP90 inhibitors. Methods: In non-alcohol fatty liver disease (NAFLD) patients, as well as in diet induced obese (DIO) mice, expression of HSP90 paralogs were analyzed by immunohistochemistry and western blot. In hepatocytes and in DIO mice, HSP90 proteins were knockdown by siRNAs/shRNAs, metabolic parameters, as well as downstream signaling were then investigated. By virtue screening, corylin was found to bind specifically to HSP90β. Using photo-affinity labeling and mass spectrum, corylin binding proteins were identified. After oral administration of corylin, its lipid lowering effects in different metabolic disease mice models were evaluated. Results: We showed that hepatic HSP90β, rather than HSP90α, was overexpressed in NAFLD patients and obese mice. Hepatic HSP90β was also clinical relevant to serum lipid level. Depletion of HSP90β promoted mature sterol regulatory element-binding proteins (mSREBPs) degradation through Akt-GSK3β-FBW7 pathway, thereby dramatically decreased the content of neutral lipids and cholesterol. We discovered an HSP90β-selective inhibitor (corylin) that only bound to its middle domain. We found that corylin treatment partially suppressed Akt activity only at Thr308 site and specifically promoted mSREBPs ubiquitination and proteasomal degradation. Corylin treatment significantly reduced lipid content in both liver cell lines and human primary hepatocytes. In animal studies, we showed that corylin ameliorated obesity-induced fatty liver disease, type 2 diabetes and atherosclerosis. Principle conclusions: HSP90β plays a parolog-specific role in regulating lipid homeostasis. Compound that selectively inhibits HSP90β could be useful in the clinic for the treatment for metabolic diseases.
Studies on the Renal Circulation and the Renal Function in Mitral Valvular Disease
Authors: LARS WERKÖ, JONAS BERGSTRÖM, HÄRJE BUCHT, JAN EK, HARALD ELIASCH, KERSTIN ERIKSSON, BENGT THOMASSON, EDVARDAS VARNAUSKAS
Journal: Circulation (1956)

Renal circulation and function were studied simultaneously with pulmonary and systemic hemodynamics in 25 patients with mitral stenosis before and six weeks after valvulotomy. Postoperatively no essential change in renal circulation or function could be demonstrated whether significant relief of pulmonary hypertension had occurred or not. However, results from follow up studies made on 21 patients up to more than three years after operation showed that renal plasma flow could be increased in patients that were hemodynamically improved at the postoperative study. The effect of exercise was investigated in eight patients before and after valvulotomy. In seven the response pattern of renal circulation and function was essentially unchanged regardless of whether improvement in pulmonary pressures and cardiac output did or did not occur. In the eighth patient, the only one with elevated right atrial pressure before operation, the response to exercise improved markedly. Preoperative results obtained on seven patients who died in connection with operation showed that a fatal outcome was not necessarily related to the degree of impairment in renal circulation or function.
Effectiveness of home-based and remotely supervised aerobic exercise in Parkinson's disease: a double-blind, randomised controlled trial
Authors: Nicolien M van der Kolk, Nienke M de Vries, Roy P C Kessels, Hilde Joosten, Aeilko H Zwinderman, Bart Post, Bastiaan R Bloem
Journal: The Lancet Neurology (2019)
Fibroblast Growth Factor 21 Drives Dynamics of Local and Systemic Stress Responses in Mitochondrial Myopathy with mtDNA Deletions
Authors: Saara Forsström, Christopher B. Jackson, Christopher J. Carroll, Mervi Kuronen, Eija Pirinen, Swagat Pradhan, Anastasiia Marmyleva, Mari Auranen, Iida-Marja Kleine, Nahid A. Khan, Anne Roivainen, Päivi Marjamäki, Heidi Liljenbäck, Liya Wang, Brendan J. Battersby, Uwe Richter, Vidya Velagapudi, Joni Nikkanen, Liliya Euro, Anu Suomalainen
Journal: Cell Metabolism (2019)
Cancer-protective effects of inhaled corticosteroids in COPD are likely related to modification of epithelial activation
Authors: Amir Soltani, Malik Q. Mahmood, David W. Reid, E. Haydn Walters
Journal: European Respiratory Journal (2019)

<b>COPD is an independent risk factor for lung cancer. Studies have suggested that inhaled corticostroids have reduced the incidence of lung cancer in these patients. This effect is likely related to modification of epithelial–mesenchymal transition (EMT).</b>http://bit.ly/2Km4VK4
Working Memory Development and Motor Vehicle Crashes in Young Drivers
Authors: Elizabeth A. Walshe, Flaura K. Winston, Laura M. Betancourt, Atika Khurana, Kristin Arena, Daniel Romer
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Adolescent drivers have the highest rate of motor vehicle crashes, and among equally novice drivers, crash risk is inversely age graded. Working memory (WM), crucial to driving hazard awareness, is also age graded, with ongoing development into late adolescence. Variability in WM capacity and growth trajectory positions WM as a candidate crash risk factor for study, clinical screening, and possible preventative intervention. <h3>Objective</h3> To test the association between crashes and differential WM development. <h3>Design, Setting, and Participants</h3> This prospective cohort study used data from a longitudinal cohort of 118 community youth in Philadelphia, Pennsylvania. Working memory and other risk factors were measured annually from age 11 to 13 years (prelicensure, in 2005) to 14 to 16 years (in 2009), and again at 18 to 20 years (in 2013). In 2015, a follow-up survey of driving experience identified 84 participants who had started driving. Latent growth curve modeling was used to examine the association between variability in the baseline (intercept) and developmental trajectory (slope) of WM and the crash outcome. <h3>Main Outcomes and Measures</h3> Self-reported crashes were the primary outcome. Variability in the relative growth of WM development along with traits and behaviors associated with risky driving were assessed. <h3>Results</h3> Of 84 participants (39 [46%] male; mean [SD] age, 20.46 [1.09] years), 25 (29.8%) reported they had been involved in at least 1 crash. Controlling for other crash risk factors, the model indicated that variation in the linear slope of WM growth was inversely associated with reporting a crash (<i>b</i> = −6.41; SE = 2.64;<i>P</i> = .02). Crashes were also associated with reckless driving behavior (<i>b</i> = 0.40; SE = 0.18;<i>P</i> = .03). Variation in the intercept of WM was not associated with crashes (<i>b</i> = −0.245; SE = 0.67;<i>P</i> = .72). <h3>Conclusions and Relevance</h3> The results suggest that a relatively slower WM growth trajectory is associated with young driver crashes. Routine assessment of WM across adolescence may help to identify at-risk teen drivers and opportunities for providing adaptive interventions (eg, driving aids or training) that can address limitations in WM-related skills that are critical for safe driving.
Identification of Genetic Pathways Controlling Resistance to Standard Combination Chemotherapy in Acute Myeloid Leukemia
Authors: Victoria Y Ling, William Godfrey, Sebastien Jacquelin, Jasmin Straube, Leanne T Cooper, Claudia Bruedigam, Siok-Keen Tey, Lars Bullinger, Marco J Herold, Megan Bywater, Steven W. Lane
Journal: Blood (2018)
Tobacco retail availability and tobacco cessation in lung and head and neck (HN) cancer survivors.
Authors: Lawson Eng, Jie Su, Steven Habbous, Katrina Hueniken, M. Catherine Brown, Deborah Saunders, John R. de Almeida, Andrew Hope, Andrea Bezjak, Frances A. Shepherd, Natasha B. Leighl, Andrew Pierre, Peter Selby, David Paul Goldstein, Wei Xu, Meredith Elana Giuliani, William K. Evans, Geoffrey Liu, Michael Chaiton
Journal: Journal of Clinical Oncology (2019)

11559 Background: Continued smoking after a cancer diagnosis is associated with poorer outcomes. Tobacco retail availability is negatively associated with cessation in non-cancer patients (pts), but has not been explored in cancer survivors. We evaluated the impact of tobacco retail availability on cessation in lung and HN cancer pts. Methods: Lung and HN cancer pts (Princess Margaret Cancer Centre, Toronto) completed questionnaires evaluating changes in tobacco use with a median of 26 months apart. Validated tobacco retail location data were obtained from Ministry of Health and pt home addresses were geocoded using ArcGIS 10.6.1, which calculated walking time/distance to nearest vendor, and vendor density within 250 meters (m) and 500m from pts. Multivariable logistic regression and Cox proportional hazard models evaluated the impact of vendor availability on cessation and time to quitting after diagnosis respectively, adjusting for significant clinico-demographic and tobacco covariates. Results: 242/721 lung and 149/445 HN pts smoked at diagnosis; subsequent overall quit rates were 66% and 49% respectively. Mean distance and walking time to a vendor was 1 km (range 0-13) and 11 min (range 0-156). On average, there was one vendor (range 0-19) within 250m and four vendors (range 0-40) within 500m from pts; 37% and 61% of pts lived within 250m and 500m from at least one vendor respectively. Greater distance (aOR 1.18 per 1000m [95% CI 1.00-1.38] p = 0.05) and increased walking time (aOR 1.01 per minute [1.00-1.02] p = 0.05) were associated with quitting at one year. Living within 250m (aOR 0.52 [0.32-0.84] p = 0.008) or 500m (aOR 0.57 [0.35-0.92] p = 0.02) to at least one vendor reduced quitting at one year. Living near more vendors within 500m had an increasing dose effect on reducing cessation rates at one year (aOR 0.96 per vendor [0.93-1.00] p = 0.05). Living within 500m to a vendor reduced chance of quitting at any time (aHR 0.66 [0.48-0.91] p = 0.01). HN and lung subgroups revealed similar associations. Conclusions: Close access to tobacco retail outlets is associated with reduced cessation rates for lung and HN cancer survivors. Reducing density of tobacco vendors is a cessation strategy that can positively impact cancer pt outcomes.
Cash strapped CCGs ask GPs not to refer some patients to hospital
Authors: Gareth Iacobucci
Journal: BMJ (2019)

GPs will be asked to avoid referring some patients to secondary care as part of a strict programme of service rationing tabled by NHS bosses in west London.

The North West London Collaboration of Clinical Commissioning Groups has also proposed cutting the number of outpatient appointments, restricting consultant to consultant referrals, and “repatriating” elective operations from specialist centres outside the area to local hospitals to help tackle a projected £112m (€125m; $140m) deficit for 2019-20—more than double the £51m the collaboration had forecast at the start of the financial year.

The CCGs, which commission care for two million patients, said that “difficult choices” were needed, as local finances had worsened significantly …
Long-term outcomes of childhood sexual abuse: an umbrella review
Authors: Helen P Hailes, Rongqin Yu, Andrea Danese, Seena Fazel
Journal: The Lancet Psychiatry (2019)

Although many meta-analyses have examined the association between childhood sexual abuse and subsequent outcomes, the scope, validity, and quality of this evidence has not been comprehensively assessed. We aimed to systematically review existing meta-analyses on a wide range of long-term psychiatric, psychosocial, and physical health outcomes of childhood sexual abuse, and evaluate the quality of the literature.
Sheffield Medical Society: February 23, 1843
Authors: A. Knight
Journal: BMJ (1843)

Our notice of the ninth edition of this well-known and popular work must be almost confined to the announcement of its appearance.It were superfluous to say anything in praise of a volume which has been distinguished beyond all others by public favor.Much of the success of Dr. Paris's Pharmacologia depends on its value as a work of science; but a much greater share, on the elegant and brilliant style which adorns commonplace truths and gives a charm of the most pleasing kind to facts or illustrations that otherwise might have been passed over unheeded.The present edition of Dr. Paris's Pharmacologia is not a mere reprint of those which have preceded it; the author is not a man to remain stationary while science is marching, or to neglect availing himself of the progress of events.Thus this editionis dedicated to Sir B. Brodie, instead of to Dr. Maton, defunct; and the discoveries bywhich chemistry and pharmacy have been enriched within the last few years are put into contribution, to render it consistent with the science of the day.The third part, " On the theory and art of pre scribing"-a subject which Dr. Paris has made com.pletely his own-is, in this edition, enriched by a comprehensive table of the different substances which are usually considered as incompatible with the dif- ferent articles of the materia medica, and of the results of their mutual actions.It were useless for us, as we have already said, to recommend in a special manner the work of Dr. Paris to the attention of our readers, because we are sure that it has found its place in the library of every intelligent practitioner in the kingdom.
Variation in the cost of treatment for colorectal cancer
Authors: S. A. Ferro, L. E. Cosler, D. A. Wolff, M. S. Poniewierski, E. Culakova, A. A. Khorana, G. H. Lyman
Journal: Journal of Clinical Oncology (2006)

3625 Background: Recent publications have drawn attention to the escalating costs of drugs utilized for the treatment and supportive care of colorectal cancer (CRC) patients. As more advanced chemotherapeutic and supportive agents are approved, the cost of treatment will likely continue to increase. The goal of this analysis was to estimate costs of frequently used CRC chemotherapeutics and other commonly prescribed agents. Methods: Costs of drugs in CRC regimens for patients participating in a prospective, observational study from 115 community oncology practices between March 2002 and March 2005 were calculated. Standard dosages and schedules were determined through literature review and an expert CRC oncologist. Trimmed mean (90%) costs were computed using average wholesale prices (AWP) retrieved from the Lexicon Database Drug Product (January 2005). All prices noted are 95% AWP. All chemotherapeutic drugs were combined to arrive at regimen specific prices. Other regimens were defined as regimens with less than four patients. Price per cycle was estimated based on a standard patient BSA of 2.0 m 2 and standard regimen schedules. Growth factor costs were derived from expected per cycle utilization, while prices for other supportive drugs were calculated using dosages for single events. Results: Patients were categorized into the following regimens ( table below). The price of a commonly used monoclonal antibody is: Bevacizumab ($2613), based on every 2 week dosing. Growth factor prices (per cycle) were estimated: Filgrastim ($2499), Pegfilgrastim ($2928), Epoetin ($552), and Darbepoetin Alfa ($1002). Prices per event for other commonly used agents were: Atropine ($245), Loperamide ($3), Ondansetron ($931), and Granisetron ($232). Conclusions: Prices of CRC regimens vary considerably, with newer agents and supportive drugs adding substantially to costs, particularly in late stage disease. Research on improved outcomes or treatment benefits associated with high cost treatment is warranted. [Table: see text] [Table: see text]
Modulating Inflammation in Monocytes Using Capillary Fiber Organic Electronic Ion Pumps
Authors: Maria Seitanidou, Robert Blomgran, Giggil Pushpamithran, Magnus Berggren, Daniel T. Simon
Journal: Advanced Healthcare Materials (2019)

Abstract An organic electronic ion pump (OEIP) delivers ions and drugs from a source, through a charge selective membrane, to a target upon an electric bias. Miniaturization of this technology is crucial and will provide several advantages, ranging from better spatiotemporal control of delivery to reduced invasiveness for implanted OEIPs. To miniaturize OEIPs, new configurations have been developed based on glass capillary fibers filled with an anion exchange membrane (AEM). Fiber capillary OEIPs can be easily implanted in proximity to targeted cells and tissues. Herein, the efficacy of such a fiber capillary OEIP for modulation of inflammation in human monocytes is demonstrated. The devices are located on inflammatory monocytes and local delivery of salicylic acid (SA) is initiated. Highly localized SA delivery results in a significant decrease in cytokine (tumor necrosis factor alpha and interleukin 6) levels after lipopolysaccharide stimulation. The findings—the first use of such capillary OEIPs in mammalian cells or systems—demonstrate the utility of the technology for optimizing transport and delivery of different therapeutic substances at low concentrations, with the benefit of local and controlled administration that limits the adverse effect of oral/systemic drug delivery.