tbuckley/cabot-search huggingface dataset:
Computational specificity in the human brain
Authors: James M Shine, Ian Eisenberg, Russell A Poldrack
Journal: Behavioral and Brain Sciences (2016)

Abstract Although meta-analytic neuroimaging studies demonstrate a relative lack of specificity in the brain, this evidence may be the result of limits inherent to these types of studies. From this perspective, we review recent findings that suggest that brain function is most appropriately categorized according to the computational capacity of each brain system, rather than the specific task states that elicit its activity.
Critical Flaws in the Validation of the Instant Blood Pressure Smartphone App—A Letter From the App Developers
Authors: Ryan Archdeacon, Ryan Schneider, Yu Jiang
Journal: JAMA Internal Medicine (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
The High Cost of Prescription Drugs in the United States
Authors: Aaron S. Kesselheim, Jerry Avorn, Ameet Sarpatwari
Journal: JAMA (2016)

<h3>Importance</h3> The increasing cost of prescription drugs in the United States has become a source of concern for patients, prescribers, payers, and policy makers. <h3>Objectives</h3> To review the origins and effects of high drug prices in the US market and to consider policy options that could contain the cost of prescription drugs. <h3>Evidence</h3> We reviewed the peer-reviewed medical and health policy literature from January 2005 to July 2016 for articles addressing the sources of drug prices in the United States, the justifications and consequences of high prices, and possible solutions. <h3>Findings</h3> Per capita prescription drug spending in the United States exceeds that in all other countries, largely driven by brand-name drug prices that have been increasing in recent years at rates far beyond the consumer price index. In 2013, per capita spending on prescription drugs was $858 compared with an average of $400 for 19 other industrialized nations. In the United States, prescription medications now comprise an estimated 17% of overall personal health care services. The most important factor that allows manufacturers to set high drug prices is market exclusivity, protected by monopoly rights awarded upon Food and Drug Administration approval and by patents. The availability of generic drugs after this exclusivity period is the main means of reducing prices in the United States, but access to them may be delayed by numerous business and legal strategies. The primary counterweight against excessive pricing during market exclusivity is the negotiating power of the payer, which is currently constrained by several factors, including the requirement that most government drug payment plans cover nearly all products. Another key contributor to drug spending is physician prescribing choices when comparable alternatives are available at different costs. Although prices are often justified by the high cost of drug development, there is no evidence of an association between research and development costs and prices; rather, prescription drugs are priced in the United States primarily on the basis of what the market will bear. <h3>Conclusions and Relevance</h3> High drug prices are the result of the approach the United States has taken to granting government-protected monopolies to drug manufacturers, combined with coverage requirements imposed on government-funded drug benefits. The most realistic short-term strategies to address high prices include enforcing more stringent requirements for the award and extension of exclusivity rights; enhancing competition by ensuring timely generic drug availability; providing greater opportunities for meaningful price negotiation by governmental payers; generating more evidence about comparative cost-effectiveness of therapeutic alternatives; and more effectively educating patients, prescribers, payers, and policy makers about these choices.
FIFA Diploma in Football Medicine: free knowledge from expert clinicians to improve sports medicine care for all football players (continuing professional development series)
Authors: Adam G Culvenor
Journal: British Journal of Sports Medicine (2016)

FIFA Medical Assessment and Research Centre (F-MARC) in collaboration with FIFA Medical Centres of Excellence.

Diploma in Football Medicine (online-learning).

‘Hey Doc, I'll be ok to take this supplement to help me recover quickly for the representative game tomorrow won't I?’ As the local football club medical attendant, the team's top midfielder throws you this question postclub match. How do you respond? Are you responsible for possibly encouraging the use of a banned substance? Where do you find the answer?

Enter the Diploma in Football Medicine—a free online course dedicated to help health and medical practitioners to manage common football-related health and injury issues and enhance sports medicine knowledge in conjunction with FIFA's sport-related risk management framework.1 Each football player around the globe sustains an average …
Evaluation and comparison of 3D intervertebral disc localization and segmentation methods for 3D T2 MR data: A grand challenge
Authors: Guoyan Zheng, Chengwen Chu, Daniel L. Belavý, Bulat Ibragimov, Robert Korez, Tomaž Vrtovec, Hugo Hutt, Richard Everson, Judith Meakin, Isabel Lŏpez Andrade, Ben Glocker, Hao Chen, Qi Dou, Pheng-Ann Heng, Chunliang Wang, Daniel Forsberg, Aleš Neubert, Jurgen Fripp, Martin Urschler, Darko Stern, Maria Wimmer, Alexey A. Novikov, Hui Cheng, Gabriele Armbrecht, Dieter Felsenberg, Shuo Li
Journal: Medical Image Analysis (2016)
An <i>XPA</i> gene splicing mutation resulting in trace protein expression in an elderly patient with xeroderma pigmentosum group A without neurological abnormalities
Authors: Y. Takahashi, Y. Endo, A. Kusaka-Kikushima, S. Nakamaura, Y. Nakazawa, T. Ogi, M. Uryu, G. Tsuji, M. Furue, S. Moriwaki
Journal: British Journal of Dermatology (2016)

A certain relationship between XPA gene mutations and the severity of symptoms has been observed in patients with xeroderma pigmentosum group A (XP-A). Patients with mutations within the DNA-binding domain usually exhibit severe symptoms, whereas splicing mutations in the same domain sometimes cause very mild symptoms. This inconsistency can be explained by a small amount of functional XPA protein produced from normally spliced transcripts. We herein report the case of an adult Japanese patient with XP-A with unusually mild symptoms. We identified a homozygous c.529G>A mutation in exon 4 of the XPA gene, which resulted in aberrant splicing with a 29-bp deletion in exon 4 causing a frameshift. Intact mRNA was observable, but a Western blot analysis failed to detect any normal XPA protein. We therefore evaluated the DNA repair capacity in normal cells in which the XPA expression was artificially diminished. The repair capacity was still present in cells with trace levels of the XPA protein. The repair capacity of the cells derived from our patient with mild symptoms was poor by comparison, but still significant compared with that of the cells derived from a patient with XP-A with severe symptoms. These results provide strong evidence that a trace level of XPA protein can still exert a relatively strong repair capacity, resulting in only a mild phenotype.
David Graeme Sinclair
Authors: Melanie Hearn
Journal: BMJ (2016)

David Graeme Sinclair was a big man in many ways. Standing 6’5” and with a military background of more than 16 years, he had a commanding physical presence. Having grown up in south Wales, he started his medical career at Birmingham University Medical School in 1976, where he was known as “Jock.” He joined the Royal Army Medical Corps in 1978, which gave him financial independence and the ability to indulge his love of cars. Alongside studying medicine and playing rugby, he rebuilt a red Triumph TR6 sports car and said that he made a profit on it (if you disregarded the hours he spent on it).

After completing house jobs in Birmingham, David undertook his military training at Sandhurst before spending two years in Fallingbostel, Germany, with the Queen’s Regiment. As he did with everything, he threw himself into his army and medical career. He took part in a tour of Northern Ireland and went to Saudi …
Phase I study combining anti-PD-L1 (MEDI4736) with BRAF (dabrafenib) and/or MEK (trametinib) inhibitors in advanced melanoma.
Authors: Antoni Ribas, Marcus Butler, Jose Lutzky, Donald P. Lawrence, Caroline Robert, Wilson Miller, Gerald P. Linette, Paolo Antonio Ascierto, Timothy Kuzel, Alain Patrick Algazi, Michael Andrew Postow, Paul D. Nathan, Brendan D. Curti, Paul B. Robbins, Xia Li, John A. Blake-Haskins, Michael S. Gordon
Journal: Journal of Clinical Oncology (2015)

3003 Background: Inhibition of the MAPK pathway with dabrafenib (D) and trametinib (T) is efficacious in BRAF-mutant melanoma. MEK inhibitors have also shown activity in BRAF WT melanoma, particularly in NRAS-mutant tumors. However, most patients (pts) develop resistance to D and T. MEDI4736 (M), a human IgG1 mAb that blocks PD-L1 binding to PD-1 and CD80 with high affinity and selectivity, has shown clinical activity with durable responses and an acceptable safety profile in multiple tumor types. Combined therapy with these agents may lead to enhanced durable tumor responses. Methods: A phase I, multicenter, open-label study (NCT02027961) evaluating the safety and efficacy of M at 3 or 10 mg/kg IV every 2 weeks (q2w) in combination with D 150 mg twice daily + T 2 mg daily, or T alone in pts with stage IIIc/IV melanoma. Pts enroll by BRAF status into dose escalation cohorts (3+3 design), followed by dose expansion: BRAF mutant in Cohort A (M+D+T); BRAF WT in Cohort B (M+T) or Cohort C (sequential T→M). Prior BRAF/MEK inhibitors were prohibited; prior immunotherapy was allowed, including anti-PD-1/anti-PD-L1 therapy. Results: As of December 5, 2014, 50 pts were treated. DLTs were observed in 1 pt in Cohort A1 (reversible grade [G] 3 thrombocytopenia) and 1 pt in Cohort B (reversible G3 choroidal effusion). No MTD was identified; M 10 mg/kg q2w was selected for expansion in all cohorts. The most frequent drug-related adverse events (AEs) by cohort were: pyrexia (63%) and fatigue (54%) (Cohort A); diarrhea (30%) and rash (25%) (Cohort B); and vomiting (67%) (Cohort C). 2 pts discontinued due to drug-related AEs (DLTs above). Clinical activity to date is shown below. Most responses are ongoing (range of duration: 0.1+ - 32+ wk). Conclusions: M can be combined with T ± D at full doses with a manageable safety profile, and evidence of clinical activity in BRAF-mutant and WT melanoma. Clinical trial information: NCT02027961. Cohort n Any AE (%) Related AE (%) Related G ≥ 3 AE (%) CR/PR (n/n)a SD (n/n)a A1 (3 mg/kg M + D + T) 6 100 100 17 6/6 0/6 A2 (10 mg/kg M + D + T) 18 94 94 39 10/15 5/15 B (10 mg/kg M + T) 20 90 85 40 3/14 6/14 C (sequential T + 10 mg/kg M) 6 100 100 17 3/6 1/6 aIncludes pts with ≥ 1 follow up scan or discontinuation due to PD or death prior to first scan (confirmed and unconfirmed CR/PR).
Interaction with Human Stromal Cells Enhances CXCR4 Expression and Engraftment of Cord Blood Lin-CD34-Cells Via Wnt Signaling.
Authors: Masayoshi Kobune, Kazuyuki Murase, Satoshi Iyama, Tsutomu Sato, Shohei Kikuchi, Yutaka Kawano, Kohichi Takada, Koji Miyanishi, Rishu Takimoto, Junji Kato
Journal: Blood (2008)
Control theory prediction of resolved Cheyne−Stokes respiration in heart failure
Authors: Scott A. Sands, Bradley A. Edwards, Kirk Kee, Christopher Stuart-Andrews, Elizabeth M. Skuza, Teanau Roebuck, Anthony Turton, Garun S. Hamilton, Matthew T. Naughton, Philip J. Berger
Journal: European Respiratory Journal (2016)

Cheyne–Stokes respiration (CSR) foretells deleterious outcomes in patients with heart failure. Currently, the size of therapeutic intervention is not guided by the patient's underlying pathophysiology. In theory, the intervention needed to resolve CSR, as a control system instability (loop gain &gt;1), can be predicted knowing the baseline loop gain and how much it falls with therapy. In 12 patients with heart failure, we administered an inspiratory carbon dioxide fraction of 1–3% during CSR (n=95 interventions) as a means to reduce loop gain. We estimated the loop gain on therapy (LG therapy ), using the baseline loop gain (using hyperpnoea length/cycle length) and its expected reduction (18% per 1% inspired carbon dioxide), and tested the specific hypothesis that LG therapy predicts CSR persistence (LG therapy &gt;1) versus resolution (LG therapy &lt;1). As predicted, when LG therapy &gt;1.0, CSR continued during therapy in 23 out of 25 (92%) trials. A borderline loop gain zone (0.8&lt;LG therapy &lt;1) yielded an unpredictable outcome, while LG therapy &lt;0.8 consistently yielded CSR resolution (37 out of 37 trials). A threshold of LG therapy =0.9 determined outcome in 76 out of 95 (80%) trials. We establish proof-of-concept that control theory provides predictive insight into CSR resolution in heart failure. Thus, we now have a means to calculate the size of interventions needed to ameliorate CSR on a patient-by-patient basis.
Diagnostic accuracy of the Salzburg EEG criteria for non-convulsive status epilepticus: a retrospective study
Authors: Markus Leitinger, Eugen Trinka, Elena Gardella, Alexandra Rohracher, Gudrun Kalss, Erisela Qerama, Julia Höfler, Alexander Hess, Georg Zimmermann, Giorgi Kuchukhidze, Judith Dobesberger, Patrick B Langthaler, Sándor Beniczky
Journal: The Lancet Neurology (2016)
Nonemergency Medical Transportation
Authors: Brian W. Powers, Scott Rinefort, Sachin H. Jain
Journal: JAMA (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Prognosis and prognostic factors of a large retrospective series of mucinous borderline tumors of the ovary (excluding peritoneal pseudomyxoma).
Authors: C. Uzan, M. Koskas, S. Gouy, P. Pautier, C. Lhomme, C. Balleyguier, C. Haie-Meder, P. Duvillard, P. Morice
Journal: Journal of Clinical Oncology (2010)

5096 Background: To determine the prognosis and prognostic factors in a large series of mucinous borderline tumors of the ovary (MBOT). Methods: A retrospective review of patients with MBOT treated or referred to our institution. Three inclusion criteria were defined: 1. centralized histological review by our expert pathologist; 2. exclusion of peritoneal pseudomyxoma and any synchronous malignant tumor in the abdominal cavity; 3. available data on the management and outcomes of patients. Results: From 1997 to 2004, 97 patients fulfilled inclusion criteria (95 stage I and 2 stage II disease). Nine patients had endocervical-like subtypes. Eight patients had stromal microinvasion and 24, intraepithelial carcinoma. Radical and conservative surgeries were performed respectively in 28 and 69 patients. After a median follow-up of 48 months, 13 patients had developed 14 recurrences: 7 were borderline and 7 were invasive lesions. The probability of recurrence in the form of carcinoma, 5 and 10 years after the diagnosis was respectively 9% and 13%. The only prognostic factor for recurrence attaining statistical significance was the use of a cystectomy (compared to other surgeries RR = 5.6; p = 0.003; compared to salpingo-oophorectomy RR = 5.5; p = 0.012). Conclusions: In the present series of 97 MBOT, mainly early-stage disease and excluding peritoneal pseudomyxoma, the cumulative risk of recurrence in the form of invasive carcinoma at 10 years was 13%. MBOT do not appear to be such a safe disease. The only prognostic factor for recurrence was the use of a cystectomy suggesting that a salpingo-oophorectomy should be preferred in case of conservative treatment. No significant financial relationships to disclose.
Assessing the Impact of Medication Adherence on Long-Term Cardiovascular Outcomes
Authors: Sameer Bansilal, Jose Maria Castellano, Ester Garrido, Henry G. Wei, Allison Freeman, Claire Spettell, Fernando Garcia-Alonso, Irene Lizano, Renee J.G. Arnold, Jay Rajda, Gregory Steinberg, Valentin Fuster
Journal: Journal of the American College of Cardiology (2016)
Gene expression combined with gene set enrichment analysis to identify markers of vinorelbine efficacy in breast cancer patients.
Authors: Robert Audet, Changyu Shen, Scooter Willis, Renata Duchnowska, Krzysztof Adamowicz, Jolanta Zok, Wojciech Rogowski, Maria Malgorzata Litwiniuk, Sylwia Debska, Magdalena Jaworska, Malgorzata Foszczynska-Kloda, Monika Kulma-Kreft, Katarzyna Zabkowska, Jacek Jassem, Susan Edgerton, Ann D. Thor, Kathy Miller, George W. Sledge, Brian Leyland-Jones
Journal: Journal of Clinical Oncology (2012)

e21099 Background: Vinorelbine (V) induces mitotic arrest and apoptosis but there are limited data on its effect on gene expression in breast cancer clinical setting. Methods: 43 adult female patients with pathologically confirmed breast cancer and locally advanced or metastatic disease were treated with V 25 mg/m 2 days 1, 8, 15 of a 28-day cycle. Gene expression was assessed in archival FFPE tissue using the microarray-based DASL assay (cDNA-mediated Annealing, Selection extension and Ligation) and correlated with time-to-progression (TTP). Using a Gene Set Enrichment Analysis (GSEA), groups of genes that share a common molecular function, chromosomal location, or regulation were identified in patients classified as having either a short (S) (n=25) or a long (L) (n=18) time to progression (TTP) divided by the median (72 days). The GSEA software ( http://www.broadinstitute.org/gsea/index.jsp ) was used for the analysis. Results: GSEA focusing on genes grouped according to similar a) molecular function: 16 out of a set of 43 genes involved in histone binding were enriched in group S (p = 0.002), consistent with higher expression in group S of HIST3H2BB and HIST1H3I as well as a nuclear transcription factor promoting their expression. b) transcription factors: 14 out of 47 genes were enriched in group S (p = 0.004) and corresponds to genes with promoter regions that match c-fos serum response element-binding transcription factor that modulates, for example, ABCC1 and ABCB1 (P-gp/MDR1) solute carriers. c) chromosomal location: in group S, genes were enriched on chromosome 11q21 (20 out of 45 genes p = 0.004) and on chromosome 12p12 (14 out of 22 genes p = 0.002). Conclusions: a) the up-regulation of histone binding genes is consonant with recent discovery of high affinity V binding to histones b) the role of P-gp/MDR1 in V transport is well known c) our observations on chromosome 11q21 and12p12 are novel. DASL expression combined with GSEA highlights gene sets that correlate with clinical outcome and may lead to predictive markers of V efficacy. Further confirmatory analysis is needed due to the limitation of small sample size and multiple comparisons.
Richter’s Syndrome In Chronic Lymphocytic Leukemia: Clinical and Laboratory Features In 119 Patients, Attempting To Identify Possible Risk Factors
Authors: Tamar Tadmor, Riva Fineman, Lev Shvidel, Osnat Bairey, Neta Goldschmidt, Rosa Ruchlemer, Naomi Rahimi Rachimi, Yair Herishanu, Mona Yuklea, Ariela Arad, Ariel Aviv, Aaron Polliack
Journal: Blood (2013)
NEMO—CXCL12/CXCR4 axis: a novel vantage point for antifibrotic therapies in chronic pancreatitis?
Authors: Albrecht Neesse, Volker Ellenrieder
Journal: Gut (2016)

Chronic pancreatitis (CP) is a common GI disorder with an incidence of 4/100 000 and a prevalence of 41/100 000.1 Owing to the chronic nature of the disease, patients with CP are often admitted to hospital and represent a serious socioeconomic burden across continents. Patients with CP have an increased mortality by more than threefold compared with the normal population, and the 20-year survival rate is reduced to 45% compared with 65% of the normal population.1 The disease mostly occurs in repeated episodes of acute inflammatory bouts of the pancreas parenchyma that progressively leads to exocrine and endocrine insufficiency, chronic pain and cachexia. Besides known lifestyle risk factors such as alcohol and nicotine, predisposing genetic mutations have been identified with cystic fibrosis transmembrane conductance regulator (CFTR), carboxypeptidase-A, cationic trypsinogen and serine protease inhibitor Kazal-type 1 being the most prominent candidates. Histologically, CP is characterised by a progressive loss of acinar cells that are replaced by activated pancreatic stellate cells (PSCs), and accumulation of extracellular matrix components such as collagen, vimentin and fibronectin. Furthermore, infiltrating immune and inflammatory cells are frequently detected in CP specimen, which has led to the notion of a ‘never healing wound’. The molecular mechanisms by which acinar damage either results in complete regeneration of the pancreas or eventually progresses to fibrosis and functional …