tbuckley/cabot-search huggingface dataset:
Francis sets out new standards of accountability and transparency for doctors
Authors: Helen Jaques
Journal: BMJ (2013)

Doctors should have a contractual duty to meet “fundamental” standards of care and could be criminally liable for shortcomings in services, Robert Francis QC has said in his report on the Mid Staffordshire NHS Foundation Trust.

He recommends introducing a statutory responsibility for NHS staff to inform their employers of any cases where patients may have experienced harm. It should also be a criminal offence for any healthcare worker to knowingly prevent another member of staff from blowing the whistle on poor care, he adds.

In 2010, the government launched a public inquiry, headed by Francis, into the poor care provided by Mid Staffordshire NHS Foundation Trust between January 2005 and March 2009. A previous inquiry, also led by Francis, heard how patients treated by the trust during this period received “appalling” care.

The three volume report of the inquiry, describes how the trust’s board failed …
Nonstructural protein 5A/P32 deletion after failure of ledipasvir/sofosbuvir in hepatitis C virus genotype 1b infection
Authors: Akira Doi, Hayato Hikita, Ryotaro Sakamori, Yuki Tahata, Yugo Kai, Ryoko Yamada, Takayuki Yakushijin, Eiji Mita, Kazuyoshi Ohkawa, Yasuharu Imai, Kunimaro Furuta, Takahiro Kodama, Tomohide Tatsumi, Tetsuo Takehara
Journal: Hepatology (2018)

Doi, Akira; Hikita, Hayato; Sakamori, Ryotaro; Tahata, Yuki; Kai, Yugo; Yamada, Ryoko; Yakushijin, Takayuki; Mita, Eiji; Ohkawa, Kazuyoshi; Imai, Yasuharu; Furuta, Kunimaro; Kodama, Takahiro; Tatsumi, Tomohide; Takehara, Tetsuo Author Information
Adeno-Associated Viral Vector (Serotype 2)–Nerve Growth Factor for Patients With Alzheimer Disease
Authors: Michael S. Rafii, Mark H. Tuszynski, Ronald G. Thomas, David Barba, James B. Brewer, Robert A. Rissman, Joao Siffert, Paul S. Aisen
Journal: JAMA Neurology (2018)

Nerve growth factor (NGF) is an endogenous neurotrophic factor that prevents the death and augments the functional state of cholinergic neurons of the basal forebrain, a cell population that undergoes extensive degeneration in Alzheimer disease (AD).To determine whether stereotactically guided intracerebral injections of adeno-associated viral vector (serotype 2)-nerve growth factor (AAV2-NGF) are well tolerated and exhibit preliminary evidence of impact on cognitive decline in mild to moderate AD-associated dementia.In a multicenter phase 2 trial, 49 participants with mild to moderate AD were randomly assigned in a 1:1 ratio to receive stereotactically guided intracerebral injections of AAV2-NGF or sham surgery. Participants were enrolled between November 2009 and December 2012. Analyses began in February 2015. The study was conducted at 10 US academic medical centers. Eligibility required a diagnosis of mild to moderate dementia due to AD and individuals aged 55 to 80 years. A total of 39 participants did not pass screening; the most common reason was Mini-Mental State Examination scores below cutoff. Analyses were intention-to-treat.Stereotactically guided intracerebral injections of AAV2-NGF into the nucleus basalis of Meynert of each hemisphere or sham surgery.Change from baseline on the Alzheimer's Disease Assessment Scale-cognitive subscale at month 24.Among 49 participants, 21 (43%) were women, 42 (86%) self-identified as white, and the mean (SD) age was 68 (6.4) years. AAV2-NGF was safe and well-tolerated through 24 months. No significant difference was noted between the treatment group and placebo on the primary outcome measure, the Alzheimer's Disease Assessment Scale-cognitive subscale (mean [SD] score, 14.52 [4.66] vs 9.11 [4.65], P = .17).This multicenter randomized clinical trial demonstrated the feasibility of sham-surgery-controlled stereotactic gene delivery studies in patients with AD. AAV2-NGF delivery was well-tolerated but did not affect clinical outcomes or selected AD biomarkers. Pathological confirmation of accurate gene targeting is needed.clinicaltrials.gov Identifier NCT00876863.
METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS CAUSING PURULENT PERICARDITIS IN THE SETTING OF INTRAVENOUS DRUG USE
Authors: Lavneet Chawla, Tasleem Katchi, Anna Koulova, Nitin Kabra, Shashvat Gupta, Srikanth Yandrapalli, Gregg Lanier, Howard Cooper
Journal: Journal of the American College of Cardiology (2018)
TWO YEAR RESULTS FROM THE COMPARE-ACUTE TRIAL
Authors: Pieter Smits, Elmir Omerovic, Mohamed Abdel-Wahab, Bianca Boxma-de Klerk, Ketil Lunde, Franz-Josef Neumann, Carl Schotborgh, David Horak, Zsolt Piroth, Adrian Wlodarczack, Paul Ong, Petr Kala, Gert Richardt, Maasstad Ziekenhuis
Journal: Journal of the American College of Cardiology (2018)
Disruption of CTCF Boundary Remodels Chromatin Domain and Reprograms HOX Gene Transcription in Acute Myeloid Leukemia
Authors: Huacheng Luo, Fei Wang, Haoli Li, Qinghua Du, Bowen Yan, Shi Chen, Baoan Chen, Yi Qiu, Mingjiang Xu, Suming Huang
Journal: Blood (2017)
Abstract P5-07-12: miR-34a as a prognostic biomarker for overall survival triple negative breast cancer within Tunisian patients
Authors: I Medimegh, H Ayari, O Baraudi, H Majoul, I Omrane, E Yousef, F Benayed, K Benromdhan, L Gaboury, S Mader, A Benammarelgaaied
Journal: Cancer Research (2018)

Abstract Introduction: miR-34a has been recently introduced to clinical trials especially in breast cancer depending on its crucial role as microRNA suppressor tumors since it regulates several oncogenes. We explore here the prognostic effect of miR-34a on triple negative breast cancer (TNBC) overall survival compared to no triple negative (NTNBC) group and its effect on PARP-1 and BRCA1 protein expression. Methods: 76 patients with TNBC and NTNBC were recruited for this study. miR-34a was quantified using qPCR Syber Green technique. PARP-1 and BRCA1 were analyzed by IHC using Tissue Micro-Array method. Results: PARP-1 is more expressed in TNBC compared to NTNBC; P = 0.04; RR= 1.8 (1.1-3.1), however, BRCA1 is less expressed in TNBC; P = 0.03; RR= 2 (1.2-12.6). Furthermore, we evaluated the relationship between miR-34a and clinicopathological features with survival rate of both studied groups, we found that miR-34a is more expressed among patients with distance metastases in TNBC group P = 0.001; RR = 6.5 (2.1-19.6). Survival analysis showed that miR-34a low expression in TNBC was remarkably related to overall survival; P=0.012. Furthermore, multivariate survival test suggested that the absence of miR-34a was linked to the poor survival within TNBC according to the presence of distance metastasis; P=0.048; HR= 2.69. Our results showed that miR-34a is decreased in triple negative breast cancer patients with a very poor prognosis. Conclusion:Our results give mechanistic insights in miR-34a as a prognostic biomarker for overall survival Triple Negative Breast Cancer within Tunisian patients through its effect on PARP-1 and BRCA1 protein expression which may open potential new strategies towards prevention and therapeutic inhibition of PARP-1 positive within mammary tumors. Citation Format: Medimegh I, Ayari H, Baraudi O, Majoul H, Omrane I, Yousef E, Benayed F, Benromdhan K, Gaboury L, Mader S, Benammarelgaaied A. miR-34a as a prognostic biomarker for overall survival triple negative breast cancer within Tunisian patients [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-07-12.
Preprocessing of 2-Dimensional Gel Electrophoresis Images Applied to Proteomic Analysis: A Review
Authors: Manuel Mauricio Goez, Maria Constanza Torres-Madroñero, Sarah Röthlisberger, Edilson Delgado-Trejos
Journal: Genomics Proteomics & Bioinformatics (2018)

Abstract Various methods and specialized software programs are available for processing two-dimensional gel electrophoresis (2-DGE) images. However, due to the anomalies present in these images, a reliable, automated, and highly reproducible system for 2-DGE image analysis has still not been achieved. The most common anomalies found in 2-DGE images include vertical and horizontal streaking, fuzzy spots, and background noise, which greatly complicate computational analysis. In this paper, we review the preprocessing techniques applied to 2-DGE images for noise reduction, intensity normalization, and background correction. We also present a quantitative comparison of non-linear filtering techniques applied to synthetic gel images, through analyzing the performance of the filters under specific conditions. Synthetic proteins were modeled into a two-dimensional Gaussian distribution with adjustable parameters for changing the size, intensity, and degradation. Three types of noise were added to the images: Gaussian, Rayleigh, and exponential, with signal-to-noise ratios (SNRs) ranging 8–20 decibels (dB). We compared the performance of wavelet, contourlet, total variation (TV), and wavelet-total variation (WTTV) techniques using parameters SNR and spot efficiency. In terms of spot efficiency, contourlet and TV were more sensitive to noise than wavelet and WTTV. Wavelet worked the best for images with SNR ranging 10–20 dB, whereas WTTV performed better with high noise levels. Wavelet also presented the best performance with any level of Gaussian noise and low levels (20–14 dB) of Rayleigh and exponential noise in terms of SNR. Finally, the performance of the non-linear filtering techniques was evaluated using a real 2-DGE image with previously identified proteins marked. Wavelet achieved the best detection rate for the real image.
A phase 1 study of CPI-1205, a small molecule inhibitor of EZH2, preliminary safety in patients with B-cell lymphomas
Authors: W. Harb, J. Abramson, M. Lunning, A. Goy, K. Maddocks, C. Lebedinsky, A. Senderowicz, P. Trojer, W.D. Bradley, I. Flinn
Journal: Annals of Oncology (2018)
Magnetic Resonance Imaging of the Sacroiliac Joints Indicating Sacroiliitis According to the Assessment of SpondyloArthritis international Society Definition in Healthy Individuals, Runners, and Women With Postpartum Back Pain
Authors: Janneke de Winter, Manouk de Hooge, Marleen van de Sande, Henriëtte de Jong, Lonneke van Hoeven, Anoek de Koning, Inger Jorid Berg, Roberta Ramonda, Dominique Baeten, Désirée van der Heijde, Angelique Weel, Robert Landewé
Journal: Arthritis & Rheumatology (2018)

Objective To compare magnetic resonance images ( MRI s) of the sacroiliac ( SI ) joints of healthy subjects and individuals with known mechanical strain acting upon the SI joints to those of patients with axial spondyloarthritis (SpA) and patients with chronic back pain. Methods Three readers who had received standardized training and were blinded with regard to study group randomly scored MRI s of the SI joints of 172 subjects, including 47 healthy individuals without current or past back pain, 47 axial SpA patients from the Spondyloarthritis Caught Early ( SPACE ) cohort (with a previous MRI confirmed positive for sacroiliitis), 47 controls with chronic back pain (irrespective of MRI results) from the SPACE cohort, 7 women with postpartum back pain, and 24 frequent runners. MRI s were scored according to the Assessment of SpondyloArthritis international Society ( ASAS ) definition and Spondyloarthritis Research Consortium of Canada ( SPARCC ) index. Results Of the 47 healthy volunteers, 11 (23.4%) had an MRI positive for sacroiliitis, compared to 43 (91.5%) of 47 axial SpA patients and 3 (6.4%) of 47 patients with chronic back pain. Three (12.5%) of the 24 runners and 4 (57.1%) of the 7 women with postpartum back pain had a positive MRI . Using a SPARCC cutoff of ≥2 for positivity, 12 (25.5%) of 47 healthy volunteers, 46 (97.9%) of 47 positive axial SpA patients, 5 (10.6%) of 47 controls with chronic back pain, 4 (16.7%) of 24 runners, and 4 (57.1%) of 7 women with postpartum back pain had positive MRI s. Deep bone marrow edema ( BME ) lesions were not found in healthy volunteers, patients with chronic back pain, or runners, but were found in 42 (89.4%) of 47 positive axial SpA patients and in 1 (14.3%) of 7 women with postpartum back pain. Conclusion A substantial proportion of healthy individuals without current or past back pain has an MRI positive for sacroiliitis according to the ASAS definition. Deep (extensive) BME lesions are almost exclusively found in axial SpA patients.
THE ANGIOTENSIN RECEPTOR NEPRILYSIN INHIBITOR (ARNI), SACUBITRIL/VALSARTAN, IMPROVES LEFT VENTRICULAR MYOCARDIAL DEFORMATION IN HEART FAILURE WITH PRESERVED EJECTION FRACTION (PARAMOUNT TRIAL)
Authors: Tor Biering-Sorensen, Amil Shah, Brian Claggett, Michael Zile, Burkert Pieske, Elisabeth Pieske-Kraigher, Adriaan Voors, Victor Shi, Martin Lefkowitz, Milton Packer, John J.V. McMurray, Scott Solomon
Journal: Journal of the American College of Cardiology (2018)
How to vaccinate your PC against cyber bugs⇓
Authors: Mark Lloyd, Jon Simmons, Helen McEvoy, Peter Butler, Simon Whithey
Journal: BMJ (2004)

<i>Email has become a common form of communication for most doctors, but did you know that your computer is at risk from infection with Trojans, viruses, and worms?</i> Mark Lloyd and colleagues <i>clarify the confusing names given to computer threats and offer practical advice on how to vaccinate your PC or Mac from cyber attack</i>
Association of age and sex with mortality following adjuvant therapy for renal cell cancer (RCC): Subgroup analysis of the ASSURE (E2805) trial.
Authors: Ronac Mamtani, Xin Victoria Wang, Robert S. DiPaola, Janice P. Dutcher, Naomi B. Haas
Journal: Journal of Clinical Oncology (2018)

575 Background: The benefit of vascular endothelial growth factor tyrosine kinase inhibitors (VEGF-TKIs) as adjuvant therapy for RCC remains a subject of controversy. Given the uncertain risk-benefit ratio, identifying subgroups expected to derive benefit or harm from therapy could lead to a more precise approach to therapy. Because of known sex-differences in the pharmacokinetics and tissue distribution of VEGF-TKIs, we assessed the interaction of age and sex on treatment outcomes among patients in the phase III ASSURE trial (Adjuvant Sorafenib or Sunitinib for Unfavorable RCC). Methods: ASSURE included 1,943 patients with ≥ pT1b resected RCC. There was no OS or DFS benefit with adjuvant sunitinib or sorafenib relative to placebo. In this post-hoc subgroup analysis of age and sex based on the median age of 56 years, Cox regression computed hazard ratios (HR) and 95% confidence intervals (CIs) for OS and DFS with sunitinib or sorafenib compared to placebo across age- and sex-specific strata (males ≤ 56 years [n = 689], males &gt; 56 years [n = 620], females ≤ 56 years [n = 317], and females &gt; 56 years [n = 317]). Models were adjusted for race, histology, and UISS risk group. A 3-way interaction term was calculated for sex, age, and treatment. Results: Treatment with sunitinib was associated with increased mortality among women &gt; 56 years (sunitinib vs placebo [HR OS 2.38; 95% CI, 1.39-4.07]), but not in women ≤ 56 years or in men of any age. Similarly, among women &gt; 56 years, the risk of disease recurrence was increased with sunitinib relative to placebo (HR DFS 1.53; 95% CI, 1.03-2.28). There were no statistically significant differences in OS or DFS associated with sorafenib (women &gt; 56 years: HR OS 1.50, 95% CI, 0.83-2.71; HR DFS 1.23, 95% CI, 0.81-1.89). The 3-way interaction between age, sex, and sunitinib treatment on mortality was statistically significant (p = 0.0166). Conclusions: Adjuvant sunitinib after nephrectomy was associated with increased mortality among older women, which may be explained by increased risk of RCC recurrence. These findings, if validated, highlight the importance of considering sex and age on VEGF-TKI treatment outcomes, future study designs, and RCC tumor biology. Clinical trial information: NCT00326898.
Hospital doctors’ pay stagnated in England in 2012
Authors: Helen Jaques
Journal: BMJ (2012)

Pay for hospital consultants and registrars in England barely changed from 2011 to 2012, annual figures from the Health and Social Care Information Centre show.

On average, hospital consultants earned £109 651 in the year ending September 2012 (down 0.8% on 2011), of …
VALIDATION OF THE PREDICTING BLEEDING COMPLICATIONS IN PATIENTS UNDERGOING STENT IMPLANTATION AND SUBSEQUENT DUAL ANTIPLATELET THERAPY (PRECISE-DAPT) SCORE IN THE ELDERLY POPULATION
Authors: David Marti, Damaris Carballeira Puentes, Jose Morales Gallardo, David Brau Queralt, Ricardo Concepcion Suarez, Andrea Rueda Linares, Carlos Jiménez Chillón, Edurne Lopez, Jorge Palazuelos, Salvador Álvarez
Journal: Journal of the American College of Cardiology (2018)
Porphyrin-grafted Lipid Microbubbles for the Enhanced Efficacy of Photodynamic Therapy in Prostate Cancer through Ultrasound-controlled <i>In Situ</i> Accumulation
Authors: Yujia You, Xiaolong Liang, Tinghui Yin, Min Chen, Chen Qiu, Chuang Gao, Xiaoyou Wang, Yongjiang Mao, Enze Qu, Zhifei Dai, Rongqin Zheng
Journal: Theranostics (2018)

Photodynamic therapy (PDT) holds promise for focal therapy of prostate cancer (PCa).However, the therapeutic efficacy needs improvement, and further development of PDT for PCa has challenges, including uncertainty of photosensitizers (PSs) accumulation at the tumor site and difficulty in visualizing lesions using conventional ultrasound (US) imaging.We have developed novel porphyrin-grafted lipid (PGL) microbubbles (MBs; PGL-MBs) and propose a strategy to integrate PGL-MBs with US imaging to address these limitations and enhance PDT efficacy.Methods: PGL-MBs have two functions: imaging guidance by contrast-enhanced ultrasound (CEUS) and targeted delivery of PSs by ultrasound targeted microbubble destruction (UTMD).PGL-MBs were prepared and characterized before and after low-frequency US (LFUS) exposure.Then, in vitro studies validated the efficacy of PDT with PGL-MBs in human prostate cancer PC3 cells.PC3-xenografted nude mice were used to validate CEUS imaging, accumulation at the tumor site, and in vivo PDT efficacy.Results: PGL-MBs showed good contrast enhancement for US imaging and were converted into nanoparticles upon LFUS exposure.The resulting uniquely structured nanoparticles avoided porphyrin fluorescence quenching and efficiently accumulated at the tumor site through the sonoporation effect created with the assistance of US to achieve excellent PDT efficacy.Conclusions: This is the first preclinical investigation of MBs applied in PDT for PCa.PGL-MBs possess favorable CEUS imaging effects to enhance the localization of tumors.PGL-MBs with LFUS control PS accumulation at the tumor site to achieve highly effective PDT of PCa.This strategy carries enormous clinical potential for PCa management.
Comparative genomic profiling (CGP) of refractory/metastatic penile (mPSCC) and non-penile cutaneous squamous cell carcinoma (mCSCC).
Authors: Joseph M Jacob, Oleg Shapiro, Elizabeth Kate Ferry, Laurie M. Gay, Julia Andrea Elvin, Jo-Anne Vergilio, James Suh, Shakti Ramkissoon, Siraj Mahamed Ali, Alexa Betzig Schrock, Jon Chung, Vincent A. Miller, Philip J. Stephens, Gennady Bratslavsky, Jeffrey S. Ross
Journal: Journal of Clinical Oncology (2018)

552 Background: mPSCC is an aggressive malignancy with limited treatment options. Using CGP, we compared the therapy impacting genomic alterations (GA) between mPSCC and cutaneous mCSCC. Methods: DNA was extracted from 40 microns of FFPE samples from 78 cases of mPSCC and 338mCSCC.Comprehensive genomic profiling (CGP) was performed using a hybrid-capture, adaptor ligation based next generation sequencing assayto a mean coverage depth of &gt; 500X. Tumor mutational burden (TMB) was determined on 1.1 Mbp of sequenced DNA and microsatellite instability (MSI) was determined on 114 loci. Results: mPSCC patients were younger than mCSCC (Table). Both tumors types feature high CDKN2A, TERT and FAT1 GA frequencies. NOTCH1 and PTCH1 GA are also more common in mCSCC than mPSCC. CD274 ( PD-L1) amplification was rare in both tumor types. Targeted therapy opportunities in mPSCC included alterations in kinase pathways ( EGFR GA in 6%; FGFR3 and ERBB2 GA in 4%); MTOR pathway ( NF1 GA in 7% and PTENGA in4%) and DNA repair pathway ( BRCA2and ATMGA in 7%). TMB was significantly higher in the UV light exposed mSCC than mPSCC with both tumor types having potential for responsiveness to immunotherapies. MSI-High status was extremely rare for both mPSCC and mCSCC. HPV viral DNA was identified in 29% on mPSCC but only in 5% of mCSCC. TP53 GA were significantly more frequent in HPV- than HPV+ mPSCC and mCSCC respectively (P &lt; 0.0001 for both). Clinical outcomes of selected patients will be presented. Conclusions: mPSCC is a unique subtype of SCC with distinctive genomic features that contrast with those identified in mCSCC of non-penile UV light exposed skin. Given the potential opportunities for targeted therapies and immunotherapies that can be uncovered, continued study of CGP for the guidance of treatment for patients with mPSCC appears warranted.[Table: see text]
Over 95% of applicants to 2015 foundation programme have been allocated, UKFPO says
Authors: Abi Rimmer
Journal: BMJ (2015)

The UK Foundation Programme Office (UKFPO) has announced that 7086 applicants (95.3%) to the 2015 foundation programme have been allocated to a foundation school. Just over 90% of applicants obtained a place at one of their top five schools, and 81% were allocated to one of their top two choices.

In January …
Galectin-3 is essential for proper bone cell differentiation and activity, bone remodeling and biomechanical competence in mice
Authors: Carla Iacobini, Claudia Blasetti Fantauzzi, Rossella Bedini, Raffaella Pecci, Armando Bartolazzi, Bruno Amadio, Carlo Pesce, Giuseppe Pugliese, Stefano Menini
Journal: Metabolism (2018)
SYMPATHETIC RENAL DENERVATION AFTER ACUTE MYOCARDIAL INFARCTION BLUNTS ADRENERGIC ACTIVATION AND INCREASED MYOCARDIAL SALVAGE IN PIGS
Authors: Luigi Emilio Pastormerlo, Vincenzo Castiglioni, Burchielli Silvia, Chrisantos Grigoratos, Giovanni Donato Aquaro, Assuero Giorgetti, Paolo Marzullo, Eleonora Benelli, Fabio Bernini, Maria Franzini, Angela Pucci, Silvia Masotti, Veronica Musetti, Claudio Passino, Michele Emdin
Journal: Journal of the American College of Cardiology (2018)