tbuckley/cabot-search huggingface dataset:
Labour calls for inquiry into NHS cyber-attack
Authors: Adrian O’Dowd
Journal: BMJ (2017)

Politicians and doctors’ leaders have called for an official inquiry into the “ransomware” cyber-attack that paralysed IT systems across 48 English NHS trusts, 13 NHS organisations in Scotland, general practices, and pharmacies on 12 May.12

Operations were postponed, appointments cancelled, and staff were asked to work over the weekend, as trusts put emergency plans into action to deal with the problem.

Barts Health NHS Trust, which runs five hospitals in east London and was one of the trusts most badly affected, was still reporting disruption to services on Monday and Tuesday, with some surgery and outpatient appointments cancelled.

The National Crime Agency has launched a criminal inquiry into who was responsible for the attack and how it was committed. But Jonathan Ashworth, Labour’s shadow health secretary, wrote to Jeremy Hunt, England’s health secretary, urging him to launch an independent inquiry into the attack and to assess whether patients’ data had been compromised. Ashworth demanded to know why NHS organisations had been left exposed to attack, what resources hospitals were being given to deal with the crisis, and what protections against cyber-attacks existed.

NHS Digital, the body responsible for ensuring that organisations meet information and security standards, said that most NHS organisations were …
Synergistic effect of Rapamycin and Casodex in inhibition of cell growth and survival as well as AR transcriptional activity in androgen dependent and independent prostate cancer cells
Authors: Yu Wang, Margarita Mikhailova, Jeffrey Kreisberg, Roble Bedolla, Naveen Krishnegowda, Paramita Ghosh
Journal: Cancer Research (2007)

988  Recurrent prostate cancer is treated with androgen deprivation, which includes suppression of androgen production alone or in combination with androgen receptor (AR) antagonists (including flutamide or bicalutamide (Casodex)). Patients usually respond initially to such treatment but frequently relapse indicative of the development of hormone refractory prostate cancer. The treatment options for such patients are limited, and while Phase I trials reveal 20-24% increased survival with docetaxel, options to prevent the progression of this disease have not been identified. Prostate cancer is characterized by frequent deletion or loss of heterozygosity in the tumor suppressor PTEN leading to activation of downstream components of the P13K pathway, including the Akt and mTOR kinases. The mTOR inhibitor rapamycin has been reported to inhibit metastatic prostate tumor growth and angiogenesis in in vivo mouse models and is currently in Phase I clinical trials. While rapamycin inhibited the growth of both androgen dependent and independent prostate cancer, it also has been shown to increase AR levels and AR transcriptional activity in vitro, resulting increased expression of prostate specific antigen (PSA), a serum biomarker which is commonly used to track changes in prostate cancer patients. In contrast, the antiandrogen Casodex has been shown to inhibit tumor growth as well as PSA expression in androgen dependent tumors, whereas androgen independent tumors were refractory to Casodex treatment. Since the effects of these two drugs on PSA levels are opposing in vitro, we investigated the effects of using the two in combination. The androgen dependent cell line LNCaP and its androgen independent sublines C4-2 and LNCaP-AI were treated with 100 nM rapamycin, 10 μM Casodex or both. Rapamycin substantially inhibited proliferation in all cells examined, whereas Casodex inhibited the growth of LNCaP cells by 50% but did not affect the growth of the androgen in dependent sublines. However, in combination, the two together had a synergistic effect and inhibited the growth of both androgen dependent and independent lines to a greater extent than either alone. While neither drug caused a substantial increase in apoptosis rates, the combination of rapamycin and Casodex caused substantial amount of apoptosis even in androgen independent cells. In addition, rapamycin increased AR and PSA levels in all 3 cell lines, whereas in combination with Casodex, AR and PSA levels were decreased in all cells examined. These results suggest that Casodex and rapamycin in combination may be of better therapeutic value than each drug individually.
IT'S NOT ‘WHO’ BUT ‘HOW BADLY’: THE ASSOCIATION OF FUNCTIONAL MOVEMENT SCREEN SCORE WITH INJURY OUTCOME IN COMMUNITY RUGBY UNION
Authors: Matt Attwood, Simon Roberts, Grant Trewartha, Mike England, Keith Stokes
Journal: British Journal of Sports Medicine (2017)

Background The use of the Functional Movement Screen (FMS) is widespread, but evidence supporting its use as an injury-screening tool in team sports such as Rugby Union is equivocal. Objective To determine the association between FMS score and match-injury incidence and match-injury burden in adult community rugby union players. Design Prospective cohort study. Setting English community rugby union clubs (2013–2014 season) with a formally qualified medical professional to diagnose and report match-injuries. FMS testing was completed during the pre-season period by the research team. Participants 436 players from 23 clubs completed the FMS. Match-injuries and individuals' match exposure data was returned for 293 players. Risk Factors Lower FMS composite score (21 point maximum), the presence of pain and/or asymmetry. Main Outcome Measurements Association of FMS composite score, pain and asymmetry with match injury incidence (≥8 days time-loss/1000 hours) severe injury incidence (&gt;28 days time-loss/1000 hours) and injury burden (total time-loss days/1000 hours). Results Poisson regression was offset for exposure (log transformed) and adjusted for random effects of club (cluster) and player. The associations between both match-injury incidence (≥8 days time-loss)(rate ratio (RR), 90% confidence interval (CI)=1.0, 0.9–1.0) and severe injury incidence (&gt;28 days time-loss) (RR, 90% CI=0.9, 0.8–1.0) with composite FMS score were trivial. A one-point increase in FMS score was associated with a 10% reduction in injury burden (RR, 90% CI=0.9, 0.8–1.0), while the presence of both pain and asymmetry was associated with a three times increase in injury burden (RR, 90% CI=2.9, 1.1–7.8). Conclusions FMS score was not associated with injury incidence, but was associated with injury burden. As the sstrongest association with injury burden was found for pain and asymmetry, clubs using the FMS may be advised to prioritise rehabilitation of players with asymmetrical, painful movement patterns.
Macrophage-derived IL-1α promotes sterile inflammation in a mouse model of acetaminophen hepatotoxicity
Authors: Chao Zhang, Jin Feng, Jun Du, Zhiyong Zhuo, Shuo Yang, Weihong Zhang, Weihong Wang, Shengyuan Zhang, Yoichiro Iwakura, Guangxun Meng, Yang-Xin Fu, Baidong Hou, Hong Tang
Journal: Cellular and Molecular Immunology (2017)
64Cu-DOTA-trastuzumab PET imaging for HER2-specific primary lesions of breast cancer
Authors: S. Sasada, H. Kurihara, T. Kinoshita, M. Yoshida, N. Honda, T. Shimoi, A. Shimomura, M. Yunokawa, K. Yonemori, C. Shimizu, A. Hamada, Y. Kanayama, Y. Watanabe, Y. Fujiwara, K. Tamura
Journal: Annals of Oncology (2017)
THE IMMUNOLOGICAL RELATIONSHIPS OF STREPTOCOCCUS VIRIDANS AND CERTAIN OF ITS CHEMICAL FRACTIONS
Authors: Rebecca C. Lancefield
Journal: The Journal of Experimental Medicine (1925)

1. The immunological behavior of two cell constituents of nonhemolytic streptococci has been studied, (a) One, the so called nucleoprotein, is relatively non-specific and gives rise to an antibody which shows group reactions with nucleoproteins of related species. (b) The other is non-protein by qualitative chemical tests. Preliminary chemical examination has indicated that it may be a carbohydrate. Although this substance is highly reactive with the specific antibodies produced by the intact bacterial cell, yet in its chemically purified condition it is probably non-antigenic. Specific serological reactions with this substance are dosely related to specific agglutination of the microorganism. 2. The study of sera prepared by immunization with the chemically extracted protein has shown the presence of antibodies for nudeoproteins alone. No antibodies against the specific soluble substance have been found in these sera. The protein antibodies are little, if at all, concerned in causing agglutination. Precipitin tests, complement fixation reactions, and absorption experiments have been used to analyze the group relationships with the nucleoproteins of other species. The proteins of each species of Gram-positive cocci studied were immunologically similar within the species and showed definite relationships to the proteins from related species. Proteins from bacteria of unrelated species did not react with antisera against streptococcus protein. 3. Two distinct antibodies have been demonstrated in antisera prepared against living bacteria. By prolonged immunization it was found possible to produce sera with a high content of protein as well as specific antibodies. With ordinary methods, however, the immune sera had a low content of relatively non-specific protein antibodies but a high titer for specific antibodies. The specific antibodies were not reactive with proteins but were active with high dilutions of the soluble specific substance and were responsible for the parallel specific agglutination. Absorption experiments showed that the two antibodies in antibacterial sera were immunologically distinct.
Post-transplantation long-term events in a cohort of HIV-positive patients affected by relapsed/refractory lymphoma.
Authors: Ernesto Zanet, Cristina Durante, Maurizio Rupolo, Mario Mazzucato, Stefania Zanussi, Paolo De Paoli, Arben Lleshi, Martina Taborelli, Diego Serraino, Umberto Tirelli, Michele Spina, Mariagrazia Michieli
Journal: Journal of Clinical Oncology (2015)

7031 Background: The advent of highly active antiretroviral therapy (HAART) allowed to extend autologous stem cell transplantation (ASCT) to the HIV-positive population. In the literature data are scarce concerning the long-term events in this population. Methods: We treated consecutively 36 HIV-positive patients (pts) affected by relapsed/refractory lymphomas with ASCT. Ten pts died during or early after ASCT due to progressive disease (4 pts), chemotherapy toxicity (1 pt) and infection (5 pts). We analyzed the post-ASCT long-term data of 26 pts, reaching a complete response after ASCT. All patients received HAART concomitantly to chemotherapy. Results: Two pts experienced a lymphoma relapse, after 4.27 and 3.08 years from ASCT, respectively. Five patients presented with a secondary malignancy (1 patient an anal squamous cell cancer, 1 patient a squamous cell carcinoma of the larynx and 1 patient a cervical intraepithelial neoplasia (CIN) grade 2, 1 patient a melanoma of the skin, 1 patient a HL developed in a patient primarily affected by NHL, respectively), with a median time of 3.01 years from ASCT. Nine patients had OI: 3 patients developed a Pneumocystis Carinii pneumonia, 1 patient a Cytomegalovirus pneumonia, 1 patient a Mycobacterium Avium Complex pneumonia, 1 patient a Herpes Simplex Chronic Ulcer, 3 patients cutaneous relapsing Herpes Zoster, respectively. The median time of OI appearance was 0.25 years (IQR: 0.11-2.33). Two pts died: one of lymphoma relapse, the other of car accident.With a median of 6-years follow up (IQR: 4.55-9.87) the OS and PFS of the entire sample of pts were 91% and 36% at 10 years, respectively. Conclusions: 24 out of 26 pts are still alive and in long-term complete remission after ASCT. These data confirm the long-term efficacy of ASCT. The appearance of OI is earlier than that of second malignancies after ASCT. The secondary malignancies developed by our pts are non-AIDS-defining cancers and at least three cases are linked to a viral pathogenesis (HPV for both anal cancer and cervical cancer precursor lesion; EBV for HL). Both OI and second malignancies were successfully managed and cured and the only long-term death occurred due to lymphoma relapse.
Long-term outcomes after endoscopic ultrasound-guided ablation of pancreatic cysts
Authors: Jun-Ho Choi, Dong Seo, Tae Song, Do Park, Sang Lee, Sung Lee, Myung-Hwan Kim
Journal: Endoscopy (2017)

Abstract Background and study aims The aim of this study was to investigate the long-term outcomes after endoscopic ultrasound (EUS)-guided pancreatic cyst ablation. Patients and methods In a single-center, prospective study, 164 patients with pancreatic cysts underwent EUS-guided cyst ablation using ethanol with paclitaxel. The inclusion criteria were as follows: unilocular or oligolocular cysts; clinically indeterminate cysts that required EUS fine-needle aspiration; and/or cysts that grew during the observation period. Treatment response was classified as complete resolution, partial resolution, or persistent cyst, with &lt; 5 %, 5 % – 25 %, and 25 % of the original cyst volume, respectively. Results The median largest diameter of the cyst was 32 mm and the median volume was 17.1 mL. Based on cyst fluid analysis there were 71 mucinous cystic neoplasms, 16 serous cystic neoplasms, 11 intraductal papillary mucinous neoplasms, 3 pseudocysts, and 63 indeterminate cysts. Sixteen treated patients (9.8 %) had adverse events (1 severe, 4 moderate, and 11 mild). Treatment response was as follows: complete resolution in 114 (72.2 %), partial resolution in 31 (19.6 %), and persistent cysts in 13 (8.2 %). Twelve of the 13 patients with persistent cysts underwent surgery. During clinical and imaging follow-up (median 72 months, interquartile range 50 – 85 months) of the 114 patients with complete resolution, only two patients (1.7 %) showed cyst recurrence. Based on multivariate analysis, the absence of septa (odds ratio [OR] 7.12, 95 % confidence interval [CI] 2.72 – 18.67) and cyst size less than 35 mm (OR 2.39, 95 %CI 1.11 – 5.16) predicted complete resolution. Conclusion Among patients with pancreatic cysts in whom complete resolution was achieved after EUS-guided cyst ablation, 98.3 % remained in remission at 6-year follow-up. Unilocular form and small cyst size were predictive of complete resolution. This treatment approach may be an effective and durable alternative to surgery. Trial registered at ClinicalTrials.gov (NCT 00689715).
Toxic Effects and Side-effects of Methylpentynol
Authors: E. Marley, J. S. W. Chambers
Journal: BMJ (1956)

The patients in the ear, nose, and throat wards were under the care of Mr. C. P. Wilson, Mr. J. P. Monkhouse, and Mr. D. Ranger, and I thank them for permission to carry out the trial. I also thank Dr. J. D. N. Nabarro for his criticisms and en couragement in the preparation of the paper; Mr. M. P. Curwen, of St. Bartholomew's Hospital, for his invaluable help with the statistics; Dr. Margaret Briggs, of Roche Products, for the pre paration and dispensing of the tablets; and the night sisters and their nursing staff, whose enthusiastic co-operation made this trial nnssiileh REFERENCES Brandman, O., Coniaris. J., and Keller, H. B. (1955). J. med. Soc. N.J., 52, 246. Cass, L. J., Frederik, W. S., and Andosca, J. B. (1955). New Engl. J. Med., 253. 586. Hare, E. H. (1955). Brit. J. prev. soc. Med., 9, 140. Kemper, H. (1955). Dtsch. med. Wschr., 80, 1034. Schmitt, W. (1955). Med. KlUn., 50, 1223.
Response by Wiberg et al to Letter Regarding Article, “Neuroprotective Effects of the Glucagon-Like Peptide-1 Analog Exenatide After Out-of-Hospital Cardiac Arrest: A Randomized Controlled Trial”
Authors: Sebastian Wiberg, Christian Hassager, Jesper Kjaergaard
Journal: Circulation (2017)

In Response:We appreciate the interest of Ma and colleagues in our article reporting the neuroprotective effects of the glucagon-like peptide-1 analog exenatide after out-ofhospital cardiac arrest. 1 Ma et al suggest that the neutral findings of our trial could be caused by propofol, which was used to sedate the patients during the period of targeted temperature management.To the best of our knowledge, no double-blind randomized studies have demonstrated the clinical superiority of any sedative agent in the cardiac arrest setting, 2,3 and accordingly, contemporary guidelines do not support the use of any particular sedative agent. 4All participants in our double-blind randomized trial were sedated with propofol and fentanyl during targeted temperature management, after which sedation was tapered and discontinued.Thus, if the neutral findings of our trial were caused by the administration of propofol, propofol would have to affect the effect of exenatide directly.We have not been able to find any suggestions of such causation in the literature.In addition, Ma et al are interested to know whether the dose and timing of opioids during admission in the intensive care unit affect patient outcomes.Fentanyl was routinely used and discontinued after targeted temperature management, and our trial was not designed to show any causation between the use of opioids and outcome.As described in our article, contrary to previous trials demonstrating organ-protective effects of glucagon-like peptide-1 analogs, we administered exenatide after return of spontaneous circulation for logistical reasons, that is, after reperfusion, which may have diminished any potential effect of exenatide.We believe that future studies examining organ-protective interventions in the cardiac arrest setting should try to initiate the intervention as soon as possible, optimally before return of spontaneous circulation.
PTU-014 Impact of Primary Care Education on the Two Week wait Referral Process for GI Cancers: Abstract PTU-014 Table
Authors: S Biswas, A Willington, A Ellis
Journal: Gut (2013)

<h3>Introduction</h3> The two week wait referral process was introduced in 2000 to improve cancer prognosis in the UK with an anticipated 20% reduction in cancer-related deaths. The cancer yield has in fact been reported as 9–16%. Referrals should be made on the basis of NICE guidance. Previous studies have highlighted that as few as 53% of referrals from Primary Care have been within NICE guidance. The Government’s nine-week “Be clear on cancer” campaign launched in January 2012 via online, TV and radio adverts to increase public awareness of bowel cancer symptoms impacted our service. The proportion of colonoscopies done for the two-week wait service increased from 27% to 48% in the month after the campaign. It is clearly important that referrals made are appropriate to justify this service requirement. This study compares referrals and outcomes before and after a GP education session. <h3>Methods</h3> Two week wait GI Referrals to the Horton General Hospital between December 2011 and February 2012 were assessed. A presentation was given to Primary Care Practitioners in May highlighting NICE guidance and referrals were re-audited in June 2012. <h3>Results</h3> 100% of referrals met the two week wait target (to clinic, CT scan or endoscopy) and the mean time to first test was 9 days. The results are summarised below. 24% of Upper GI referrals did not meet NICE guidance, mostly patients referred with anaemia above the referral threshold or for dyspepsia without concerning features. The cancer pick-up was 8.6% (2 oesophageal, 2 gastric and 4 pancreatico-biliary). 26% of Lower GI referrals were non-compliant with guidance (mostly due to rectal bleeding or change in bowel habit shorter than the required time). Cancer pick-up was 5.1%. All but one GI cancer was detected in appropriately referred patients. In June 2012 compliance improved to 81% of upper GI and 79% of lower GI referrals. Reasons for referral outside NICE guidance were similar to the previous cohort. Cancer detection rose to 12.9% for Upper GI and 8.6% for Lower GI cancers. All cancers in the second audit were in appropriately referred patients. <h3>Conclusion</h3> The study highlights the importance of communication with Primary Care Practitioners who are responsible for referrals for GI cancer exclusion. There have been previous education sessions but despite this there remains an advantage in re-stating the message and keeping regular contact. The cancer detection rate improved with better compliance with NICE guidance and may indicate the value of adhering to this guidance. Larger studies are required to validate this. <h3>Disclosure of Interest</h3> None Declared
Transmembrane activator, calcium modulator, and cyclophilin ligand interactor drives plasma cell differentiation in LPS-activated B cells
Authors: Esra Ozcan, Lilit Garibyan, John Jhe-Yun Lee, Richard J. Bram, Kong-Peng Lam, Raif S. Geha
Journal: Journal of Allergy and Clinical Immunology (2009)
Bedaquiline-based treatment regimen for multidrug-resistant tuberculosis
Authors: Ioana D. Olaru, Jan Heyckendorf, Sönke Andres, Barbara Kalsdorf, Christoph Lange
Journal: European Respiratory Journal (2017)

Treatment outcomes for multidrug-resistant (MDR) tuberculosis (TB) are poor with only approximately 50% of patients attaining treatment success [1]. An important driver of treatment failure in many settings is the unavailability of effective drugs for MDR- and extensively drug-resistant (XDR)-TB. Bedaquiline-based therapy leads to high rates of culture conversion in the treatment of MDR-TB <http://ow.ly/RGr230bqlVD>
Epigenetic aspects of triple-negative in patients with breast cancer.
Authors: Joaquina Martínez-Galan, Sandra Rios, Juan Ramon Delgado, Blanca Torres-Torres, Jesus Lopez-Peñalver, M. Isabel Núñez
Journal: Journal of Clinical Oncology (2012)

1041 Background: Identification of gene expression-based breast cancer subtypes is considered a critical means of prognostication. Genetic mutations along with epigenetic alterations contribute to gene-expression changes occurring in breast cancer. However, the reproducibility of differential DNA methylation discoveries for cancer and the relationship between DNA methylation and aberrant gene expression have not been systematically analysed. The present study was undertaken to dissect the breast cancer methylome and to deliver specific epigenotypes associated with particular breast cancer subtypes. Methods: By using Real Time QMSPCR SYBR green we analyzed DNA methylation in regulatory regions of 107 pts with breast cancer and analyzed association with prognostics factor in triple negative breast cancer and methylation promoter ESR1, APC, E-Cadherin, Rar B and 14-3-3 sigma. Results: We identified novel subtype-specific epigenotypes that clearly demonstrate the differences in the methylation profiles of basal-like and human epidermal growth factor 2 (HER2)-overexpressing tumors. Of the cases, 37pts (40%) were Luminal A (LA), 32pts (33%) Luminal B (LB), 14pts (15%) Triple-negative (TN), and 9pts (10%) HER2+. DNA hypermethylation was highly inversely correlated with the down-regulation of gene expression. Methylation of this panel of promoter was found more frequently in triple negative and HER2 phenotype. ESR1 was preferably associated with TN(80%) and HER2+(60%) subtype. With a median follow up of 6 years, we found worse overall survival (OS) with more frequent ESR1 methylation gene(p&gt;0.05), Luminal A;ESR1 Methylation OS at 5 years 81% vs 93% when was ESR1 Unmethylation. Luminal B;ESR1 Methylation 86% SG at 5 years vs 92% in Unmethylation ESR1. Triple negative;ESR1 Methylation SG at 5 years 75% vs 80% in unmethylation ESR1. HER2;ESR1 Methylation SG at 5 years was 66.7% vs 75% in unmethylation ESR1. Conclusions: Our results provide evidence that well-defined DNA methylation profiles enable breast cancer subtype prediction and support the utilization of this biomarker for prognostication and therapeutic stratification of patients with breast cancer.
A Controlled Trial of the Effect of Calcium Supplementation on Bone Density in Postmenopausal Women
Authors: Bess Dawson-Hughes, Gerald E. Dallal, Elizabeth A. Krall, Laura Sadowski, Nadine Sahyoun, Saul Tannenbaum
Journal: New England Journal of Medicine (1990)

The effectiveness of calcium in retarding bone loss in older postmenopausal women is unclear. Earlier work suggested that the women who were most likely to benefit from calcium supplementation were those with low calcium intakes.