tbuckley/cabot-search huggingface dataset:
The association and prognostic significance of programmed death-ligand 1 (PD-L1) and isocitrate dehydrogenase (IDH-1) mutation in glioblastome multiforme(GBM) patients.
Authors: Didem Sener Dede, Hayriye Tatlı Doğan, Fatma Betul Asan, Berrak Gumuskaya, Sule Ayik, Mehmet Ali Nahit Sendur, Arife Ulas, Burak Bilgin, Mutlu Hizal, Bulent Akinci, Kamile Silay, Bulent Yalcin
Journal: Journal of Clinical Oncology (2017)

e13536 Background: We aimed to assessed thePD-L1, PD-1 expression, TILs and IDH-1 mutation associations and their prognostic importance in GBM. Methods: Newly diagnosed and all were operated GBM patients who folllowed between February 2006 to February 2017 were included retrospectively in the study. We assessed the PD-L1, PD-1 expression, CD4(+) ve CD8(+)TILs, IDH-1 mutation in initial tumor specimens. Immunohistochemistry was performed using Ventana® antibody (clon-SP263, ROCHE) for PD-L1 and PD-1, real time PCR used for IDH-1 mutation analysis. Intensity was graded as low, moderate, dense for PD-1, CD4, CD8 TILs. PD-L1 evaluated in percents. The cutoff value assumed as ≥5% for PD-L1 positivity. We used Kaplan Meier, Cox regression tests and SPSS 23. Results: Fourty eight patients included in the study. The mean age was 54± 14,4 and 34 (70%) patients were male. Thirty (70 %) patients were received chemoradiotherapy with temozolamide and 20 (41%) of them also received chemotherapy.We identified two different staining pattern of PD-L1 expression as diffuse fibrillary [13(27%)] and membranous staining [14(29%)]. IDH-1 mutation was found in 30 (62%) patients. We found that TILs were more intensely located in the perivascular area than intratumoral area and in that TILs, PD-1 intensity were dense. We also found a correlation between the percentages of PD-L1 positivity and the density of TILs in the intratumoral and perivascular areas (p &lt; 0,002, r = 0,46). The intensity of both TILs in perivascular areas were significantly lower in PD-L1 (-) tumors than in PD-L1 (+) tumors (p &lt; 0,001). We didn’t find any association between IDH-1 and PD-L1 or TILs. According to survival and multivariate analysis; age, sex, PD-L1 positivity and IDH-1 mutation status did not appear to have a significant effect on survival. (log rank 0,08; 0,30; 0,89; 0,14 respectively) The presence of dense intratumoral CD8(+) and PD-1 (+)TILs were found as positive; advanced age and membranous PD-L1 staining was found as negative independent prognostic factors. Conclusions: Different staining pattern of PD-L1 in tumor tissue and PD-1 positivity in TILs may be a prognostic importance in GBM
Iron deficiency across chronic inflammatory conditions: International expert opinion on definition, diagnosis, and management
Authors: Maria Domenica Cappellini, Josep Comin‐Colet, Angel de Francisco, Axel Dignass, Wolfram Doehner, Carolyn S. Lam, Iain C. Macdougall, Gerhard Rogler, Clara Camaschella, Rezan Kadir, Nicholas J. Kassebaum, Donat R. Spahn, Ali T. Taher, Khaled M. Musallam
Journal: American Journal of Hematology (2017)

Abstract Iron deficiency, even in the absence of anemia, can be debilitating, and exacerbate any underlying chronic disease, leading to increased morbidity and mortality. Iron deficiency is frequently concomitant with chronic inflammatory disease; however, iron deficiency treatment is often overlooked, partially due to the heterogeneity among clinical practice guidelines. In the absence of consistent guidance across chronic heart failure, chronic kidney disease and inflammatory bowel disease, we provide practical recommendations for iron deficiency to treating physicians: definition, diagnosis, and disease‐specific diagnostic algorithms. These recommendations should facilitate appropriate diagnosis and treatment of iron deficiency to improve quality of life and clinical outcomes.
Indoleamine 2,3-Dioxygenase (IDO1) Levels and Activity Are Increased in Early Chronic Phase Chronic Myelogenous Leukemia (CML-CP) and Correlate with Molecular Response to Nilotinib Therapy
Authors: Sieghart Sopper, Satu Mustjoki, Gunther Gastl, Zlatko Trajanoski, Frank Giles, Andreas Hochhaus, Simon Geisler, Dietmar Fuchs, Dominik Wolf, Jeroen J.W.M. Janssen
Journal: Blood (2016)
Shortened multidrug-resistant tuberculosis treatment in settings with a high prevalence of ofloxacin resistance
Authors: Lorenzo Guglielmetti, Francis Varaine, Helena Huerga, Maryline Bonnet, Michael L. Rich, Carole D. Mitnick
Journal: European Respiratory Journal (2017)

We read with interest the research letter by Javaid et al . [1] in a recent issue of the European Respiratory Journal . The authors aptly note some uncertainty in current World Health Organization (WHO) guidelines [2]. Nevertheless, we question the authors’ main assertion that “high prevalence of ofloxacin resistance should not limit the applicability of the new shorter regimen”. The shortened regimen has indeed produced promising results in a number of settings, albeit in populations carefully selected for their limited exposure and resistance to second-line drugs [3–5]. That this should be extended to settings with a high prevalence of fluoroquinolone resistance, without individual, rapid molecular testing for such resistance, is not supported by data or the WHO. Shortened MDR-TB treatment requires individual, rapid resistance testing for fluoroquinolone resistance <http://ow.ly/sufM30cjQYM> L. Guglielmetti, F. Varaine, H. Huerga, M. Bonnet, M.L. Rich and C.D. Mitnick contributed to the design of the manuscript. L. Guglielmetti, F. Varaine and C.D. Mitnick wrote the first draft and L. Guglielmetti, F. Varaine, H. Huerga, M. Bonnet, M.L. Rich and C.D. Mitnick reviewed and approved the manuscript for publication.
TCR Repertoire of Lung Cancer: An Association with Tumor Molecular and Clinicopathological Features
Authors: A. Reuben, R. Gittelman, J. Zhang, C.-J. Wu, J. Zhang, J. Fujimoto, J. Rodriguez-Canales, S. Swisher, J.V. Heymach, H. Robins, J.J. Lee, A. Futreal, I.I. Wistuba, J. Zhang
Journal: Journal of Thoracic Oncology (2017)
Retardation of Antigen Release from DNA Hydrogel Using Cholesterol‐Modified DNA for Increased Antigen‐Specific Immune Response
Authors: Yuka Umeki, Masaaki Saito, Yuki Takahashi, Yoshinobu Takakura, Makiya Nishikawa
Journal: Advanced Healthcare Materials (2017)

Abstract Our previous study indicates that cationization of an antigen is effective for sustained release of both immunostimulatory DNA containing unmethylated cytosine‐phosphate‐guanine (CpG) dinucleotides, or CpG DNA, and antigen from a DNA hydrogel. Another approach to sustained antigen release would increase the applicability and versatility of the system. In this study, a hydrophobic interaction‐based sustained release system of ovalbumin (OVA), a model antigen, from immunostimulatory CpG DNA hydrogel is developed by the use of cholesterol‐modified DNA and urea‐denatured OVA (udOVA). Cholesterol‐modified DNA forms a hydrogel, Dgel(chol), and induces IL‐6 mRNA expression in mouse skin after intradermal injection, as DNA without cholesterol does. Cholesterol‐modified DNA associated with OVA and denaturation of OVA using urea increases the interaction. The release of udOVA from Dgel(chol) is significantly slower than that from DNA hydrogel with no cholesterol, Dgel. Moreover, intratumoral injections of udOVA/Dgel(chol) significantly inhibit the growth of EG7‐OVA tumors in mice. These results indicate that sustained release of antigen from Dgel can be achieved by the combination of urea denaturation and cholesterol modification, and retardation of antigen release is effective to induce antigen‐specific cancer immunity.
OP0140-HPR Acceptance and commitment therapy: a retrospective study of outcomes from a hospital-based, group, pain rehabilitation programme in rheumatology services in the south east of ireland
Authors: N Nealon Lennox, S O'Neill, A Hannigan
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Acceptance and Commitment Therapy (ACT) is a form of cognitive behavioural therapy (CBT), which focuses on psychological flexibility and behavior change. ACT has been advocated for the treatment of Persistent Pain. A systematic review concluded that ACT is efficacious for enhancing physical functioning and decreasing distress amongst adults with chronic pain attending Pain Rehabilitation Programmes (Hann &amp; McCracken 2014). A call was made for further studies to examine outcomes from more homogenous groups. <h3>Objectives</h3> To assess the effects of an eight-week group ACT, Rheumatology based programme, for people with persistent pain, on pain acceptance, activity engagement, psychological distress and self-efficacy. <h3>Methods</h3> Patients were referred to the programme by three Consultant Rheumatologists over a five-year period. Over one hundred patients9 outcome measures were available for this retrospective study from a convenience sample. Consent had been sought routinely from patients who attended the ACT programme and ethical approval was granted from the Hospital Research Ethics Committee (REC) and Ulster University REC. Baseline measures were taken at assessment, on the final day of the programme and at the follow up six-month review. Data was analysed with One Way Repeated Measures ANOVA using SPSSv20. Effect sizes were calculated using Partial Eta Squared and interpreted using the guidelines proposed by Cohen (1998). <h3>Results</h3> For those with scores at all three time points, mean depression scores, anxiety scores and self-efficacy scores were statistically significantly different over time. In addition, for those with activity engagement and pain willingness scores at all three time points, scores were statistically significantly different over time. <h3>Conclusions</h3> The ACT Pain Rehabilitation Programme at University Hospital Waterford in Ireland has provided significant outcomes for reducing depression and anxiety amongst its participants as measured by the Hospital Anxiety and Depression Scale (HADS). Increases in self-efficacy were also found to be statistically significant. Increases in activity engagement &amp; pain acceptance, as measured by the Chronic Pain Acceptance Questionnaire (CPAQ) also showed statistically significant increases. A number of limitations should be noted i.e. this was a retrospective study and depended on self report measures only. However, positive outcomes suggest ACT is a helpful intervention for people with persistent pain. <h3>References</h3> Hann, K.E.J., McCracken, L.M. (2014). A systematic review of randomized controlled trials of Acceptance and Commitment Therapy for adults with chronic pain: Outcome domains, design quality, and efficacy. Jounal of Contextual Behavioural Science 3, 217–222. <h3>Disclosure of Interest</h3> None declared
Exposure to biological therapies during conception and pregnancy: a systematic review
Authors: E. Pottinger, R.T. Woolf, L.S. Exton, A.D. Burden, C. Nelson‐Piercy, C.H. Smith
Journal: British Journal of Dermatology (2017)

Biological therapies are effective treatments for psoriasis and are often prescribed to women of child‐bearing age. To evaluate the safety of biological therapy in conception and/or pregnancy. We performed a systematic review of PubMed, MEDLINE, Embase and Cochrane databases for multivariate‐adjusted studies of women exposed to biologics relevant to the treatment of psoriasis during conception and/or pregnancy. We identified four population‐based cohort studies involving 1300 women exposed to tumour necrosis factor (TNF)‐α inhibitors (TNFi) 3 months prior to or during the first 3 months of pregnancy. These studies showed a trend towards drug‐specific harm with TNFi exposure in women with different inflammatory diseases, with an increased risk of congenital malformations [three studies; odds ratio (OR) range 1·32–1·64] and preterm birth (one study; OR 1·69, 95% confidence interval 1·10–2·60). This trend did not reach statistical significance in all studies; study heterogeneity, variation across comparator cohorts, inadequate adjustment for important confounding variables such as co‐therapy, and an absence of a common constellation of malformations means there is uncertainty about the causal role of TNFi. No studies specifically addressed the effect of TNFi exposure in psoriasis during conception and/or pregnancy, or of interleukin (IL)‐17 and IL‐12/23 antagonists in any indication. When counselling women these findings must be balanced against the potential impact of untreated severe psoriasis on conception and/or pregnancy and maternal wellbeing; ongoing pharmacovigilance via registries remains essential to address this evidence gap.
Association of Risk of Suicide Attempts With Methylphenidate Treatment
Authors: Kenneth K. C. Man, David Coghill, Esther W. Chan, Wallis C. Y. Lau, Chris Hollis, Elizabeth Liddle, Tobias Banaschewski, Suzanne McCarthy, Antje Neubert, Kapil Sayal, Patrick Ip, Martijn J. Schuemie, Miriam C. J. M. Sturkenboom, Edmund Sonuga-Barke, Jan Buitelaar, Sara Carucci, Alessandro Zuddas, Hanna Kovshoff, Peter Garas, Peter Nagy, Sarah K. Inglis, Kerstin Konrad, Alexander Häge, Eric Rosenthal, Ian C. K. Wong
Journal: JAMA Psychiatry (2017)

Patients with attention-deficit/hyperactivity disorder (ADHD) are at an increased risk of attempting suicide. Stimulants, such as methylphenidate hydrochloride, are the most common treatment for ADHD, but the association between their therapeutic use and suicide is unclear.To investigate the association between methylphenidate and the risk of suicide attempts.A population-based, electronic medical records database from the Hong Kong Clinical Data Analysis & Reporting System was used to identify 25 629 individuals aged 6 to 25 years who were treated with methylphenidate between January 1, 2001, and December 31, 2015. Those who had attempted suicide were included in the analysis. A self-controlled case series design was used to control for time-invariant characteristics of the patients.Relative incidence of suicide attempt during periods when patients were exposed to methylphenidate compared with nonexposed periods.Among 25 629 patients with methylphenidate prescriptions, 154 had their first recorded suicide attempt within the study period; of these individuals, 111 (72.1%) were male; mean (SD) age at baseline was 7.15 (2.19) years. The overall incidence of suicide attempts during methylphenidate treatment was 9.27 per 10 000 patient-years. An increased risk of suicide attempts was detected during the 90-day period before methylphenidate was initiated, with an incidence rate ratio (IRR) of 6.55 (95% CI, 3.37-12.72). The IRR remained elevated during the first 90 days of treatment (IRR, 3.91; 95% CI, 1.62-9.42) before returning to baseline levels during ongoing treatment (IRR, 1.35; 95% CI, 0.77-2.38). When the risk during the first 90 days of treatment was compared with the 90 days preceding first treatment, the incidence of suicide attempts was not elevated (IRR, 0.78; 95% CI, 0.26-2.35).The incidence of suicide attempts was higher in the period immediately before the start of methylphenidate treatment. The risk remained elevated immediately after the start of methylphenidate treatment and returned to baseline levels during continuation of methylphenidate treatment. The observed higher risk of suicide attempts before treatment may reflect emerging psychiatric symptoms that trigger medical consultations that result in a decision to begin ADHD treatment. Therefore, this study's results do not support a causal association between methylphenidate treatment and suicide attempts.
NiCord single unit expanded umbilical cord blood transplantation: Results of phase I/II trials.
Authors: Mitchell Horwitz, Pau Montesinos, Joanne Kurtzberg, David Valcarcel, Madan H. Jagasia, Daniela Cilloni, Jaap Jan Boelens, Guillermo F. Sanz
Journal: Journal of Clinical Oncology (2016)

7004 Background: Delayed or failed engraftment after cord blood transplantation is a major barrier to the success of the procedure, limiting its applicability as a graft source. Increasing the number of hematopoietic stem cells (HSC) within the donor graft may overcome this limitation. NiCord is an ex vivo-expanded, cryopreserved graft derived from an entire cord blood unit (CBU). In the pilot study, NiCord was transplanted with a second CBU following myeloablative conditioning (MAC) in patients with hematologic malignancies (Horwitz M, JCI 2014). Methods: We now report results of a subsequent study that explored use of NiCord as a single graft. Sixteen adult patients, median FU of 355 (232 – 373) days, with AML CR1 (5), ALL CR1/2 (5), MDS (3), CML (2), HD (1), were transplanted at 6 sites in the USA and EU. All patients received MAC with TBI/Flu ± Cy (n=8) or with thiotepa/Bu/Flu (n =8). GvHD prophylaxis consisted of tacrolimus or cyclosporine and MMF. HLA-matching was 4/6 (n=10), 5/6 (n=4) or 6/6 (n=2). NiCord median fold expansion of CD34+ cells was 104 (47-245). After expansion, the TNC and CD34+ cell doses were 3.85 x 107/kg (1.8-7.5) and 6.7 x 106/kg (3.3-14.9), respectively. Results: All patients engrafted. One patient had secondary graft failure attributed to HHV6 viremia. Neutrophil and platelet engraftment were achieved at median of 10 (6 – 26) and 32 (26 – 96) days, respectively. All engrafted patients achieved full donor myeloid and lymphoid chimerism. At day 100, median absolute lymphocyte and T cell counts were 1031.5/µl (345-1512/µl) and 285.5/µl (84 – 595µl). Non-relapse mortality was 12.5% at 100 days. Grade III-IV aGvHD was 13%. Grade III infections were observed in two patients. With a median FU of 355 (232 – 373) days, overall survival at 180 and 365 days is 81.2% and 64%, respectively. The results of this trial and the understanding of multi-site practices have provided the basis for design of the registration phase III, prospective randomized controlled study to begin in 2016. Conclusions: NiCord has the potential to broaden accessibility to HSC transplantation and become the graft of choice for patients without a timely or suitably matched adult donor. Clinical trial information: NCT01816230.
High-Sensitivity Cardiac Troponin Concentration and Risk of First-Ever Cardiovascular Outcomes in 154,052 Participants
Authors: Peter Willeit, Paul Welsh, Jonathan D.W. Evans, Lena Tschiderer, Charles Boachie, J. Wouter Jukema, Ian Ford, Stella Trompet, David J. Stott, Patricia M. Kearney, Simon P. Mooijaart, Stefan Kiechl, Emanuele Di Angelantonio, Naveed Sattar
Journal: Journal of the American College of Cardiology (2017)

High-sensitivity assays can quantify cardiac troponins I and T (hs-cTnI, hs-cTnT) in individuals with no clinically manifest myocardial injury.The goal of this study was to assess associations of cardiac troponin concentration with cardiovascular disease (CVD) outcomes in primary prevention studies.A search was conducted of PubMed, Web of Science, and EMBASE for prospective studies published up to September 2016, reporting on associations of cardiac troponin concentration with first-ever CVD outcomes (i.e., coronary heart disease [CHD], stroke, or the combination of both). Study-specific estimates, adjusted for conventional risk factors, were extracted by 2 independent reviewers, supplemented with de novo data from PROSPER (Pravastatin in Elderly Individuals at Risk of Vascular Disease Study), then pooled by using random effects meta-analysis.A total of 28 relevant studies were identified involving 154,052 participants. Cardiac troponin was detectable in 80.0% (hs-cTnI: 82.6%; hs-cTnT: 69.7%). In PROSPER, positive associations of log-linear shape were observed between hs-cTnT and CVD outcomes. In the meta-analysis, the relative risks comparing the top versus the bottom troponin third were 1.43 (95% confidence interval [CI]: 1.31 to 1.56) for CVD (11,763 events), 1.67 (95% CI: 1.50 to 1.86) for fatal CVD (7,775 events), 1.59 (95% CI: 1.38 to 1.83) for CHD (7,061 events), and 1.35 (95% CI: 1.23 to 1.48) for stroke (2,526 events). For fatal CVD, associations were stronger in North American studies (p = 0.010) and those measuring hs-cTnT rather than hs-cTnI (p = 0.027).In the general population, high cardiac troponin concentration within the normal range is associated with increased CVD risk. This association is independent of conventional risk factors, strongest for fatal CVD, and applies to both CHD and stroke.
Persistent Expression of VCAM1 in Radial Glial Cells Is Required for the Embryonic Origin of Postnatal Neural Stem Cells
Authors: Xiao-Ling Hu, Guo Chen, Sanguo Zhang, Jiangli Zheng, Jun Wu, Qing-Ran Bai, Yue Wang, Ji Li, Huanhuan Wang, Han Feng, Jia Li, Xicai Sun, Qijun Xia, Fan Yang, Jing Hang, Chang Qi, Timothy N. Phoenix, Sally Temple, Qin Shen
Journal: Neuron (2017)
Early Orthostatic Hypotension and Orthostatic Intolerance—More Than an Observation or Annoyance
Authors: Wolfgang Singer, Phillip A. Low
Journal: JAMA Internal Medicine (2017)

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Bout of the corner men and not the boxers? Contextual effects flex their muscles
Authors: Martin Englund
Journal: Annals of the Rheumatic Diseases (2017)

Increased use of MRI in the quest to explain symptoms, and patients’ hope for a ‘quick-fix’, often challenge healthcare professionals in their choice of treatment for the painful ageing knee. In the USA, there are about one million knee arthroscopies per year and the majority involve removal of torn meniscal tissue in middle-aged patients. The absolute number of arthroscopic partial meniscectomies (APMs) in Europe is unknown but may be even greater due to the larger European population. The popularity of this procedure is understandable — multiple case series and randomised controlled trials (RCTs), not to mention doctors’ personal observations of patients, show sustained improvement after APM. However, the last few years, the efficacy of the actual therapeutic element , resection of meniscal tissue, has been called into question.

A hallmark RCT is the exquisitely designed, randomised, double-blinded, sham-surgery-controlled Finnish Degenerative Meniscal Lesion Study (FIDELITY).1 The main findings of the trial so far are summarised in these short film clips:



In the provocative New Engl J Med article from 2013, Sihvonen et al reported that outcomes in the middle-aged patients, where resection of meniscus was only simulated during the diagnostic arthroscopy, were very similar to those of actual APM. Patients in both the APM arm and the sham-surgery arm improved substantially and sustainably, indicating that the improvement observed after APM is attributable to what are collectively referred to as contextual effects. Thus, it was not the actual therapeutic element of the surgery, which is resection of torn meniscal tissue. Now, in the present 2-year follow-up of the FIDELITY patients,2 Sihvonen et al strengthen their original …
FISH Analysis of Crizotinib Target Genes ROS1 / ALK / MET in Malignant Mesothelioma
Authors: Sandra Salvi, Serena Varesano, Simona Boccardo, Jean Louis Ravetti, Pier Aldo Canessa, Maria Pia Pistillo, Paola Ferro, Franco Fedeli, Silvio Roncella
Journal: Journal of Thoracic Oncology (2017)