tbuckley/cabot-search huggingface dataset:
EPND-03. RNA-SEQ GENE EXPRESSION ANALYSIS OF 106 FORMALIN-FIXED PARAFFIN-EMBEDDED PAEDIATRIC EPENDYMOMAS
Authors: Timothy Ritzmann, Hazel Rogers, Andrew M Donson, Rebecca Chapman, Lisa Storer, Jennifer Ward, Alex Virasami, Thomas S Jacques, Simon ML Paine, Nicholas Foreman, Richard G Grundy
Journal: Neuro-Oncology (2017)

BACKGROUND: Although ependymoma is the second most common malignant childhood brain tumour, obtaining frozen samples from extended cohorts is challenging. A large proportion of research tissue is stored in formalin-fixed, paraffin-embedded (FFPE) blocks, some many decades old. Use of these for RNA sequencing would facilitate biological studies of this enigmatic tumour. AIMS: 106 historical ependymomas were analysed to investigate the feasibility and challenges of using FFPE samples for RNA-seq and whether previously described gene expression patterns from frozen material would be replicated. METHODS: Ethics approval and consent were obtained. Pathologist confirmed ependymoma samples were collected from UK centres. 14 cases had matched frozen samples. RNA was extracted using the Qiagen FFPE Allprep kit and 1000ng per sample underwent whole transcriptome library preparation. Sequencing had a target depth of 50 million paired-end reads. Following quality control, samples were aligned using TopHat2. Differential expression analysis (DEA) was performed using EdgeR. RESULTS: Libraries were produced from all samples. The proportion of FFPE reads aligning to the genome was less than for frozen equivalents (54.2%) and showed higher inter-sample variation. Interestingly, samples with lower alignment to the genome had more reads aligning to bacterial sequences, suggesting potential contamination of the blocks. FFPE had more adapter read through when compared to the frozen samples. Clustering demonstrated 4 groups; poor quality samples, supratentorial tumours and two posterior fossa (PF) tumour groups. DEA of the PF groups showed good concordance with PFA and PFB gene expression patterns. CONCLUSIONS: RNA sequencing of historical FFPE ependymomas replicates subgroups. The benefit of investigating a wider range of samples has to be weighed against some compromise on quality. Researchers must be aware of the potential for bacterial contamination. Greater sequencing depth and more samples in addition to care over storage may help ameliorate quality issues.
The “item” as a window into how prior knowledge guides visual search
Authors: Rachel Wu, Jiaying Zhao
Journal: Behavioral and Brain Sciences (2017)

Abstract We challenge the central idea proposed in Hulleman &amp; Olivers (H&amp;O) by arguing that the “item” is still useful for understanding visual search and for developing new theoretical frameworks. The “item” is a flexible unit that represents not only an individual object, but also a bundle of objects that are grouped based on prior knowledge. Uncovering how the “item” is represented based on prior knowledge is essential for advancing theories of visual search.
Autoimmune neutropenia of childhood secondary to other autoimmune disorders: Data from the Italian neutropenia registry
Authors: Piero Farruggia, Giuseppe Puccio, Francesca Fioredda, Tiziana Lanza, Laura Porretti, Ugo Ramenghi, Angelica Barone, Sonia Bonanomi, Andrea Finocchi, Roberta Ghilardi, Saverio Ladogana, Nicoletta Marra, Baldassare Martire, Lucia Dora Notarangelo, Daniela Onofrillo, Marta Pillon, Giovanna Russo, Laura Lo Valvo, Jessica Serafinelli, Fabio Tucci, Fiammetta Zunica, Federico Verzegnassi, Carlo Dufour
Journal: American Journal of Hematology (2017)
A Framework for the Assessment of Graduate Medical Education
Authors: Morgan M. Sellers, Bijan A. Niknam, Rachel R. Kelz
Journal: JAMA Surgery (2017)

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 Surgery 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 Surgery journal
A survey of clinical prediction tools in colorectal and lung cancers and melanoma.
Authors: Alyson L. Mahar, Susan Halabi, Lisa M. McShane, Patricia A. Groome, Carolyn C. Compton
Journal: Journal of Clinical Oncology (2013)

1592 Background: Clinical prediction in cancer depends on a myriad of prognostic factors, and relies on sound methodology for model building and validation. Increased understanding of complex tumour biology allows for simultaneous consideration of biological markers and standard clinical and pathological factors for prediction. We evaluated published studies supporting existing prediction tools in three cancers. Methods: Scientific literature and online resources were searched for clinical prediction tools for survival in three cancers: colorectal, lung, and melanoma. A priori criteria determined by the Molecular Modellers Working Group of the AJCC were evaluated and included: defined patient population, consideration of standard prognostic variables, model development approaches, validation strategies, performance metrics, presentation form of prediction tool, and intended clinical use. Results: Seventy-eight tools intended for prediction of survival were identified for the three cancers: 41 in colorectal, 23 in lung, and 14 in melanoma. Clinical presentations varied within each: 23 of the colorectal cancer tools focused on advanced disease with liver metastases and the remaining varied by stage; 16 lung cancer tools focused on NSCLC and 7 on SCLC. Even in narrowly defined situations, there was no consensus on key variables; for example, no variables were common to all 8 prediction tools for metastatic lung cancer. Variable definitions were missing or vague and the form of the model was often not provided, hampering independent validation and usability. Only 32/78 tools were supported by appropriate internal validity statistics and 21/78 with external validation. Often the development of risk scores did not create groups for whom treatment decisions would be similar. Conclusions: The quality of the literature supporting clinical prediction tools is variable, and the accuracy and utility of many existing tools is undetermined. Methodological guidelines for prediction tool development and validation should be adopted and adhered to. Studies developing and validating clinical prediction tools in cancer must be reported in complete and transparent fashion to facilitate proper interpretation and judgment of utility.
Endoplasmic reticulum stress and inflammation in the central nervous system
Authors: Neil T. Sprenkle, Savannah G. Sims, Cristina L. Sánchez, Gordon P. Meares
Journal: Molecular Neurodegeneration (2017)

Persistent endoplasmic reticulum (ER) stress is thought to drive the pathology of many chronic disorders due to its potential to elicit aberrant inflammatory signaling and facilitate cell death. In neurodegenerative diseases, the accumulation of misfolded proteins and concomitant induction of ER stress in neurons contributes to neuronal dysfunction. In addition, ER stress responses induced in the surrounding neuroglia may promote disease progression by coordinating damaging inflammatory responses, which help fuel a neurotoxic milieu. Nevertheless, there still remains a gap in knowledge regarding the cell-specific mechanisms by which ER stress mediates neuroinflammation. In this review, we will discuss recently uncovered inflammatory pathways linked to the ER stress response. Moreover, we will summarize the present literature delineating how ER stress is generated in Alzheimer’s disease, Parkinson’s disease, Amyotrophic Lateral Sclerosis, and Multiple Sclerosis, and highlight how ER stress and neuroinflammation intersect mechanistically within the central nervous system. The mechanisms by which stress-induced inflammation contributes to the pathogenesis and progression of neurodegenerative diseases remain poorly understood. Further examination of this interplay could present unappreciated insights into the development of neurodegenerative diseases, and reveal new therapeutic targets.
Mortality among twins and singletons in sub-Saharan Africa between 1995 and 2014: a pooled analysis of data from 90 Demographic and Health Surveys in 30 countries
Authors: Christiaan W S Monden, Jeroen Smits
Journal: The Lancet Global Health (2017)

BackgroundSub-Saharan Africa has the world's highest under-5 and neonatal mortality rates as well as the highest naturally occurring twin rates. Twin pregnancies carry high risk for children and mothers. Under-5 mortality has declined in sub-Saharan Africa over the last decades. It is unknown whether twins have shared in this reduction.MethodsWe pooled data from 90 Demographic and Health Surveys for 30 sub-Saharan Africa countries on births reported between 1995 and 2014. We used information on 1 685 110 singleton and 56 597 twin livebirths to compute trends in mortality rates for singletons and twins. We examined whether the twin–singleton rate ratio can be attributed to biological, socioeconomic, care-related factors, or birth size, and estimated the mortality burden among sub-Saharan African twins.FindingsUnder-5 mortality among twins has declined from 327·7 (95% CI 312·0–343·5) per 1000 livebirths in 1995–2001 to 213·0 (196·7–229·2) in 2009–14. This decline of 35·0% was much less steep than the 50·6% reduction among singletons (from 128·6 [95% CI 126·4–130·8] per 1000 livebirths in 1995–2001 to 63·5 [61·6–65·3] in 2009–14). Twins account for an increasing share of under-5 deaths in sub-Saharan Africa: currently 10·7% of under-5 mortality and 15·1% of neonatal mortality. We estimated that about 315 000 twins (uncertainty interval 289 000–343 000) die in sub-Saharan African each year. Excess twin mortality cannot be explained by common risk factors for under-5 mortality, including birthweight. The difference with singletons was especially stark for neonatal mortality (rate ratio 5·0, 95% CI 4·5–5·6). 51·7% of women pregnant with twins reported receiving medical assistance at birth.InterpretationThe fate of twins in sub-Saharan Africa is lagging behind that of singletons. An alarming one-fifth of twins in the region dies before age 5 years, three times the mortality rate among singletons. Twins account for a substantial and growing share of under-5 and neonatal mortality, but they are largely neglected in the literature. Coordinated action is required to improve the situation of this extremely vulnerable group.FundingNone.
Rapid generations of de novo biological pathways from large-scale gene expression data using the Ingenuity Pathways Analysis application.
Authors: Daniel C. Siu, Megan Laurance
Journal: Cancer Research (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

3265 

This presentation describes the use of a novel bioinformatics knowledge base system to create relevant biological pathways using large gene expression data sets. This knowledge base system –the Ingenuity Pathways Analysis, is created from modeling of millions of scientific findings and biological relationships between genes, proteins, cells, tissues, drugs and diseases. With gene expression data collected from cancer samples using the Affymetrix GeneChip® microarray system, the Ingenuity Pathways Analysis dynamically and simultaneously computes multiple networks of pathways. Functional and physical relationships such gene regulations, protein-protein interactions, post-translational modifications, and drug-target interactions were displayed at the gene, protein, cellular and tissue levels. The outputs provide semantically consistent representations of biological pathways and biological functions implicated by the empirical data sets, and help users to compile panels of biomarkers for follow-on screening assays.
The use of clip anchoring to ensure safe transgastric puncture during endoscopic ultrasound-guided transmural drainage
Authors: Shinichi Morita, Kazuo Hara, Takeshi Suda, Susumu Hijioka, Nozomi Okuno, Masaaki Kobayashi, Shuji Terai
Journal: Endoscopy (2017)

Endoscopic ultrasound (EUS)-guided transmural drainage (EUS-TD) was recently developed and has proven to be a useful alternative approach for various intra-abdominal conditions [1] [2] [3]. In this procedure, an intrathoracic passage should be avoided, because it causes severe complications, such as mediastinitis [4] [5]. Unfortunately, however, it is difficult to confirm whether a puncture route can be used to pass the thorax using EUS observation alone when approaching from the gastric cardia. Here, we describe the usefulness of clip anchoring at the esophagogastric junction to minimize the risk associated with intrathoracic passage.
NK1 receptor antagonists for the prevention of chemotherapy-induced nausea and vomiting: An updated meta-analysis.
Authors: Lucas Vieira dos Santos, Andre Tesainer Brunetto, Andre Deeke Sasse, Fabiano Hahn Souza, Joao Paulo Lima
Journal: Journal of Clinical Oncology (2013)

e20506 Background: We have previously shown (dos Santos JNCI 2012) that NK1 receptor antagonists (NK1RA), such as aprepitant and casopitant, improve chemotherapy-induced nausea and vomiting (CINV) at the cost of increasing severe infection risk. Herein, we update our results. Methods: We searched MEDLINE, EMBASE, CENTRAL and meeting proceedings to identify randomized controlled trials (RCTs) comparing standard antiemetic therapy (dexamethasone + 5-HT3R inhibitors) versus NK1RA plus standard therapy for CINV prevention. Complete response (CR) was defined as absence of emesis and rescue therapy. The endpoints were CR post-chemotherapy in the overall phase (first 120 hours), CR in the acute phase (first 24 hours), and the delayed phase (24–120 hours), nausea, and toxicity. Subgroup analyses evaluated the type of NK1RA, the emetogenic potential of the chemotherapy, and prolonged use of 5-HT3R inhibitor. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random-effects model. Results: A total of 20 trials (9,935 patients) were included. NK1RA increased CR rate and nausea in all phases and subgroups. The CR in overall phase improved from 56% to 72% (OR = 0.52, 95% CI = 0.46 to 0.59, P &lt; .00001, NNT=6). The side effects of NK1RA followed our previous report: the severe infection rate increased from 2.4% to 5.6% in the NK1RA group (four trials, 1656 patients; OR = 2.87; 95% CI = 1.58 to 5.19, P = .0005, NNH=31). Conclusions: NK1RA consistently improve CINV control in the acute, delayed, and overall phases, either for moderately or highly emetogenic chemotherapy regimens. Their use might be associated with increased infection rate, and a patient-level meta-analysis is warranted to clarify this safety issue.
Hepaticogastrostomie permanente avec dilatation transgastrique récurrente: une nouvelle alternative endoscopique pour le traitment des sténoses biliaires anastomotiques
Authors: P Miranda Garcia, JM Gonzalez, A Culetto, J Tellechea, M Barthet
Journal: Endoscopy (2016)

Les sténoses anastomotiques biliaires postopératoires sont une complication majeure de la chirurgie biliaire et elles sont difficiles à traiter en raison de la modification de l'anatomie. Nous présentons une alternative endoscopique à la radiologie interventionnelle utilisant une nouvelle approche antérograde en deux temps pour traiter ces obstructions biliaires bénignes.
New WHO chief pledges to strengthen fundraising capacity
Authors: Anne Gulland
Journal: BMJ (2017)

The new director general of the World Health Organization has said that it must focus on new ways of fundraising.

In his first press conference after his election by the World Health Assembly on 23 May, Tedros Adhanom Ghebreyesus was asked about the implications for WHO of cuts to the US diplomacy and aid budgets of nearly $19bn (£14.7bn; €17bn) announced this week. Analysis by the US based think tank the Kaiser Family Foundation has shown that the US is the largest state donor to WHO, providing 16% of WHO’s budget in 2016,1 at a total of $341m. The largest single donor was the Bill and Melinda Gates …
Designing Clinical Trials That Accept New Arms: An Example in Metastatic Breast Cancer
Authors: Steffen Ventz, Brian M. Alexander, Giovanni Parmigiani, Richard D. Gelber, Lorenzo Trippa
Journal: Journal of Clinical Oncology (2017)

Purpose The majority of randomized oncology trials are two-arm studies that test the efficacy of new therapies against a standard of care, thereby assigning a large proportion of patients to nonexperimental therapies. In contrast, multiarm studies efficiently share a common control arm while evaluating multiple experimental therapies. A major bottleneck for traditional multiarm trials is the requirement that all therapies-often drugs from different companies-have to be available at the same time when the trial starts. We evaluate the potential gains of a platform design-the rolling-arms design-that adds and removes arms on a rolling basis. Methods We define the rolling-arms design with the goal of minimizing the complexity of random assignment and data analyses of a platform trial. We then evaluate its potential advantages in hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer. Multiple pharmaceutical companies currently test CDK4/6 inhibitors in combination with letrozole in independent two-arm trials. We conducted a simulation study to quantify the reduction in sample size, number of patients treated with the standard of care, and the average time to treatment discovery if these therapies had been tested in a rolling-arms trial. Results A rolling-arms platform design with two to five experimental treatments can reduce the overall sample size requirement by up to 30% compared with standard two-arm studies. It assigns up to 60% fewer patients to the control arm compared with five independent trials that test distinct treatments. Moreover, under realistic scenarios, effective experimental treatments are discovered up to 15 months earlier compared with separate two-arm trials. Conclusion The rolling-arms platform design is applicable to a broad variety of diseases, and under realistic scenarios, it is substantially more efficient than standard two-arm randomized trials.
DNA Damage Repair Pathway Alterations in Multiple Myeloma Predict Poor Prognosis, but Correlate with Sensitivity to IGF1R-PI3K-mTOR and HDAC Inhibitors
Authors: Muntasir M Majumder, David Tamborero, Pekka Anttila, Raija Silvennoinen, Samuli Eldfors, Ashwini Kumar, Juha Lievonen, Alun Parsons, Minna Suvela, Esa Jantunen, Kimmo Porkka, Caroline A Heckman
Journal: Blood (2016)
A randomized, double-blind study of “Scrambler” therapy versus sham for painful chemotherapy-induced peripheral neuropathy (CIPN).
Authors: Toby Christopher Campbell, Amit J Nimunkar, Janet Retseck, Jens C. Eickhoff, Miroslav Backonja, James F. Cleary, Kristine L Kwekkeboom, Thomas Y Yen
Journal: Journal of Clinical Oncology (2013)

9635 Background: CIPN is a debilitating, dose-limiting toxicity. The MC5A is a non-invasive electro-analgesia device delivering “Scrambler Therapy,” which has shown benefit for painful CIPN in uncontrolled studies. No sham-controlled trials of MC5A have been performed. Methods: Eligible patients included adults with neuropathic pain (NP) for &gt; 6 months, pain scores ≥4/10 numerical rating scale (NRS), and no history of diabetes or other peripheral neuropathies. Patients received up to 10 daily sessions of 50 minutes with either MC5A or a novel active sham device constructed to deliver a just perceptible electrical sensation. Sham output is neither a TENS nor MC5A and is designed to be nontherapeutic. Active and sham treatments were applied to the affected limbs. 14 patients were randomized with no baseline differences. Patients and evaluators were blinded to study arm. Pain was measured before, daily during, after and 3 months post-treatment (verbal NRS). The primary endpoint was change in pain. Secondary endpoints included quantitative neurosensory testing (QST), validated patient-report measures, and cytokines. Results: There were 7 patients in each arm. The table shows changes in pain scores pre- and post-treatment by day and group. There was no difference between arms and no arm x day interaction. There was no significant day or arm effect for the function sub scales. Conclusions: In a small pilot study, MC5A was not significantly different from sham therapy for the primary outcome. The sham is feasible and provides a mechanism for future controlled studies with MC5A. Secondary endpoints, e.g. QST are forthcoming. Clinical trial information: NCT01261780. [Table: see text]
Akt Signaling Is Sustained by a CD44 Splice Isoform–Mediated Positive Feedback Loop
Authors: Sali Liu, Chonghui Cheng
Journal: Cancer Research (2017)

Abstract Tumor cells nearly invariably evolve sustained PI3K/Akt signaling as an effective means to circumvent apoptosis and maintain survival. However, for those tumor cells that do not acquire PI3K/Akt mutations to achieve this end, the underlying mechanisms have remained obscure. Here, we describe the discovery of a splice isoform–dependent positive feedback loop that is essential to sustain PI3K/Akt signaling in breast cancer. Splice isoform CD44s promoted expression of the hyaluronan synthase HAS2 by activating the Akt signaling cascade. The HAS2 product hyaluronan further stimulated CD44s-mediated Akt signaling, creating a feed-forward signaling circuit that promoted tumor cell survival. Mechanistically, we identified FOXO1 as a bona fide transcriptional repressor of HAS2. Akt-mediated phosphorylation of FOXO1 relieved its suppression of HAS2 transcription, with FOXO1 phosphorylation status maintained by operation of the positive feedback loop. In clinical specimens of breast cancer, we established that the expression of CD44s and HAS2 was positively correlated. Our results establish a positive feedback mechanism that sustains PI3K/Akt signaling in tumor cells, further illuminating the nearly universal role of this pathway in cancer cell survival. Cancer Res; 77(14); 3791–801. ©2017 AACR.
Effects on Survival and Neurocognitive Functions of Whole-Brain Radiotherapy (WBRT) and Autologous Stem Cell Transplantation (ASCT) as Consolidation Options after High-Dose Methotrexate-Based Chemoimmunotherapy in Patients with Newly Diagnosed Primary CNS Lymphoma (PCNSL): Results of the Second Randomization of the IELSG32 Trial
Authors: Andrés J.M. Ferreri, Kate Cwynarski, Elisa Jacobsen Pulczynski, Christopher P. Fox, Elisabeth Schorb, Paul La Rosée, Mascha Binder, Alberto Fabbri, Valter Torri, Eleonora Minacapelli, Monica Falautano, Fiorella Ilariucci, Achille Ambrosetti, Alexander Röth, Claire Jane Hemmaway, Peter M Johnson, Kim Linton, Tobias Pukrop, Jette Sonderskov Gorlov, Monica Balzarotti, Georg Hess, Ulrich Keller, Stephan Stilgenbauer, Jens P. Panse, Alessandra Tucci, Lorella Orsucci, Francesco Pisani, Alessandro Levis, Stefan W. Krause, Hans-Joachim Schmoll, Bernd Hertenstein, Mathias Rummel, Jeffery Smith, Michael Pfreundschuh, Giuseppina Cabras, Francesco Angrilli, Maurilio Ponzoni, Martina Deckert, Letterio S. Politi, Jurgen Finke, Michele Reni, Franco Cavalli, Emanuele Zucca, Gerald Illerhaus
Journal: Blood (2016)