tbuckley/cabot-search huggingface dataset:
Cervical Cancer, Version 2.2015
Authors: Wui-Jin Koh, Benjamin E. Greer, Nadeem R. Abu-Rustum, Sachin M. Apte, Susana M. Campos, Kathleen R. Cho, Christina Chu, David Cohn, Marta Ann Crispens, Oliver Dorigo, Patricia J. Eifel, Christine M. Fisher, Peter Frederick, David K. Gaffney, Ernest Han, Warner K. Huh, John R. Lurain, David Mutch, Amanda Nickles Fader, Steven W. Remmenga, R. Kevin Reynolds, Nelson Teng, Todd Tillmanns, Fidel A. Valea, Catheryn M. Yashar, Nicole R. McMillian, Jillian L. Scavone
Journal: Journal of the National Comprehensive Cancer Network (2015)

The NCCN Guidelines for Cervical Cancer provide interdisciplinary recommendations for treating cervical cancer. These NCCN Guidelines Insights summarize the NCCN Cervical Cancer Panel’s discussion and major guideline updates from 2014 and 2015. The recommended systemic therapy options for recurrent and metastatic cervical cancer were amended upon panel review of new survival data and the FDA’s approval of bevacizumab for treating late-stage cervical cancer. This article outlines relevant data and provides insight into panel decisions regarding various combination regimens. Additionally, a new section was added to provide additional guidance on key principles of evaluation and surgical staging in cervical cancer. This article highlights 2 areas of active investigation and debate from this new section: sentinel lymph node mapping and fertility-sparing treatment approaches.
Pediatric-Like Acute Lymphoblastic Leukemia Therapy in Adults With Lymphoblastic Lymphoma: The GRAALL-LYSA LL03 Study
Authors: Stéphane Lepretre, Aurore Touzart, Thomas Vermeulin, Jean-Michel Picquenot, Aline Tanguy-Schmidt, Gilles Salles, Thierry Lamy, Marie-Christine Béné, Emmanuel Raffoux, Françoise Huguet, Patrice Chevallier, Serge Bologna, Réda Bouabdallah, Jacques Benichou, Josette Brière, Anne Moreau, Valérie Tallon-Simon, Stéphanie Seris, Carlos Graux, Vahid Asnafi, Norbert Ifrah, Elizabeth Macintyre, Hervé Dombret
Journal: Journal of Clinical Oncology (2015)

This study evaluated the efficacy of pediatric-like acute lymphoblastic leukemia (ALL) therapy in adults with lymphoblastic lymphoma (LL).This was a prospective phase II study in adults 18 to 59 years old with previously untreated LL. Patients were treated with an adapted pediatric-like ALL protocol, which included a corticosteroid prephase, a five-drug induction reinforced by sequential cyclophosphamide administration, dose-dense consolidation, late intensification, CNS prophylaxis, and a 2-year maintenance phase. Treatment response was assessed by computed tomography and optional positron emission tomography. Allogeneic hematopoietic stem cell transplant was offered to selected patients in first complete remission (CR) or unconfirmed CR.The study enrolled 148 patients (131 with T-lineage LL [T-LL] and 17 with B-lineage LL [B-LL]). A total of 119 patients with T-LL (90.8%) and 13 with B-LL (76.5%) reached CR/unconfirmed CR, including 26 with T-LL and two with B-LL who needed a second induction salvage course. Relapse occurred in 34 patients with T-LL and four with B-LL. In patients with T-LL, 3-year event-free survival was 63.3% (95% CI, 54.2% to 71.0%), disease-free survival was 72.4% (95% CI, 63.0% to 79.7%), and overall survival was 69.2% (95% CI, 60.0% to 76.7%). Multivariate analysis identified serum lactate dehydrogenase level and the NOTCH1/FBXW7/RAS/PTEN oncogene (a four-gene oncogenetic classifier) status but not positron emission tomography or hematopoietic stem cell transplant as independent prognostic factors for outcome in T-LL.In adults with LL, an intensive pediatric-like ALL treatment protocol was associated with a good response rate and outcome. In patients with T-LL, the four-gene oncogenetic classifier and lactate dehydrogenase level were independent prognostic indicators.
Catalans push for therapeutic use of cannabis
Authors: Xavier Bosch
Journal: BMJ (2001)

All five political parties in the Catalan parliament in Spain have signed a proposal to legalise the use of cannabis for therapeutic purposes. The agreement asks the Catalan government to negotiate with the Spanish authorities so that cannabis—either as a drug or as a standardised extract of the plant—may be used to treat medical disorders.

Once the bill is approved in the Catalan parliament, it may be submitted to the Spanish parliament for discussion and eventual voting.

The initiative came from a collective of 300 women with breast cancer called the “Agata group” (after Saint Agata, who had her breasts removed under torture) and from a journalist, Nuria Nogueras, who recently died of the disease and who found the drug helpful during chemotherapy. Since last September, the Agata collective has held meetings with representatives of the five Catalan parties, as well as with the Catalan health department, oncologists, and pharmacologists.


After these meetings, all political parties agreed to draft and release a consensus report to the Catalan parliament to decriminalise the therapeutic use of cannabis. But the measure, even if approved in the Catalan parliament—as is forecast—can take effect only if the Spanish ministry of health gives the go-ahead. The ministry is the only body with the power to authorise new drugs in Spain. 





AP PHOTO/PAUL WHITE
British Society for Skin Care in Immunocompromised Individuals
Journal: British Journal of Dermatology (2012)

British Journal of DermatologyVolume 167, Issue s1 p. 114-126 Free Access British Society for Skin Care in Immunocompromised Individuals First published: 03 July 2012 https://doi.org/10.1111/j.1365-2133.2012.10976.xAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Volume167, Issues1Special Issue: Abstracts for the British Association of Dermatologists 92nd Annual Meeting. Birmingham, U.K. 3-5 July 2012.July 2012Pages 114-126 RelatedInformation
Hospital prescribing of antibiotics rose significantly between 2011 and 2014
Authors: Nigel Hawkes
Journal: BMJ (2015)

GPs in England are issuing fewer prescriptions for antibiotics, but total consumption in primary care continues to rise, Public Health England has said in a new issue of Health Matters, a publication aimed at doctors and public health professionals.1

The discrepancy may be accounted for by longer courses or higher doses being prescribed, Public Health England said in the report of its surveillance programme published in October.2 That report also showed that prescribing of antibiotics in hospitals rose significantly between 2011 and 2014, by 11.7% to inpatients and 8.5% to outpatients.

Combining data …
Genomic legacy of the African cheetah, Acinonyx jubatus
Authors: Pavel Dobrynin, Shiping Liu, Gaik Tamazian, Zijun Xiong, Andrey A. Yurchenko, Ksenia Krasheninnikova, Sergey Kliver, Anne Schmidt-Küntzel, Klaus-Peter Koepfli, Warren Johnson, Lukas F.K. Kuderna, Raquel García-Pérez, Marc de Manuel, Ricardo Godinez, Aleksey Komissarov, Alexey Makunin, Vladimir Brukhin, Weilin Qiu, Long Zhou, Fang Li, Jian Yi, Carlos Driscoll, Agostinho Antunes, Taras K. Oleksyk, Eduardo Eizirik, Polina Perelman, Melody Roelke, David Wildt, Mark Diekhans, Tomas Marques-Bonet, Laurie Marker, Jong Bhak, Jun Wang, Guojie Zhang, Stephen J. O’Brien
Journal: Genome biology (2015)

Patterns of genetic and genomic variance are informative in inferring population history for human, model species and endangered populations. Here the genome sequence of wild-born African cheetahs reveals extreme genomic depletion in SNV incidence, SNV density, SNVs of coding genes, MHC class I and II genes, and mitochondrial DNA SNVs. Cheetah genomes are on average 95 % homozygous compared to the genomes of the outbred domestic cat (24.08 % homozygous), Virunga Mountain Gorilla (78.12 %), inbred Abyssinian cat (62.63 %), Tasmanian devil, domestic dog and other mammalian species. Demographic estimators impute two ancestral population bottlenecks: one >100,000 years ago coincident with cheetah migrations out of the Americas and into Eurasia and Africa, and a second 11,084–12,589 years ago in Africa coincident with late Pleistocene large mammal extinctions. MHC class I gene loss and dramatic reduction in functional diversity of MHC genes would explain why cheetahs ablate skin graft rejection among unrelated individuals. Significant excess of non-synonymous mutations in AKAP4 (p<0.02), a gene mediating spermatozoon development, indicates cheetah fixation of five function-damaging amino acid variants distinct from AKAP4 homologues of other Felidae or mammals; AKAP4 dysfunction may cause the cheetah's extremely high (>80 %) pleiomorphic sperm. The study provides an unprecedented genomic perspective for the rare cheetah, with potential relevance to the species' natural history, physiological adaptations and unique reproductive disposition.
Impact of sleep disturbances on kidney function decline in the elderly
Authors: Isabelle Jaussent, Jean-Paul Cristol, Benedicte Stengel, Marie-Laure Ancelin, Anne-Marie Dupuy, Alain Besset, Catherine Helmer, Karen Ritchie, Claudine Berr, Yves Dauvilliers
Journal: European Respiratory Journal (2015)

While sleep disturbances are frequent in renal disease patients, no studies have examined prospectively the associations between sleep disturbances and kidney function decline in community-dwelling elderly subjects. Glomerular filtration rates (eGFRs) were estimated at baseline and at 11-year follow-up. A glomerular filtration decline over the follow-up period was defined as a percentage decline greater than or equal to the cut-off value of the highest tertile of kidney function decline (22%) in 1105 subjects. Excessive daytime sleepiness (EDS) and insomnia complaints were self-rated at baseline. Restless legs syndrome (RLS) and its age at onset were assessed at study end-point. An ambulatory polysomnography recording was performed during the follow-up in 277 subjects. Apnoea-hypopnoea index (AHI), periodic limb movements during sleep (PLMS) and total sleep time were analysed. An increased risk of eGFR decline was associated with EDS (OR 1.67, 95% CI 1.18–2.34) and RLS (OR 1.98, 95% CI 1.18–3.30) independently of potential confounders including cardiovascular risk factors. Among insomnia complaints, a borderline association with eGFR decline was found for early morning awakening only. High AHI (≥30 events·h −1 ) and short total sleep time (&lt;6 h), but not PLMS were linked to eGFR decline in crude associations, but only AHI remained significantly associated after multi-adjustments. EDS, RLS and AHI constitute independent risk factors for kidney glomerular function decline.
Potential of digital technologies and therapies for children and young people
Authors: Faraz Mughal, Elizabeth England
Journal: BMJ (2015)

Dowrick discusses the role of computerised cognitive behavioural therapy (cCBT) in guided self help among adults.1 For mental health illness in children and young people, such help potentially offers a familiar and accessible means of accessing therapy. In an average class of 30 schoolchildren, 10% will have experienced mental health illness. …
Microstructure of Peripapillary Atrophy and Subsequent Visual Field Progression in Treated Primary Open-Angle Glaucoma
Authors: Hiroshi Yamada, Tadamichi Akagi, Hideo Nakanishi, Hanako O. Ikeda, Yugo Kimura, Kenji Suda, Tomoko Hasegawa, Munemitsu Yoshikawa, Yuto Iida, Nagahisa Yoshimura
Journal: Ophthalmology (2015)
Autologous T cells expressing CD30 chimeric antigen receptors for relapsed or refractory Hodgkin's lymphoma: an open-label phase 1 trial
Authors: Chun-Meng Wang, Zhi-Qiang Wu, Yao Wang, Ye-Lei Guo, Xiao-Hui Wang, Xiang Li, Han-Ren Dai, Ya-Jing Zhang, Wen-Ying Zhang, Mei-Xia Chen, Yan Zhang, Kai-Chao Feng, Zhi-Gang Cao, Su-Xia Li, Qing-Ming Yang, Wei-Dong Han
Journal: The Lancet (2015)
Weight Loss Decreases Excess Pancreatic Triacylglycerol Specifically in Type 2 Diabetes
Authors: Sarah Steven, Kieren G. Hollingsworth, Peter K. Small, Sean A. Woodcock, Andrea Pucci, Benjamin Aribisala, Ahmad Al-Mrabeh, Ann K. Daly, Rachel L. Batterham, Roy Taylor
Journal: Diabetes Care (2015)

OBJECTIVE This study determined whether the decrease in pancreatic triacylglycerol during weight loss in type 2 diabetes mellitus (T2DM) is simply reflective of whole-body fat or specific to diabetes and associated with the simultaneous recovery of insulin secretory function. RESEARCH DESIGN AND METHODS Individuals listed for gastric bypass surgery who had T2DM or normal glucose tolerance (NGT) matched for age, weight, and sex were studied before and 8 weeks after surgery. Pancreas and liver triacylglycerol were quantified using in-phase, out-of-phase MRI. Also measured were the first-phase insulin response to a stepped intravenous glucose infusion, hepatic insulin sensitivity, and glycemic and incretin responses to a semisolid test meal. RESULTS Weight loss after surgery was similar (NGT: 12.8 ± 0.8% and T2DM: 13.6 ± 0.7%) as was the change in fat mass (56.7 ± 3.3 to 45.4 ± 2.3 vs. 56.6 ± 2.4 to 43.0 ± 2.4 kg). Pancreatic triacylglycerol did not change in NGT (5.1 ± 0.2 to 5.5 ± 0.4%) but decreased in the group with T2DM (6.6 ± 0.5 to 5.4 ± 0.4%; P = 0.007). First-phase insulin response to a stepped intravenous glucose infusion did not change in NGT (0.24 [0.13–0.46] to 0.23 [0.19–0.37] nmol ⋅ min−1 ⋅ m−2) but normalized in T2DM (0.08 [−0.01 to –0.10] to 0.22 [0.07–0.30]) nmol ⋅ min−1 ⋅ m−2 at week 8 (P = 0.005). No differential effect of incretin secretion was observed after gastric bypass, with more rapid glucose absorption bringing about equivalently enhanced glucagon-like peptide 1 secretion in the two groups. CONCLUSIONS The fall in intrapancreatic triacylglycerol in T2DM, which occurs during weight loss, is associated with the condition itself rather than decreased total body fat.
Randomised comparison of ABVD with two multi-drug regimens (MDRs) in the treatment of advanced Hodgkin lymphoma (HL): Initial results of the UKLG LY09 study (ISRCTN 97144519).
Authors: PM Johnson, J Radford, MH Cullen, W Jan, Sydes, D Ryder, P Smith, S Clawson, SP Stenning, B Hancock
Journal: Blood (2003)
A Cross-Species Analysis in Pancreatic Neuroendocrine Tumors Reveals Molecular Subtypes with Distinctive Clinical, Metastatic, Developmental, and Metabolic Characteristics
Authors: Anguraj Sadanandam, Stephan Wullschleger, Costas A. Lyssiotis, Carsten Grötzinger, Stefano Barbi, Samantha Bersani, Jan Körner, Ismael Wafy, Andrea Mafficini, Rita T. Lawlor, Michele Simbolo, John M. Asara, Hendrik Bläker, Lewis C. Cantley, Bertram Wiedenmann, Aldo Scarpa, Douglas Hanahan
Journal: Cancer Discovery (2015)

Seeking to assess the representative and instructive value of an engineered mouse model of pancreatic neuroendocrine tumors (PanNET) for its cognate human cancer, we profiled and compared mRNA and miRNA transcriptomes of tumors from both. Mouse PanNET tumors could be classified into two distinctive subtypes, well-differentiated islet/insulinoma tumors (IT) and poorly differentiated tumors associated with liver metastases, dubbed metastasis-like primary (MLP). Human PanNETs were independently classified into these same two subtypes, along with a third, specific gene mutation-enriched subtype. The MLP subtypes in human and mouse were similar to liver metastases in terms of miRNA and mRNA transcriptome profiles and signature genes. The human/mouse MLP subtypes also similarly expressed genes known to regulate early pancreas development, whereas the IT subtypes expressed genes characteristic of mature islet cells, suggesting different tumorigenesis pathways. In addition, these subtypes exhibit distinct metabolic profiles marked by differential pyruvate metabolism, substantiating the significance of their separate identities.This study involves a comprehensive cross-species integrated analysis of multi-omics profiles and histology to stratify PanNETs into subtypes with distinctive characteristics. We provide support for the RIP1-TAG2 mouse model as representative of its cognate human cancer with prospects to better understand PanNET heterogeneity and consider future applications of personalized cancer therapy.
Evaluation of Screening for Retinopathy of Prematurity by ROPtool or a Lay Reader
Authors: Ashkan M. Abbey, Cagri G. Besirli, David C. Musch, Chris A. Andrews, Antonio Capone, Kimberly A. Drenser, David K. Wallace, Susan Ostmo, Michael Chiang, Paul P. Lee, Michael T. Trese
Journal: Ophthalmology (2015)
TCF1 links GIPR signaling to the control of beta cell function and survival
Authors: Jonathan E Campbell, John R Ussher, Erin E Mulvihill, Jelena Kolic, Laurie L Baggio, Xiemen Cao, Yu Liu, Benjamin J Lamont, Tsukasa Morii, Catherine J Streutker, Natalia Tamarina, Louis H Philipson, Jeffrey L Wrana, Patrick E MacDonald, Daniel J Drucker
Journal: Nature Medicine (2015)
Interleukin-15 is associated with disease severity in viral bronchiolitis
Authors: T. Ronan Leahy, Ross McManus, Derek G. Doherty, Robert Grealy, Tanya Coulter, Paul Smyth, Gordon Blackshields, Orla Sheils, Michael J. Carr, Nikhil Purandare, Michael Geary, Hennie M. Hodemaekers, Riny Janssen, Louis Bont, Dubhfeasa Slattery, Thomas Ryan
Journal: European Respiratory Journal (2015)

Disease severity in viral bronchiolitis in infancy is difficult to predict and has been linked to host innate immunity. The study aimed to investigate the innate cytokine interleukin-15 (IL-15) as a marker of disease severity. A prospective single-centre observational study was conducted in a university-affiliated paediatric teaching hospital, comparing children (0–18 months) hospitalised for viral bronchiolitis, those admitted to the paediatric intensive care unit with severe disease and healthy age-matched controls. IL-15-related parameters were compared between groups. PCR and microRNA (miRNA) sequencing was undertaken on natural killer (NK) cells collected from study participants. Samples from 88 children with viral bronchiolitis and 43 controls enrolled between 2009 and 2012 were analysed. Peripheral blood mononuclear cell (PBMC) IL-15 mRNA expression was significantly higher in those with moderate severity bronchiolitis compared with controls and those with severe disease. Serum IL-15 levels correlated with disease severity. The relative frequency of NK cells in peripheral blood was significantly reduced in participants with bronchiolitis. The NK cell miRNA transcriptome in bronchiolitis was distinct. Targets of de-regulated miRNA were differentially expressed in bronchiolitis, including JAK3 , STAT5A and NFKB1 on the IL-15 signalling pathway. IL-15 is associated with disease severity in children hospitalised with viral bronchiolitis.
Nuclear-enriched abundant transcript 1 as a diagnostic and prognostic biomarker in colorectal cancer
Authors: Yuchen Wu, Li Yang, Jiang Zhao, Cong Li, Jia Nie, Fangqi Liu, Changhua Zhuo, Yaxin Zheng, Bin Li, Zhimin Wang, Ye Xu
Journal: Molecular Cancer (2015)

High expression of the long non-coding RNA nuclear-enriched abundant transcript 1 (NEAT1) in whole blood has been reported in colorectal cancer patients; however, its' clinical significance and origin are unclear. We evaluated the diagnostic and prognostic value, and origin of whole blood NEAT1 in colorectal cancer. Expression of NEAT1 variants, NEAT1_v1 and NEAT1_v2 were determined using real-time quantitative PCR. The diagnostic value of whole blood NEAT1 expression was evaluated in test (n = 60) and validation (n = 200) cohorts of colorectal cancer patients and normal controls (NCs). To identify the origin of NEAT1, its expression was analyzed in blood, matched primary tumor tissues, para-tumor tissues, metastatic tissues, and also immune cells from patients or NCs. Function of NEAT1 in colorectal cell lines was also assessed. The correlation of NEAT1 expression with clinical outcomes was assessed in 191 patients. Whole blood NEAT1 expression was significantly higher in colorectal cancer patients than in NCs. NEAT1_v1 and NEAT1_v2 expression were highly accurate in distinguishing colorectal cancer patients from NCs (area under the curve: 0.787 and 0.871, respectively). Knockdown of NEAT1_v1 in vitro could inhibit cell invasion and proliferation, while knockdown of NEAT1_v2 promoted cell growth. However, whole blood expression was not correlated with matched tissues. An elevated expression was seen in neutrophils from CRC patients. Furthermore, high expression of NEAT1_v1 was correlated with worse overall survival. In contrast, high expression of NEAT1_v2 alone was correlated with better overall survival. Whole blood NEAT1 expression is a novel diagnostic and prognostic biomarker of overall survival in colorectal cancer. Elevated NEAT1 may derive from neutrophils.
Role of transcription factors ASCL1 and HES1 expression in diffuse idiopathic neuroendocrine cell hyperplasia (DIPNECH) and pulmonary carcinoids
Authors: Beate Ebert, Furqan Bari, David Snead, Daniel Mitchell
Journal: European Respiratory Journal (2013)

Background  Carcinoid tumours are common neuroendocrine tumours in the lung. The majority of cases appear to be solitary; multiple tumours occur in patients with diffuse idiopathic pulmonary neuroendocrine cell heperplasia (DIPNECH), characterised by multiple hyperplastic neuroendocrine (NE) cell foci throughout the lung fields. In these patients DIPNECH appears to be the precursor lesion in the development of carcinoid tumours.  Aims  ASCL1 (Achaete-scute homolog 1) and HES1 (Hairy and enhancer of split 1) are transcription factors important in neuroendocrine development in the lung.  We hypothesised that pathways involving these genes may be deranged in patients with DIPNECH and aimed to study their expression in sporadic and DIPNECH carcinoids.  Methods  Formalin fixed paraffin embedded (FFPE) samples from 25 carcinoid tumour cases (19 sporadic pulmonary carcinoids, 6 DIPNECH carcinoids) were studied. Expression of ASCL1 and HES1 was studied by real time PCR and immunohistochemistry (IHC).  Results  ASCL1 was more highly expressed in tumour samples than background lung (p=0.0149). HES1 was more highly expressed in background lung and DIPNECH compared to tumour samples (p=0.0016).  HES1 staining was positive in all carcinoid tumours with no difference between DIPNECH and sporadic cases. ASCL1 staining was positive in 4 of 6 DIPNECH carcinoids, compared to 3 of 19 sporadic carcinoids (p=0.0324).  Conclusion  ASCL1 expression was significantly higher in DIPNECH carcinoids compared to sporadic cases, and was also present in NE foci suggesting an alteration in the pathway of this gene in DIPNECH patients and the carcinoid tumours found in this condition.
Abstract 14520: Ultrasound-Mediated Anti-apoptotic Gene Therapy for Doxorubicin-Induced Cardiomyopathy
Authors: Paul J Lee, Hiroko Fujii, Dmitriy Rudenko, Christine Liao, Michael A Kuliszewski, Howard Leong-Poi
Journal: Circulation (2010)

Background: Progressive apoptosis following the primary injury has been implicated in the progression to end-stage heart failure. Survivin, a member of the inhibitor of apoptosis protein, is one of...
US Senate launches hearings into soaring prices of off-patent drugs
Authors: Michael McCarthy
Journal: BMJ (2015)

The US government may need to act to discourage drug companies from hiking the prices of off-patent drugs, senators from both main parties said at the first of a series of hearings on soaring drug prices held by the Senate Special Committee on Aging on 9 December.

The hearings were prompted by recent reports of drug companies increasing prices by as much as 40-fold for off-patent drugs for which there was no current competition from generic versions. In one case the New York City based Turing Pharmaceuticals acquired pyrimethamine (Daraprim), an antiparasitic drug used in the United …