tbuckley/cabot-search huggingface dataset:
Many Roads Lead to snoRNAs: The Ever‐Expanding Universe of Non‐Coding RNAs in Acute Myeloid Leukemia
Authors: Stefan Fröhling
Journal: HemaSphere (2017)

While chimeric fusion genes resulting from balanced chromosomal translocations have long been recognized as "drivers" of acute myeloid leukemia (AML), their critical downstream mediators are incompletely understood. In particular, common effector programs that are shared by various leukemogenic fusion genes, and may thus represent attractive targets for therapeutic intervention, remain elusive. Carsten Müller-Tidow and colleagues now demonstrate that fusion oncoproteins such as RUNX1T1-RUNX1 (also known as AML1-ETO) and MLLT3-KMT2A (also known as MLL-AF9) contribute to AML development by upregulating the expression of a distinct subset of small nucleolar RNAs (snoRNAs) that promote leukemogenesis via enhanced formation of snoRNA ribonucleoprotein complexes, induction of rRNA methylation, increased protein translation, and possibly other mechanisms. This first investigation into the functional consequences of aberrant snoRNA expression in AML adds to the ever-expanding catalog of non-coding RNAs involved in myeloid leukemogenesis, and raises the intriguing possibility that snoRNA deregulation may be a unifying feature of this disease. Furthermore, these data provide a starting point for future studies of the mechanistic link(s) between different types of leukemogenic driver mutations and snoRNA expression and the potential of snoRNAs as tractable therapeutic targets. Link to: Zhou et al. Nat Cell Biol. 2017;19(7):844–855. PMID: 28650479; https://www.nature.com/articles/ncb3563Figure 1: Zhou et al. have discovered that AML1-ETO promotes leukemogenesis through snoRNA formation mediated by interaction of Amino Enhancer of Split (AES) with the RNA helicase DDX21 and snoRNA ribonucleoprotein (snoRNP) complexes. Of note, leukemogenesis is inhibited by AES depletion, whereas normal hematopoietic cells lacking AES or other snoRNP complex members survive in vitro and in vivo and AES gene knockout is not lethal in mice.
Use of the hCONSORT criteria as a reporting standard for herbal interventions for common dermatoses: a systematic review
Authors: J. Ornelas, E. Routt, P. Kallis, H. Lev-Tov
Journal: British Journal of Dermatology (2017)

Summary Background The use of complementary and alternative medicine (CAM) is increasing in Western countries, including in the area of dermatology. However, Western healthcare providers have not integrated CAM into regular practice owing to a lack of reliable data supporting its use. To encourage high-quality research related to the use of CAM and specifically herbal interventions, the CONsolidated Standards Of Reporting Trials (CONSORT) extension criteria on reporting herbal interventions (hCONSORT) were published in 2006. Objectives To evaluate the adherence of randomized controlled trials (RCTs) investigating herbal interventions for acne, atopic dermatitis (AD) and psoriasis to the hCONSORT criteria. Methods A comprehensive search of the PubMed, Embase and Cochrane Library databases was conducted. RCTs published between 2009 and 2014 assessing therapeutic outcomes of plant-based interventions for acne, AD or psoriasis were included. Investigators determined the number of unique hCONSORT criteria satisfied per report. anova was used to examine differences in scores by disease entity. Results The vast majority of reviewed studies reported &amp;lt; 50% of information recommended in the hCONSORT criteria. Limitations include the small number of dermatological conditions examined, exclusion of reports based on language and lack of assessment of overall adherence to CONSORT criteria. Conclusions Our data indicate lack of adherence to hCONSORT extension criteria. Adherence to hCONSORT guidelines should be encouraged in order to provide high-quality reporting of research on herbal interventions in dermatology. Doing so may ease the integration of CAM into conventional medical practice and provide actionable data to providers.
Low-dose CT lung cancer screening in the community: A prospective cohort study.
Authors: Vincent K. Lam, Mary Miller, Lynn Dowling, Shyamali Singhal, Robert P Young, Elwyn Clement Cabebe
Journal: Journal of Clinical Oncology (2014)

1566 Background: Results from the National Lung Screening Trial (NLST) in 2011 showed that low-dose CT screening in high-risk groups reduces lung cancer deaths. Major professional organizations, as well as the USPSTF, have endorsed low-dose CT screening in these select populations. However, major questions remain about whether widespread deployment of CT screening can achieve results similar to the NLST, especially in the community setting. Methods: A prospective cohort study was initiated in November 2010. High-risk participants (age at least 50 years old and history of cigarette smoking of at least 20 pack-years) underwent low-dose CT screening, performed and interpreted at El Camino Hospital in Mountain View, California. Diagnostic follow-up for positive scans were recommended per International Early Lung Cancer Action Program (I-ELCAP) guidelines. Participants were followed for events that occurred through December 31, 2013. Results: 157 participants underwent low-dose CT screening with mean follow-up of 2.2 years. Median age at entry was 64 (range 50-95). 59% of the participants are women and 94% are Caucasian. Over 80% also satisfied the more stringent NLST inclusion criteria for smoking history. The rate of positive initial screening tests was 35.7%. One positive screen (3.2%) required invasive diagnostic follow-up, which was uncomplicated. No interval lung cancer was detected. One incident case of small cell lung cancer resulted in death. The rate of timely adherence to diagnostic follow-up was only 43%. Late follow-up was often due to participant or primary care provider preference (68%), with participants lost to follow-up (18%) and lack of insurance (10%) also contributing. Conclusions: To our knowledge, this is the first community-based prospective study of low-dose CT lung cancer screening. Compared to the NLST, the higher rate of positive initial screening tests (36% vs 27%), higher overall false positive rate, and significantly decreased adherence (43% vs 95%) in this study highlight the difficulties of generalizing the NLST mortality benefits in the broad deployment of CT screening. Our results support current recommendations that CT screening be performed in a highly structured and integrated setting.
A retrospective study to evaluate the relationship between bone marrow infiltration in first diagnostic aspirate with morphology of megakaryocytes and platelets count, in cases of pediatric malignant round cell tumor: Experience from AIIMS, New Delhi.
Authors: Pranay Tanwar, Ritu Gupta, Sameer Bakhshi
Journal: Journal of Clinical Oncology (2014)

e21010 Background: Malignant round cell tumors which include Ewings sarcoma/PNET, neuroblastoma and retinoblastoma are included in the common cause list for childhood mortality. A number of cases presented to hospital first time directly with Stage IV disease in the form of bone marrow infiltration by the tumor cells. During standard therapy and follow up, some cases may infiltrate bone marrow in future. The peculiar morphological observation, which showed temporal association between adequate number of megakaryocytes (with multilobated nuclei) correlating more with bone marrow free of tumor infiltration sensitized us, to carry out this study. The aim of study was to find relationship between bone marrow infiltration in first diagnostic aspirate with morphology of megakaryocytes and platelets count, in cases of pediatric malignant round cell tumor. Methods: This is a retrospective study in which bone marrow aspirate from Jan-2011 to Dec-2012 of all cases (213) of pediatric malignant round cell tumor which included Ewings sarcoma/PNET (154), retinoblastoma (36), and neuroblastoma (33) were studied.The bone marrow aspirates archival smears and H&E stained biopsies of all the cases were studied by two independent pathologists with complete blinding.The platelets count, cellularity, morphology of megakaryocytes were studied on aspirate which were confirmed on bone marrow biopsy. Results: The presence of low platelets (<1,50,000/µl) was statistically siginificant(p<001) in cases with marrow infiltartion by tumor cells. Low cellularity and presence of hypolobated forms of megakaryocytes were also more in favor of bone marrow infiltration at the time of primary staging of disease. Conclusions: Megakaryocytes morphology along with platelets count can be helpful diagnostic clue in staging of the disease, specially in cases where aspirate is pauci-cellular and biopsy is unavailable . This needs validation with the help of image morphometry with larger number of cases to reach to statistically significant conclusion.
PTH-106 Phenotypic characterisation of elderly – onset inflammatory bowel disease – ibd at 60 and beyond
Authors: U Nosegbe, B Miller, B Crooks, J Scott, J Limdi
Journal: Gut (2017)

Introduction  The incidence of inflammatory bowel disease (IBD) is increasing globally in all age groups however data on elderly onset IBD (age 60 and over) is limited. We aimed to study the phenotypic characteristics of elderly onset IBD.  Method  A retrospective analysis of 142 patients diagnosed with IBD at 60 years or above at our institution between 1995 and 2016 was conducted. Electronic case notes were reviewed to collect data on demographics, Montreal classification and treatment  Results  Of 142 patients in our cohort, 71 were male. Median age was 71 years (range 62–91) and median age at diagnosis was 65 years (range 60–85). 50 patients had Crohn’s disease (CD) (35.2%), 81 Ulcerative colitis (UC) (57.0%) and 11 (7.8%) IBD-unspecified (IBDU).  Montreal classification for UC was proctitis (E1) in 27, left sided colitis (E2) in 30 and pancolitis (E3) in 22. Two patients with proctosigmoiditis await classification. Montreal classification for CD was ileal structuring (L1 B2) in 18 : colonic (L2 B1 in 14 patients and L2 B2 in 5 patients. Ileo-colonic (L3) disease was found in 12 (7 B1 and 5 B2) patients.  At diagnosis 88 patients were prescribed 5ASA’s (18 topical and 6 combined with oral 5ASA’s). Corticosteroids were prescribed at diagnosis in 44 (31.4%) patients. Azathioprine was used in 3 (2 E3 and 1 L2B2) patients and 3 patients commenced Infliximab at diagnosis (L3B1 and L1B2 CD and E3 UC).  At most recent follow up 26 patients were on corticosteroids, 35 were on immunomodulation (26 on Azathioprine, 5 on 6MP and 4 on Methotrexate) with a mean time to immunomodulation being 29.4 months (range 0–137). 16 were on biologics (14 Infliximab and 2 Adalimumab) with a mean time to therapy of 33.7 months (range 0–189 months). 15 patients (10.7%) had surgery related to IBD: 2 UC vs 13 CD and median time to surgery was 20 months (range 0–132 with 2 patients being diagnosed at initial surgery). Colon cancer was diagnosed in 1 patient with L2B1 and curative resection was undertaken. 4 deaths occurred: 1 from CLL (not on immunomodulation), 1 klebsiella pneumonia on Azathioprine, 1 from cryptococcal meningitis on Azathioprine and Infliximab and 1 from prostate cancer.  Conclusion  We noted a higher prevalence of UC with E2 and E3 disease and a colonic phenotype in CD corroborating with data from the EPIMAD registry1.. A large proportion of patients received immunomodulation which is an area of concern and needs careful consideration There is an urgent need for more data on disease presentation, natural history and treatment paradigms for the considered and optimal management of elderly patients with IBD.  Reference  Charpentier C, et al. Natural history of elderly-onset inflammatory bowel disease: a population-based cohort study. Gut2014;63(3):423–32  Disclosure of Interest  None Declared
Relationship Between the Elevated Muscle FDG Uptake in the Distal Upper Extremities on PET/CT Scan and Prescan Utilization of Mobile Devices in Young Patients
Authors: Xia Bai, Xuemei Wang, Hongming Zhuang
Journal: Clinical Nuclear Medicine (2017)

It is common to notice increased FDG activity in the muscles of the forearms or hands on PET/CT images. The purpose of this study was to determine relationship between the prevalence of increased FDG activity in the forearms or hands and using mobile devices prior to the FDG PET/CT study.A total of 443 young patients with ages between 5 and 19 years who underwent FDG PET/CT scan were included in this retrospective analysis. All patients had FDG PET/CT with their arms within the field of views. The images were reviewed for elevated activity in the muscles of the distal upper extremities (DUEs), which include forearms and hands. The preimaging questionnaire/interview records regarding using mobile devices prior to FDG PET/CT were also reviewed and compared with the imaging findings.Most patients (72.0% [319/443]) used mobile devices more than 60 minutes in the period of 24 hours prior to the FDG PET/CT study. Elevated uptake in the muscles in the DUEs was observed in 38.6% (123/319) of these patients. In contrast, among 124 patients who did not use the mobile devices or used the mobile device minimally prior to the study, only 6.5% (8/124) of them had elevated FDG activity in the DUEs. The difference persisted following stratification analysis for sex, age, and serum glucose level in our patient population.Increased FDG uptake in the muscles of the DUEs in young patients is commonly seen in those who used mobile devices prior to PET/CT study. Recommendation should be considered to reduce using mobile devices prior to FDG PET/CT study in young patient population.
Phosphorylation of intracellular signalling molecules in peripheral blood cells from patients with psoriasis on originator or biosimilar infliximab
Authors: A.K. Aarebrot, S.M. Solberg, R. Davies, L.I. Bader, T.D. Holmes, S. Gavasso, Y.T. Bryceson, R. Jonsson, L.F. Sandvik, S. Appel
Journal: British Journal of Dermatology (2017)

Psoriasis vulgaris is a chronic, inflammatory skin disease characterized by a dysregulated immune response and it is associated with substantial systemic comorbidities. Biological drugs such as tumour necrosis factor (TNF)‐α inhibitors can ameliorate the disease but are expensive. Biosimilar drugs have the same amino‐acid sequence as the originator, but differences in manufacturing can affect biological activity, efficacy and tolerability. To explore potential differences in intracellular phosphorylation of signalling molecules in peripheral blood cells from patients with psoriasis treated with the TNF‐α inhibitor infliximab compared with healthy controls, and to investigate if the phosphorylation pattern was influenced by switching from the originator infliximab to the biosimilar CT‐P13. By flow cytometry, we measured phosphorylation of nuclear factor kappa B, extracellular signal‐regulated kinase 1/2, p38 mitogen‐activated protein kinase and signal transducer and activator of transcription 3, before and after TNF‐α stimulation in monocytes and T, B, natural killer and CD3+ CD56+ cells from 25 patients with psoriasis treated with infliximab and 19 healthy controls. At inclusion, phosphorylation levels of peripheral blood mononuclear cells (PBMCs) were increased in patients with psoriasis compared with healthy controls, even though clinical remission had already been achieved. Phosphorylation levels declined in patients on both originator infliximab and biosimilar during continued treatment. No significant differences were detected between the two medications after 12 months. Patients with psoriasis on infliximab have higher activation levels of PBMCs than do healthy controls, possibly reflecting systemic inflammation. Switching from the originator infliximab to biosimilar CT‐P13 did not affect phosphorylation levels or clinical parameters, suggesting that CT‐P13 is a noninferior treatment alternative to the originator infliximab.
2D MoS<sub>2</sub> Nanostructures for Biomedical Applications
Authors: Teng Liu, Zhuang Liu
Journal: Advanced Healthcare Materials (2017)

Abstract MoS 2 nanosheets, a typical kind of layered transition metal dichalcogenides with the 2D structure and many unique physical and chemical properties, have attracted a lot of research interests in various fields. Typically, MoS 2 nanosheets present similarities to graphene in terms of their large surface area and strong absorbance in near‐infrared region, which in combination with their easily functionalized surface make them promising nanoplatforms in biomedical applications. Herein, the progress of MoS 2 nanosheets and their composites in the area of nanomedicine, with the emphasis on their synthesis and modification strategies, their biomedical applications in biosensing, imaging and therapy, as well as evaluations of their in vivo behaviors and toxicology profiles are summarized. Finally, the challenges and opportunities of applying MoS 2 ‐based nanomaterials in the biomedicine areas will be discussed.
Decreased expression and aberrant hypermethylation of the SFRP genes in human gastric cancer
Authors: Satoshi Otani, Takashi Kinoshita, Shuji Nomoto, Hideki Kasuya, Hiroyuki Sugimoto, Naohito Kanasumi, Shin Takeda, Akimasa Nakao
Journal: Cancer Research (2007)

1788  It has recently been reported that the expression of secreted frizzled-related protein (SFRP) genes is silenced by aberrant methylation of the promoter region in several cancers. Chromosomal aberrations in gastric cancer have been extensively studied and many chromosomal loci have been discovered. SFRP genes have recently been mapped on chromosome 8p12-p12.1 (SFRP1), 4q31.3 (SFRP2) and 10q24.1 (SFRP5), respectively. Interestingly, the SFRP family genes are located where the frequent LOH have been shown in gastric cancer samples. In the current study, the methylation status and expression of SFRP genes were investigated in gastric cancer cell lines and surgically resected specimens. A significant decrease in the expression of SFRP1 and 5 was observed in gastric cancer compared with corresponding normal gastric tissues. Among the clinical samples, the SFRP1 gene was hypermethylated in all 35 cancer tissues and corresponding non-cancerous tissues as well as all seven gastric cancer cell lines, whereas SFRP2 gene was methylated in 83% (29/35) of cancer tissues and 69% (24/35) of the normal epithelium, and SFRP5 in 43% (15/35) of cancer tissues and 54% (19/35) of the normal epithelium, respectively. Although gender, age, tumor size, pathological type, depth of tumor and TNM stage were not significantly correlated with the expression of SFRP genes, a significant decrease in the SFRP1 expression score was observed among gastric cancer with lymph node metastasis. These results indicate the possibility that SFRP1 and 5 genes function as tumor suppressors, the down-regulation of which not only contribute to carcinogenesis but is also associated to some extent with the metastatic potential of cancer cells.
Age should not be a barrier for pulmonary endarterectomy in carefully selected patients
Authors: Michael Newnham, Jules Hernández-Sánchez, John Dunning, Choo Ng, Steven Tsui, Katherine Bunclark, Karen Sheares, Dolores Taboada, Mark Toshner, Joanna Pepke-Zaba, David Jenkins, John Cannon
Journal: European Respiratory Journal (2017)

Pulmonary endarterectomy (PEA) is the treatment of choice in operable chronic thromboembolic pulmonary hypertension (CTEPH) with excellent long-term outcomes [1]. It is a complex surgical procedure requiring cardiopulmonary bypass and removal of obstructive thromboembolic material during periods of deep hypothermic circulatory arrest [1]. We have observed an increase in the number of older CTEPH patients referred for consideration of PEA, which is consistent with other cardiothoracic surgeries. The UK population is ageing with a projected 3% increase in subjects aged >85 years in the next 20 years [2]. This may be mirrored by patients with CTEPH getting older, as the incidence of pulmonary embolism, which frequently precedes CTEPH, markedly increases with age [3, 4]. Furthermore, an epidemiological analysis by Gall et al. [5] has projected that the annual incidence of CTEPH will increase over the next 10 years. Therefore, the management of CTEPH in older patients is a pertinent topic for investigation. CTEPH patients over 80 years old undergoing pulmonary endarterectomy have similar outcomes to those under 80 years <http://ow.ly/MlCj30guFPu> The authors wish to thank the National Pulmonary Hypertension Centres UK and Ireland for referring the patients that were considered for PEA.
Prediction of a multiple sclerosis diagnosis in patients with clinically isolated syndrome using the 2016 MAGNIMS and 2010 McDonald criteria: a retrospective study
Authors: Massimo Filippi, Paolo Preziosa, Alessandro Meani, Olga Ciccarelli, Sarlota Mesaros, Alex Rovira, Jette Frederiksen, Christian Enzinger, Frederik Barkhof, Claudio Gasperini, Wallace Brownlee, Jelena Drulovic, Xavier Montalban, Stig P Cramer, Alexander Pichler, Marloes Hagens, Serena Ruggieri, Vittorio Martinelli, Katherine Miszkiel, Mar Tintorè, Giancarlo Comi, Iris Dekker, Bernard Uitdehaag, Irena Dujmovic-Basuroski, Maria A Rocca
Journal: The Lancet Neurology (2017)
Risk of Soft-Tissue Sarcoma Among 69 460 Five-Year Survivors of Childhood Cancer in Europe
Authors: Chloe J Bright, Mike M Hawkins, David L Winter, Daniela Alessi, Rodrigue S Allodji, Francesca Bagnasco, Edit Bárdi, Andrea Bautz, Julianne Byrne, Elizabeth A M Feijen, Miranda M Fidler, Stanislaw Garwicz, Desiree Grabow, Thorgerdur Gudmundsdottir, Joyeeta Guha, Nadia Haddy, Momcilo Jankovic, Peter Kaatsch, Melanie Kaiser, Claudia E Kuehni, Helena Linge, Hilde Øfstaas, Cecile M Ronckers, Roderick Skinner, Jop C Teepen, Monica Terenziani, Giao Vu-Bezin, Finn Wesenberg, Thomas Wiebe, Carlotta Sacerdote, Zsuzsanna Jakab, Riccardo Haupt, Päivi Lähteenmäki, Lorna Zadravec Zaletel, Rahel Kuonen, Jeanette F Winther, Florent de Vathaire, Leontien C Kremer, Lars Hjorth, Raoul C Reulen
Journal: JNCI Journal of the National Cancer Institute (2017)

Childhood cancer survivors are at risk of subsequent primary soft-tissue sarcomas (STS), but the risks of specific STS histological subtypes are unknown. We quantified the risk of STS histological subtypes after specific types of childhood cancer. We pooled data from 13 European cohorts, yielding a cohort of 69 460 five-year survivors of childhood cancer. Standardized incidence ratios (SIRs) and absolute excess risks (AERs) were calculated. Overall, 301 STS developed compared with 19 expected (SIR = 15.7, 95% confidence interval [CI] = 14.0 to 17.6). The highest standardized incidence ratios were for malignant peripheral nerve sheath tumors (MPNST; SIR = 40.6, 95% CI = 29.6 to 54.3), leiomyosarcomas (SIR = 29.9, 95% CI = 23.7 to 37.2), and fibromatous neoplasms (SIR = 12.3, 95% CI = 9.3 to 16.0). SIRs for MPNST were highest following central nervous system tumors (SIR = 80.5, 95% CI = 48.4 to 125.7), Hodgkin lymphoma (SIR = 81.3, 95% CI = 35.1 to 160.1), and Wilms tumor (SIR = 76.0, 95% CI = 27.9 to 165.4). Standardized incidence ratios for leiomyosarcoma were highest following retinoblastoma (SIR = 342.9, 95% CI = 245.0 to 466.9) and Wilms tumor (SIR = 74.2, 95% CI = 37.1 to 132.8). AERs for all STS subtypes were generally low at all years from diagnosis (AER < 1 per 10 000 person-years), except for leiomyosarcoma following retinoblastoma, for which the AER reached 52.7 (95% CI = 20.0 to 85.5) per 10 000 person-years among patients who had survived at least 45 years from diagnosis of retinoblastoma. For the first time, we provide risk estimates of specific STS subtypes following childhood cancers and give evidence that risks of MPNSTs, leiomyosarcomas, and fibromatous neoplasms are particularly increased. While the multiplicative excess risks relative to the general population are substantial, the absolute excess risk of developing any STS subtype is low, except for leiomyosarcoma after retinoblastoma. These results are likely to be informative for both survivors and health care providers.