tbuckley/cabot-search huggingface dataset:
Longitudinal evaluation of health status and chronic conditions in aging pediatric astrocytoma survivors: A Childhood Cancer Survivor Study (CCSS) report.
Authors: Karen Elizabeth Effinger, Paul Graham Fisher, Kirsten K. Ness, Kevin R. Krull, Neyssa Marina, Marilyn Stovall, Kevin C. Oeffinger, Gregory T. Armstrong, Leslie L. Robison, Paul C. Nathan, Wendy M. Leisenring, Melissa M. Hudson
Journal: Journal of Clinical Oncology (2015)

10067 Background: Astrocytoma is a common pediatric central nervous system tumor. However, little is known about the health status and chronic conditions and their association with social outcomes in aging survivors. Methods: We evaluated 1,073 5-year astrocytoma survivors (median age: 28 years, range 9-56; median time from diagnosis: 21 years, range 7-38) and 4,023 siblings enrolled in the CCSS at up to 3 time points. We estimated the prevalence of poor health status in 6 domains (general health, functional impairment, activity limitation, mental health, cancer-related pain, cancer-related anxiety); severe, disabling, or life-threatening chronic conditions; and social outcomes (marriage, education, employment, income) in those ≥ 25 years of age. We compared outcomes between survivors and siblings as a function of attained age using generalized linear models with robust variances adjusted for race, sex, and body mass index. Results: Compared with siblings, astrocytoma survivors were more likely to report poor health status across all domains, more chronic conditions, and poor social outcomes. Among survivors, increasing numbers of chronic conditions were associated with lower marriage and employment rates, lower income, and poor health status in all domains. All domains of poor health status were associated with unemployment. Conclusions: Pediatric astrocytoma survivors have increased odds of poor health status, chronic health conditions, and poor social outcomes compared with siblings. Chronic conditions impact health status and social outcomes highlighting the need for regular screening and early interventions. Survivors (%) Siblings (%) Odds Ratio (95% Confidence Interval) Poor general health 16.0 5.1 3.6 (3.0-4.3) Functional impairment 32.7 3.7 13.3 (11.1-16.0) Activity limitation 20.3 5.6 4.6 (3.9-5.5) Poor mental health 21.0 10.9 2.0 (1.7-2.4) Cancer-related pain 12.4 NA - Cancer-related anxiety 12.8 NA - Chronic conditions 47.7 9.9 9.1 (7.7-10.6) Married 41.3 69.3 0.32 (0.27-0.37) Graduated college 40.5 55.1 0.61 (0.52-0.71) Employed 64.7 87.1 0.26 (0.22-0.31) Income > $20,000 79.7 95.0 0.24 (0.19-0.30)
MIR142 Loss-of-Function Mutations Promote Leukemogenesis through Derepression of ASH1L Resulting in Increased HOX Gene Expression
Authors: Juo-Chin Yao, Terrence Neal Wong, Maria Trissal, Rahul Ramaswamy, Yaping Sun, Timothy J. Ley, Pavan R. Reddy, Daniel C. Link
Journal: Blood (2016)
Caesarean section raises risk of complications after hysterectomy, study finds
Authors: Zosia Kmietowicz
Journal: BMJ (2017)

Having a previous caesarean delivery may considerably increase the risk of reoperation and complications in women who have a hysterectomy later in life, a study published in JAMA Surgery has found.1

The finding supports efforts to prevent caesarean deliveries that are not clinically indicated, said the authors from Aalborg University, Denmark, and Harvard TH Chan School of Public Health in Boston, USA. Caesarean delivery is the most commonly performed major surgery in the world, with an estimated global average rate …
Investigation of epidermal growth factor receptor and erbB-2 molecular targeted therapies in undifferentiated thyroid cancer cell lines
Authors: Yasuyuki Nobuhara, Naoyoshi Onoda, Yoshito Yamashita, Masanao Yamazaki, Shigehito Yamagata, Akiko Tachimori, Rie Ishibashi, Tsutomu Takashima, Masakazu Yashiro, Tetsuro Ishikawa, Kosei Hirakawa
Journal: Cancer Research (2004)

4532   Objectives: To measure the expression of epidermal growth factor receptor (EGFR) and erbB-2 in undifferentiated thyroid cancer cell lines and to explore the potential of therapies targeting these molecules as a new therapeutic approach. Materials and methods: Using five undifferentiated thyroid cancer cell lines (OCUT-1, 2, ACT-1, KTC-1, TTA-1), expression of EGFR and erbB-2 mRNA was measured by reverse transcriptase polymerase chain reaction and their protein expression measured by flow cytometry. The inhibitory effects of gefitinib (‘Iressa’, ZD1839) and trastuzumab, molecular targeted inhibitors of EGFR and erbB-2, respectively, on the proliferation of these cell lines was measured by cell counting and MTT assay. Results: The expression of EGFR and erbB-2 mRNA and protein was observed in all cell lines. EGFR expression was low in OCUT-2 and the levels of erbB-2 expression were low in all five cell lines. There was no correlation between expression of mRNA and protein. The cell proliferation of ACT-1 and TTA-1 was significantly enhanced by the addition of EGF (1 ng/ml) and this enhanced cell proliferation was inhibited by the addition of gefitinib (10-100 nM). However, the proliferation of OCUT-2 was neither enhanced by EGF nor inhibited by gefitinib. When the inhibitory effects of gefitinib and trastuzumab used alone in the presence of 10% fetal calf serum were assessed by MTT assay, both agents required a high concentration (IC50=20 μM) to inhibit cell proliferation, even in cell lines against which they had the most potent inhibitory effect. Conclusion: We confirmed expression of EGFR and erbB-2 in a number of undifferentiated thyroid cancer cell lines and inhibition of EGFR-mediated cell proliferation by gefitinib.
Developmental follow-up of children and young people born preterm: summary of NICE guidance
Authors: Maija Kallioinen, Hilary Eadon, M Stephen Murphy, Gillian Baird
Journal: BMJ (2017)

#### What you need to know

Preterm birth, defined as birth before 37+0 weeks’ gestation, is associated with short and long term problems. While most babies born preterm have good developmental outcomes and quality of life, some experience problems which can affect learning and function, activities, and participation.

Around 7.5% of babies are born preterm in England and Wales, and approximately 0.4% are born extremely preterm (<28+0 weeks’ gestation). In 2015, this amounted to 53 209 babies born preterm and 3014 born extremely preterm.1

This article summarises the recent NICE guidance on the developmental follow-up of children and young people born preterm2 and was commissioned to improve the early identification of developmental problems and disorders in children born preterm and to alert health professionals to risk factors that may increase the likelihood of problems.

Much of the developmental support …
Interference with Gsα-Coupled Receptor Signaling in Renin-Producing Cells Leads to Renal Endothelial Damage
Authors: Peter Lachmann, Linda Hickmann, Anne Steglich, Moath Al-Mekhlafi, Michael Gerlach, Niels Jetschin, Steffen Jahn, Brigitte Hamann, Monika Wnuk, Kirsten Madsen, Valentin Djonov, Min Chen, Lee S. Weinstein, Bernd Hohenstein, Christian P.M. Hugo, Vladimir T. Todorov
Journal: Journal of the American Society of Nephrology (2017)

Intracellular cAMP, the production of which is catalyzed by the α -subunit of the stimulatory G protein (Gs α ), controls renin synthesis and release by juxtaglomerular (JG) cells of the kidney, but may also have relevance for the physiologic integrity of the kidney. To investigate this possibility, we generated mice with inducible knockout of Gs α in JG cells and monitored them for 6 months after induction at 6 weeks of age. The knockout mapped exclusively to the JG cells of the Gs α -deficient animals. Progressive albuminuria occurred in Gs α -deficient mice. Compared with controls expressing wild-type Gs α alleles, the Gs α -deficient mice had enlarged glomeruli with mesangial expansion, injury, and FSGS at study end. Ultrastructurally, the glomerular filtration barrier of the Gs α -deficient animals featured endothelial gaps, thickened basement membrane, and fibrin-like intraluminal deposits, which are classic signs of thrombotic microangiopathy. Additionally, we found endothelial damage in peritubular capillaries and vasa recta. Because deficiency of vascular endothelial growth factor (VEGF) results in thrombotic microangiopathy, we addressed the possibility that Gs α knockout may result in impaired VEGF production. We detected VEGF expression in JG cells of control mice, and cAMP agonists regulated VEGF expression in cultured renin-producing cells. Our data demonstrate that Gs α deficiency in JG cells of adult mice results in kidney injury, and suggest that JG cells are critically involved in the maintenance and protection of the renal microvascular endothelium.
Non-Catalytic Role of SETD1A Regulates DNA Repair in Leukemia
Authors: Takayuki Hoshii, Paolo Cifani, Tomoyoshi Nakadai, Zhaohui Feng, Chun-Hao Huang, Richard Koche, Christopher D Delaney, Chun-Wei David Chen, Scott W. Lowe, Robert Roeder, Alex Kentsis, Scott A. Armstrong
Journal: Blood (2016)
04.13 The transcription factor foxo3 differentially regulates the expression of proinflammatory genes in rheumatoid fibroblast-like synoviocytes
Authors: Bernhard Brandstetter, Karoline Dalwigk, Gregory I Vladimer, Günter Steiner, Josef S Smolen, Hans P Kiener, Thomas Karonitsch
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Objective</h3> The transcription factor (TF) FOXO3 is known to integrate information from multiple upstream signals (eg, cytokines, oxidative stress, growth factors) in order to maintain tissue homeostasis during stress. Interestingly, although an association between a FOXO3 genotype (SNP) and the severity of rheumatoid arthritis (RA) was recently reported, the role of this TF in rheumatoid fibroblast-like synoviocytes (FLS) has not yet been investigated. <h3>Methods</h3> With approval by the ethics committee synovial tissues from patients fulfilling the ACR/EULAR classification criteria for RA were obtained as discarded specimens following synovectomy. RA-FLS were isolated according to standard procedures. FOXO3 phosphorylation was determined by western blots. MK2206 was used to inhibit AKT. Nuclear-cytoplasmatic shuttling of FOXO3 was visualised and quantified by confocal immunofluorescence microscopy. FLS were transfected either with control or FOXO3 siRNA pools in order to investigate the role of FOXO3 in the TNF-induced inflammatory response. The expression of cytokines, chemokines and proteases, that are all known to be involved in RA pathogenesis, was assessed by ELISA, qPCR and western blots. <h3>Results</h3> TNF, which is well known to be at the apex of the inflammatory cytokine network in RA, promoted the phosphorylation and nuclear export (inhibition) of FOXO3 in FLS. FOXO3 phosphorylation by TNF was inhibited by the AKT-inhibitor MK2206, demonstrating that TNF induces AKT phosphorylation to subsequently control FOXO3 activity in FLS. To further investigate the role of FOXO3 in the TNF-induced inflammatory response we silenced FOXO3 expression by using specific siRNA pools. Interestingly, while IL6 and IL8 expression was not affected by FOXO3 knockdown, a significant reduction in MMP3 expression was observed. In contrast, FOXO3 knockdown by siRNA promoted the TNF-induced expression of BAFF, TNFSF10 and CXCL11, suggesting that FOXO3 is a negative regulator of these genes. <h3>Conclusions</h3> Our data reveal differential regulation of arthritis-associated genes by FOXO3 in FLS and thus support the idea that FOXO3 plays a crucial role in rheumatoid synovitis.
Risk factors for overuse shoulder injuries in a mixed-sex cohort of 329 elite handball players: previous findings could not be confirmed
Authors: Stig Haugsboe Andersson, Roald Bahr, Benjamin Clarsen, Grethe Myklebust
Journal: British Journal of Sports Medicine (2017)

Shoulder injuries are common among handball players and predominantly characterised by overuse characteristics. Reduced total glenohumeral rotation, external rotation weakness and scapular dyskinesis have been identified as risk factors among elite male handball players.To assess whether previously identified risk factors are associated with overuse shoulder injuries in a large cohort of elite male and female handball players.329 players (168 male, 161 female) from the two upper divisions in Norway were included and tested prior to the 2014-2015 season. Measures included glenohumeral internal and external rotation range of motion, isometric internal and external rotation strength, and assessment of scapular dyskinesis. Players were followed prospectively for one competitive season, with prevalence and severity of shoulder problems registered monthly using the Oslo Sports Trauma Research Center Overuse Injury Questionnaire. A severity score based on players' questionnaire responses was used as the outcome measure in multivariable logistic regression to investigate associations between candidate risk factors and overuse shoulder injury.No significant associations were found between total rotation (OR 1.05 per 5° change, 95% CI 0.98 to 1.13), external rotation strength (OR 1.05 per 10 N change, 95% CI 0.92 to 1.20) or obvious scapular dyskinesis (OR 1.23, 95% CI 0.25 to 5.99) and overuse shoulder injury. A significant positive association was found between greater internal rotation (OR 1.16 per 5° change, 95% CI 1.00 to 1.34) and overuse shoulder injury.None of the previously identified risk factors were associated with overuse shoulder injuries in a mixed-sex cohort of elite handball players.
Harmonization of community health worker programs for HIV: A four-country qualitative study in Southern Africa
Authors: Jan-Walter De Neve, Henri Garrison-Desany, Kathryn G. Andrews, Nour Sharara, Chantelle Boudreaux, Roopan Gill, Pascal Geldsetzer, Maria Vaikath, Till Bärnighausen, Thomas J. Bossert
Journal: PLoS Medicine (2017)

Background Community health worker (CHW) programs are believed to be poorly coordinated, poorly integrated into national health systems, and lacking long-term support. Duplication of services, fragmentation, and resource limitations may have impeded the potential impact of CHWs for achieving HIV goals. This study assesses mediators of a more harmonized approach to implementing large-scale CHW programs for HIV in the context of complex health systems and multiple donors. Methods and findings We undertook four country case studies in Lesotho, Mozambique, South Africa, and Swaziland between August 2015 and May 2016. We conducted 60 semistructured interviews with donors, government officials, and expert observers involved in CHW programs delivering HIV services. Interviews were triangulated with published literature, country reports, national health plans, and policies. Data were analyzed based on 3 priority areas of harmonization (coordination, integration, and sustainability) and 5 components of a conceptual framework (the health issue, intervention, stakeholders, health system, and context) to assess facilitators and barriers to harmonization of CHW programs. CHWs supporting HIV programs were found to be highly fragmented and poorly integrated into national health systems. Stakeholders generally supported increasing harmonization, although they recognized several challenges and disadvantages to harmonization. Key facilitators to harmonization included (i) a large existing national CHW program and recognition of nongovernmental CHW programs, (ii) use of common incentives and training processes for CHWs, (iii) existence of an organizational structure dedicated to community health initiatives, and (iv) involvement of community leaders in decision-making. Key barriers included a wide range of stakeholders and lack of ownership and accountability of non-governmental CHW programs. Limitations of our study include subjectively selected case studies, our focus on decision-makers, and limited generalizability beyond the countries analyzed. Conclusion CHW programs for HIV in Southern Africa are fragmented, poorly integrated, and lack long-term support. We provide 5 policy recommendations to harmonize CHW programs in order to strengthen and sustain the role of CHWs in HIV service delivery.
多価ヒアルロン酸のバイオコンジュゲートは,in vitroでのsFlt‐1活性を改善する【Powered by NICT】
Authors: I Altiok Eda, L Santiago-Ortiz Jorge, L Svedlund Felicia, Zbinden Aline, K Jha Amit, Bhatnagar Deepika, Loskill Peter, M Jackson Wesley, V Schaffer David, E Healy Kevin
Journal: Biomaterials (2016)
Chemical Activation of the SHIP1 Inositol Lipid Phosphatase: A Novel Therapeutic Strategy to Suppress B-Cell Receptor Signaling and CXCR4 Expression in Malignant Human B Cells
Authors: Graham Packham, Beatriz Valle-Argos, Elizabeth Lemm, Lindsay D Smith, Nicola J Weston-Bell, Yohannes Gebreselassie, Andrew J Steele, Freda K Stevenson, Mark S Cragg, Francesco Forconi, Jennifer Cross, Curtis Harwig, Lloyd Mackenzie
Journal: Blood (2016)
NIH Centers for Accelerated Innovations Program: principles, practices, successes and challenges
Authors: Elliott M. Antman, Paul E. Di Corleto, Mason W. Freeman, Tomas Ganz, David E. Golan, Roger Kitterman, Joseph Loscalzo, Mark Low, Erin McKenna, Alan C. O'Connor, Michael Palazzolo, John Parrish, Ofer Reizes, Robert S. Ross, Cheryl Vaughan, D. Geoffrey Vince, Lesley Watts
Journal: Nature Reviews Drug Discovery (2017)
Brief Summary of the Third Joint Meeting of the United States-Japan Cooperative Cancer Research Program on Cell Interactions and Cancer
Authors: Pastan, Ira, Ikawa, Yoji
Journal: JNCI Journal of the National Cancer Institute (1982)

Journal Article Brief Summary of the Third Joint Meeting of the United States-Japan Cooperative Cancer Research Program on Cell Interactions and Cancer Get access Ira Pastan, M.D., Ira Pastan, M.D. National Cancer Institute, Building 37, Room 4B27 Bethesda, Maryland 20205 Search for other works by this author on: Oxford Academic PubMed Google Scholar Yoji Ikawa, M.D. Yoji Ikawa, M.D. Department of Viral Oncology Cancer Institute, Kami-Ikebukuro, Toshima-ku, 170 Tokyo, Japan Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 69, Issue 2, August 1982, Pages 544–545, https://doi.org/10.1093/jnci/69.2.544 Published: 01 August 1982
PTENがん抑制遺伝子:単一コピーのSleeping Beautyトランスポゾンによる変異誘発スクリーニングからPTENと協調する新しいがん抑制遺伝子が明らかになる
Authors: DE La Rosa Jorge, Friedrich Mathias Josef, LI Yilong, Rad Lena, Ponstingl Hannes, Liang Qi, DE Quiros Sandra Bernaldo, Noorani Imran, Metzakopian Emmanouil, Strong Alexander, LI Meng Amy, Hoffman Gary J, Fuente Rocio, Vassiliou George S, Rad Roland, Bradley Allan, Cadinanos Juan, Lopez‐Otin Carlos, Weber Julia, Astudillo Aurora, Fernandez‐Garcia Maria Teresa, Fernandez‐Garcia Maria Soledad
Journal: Nature Genetics (2017)
Immunotherapeutic Targeting of ROR1-Dependent, Non-Canonical Wnt5a-Signaling By Cirmtuzumab: A First-in-Human Phase I Trial for Patients with Intractable Chronic Lymphocytic Leukemia
Authors: Michael Y. Choi, George F. Widhopf, Jian Yu, Reilly L Kidwell, Laura Z. Rassenti, Charlene Gutierrez, Susette Gorak, Tiffany Juarez, Emily Pittman, Hongying Li, Karen Messer, Charles Prussak, Januario E. Castro, Catriona Jamieson, Thomas J. Kipps
Journal: Blood (2016)
Establishment and characterization of a human A549 non small cell lung cancer cell line resistant to the novel vectorized cytotoxic drug F14512
Authors: Jean-Philippe Annereau, Stephane Vispe, Laurent Creancier, Laurence Lacastaigneratte, Natacha Novosad, Jerome Verdier, Aline Stennevin, Karine Andre, Marie-Laure Marionneau, Vanessa Offrete, Yves Guminski, Thierry Imbert, Viviane Brel, Nicolas Guilbaud, Jean-Marc Barret, Christian Bailly
Journal: Cancer Research (2008)

3237  F14512, a novel anticancer drug in pre-clinical development, combines a spermine chain with an epipodophyllotoxin warhead. Part of the benefit introduced by the spermine moiety of F14512 relies on a specific vectorization towards cancer cells mediated though the Polyamine Transport System (PTS). One of the most important challenges in chemotherapeutic treatment is to impede drug resistance. Along this line, we studied the profile of chemo-resistance induced by F14512, which was previously shown to display strong anti-proliferative activities both in vitro and in vivo. We performed the selection of a stable resistant A549 lung carcinoma cell line after 36 treatments with F14512 over 8 months. Interestingly, the pair-wise comparison of the selected A549 F0.5X sub-cell line and the parental cell line indicated that the long exposure to F14512 led to a moderate level of resistance (10 fold). The profile of drug response against a panel of clinically used reference compounds demonstrated that the F14512-resistant cell line is specifically but moderately cross-resistant to etoposide and doxorubicin. This result is consistent with the cross resistance of F14152 toward the mitoxantrone-resistant HL-60-MX2 cell line that arbors a mutated and reduced expression of the topoisomerase II target. In contrast to other epipodophyllotoxin-selected cell lines, none of the ABC transporters involved in clinical resistance phenotype (MDR1, MRP1, MRP2 and ABCG2) were found significantly over-expressed in the F14512-selected A549 cell line. Consistently, the A549 F0.5X sub-cell line displays a pattern of sensitivity against substrates of MDR1/MRP1 such as paclitaxel, navelbine, and displays a marked collateral sensitivity towards the antimetabolite gemcitabine. Proteomic analyses reveal few changes of protein expression between the resistant and parental cell lines, but we observed consistent down-regulation of a subset of proteins involved in the mitochondrial pathway, which is not classically associated with anticancer drug resistance. In conclusion, the spermine moiety of F14152 not only enhances markedly the anti-proliferative potency of the drug but also, and in contrast to conventional epipodophyllotoxins, it restricts the induction of ABC transporter-mediated drug resistance. F14512 appears as a novel drug candidate for the treatment of chemo-resistant tumors.
Out-of-Pocket Costs, Financial Distress, and Underinsurance in Cancer Care
Authors: Fumiko Chino, Jeffrey M. Peppercorn, Christel Rushing, Arif H. Kamal, Ivy Altomare, Greg Samsa, S. Yousuf Zafar
Journal: JAMA Oncology (2017)

This cross-sectional survey study examines financial distress and cost expectations among patients with cancer presenting for anticancer therapy.
神経膠芽腫:サブタイプのゲノムワイド関連解析から,神経膠芽腫と膠芽腫以外の神経膠腫との遺伝性発症リスクの差異が明らかになる
Authors: Melin Beatrice S, Andersson Ulrika, Barnholtz‐Sloan Jill S, Ostrom Quinn T, Chen Yanwen, Wrensch Margaret R, Wiencke John K, Hansen Helen, Mccoy Lucie, Rice Terri, Johansen Christoffer, Il’Yasova Dora, Shildkraut Joellen, Ali‐Osman Francis, Kinnersley Ben, Labreche Karim, Broderick Peter, Schoemaker Minouk J, Swerdlow Anthony, Houlston Richard S, Labussiere Marianne, Idbaih Ahmed, Hoang‐Xuan Khe, DI Stefano Anna‐Luisa, Mokhtari Karima, Delattre Jean‐Yves, Sanson Marc, Armstrong Georgina, Liu Yanhong, Bondy Melissa L, Eckel‐Passow Jeanette E, Decker Paul A, Kosel Matthew L, Sicotte Hugues, Galan Pilar, Gousias Konstantinos, Schramm Johannes, Simon Matthias, Fleming Sarah J, Herms Stefan, Heilmann Stefanie, Noethen Markus M, Wichmann Heinz‐Erich, Schreiber Stefan, Lathrop Mark, Rajaraman Preetha, Chanock Stephen, Linet Martha, Wang Zhaoming, Yeager Meredith, Amos Christopher I, Bernstein Jonine L, Olson Sara H, Davis Faith, Lachance Dan, Lau Ching, Scheurer Michael, Merrell Ryan T, Sadetzki Siegal, Shete Sanjay, Lai Rose K, Claus Elizabeth B, Jenkins Robert B
Journal: Nature Genetics (2017)
Enhanced photothermal therapy of biomimetic polypyrrole nanoparticles through improving blood flow perfusion
Authors: Xuejun Wang, Haichun Li, Xianping Liu, Ye Tian, Huishu Guo, Ting Jiang, Zimiao Luo, Kai Jin, Xinping Kuai, Yao Liu, Zhiqing Pang, Wuli Yang, Shun Shen
Journal: Biomaterials (2017)
关于酒精的知识（二）：酒精相关问题的治疗
Authors: Bruce, Ritson, 齐颖（译）, 夏志伟（校）
Journal: BMJ (2005)

如果社区诊所或医院首次发现患者存在与饮酒相关的问题，应立即对患者进行简要的干预，包括用10分钟时间与患者进行讨论并作出解释、向患者提供自助手册、预约患者在1—2周内进一步随诊。与在正常治疗过程中实施干预相比，这样做可能占用一些时间，但其费用效益比已得到证实。应当考虑培训和雇佣一些专业人员来承担这项工作。