tbuckley/cabot-search huggingface dataset:
SHMT2 Desuccinylation by SIRT5 Drives Cancer Cell Proliferation
Authors: Xin Yang, Zhe Wang, Xin Li, Boya Liu, Minghui Liu, Lu Liu, Shuaiyi Chen, Mengmeng Ren, Yankun Wang, Miao Yu, Bo Wang, Junhua Zou, Wei-Guo Zhu, Yuxin Yin, Wei Gu, Jianyuan Luo
Journal: Cancer Research (2017)

The mitochondrial serine hydroxymethyltransferase SHMT2, which catalyzes the rate-limiting step in serine catabolism, drives cancer cell proliferation, but how this role is regulated is undefined. Here, we report that the sirtuin SIRT5 desuccinylates SHMT2 to increase its activity and drive serine catabolism in tumor cells. SIRT5 interaction directly mediated desuccinylation of lysine 280 on SHMT2, which was crucial for activating its enzymatic activity. Conversely, hypersuccinylation of SHMT2 at lysine 280 was sufficient to inhibit its enzymatic activity and downregulate tumor cell growth in vitro and in vivo Notably, SIRT5 inactivation led to SHMT2 enzymatic downregulation and to abrogated cell growth under metabolic stress. Our results reveal that SHMT2 desuccinylation is a pivotal signal in cancer cells to adapt serine metabolic processes for rapid growth, and they highlight SIRT5 as a candidate target for suppressing serine catabolism as a strategy to block tumor growth.Significance: These findings reveal a novel mechanism for controlling cancer cell proliferation by blocking serine catabolism, as a general strategy to impede tumor growth. Cancer Res; 78(2); 372-86. ©2017 AACR.
An integrative translational approach to study heart failure with preserved ejection fraction: a position paper from the Working Group on Myocardial Function of the European Society of Cardiology
Authors: Andre P. Lourenço, Adelino F. Leite‐Moreira, Jean‐Luc Balligand, Johann Bauersachs, Dana Dawson, Rudolf A. de Boer, Leon J. de Windt, Inês Falcão‐Pires, Ricardo Fontes‐Carvalho, Stefan Franz, Mauro Giacca, Denise Hilfiker‐Kleiner, Emilio Hirsch, Christoph Maack, Manuel Mayr, Burkert Pieske, Thomas Thum, Carlo G. Tocchetti, Dirk L. Brutsaert, Stephane Heymans
Journal: European Journal of Heart Failure (2017)
Safety and antitumor activity of arsenic trioxide (ATO) plus infusional 5-FU, leucovorin and irinotecan (FOLFIRI) as second-line treatment for refractory metastatic colorectal cancer: Preliminary results from a pilot study
Authors: T. Chaudhuri, K.C. Lakshmaiah, K.G. Babu, L. Dasappa, L.A. Jacob, M.C.S. Babu, A.H. Rudresha, K.N. Lokesh, L.K. Rajeev
Journal: Annals of Oncology (2017)
The addition of IMiDs for patients with daratumumab-refractory multiple myeloma can overcome refractoriness to both agents
Authors: Maria Gavriatopoulou, Efstathios Kastritis, Ioannis Ntanasis-Stathopoulos, Despina Fotiou, Maria Roussou, Magdalini Migkou, Dimitrios C. Ziogas, Nikolaos Kanellias, Evangelos Terpos, Meletios Athanasios Dimopoulos
Journal: Blood (2017)
Evidence from machines that learn and think like people
Authors: Kenneth D Forbus, Dedre Gentner
Journal: Behavioral and Brain Sciences (2017)

Abstract We agree with Lake et al.'s trenchant analysis of deep learning systems, including that they are highly brittle and that they need vastly more examples than do people. We also agree that human cognition relies heavily on structured relational representations. However, we differ in our analysis of human cognitive processing. We argue that (1) analogical comparison processes are central to human cognition; and (2) intuitive physical knowledge is captured by qualitative representations, rather than quantitative simulations.
Lugol Chromoendoscopy Detects Esophageal Dysplasia With Low Levels of Sensitivity in a High-Risk Region of China
Authors: Jingjing Li, Ruiping Xu, Mengfei Liu, Hong Cai, Changqi Cao, Fangfang Liu, Fenglei Li, Chuanhai Guo, Yaqi Pan, Zhonghu He, Yang Ke
Journal: Clinical Gastroenterology and Hepatology (2017)
The clinical epidemiology of sickle cell anemia In <scp>A</scp>frica
Authors: Alex W. Macharia, George Mochamah, Sophie Uyoga, Carolyne M. Ndila, Gideon Nyutu, Johnstone Makale, Metrine Tendwa, Emily Nyatichi, John Ojal, Mohammed Shebe, Kennedy O. Awuondo, Neema Mturi, Norbert Peshu, Benjamin Tsofa, J. Anthony G. Scott, Kathryn Maitland, Thomas N. Williams
Journal: American Journal of Hematology (2017)

Sickle cell anemia (SCA) is the commonest severe monogenic disorders of humans. The disease has been highly characterized in high-income countries but not in sub-Saharan Africa where SCA is most prevalent. We conducted a retrospective cohort study of all children 0-13 years admitted from within a defined study area to Kilifi County Hospital in Kenya over a five-year period. Children were genotyped for SCA retrospectively and incidence rates calculated with reference to population data. Overall, 576 of 18,873 (3.1%) admissions had SCA of whom the majority (399; 69.3%) were previously undiagnosed. The incidence of all-cause hospital admission was 57.2/100 person years of observation (PYO; 95%CI 52.6-62.1) in children with SCA and 3.7/100 PYO (95%CI 3.7-3.8) in those without SCA (IRR 15.3; 95%CI 14.1-16.6). Rates were higher for the majority of syndromic diagnoses at all ages beyond the neonatal period, being especially high for severe anemia (hemoglobin <50 g/L; IRR 58.8; 95%CI 50.3-68.7), stroke (IRR 486; 95%CI 68.4-3,450), bacteremia (IRR 23.4; 95%CI 17.4-31.4), and for bone (IRR 607; 95%CI 284-1,300), and joint (IRR 80.9; 95%CI 18.1-362) infections. The use of an algorithm based on just five clinical features would have identified approximately half of all SCA cases among hospital-admitted children with a number needed to test to identify each affected patient of only fourteen. Our study illustrates the clinical epidemiology of SCA in a malaria-endemic environment without specific interventions. The targeted testing of hospital-admitted children using the Kilifi Algorithm provides a pragmatic approach to early diagnosis in high-prevalence countries where newborn screening is unavailable.
Coeliac biopsies: numbers are valid, alphabets not
Authors: Kamran Rostami, Arzu Ensari, Carolina Ciacci, Amitabh Srivastava, Umberto Volta, Vincenzo Villanacci, Michael N Marsh
Journal: Gut (2017)

We thank Gut for requesting responses to this letter from Oberhuber and colleagues.1 We were amazed that they chose to dismiss our intraepithelial lymphocytes (IEL) data as invalid2 on grounds of not being age/gender matched with controls. But this disregards all the other data of clinicians and pathologists in the field, and the rigorous reviewing processes that our article went through before publication in Gut . This dismissal reflects an aberrant viewpoint1 lacking widespread support. In real life, pathologists do sign off biopsies, while diagnoses are rendered without full clinical details, although with appropriately worded caveats.

We aimed, specifically, to reduce the enormous …
A Versatile Nanowire Platform for Highly Efficient Isolation and Direct PCR-free Colorimetric Detection of Human Papillomavirus DNA from Unprocessed Urine
Authors: HyungJae Lee, Mihye Choi, Sang-Hyun Hwang, Youngnam Cho
Journal: Theranostics (2017)

Purpose: As human papillomavirus (HPV) is primarily responsible for the development of cervical cancer, significant efforts have been devoted to develop novel strategies for detecting and identifying HPV DNA in urine.The analysis of target DNA sequences in urine offers a potential alternative to conventional methods as a non-invasive clinical screening and diagnostic assessment tool for the detection of HPV.However, the lack of efficient approaches to isolate and directly detect HPV DNA in urine has restricted its potential clinical use.In this study, we demonstrated a novel approach of using polyethylenimine-conjugated magnetic polypyrrole nanowires (PEI-mPpy NWs) for the extraction, identification, and PCR-free colorimetric detection of high-risk strains of HPV DNA sequences, particularly HPV-16 and HPV-18, in urine specimens of cervical cancer patients.Materials and Methods: We fabricated and characterized polyethylenimine-conjugated magnetic nanowires (PEI/mPpy NWs).PEI/mPpy NWs-based HPV DNA isolation and detection strategy appears to be a cost-effective and practical technology with greater sensitivity and accuracy than other urine-based methods.Results: The analytical and clinical performance of PEI-mPpy NWs was evaluated and compared with those of cervical swabs, demonstrating a superior type-specific concordance rate of 100% between urine and cervical swabs, even when using a small volume of urine (300 µL).Conclusion: We envision that PEI-mPpy NWs provide substantive evidence for clinical diagnosis and management of HPV-associated disease with their excellent performance in the recovery and detection of HPV DNA from minimal amounts of urine samples.
Geographic Distribution of Nonphysician Clinicians Who Independently Billed Medicare for Common Dermatologic Services in 2014
Authors: Adewole S. Adamson, Elizabeth A. Suarez, Philip McDaniel, Paul A. Leiphart, Alana Zeitany, Joslyn S. Kirby
Journal: JAMA Dermatology (2017)

Nurse practitioners (NPs) and physician assistants (PAs) are nonphysician clinicians (NPCs) who can deliver dermatology services. Many of these services are provided independently. Little is known about the types of services provided or where NPCs provide independent care.To examine characteristics of dermatology care for Medicare enrollees billed independently by NPCs.Retrospective review of the 2014 Medicare Provider Utilization and Payment Data: Physician and Other Supplier Public Use File, which reflects fee-for-service payments to clinicians for services rendered to Medicare beneficiaries. Clinician location was matched with county-level demographic data from the American Community Survey, US Census Bureau. Clinicians identified using National Provider Identifier as NPs or PAs with at least 11 claims for common dermatology-associated Healthcare Common Procedure Coding System procedure codes were included.Total services provided by service type category, density of dermatologists and nondermatologists who perform dermatology-related services, and geographic location by county.Among the cohort of NPCs were 824 NPs (770 [93.5%] female) and 2083 PAs (1602 [76.9%] female) who independently billed Medicare $59 438 802 and $171 645 943, respectively. Dermatologists were affiliated with 2667 (92%) independently billing NPCs. Most payments were for non-evaluation and management services including destruction of premalignant lesions, biopsies, excisions of skin cancer, surgical repairs, flaps/grafts, and interpretation of pathologic analysis. Nurse practitioners and PAs billed for a similar distribution of service categories overall. A total of 2062 (70.9%) NPCs practiced in counties with dermatologist density of greater than 4 per 100 000 population. Only 3.0% (86) of independently billing NPCs practiced in counties without a dermatologist. Both dermatologists and NPCs were less likely to be in rural counties than in urban counties.Nonphysician clinicians independently billed for a wide variety of complex dermatologic procedures. Most independently billing NPCs practice in counties with higher dermatologist densities, and nearly all these NPCs were affiliated with dermatologists. Further study of NPC training and integration with the dermatology discipline is an important part of addressing the changing US dermatology workforce.
P1.06-004 Evaluating the Non-Small Cell Lung Cancer Symptom Assessment Questionnaire (NSCLC-SAQ): Preliminary Results from the Quantitative Pilot Study
Authors: Astra Liepa, Donald Bushnell, Thomas Atkinson, Kendra Debusk, Kelly Mccarrier, Mona Martin, Stephen Coons
Journal: Journal of Thoracic Oncology (2017)
Association of Parathyroid Hormone Level With Postthyroidectomy Hypocalcemia
Authors: Aarti Mathur, Neeraja Nagarajan, Stacie Kahan, Eric B. Schneider, Martha A. Zeiger
Journal: JAMA Surgery (2017)

<h3>Importance</h3> There has been an increased interest in measuring parathyroid hormone (PTH) levels as an early predictive marker for the development of hypocalcemia after total thyroidectomy. However, significant variation exists in the timing, type of assay, and thresholds of PTH in the literature. <h3>Objective</h3> We performed a systematic review to examine the utility of PTH levels in predicting temporary postthyroidectomy hypocalcemia. <h3>Evidence Review</h3> A systematic literature review of studies published prior to May 25, 2016 was performed within PubMed, EMBASE, SCOPUS, and Cochrane databases using the following terms and keywords: "thyroidectomy," "parathyroid hormone," and "hypocalcaemia," "calcium," or "calcitriol." Each candidate full-text publication was reviewed by 2 independent reviewers and selected for data extraction if the study examined the prognostic significance of PTH obtained within 24 hours after thyroidectomy to predict hypocalcaemia. Studies were excluded if calcium supplementation was used routinely or based on a PTH level. Study characteristics, PTH parameters used to predict hypocalcemia, and their respective accuracies were summarized. <h3>Findings</h3> The initial search yielded 2417 abstracts. Sixty-nine studies, comprising 9163 patients, were included. Overall, for an absolute PTH threshold, the median accuracy, sensitivity, and specificity were 86%, 85%, and 86%, respectively. For a percentage change over time the median accuracy, sensitivity, and specificity were 89%, 88%, and 90%, respectively. <h3>Conclusions and Relevance</h3> The existing literature regarding PTH levels to predict postthyroidectomy hypocalcemia is extremely heterogeneous. A single PTH threshold is not a reliable measure of hypocalcemia. Additional prospective studies controlled for timing of laboratory draws and a priori defined PTH thresholds need to be performed to ascertain the true prognostic significance of PTH in predicting postthyroidectomy hypocalcaemia.
Abstract 19396: Role and Factors Associated With Removal of Retrievable Inferior Vena Cava Filter in Venous Thromboembolism
Authors: Yasuji Doi, Keiji Hirooka, Ken-ichiro Okada, Mayu Nishio, Koichi Miyazaki, Akiya Sakatani, Tomoya Nagano, Reiko Matsuoka, Masaya Morita, Takayuki Otani, Tomoaki Natsukawa, Hirotaka Sawano, Tatsuro Kai, Toru Hayashi
Journal: Circulation (2016)

It has been recommended that implanting physicians and clinicians responsible for the ongoing care of patients with retrievable inferior vena cava filters (IVCFs) consider removing the filter as soon as protection from pulmonary embolism (PE) is no longer needed. To investigate factors associated with IVCF retrieval, we studied 228 consecutive patients with venous thromboembolism (VTE) in whom retrievable IVCFs were placed to prevent massive PE. The mean age of the patients was 66 years (range, 17-96 years), and 118 (52%) of them were female. Of the 228 patients, 76 (33%) had PE. In addition to VTE, major underlying conditions were trauma (24%), malignancy (18%), central nervous system disturbance (18%), cranial hemorrhage (6%), gastrointestinal tract bleeding (12%), other hemorrhagic events (11%), patient non-compliance (9%), and inability to anticoagulant after surgery (4%). After IVCF placement, no PE events were recorded with the IVCF in place. Of the 228 patients 35 died of underlying diseases, in whom IVCF removals were not attempted due to the severity or the prognosis of underlying diseases. Of the other 193 patients, 64 non-surgical retrieval attempts (33%) were made. Retrieval attempts were increased after the retrieval recommendation by the Food and Drug Administration in 2010 (p
Prognostic significance of tumor-infiltrating lymphocytes (TILs) in patients with early-stage triple-negative breast cancer (TNBC) treated with curative resection alone
Authors: J.H. Park, H.J. Lee, J-H Ahn, J.E. Kim, K.H. Jung, G. Gong, S-B Kim
Journal: Annals of Oncology (2017)
Abstract #5578: Inhibition of FGFR/PDGFR/VEGFR signaling reduces pancreatic cancer growth by direct effects on tumor cells, endothelial cells and pericytes
Authors: Sven Lang, Johannes Taeger, Christian Moser, Christina Hackl, Hans Schlitt, Edward Geissler, Oliver Stoeltzing
Journal: Cancer Research (2009)

Activation of certain receptor tyrosine kinases (RTKs), such as FGFR, PDGFR, and VEGFR, has been implicated in tumor angiogenesis and progression of human cancers. In particular, bFGF and PDGF may promote cancer cell motility and tumor cell proliferation, whereas recruitment and proliferation of endothelial cells (ECs) and pericytes (vascular smooth muscle cells, VSMCs), two essential steps in angiogenesis, are mediated by activation of VEGFR and PDGFR. We therefore hypothesized that targeting the receptors to bFGF, PDGF and VEGF could prove valuable for therapy of pancreatic cancer, as these tyrosine kinases have been implicated in growth and angiogenesis of this aggressive cancer entity.  Human pancreatic cancer cells, ECs and VSMCs were used for the experiments. Blockade of FGFR/PDGFR/VEGFR was achieved by using a novel small molecule tyrosine kinase inhibitor (TKI) (NVP-TKI258, Novartis Oncology). Effects of TKI on the proliferation of tumor cells, ECs and VSMCs were determined by MTT assays. Changes in motility of either cell type were determined in modified Boyden chambers. The inhibitory effects of FGFR/PDGFR/VEGFR inhibition in terms of phosphorylation of signaling intermediates were investigated by Western blotting. Changes in VEGF, survivin and DLL4 expression (as measures for endothelial survival function) were assessed by RT-PCR. Effects of NVP-TKI258 on tumor growth  in vivo  were investigated in a subcutaneous tumor model. Results showed that inhibition of multiple RTKs impaired growth of tumor cells, ECs and VSMCs in a dose-dependent manner  in vitro . In addition, the bFGF- and FGF-7- induced tumor cell migratory properties were significantly diminished by NVP-TKI258 ( P  P  In vivo,  NVP-TKI258 (30 mg/kg/daily) significantly reduced tumor growth rates ( P  P    Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 5578.
Prognostic Value of Clinical vs Pathologic Stage in Rectal Cancer Patients Receiving Neoadjuvant Therapy
Authors: Daniel Delitto, Thomas J George, Tyler J Loftus, Peihua Qiu, George J Chang, Carmen J Allegra, William A Hall, Steven J Hughes, Sanda A Tan, Christiana M Shaw, Atif Iqbal
Journal: JNCI Journal of the National Cancer Institute (2017)

Neoadjuvant chemoradiation is currently standard of care in stage II-III rectal cancer, resulting in tumor downstaging for patients with treatment-responsive disease. However, the prognosis of the downstaged patient remains controversial. This work critically analyzes the relative contribution of pre- and post-therapy staging to the anticipated survival of downstaged patients.The National Cancer Database (NCDB) was queried for patients with rectal cancer treated with transabdominal resection between 2004 and 2014. Stage II-III patients downstaged with neoadjuvant radiation were compared with stage I patients treated with definitive resection alone. Patients with positive surgical margins were excluded. Overall survival was evaluated using both Kaplan-Meier analyses and Cox proportional hazards models. All statistical tests were two-sided.A total of 44 320 patients were eligible for analysis. Survival was equivalent for patients presenting with cT1N0 disease undergoing resection (mean survival = 113.0 months, 95% confidence interval [CI] = 110.8 to 115.3 months) compared with those downstaged to pT1N0 from both cT3N0 (mean survival = 114.9 months, 95% CI = 110.4 to 119.3 months, P = .12) and cT3N1 disease (mean survival = 115.4 months, 95% CI = 110.1 to 120.7 months, P = .22). Survival statistically significantly improved in patients downstaged to pT2N0 from cT3N0 disease (mean survival = 109.0 months, 95% CI = 106.7 to 111.2 months, P < .001) and cT3N1 (mean survival = 112.8 months, 95% CI = 110.0 to 115.7 months, P < .001), compared with cT2N0 patients undergoing resection alone (mean survival = 100.0 months, 95% CI = 97.5 to 102.5 months). Multiple survival analysis confirmed that final pathologic stage dictated long-term outcomes in patients undergoing neoadjuvant radiation (hazard ratio [HR] of pT2 = 1.24, 95% CI = 1.10 to 1.41; HR of pT3 = 1.81, 95% CI = 1.61 to 2.05; HR of pT4 = 2.72, 95% CI = 2.28 to 3.25, all P ≤ .001 vs pT1; HR of pN1 = 1.50, 95% CI = 1.41 to 1.59; HR of pN2 = 2.17, 95% CI = 2.00 to 2.35, both P < .001 vs pN0); while clinical stage at presentation had little to no predictive value (HR of cT2 = 0.81, 95% CI = 0.69 to 0.95, P = .008; HR of cT3 = 0.83, 95% CI = 0.72 to 0.96, P = .009; HR of cT4 = 1.02, 95% CI = 0.85 to 1.21, P = .87 vs cT1; HR of cN1 = 0.96, 95% CI = 0.91 to 1.02, P = .19; HR of cN2 = 0.96, 95% CI = 0.86 to 1.08, P = .48 vs cN0).Survival in patients with rectal cancer undergoing neoadjuvant radiation is driven by post-therapy pathologic stage, regardless of pretherapy clinical stage. These data will further inform prognostic discussions with patients.
Atad3a suppresses Pink1-dependent mitophagy to maintain homeostasis of hematopoietic progenitor cells
Authors: Guoxiang Jin, Chuan Xu, Xian Zhang, Jie Long, Abdol Hossein Rezaeian, Chunfang Liu, Mark E. Furth, Steven Kridel, Boris Pasche, Xiu-Wu Bian, Hui-Kuan Lin
Journal: Nature Immunology (2017)
P1.06-005 An International Cohort of Patients with Small Cell Lung Cancer after a Non-Small Cell Lung Carcinoma Oncogene or Non-Oncogene Addicted
Authors: Matteo Giaj Levra, Silvia Novello, Leonie Ferrer, Fausto Barbieri, Julien Mazieres, Virginie Westeel, Nicolas Girard, Michel Poudenx, Jacques Le Treut, Maria Rita Migliorino, Clarisse Audigier Valette, Anne Madroszyk, Charlotte Leduc, Myriam Locatelli- Sanchez, Anne Claire Toffart, Denis Moro-Sibilot
Journal: Journal of Thoracic Oncology (2017)
The elusive constellations of poverty
Authors: Seger M. Breugelmans, Arnoud Plantinga, Marcel Zeelenberg, Olga Poluektova, Maria Efremova
Journal: Behavioral and Brain Sciences (2017)

Abstract Pepper &amp; Nettle describe possible processes underlying what they call a behavioral constellation of deprivation (BCD). Although we are certain about the application of evolutionary models to our understanding of poverty, we are less certain about the utility of behavioral constellations. The empirical record on poverty-related behaviors is much more divergent and broad than such constellations suggest.
Randomized, non-inferiority, phase III trial of second-line chemotherapy for metastatic colorectal cancer (mCRC), comparing the efficacy and safety of XELIRI + bevacizumab versus FOLFIRI + bevacizumab (AXEPT)
Authors: T.W. Kim, Y.S. Park, K. Muro, R. Xu, S. Han, K. Yamazaki, W. Wang, J.B. Ahn, H. Uetake, Y. Deng, S. Cho, H. Matsumoto, Y. Ba, K-W Lee, T. Nishina, T. Zhang, S. Iwasa, S. Morita, J. Sakamoto
Journal: Annals of Oncology (2017)