tbuckley/cabot-search huggingface dataset:
Airborne Fine Particles and Risk of Hospital Admissions for Understudied Populations: Effects by Urbanicity and Short-Term Cumulative Exposures in 708 U.S. Counties
Authors: Mercedes A. Bravo, Keita Ebisu, Francesca Dominici, Yun Wang, Roger D. Peng, Michelle L. Bell
Journal: Environmental Health Perspectives (2016)

Background:Evidence of health risks associated with ambient airborne fine particles in nonurban populations is extremely limited.Objective:We estimated the risk of hospitalization associated with short-term exposures to particulate matter with an aerodynamic diameter < 2.5 μm (PM2.5) in urban and nonurban counties with population ≥ 50,000.Methods:We utilized a database of daily cardiovascular- and respiratory-related hospitalization rates constructed from Medicare National Claims History files (2002–2006), including 28 million Medicare beneficiaries in 708 counties. Daily PM2.5 exposures were estimated using the Community Multiscale Air Quality (CMAQ) downscaler. We used time-series analysis of hospitalization rates and PM2.5 to evaluate associations between PM2.5 levels and hospitalization risk in single-pollutant models.Results:We observed an association between cardiovascular hospitalizations and same-day PM2.5 with higher risk in urban counties: 0.35% [95% posterior interval (PI): –0.71%, 1.41%] and 0.98% (95% PI: 0.73%, 1.23%) increases in hospitalization risk per 10-μg/m3 increment in PM2.5 were observed in the least-urban and most-urban counties, respectively. The largest association for respiratory hospitalizations, a 2.57% (95% PI: 0.87%, 4.30%) increase per 10-μg/m3 increase in PM2.5, was observed in the least-urban counties; in the most-urban counties, a 1.13% (0.73%, 1.54%) increase was observed. Effect estimates for cardiovascular hospitalizations were highest for smaller lag times, whereas effect estimates for respiratory hospitalizations increased as more days of exposure were included.Conclusion:In nonurban counties with population ≥ 50,000, exposure to PM2.5 is associated with increased risk for respiratory hospitalizations; in urban counties, exposure is associated with increased risk of cardiovascular hospitalizations. Effect estimates based on a single day of exposure may underestimate true effects for respiratory hospitalizations.Citation:Bravo MA, Ebisu K, Dominici F, Wang Y, Peng RD, Bell ML. 2017. Airborne fine particles and risk of hospital admissions for understudied populations: effects by urbanicity and short-term cumulative exposures in 708 U.S. counties. Environ Health Perspect 125:594–601; http://dx.doi.org/10.1289/EHP257
Proximal and distal colon tumors as distinct biologic entities with different prognoses.
Authors: Edoardo Missiaglia, Bart Jacobs, Antonio Fabio Di Narzo, Charlotte Soneson, Arnaud Roth, Fred Bosman, Giovanni d'Ario, Dirk Klingbiel, Pu Yan, Mauro Delorenzi, Sabine Tejpar
Journal: Journal of Clinical Oncology (2013)

3526 Background: It has been shown that tumors arising in the proximal and distal colon, defined by the embryological midgut and hindgut, have distinctive clinical and molecular features, but very little is known concerning the differences in the mechanism of tumorigenesis and the effect that this could have on therapy. Methods: The distribution of clinico-pathological and molecular features was evaluated between proximal (N = 1110, Caecum to hepatic flexure) and distal colon (N = 1728, splenic flexure down to sigmoid) in patients included in the PETACC3 trial. Gene expression profile was also available from 783 tumors and 32 normal colon. A further set of 473 metastatic patients treated with cetuximab combined with chemotherapy (De Roock Lancet Oncol. 2010) was used to test tumor location with response. Results: Pathological features, such as tumor differentiation, and mucinous histology as well as molecular characteristics, such as MSI status, BRAF, PIK3Ca mutations and LOH18q loss show higher frequency in proximal compared to distal colon (N = 1214; Fisher test, P&lt;0.001). Proximal tumors showed a significantly worse overall survival (N= 2838; HR=1.4 [1.18 - 1.64] P&lt;0.001) and survival after relapse (N = 861; HR=1.97 [1.65 - 2.35] P &lt;0.001) only if they were stage III at diagnosis, while no difference was observed for relapse free survival. Microarray profiling identified 997 genes differentially expressed between the two anatomical sites, after adjustment for age, gender, mucinous histology, BRAF, KRAS and MSI status. Only 20 of those were present in normal colon site comparison indicating tumor specificity. Data mining analysis of the differentially expressed genes showed that the distal colon is characterized by an enrichment for MAPK activated pathways as well as for the cetuximab response gene signature (Khambata-Ford JCO 2007). In fact, cetuximab treated KRAS/BRAF wild-type tumors in distal colon had prolonged PFS and a 2-fold higher response rate then proximal. Conclusions: Proximal and distal colon tumors have distinctive patterns of clinical-pathological and molecular features. These biological differences likely have significant prognostic and therapeutic implications.
Case 50-1962
Authors: Howard Ulfelder, Benjamin Castleman
Journal: New England Journal of Medicine (1962)

Presentation of CaseA thirty-two-year-old woman entered the hospital because of chills, fever and an abdominal mass.The patient first noticed a slowly enlarging, painless mass in the lower portion of the abdomen five months before admission. She did not seek medical attention and was otherwise asymptomatic until three months before entry, when anorexia developed. Her menstrual periods, which had previously been irregular and profuse, became more regular. Mild constipation had been present for three years, but six weeks before entry she began to have 2 to 6 bowel movements daily, with the passage of loose stools. A small perineal . . .
Effect of Single Nucleotide Polymorphism in the Gene RBM8A Together with the Microdeletion 1q21 in Thrombocytopenia-Absent Radii Syndrome.
Authors: Harald Schulze, Cornelis A Albers, Gabriele Strauss, Janine Fiedler, Markus Schmugge, Willem H Ouwehand, Kathleen Freson, Ruth Newbury-Ecob, Cedric Ghaevert
Journal: Blood (2012)
Mer Tyrosine Kinase Regulates the Activation of Myeloid Cells and Innate Immune Responses in Acute-on-Chronic Liver Failure
Authors: A. Singanayagam, E. Triantafyllou, V.C. Patel, C. Bernsmeier, C. Weston, S. Curbishley, C. Willars, W. Bernal, G. Auzinger, M. Heneghan, A. Dhar, D. Adams, M. Thursz, J. Wendon, C.G. Antoniades
Journal: Journal of Hepatology (2016)
Reliability of mSASSS scoring in everyday practice in DESIR-cohort study centres: cross-sectional study of agreement with trained readers
Authors: Pascal Claudepierre, Manouk Sumudu Madushani de Hooge, Antoine Feydy, Monique Reijnierse, Alain Saraux, Maxime Dougados, Désirée van der Heijde
Journal: Annals of the Rheumatic Diseases (2016)

The assessment of axial SpondyloArthritis (axSpA) lesions is important; not only to evaluate a major contributor to disease severity, but also to determine whether drugs are effective in inhibiting structural progression. In trials, assessment of axSpA lesions can be done locally in a study centre, or in a centralised manner by specifically trained readers. The potential impact of choosing one method rather than the other is unknown. In earlier work, we found the same—moderate—level of agreement between local reading (LocR) and central reading (CentR) as between the two central readers regarding radiographic sacroiliitis assessment.1 However, differences between LocR and CentR resulted in misclassification of some patients (ankylosing spondylitis (AS) or axSpA meeting Assessment of SpondyloArthritis international Society (ASAS) criteria).2 The modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) is the recommended tool to assess erosions, sclerosis, squaring and (bridging) syndesmophytes at each anterior vertebral corner of the cervical and lumbar spine.3 ,4 The objective of this study was to assess the agreement between baseline mSASSS values of patients with recent-onset inflammatory back pain (devenir des spondyloarthrites indifferenciees recentes (DESIR) …
WPA Position Statement on Gender Identity and Same‐Sex Orientation, Attraction and Behaviours
Authors: Dinesh Bhugra, Kristen Eckstrand, Petros Levounis, Anindya Kar, Kenneth R. Javate
Journal: World Psychiatry (2016)

Recent controversies in many countries suggest a need for clarity on same-sex orientation, attraction and behaviour (formerly referred to as homosexuality). Along with other international organizations, the WPA considers sexual orientation to be innate and determined by biological, psychological, developmental and social factors. Over 50 years ago, Kinsey et al1 documented a diversity of sexual behaviours among people. Surprisingly for the time, he described that for over 10% of individuals this included same-sex sexual behaviours. Subsequent population research has demonstrated that approximately 4% of people identify with a same-sex sexual orientation (e.g., gay, lesbian and bisexual orientations). Another 0.5% identify with a gender identity other than the gender assigned at birth (e.g., transgender)2. Globally, this equates to over 250 million individuals. There is a recognized need for moving towards a non-binary gender identity. Psychiatrists have a social responsibility to advocate for a reduction in social inequalities for all individuals, including inequalities related to gender identity and sexual orientation. Despite an unfortunate history of perpetuating stigma and discrimination, it has been decades since modern medicine abandoned pathologizing same-sex orientation and behaviour3. The World Health Organization (WHO) accepts same-sex orientation as a normal variant of human sexuality4. The United Nations Human Rights Council5 values lesbian, gay, bisexual and transgender (LGBT) rights. In two major diagnostic and classification systems (ICD-10 and DSM-5), same-sex sexual orientation, attraction and behaviour are not seen as pathologies. There is considerable research evidence to suggest that sexual behaviours and sexual fluidity depend upon a number of factors6. Furthermore, it has been shown conclusively that LGBT individuals have higher than expected rates of psychiatric disorders7, 8, and once their rights and equality are recognized these rates start to drop9-12. People with diverse sexual orientations and gender identities may have grounds for exploring therapeutic options to help them live more comfortably, reduce distress, cope with structural discrimination, and develop a greater degree of acceptance of their sexual orientation or gender identity. Such principles apply to any individual who experiences distress relating to an aspect of their identity, including heterosexual individuals. Dinesh Bhugra1, Kristen Eckstrand2, Petros Levounis3, Anindya Kar4, Kenneth R. Javate5 1Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK; 2Vanderbilt University School of Medicine, Nashville, TN, USA; 3Addiction Institute of New York, New York, NY, USA; 4Calcutta National Medical College & Hospital, Calcutta, India; 5The Medical City, Manila, Philippines
The Prevalence and Predictors of Cardiovascular Events Post-Liver Transplantation
Authors: L. De Luca, M. Kalafateli, S. Bianchi, N. Alasaker, E. Buzzetti, D. Thorburn, D. Patch, J. O’Beirne, R. Westbrook, E. Tsochatzis
Journal: Journal of Hepatology (2016)
UNC2025, a MERTK Small-Molecule Inhibitor, Is Therapeutically Effective Alone and in Combination with Methotrexate in Leukemia Models
Authors: Deborah DeRyckere, Alisa B. Lee-Sherick, Madeline G. Huey, Amanda A. Hill, Jeffrey W. Tyner, Kristen M. Jacobsen, Lauren S. Page, Gregory G. Kirkpatrick, Fatma Eryildiz, Stephanie A. Montgomery, Weihe Zhang, Xiaodong Wang, Stephen V. Frye, H. Shelton Earp, Douglas K. Graham
Journal: Clinical Cancer Research (2016)

Abstract Purpose: MERTK tyrosine kinase is ectopically expressed in 30% to 50% of acute lymphoblastic leukemias (ALL) and more than 80% of acute myeloid leukemias (AML) and is a potential therapeutic target. Here, we evaluated the utility of UNC2025, a MERTK tyrosine kinase inhibitor, for treatment of acute leukemia. Experimental Design: Preclinical in vitro and in vivo assays using cell lines and primary leukemia patient samples were used to evaluate antileukemic effects of UNC2025. Results: UNC2025 potently inhibited prosurvival signaling, induced apoptosis, and reduced proliferation and colony formation in MERTK-expressing ALL and AML cell lines and patient samples. Approximately 30% of primary leukemia patient samples (78 of 261 total) were sensitive to UNC2025. Sensitive samples were most prevalent in the AML, T-ALL, and minimally differentiated (M0) AML subsets. UNC2025 inhibited MERTK in bone marrow leukemia cells and had significant therapeutic effects in xenograft models, with dose-dependent decreases in tumor burden and consistent two-fold increases in median survival, irrespective of starting disease burden. In a patient-derived AML xenograft model, treatment with UNC2025 induced disease regression. In addition, UNC2025 increased sensitivity to methotrexate in vivo, suggesting that addition of MERTK-targeted therapy to current cytotoxic regimens may be particularly effective and/or allow for chemotherapy dose reduction. Conclusions: The broad-spectrum activity mediated by UNC2025 in leukemia patient samples and xenograft models, alone or in combination with cytotoxic chemotherapy, supports continued development of MERTK inhibitors for treatment of leukemia. Clin Cancer Res; 23(6); 1481–92. ©2016 AACR.
The whole genome sequence of the Mediterranean fruit fly, Ceratitis capitata (Wiedemann), reveals insights into the biology and adaptive evolution of a highly invasive pest species
Authors: Alexie Papanicolaou, Marc F. Schetelig, Peter Arensburger, Peter W. Atkinson, Joshua B. Benoit, Kostas Bourtzis, Pedro Castañera, John P. Cavanaugh, Hsu Chao, Christopher Childers, Ingrid Curril, Huyen Dinh, HarshaVardhan Doddapaneni, Amanda Dolan, Shannon Dugan, Markus Friedrich, Giuliano Gasperi, Scott Geib, Georgios Georgakilas, Richard A. Gibbs, Sarah D. Giers, Ludvik M. Gomulski, Miguel González-Guzmán, Ana Guillem-Amat, Yi Han, Artemis G. Hatzigeorgiou, Pedro Hernández-Crespo, Daniel S. T. Hughes, Jeffery W. Jones, Dimitra Karagkouni, Panagiota Koskinioti, Sandra L. Lee, Anna R. Malacrida, Mosè Manni, Kostas Mathiopoulos, Angela Meccariello, Shwetha C. Murali, Terence D. Murphy, Donna M. Muzny, Georg Oberhofer, Félix Ortego, Maria D. Paraskevopoulou, Monica Poelchau, Jiaxin Qu, Martin Reczko, Hugh M. Robertson, Andrew J. Rosendale, Andrew E. Rosselot, Giuseppe Saccone, Marco Salvemini, Grazia Savini, Patrick Schreiner, Francesca Scolari, Paolo Siciliano, Sheina B. Sim, George Tsiamis, Enric Ureña, Ioannis S. Vlachos, John H. Werren, Ernst A. Wimmer, Kim C. Worley, Antigone Zacharopoulou, Stephen Richards, Alfred M. Handler
Journal: Genome biology (2016)

The Mediterranean fruit fly (medfly), Ceratitis capitata, is a major destructive insect pest due to its broad host range, which includes hundreds of fruits and vegetables. It exhibits a unique ability to invade and adapt to ecological niches throughout tropical and subtropical regions of the world, though medfly infestations have been prevented and controlled by the sterile insect technique (SIT) as part of integrated pest management programs (IPMs). The genetic analysis and manipulation of medfly has been subject to intensive study in an effort to improve SIT efficacy and other aspects of IPM control. The 479 Mb medfly genome is sequenced from adult flies from lines inbred for 20 generations. A high-quality assembly is achieved having a contig N50 of 45.7 kb and scaffold N50 of 4.06 Mb. In-depth curation of more than 1800 messenger RNAs shows specific gene expansions that can be related to invasiveness and host adaptation, including gene families for chemoreception, toxin and insecticide metabolism, cuticle proteins, opsins, and aquaporins. We identify genes relevant to IPM control, including those required to improve SIT. The medfly genome sequence provides critical insights into the biology of one of the most serious and widespread agricultural pests. This knowledge should significantly advance the means of controlling the size and invasive potential of medfly populations. Its close relationship to Drosophila, and other insect species important to agriculture and human health, will further comparative functional and structural studies of insect genomes that should broaden our understanding of gene family evolution.
Natural Killer (NK) Alloreactivity Seems Not to Play a Role in Preventing Leukemia Relapse in Unmanipulated Haploidentical Bone Marrow Transplantation with Post-Transplant Cyclophosphamide
Authors: Federica Galaverna, Fabio Guolo, Daniela Pende, Alida Dominietto, Raffaella Meazza, Michela Falco, Carmen Di Grazia, Anna Maria Raiola, Anna Ghiso, Riccardo Varaldo, Francesca Gualandi, Carlo Marani, Maria Teresa van Lint, Roberto Massimo Lemoli, Marco Gobbi, Paola Minetto, Andrea Bacigalupo
Journal: Blood (2015)
Increasing physicians in hospital staff does not improve quality of care, US study suggests
Authors: Michael McCarthy
Journal: BMJ (2016)

The proportion of hospitals employing physicians in the United States has increased sharply, but the switch to the physician-employment model has not been associated with improved quality of care, a study has found.1

Researchers looked at quality measures in 803 hospitals that switched from the traditional hospital-physician business model, in which the hospitals and hospital staff physicians are largely independent of each other, to an arrangement in which at …
Predictors of Hepatic Decompensation during Ombitasvir/Paritaprevir/Ritonavir ± Dasabuvir ± Ribavirin Treatment of Genotype 1 and 4 HCV Infected Patients (Real Life Amber Study)
Authors: R. Flisiak, J. Jaroszewicz, E. Janczewska, M. Wawrzynowicz-Syczewska, A. Grabinska, B. Bolewska, A. Pisula, E. Karpinska, I. Mozer-Lisewska, G. Madej
Journal: Journal of Hepatology (2016)
Nivolumab (anti-PD-1; BMS-936558; ONO-4538) in patients with advanced solid tumors: Survival and long-term safety in a phase I trial.
Authors: Suzanne Louise Topalian, Mario Sznol, Julie R. Brahmer, David F. McDermott, David C. Smith, Scott N. Gettinger, Janis M. Taube, Charles G. Drake, Drew M. Pardoll, John D. Powderly, Richard D. Carvajal, Jeffrey Alan Sosman, Michael B. Atkins, Scott J. Antonia, David R. Spigel, Donald P. Lawrence, Georgia Kollia, Ashok Kumar Gupta, Jon M. Wigginton, F. Stephen Hodi
Journal: Journal of Clinical Oncology (2013)

3002^ Background: Blockade of programmed death-1 (PD-1), a co-inhibitory receptor expressed by activated T cells, can overcome immune resistance and mediate tumor regression (Topalian et al., NEJM 2012). Here we present long-term safety and efficacy outcomes from a phase I study of nivolumab, a PD-1 blocking mAb, in patients (pts) with advanced solid tumors. Methods: Pts enrolled between 2008-2012 received nivolumab (0.1−10 mg/kg IV Q2W) during dose escalation and/or cohort expansion. Tumors were assessed by RECIST 1.0 after each 4-dose cycle. Pts received ≤12 cycles until unacceptable toxicity, confirmed progression, or CR. Results: 304 pts with non-small cell lung cancer (NSCLC, n=127, squamous and nonsquamous), melanoma (MEL, n=107), renal cell (RCC, n=34), colorectal (n=19) or prostate cancer (n=17) were treated. Durable ORs (CR/PR) were observed in MEL, NSCLC and RCC (Table); in 54 responders with ≥1 yr follow-up, 28 lasted ≥1 yr. Median OS in these heavily pretreated pts (47% with 3-5 prior systemic therapies) compared favorably with expected outcomes as of July 2012. Drug-related AEs (any grade) occurred in 72% (220/304) and G3/G4 AEs in 15% (45/304) of pts. Drug-related pneumonitis occurred in 3% (10/304), including G3/G4 in 1% (3/304), resulting in 3 deaths early in the trial, which led to increased clinical monitoring and an emphasis on management algorithms. Nivolumab-related pneumonitis characteristics and management will be summarized. Updated survival and safety data from Feb 2013 (≥1 yr follow-up all pts) will be presented, including OS at 3 yr. Conclusions: Nivolumab produced sustained survival with a manageable long-term safety profile in advanced MEL, NSCLC and RCC, supporting its ongoing clinical development in controlled phase III trials with survival endpoints. Clinical trial information: NCT00730639. [Table: see text]
Effects of Dimiracetam on oxaliplatin-induced hyperalgesia and allodynia in the rat.
Authors: Lorenzo Di Cesare Mannelli, Laura Micheli, Carlo Farina, Michael Scherz, Carla Ghelardini
Journal: Journal of Clinical Oncology (2015)

e20650 Background: Painful neuropathy is a common adverse event associated with oxaliplatin treatment. It can occur within the first days and may persist from months to years beyond chemotherapy completion, negatively impacting the quality of life of cancer survivors. It is a frequent cause of chemotherapy dose reduction or early treatment discontinuation. The 2014 ASCO clinical practical guideline states there are no agents recommended for the treatment of chemotherapy-induced peripheral neuropathy. Dimiracetam, a compound originally developed as a cognition enhancer, is effective in the treatment of neuropathic pain in several rat models. Here we report that dimiracetam is also effective for prevention of oxaliplatin-induced neuropathy when administered orally, concomitantly with the chemotherapeutic agent. We have used duloxetine and vehicle as comparators. Methods: Oxaliplatin (2.4 mg/kg ip) was administered qd; concomitant dimiracetam (75 and 150 mg/kg po) or duloxetine (5 and 15 mg/kg po) or vehicle, were administered bid. Results: Repeated administration of dimiracetam from day 1 to day 21 of oxaliplatin treatment prevented the development of mechanical hyperalgesia, as assessed by the Randall-Selitto analgesymeter. Mechanical and thermal allodynia were also prevented, as assessed by Von Frey and Cold Plate tests, respectively. The effect of dimiracetam was dose-dependent and persisted throughout the 21-day treatment period. In a second experimental protocoloxaliplatin was co-administered from day 1 to day 11 with twice-daily dimiracetam or duloxetine or vehicle. Dimiracetam and duloxetine completely prevented the development of both mechanical hyperalgesia and allodynia. Both doses of dimiracetam were similarly effective to the higher dose of duloxetine. The effect of both compounds persisted up to day 16, five days after treatment discontinuation. Conclusions: In a rat model of oxaliplatin-induced peripheral neuropathy, dimiracetam prevented oxaliplatin-induced peripheral neuropathy, exhibiting efficacy also in the post-treatment period. Dimiracetam is a promising drug candidate for prevention of oxaliplatin-induced neuropathy and warrants further investigation in clinical trials.
Crosstalk between TGF-B-Induced Epithelial-Mesenchymal Transition and Stemness in Hepatocellular Carcinoma
Authors: A. Malfettone, J. Soukupova, J. Fernando, P. Koudelkova, E. Bertran, A. Fabra, M. Grubinger, B. Rani, G. Giannelli, W. Mikulits, I. Fabregat
Journal: Journal of Hepatology (2016)
Sofosbuvir/Ledipasvir without Ribavirin in the Treatment of Asians with Chronic Hepatitis C Virus Genotype 6 in the United States: Community-Based Real World Outcomes
Authors: R. Wong, M. Nguyen, H. Trinh, A. Huynh, M. Ly, H. Nguyen, K. Nguyen, J. Yang, R. Garcia, E. DaSilvera, R. Gish
Journal: Journal of Hepatology (2016)