tbuckley/cabot-search huggingface dataset:
Signatures of Divergence, Invasiveness, and Terrestrialization Revealed by Four Apple Snail Genomes
Authors: Jin Sun, Huawei Mu, Jack C H Ip, Runsheng Li, Ting Xu, Alice Accorsi, Alejandro Sánchez Alvarado, Eric Ross, Yi Lan, Yanan Sun, Alfredo Castro-Vazquez, Israel A Vega, Horacio Heras, Santiago Ituarte, Bert Van Bocxlaer, Kenneth A Hayes, Robert H Cowie, Zhongying Zhao, Yu Zhang, Pei-Yuan Qian, Jian-Wen Qiu
Journal: Molecular Biology and Evolution (2019)

The family Ampullariidae includes both aquatic and amphibious apple snails. They are an emerging model for evolutionary studies due to the high diversity, ancient history, and wide geographical distribution. Insight into drivers of ampullariid evolution is hampered, however, by the lack of genomic resources. Here, we report the genomes of four ampullariids spanning the Old World (Lanistes nyassanus) and New World (Pomacea canaliculata, P. maculata, and Marisa cornuarietis) clades. The ampullariid genomes have conserved ancient bilaterial karyotype features and a novel Hox gene cluster rearrangement, making them valuable in comparative genomic studies. They have expanded gene families related to environmental sensing and cellulose digestion, which may have facilitated some ampullarids to become notorious invasive pests. In the amphibious Pomacea, novel acquisition of an egg neurotoxin and a protein for making the calcareous eggshell may have been key adaptations enabling their transition from underwater to terrestrial egg deposition.
Sarcoma risk after laparoscopic surgery: A retrospective analysis.
Authors: Wolfgang Nemec, Monika Klinkhammer-Schalke, Olaf Ortmann, Stefan Buchholz
Journal: Journal of Clinical Oncology (2015)

e21529 Background: The US Food and Drug Administration (FDA) advisory panel has discouraged the use of laparoscopic power morcellators (LPM) for removal of uterus or uterine fibroids in April 2014. The minimal invasive approach for surgery of uterine fibroids is considered standard of care. Does the sarcoma risk abundant the laparoscopic approach with morcellment? The retrospective Analysis evaluates the incidence rates and the prognosis of occult uterine leiomyosarcoma (LMS) Methods: The medical reports of 594 Patients with benigne surgery for uterine fibroids between 2008 and 2013 were anaylsed for occult LMS to confirm the incidence rate. The clinical cancer registry Regensburg (Germany) registered 71 known patients between 2004 and 2013 with uterine LMS. Outcome, survival and recurrence rates were evaluated for Patients who underwent laparoscopic and abdominal surgery. The significance of preopereative uterine LMS diagnostical tools such as magnetic resonance imaging (MRI), elevated lactate dehydrogenase level, rapid growth, and pre/post menopausal bleeding were evaluated in the cohort. Results: In our Cohort of 594 patients 0,51% were diagnosed with an occult LMS with laparoscopic surgery and 0,34% with open surgery. The prognosis of the patients with laparocscopic surgery was not significantly different to those of an abdominal surgery. Conclusions: The minimal invasive approach is according to our data still standard of care in the treatment of uterine fibroids.
Abstract 24060: Alpha Calcitonin Gene-Related Peptide (CGRP) Protects Against Pressure-induced Heart Failure
Authors: Ambrish Kumar, Scott Supowit, Jay D Potts, Donald J DiPette
Journal: Circulation (2017)

Introduction: Calcitonin gene-related peptide (CGRP), a 37 amino acid neuropeptide, is a potent vasodilator, and plays a critical role in the efferent functions of the sensory nervous system. A protective role for CGRP in cardiovascular diseases (hypertension, cardiac ischemia, and failure) has been well established by our laboratory and others. In the present study we determined whether long-term exogenous administration of α-CGRP protects against pressure-induced heart failure. Method: Three groups of nine-week-old C57/BL6 mice were studied: one group received a sham procedure (n= 4) and two groups underwent transverse aortic constriction (TAC). Two days after TAC, one group had CGRP-filled osmotic pumps (4 mg/kg bwt/day) implanted subcutaneously (n= 7) while the second group was TAC-only (n=6). At day 28, all groups had echocardiography performed and were sacrificed and heart tissue collected. Results: Echocardiographic and histological data showed that TAC markedly decreased fractional shortening (FS) and ejection fraction and increased heart and lung weight, cardiac hypertrophy, and fibrosis compared to sham. However, the TAC-CGRP mice had preserved cardiac function and less cardiac fibrosis (FS ±SEM: sham 46.2±1.8% vs TAC 25.4±1.1%, p &lt; 0.001; and TAC 25.4±1.1% vs TAC-CGRP 36.6±1.2%, p &lt; 0.001). CGRP significantly reduced apoptotic cell death and lipid peroxidation (an oxidative stress marker measured by malondialdehyde and 4-HNE staining) in the TAC hearts [malondialdehyde (nmol/mg protein) ±SEM: sham 3.5±0.19 vs TAC 14.3±0.57, p &lt; 0.05; and TAC 14.3±0.57 vs TAC-CGRP 5.5±0.12, p &lt; 0.05]. TAC alone decreased the level of p-ERK1/2 and increased p-JNK compared to sham. CGRP-TAC hearts had higher p-ERK1/2 levels but equal p-JNK levels compared to the TAC hearts. HIF1α and nrf2 protein levels were not different between experimental groups. Compared to TAC hearts, TAC-CGRP hearts had lower p-AMPK and nuclear Sirt1 level, regulatory proteins of energy metabolism. Conclusion: Our results suggest that CGRP, mediated through energy metabolic, and oxidative stress pathways, decreases myocyte apoptosis and is protective in pressure-induced heart failure. Thus, CGRP is a potential therapeutic agent in preventing the progression of heart failure.
THU-111-High efficacy and safety of the combination HCV regimen elbasvir and grazoprevir for 8 weeks in treatment-naive non-severe fibrosis HCVGT1b-infected patients: Final results of the STREAGER study
Authors: Armand Abergel, Christophe Hezode, Tarik Asselah, Dominique Larrey, Jérôme Gournay, Veronique Loustaud-Ratti, vincent di martino, Isabelle Fouchard Hubert, Pol Stanislas, Francois Bailly, Didier Samuel, Tran Albert, Brigitte Chanteranne, Marie Dodel, Frederic Faure, Bruno Pereira, Géraldine Lamblin, Leon Muti, Cecile Campos, Maud Reymond, Camille Teilhet, Benjamin Buchard
Journal: Journal of Hepatology (2019)
Prevalence of Bacteremia and Bacterial Meningitis in Febrile Neonates and Infants in the Second Month of Life
Authors: Eric A. Biondi, Brian Lee, Shawn L. Ralston, Jared M. Winikor, Justin F. Lynn, Angela Dixon, Russell McCulloh
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Febrile neonates (persons in the first month of life) are believed to be at higher risk for bacteremia or bacterial meningitis than infants in their second month of life. However, the true prevalence is unclear. <h3>Objective</h3> To determine modern rates of bacteremia and bacterial meningitis in febrile neonates and infants in the second month of life presenting to an ambulatory setting. <h3>Data Sources</h3> A comprehensive, no-limit search was conducted in PubMed using previously published search terms in February 2015 and repeated in September 2016. <h3>Study Selection</h3> Abstracts and full texts were reviewed independently by several investigators. Studies were included if data regarding blood cultures or cerebrospinal fluid cultures from consecutive febrile infants in an ambulatory setting could be extrapolated within the age groups. To limit the analysis to the period after the availability of the<i>Haemophilus influenzae</i>type b vaccination, studies that collected data before 1990 were excluded. <h3>Data Extraction and Synthesis</h3> Data were extracted in accordance with the Meta-analyses of Observational Studies in Epidemiology (MOOSE) reporting guidelines via independent abstraction by several investigators. The Newcastle-Ottawa Scale was used to assess bias. <h3>Main Outcomes and Measures</h3> The primary outcomes were prevalence rates of bacteremia and bacterial meningitis in febrile neonates and infants in the second month of life. In neonates, prevalence rates were also estimated in the era of group B<i>Streptococcus</i>intrapartum antibiotic prophylaxis (after 1996). <h3>Results</h3> In total, 7264 abstracts were screened, resulting in 188 full-text manuscripts reviewed, with 12 meeting inclusion criteria (with 15 713 culture results). For febrile neonates, the prevalence of bacteremia was 2.9% (95% CI, 2.3%-3.7%;<i>I</i><sup>2</sup> = 50%; n = 5145) and the prevalence of bacterial meningitis was 1.2% (95% CI, 0.8%-1.9%;<i>I</i><sup>2</sup> = 27%; n = 3288). In neonates in the era after group B<i>Streptococcus</i>prophylaxis, the prevalence of bacteremia was 3.0% (95% CI, 2.3%-3.9%;<i>I</i><sup>2</sup> = 6%; n = 2055) and the prevalence of meningitis was 1.0% (95% CI, 0.4%-2.1%;<i>I</i><sup>2</sup> = 28%; n = 1739). For febrile infants in the second month of life, the prevalence of bacteremia was 1.6% (95% CI, 0.9%-2.7%;<i>I</i><sup>2</sup> = 78%; n = 4778) and the prevalence of meningitis was 0.4% (95% CI, 0.2%-1.0%;<i>I</i><sup>2</sup> = 33%; n = 2502). <h3>Conclusions and Relevance</h3> These findings suggest that febrile neonates have approximately twice the rate of bacteremia and meningitis as febrile infants in their second month of life.
Abstract 16783: Diagnostic Accuracy of Coronary Computed Tomography Angiography in Patients Undergoing Cardiac Valve Surgery: Systematic Review and Meta-analysis
Authors: Kongkiat Chaikriangkrai, Ghanshyam Palamaner Subash Shanta, Aref Bin Abdulhak, Hye Yeon Jhun, Jay K Bhama, Gardar Sigurdsson
Journal: Circulation (2016)

Introduction: The objective of this study is to investigate the diagnostic accuracy of coronary computed tomography angiography (CCTA) in patients undergoing cardiac valve surgery using invasive co...
FRI-207-Subgroup analysis of patients undergoing switch of nucleos (t)ide regimen for HBV treatment during the prospective BONIKA trial
Authors: Kathrin Sprinzl, Svenja Steinhoff, Johannes Vermehren, Tania Welzel, Stefan Zeuzem, Martin Sprinzl, Christoph Sarrazin
Journal: Journal of Hepatology (2019)
Pemetrexed (Pem), carboplatin (Cb), and bevacizumab (Bev) in patients with nonsquamous NSCLC without or with activating EGFR mutation (CJLSG0909/0910).
Authors: Tomoki Kimura, Hiroyuki Taniguchi, Tomohiko Ogasawara, Masashi Kondo, Ryujiro Suzuki, Masashi Yamamoto, Joe Shindo, Osamu Hataji, Norio Yoshida, Eiji Kojima, Yoshinori Hasegawa, Hiroshi Saito
Journal: Journal of Clinical Oncology (2015)

e19038 Background: Treatment strategies for advanced non-squamous (sq) non-small cell lung cancer (NSCLC) are divided by EGFR mutations. However, there has been no previous report about efficacy of cytotoxic agent separated by EGFR mutations. In addition, the influence of the EGFR mutations on the maintenance therapy with Pem or Bev has not been elucidated. We planned two studies designed to evaluate the efficacy and safety of combination therapy with Pem, Cb and Bev followed by Pem+Bev maintenance therapy for non-sq NSCLC patients without or with activating EGFR mutation. Methods: We undertook two multicenter, open-label, single-arm, phase II studies. Patients with wild type EGFR or with EGFR mutation (exon 19 deletions or exon 21 point mutation) entered CJLSG0909 or 0910, respectively. Patients receive Pem 500mg/m2, Cb AUC 6, and Bev 15mg/kg, every 3 weeks, 4 to 6 cycles. Patients who achieved disease control receive Pem+Bev maintenance therapy until PD. Results: In CJLSG0909, 50 patients received treatment. They had a median age of 64 years and were predominantly men (80%) with adenocarcinoma (94%), stage IV (80%), and a performance status (PS) of 1 (80%). Median of induction therapy is 5 cycles, and 70% of patients received maintenance therapy, the median was 5 cycles. Response rate (RR) was 80%, disease control rate (DCR) was 92%, and median PFS was 6.8 months. Grade 3/4 toxicities (above 5%) included neutropenia (40%), thrombocytopenia (24%), anemia (16%), nausea (8%), anorexia (6%) and ALT elevation (6%). In CJLSG0910, 30 patients received treatment. They had a median age of 65.5 years and were predominantly women (57%) with adenocarcinoma (97%), stage IV (90%), and a PS of 0 (77%). Median of induction therapy is 6 cycles, and 830% of patients received maintenance therapy, the median was 8.5 cycles. RR was 50%, DCR was 100%, and median PFS was 10.5 months. Grade 3/4 toxicities included neutropenia (47%), thrombocytopenia (20%), anemia (20%), and diarrhea (7%). Conclusions: These studies suggested that chemotherapy with Pem+Cb+Bev, including maintenance therapy is candidate for first line therapy in non-sq NSCLC patients regardless of the activating EGFR mutations. Clinical trial information: UMIN000003736, UMIN000003737.
APOBEC-mediated Mutagenesis as a Likely Cause of FGFR3 S249C Mutation Over-representation in Bladder Cancer
Authors: Ming-Jun Shi, Xiang-Yu Meng, Philippe Lamy, A. Rouf Banday, Jie Yang, Aura Moreno-Vega, Chun-Long Chen, Lars Dyrskjøt, Isabelle Bernard-Pierrot, Ludmila Prokunina-Olsson, François Radvanyi
Journal: European Urology (2019)
The synergistic anti-lymphoma effects of PIM kinase inhibitors in combination with DNA damaging agents.
Authors: Jeffrey Altenburg, Shuhong Zhang, Xingkui Xue, Sherif Farag
Journal: Journal of Clinical Oncology (2015)

e19522 Background: Burkitt’s lymphoma is a highly aggressive mature B-cell neoplasm that involves translocation of the c-Myc gene. Conventional therapies have proven unsuccessful for treating Burkitt’s lymphoma. Therefore new therapies are still needed. The PIM kinases are a family of proteins that have been implicated in several cancers and identified as a target for chemotherapy. Overexpression of the PIM kinases leads to the activation of several cell-cycle progression and anti-apoptotic proteins. The PIM kinases have been identified as important factors in the DNA repair response through the ATM pathway. In this study we investigated the effects and associated mechanisms of the pan-PIM kinase inhibitor CX6258 on Burkitt’s lymphoma cell lines in combination with doxorubicin or cyclophosphamide. Methods: Cell toxicity was analyzed with MTS assays. Combination Indexes were calculated to determine the degrees of synergy between the drugs. Effects on pathway proteins were analyzed by western blot. Acridine orange staining was used to analyze cellular DNA damage. Change in PIM expression was analyzed by RT-PCR. Results: CX6258 inhibited cell growth in all cell lines with varying degrees of potency. We observed synergistic inhibition of cell proliferation for CX6258 in combination with Doxorubicin. Doxorubicin treatment resulted in increased transcripts of PIM1 and PIM2. We next analyzed the drug effects on DNA damage and repair response. Combinations of doxorubicin and CX6258 synergistically increased DNA damage. The doxorubicin-induced DNA repair response was attenuated by the PIM inhibitors. Similar results were observed with another DNA damaging agent cyclophosphamide. Conclusions: Taken together our data suggest for the first time a mechanism for synergy where doxorubicin damages the cellular DNA, resulting in upregulated PIM kinase expression and the subsequent initiation of the repair response. CX6258 addition inhibits the upregulated PIM kinases from activating the proteins involved in the response, leading to increased DNA damage and elevated cell toxicity. Our study identifies PIM kinase inhibition as a potentially effective enhancer for DNA damaging agents in Burkitt’s lymphoma treatment.
Abstract 12291: Intravenous Recombinant Tissue Plasminogen Activator in Acute Ischemic Stroke Patients With Gastrointestinal Malignancy or Recent Bleeding
Authors: Taku Inohara, Li Liang, Andrzej Kosinski, Eric E Smith, Lee H Schwamm, Adrian F Hernandez, Deepak L Bhatt, Gregg C Fonarow, Eric D Peterson, Ying Xian
Journal: Circulation (2018)

Introduction: Based on expert consensus, the use of intravenous recombinant tissue plasminogen activator (rtPA) for treating acute ischemic stroke (AIS) is contraindicated in patients with a gastro...
Prognosis Reconsidered in Light of Ancient Insights—From Hippocrates to Modern Medicine
Authors: John M. Thomas, Leo M. Cooney, Terri R. Fried
Journal: JAMA Internal Medicine (2019)

Whereas modern clinicians are often reluctant to discuss prognosis with their patients, such discussions were central to medical practice in ancient Greece. A historical analysis has the potential to explain the reasons for this difference in prognostic practices and provide insights into overcoming current challenges. Many scholars consider prognosis to be the principal scientific achievement of the Hippocratic tradition. The earliest treatise on the subject,<i>On Prognostics</i>, defines prognosis broadly as "foreseeing and foretelling, by the side of the sick, the present, the past, and the future." This definition makes clear that prognosis is not simply about predicting the future, but also involves an appreciation for the continuity of past, present, and future as sequences of connected events, or trajectories, that can be pieced together into a comprehensive story of the patient's health. In modern medicine, prognosis has lagged behind diagnosis and treatment in its establishment as a central component of medical care. An important basis for understanding this lies in the paradigm change that occurred with the discovery of pathogens as agents of disease, shifting attention toward individual diseases and away from diseased individuals. With this shift, diagnostics and treatments advanced dramatically and prognosis fell to the background. More recent attempts to advance prognosis have focused on narrower uses of the term, such as estimates of life expectancy and mortality risk. However, physicians have expressed a number of reservations about the use of such estimates in the care of patients, and patients have indicated the desire for a wide variety of predictive information. Adopting the broadness of the Hippocratic definition may allow clinicians to overcome their hesitancy and provide much-needed information to their patients.
Is there a benefit of TKIs among the elderly compared with younger patients in non-small cell lung cancer? a meta-analysis.
Authors: Thierry Landre, Patrick Nicolas, Bernard Uzzan, Kader Chouahnia, Cherifa Taleb, Hanene Boudabous, Laurent H. Zelek, Gaetan Des Guetz
Journal: Journal of Clinical Oncology (2015)

e20515 Background: Tyrosine kinase inhibitors (TKIs) have a much better benefit to risk balance among the elderly compared with younger patients and to chemotherapy. To our knowledge, there is no meta-analysis (MA) comparing the benefit of TKIs versus chemotherapy in Non–small-cell lung cancer (NSCLC) among elderly or younger patients. Methods: We did a PubMed query using keywords simultaneously (lung neoplasm, elderly, TKI, EGFR mutation, survival, randomized controlled trials). We also searched for relevant abstracts in annual proceedings of ASCO, ESMO, WCLC meetings. We cross checked all references from all articles. Only phase III randomized controlled trials comparing TKI and chemotherapy between two age groups were included. We used Comprehensive MA software. A random effect model was used due to heterogeneity between studies. We performed 2 distinct MAs, one among the elderly and the other among the younger patients. Then, we calculated the ratio of relative risk with its 95% interval to compare the TKI effect among elderly and younger patients. Results: The 6 eligible studies included 2481 patients (684 males, 1797 females, median age 60 years old, 733 elderly and 1748 younger, mostly Asian, 2388 adenocarcinomas (98%), 1491 mutated tumors, mostly never smokers (86 %). Two studies assessed gefitinib, 2 erlotinib and 2 afatinib. Chemotherapies were doublets including a platinum salt. TKIs compared to chemotherapy significantly improved PFS among elderly patients (HR = 0.28, 95 % CI 0.14-0.59) but did not improved OS (HR = 0.81, 95 % CI 0.64-1.02). Among younger patients, there was no statistically significant difference for OS (HR = 0.93, 95 % CI 0.83-1.05) but statistically significant difference in PFS (HR = 0.34, 95 % CI 0.23-0.53). Also, compared to chemotherapy, EGFR TKIs had a similar benefit among the elderly and the younger patients both in terms of OS (p = 0.294) and PFS (p = 0.628). Conclusions: There was a similar benefit of TKIs compared to chemotherapy in NSCLC between the elderly and the younger patients both in terms of PFS and OS. These findings might be explained by similar clinical characteristics in both groups (number of fit patients, age range not so different between both groups).
THU-135-Real-world HCV treatment in HCV-HIV coinfected population: Data from the TRIO network
Authors: Dushyantha Jayaweera, Janna Radtchenko, Keri Althoff, Jason Gillman, Joseph Eron, Steven Santiago, Karam Mounzer, Paul Sax, Anthony Mills, Gregory Huhn, Graeme Moyle, Matthew Budday, Rick Elion
Journal: Journal of Hepatology (2019)
Reduced-, and no-dose thin-section radiologic examinations: Comparison of capability for nodule detection in patients having pulmonary nodules
Authors: W. Tang, Q. Peng, Y. Huang, N. Wu, H. Ouyang
Journal: Annals of Oncology (2019)

Background: To evaluate the capability of pulmonary MR imaging with zero echo time (ZTE) in pulmonary nodules assessments, using low-dose computed tomography (LDCT) as the reference standard. Methods: Institutional review board approval and informed consent were obtained. Eight-nine consecutive patients (51 males: mean age, 69 years and 38 females: mean age, 71 years) with various pulmonary nodules were examined with chest LDCT and pulmonary MR imaging with ZTE. The interval between two examinations was within two weeks for each patient. Lung images were visually scored by two experienced radiologists who assessed the probability of nodule presence in comparison with LDCT. To compare nodule detection capability of the two methods, consensus for performances was evaluated by means of kappa statistics and χ2 test, and receiver operating characteristic analyses were used to compare diagnostic performance of both methods. Results: There was no significant difference (F = 0.75, p = 0.56) in figure of merit between methods (LDCT, 0.84 Vs. MR imaging with ZTE, 0.86). Intermethod agreements between ZTE MR imaging and LDCT were significant (0.70 ≤ κ ≤ 0.98; P < 0.001). Areas under the curve for pulmonary nodules on LDCT were significantly larger than those on MR imaging with ZTE (p = 0.02). Conclusions: Pulmonary thin-section MR imaging with ZTE was useful in nodule detection, and it is considered at least as effective as low-dose thin-section CT. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.