tbuckley/cabot-search huggingface dataset:
Abstract 17571: Use of Goal Directed Transesophageal Echocardiography in the Arresting Patient
Authors: Shoeb Ahsan, Robert Arntfield
Journal: Circulation (2015)

Background: With outcomes from cardiac arrest remaining generally poor, there is an urgency to evaluate interventions that allow physicians to manage cardiac arrest more effectively. Transesophageal echocardiography (TEE) can be used at the point of care in a goal-directed manner and can rapidly provide a flurry of data on cardiac structure and function. TEE in the arrested patient is unobtrusive to resuscitation and can provide vital information regarding the potential etiology of arrest, guidance of certain procedures and prognosis. As such, some centers, including our own, have adopted increasingly routine use of TEE in this context. Given the paucity of data in this area, we sought to examine the influence of point-of-care TEE conducted by emergency physicians or intensivists at our institution for patients in or immediately after cardiac arrest. Methods: Goal-directed TEE in the emergency department (ED) or intensive care units (ICU) and their reports were archived in a dedicated point-of-care ultrasound imaging database. We conducted a search of all TEE examinations archived between December 2012 and April 2015 in the peri-arrest period (in or immediately after cardiac arrest). The details from reports were abstracted. TEE-directed management changes were noted when recommendation(s) regarding initiation/escalation of inotropes, fluid administration, termination of resuscitation or surgical procedure were featured in the TEE report. Results: A total of 57 peri-arrest TEE exams were identified (21 in ICUs and 36 in EDs). Goal-directed TEE changed management in 61.4% of cases. TEE facilitated the escalation/initiation of inotropes (35.3%), decision to terminate resuscitation (32.4%), guided fluid management (23.5%) and surgical procedures (8.8%). TEE studies altered management in 66.7% of cases in the Intensive Care Unit and in 58.3% of cases in the Emergency Department. Conclusions: Goal-directed TEE performed by emergency physicians or intensivists has an impact on management on patients in the peri-arrest setting the majority of the time. Given the lack of reliable diagnostic and therapeutic options in arresting patients, a larger study examining the influence of goal-directed TEE on patient outcomes in cardiac arrest should be carried out.
GW29-e1819 Association of cholesterol efflux capacity of high-density lipoprotein with coronary collateralization in patients with stable angina and chronic total occlusion
Authors: Xiaoqun Wang, Ying Shen, Fenghua Ding, Chang Li, Jiawei Chen, Ruiyan Zhang, Lin Lu, Weifeng Shen
Journal: Journal of the American College of Cardiology (2018)
Living with Buildings: new Wellcome show looks at urban architecture and health
Authors: Juliet Dobson
Journal: BMJ (2018)

Last year’s Grenfell Tower fire in London is a recent and shocking reminder of what can happen if building safety is compromised and of society’s obligation to provide safe social housing for the world’s growing urban populations.

A new exhibition at the Wellcome Collection in London, Living with Buildings, explores the positive and negative effects that architecture, town planning, and design have on people’s health and wellbeing. It looks at the overcrowded conditions and poor sanitation …
2019 Canadian guideline for physical activity throughout pregnancy
Authors: Michelle F Mottola, Margie H Davenport, Stephanie-May Ruchat, Gregory A Davies, Veronica J Poitras, Casey E Gray, Alejandra Jaramillo Garcia, Nick Barrowman, Kristi B Adamo, Mary Duggan, Ruben Barakat, Phil Chilibeck, Karen Fleming, Milena Forte, Jillian Korolnek, Taniya Nagpal, Linda G Slater, Deanna Stirling, Lori Zehr
Journal: British Journal of Sports Medicine (2018)

The objective is to provide guidance for pregnant women and obstetric care and exercise professionals on prenatal physical activity. The outcomes evaluated were maternal, fetal or neonatal morbidity, or fetal mortality during and following pregnancy. Literature was retrieved through searches of MEDLINE, EMBASE, PsycINFO, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Scopus and Web of Science Core Collection, CINAHL Plus with Full Text, Child Development & Adolescent Studies, Education Resources Information Center, SPORTDiscus, ClinicalTrials.gov and the Trip Database from inception up to 6 January 2017. Primary studies of any design were eligible, except case studies. Results were limited to English-language, Spanish-language or French-language materials. Articles related to maternal physical activity during pregnancy reporting on maternal, fetal or neonatal morbidity, or fetal mortality were eligible for inclusion. The quality of evidence was rated using the Grading of Recommendations Assessment, Development and Evaluation methodology. The Guidelines Consensus Panel solicited feedback from end users (obstetric care providers, exercise professionals, researchers, policy organisations, and pregnant and postpartum women). The development of these guidelines followed the Appraisal of Guidelines for Research and Evaluation II instrument. The benefits of prenatal physical activity are moderate and no harms were identified; therefore, the difference between desirable and undesirable consequences (net benefit) is expected to be moderate. The majority of stakeholders and end users indicated that following these recommendations would be feasible, acceptable and equitable. Following these recommendations is likely to require minimal resources from both individual and health systems perspectives.
Hsa-miR-106b-5p Negatively Regulates LEF1
Authors: Annada Anil Joshi, Alka Vishwas Nerurkar, Neelam Vishwanath Shirsat
Journal: Cancer Research (2018)

Aberrant expression of the genes involved in Wnt signaling pathway, one of the most important developing pathways, is observed in many malignancies. Reports show that Wnt/β-catenin activation is critical for cancer development, angiogenesis, migration, and invasion. LEF1 belongs to the T cell Factor (TCF)/LEF family of transcription factors and plays the role of nuclear effector in the Wnt/β-catenin signaling pathway. LEF1 has central role as a transcription factor in the Wnt/β-catenin signaling pathway which makes it an ideal target for therapeutic treatment in dealing with cancer proliferation. It can act as an oncogene or a tumor suppressor in cellular context dependent manner. miRNAs are aberrantly expressed in cancers and can act as tumor suppressors or oncomirs depending upon the type of carcinomas. Studies show that miRNAs can be used as novel agents for targeted cancer therapy. miR-106b, which belong to miR-17-92 paralog cluster, is reported to be overexpressed in multiple tumor types including medulloblastomas, breast, colon, kidney, gastric, lung cancer and HCC. In this study we have demonstrated that over-expression of miR-106b-5p down-regulates the endogenous expression of LEF1 in HEK293FT cells, thereby affecting the expression of N-Myc, downstream gene of Wnt signaling. Therefore, our results suggest that miR-106b-5p plays a significant role in suppressing the carcinomas resulted due to the over-expression of LEF1 and/or activation of Wnt pathway and may prove to be a potential target for novel cancer therapy. It may helpful in developing therapeutic strategies for cancer treatments.
A prospective observational study of HER2 alterations in NSCLCs: HOT1303-A
Authors: T. Goda, I. Kinoshita, S. Oizumi, K. Nakano, T. Harada, Y. Kawai, J. Sakakibara-Konishi, H. Yokouchi, N. Morikawa, N. Yamada, S. Yamazaki, S. Sugawara, H. Asahina, T. Amano, Y. Hatanaka, Y. Matsuno, H. Nishihara, H. Isobe, M. Nishimura, H. Dosaka-Akita
Journal: Annals of Oncology (2018)
Abstract 11583: Liver Stiffness Assessed by Fib4 Index Predicts Mortality in Heart Failure Patients
Authors: Yu Sato, Akiomi Yoshihisa, Shunsuke Watanabe, Tetsuro Yokokawa, Shunsuke Miura, Takamasa Sato, Satoshi Suzuki, Masayoshi Oikawa, Atsushi Kobayashi, Takayoshi Yamaki, Hiroyuki Kunii, Shu-ichi Saitoh, Yasuchika Takeishi
Journal: Circulation (2016)

Background: Liver dysfunction due to heart failure (HF) is often referred as cardiac or congestive hepatopathy. FIB4 index (age [years] х aspartate aminotransferase [IU/L] / platelet count [10 -9 /L] х radical alanine aminotransferase [IU/L]) is expected to be useful for evaluating liver fibrosis in patients with nonalcoholic fatty liver disease. It has been recently reported that liver stiffness assessed by transient elastography predicts adverse prognosis in HF patients. We aimed to investigate the impact of FIB4 index on prognosis of HF and compare the underlying cardiac function. Methods and Results: We analyzed 1268 HF patients who admitted to our hospital. Out of these patients, patients with hepatitis and chronic liver disease were excluded, and 1058 patients were finally analyzed. These patients were divided into 3 groups based on the FIB4 index: 1st, 2nd and 3rd tertile (n=353, each). In the follow-up period (mean 1047 days), 246 deaths (122 cardiac deaths and 124 non-cardiac deaths) occurred. In the Kaplan-Meier analysis, all-cause mortality progressively increased from 1 st to 2 nd and 3 rd groups (12.2, 21.0 and 36.6%, P &lt;0.001). In the Cox proportional hazard analysis, FIB4 index was an independent predictor of all-cause mortality in HF patients (hazard ratio 1.79, 95% confidence interval 1.29-2.49, P&lt;0.001). In addition, we compared echocardiographic findings among the three groups. Left ventricular ejection fraction and right ventricular fractional area change did not differ among three groups. In contrast, the 3rd tertile, compared to 2nd and 1st tertiles, had higher levels of left atrial volume (92.5 vs. 82.8, and 74.9 ml, P &lt; 0.01), mitral valve E/e’ (16.6 vs. 15.3, and 13.8, P &lt; 0.01), inferior vena cava diameter (16.2 vs. 14.5, and 14.4 mm, P &lt; 0.01) and right atrial area (20.9 vs. 17.4, and 17.6 cm 2 , P &lt; 0.01). Conclusion: FIB4 index, a marker of liver stiffness, is associated with larger right and left heart volume overload, and higher mortality in HF.
GW29-e0556 Prognostic significance of methylation levels of FOXP3 in patients with acute coronary syndrome
Authors: Ling Zhu, Yin Liu, Zhongwei Liu, Fuqiang Liu, Yong Zhang, Gongchang Guan, Junkui Wang, Rutai Hui, Lei Jia
Journal: Journal of the American College of Cardiology (2018)
Increase in tumor-infiltrating FoxP3-positive regulatory T cells in left-sided colorectal cancer tissues after preoperative oral uracil and tegafur/leucovorin chemotherapy
Authors: S. Sadahiro, T. Suzuki, A. Tanaka, K. Okada, G. Saito, H. Miyakita, H. Kajiwara, H. Nagase
Journal: Annals of Oncology (2018)
Gene expression profile of malignant human colon cancer SW480 cells transformed by BMP-4 overexpression
Authors: Weng-Lang Yang, Haiyun Deng, T. Ravikumar
Journal: Cancer Research (2008)

4521  Introductions: Bone morphogenetic proteins (BMP), a member of the TGF-β superfamily, involve in regulating various cellular behaviors. Previously, we demonstrated that BMP-4 is upregulated in colonic adenocarcinoma and can transform human colon cancer HCT116 cells to become more aggressive. In canonical BMP signaling pathway, Smad4 is a central mediator for regulating the expression of target genes, while the frequency of Smad4 inactivation is markedly increased in metastatic colorectal cancers. Here, we examined whether elevated BMP-4 levels were able to stimulate cell invasiveness in SW480 cells which are Smad4-deficient. We further performed gene expression microarray analysis to explore the potential target genes responding to BMP-4 overexpression in SW480 cells.  Methods: BMP-4 coding region was subcloned into a pcDNA3.1 vector. The BMP-4 expression plasmid and an empty vector was transfected into SW480 cells. Individual stable clones were generated by geneticin selection. The expression levels of BMP-4, phospho-Smad1, and vimentin were analyzed by Western blotting. Cell migration and invasion assays were conducted in a Boyden chamber without coating or coated with Matrigel, respectively, for 48 h using 10% serum as chemotactic stimulus. Rac activity was assessed by GST-PBD pull-down assay. An oligonucleotide microarray containing 46, 000 genes (Illumina) was used to compare gene expression profile between BMP-4 overexpressing cells and empty vector controls. Data were acquired from Illumina BeadStudio and analyzed by GeneSpring.  Results: The levels of BMP-4 in cell lysate and conditioned medium were barely detected in empty vector controls, whereas they were very intense in SW480 cells stably carrying a BMP-4 expression plasmid. BMP-4 overexpressing cells exhibited higher levels of phosphorylated Smad1 than controls, indicating that SW480 cells have functional receptors for transmitting the autocrine BMP signaling. Overexpression of BMP-4 resulted in an increased expression of vimentin, a marker of epithelial-messenchymal transition. Cell migration and invasion potentials in BMP-4 overexpressing cells were increased by 2.4~3.4- and 5.2~7.0-fold, respectively, compared to controls. The activity of Rac was highly activated in BMP-4 overexpressing cells in comparison to controls. In the analysis of microarray data, 99 genes (70 up-regulated and 29 down-regulated) with 2-fold difference has been identified. Six genes (CEBP, CTGF, CTHRC1, G0S2, IFITM1, and OPG) have been previously reported as targets of BMP pathway.  Conclusions: This study demonstrates that an elevated expression of BMP-4 can transform colon cancer cells to become more invasive and Smad4 is dispensable for this process. Microarray analysis reveals that several known BMP-target genes can be activated by BMP-4 through non-canonical pathways.
Can we cure patients with abdominal desmoplastic small round cell tumor? Results of a retrospective multicentric study on 100 patients
Authors: J.-B. Delhorme, E. Nassif, G. Ferron, E. Bompas, J. Adam, O. Glehen, A. Italiano, F. Bertucci, D. Orbach, A. Le Cesne, J.Y. Blay, C.M. Chevreau, O. Mir, C. Honoré
Journal: Annals of Oncology (2018)
Treatment of Severe Hailey-Hailey Disease With Apremilast
Authors: Julie Kieffer, Florence Le Duff, Henri Montaudié, Christine Chiaverini, Jean-Philippe Lacour, Thierry Passeron
Journal: JAMA Dermatology (2018)

Hailey-Hailey disease (HHD) is a rare, autosomal-dominant acantholytic dermatosis characterized clinically by development of recurrent blisters and erosions in friction areas. Despite progression in our understanding of the molecular genetics of HHD, therapy remains suboptimal and there is no known cure.To determine whether the novel phosphodiesterase-4 inhibitor apremilast is effective in the treatment of HHD.Clinical case series of 4 patients with severe, treatment-resistant HHD at an outpatient clinic in the Department of Dermatology of Nice University Hospital, Nice, France. The patients were treated with apremilast; after the initial titration, the dose was 30 mg, twice daily.Objective clinical response was assessed by the treating dermatologist using the physician global assessment score; recorded adverse effects were monitored throughout the treatment at intervals of 2 to 3 months.Three women and 1 man, with a mean age of 56 years, were treated and followed up for 6 to 10 months. Family history of the disease was noted in 3 (75%) of the cases. The lesions affected the axillary regions (75%), submammary regions (75%), inguinal regions (100%), and back and neck areas (50%). An improvement in the symptoms was reported by all of the patients after a treatment period of 1 month. After 6 months, the improvement of HHD lesions was reported as moderate to almost cleared among the patients. However, 2 patients developed some flares after 6 to 10 months of treatment and stopped apremilast therapy. One of the patients developed uncontrolled diffuse lesions and apremilast was reintroduced, resulting in partial control of her disease.Apremilast appears to offer a low-risk therapeutic alternative or adjunct in resistant and severe forms of HHD. A prospective controlled trial with long-term follow-up is required to confirm these preliminary observations.
Relapse after complete response in newly diagnosed multiple myeloma: implications of duration of response and patterns of relapse
Authors: Surbhi Sidana, Nidhi Tandon, Angela Dispenzieri, Morie A. Gertz, Francis K. Buadi, Martha Q. Lacy, David Dingli, Amie L. Fonder, Suzanne R. Hayman, Miriam A. Hobbs, Wilson I. Gonsalves, Rahma M. Warsame, Taxiarchis Kourelis, Yi Lisa Hwa, Prashant Kapoor, Robert A. Kyle, Nelson Leung, Ronald S. Go, S. Vincent Rajkumar, Shaji K. Kumar
Journal: Leukemia (2018)
Publisher Correction: Robust prediction of response to immune checkpoint blockade therapy in metastatic melanoma
Authors: Noam Auslander, Gao Zhang, Joo Sang Lee, Dennie T. Frederick, Benchun Miao, Tabea Moll, Tian Tian, Zhi Wei, Sanna Madan, Ryan J. Sullivan, Genevieve Boland, Keith Flaherty, Meenhard Herlyn, Eytan Ruppin
Journal: Nature Medicine (2018)
Effect of Evolocumab on Coronary Plaque Composition
Authors: Stephen J. Nicholls, Rishi Puri, Todd Anderson, Christie M. Ballantyne, Leslie Cho, John J.P. Kastelein, Wolfgang Koenig, Ransi Somaratne, Helina Kassahun, Jingyuan Yang, Scott M. Wasserman, Satoshi Honda, Daisuke Shishikura, Daniel J. Scherer, Marilyn Borgman, Danielle M. Brennan, Kathy Wolski, Steven E. Nissen
Journal: Journal of the American College of Cardiology (2018)
Germline loss-of-function SAMD9 and SAMD9L alterations in adult myelodysplastic syndromes
Authors: Yasunobu Nagata, Satoshi Narumi, Yihong Guan, Bartlomiej P. Przychodzen, Cassandra M. Hirsch, Hideki Makishima, Hirohito Shima, Mai Aly, Victor Pastor, Teodora Kuzmanovic, Tomas Radivoyevitch, Vera Adema, Hassan Awada, Kenichi Yoshida, Samuel Li, Francesc Sole, Rabi Hanna, Babal K. Jha, Thomas LaFramboise, Seishi Ogawa, Mikkael A. Sekeres, Marcin W. Wlodarski, Jörg Cammenga, Jaroslaw P. Maciejewski
Journal: Blood (2018)
Frequency and clinical impact of compound mutation in chronic myeloid leukemia patients resistant to tyrosine kinase inhibitor
Authors: S. Bonecker, M. Carneiro, M. Bonamino, I. Zalcberg
Journal: Annals of Oncology (2018)

Background: Chronic myeloid leukemia is characterized by onco-protein BCR-ABL1 which is constitutively activated. This particularity allowed the development of the first specific tyrosine kinase inhibitor (TKI) which changed the course of this disease. However, resistance to TKI is still a growing clinical problem. The canonical mechanism of resistance is point mutation in ABL1 kinase domain (KD). After the introduction of second and third TKI, the presence of multiple mutations was grown and the clinical importance is still controversial. Methods: We included 21 resistant patients with two BCR-ABL1 KD mutations detected by direct sequencing. 43% failed to two therapies, 8 to three and 4 failed only to imatinib. For two patients we had sequential samples. We cloned ABL1 region and sequenced minimum of 10 clones. In order to evaluate the frequency of false compound mutation we cloned sample with only T315I mutation, other with F317L and 1:1 dilution of both samples. Results: We observed that 66.7% of double mutations detected by direct sequencing were compound mutations. Our ratio of false positive compound mutation was 9%. T315I plus other mutation was the most frequently compound mutation in our cohort. Patients who failed to more than one TKI had higher frequency of compound mutation. Analyzing sequential samples we observed mutated clones in samples up to 5 months earlier than direct sequencing. The frequency of clones harboring compound mutations with more than two missense mutations was low (6%), comparing with silent mutations, suggesting a limited tolerance for BCR-ABL1 KD missense mutations. The number of transition was higher than transversion. Among patients with compound mutations: 5/7 progressed to advanced phases presented compound mutation, 1/2 died, 5/8 achieved molecular response (MR) during second or third line therapy and 3/4 did not achieve MR (median follow up 26 months). Conclusions: We did not find correlation between presence of compound mutation and probability to respond therapy or progression. Analyze higher number of sample is needed. Indeed, the importance to detect clones harboring high resistance mutation such T315I earlier could help the clinician to choose the therapy to avoid clone progression. Legal entity responsible for the study: Instituto Nacional do Câncer. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Determinants of Intensive Care Unit Telemedicine Effectiveness. An Ethnographic Study
Authors: Jeremy M. Kahn, Kimberly J. Rak, Courtney C. Kuza, Laura Ellen Ashcraft, Amber E. Barnato, Jessica C. Fleck, Tina B. Hershey, Marilyn Hravnak, Derek C. Angus
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Rationale: Telemedicine is an increasingly common care delivery strategy in the ICU. However, ICU telemedicine programs vary widely in their clinical effectiveness, with some studies showing a large mortality benefit and others showing no benefit or even harm.Objectives: To identify the organizational factors associated with ICU telemedicine effectiveness.Methods: We performed a focused ethnographic evaluation of 10 ICU telemedicine programs using site visits, interviews, and focus groups in both facilities providing remote care and the target ICUs. Programs were selected based on their change in risk-adjusted mortality after adoption (decreased mortality, no change in mortality, and increased mortality). We used a constant comparative approach to guide data collection and analysis.Measurements and Main Results: We conducted 460 hours of direct observation, 222 interviews, and 18 focus groups across six telemedicine facilities and 10 target ICUs. Data analysis revealed three domains that influence ICU telemedicine effectiveness: 1) leadership (i.e., the decisions related to the role of the telemedicine, conflict resolution, and relationship building), 2) perceived value (i.e., expectations of availability and impact, staff satisfaction, and understanding of operations), and 3) organizational characteristics (i.e., staffing models, allowed involvement of the telemedicine unit, and new hire orientation). In the most effective telemedicine programs these factors led to services that are viewed as appropriate, integrated, responsive, and consistent.Conclusions: The effectiveness of ICU telemedicine programs may be influenced by several potentially modifiable factors within the domains of leadership, perceived value, and organizational structure.