tbuckley/cabot-search huggingface dataset:
Thermophilic Adaptation in Prokaryotes Is Constrained by Metabolic Costs of Proteostasis
Authors: Sergey V Venev, Konstantin B Zeldovich
Journal: Molecular Biology and Evolution (2017)

Prokaryotes evolved to thrive in an extremely diverse set of habitats, and their proteomes bear signatures of environmental conditions. Although correlations between amino acid usage and environmental temperature are well-documented, understanding of the mechanisms of thermal adaptation remains incomplete. Here, we couple the energetic costs of protein folding and protein homeostasis to build a microscopic model explaining both the overall amino acid composition and its temperature trends. Low biosynthesis costs lead to low diversity of physical interactions between amino acid residues, which in turn makes proteins less stable and drives up chaperone activity to maintain appropriate levels of folded, functional proteins. Assuming that the cost of chaperone activity is proportional to the fraction of unfolded client proteins, we simulated thermal adaptation of model proteins subject to minimization of the total cost of amino acid synthesis and chaperone activity. For the first time, we predicted both the proteome-average amino acid abundances and their temperature trends simultaneously, and found strong correlations between model predictions and 402 genomes of bacteria and archaea. The energetic constraint on protein evolution is more apparent in highly expressed proteins, selected by codon adaptation index. We found that in bacteria, highly expressed proteins are similar in composition to thermophilic ones, whereas in archaea no correlation between predicted expression level and thermostability was observed. At the same time, thermal adaptations of highly expressed proteins in bacteria and archaea are nearly identical, suggesting that universal energetic constraints prevail over the phylogenetic differences between these domains of life.
TCT-439 Trans-Apical Aortic Valve Replacement in Patients with History of Coronary Artery Bypass Grafting Surgery: An Analysis of the National Inpatient Sample Database
Authors: Konstantinos Voudris, Dmitriy Feldman, Robert Minutello, Luke Kim, Konstantinos Charitakis, Harsimran Singh, Geoffrey Bergman, Arash Salemi, S. Chiu Wong
Journal: Journal of the American College of Cardiology (2017)
A novel pretherapeutic gene expression-based risk score for treatment guidance in gastric cancer
Authors: L. Bauer, A. Hapfelmeier, S. Blank, M. Reiche, J. Slotta-Huspenina, M. Jesinghaus, A. Novotny, T. Schmidt, B. Grosser, M. Kohlruss, W. Weichert, K. Ott, G. Keller
Journal: Annals of Oncology (2017)
CRISPR Genome Engineering for Human Pluripotent Stem Cell Research
Authors: Somali Chaterji, Eun Hyun Ahn, Deok-Ho Kim
Journal: Theranostics (2017)

The emergence of targeted and efficient genome editing technologies, such as repurposed bacterial programmable nucleases (e.g., CRISPR-Cas systems), has abetted the development of cell engineering approaches.Lessons learned from the development of RNA-interference (RNA-i) therapies can spur the translation of genome editing, such as those enabling the translation of human pluripotent stem cell engineering.In this review, we discuss the opportunities and the challenges of repurposing bacterial nucleases for genome editing, while appreciating their roles, primarily at the epigenomic granularity.First, we discuss the evolution of high-precision, genome editing technologies, highlighting CRISPR-Cas9.They exist in the form of programmable nucleases, engineered with sequence-specific localizing domains, and with the ability to revolutionize human stem cell technologies through precision targeting with greater on-target activities.Next, we highlight the major challenges that need to be met prior to bench-to-bedside translation, often learning from the path-to-clinic of complementary technologies, such as RNA-i.Finally, we suggest potential bioinformatics developments and CRISPR delivery vehicles that can be deployed to circumvent some of the challenges confronting genome editing technologies en route to the clinic.
The current status and problems of an educational class for pancreatic cancer patients - a palliative CTx and QOL -
Authors: Masami Yamada, Suetumi Okagaki, Tomoe Sasada, Yuko So, Yukio Kadokawa, Masaharu Shima, Ryoji Takada, Tatuya Ioka, Kazuhiro Katayama, Masato Sakon
Journal: Annals of Oncology (2017)
A sentimental education: The place of sentiments in personality and social psychology
Authors: Nick Haslam
Journal: Behavioral and Brain Sciences (2017)

Abstract “Sentiment” is a potentially appealing concept for social and personality psychologists. It can render some complex affective phenomena theoretically tractable, help refine accounts of social perception, and illuminate some personality dispositions. The success of a future sentimental psychology depends on whether “sentiment” can be delimited as a distinct domain, and whether a credible classification of sentiments can be developed.
Recomendaciones europeas para el manejo del personal sanitario expuesto a los virus de la Hepatitis B (VHB) y C (VHC)
Authors: V Puro, G De Carli, S Cicalini, F Soldani, U Balslev, J Begovac, L Boaventura, M Campins Marti, M J Hernández Navarrete, R Kammerlander, C Larsen, F Lot, S Lunding, U Marcus, L Payne, A A Pereira, T Thomas, G Ippolito
Journal: Eurosurveillance (2005)

La prevencion de la exposicion es la estrategia mas eficaz para la reduccion del riesgo de infecciones ocupacionales transmitidas por via sanguinea en personal sanitario. Los profesionales sanitarios tambien deberian estar sensibilizados de la importancia en terminos medicolegales y clinicos de declarar cualquier exposicion, asi como tener acceso a expertos para recibir los consejos, la atencion y el control adecuados. 
Se recomienda especialmente la vacunacion contra el virus de la Hepatitis B (VHB) y una prueba de esta inmunizacion antes de la contratacion laboral. El personal sanitario con niveles de anticuerpos anti-VHB post vacunales g10 mUI/mL, 1-2 meses despues de ser administrada la vacuna, se consideran como respondedores, estando protegidos contra la infeccion por el VHB. Por eso en estos trabajadores no se aconsejan las dosis de refuerzo o el despistaje periodico de la concentracion de anticuerpos. Se deberian adoptar estrategias alternativas para vencer la no-respuesta. 
Los profesionales sanitarios anti-HBc positivos tendrian que hacer pruebas para los niveles de IgM anti-HBc y de ADN-VHB: si estos son negativos, la respuesta anti-HBs a la vacuna puede diferenciar una infeccion antigua (anti-HBs g 50 mUI/ml 30 dias tras la primera dosis de vacuna: respuesta anamnesica) o falsos resultados positivos (anti-HBs g 10 mUI/ml 30 dias tras la tercera dosis: respuesta primaria): los pacientes verdaderamente positivos resisten a una re-infeccion. 
La gestion de la exposicion ocupacional al VHB depende de la susceptibilidad del personal expuesto y del estatus serologico de la fuente. En el caso de que fuera necesario, debe iniciarse lo antes posible la profilaxis post-exposicion con la vacuna anti-VHB, las inmunoglobinas de la hepatitis B o ambos (dentro de los siete primeros dias). 
En ausencia de profilaxis contra el virus de la hepatitis C (VHC), la gestion del seguimiento de las exposiciones al VHC depende de si se decidio aplicar un tratamiento antiviral durante la fase aguda. Se tendrian que realizar pruebas de anticuerpos VHC en los profesionales sanitarios, a niveles basales y a los 6 meses; y de nuevo a los 12 meses para las fuentes de coinfeccion VIH-VHC. En el caso de recomendarse un tratamiento, hay que realizar la prueba de actividad de ALT (alanina aminotransferasa) a nivel basal y cada mes durante los cuatro meses siguientes a la exposicion y el ARN-VHC cualitativo cuando se detecte un aumento.
Homologous Recombination DNA Repair Pathway Disruption and Retinoblastoma Protein Loss Are Associated with Exceptional Survival in High-Grade Serous Ovarian Cancer
Authors: Dale W. Garsed, Kathryn Alsop, Sian Fereday, Catherine Emmanuel, Catherine J. Kennedy, Dariush Etemadmoghadam, Bo Gao, Val Gebski, Valérie Garès, Elizabeth L. Christie, Maartje C.A. Wouters, Katy Milne, Joshy George, Ann-Marie Patch, Jason Li, Gisela Mir Arnau, Timothy Semple, Sreeja R. Gadipally, Yoke-Eng Chiew, Joy Hendley, Thomas Mikeska, Giada V. Zapparoli, Kaushalya Amarasinghe, Sean M. Grimmond, John V. Pearson, Nicola Waddell, Jillian Hung, Colin J.R. Stewart, Raghwa Sharma, Prue E. Allan, Peter F. Rambau, Orla McNally, Linda Mileshkin, Anne Hamilton, Sumitra Ananda, Marisa Grossi, Paul A. Cohen, Yee C. Leung, Robert M. Rome, Philip Beale, Penny Blomfield, Michael Friedlander, Alison Brand, Alexander Dobrovic, Martin Köbel, Paul Harnett, Brad H. Nelson, David D. L. Bowtell, Anna deFazio
Journal: Clinical Cancer Research (2017)

Abstract Purpose: Women with epithelial ovarian cancer generally have a poor prognosis; however, a subset of patients has an unexpected dramatic and durable response to treatment. We sought to identify clinical, pathological, and molecular determinants of exceptional survival in women with high-grade serous cancer (HGSC), a disease associated with the majority of ovarian cancer deaths. Experimental Design: We evaluated the histories of 2,283 ovarian cancer patients and, after applying stringent clinical and pathological selection criteria, identified 96 with HGSC that represented significant outliers in terms of treatment response and overall survival. Patient samples were characterized immunohistochemically and by genome sequencing. Results: Different patterns of clinical response were seen: long progression-free survival (Long-PFS), multiple objective responses to chemotherapy (Multiple Responder), and/or greater than 10-year overall survival (Long-Term Survivors). Pathogenic germline and somatic mutations in genes involved in homologous recombination (HR) repair were enriched in all three groups relative to a population-based series. However, 29% of 10-year survivors lacked an identifiable HR pathway alteration, and tumors from these patients had increased Ki-67 staining. CD8+ tumor-infiltrating lymphocytes were more commonly present in Long-Term Survivors. RB1 loss was associated with long progression-free and overall survival. HR deficiency and RB1 loss were correlated, and co-occurrence was significantly associated with prolonged survival. Conclusions: There was diversity in the clinical trajectory of exceptional survivors associated with multiple molecular determinants of exceptional outcome in HGSC patients. Concurrent HR deficiency and RB1 loss were associated with favorable outcomes, suggesting that co-occurrence of specific mutations might mediate durable responses in such patients. Clin Cancer Res; 24(3); 569–80. ©2017 AACR. See related commentary by Peng and Mills, p. 508
An Unexpected and Less Recognized Altered Distribution on Bone Scintigraphy; Possibility of 99mTc-Dextrose Complex as a Cause
Authors: Mohsen Qutbi, Babak Shafiei, Sepideh Khoshbakht, Ali Asadi, Isa Neshandar Asli
Journal: Clinical Nuclear Medicine (2017)

Optimal performance of diagnostic tests and correct interpretation depend on multiple factors, one of which is proper radiopharmaceutical preparation. Unwanted impurities result in altered distribution of radiopharmaceuticals and then poor-quality or uninterpretable studies. Therefore, following the reconstitution steps according to standard and validated protocols by the technologist is mandatory. Here, we present 2 cases with unexpected and less recognized distribution of Tc-methylene diphosphonate on bone scintigraphy.
The frequency of febrile neutropenia in Japanese patients with breast cancer received perioperative chemotherapy
Authors: Keisuke Miwa, Miki Yamaguchi, Hiroko Otsuka, Goichi Nakayama, Haruhiro Hino, Shiro Kibe, Naotaka Murakami, Kazuo Shirouzu, Yoshito Akagi, Maki Tanaka
Journal: Annals of Oncology (2017)
Response to Loss-of-Function Mutation in Tryptophan Hydroxylase-2 Identified in Unipolar Major Depression. Neuron 45, 11–16
Authors: Zhifeng Zhou, Eric J. Peters, Steven P. Hamilton, Francis McMahon, Christee Thomas, Patrick J. McGrath, John Rush, Madhukar H. Trivedi, Dennis S. Charney, Alec Roy, Stephen Wisniewski, Robert Lipsky, David Goldman
Journal: Neuron (2005)
E-Cigarettes: Use, Effects on Smoking, Risks, and Policy Implications
Authors: Stanton A. Glantz, David W. Bareham
Journal: Annual Review of Public Health (2018)

Since e-cigarettes appeared in the mid-2000s, some practitioners, researchers, and policy makers have embraced them as a safer alternative to conventional cigarettes and an effective way to stop smoking. While e-cigarettes deliver lower levels of carcinogens than do conventional cigarettes, they still expose users to high levels of ultrafine particles and other toxins that may substantially increase cardiovascular and noncancer lung disease risks, which account for more than half of all smoking-caused deaths, at rates similar to conventional cigarettes. Moreover, rather than stimulating smokers to switch from conventional cigarettes to less dangerous e-cigarettes or quitting altogether, e-cigarettes are reducing smoking cessation rates and expanding the nicotine market by attracting youth.
Dysregulated Expression of the MicroRNA miR-137 and Its Target YBX1 Contribute to the Invasive Characteristics of Malignant Pleural Mesothelioma
Authors: Thomas G. Johnson, Karin Schelch, Yuen Y. Cheng, Marissa Williams, Kadir H. Sarun, Michaela B. Kirschner, Steven Kao, Anthony Linton, Sonja Klebe, Brian C. McCaughan, Ruby C.Y. Lin, Christine Pirker, Walter Berger, Annette Lasham, Nico van Zandwijk, Glen Reid
Journal: Journal of Thoracic Oncology (2017)

Malignant pleural mesothelioma (MPM) is an aggressive malignancy linked to asbestos exposure. On a genomic level, MPM is characterized by frequent chromosomal deletions of tumor suppressors, including microRNAs. MiR-137 plays a tumor suppressor role in other cancers, so the aim of this study was to characterize it and its target Y-box binding protein 1 (YBX1) in MPM.Expression, methylation, and copy number status of miR-137 and its host gene MIR137HG were assessed by polymerase chain reaction. Luciferase reporter assays confirmed a direct interaction between miR-137 and Y-box binding protein 1 gene (YBX1). Cells were transfected with a miR-137 inhibitor, miR-137 mimic, and/or YBX1 small interfering RNA, and growth, colony formation, migration and invasion assays were conducted.MiR-137 expression varied among MPM cell lines and tissue specimens, which was associated with copy number variation and promoter hypermethylation. High miR-137 expression was linked to poor patient survival. The miR-137 inhibitor did not affect target levels or growth, but interestingly, it increased miR-137 levels by means of mimic transfection suppressed growth, migration, and invasion, which was linked to direct YBX1 downregulation. YBX1 was overexpressed in MPM cell lines and inversely correlated with miR-137. RNA interference-mediated YBX1 knockdown significantly reduced cell growth, migration, and invasion.MiR-137 can exhibit a tumor-suppressive function in MPM by targeting YBX1. YBX1 knockdown significantly reduces tumor growth, migration, and invasion of MPM cells. Therefore, YBX1 represents a potential target for novel MPM treatment strategies.
“Job Lock” Among Long-term Survivors of Childhood Cancer
Authors: Anne C. Kirchhoff, Ryan Nipp, Echo L. Warner, Karen Kuhlthau, Wendy M. Leisenring, Karen Donelan, Julia Rabin, Giselle K. Perez, Kevin C. Oeffinger, Paul C. Nathan, Leslie L. Robison, Gregory T. Armstrong, Elyse R. Park
Journal: JAMA Oncology (2017)

Childhood cancer survivors may be reluctant to make changes in their employment because of access to health insurance.To examine the prevalence of "job lock" (staying at a job to keep work-related health insurance) in a sample drawn from an established, multi-institutional cohort of full-time employed childhood cancer survivors compared with a random sample of siblings and to explore factors associated with job lock among cancer survivors.Cross-sectional survey of full-time employed adult survivors of childhood cancer and a random sample of siblings derived from a cohort of 25 US pediatric oncology centers.Data collection included sociodemographic factors, insurance coverage, chronic medical conditions, and treatment.Self-report of job lock and factors associated with job lock.Among the 522 participants, 394 were cancer survivors (54.5% male) and 128 were siblings (51.5% male). Job lock was reported by 23.2% (95% CI, 18.9%-28.1%) of survivors, compared with 16.9% (95% CI, 11.1%-25.0%) of siblings (P = .16). Job lock was more common among survivors reporting previous health insurance denial (relative risk [RR], 1.60; 95% CI, 1.03-2.52) and problems paying medical bills (RR, 2.43; 95% CI, 1.56-3.80). Among survivors, being female (RR, 1.70; 95% CI, 1.11-2.59; P = .01) and having a severe, disabling, or life-threatening health condition (RR, 1.72; 95% CI, 1.09-2.69; P = .02) were associated with job lock.Job lock is common among long-term childhood cancer survivors who are employed full-time. A survivor's decision to remain employed at a job in order to maintain health insurance coverage may affect career trajectory, diminish potential earning power, and ultimately impact quality of life.
Osseointegrated Implants: Strategies for Optimizing the Soft Tissue Seal around Osseointegrated Implants (Adv. Healthcare Mater. 20/2017)
Authors: Mohamed‐Nur Abdallah, Zahi Badran, Ovidiu Ciobanu, Nader Hamdan, Faleh Tamimi
Journal: Advanced Healthcare Materials (2017)

Establishing a strong soft tissue seal around bone-anchored implants, such as orthopedic and dental implants, is critical for preventing bacterial infections and enhancing their long-term success. The recent findings and challenges concerning the establishment of such a strong soft tissue attachment are reviewed by Mohamed-Nur Abdallah, Zahi Badran, Ovidiu Ciobanu, Nader Hamdan, and Faleh Tamimi in article number 1700549.
Is there a correlation between coaches’ leadership styles and injuries in elite football teams? A study of 36 elite teams in 17 countries
Authors: Jan Ekstrand, Daniel Lundqvist, Lars Lagerbäck, Marc Vouillamoz, Niki Papadimitiou, Jon Karlsson
Journal: British Journal of Sports Medicine (2017)

Do coaches' leadership styles affect injury rates and the availability of players in professional football? Certain types of leadership behaviour may cause stress and have a negative impact on players' health and well-being.To investigate the transformational leadership styles of head coaches in elite men's football and to evaluate the correlation between leadership styles, injury rates and players' availability.Medical staff from 36 elite football clubs in 17 European countries produced 77 reports at four postseason meetings with a view to assessing their perception of the type of leadership exhibited by the head coaches of their respective teams using the Global Transformational Leadership scale. At the same time, they also recorded details of individual players' exposure to football and time-loss injuries.There was a negative correlation between the overall level of transformational leadership and the incidence of severe injuries (rho=-0.248; n=77; p=0.030); high levels of transformational leadership were associated with smaller numbers of severe injuries. Global Transformational Leadership only explained 6% of variation in the incidence of severe injuries (r2=0.062). The incidence of severe injuries was lower at clubs where coaches communicated a clear and positive vision, supported staff members and gave players encouragement and recognition. Players' attendance rates at training were higher in teams where coaches gave encouragement and recognition to staff members, encouraged innovative thinking, fostered trust and cooperation and acted as role models.There is an association between injury rates and players' availability and the leadership style of the head coach.
Intraoperative clonidine for prevention of postoperative agitation in children anaesthetised with sevoflurane (PREVENT AGITATION): a randomised, placebo-controlled, double-blind trial
Authors: Mogens Ydemann, Bettina Nygaard Nielsen, Steen Henneberg, Janus Christian Jakobsen, Jørn Wetterslev, Torsten Lauritsen, Nick Steen, Birgitte Edstrøm, Arash Afshari, Solveig Bruun, Bende Burgdorf, Susanne Born Christensen, Marguerite Ellekvist, Lars Falcon, Louise Salling Goth, Kim Vinther Gullaksen, Øivind Jans, Mona Kildahl Jensen, Mathias Johansen, Kirsten Knage, Troels Haxholdt Lunn, Frederik Mondrup, Mark Niegsch, Isabell Nielsen, Sidsel Reinhardt
Journal: The Lancet Child & Adolescent Health (2017)
Taxane Followed by Anthracycline or Vice Versa: Impact of Sequential Order on Breast Cancer Recurrence?
Authors: Kadri Altundag
Journal: JAMA Oncology (2017)

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The human lncRNA LINC-PINT inhibits tumor cell invasion through a highly conserved sequence element
Authors: Oskar Marín-Béjar, Aina M. Mas, Jovanna González, Dannys Martinez, Alejandro Athie, Xabier Morales, Mikel Galduroz, Ivan Raimondi, Elena Grossi, Shuling Guo, Ana Rouzaut, Igor Ulitsky, Maite Huarte
Journal: Genome biology (2017)

It is now obvious that the majority of cellular transcripts do not code for proteins, and a significant subset of them are long non-coding RNAs (lncRNAs). Many lncRNAs show aberrant expression in cancer, and some of them have been linked to cell transformation. However, the underlying mechanisms remain poorly understood and it is unknown how the sequences of lncRNA dictate their function. Here we characterize the function of the p53-regulated human lncRNA LINC-PINT in cancer. We find that LINC-PINT is downregulated in multiple types of cancer and acts as a tumor suppressor lncRNA by reducing the invasive phenotype of cancer cells. A cross-species analysis identifies a highly conserved sequence element in LINC-PINT that is essential for its function. This sequence mediates a specific interaction with PRC2, necessary for the LINC-PINT-dependent repression of a pro-invasion signature of genes regulated by the transcription factor EGR1. Our findings support a conserved functional co-dependence between LINC-PINT and PRC2 and lead us to propose a new mechanism where the lncRNA regulates the availability of free PRC2 at the proximity of co-regulated genomic loci.