tbuckley/cabot-search huggingface dataset:
Effectiveness of interventions to support the early detection of skin cancer through skin self‐examination: a systematic review and meta‐analysis
Authors: S.J. Ersser, A. Effah, J. Dyson, I. Kellar, S. Thomas, E. McNichol, E. Caperon, C. Hewitt, A.J. Muinonen‐Martin
Journal: British Journal of Dermatology (2018)

As skin cancer incidence rises, there is a need to evaluate early detection interventions by the public using skin self-examination (SSE); however, the literature focuses on primary prevention. No systematic reviews have evaluated the effectiveness of such SSE interventions.To systematically examine, map, appraise and synthesize, qualitatively and quantitatively, studies evaluating the early detection of skin cancer, using SSE interventions.This is a systematic review (narrative synthesis and meta-analysis) examining randomized controlled trials (RCTs) and quasiexperimental, observational and qualitative studies, published in English, using PRISMA and National Institute for Health and Care Excellence guidance. The MEDLINE, Embase and PsycINFO databases were searched through to April 2015 (updated in April 2018 using MEDLINE). Risk-of-bias assessment was conducted.Included studies (n = 18), totalling 6836 participants, were derived from 22 papers; these included 12 RCTs and five quasiexperiments and one complex-intervention development. More studies (n = 10) focused on targeting high-risk groups (surveillance) than those at no higher risk (screening) (n = 8). Ten (45%) study interventions were theoretically underpinned. All of the study outcomes were self-reported, behaviour related and nonclinical in nature. Meta-analysis demonstrated the impact of the intervention on the degree of SSE activity from five studies, especially in the short term (up to 4 months) (odds ratio 2·31, 95% confidence interval 1·90-2·82), but with small effect sizes. Risk-of-bias assessment indicated that 61% of the studies (n = 11) were of weak quality.Four RCTs and a quasiexperimental study indicate that some interventions can enhance SSE activity and so are more likely to aid early detection of skin cancer. However, the actual clinical impact remains unclear, and this is based on overall weak study (evidence) quality.
IDPoor: a poverty identification programme that enables collaboration across sectors for maternal and child health in Cambodia
Authors: Mary White Kaba, Klaus Baesel, Bunnak Poch, Samnang Bun, Sabine Cerceau, Louise Bury, Bastian Schwarz, Ouly Keo, Rathavy Tung, Kannitha Cheang, Kumanan Rasanathan
Journal: BMJ (2018)

<b>Mary White Kaba and colleagues</b> describe how Cambodia's national poverty identification system, IDPoor, has provided a nexus for different sectors' contributions to maternal and child health among the poor
Assessment of Instruments for Measurement of Delirium Severity
Authors: Richard N. Jones, Sevdenur Cizginer, Laura Pavlech, Asha Albuquerque, Lori A. Daiello, Kumar Dharmarajan, Lauren J. Gleason, Benjamin Helfand, Lauren Massimo, Esther Oh, Olivia I. Okereke, Patricia Tabloski, Laura A. Rabin, Jirong Yue, Edward R. Marcantonio, Tamara G. Fong, Tammy T. Hshieh, Eran D. Metzger, Kristen Erickson, Eva M. Schmitt, Sharon K. Inouye
Journal: JAMA Internal Medicine (2018)

Measurement of delirium severity has been recognized as highly important for tracking prognosis, monitoring response to treatment, and estimating burden of care for patients both during and after hospitalization. Rather than simply rating delirium as present or absent, the ability to quantify its severity would enable development and monitoring of more effective treatment approaches for the condition. To present a comprehensive review of delirium severity instruments, conduct a methodologic quality rating of the original validation study of the most commonly used instruments, and select a group of top-rated instruments. This systematic review was conducted using literature from Embase, PsycINFO, PubMed, Web of Science, and Cumulative Index to Nursing and Allied Health Literature, from January 1, 1974, through March 31, 2017, with the key words delirium, severity, tests, measures, and intensity. Inclusion criteria were original articles assessing delirium severity and using a delirium-specific severity instrument. Final listings of articles were supplemented with hand searches of reference listings to ensure completeness. At least 2 reviewers independently completed each step of the review process: article selection, data extraction, and methodologic quality assessment of relevant articles using a validated rating scale. All discrepancies between raters were resolved by consensus. Of 9409 articles identified, 228 underwent full text review, and we identified 42 different instruments of delirium severity. Eleven of the 42 tools were multidomain, delirium-specific instruments providing a quantitative rating of delirium severity; these instruments underwent a methodologic quality review. Applying prespecified criteria related to frequency of use, methodologic quality, construct or predictive validity, and broad domain coverage, an expert panel used an iterative modified Delphi process to select 6 final high-quality instruments meeting these criteria: the Confusion Assessment Method-Severity Score, Confusional State Examination, Delirium-O-Meter, Delirium Observation Scale, Delirium Rating Scale, and Memorial Delirium Assessment Scale. The 6 instruments identified may enable accurate measurement of delirium severity to improve clinical care for patients with this condition. This work may stimulate increased usage and head-to-head comparison of these instruments.
Abstract 15364: Application of an Enhanced Device to Transluminal Retrieval of Malappositioned Coronary Stents
Authors: Masayuki Mori, Kenji Sakata, Junichiro Yokawa, Chiaki Nakanishi, Hirofumi Okada, Masaya Shimojima, Shohei Yoshida, Tsuyoshi Yoshimuta, Masa-aki Kawashiri, Kenshi Hayashi, Masakazu Yamagishi
Journal: Circulation (2017)

Introduction: Recurrence of in-stent restenosis and stent thrombosis still remains to be resolved. Under these conditions, it is sometimes necessary to retrieve malfunctional stents responsible for...
Loss of Endothelium-Derived Wnt5a Is Associated With Reduced Pericyte Recruitment and Small Vessel Loss in Pulmonary Arterial Hypertension
Authors: Ke Yuan, Elya A. Shamskhou, Mark E. Orcholski, Abinaya Nathan, Sushma Reddy, Hiroaki Honda, Vigneshwaran Mani, Yitian Zeng, Mehmet O. Ozen, Lingli Wang, Utkan Demirci, Wen Tian, Mark R. Nicolls, Vinicio A. de Jesus Perez
Journal: Circulation (2019)

Pulmonary arterial hypertension (PAH) is a life-threatening disorder of the pulmonary circulation associated with loss and impaired regeneration of microvessels. Reduced pericyte coverage of pulmonary microvessels is a pathological feature of PAH and is caused partly by the inability of pericytes to respond to signaling cues from neighboring pulmonary microvascular endothelial cells (PMVECs). We have shown that activation of the Wnt/planar cell polarity pathway is required for pericyte recruitment, but whether production and release of specific Wnt ligands by PMVECs are responsible for Wnt/planar cell polarity activation in pericytes is unknown.Isolation of pericytes and PMVECs from healthy donor and PAH lungs was carried out with 3G5 or CD31 antibody-conjugated magnetic beads. Wnt expression profile of PMVECs was documented via quantitative polymerase chain reaction with a Wnt primer library. Exosome purification from PMVEC media was carried out with the ExoTIC device. Hemodynamic profile, right ventricular function, and pulmonary vascular morphometry were obtained in a conditional endothelium-specific Wnt5a knockout ( Wnt5aECKO) mouse model under normoxia, chronic hypoxia, and hypoxia recovery.Quantification of Wnt ligand expression in healthy PMVECs cocultured with pericytes demonstrated a 35-fold increase in Wnt5a, a known Wnt/planar cell polarity ligand. This Wnt5a spike was not seen in PAH PMVECs, which correlated with an inability to recruit pericytes in Matrigel coculture assays. Exosomes purified from media demonstrated an increase in Wnt5a content when healthy PMVECs were cocultured with pericytes, a finding that was not observed in exosomes of PAH PMVECs. Furthermore, the addition of either recombinant Wnt5a or purified healthy PMVEC exosomes increased pericyte recruitment to PAH PMVECs in coculture studies. Although no differences were noted in normoxia and chronic hypoxia, Wnt5aECKO mice demonstrated persistent pulmonary hypertension and right ventricular failure 4 weeks after recovery from chronic hypoxia, which correlated with significant reduction, muscularization, and decreased pericyte coverage of microvessels.We identify Wnt5a as a key mediator for the establishment of pulmonary endothelium-pericyte interactions, and its loss could contribute to PAH by reducing the viability of newly formed vessels. We speculate that therapies that mimic or restore Wnt5a production could help prevent loss of small vessels in PAH.
Abstract 17545: Vasoconstriction During Mental Stress Predicts Severity of Mental Stress Induced Myocardial Ischemia
Authors: Nino Isakadze, Ayman Alkhoder, Arshed A Quyyumi, Viola Vaccarino, J. Douglas Bremner, Ernest Garcia, Jonathon Nye, Kobina Wilmont, Ibhar A Mheid, Paolo Raggi, Michael Kutner, Malik Obideen, Naser Abdelhadi, Amit Shah
Journal: Circulation (2015)

Background: Evidence supports that peripheral vasoconstriction during mental stress predicts mental stress induced ischemia (MSIMI). However, whether a dose response relationship exists with ischemia severity has not been evaluated; additionally, whether peripheral vascular function during the recovery phase is also related to MSIMI is not known. Hypothesis: We hypothesized that increased digital microvascular constriction during both mental stress and recovery are predictive of increased severity of mental stress ischemia. Methods: We evaluated 204 patients with stable CAD with high quality vascular data using a standardized mental stress test using a public speaking task. Peripheral artery tonometry (PAT) (Itamar Inc) was used to assess digital microvascular tone. Vasoconstriction was calculated as the ratio of pulse wave amplitude during speech/recovery and the last 3 minutes of baseline, with lower ratio indicating more vasoconstriction. 99mTc sestamibi myocardial perfusion imaging was performed at rest and with mental stress. A summed difference score (SDS) quantifying severity of reversible perfusion defects (inducible ischemia) comparing rest and stress images was computed using a standard 17-segment model. Four categories of increasing severity were based on cut points of 0, 3, and 6. Results: The mean (SD) age was 64 (8), 16% were women, and 28% were African American. Each category of increase in ischemia severity was associated with a 10% (p=0.04) decrease in speech PAT ratio (Figure) and 11% (p=0.02) decrease in recovery PAT ratio. After multivariable adjustment for sociodemographics, traditional risk factors, medical history, medication use, and psychological risk factors, the associations persisted, with B=-11%, p=0.02 for speech PAT ratio, and B=-8%, p=0.04 for recovery ratio. Conclusion: Peripheral vasoconstriction during mental stress speech as well as recovery predicts MSI severity in a dose-response relationship.
The Senescence-associated Secretory Phenotype Mediates Oncogene-induced Senescence in Pediatric Pilocytic Astrocytoma
Authors: Juliane L. Buhl, Florian Selt, Thomas Hielscher, Romain Guiho, Jonas Ecker, Felix Sahm, Johannes Ridinger, Dennis Riehl, Diren Usta, Britta Ismer, Alexander C. Sommerkamp, J.P. Martinez-Barbera, Annika K. Wefers, Marc Remke, Daniel Picard, Stefan Pusch, Jan Gronych, Ina Oehme, Cornelis M. van Tilburg, Marcel Kool, Daniela Kuhn, David Capper, Andreas von Deimling, Martin U. Schuhmann, Christel Herold-Mende, Andrey Korshunov, Tilman Brummer, Stefan M. Pfister, David T.W. Jones, Olaf Witt, Till Milde
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Pilocytic astrocytoma is the most common childhood brain tumor, characterized by constitutive MAPK activation. MAPK signaling induces oncogene-induced senescence (OIS), which may cause unpredictable growth behavior of pilocytic astrocytomas. The senescence-associated secretory phenotype (SASP) has been shown to regulate OIS, but its role in pilocytic astrocytoma remains unknown. Experimental Design: The patient-derived pilocytic astrocytoma cell culture model, DKFZ-BT66, was used to demonstrate presence of the SASP and analyze its impact on OIS in pilocytic astrocytoma. The model allows for doxycycline-inducible switching between proliferation and OIS. Both states were studied using gene expression profiling (GEP), Western blot, ELISA, and cell viability testing. Primary pilocytic astrocytoma tumors were analyzed by GEP and multiplex assay. Results: SASP factors were upregulated in primary human and murine pilocytic astrocytoma and during OIS in DKFZ-BT66 cells. Conditioned medium induced growth arrest of proliferating pilocytic astrocytoma cells. The SASP factors IL1B and IL6 were upregulated in primary pilocytic astrocytoma, and both pathways were regulated during OIS in DKFZ-BT66. Stimulation with rIL1B but not rIL6 reduced growth of DKFZ-BT66 cells and induced the SASP. Anti-inflammatory treatment with dexamethasone induced regrowth of senescent cells and inhibited the SASP. Senescent DKFZ-BT66 cells responded to senolytic BCL2 inhibitors. High IL1B and SASP expression in pilocytic astrocytoma tumors was associated with favorable progression-free survival. Conclusions: We provide evidence for the SASP regulating OIS in pediatric pilocytic astrocytoma, with IL1B as a relevant mediator. SASP expression could enable prediction of progression in patients with pilocytic astrocytoma. Further investigation of the SASP driving the unpredictable growth of pilocytic astrocytomas, and its possible therapeutic application, is warranted.
Nutrient Stress–Dysregulated Antisense lncRNA GLS-AS Impairs GLS-Mediated Metabolism and Represses Pancreatic Cancer Progression
Authors: Shi-Jiang Deng, Heng-Yu Chen, Zhu Zeng, Shichang Deng, Shuai Zhu, Zeng Ye, Chi He, Ming-Liang Liu, Kang Huang, Jian-Xin Zhong, Feng-Yu Xu, Qiang Li, Yang Liu, Chunyou Wang, Gang Zhao
Journal: Cancer Research (2018)

Cancer cells are known to undergo metabolic reprogramming, such as glycolysis and glutamine addiction, to sustain rapid proliferation and metastasis. It remains undefined whether long noncoding RNAs (lncRNA) coordinate the metabolic switch in pancreatic cancer. Here we identify a nuclear-enriched antisense lncRNA of glutaminase (GLS-AS) as a critical regulator involved in pancreatic cancer metabolism. GLS-AS was downregulated in pancreatic cancer tissues compared with noncancerous peritumor tissues. Depletion of GLS-AS promoted proliferation and invasion of pancreatic cancer cells both in vitro and in xenograft tumors of nude mice. GLS-AS inhibited GLS expression at the posttranscriptional level via formation of double stranded RNA with GLS pre-mRNA through ADAR/Dicer-dependent RNA interference. GLS-AS expression was transcriptionally downregulated by nutrient stress-induced Myc. Conversely, GLS-AS decreased Myc expression by impairing the GLS-mediated stability of Myc protein. These results imply a reciprocal feedback loop wherein Myc and GLS-AS regulate GLS overexpression during nutrient stress. Ectopic overexpression of GLS-AS inhibited proliferation and invasion of pancreatic cancer cells by repressing the Myc/GLS pathway. Moreover, expression of GLS-AS and GLS was inversely correlated in clinical samples of pancreatic cancer, while low expression of GLS-AS was associated with poor clinical outcomes. Collectively, our study implicates a novel lncRNA-mediated Myc/GLS pathway, which may serve as a metabolic target for pancreatic cancer therapy, and advances our understanding of the coupling role of lncRNA in nutrition stress and tumorigenesis.Significance: These findings show that lncRNA GLS-AS mediates a feedback loop of Myc and GLS, providing a potential therapeutic target for metabolic reprogramming in pancreatic cancer.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/79/7/1398/F1.large.jpg.See related commentary by Mafra and Dias, p. 1302.
Urethra and Ejaculation Preserving Robot-assisted Simple Prostatectomy: Near-infrared Fluorescence Imaging-guided Madigan Technique
Authors: Giuseppe Simone, Leonardo Misuraca, Umberto Anceschi, Francesco Minisola, Mariaconsiglia Ferriero, Salvatore Guaglianone, Gabriele Tuderti, Michele Gallucci
Journal: European Urology (2018)
Cardiovascular Health of Offspring of Diabetic Mothers From the Fetal Through Late-Infancy Stages
Authors: Victor Do, Halima Al-Hashmi, Tiina Ojala, Venu Jain, Tim Colen, Silvia Goncalvez-Alvarez, Sandra T. Davidge, Najlaa Al-Rajaa, Jesus Serrano-Lomelin, Michael K. Stickland, Lisa K. Hornberger
Journal: JACC. Cardiovascular imaging (2018)
Exploring Dynamics and Structure of Biomolecules, Cryoprotectants, and Water Using Molecular Dynamics Simulations: Implications for Biostabilization and Biopreservation
Authors: Lindong Weng, Shannon L. Stott, Mehmet Toner
Journal: Annual Review of Biomedical Engineering (2018)

Successful stabilization and preservation of biological materials often utilize low temperatures and dehydration to arrest molecular motion. Cryoprotectants are routinely employed to help the biological entities survive the physicochemical and mechanical stresses induced by cold or dryness. Molecular interactions between biomolecules, cryoprotectants, and water fundamentally determine the outcomes of preservation. The optimization of assays using the empirical approach is often limited in structural and temporal resolution, whereas classical molecular dynamics simulations can provide a cost-effective glimpse into the atomic-level structure and interaction of individual molecules that dictate macroscopic behavior. Computational research on biomolecules, cryoprotectants, and water has provided invaluable insights into the development of new cryoprotectants and the optimization of preservation methods. We describe the rapidly evolving state of the art of molecular simulations of these complex systems, summarize the molecular-scale protective and stabilizing mechanisms, and discuss the challenges that motivate continued innovation in this field.
A defined synthetic substrate for serum-free culture of human stem cell derived cardiomyocytes with improved functional maturity identified using combinatorial materials microarrays
Authors: Asha K. Patel, Adam D. Celiz, Divya Rajamohan, Daniel G. Anderson, Robert Langer, Martyn C. Davies, Morgan R. Alexander, Chris Denning
Journal: Biomaterials (2015)

Cardiomyocytes from human stem cells have applications in regenerative medicine and can provide models for heart disease and toxicity screening. Soluble components of the culture system such as growth factors within serum and insoluble components such as the substrate on which cells adhere to are important variables controlling the biological activity of cells. Using a combinatorial materials approach we develop a synthetic, chemically defined cellular niche for the support of functional cardiomyocytes derived from human embryonic stem cells (hESC-CMs) in a serum-free fully defined culture system. Almost 700 polymers were synthesized and evaluated for their utility as growth substrates. From this group, 20 polymers were identified that supported cardiomyocyte adhesion and spreading. The most promising 3 polymers were scaled up for extended culture of hESC-CMs for 15 days and were characterized using patch clamp electrophysiology and myofibril analysis to find that functional and structural phenotype was maintained on these synthetic substrates without the need for coating with extracellular matrix protein. In addition, we found that hESC-CMs cultured on a co-polymer of isobornyl methacrylate and tert-butylamino-ethyl methacrylate exhibited significantly longer sarcomeres relative to gelatin control. The potential utility of increased structural integrity was demonstrated in an in vitro toxicity assay that found an increase in detection sensitivity of myofibril disruption by the anti-cancer drug doxorubicin at a concentration of 0.05 μM in cardiomyocytes cultured on the co-polymer compared to 0.5 μM on gelatin. The chemical moieties identified in this large-scale screen provide chemically defined conditions for the culture and manipulation of hESC-CMs, as well as a framework for the rational design of superior biomaterials.
Probability of TCD-Normalization in the "Drepagreffe" Trial Comparing Transplantation to Chronic Transfusion in Sickle Cell Anemia Children with Abnormal-Transcranial Doppler Is Associated with Lower Ang-2 and BDNF Plasma Levels
Authors: Myriam Bernaudin, Yacine Khelif, Philippe Chadebech, Gwellaouen Bodivit, Alicia Jouard, Suzanne Verlhac, Catherine Paillard, Isabelle Thuret, Corinne Guitton, Camille Runel, Florence Missud, Cécile Arnaud, Annie Kamdem, Corinne Pondarré, France Pirenne, Francoise Bernaudin
Journal: Blood (2018)
Safety and clinical outcome in patients with microsatellite-stable, metastatic colorectal or pancreatic cancer treated with the CXCL12 inhibitor NOX-A12 in combination with PD-1 checkpoint inhibitor pembrolizumab
Authors: N. Halama, U. Prüfer, A. Frömming, D. Beyer, D. Eulberg, J. Jungnelius, A. Mangasarian
Journal: Annals of Oncology (2018)

Background: NOX-A12 is an inhibitor of the chemokine CXCL12 for treatment of solid tumors. Binding of CXCL12 by NOX-A12 prevents receptor engagement and blocks the ability of CXCL12 to form a chemotactic concentration gradient. The Opera study (NCT03168139) is a Phase 1/2 study to evaluate pharmacodynamic effects and safety of monotherapy with NOX-A12 as well as safety and efficacy of a combination of NOX-A12 with pembrolizumab in metastatic microsatellite-stable colorectal (CRC) and pancreatic (PaC) cancer. Methods: Patients received 300 mg NOX-A12 twice weekly during the two-week monotherapy phase. Biopsies were taken from liver metastases before treatment and after NOX-A12 monotherapy for analysis of immune cell infiltration and cytokine signature. In the combination phase, patients received repeated 21-day cycles of 300 mg NOX-A12 and 200 mg pembrolizumab. Results: 20 patients were recruited, thereof 11 with CRC and 9 with PaC. 15 of the patients (75%) are male, with a median age of 62 (CRC) and 68 years (PaC). Patients were heavily pretreated with a median of 5 (CRC) and 3 lines (PaC) of prior treatment. Known best responses to last prior treatment was PD for 16 out of 20 patients. The AE profile was comparable with the pembrolizumab profile or typical for the underlying diseases. Thus far, 5 of the patients (25%) achieved a stable disease (3 CRC and 2 PaC). Interestingly, some of the patients with SD or clinical benefit also showed a favorable tissue cytokine response upon NOX-A12 monotherapy. Higher changes of CXCL12 levels in tissue observed upon monotherapy – indicating more complete CXCL12 neutralization – correlated with a favorable cytokine profile. Conclusions: NOX-A12 alone and combined with pembrolizumab was safe and well tolerated. Changes in the cytokine signature in tumor tissue suggest that NOX-A12 modulates the tumor microenvironment and induces an immune-stimulatory Th1-like signature in multiple patients of which some show signs of disease stabilization or clinical benefit. The observed time of treatment compares favorably with the expected clinical course of such end-stage and heavily pre-treated patient population. Clinical trial identification: EudraCT: 2016-003657-15. Legal entity responsible for the study: Noxxon Pharma. Funding: Noxxon Pharma AG. Disclosure: N. Halama, U. Prüfer: Research funded by Noxxon Pharma AG. A. Frömming, D. Beyer, D. Eulberg, J. Jungnelius, A. Mangasarian: Employee of Noxxon Pharma AG.