tbuckley/cabot-search huggingface dataset:
Systems-Wide Approaches in Induced Pluripotent Stem Cell Models
Authors: Edward Lau, David T. Paik, Joseph C. Wu
Journal: Annual Review of Pathology Mechanisms of Disease (2018)

Human induced pluripotent stem cells (iPSCs) provide a renewable supply of patient-specific and tissue-specific cells for cellular and molecular studies of disease mechanisms. Combined with advances in various omics technologies, iPSC models can be used to profile the expression of genes, transcripts, proteins, and metabolites in relevant tissues. In the past 2 years, large panels of iPSC lines have been derived from hundreds of genetically heterogeneous individuals, further enabling genome-wide mapping to identify coexpression networks and elucidate gene regulatory networks. Here, we review recent developments in omics profiling of various molecular phenotypes and the emergence of human iPSCs as a systems biology model of human diseases.
Abstract 20787: Maternal Obesity Causes Contractile Dysfunction of Term Fetal Sheep Cardiomyocytes
Authors: Qiurong Wang, Chaoqun Zhu, Mingming Sun, Nan Hu, Stephen P Ford, Peter W Nathanielsz, Jun Ren, Wei Guo
Journal: Circulation (2016)

Background: Maternal obesity (MO), in pregnancy, predisposes offspring to a higher risk of obesity, heart disease, hypertension, and vascular dysfunction, known as fetal programming. However, the e...
Differentiated Thyroid Cancer Outcomes After Surgery and Activity-Adjusted 131I Theragnostics
Authors: Anca M. Avram, Natalja Rosculet, Nazanene H. Esfandiari, Paul G. Gauger, Barbra S. Miller, Mark Cohen, David T. Hughes
Journal: Clinical Nuclear Medicine (2018)

The aim of this study was to determine clinical outcomes in patients with differentiated thyroid cancer after surgery and activity-adjusted I therapy informed by diagnostic I scans with SPECT/CT (Dx scan).Single-institution retrospective cohort study analysis of clinical outcomes after 1 to 5 years (mean, 39.6 ± 23.4 months) of follow-up in 350 patients with differentiated thyroid cancer associated with histopathologic risk factors, nodal metastases, and/or distant metastases. Postoperatively, all patients underwent Dx scans for completion of staging and risk stratification, and I therapy was based on integration of information from histopathology, stimulated thyroglobulin and scintigraphy.Twenty-three patients (6.6%) underwent reoperative neck dissection for removal of unsuspected residual nodal metastases identified on Dx scans. Clinical outcomes were as follows: 84.3% complete response, 1.4% biochemical incomplete response, 2.3% indeterminate response, and 12% structural incomplete response. Of the entire cohort, only 8 patients (2.3%) had persistent iodine-avid metastatic disease, which required repeated I therapy. Of 31 patients with iodine-avid distant metastases identified on Dx scans, 13 patients (42%) achieved complete response with a single I treatment.Detection of regional and distant metastases on postoperative Dx scans permits adjustment of prescribed I activity for targeted treatment, as compared with fixed-activity ablation. This approach resulted in complete response after a single I treatment in 88% patients with histopathologic risk factors and regional metastases and 42% patients with distant metastases. Most patients with structural incomplete response (81%) had elevated thyroglobulin levels with negative follow-up I scans and positive PET/CT and/or CT scans consistent with altered tumor biology (non-iodine-avid disease).
Is There Any Current Role for Bare-Metal Coronary Stents?
Authors: Ajay J. Kirtane
Journal: JAMA Cardiology (2018)

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Genomes of Escherichia coli bacteraemia isolates originating from urinary tract foci contain more virulence-associated genes than those from non-urinary foci and neutropaenic hosts
Authors: Adam P. Dale, Anish K. Pandey, Richard J. Hesp, Konstantinos Belogiannis, Jay R. Laver, Clifford C. Shone, Robert C. Read
Journal: Journal of Infection (2018)

Escherichia coli is the leading cause of bacteraemia. In an era of emerging multi-drug-resistant strains, development of effective preventative strategies will be informed by knowledge of strain diversity associated with specific infective syndromes/patient groups. We hypothesised that the number of virulence factor (VF) genes amongst bacteraemia isolates from neutropaenic patients would be lower than isolates from immunocompetent patients.Immunocompetent and neutropaenic adults with E. coli bacteraemia were recruited prospectively and the source of bacteraemia determined. VF gene profiles were established in silico following whole genome sequencing.Isolates from individual patients were monoclonal. Strains from immunocompetent patients with urinary tract infective foci (UTIF) harboured more VF genes (median number of VF genes 16, range 8-24) than isolates from both immunocompetent patients with non-UTIF (10, 2-22, p = 0.0058) and neutropaenic patients with unknown focus of infection (NPUFI) (8, 3-13, p < 0.0001). Number of VF genes (OR 1.21, 95% CIs 1.01-1.46, p = 0.039) and urinary catheter/recurrent urinary tract infection (OR 12.82, 95% CIs 1.24-132.65, p = 0.032) were independent predictors of bacteraemia secondary to UTIF vs. non-UTIF in immunocompetent patients. papA, papC, papE/F, papG, agn43, tia, iut, fyuA, kpsM and sat were significantly more prevalent amongst UTIF- vs non-UTIF-originating isolates amongst immunocompetent patients, while papC, papE/F, papG, agn43, tia, fyuA, hlyA, usp and clb were significantly more prevalent amongst UTIF- vs NPUFI-associated isolates.Bacteraemia-associated E. coli strains originating from UTIF have distinct VF gene profiles from strains associated with non-UTIF- and NPUFI. This diversity must be addressed in the design of future vaccines to ensure adequate coverage of strains responsible for site-specific disease.
Challenges and Opportunities in the Clinical Development of Immune Checkpoint Inhibitors for Hepatocellular Carcinoma
Authors: Michael J. Flynn, Anwar A. Sayed, Rohini Sharma, Abdul Siddique, David J. Pinato
Journal: Hepatology (2018)

After a decade of stagnation in drug development, therapeutic reversal of immune-exhaustion with immune checkpoint inhibitors (ICPIs) has been shown to be effective in advanced hepatocellular carcinoma (HCC). The clinical development of novel ICPIs continues at a rapid pace, with more than 50 clinical trials of immunotherapeutic agents registered as of May 2018 for this indication. The development of ICPI is particularly challenging in patients with HCC, a population with unique features which impact on safety and efficacy of immune-modulating therapies. In this review, we discuss the biological foundations supporting the development of ICPIs across the advancing stages of HCC, focusing on the rational positioning of ICPIs across the various Barcelona-Clinic Liver Cancer (BCLC) stages of the disease. Translational studies should guide adequate prioritization of those therapeutic agents and combination strategies which are most likely to achieve patient benefit based on solid mechanistic and clinical justifications.
Beverley John Abel
Authors: Kenneth Stephen
Journal: BMJ (2018)

Beverley John Abel (“Bev”) was an eminent urologist and one of Glasgow’s earliest pioneers of percutaneous lithotripsy, a treatment that helped transform care in the city for patients with kidney stones. As a surgical research fellow at Liverpool he published several influential papers on the treatment of bladder and kidney conditions—particularly with regard to spinal injury—which marked him out as one of the finest medical minds of his generation.

As senior registrar and later as consultant urological surgeon at the Victoria Infirmary, Glasgow, Bev was a pioneering advocate— with his colleague, Archie Hutchison—of percutaneous lithotripsy under x-ray control, relieving the acute pain experienced by countless patients with kidney stones. The pair led a urology unit that was lauded as a UK exemplar, hosting many fact finding tours from visiting departments. Bev’s work in championing …
Abstract 13536: Vascular Function is Predictive of Functional Outcomes in Adolescent and Young Adult Fontan Survivors
Authors: Bryan H Goldstein, Elaine M Urbina, Philip R Khoury, Zhiqian Gao, Michelle A Amos, Wayne A Mays, Andrew Redington, Bradley S Marino
Journal: Circulation (2015)

Introduction: Fontan survivors demonstrate diminished vascular function and functional outcomes. The relationships between measures of vascular function and functional outcomes have not been established. Methods: Cross-sectional single-institution study of Fontan survivors ages 8-25 years. Multimodality assessment of endothelial function (reactive hyperemia index [RHI] and flow mediated dilation [FMD]) and arterial stiffness (augmentation index [AI] and baseline pulse amplitude [BPA]) was performed with peripheral arterial tonometry (PAT), brachial FMD and pulse wave analysis (PWA). Aerobic capacity was determined using cardiopulmonary exercise testing with cycle ergometry and a ramp protocol. Quality of life (QOL) was assessed using the pediatric QOL inventory (PedsQL) and physical activity (PA) was assessed using the PA Questionnaire (PAQ). Vascular measures served as predictor variables while functional outcome measures served as outcome variables. Bivariate predictors (p&lt;0.1) were candidates for inclusion in multivariable models. Model development utilized linear regression and ordered logistic regression techniques. Results: Sixty patients (52% male) completed the protocol with a mean age of 13.9 ± 4.1 years and duration of Fontan circulation of 9.9 ± 4.2 years. Maximal (max) exercise was achieved in 54 subjects with mean peak and %-predicted oxygen consumption (VO 2 ) of 27.8 ± 7.6 ml/kg/min and 71.0 ± 21.2%, respectively. FMD-RHI (p&lt;0.05) was associated with VO 2 at anaerobic threshold (AT, R 2 0.33). PAT-BPA (p&lt;0.05) was associated with the ratio of minute ventilation to carbon dioxide at AT (R 2 0.40). FMD-RHI, PAT-AI and PWA-AI (p&lt;0.05) were associated with max VO 2 (R 2 0.36-0.53), %-predicted max VO 2 (R 2 0.40-0.56) and max O 2 pulse (R 2 0.26-0.31). PAT-AI and PAT-BPA (p&lt;0.05) were associated with PedsQL total (R 2 0.19-0.34) and physical heath summary score (R 2 0.36-0.41). FMD max and PAT-BPA (p&lt;0.05) were associated with PAQ score (R 2 0.33-0.38). Conclusions: Increased arterial stiffness and decreased endothelial function are associated with lower aerobic capacity, QOL and physical activity in adolescent and young adult Fontan survivors. Vascular dysfunction may be an important target for future therapeutic trials.
Metabolic Pathways in Kidney Cancer: Current Therapies and Future Directions
Authors: W. Kimryn Rathmell, Jeffrey C. Rathmell, W. Marston Linehan
Journal: Journal of Clinical Oncology (2018)

Renal cell carcinoma (RCC) has become known as a metabolic disease, owing to the diverse array of metabolic defects and perturbations that occur as a result of the unique genetics that can drive these tumors. Recent attention to this feature of RCCs has fueled interest in targeting metabolism as a therapeutic strategy.
Abstract 17857: Geriatric Nutritional Risk Index at Hospital Discharge is a Useful Predictor of Adverse Outcome in Hospitalized Patient With Acute Decompensated Heart Failure
Authors: Masafumi Ono, Atsushi Mizuno, Syun Kohsaka, Ryoma Fukuoka, Nobuyuki Komiyama, Yasuyuki Shiraishi, Takashi Kohno, Yuji Nagatomo, Ayumi Goda, Tsutomu Yoshikawa
Journal: Circulation (2017)

Introduction: Geriatric Nutritional Risk Index (GNRI) is a simple nutritional evaluation tool for elderly patients, and can be calculated from serum albumin and body mass index (BMI). Previous reports revealed lower GNRI on admission associates with higher mortality rate in hospitalized patients with acute decompensated heart failure (ADHF). Purpose: To investigate the relationship between d-GNRI and worse outcomes in ADHF patients. Methods: We retrospectively analyzed using database of the West Tokyo Heart Failure (WET-HF) Registry (total 3545 hospitalized patients with ADHF). We excluded the patients whose d-GNRI was not available. d-GNRI was calculated as follows: 14.89хserum albumin (g/dl)+41.7х(BMI at discharge)/22. All-cause mortality rate was compared between 2 groups: lower GNRI ( =92) with no or low nutritional risk as previously defined. Results: Total 2519 patients (mean age, 73.6 years; 61% male) were analyzed. The absolute value ...
Swedish company launches NHS partnership in bid to enter GP app market
Authors: Gareth Iacobucci
Journal: BMJ (2018)

A Swedish smartphone app has launched a partnership with 40 NHS general practices to offer video consultations to patients, as it seeks to gain a foothold in the growing UK market for online services alongside other providers such as Babylon.

LIVI, which trades as Kry in Sweden and Norway, has signed a deal with a federation of 40 practices in Surrey to allow patients registered at these practices to access NHS GP consultations, prescriptions, and medical advice on their smartphone or tablet.

In contrast to Babylon’s GP at Hand partnership with a general practice in west London, which has used regulations on patient choice to …
Cancer from the perspective of stem cells and misappropriated tissue regeneration mechanisms
Authors: Mariusz Z. Ratajczak, Kamila Bujko, Aaron Mack, Magda Kucia, Janina Ratajczak
Journal: Leukemia (2018)

Tumorigenesis can be considered as pathologically misappropriated tissue regeneration. In this review we will address some unresolved issues that support this concept. First, we will address the issue of the identity of cancer-initiating cells and the presence of cancer stem cells in growing tumors. We will also ask are there rare and distinct populations of cancer stem cells in established tumor cell lines, or are all of the cells cancer stem cells? Second, the most important clinical problem with cancer is its metastasis, and here a challenging question arises: by employing radio-chemotherapy for tumor treatment, do we unintentionally create a prometastatic microenvironment in collateral organs? Specifically, many factors upregulated in response to radio-chemotherapy-induced injury may attract highly migratory cancer cells that survived initial treatment. Third, what is the contribution of normal circulating stem cells to the growing malignancy? Do circulating normal stem cells recognize a tumor as a hypoxia-damaged tissue that needs vascular and stromal support and thereby contribute to tumor expansion? Fourth, is it reasonable to inhibit only one prometastatic ligand–receptor axis when cancer stem cells express several receptors for several chemotactic factors that may compensate for inhibition of the targeted receptor? Fifth, since most aggressive cancer cells mimic early-development stem cells, which properties of embryonic stem cells are retained in cancer cells? Would it be reasonable to inhibit cancer cell signaling pathways involved in the migration and proliferation of embryonic stem cells? We will also briefly address some new players in cancerogenesis, including extracellular microvesicles, bioactive phospholipids, and extracellular nucleotides.
OP0212 Mobile phone text messages for improving allopurinol adherence: a randomised controlled trial of text message reminders
Authors: K. Bunphong, P. Narongroeknawin
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Medication adherence is important to treatment success, particularly in gout where the target level achievement is critical. However, there is no evidence that mobile phone text message reminder is effective in improving treatment adherence and clinical outcomes for gout. <h3>Objectives</h3> To evaluate the effect of mobile phone text messaging on the adherence to allopurinol treatment and serum uric acid (SUA) level of patient with gout in a randomized-controlled trial. <h3>Methods</h3> Adult patients who were diagnosed of gout by 1977 ARA classification criteria for gout, receiving at least 1 month of allopurinol, and had estimated glomerular filtration rate greater than 30 mL/min/1.73 m<sup>2</sup> were enrolled and randomly assigned to 2 groups by block randomization. Patients in the intervention group received a daily short message reminder to take allopurinol for 90 days. Patients in the control group received a weekly short message information about non-pharmacologic treatment for gout in plain language. The primary outcomes were allopurinol adherence, defined as the Medication Taking Behaviour for Thai patient (MTB-Thai) score &gt;21, and SUA level at 12 weeks. The primary analysis was by intention-to-treat. This trial is registered with Thai Clinical Trials Registry, TCTR20171229004. <h3>Results</h3> Eighty-two patients were randomised, with 42 in the intervention group and 40 in the control group. No significant different of baseline characteristic, SUA (7.66±1.24 vs 7.78±1.17 mg/dL) and MTB-Thai score (18.38±0.73 vs 18.37±0.95) between two groups. At week 12, 37 patients (88.1%) in the intervention group achieved adherence compared with none of patient in the control group (RR for adherence 71.5, 95% CI: 4.54 to 1126.80; p=0.002). SUA level was decreased significantly from baseline in both study groups, however, the reduction in the intervention group was significantly greater than in the control group (−1.47±0.86 vs −0.28±0.39 mg/dL, p&lt;0.001). Serum creatinine was significantly decreased in the intervention group (−0.03±0.09 mg/dL, p&lt;0.031), while serum creatinine was unchanged in the control group (0.01±0.08 mg/dL, p=0.84). <h3>Conclusions</h3> Patients who received daily short message reminder had significantly improved adherence and reduction in SUA compared with the control individuals. Mobile phones text reminders may be an important tool to enhance allopurinol adherence and help in controlling SUA level in gout patients. <h3>Disclosure of Interest</h3> None declared
Healthcare Costs in Patients with Cancer Increase with Increasing Risk of Venous Thromboembolism
Authors: Michael B. Streiff, Keith R. McCrae, Nicole M. Kuderer, Dejan Milentijevic, Guillaume Germain, François Laliberté, Nguyen Le, Patrick Lefebvre, Gary H. Lyman, Alok A. Khorana
Journal: Blood (2018)
David Oliver: Incendiary healthcare hashtags
Authors: David Oliver
Journal: BMJ (2018)

I probably spend too much time on “healthcare” Twitter. Twitter is a fantastic place for learning, sharing, networking, and debate. It can be compulsive and distracting, joyous, warm, and enlightening. It’s also sometimes fractious, factional, and shouty, leaving users upset. The ongoing saga of the #doctorsaredickheads hashtag is a prime example.

Healthcare workers, researchers, reporters, and policy makers can use Twitter to engage directly with people who use services and with the wider public, who in turn use Twitter for peer support, discussion, lobbying, and speaking directly to people in power (including clinical professionals). They also use it for sharing experiences of illness, including frustrations with health services. Sometimes on Twitter these professional and patient circles intersect and something sparks, as with #doctorsaredickheads.

This hashtag …
Long-term Mortality After Kidney Transplantation in a Nationwide Cohort of Patients With Type 1 Diabetes in Finland
Authors: Fernanda Ortiz, Valma Harjutsalo, Ilkka Helanterä, Marko Lempinen, Carol Forsblom, Per-Henrik Groop
Journal: Diabetes Care (2018)

OBJECTIVE To examine time trends in mortality rates and causes of death in patients with type 1 diabetes and end-stage renal disease on dialysis and after kidney transplantation. RESEARCH DESIGN AND METHODS In a nationwide retrospective cohort analysis, all patients with type 1 diabetes in Finland who received a kidney transplant alone were compared with patients who remained on dialysis. The main outcome was patient survival after starting dialysis. The cohort was divided into dialysis, functioning kidney transplant, and dialysis after transplant loss. Causes of death were retrieved and standardized mortality ratios calculated. RESULTS We studied 2,383 patients. Patients survived a median of 15.9 years after a successful transplant, 11.2 years if transplant function was lost, and 2.9 years if they remained on chronic dialysis. Standardized mortality ratio decreased in all subgroups during the past four decades: from 2005 onwards, it was 3.9 in patients receiving a kidney transplant, 11.5 in patients with graft loss, and 32.5 in patients on dialysis. The most common cause of death in all patients was ischemic heart disease (45%) followed by infection (18%), which was more common in patients on dialysis. CONCLUSIONS Kidney transplantation is the treatment of choice for patients with type 1 diabetes and end-stage renal disease because it substantially reduces the excess death risk when compared with dialysis. Even when kidney graft function is lost, the excess death risk is still considerably lower. Although overall mortality has decreased over the years, premature death due to ischemic heart disease remains high.
Trends in the Incidence of and Charges Associated With Firearm-Related Injuries Among Pediatric Patients, 2006-2014
Authors: Faiz Gani, Joseph K. Canner
Journal: JAMA Pediatrics (2018)

Leonardo Mariño-Ramírez, PhD; I. King Jordan, PhD; Anna María Nápoles, PhD; Eliseo J. Pérez-Stable, MD
Retinoic acid and BMP4 cooperate with p63 to alter chromatin dynamics during surface epithelial commitment
Authors: Jillian M. Pattison, Sandra P. Melo, Samantha N. Piekos, Jessica L. Torkelson, Elizaveta Bashkirova, Maxwell R. Mumbach, Charlotte Rajasingh, Hanson Hui Zhen, Lingjie Li, Eric Liaw, Daniel Alber, Adam J. Rubin, Gautam Shankar, Xiaomin Bao, Howard Y. Chang, Paul A. Khavari, Anthony E. Oro
Journal: Nature Genetics (2018)
Paradoxical effects of obesity on T cell function during tumor progression and PD-1 checkpoint blockade
Authors: Ziming Wang, Ethan G. Aguilar, Jesus I. Luna, Cordelia Dunai, Lam T. Khuat, Catherine T. Le, Annie Mirsoian, Christine M. Minnar, Kevin M. Stoffel, Ian R. Sturgill, Steven K. Grossenbacher, Sita S. Withers, Robert B. Rebhun, Dennis J. Hartigan-O’Connor, Gema Méndez-Lagares, Alice F. Tarantal, R. Rivkah Isseroff, Thomas S. Griffith, Kurt A. Schalper, Alexander Merleev, Asim Saha, Emanual Maverakis, Karen Kelly, Raid Aljumaily, Sami Ibrahimi, Sarbajit Mukherjee, Michael Machiorlatti, Sara K. Vesely, Dan L. Longo, Bruce R. Blazar, Robert J. Canter, William J. Murphy, Arta M. Monjazeb
Journal: Nature Medicine (2018)