tbuckley/cabot-search huggingface dataset:
Abstract 14773: A Promising in vitro Treatment to Reduce Tumorigenicity in iPSC-Based Cardiomyogenesis Therapy by Antibody-Drug Conjugate Selectively Targeting Undifferentiated iPSCs Contaminating in the Graft
Authors: Nagako Sougawa, Shigeru Miyagawa, Satsuki Fukushima, Ai Kawamura, Emiko Ito, Junya Yokoyama, Shigeo Masuda, Atsuhiro Saito, Yoshiki Sawa
Journal: Circulation (2016)

Background:  Although induced pluripotent stem cell (iPSC) is a promising candidate which induces cardiomyogenesis in the failing heart, its clinical application is concerned with teratoma/tumor formation from undifferentiated iPSCs contaminating in the graft. We herein hypothesized that an antibody-cytotoxic drug conjugate which targets a specific antigen on undifferentiated iPSC membrane may eliminate residual undifferentiated cell fraction, resulting in avoidance of teratoma/tumor formation  in vivo .   Methods and Results:  Comprehensive flow cytometry analysis identified a consistent expression of CD30 in the undifferentiated human iPSCs (87.7±9.2%), but rarely in the cardiomyogenically differentiated iPSCs. Addition of anti-CD30 antibody-drug conjugate (brentuximab vedotin), which is clinically used for lymphoma therapy,  in vitro  for 72 hours efficiently induced cell death in human iPSCs (3.3±0.4% survival) associated with increase in the ratio of G2/M phase (from 9.3±1.1% to 17.1±2.3%), but failed to affect survival of the normal human dermal fibroblasts (99.7±0.3% survival). In addition, percentage of Annexin-V positive cells after the brentuximab vedotin treatment was significantly higher in the human iPSCs (71.5±10.9%) than that in the human fibroblasts (2.8±0.6%). Moreover, the brentuximab vedotin treatment significantly reduced expression of  Lin28 , an undifferentiated cell marker, in the cardiomyogenically differentiated human iPSC preparation (39±26% reduction compared to untreated cells). Transplantation of untreated human iPSC-derived cardiac tissue into the NOG mouse consistently induced teratoma/tumor formation with a substantial number of Ki-67 positive cells in the graft (240.8±27.9 /mm 2 ) at 16 weeks post-transplant (n=6), whereas that treated with brentuximab vedotin prior to the transplantation failed to induce teratoma/tumor formation, associated with absence of Ki-67 positive cells in the graft over the same period (n=8).   Conclusion:  In vitro  treatment with brentuximab vedotin targeting CD30-positive undifferentiated iPSC fraction reduced tumorigenicity in the human iPSC-derived cardiac tissue, warranting enhanced safety in the iPSC-based cardiomyogenesis therapy in clinical scenario.
Drug delivery systems and materials for wound healing applications
Authors: Saghi Saghazadeh, Chiara Rinoldi, Maik Schot, Sara Saheb Kashaf, Fatemeh Sharifi, Elmira Jalilian, Kristo Nuutila, Giorgio Giatsidis, Pooria Mostafalu, Hossein Derakhshandeh, Kan Yue, Wojciech Swieszkowski, Adnan Memic, Ali Tamayol, Ali Khademhosseini
Journal: Advanced Drug Delivery Reviews (2018)
A phase II trial of GSK2256098 and trametinib in patients with advanced pancreatic ductal adenocarcinoma (PDAC) (MOBILITY-002 Trial, NCT02428270).
Authors: Kyaw Lwin Aung, Elaine McWhirter, Stephen Welch, Lisa Wang, Sophia Lovell, Lee-Anne Stayner, Saara Ali, Anne Malpage, Barbara Makepeace, Makilpriya Ramachandran, Neesha C. Dhani, David W. Hedley, Jennifer J. Knox, Lillian L. Siu, Rachel Anne Goodwin, Philippe L. Bedard
Journal: Journal of Clinical Oncology (2018)

409 Background: MEK (mitogen-activated protein kinase kinase) is activated through mutated KRAS in &gt; 90% of PDAC. Focal adhesion kinase (FAK) integrates signals from integrins and growth factor receptors. MEK and FAK are frequently co-activated in PDAC providing a rationale for dual inhibition with GSK2256098, an oral FAK inhibitor, and trametinib, an oral allosteric MEK1/2 inhibitor. Methods: Patients with advanced PDAC patients who progressed after first line chemotherapy were treated with GSK2256098 250mg twice daily and trametinib 0.5mg once daily in 28 day cycles. The primary endpoint was antitumor activity measured by clinical benefit (CB; complete response, partial response, or stable disease ≥24 weeks) by RECIST 1.1. We planned to enrol 24 patients using a 2-stage minimax design (p0 = 0.15, p1 = 0.40; alpha = 0.05, power 0.86). The combination would be considered active if &gt; 7/24 response-evaluable patients achieved CB; and inactive if 2/12 or fewer patients achieved CB at the end of stage 1. Response assessment was performed every 2 cycles. Results: Between June/16 and June/17, 16 patients were enrolled. Five were not evaluable for response. Of 11 evaluable patients, 10 had PD as best tumor response and one had SD for 4 months. One response unevaluable patient who had rapidly progressed on 1 st line FOLFIRINOX chemotherapy with a basal-like tumor by RNA-sequencing and KRAS amplification achieved clinical stability for 5 months with a &gt; 50% decline in serum CA19-9 after 3 months of treatment and symptomatic improvement. No treatment related Grade≥3 adverse events (AEs) were observed. The most common treatment related grade 2 AEs were acneiform rash (19%), diarrhea (13%), nausea (6%), fatigue (6%), proteinuria (6%), paronychia (6%), and retinal detachment (6%). The median progression free survival was 1.6 (95% CI 1.5-1.8) months and the median overall survival was 3.6 (95% CI 2.7-not reached) months. Conclusions: GSK2256098 and trametinib was well tolerated but was not active in unselected advanced PDAC. Correlative studies are ongoing to evaluate RNA-expression subtypes and dynamic markers of pathway inhibition from serial tumor biopsies and cell free DNA. Clinical trial information: NCT02428270.
Characteristics and Ongoing Autoimmunity of Patients With Long-standing Type 1 Diabetes Living in China
Authors: Wei Liu, Xueyao Han, Yanai Wang, Siqian Gong, Yumin Ma, Simin Zhang, Xueying Gao, Linong Ji
Journal: Diabetes Care (2018)

No study to date has established the clinical features of long-duration type 1 diabetes in a non-Caucasian population. We identified people who survived ≥30 years with type 1 diabetes across China through a national program and performed the current study to establish the profile of this population.

Between 2015 and 2016, all of the registered subjects ( n = 105) were contacted, and 95 of them completed the study visit. Demographic and socioeconomic data, body weight, height, and blood pressure were collected by study physicians, and blood and urine samples were collected locally and transported to a central laboratory.

Clinical characteristics were consistent with type 1 diabetes: mean (± SD) age at onset was 17.1 (± 8.6) years, and mean BMI was 22.48 (± 2.75) kg/m2. Mean LDL level was 2.87 (± 1.02) mg/dL, with only 12.6% of participants using statins (Table 1). Meanwhile, 42.9% of participants reported hypertension and 14.3% had cardiovascular disease. A high proportion of the participants remained free from diabetic nephropathy (65.9%), while the proportions reporting retinopathy and neuropathy were 67.9% and 60.7%, respectively. Among those with retinopathy, 50.0% had received laser therapy. Autoantibodies against GAD, IA-2, and zinc transporter 8 were detected in …
Practical Guide to Surgical Data Sets: Veterans Affairs Surgical Quality Improvement Program (VASQIP)
Authors: Nader N. Massarweh, Amy H. Kaji, Kamal M. F. Itani
Journal: JAMA Surgery (2018)

This Guide to Statistics and Methods summarizes the advent, data considerations, utility and unique features, and statistical considerations of the Veterans Affairs National Surgical Quality Improvement Program for use in surgical quality improvement research.
Task Shifting in Dermatology—A Call to Action
Authors: Anuradha Bishnoi, Keshavamurthy Vinay, Sunil Dogra
Journal: JAMA Dermatology (2018)

To the Editor In response to the Evidence Synopsis by Brown et al1 on the practice of task shifting, we would like to highlight how task shifting is currently being successfully implemented in health programs in India, with emphasis on National Leprosy Eradication Program.
Comparable outcomes of patients eligible vs ineligible for SWOG leukemia studies
Authors: Abby Statler, Megan Othus, Harry P. Erba, Thomas R. Chauncey, Jerald P. Radich, Steven Coutre, Anjali Advani, Sucha Nand, Farhad Ravandi, Sudipto Mukherjee, Mikkael A. Sekeres
Journal: Blood (2018)
Learning to talk to ourselves: Development, ignorance, and agency
Authors: Stuart I Hammond
Journal: Behavioral and Brain Sciences (2018)

Abstract Although anti-reflectivism seems to preclude a role for reflection, this dichotomy could be synthesized in a Piagetian developmental framework. Development integrates a role for error and ignorance in reflection, and supports Doris's espousal of valuation, collaboration, and pluralism, and the importance of extrinsic factors to the self.
Abstract P070: Long-term Cumulative Blood Pressure Improves CVD Risk Prediction Algorithms
Authors: Norrina B Allen, Hongyan Ning, Donald Lloyd-Jones
Journal: Circulation (2016)

Background: Published risk prediction algorithms only include current BP; however, long-term BP patterns are associated with atherosclerotic (AS)CVD incidence. We tested whether the long-term (5- and 10-year) cumulative blood pressure improves 10 year ASCVD prediction. Methods: This study used the Lifetime Risk Pooling Project (LRPP) including the Framingham, CARDIA and ARIC cohorts. Participants with 15- and 20-year follow-up (5- and 10- years prior to risk calculation and 10 year follow-up), no history of prior CVD, and between the ages of 45 and 65 at the time of risk estimation were included. We calculated 10 year ASCVD risk using the 2013 ACC/AHA 10-year ASCVD Pooled Cohort Equations. Study-specific coefficients were calculated. Differences in the C-statistic, the category-free net reclassification index (NRI) and improved discrimination index (IDI) were examined between the model with baseline as compared to the model with cumulative SBP. Analyses were stratified by gender. Results: Among 11,475 individuals (42.4% male and 12.7% African American), those in the highest tertile of cumulative SBP were older, more likely to be male, and had a higher burden of other CVD risk factors. Overall, 1,487 (13%) participants experienced a CVD event (mean follow-up time was 12 years). ASCVD incidence rates increased with higher tertiles of cumulative SBP from 4 events per 1,000 person-years in the lowest tertile to 8 and 18 in the second and third tertiles, respectively. No significant improvements were seen in the C-statistic when including 5- or 10-year cumulative SBP (see table). However, the replacement cumulative SBP resulted in significant improvements in model reclassification of NRI and IDI with greater improvements for the 10- than 5-year cumulative measure. Conclusions: Measures of cumulative BP can improve the ability of CVD risk prediction models to correctly classify individuals. Additional studies on the inclusion of these measures in future risk prediction algorithms are warranted.
John Sloan McLintock
Authors: Derek McLintock
Journal: BMJ (2018)

John Sloan McLintock was born on in Alexandria, Dunbartonshire, on 9 November 1919. He attended Dumbarton Academy and read medicine at Glasgow University. On graduating in 1942, he joined the Royal Army Medical Corps and was posted to south London and then to Normandy on D-Day+6. During home …
<i>In vitro</i>, <i>in silico</i> and <i>in vivo</i> study challenges the impact of bronchial thermoplasty on acute airway smooth muscle mass loss
Authors: Igor L. Chernyavsky, Richard J. Russell, Ruth M. Saunders, Gavin E. Morris, Rachid Berair, Amisha Singapuri, Latifa Chachi, Adel H. Mansur, Peter H. Howarth, Patrick Dennison, Rekha Chaudhuri, Stephen Bicknell, Felicity R.A.J. Rose, Salman Siddiqui, Bindi S. Brook, Christopher E. Brightling
Journal: European Respiratory Journal (2018)

Bronchial thermoplasty is a treatment for asthma. It is currently unclear whether its histopathological impact is sufficiently explained by the proportion of airway wall that is exposed to temperatures necessary to affect cell survival.Airway smooth muscle and bronchial epithelial cells were exposed to media (37-70°C) for 10 s to mimic thermoplasty. In silico we developed a mathematical model of airway heat distribution post-thermoplasty. In vivo we determined airway smooth muscle mass and epithelial integrity pre- and post-thermoplasty in 14 patients with severe asthma.In vitro airway smooth muscle and epithelial cell number decreased significantly following the addition of media heated to ≥65°C. In silico simulations showed a heterogeneous heat distribution that was amplified in larger airways, with <10% of the airway wall heated to >60°C in airways with an inner radius of ∼4 mm. In vivo at 6 weeks post-thermoplasty, there was an improvement in asthma control (measured via Asthma Control Questionnaire-6; mean difference 0.7, 95% CI 0.1-1.3; p=0.03), airway smooth muscle mass decreased (absolute median reduction 5%, interquartile range (IQR) 0-10; p=0.03) and epithelial integrity increased (14%, IQR 6-29; p=0.007). Neither of the latter two outcomes was related to improved asthma control.Integrated in vitro and in silico modelling suggest that the reduction in airway smooth muscle post-thermoplasty cannot be fully explained by acute heating, and nor did this reduction confer a greater improvement in asthma control.
Eukaryotic initiation factor 4A2 (EIF4A2) expression in colorectal cancer and prediction of prognosis.
Authors: Zhan-Hong Chen, Qinian Wu, Jiahuan Lu, Le-zong Chen, Xiang-yuan Wu, Yun Wang, Huaiqiang Ju, Yun-xin Lu, Ya Chen, Feng Wang, Rui-hua Xu
Journal: Journal of Clinical Oncology (2018)

664 Background: Eukaryotic initiation factor 4A2(EIF4A2) is a member of the eukaryotic initiation factor 4A family and it is one of the protein-synthesis initiation factors, which are involved in the binding of messenger RNA to the ribosome. The prognostic roles of EIF4A2 in breast cancer, melanoma and lung cancer have been studied. However, the clinical significance and biologic role of EIF4A2 in colorectal cancer remain unknown. Methods: We used quantitative real-time polymerase chain reaction to compare expression of eIF4A2 mRNA between 72 paired colorectal cancer tissues and non-tumor colorectal tissues. We used immunohistochemistry to study the expression of EIF4A2 in 310 colorectal cancer patients under surgical resection, 247 of them received curative surgery. We also analyzed correlation between EIF4A2 expression and clinicopathological characteristics. The biological function of EIF4A2 on colorectal cancer cells were determined in vitro by knock-downing EIF4A2 in HCT116 and DLD1 cell lines. We performed MTT tests, colony formation assays, transwell and wound healing assays. Results: EIF4A2 mRNA was significantly higher in colorectal cancer tissues compared to the paired non-tumor colorectal tissues(P = 0.0034). Over-expression of EIF4A2 was prognostic of shorter overall survival(P = 0.002) and shorter disease-free survival(P = 0.042). Over-expression of EIF4A2 was significantly correlated with more TNM stage IV(P = 0.012). Multivariate analysis suggested EIF4A2 as an independent predictor of overall survival (hazard ratio 2.041[95% CI 1.385 to 3.008], P &lt; 0.001) and disease-free survival (hazard ratio 1.537[95% CI 1.003 to 2.355], P = 0.049). Functionally, knockdown of EIF4A2 in HCT116 and DLD1 cell lines exerted tumor-suppressive effects by significantly inhibiting cell proliferation, colony formation,migration and invasion(P &lt; 0.05). Conclusions: EIF4A2 is highly expressed in colorectal cancer and predicts poor prognosis. EIF4A2 could be served as a potential prognostic marker for colorectal cancer patients.
Neuronal Activity-Dependent Control of Postnatal Neurogenesis and Gliogenesis
Authors: Ragnhildur T. Káradóttir, Chay T. Kuo
Journal: Annual Review of Neuroscience (2018)

The addition of new neurons and oligodendroglia in the postnatal and adult mammalian brain presents distinct forms of gray and white matter plasticity. Substantial effort has been devoted to understanding the cellular and molecular mechanisms controlling postnatal neurogenesis and gliogenesis, revealing important parallels to principles governing the embryonic stages. While during central nervous system development, scripted temporal and spatial patterns of neural and glial progenitor proliferation and differentiation are necessary to create the nervous system architecture, it remains unclear what driving forces maintain and sustain postnatal neural stem cell (NSC) and oligodendrocyte progenitor cell (OPC) production of new neurons and glia. In recent years, neuronal activity has been identified as an important modulator of these processes. Using the distinct properties of neurotransmitter ionotropic and metabotropic channels to signal downstream cellular events, NSCs and OPCs share common features in their readout of neuronal activity patterns. Here we review the current evidence for neuronal activity-dependent control of NSC/OPC proliferation and differentiation in the postnatal brain, highlight some potential mechanisms used by the two progenitor populations, and discuss future studies that might advance these research areas further.
Effective cancer immunotherapy in mice by polyIC-imiquimod complexes and engineered magnetic nanoparticles
Authors: Ana Isabel Bocanegra Gondan, Ane Ruiz-de-Angulo, Aintzane Zabaleta, Nina Gómez Blanco, Beatriz Macarena Cobaleda-Siles, María Jesús García-Granda, Daniel Padro, Jordi Llop, Blanca Arnaiz, María Gato, David Escors, Juan C. Mareque-Rivas
Journal: Biomaterials (2018)
123I-FP-CIT SPECT and MRI Findings in a Patient With Parkinsonism After Fenpyroximate Intoxication
Authors: Kyeong Joon Kim, Jong-Min Kim, Yun Jung Bae, Yoo Sung Song, Sang Eun Kim
Journal: Clinical Nuclear Medicine (2018)

Abstract Fenpyroximate is a widely used acaricide. Its main action is to inhibit the mitochondrial respiratory chain. Chronic exposure to fenpyroximate is associated with dopaminergic cell loss and parkinsonism; however, to date, there has not been a reported case of parkinsonism as a result of acute fenpyroximate intoxication. Here, we report a 58-year-old man who developed parkinsonism after deliberate fenpyroximate intoxication, but with normal presynaptic 123 I-Ioflupane SPECT image.
Association of Medical and Adult-Use Marijuana Laws With Opioid Prescribing for Medicaid Enrollees
Authors: Hefei Wen, Jason M. Hockenberry
Journal: JAMA Internal Medicine (2018)

Overprescribing of opioids is considered a major driving force behind the opioid epidemic in the United States. Marijuana is one of the potential nonopioid alternatives that can relieve pain at a relatively lower risk of addiction and virtually no risk of overdose. Marijuana liberalization, including medical and adult-use marijuana laws, has made marijuana available to more Americans.To examine the association of state implementation of medical and adult-use marijuana laws with opioid prescribing rates and spending among Medicaid enrollees.This cross-sectional study used a quasi-experimental difference-in-differences design comparing opioid prescribing trends between states that started to implement medical and adult-use marijuana laws between 2011 and 2016 and the remaining states. This population-based study across the United States included all Medicaid fee-for-service and managed care enrollees, a high-risk population for chronic pain, opioid use disorder, and opioid overdose.State implementation of medical and adult-use marijuana laws from 2011 to 2016.Opioid prescribing rate, measured as the number of opioid prescriptions covered by Medicaid on a quarterly, per-1000-Medicaid-enrollee basis.State implementation of medical marijuana laws was associated with a 5.88% lower rate of opioid prescribing (95% CI, -11.55% to approximately -0.21%). Moreover, the implementation of adult-use marijuana laws, which all occurred in states with existing medical marijuana laws, was associated with a 6.38% lower rate of opioid prescribing (95% CI, -12.20% to approximately -0.56%).The potential of marijuana liberalization to reduce the use and consequences of prescription opioids among Medicaid enrollees deserves consideration during the policy discussions about marijuana reform and the opioid epidemic.
Structural DNA Nanotechnology: Artificial Nanostructures for Biomedical Research
Authors: Yonggang Ke, Carlos Castro, Jong Hyun Choi
Journal: Annual Review of Biomedical Engineering (2018)

Structural DNA nanotechnology utilizes synthetic or biologic DNA as designer molecules for the self-assembly of artificial nanostructures. The field is founded upon the specific interactions between DNA molecules, known as Watson–Crick base pairing. After decades of active pursuit, DNA has demonstrated unprecedented versatility in constructing artificial nanostructures with significant complexity and programmability. The nanostructures could be either static, with well-controlled physicochemical properties, or dynamic, with the ability to reconfigure upon external stimuli. Researchers have devoted considerable effort to exploring the usability of DNA nanostructures in biomedical research. We review the basic design methods for fabricating both static and dynamic DNA nanostructures, along with their biomedical applications in fields such as biosensing, bioimaging, and drug delivery.
Hospital doctors face unfair disciplinary procedures, says defence organisation
Authors: Clare Dyer
Journal: BMJ (2018)

Unfair and inconsistent disciplinary procedures against NHS hospital doctors are reinforcing a culture of fear in healthcare, one of the UK’s largest medical defence organisations has claimed.

The Medical Protection Society (MPS), which advises and helps doctors, acknowledges that some NHS trusts have effective disciplinary processes. But in a new paper, Getting it Right ,1 it accuses others of using legally flawed procedures, prolonging cases unnecessarily, and failing to inform doctors early enough of the allegations they face.

Some trusts exclude doctors from work as a default mechanism regardless of the …
BMA registers interest in Bawa-Garba’s appeal against erasure
Authors: Clare Dyer
Journal: BMJ (2018)

The BMA is applying to intervene as an interested party in the appeal by the paediatric trainee Hadiza Bawa-Garba against her erasure from the UK medical register.1

The doctors’ trade union has instructed Mary O’Rourke QC, who acted for the consultant paediatrician David Southall in 2010 when he won an appeal against a High Court decision that he should be struck off the register.2 O’Rourke has a strong record of defending doctors against the General Medical Council (GMC), Bawa-Garba’s opponent in the appeal.

In November 2015 Bawa-Garba was convicted by a jury …
Concerns Regarding Resource Use and Outcomes in Subsets of Clinicians
Authors: Venkataraman Palabindala, Raj Sehgal, Sarah Stella
Journal: JAMA Internal Medicine (2018)

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