tbuckley/cabot-search huggingface dataset:
Abstract P043: Twelve-Year Trajectories of Insulin Sensitivity from Oral Glucose Tolerance Tests Are Associated With Incident Dyslipidemia: The Ansan-Ansung Community Cohort Study
Authors: Ju-mi Lee, Kyoungmin Kim, Soo Lim
Journal: Circulation (2019)

Introduction: Insulin resistance and dyslipidemia are often comorbid. Although possible biochemical explanations exist, there are inadequate longitudinal data to support the theory directly. Objectives: This study aimed to test the association between twelve-year trajectories of insulin sensitivity from oral glucose tolerance test (OGTT) and the incidence of dyslipidemia in a community cohort. Secondly, we tested which lipidemia profile is associated with trajectories. Methods: Participants (n=3899; aged 40-69 years, during 1 to 7 visit, mean follow-up 12 years) were recruited from the Ansan-Ansung cohort study, a subset of Korean Genome Epidemiology Study. OGTT were measured at every visit. Matsuda index of each visit was calculated by the formula 10 4 /((GLU0xINS0xGLU60xINS60) 0.5 ). We used total seven times of OGTT (28 OGTT index) for trajectories. Latent mixture modeling was used to identify trajectories in Matsuda index for 12 years. The associations of Matsuda index trajectories with the incidence of dyslipidemia and each component of the lipid profile during 12 years were assessed by logistic regression. Age, body mass index, alcohol drinking, cigarette smoking, c reactive protein, education level, and income were adjusted at the final model. Results: Three distinct insulin sensitivity trajectories were identified: low-stable (Group 1; 88.8%), steady decreasing (Group 2; 9.7%), and fast decreasing (Group 3; 1.5%). Low stable cluster (referent: steady decreasing) was associated with greater incident dyslipidemia in total (OR=1.61, 1.25-2.07), and men (OR=2.03, 1.45-2.86) before and after adjustment (OR=2.03, 1.32-3.12, OR=2.08, 1.35-3.22). The low stable cluster was associated with the greater incidence of triglycerides≥200mg/dl in total (OR=1.61, 1.18-2.19), and men (OR=1.59, 1.06-2.40). Also, the low stable cluster was associated with greater incident HDL&lt;40mg/dl in total (OR=1.35, 1.06-1.71), and men (OR=1.81, 1.30-2.53). However low stable cluster was not associated with LDL and total cholesterol. Conclusions: Longterm low stable insulin sensitivity trajectory had increased associations with future incident dyslipidemia especially TG and HDL component.
Lack of insurance as an independent predictor for poor outcome in post-radiation nasopharyngeal carcinoma (NPC) patients.
Authors: Kun Xiao, Zhesi Lian, Yanru Wang, Shenjun Zhu, Hugo Akabane, Zachary Spigelman
Journal: Journal of Clinical Oncology (2015)

e17763 Background: Low socioeconomic status is a risk factor for increased mortality in patients with NPC in Southeast Asia. The United States has low NPC incidence. It remains unclear if lack of insurance is associated with inferior prognosis in this region. Methods: We used Surveillance, Epidemiology, and End Result program (SEER) database to identify patients between 18 and 85 years of age who had histologically-confirmed NPC as the first malignancy diagnosis from 2007 to 2011 and received radiation therapy. Patients with non-NPC histopathology or no active follow-up were excluded. Patients were considered to have insurance coverage if they were covered by non-Medicaid, Medicaid, or any kind of private insurance at the time of diagnosis. Patients who were older than 65 at the time of diagnosis were also considered covered by insurance since they are Medicare-eligible. Survival time is from NPC diagnosis until death or last follow-up. Categorical variables were compared using Chi-square test. Kaplan-Meier method was used for survival analysis. Univariate and multivariate analysis of outcomes were performed using Cox-proportional hazard model. A two-sided P-value < 0.05 was considered statistically significant. Results: A total of 701 patients were identified. Thirty-seven (5.3%) patients were either uninsured or have unknown insurance status. Compared to patients with insurance, patients without insurance was younger (p = 0.008), more likely to be male (p = 0.002), and more likely to present with tumor size ≧ 3 cm (p = 0.027). There was no difference in race, WHO classification, and the presence of multiple malignancies. Patients with insurance had superior 5-years overall survival (0.631 vs 0.390, p = 0.006) and 5-year NPC specific survival (0.682 vs 0.407, p = 0.012) compared to patient without insurance. After adjusted for age and WHO Type I histology, lack of insurance remained a significant predictor for both 5-year overall survival (HR 2.55, 95%CI: 1.43 - 4.56) and NPC-specific survival (HR 2.93, 95%CI: 1.59 - 5.38). Conclusions: Lack of insurance is an independent prognostic factor for poor outcome in post-radiation NPC patients in the United States.
Magnetic Nanoparticles‐Embedded Enzyme‐Inorganic Hybrid Nanoflowers with Enhanced Peroxidase‐Like Activity and Substrate Channeling for Glucose Biosensing
Authors: Hong Jae Cheon, Manab Deb Adhikari, Minsoo Chung, Tai Duc Tran, Jungbae Kim, Moon Il Kim
Journal: Advanced Healthcare Materials (2019)

Abstract It is reported that glucose oxidase (GOx)‐copper hybrid nanoflowers embedded with Fe 3 O 4 magnetic nanoparticles (MNPs) exhibit superior peroxidase‐mimicking activity as well as substrate channeling for glucose detection. This is due to the synergistic integration of GOx, crystalline copper phosphates and MNPs being in close proximity within the nanoflowers. The preparation of MNP‐embedded GOx‐copper hybrid nanoflowers (MNPs‐GOx NFs) begins with the facile conjugation of amine‐functionalized MNPs with GOx molecules via electrostatic attraction, followed by the addition of copper sulfate that leads to full blooming of the hybrid nanoflowers. In the presence of glucose, the catalytic action of GOx entrapped in the nanoflowers generates H 2 O 2 , which is subsequently used by peroxidase‐mimicking MNPs and copper phosphate crystals, located close to GOx molecules, to convert Amplex UltraRed substrate into a highly fluorescent product. Using this strategy, the target glucose is successfully determined with excellent selectivity, stability, and magnetic reusability. This biosensor based on hybrid nanoflowers also exhibits a high degree of precision and reproducibility when applied to real human blood samples. Such novel MNP‐embedded enzyme‐inorganic hybrid nanoflowers have a great potential to be expanded to any oxidases, which will be highly beneficial for the detection of various other clinically important target molecules.
Abstract P063: Serum Calcification Propensity and Cardiovascular Disease Events Among Patients With Chronic Kidney Disease: the CRIC Study
Authors: Joshua D Bundy, Xuan Cai, Rupal Mehta, Julia J Scialla, Geoffrey A Block, Harold I Feldman, Ian H de Boer, James P Lash, Jing Chen, Chi-yuan Hsu, Mirela A Dobre, Mary B Leonard, Panduranga S Rao, Alan S Go, Raymond R Townsend, Edward R Smith, Andreas Pasch, Tamara Isakova
Journal: Circulation (2019)

Introduction: Patients with chronic kidney disease (CKD) are at high risk for cardiovascular disease (CVD) events and vascular calcification is one pathway by which risk is increased. Hypothesis: We assessed the hypothesis that a novel measure of serum calcification propensity is associated with CVD events among patients with CKD stages 2-4. Methods: Among 3397 participants from the prospective longitudinal Chronic Renal Insufficiency Cohort (CRIC) Study, calcification propensity was quantified at baseline as the transformation time (T 50 ) from primary to secondary calciprotein particles, with lower T 50 corresponding to higher calcification propensity. CVD events are reported every six months and confirmed by medical record adjudication. Multivariable-adjusted Cox proportional hazards regression models, stratified by study site, were used to assess the associations of T 50 with risks of atherosclerotic CVD events (myocardial infarction, stroke, and peripheral artery disease) and congestive heart failure (CHF) events. Results: Over an average 7.1-year follow-up, we observed 571 atherosclerotic CVD events (312 myocardial infarction, 120 stroke, and 139 peripheral artery disease events) and 633 CHF events. The mean (standard deviation) T 50 was 313.4 (79.1) minutes. After adjustment for traditional CVD risk factors, lower T 50 was significantly associated with higher risk of atherosclerotic CVD, but not with risk of CHF. The addition of T 50 modestly improved atherosclerotic CVD event discrimination beyond ACC/AHA atherosclerotic CVD risk score variables (c-statistic 0.713 vs. 0.710; p&lt;0.001). Adjustment for kidney function attenuated the association between T 50 and CVD events (Table). Conclusions: Among patients with CKD stages 2-4, higher serum calcification propensity is significantly associated with atherosclerotic CVD events, but not with CHF events. Future studies should evaluate whether T 50 and its determinants represent novel therapeutic targets.
Deciphering the Chronology of Copy Number Alterations in Multiple Myeloma (MM): What Comes First?
Authors: Anil Aktas Samur, Mehmet Kemal Samur, Stephane Minvielle, Florence Magrangeas, Masood A. Shammas, Mariateresa Fulciniti, Michel Attal, Philippe Moreau, Kenneth Anderson, Giovanni Parmigiani, Hervé Avet-Loiseau, Nikhil Munshi
Journal: Blood (2018)
Inhibition of mutant PPM1D enhances DNA damage response and growth suppressive effects of ionizing radiation in diffuse intrinsic pontine glioma
Authors: Mwangala Precious Akamandisa, Kai Nie, Rita Nahta, Dolores Hambardzumyan, Robert Craig Castellino
Journal: Neuro-Oncology (2019)

Children with diffuse intrinsic pontine glioma (DIPG) succumb to disease within 2 years of diagnosis despite treatment with ionizing radiation (IR) and/or chemotherapy. Our aim was to determine the role of protein phosphatase, magnesium-dependent 1, delta (PPM1D) mutation, present in up to 25% of cases, in DIPG pathogenesis and treatment.Using genetic and pharmacologic approaches, we assayed effects of PPM1D mutation on DIPG growth and murine survival. We assayed effects of targeting mutated PPM1D alone or with IR on signaling, cell cycle, proliferation, and apoptosis in patient-derived DIPG cells in vitro, in organotypic brain slices, and in vivo.PPM1D-mutated DIPG cell lines exhibited increased proliferation in vitro and in vivo, conferring reduced survival in orthotopically xenografted mice, through stabilization of truncated PPM1D protein and inactivation of DNA damage response (DDR) effectors p53 and H2A.X. PPM1D knockdown or treatment with PPM1D inhibitors suppressed growth of PPM1D-mutated DIPGs in vitro. Orthotopic xenografting of PPM1D short hairpin RNA-transduced or PPM1D inhibitor-treated, PPM1D-mutated DIPG cells into immunodeficient mice resulted in reduced tumor proliferation, increased apoptosis, and extended mouse survival. PPM1D inhibition had similar effects to IR alone on DIPG growth inhibition and augmented the anti-proliferative and pro-apoptotic effects of IR in PPM1D-mutated DIPG models.PPM1D mutations inactivate DDR and promote DIPG growth. Treatment with PPM1D inhibitors activated DDR pathways and enhanced the anti-proliferative and pro-apoptotic effects of IR in DIPG models. Our results support continued development of PPM1D inhibitors for phase I/II trials in children with DIPG.
Skeletal morbidities in the prostate cancer (PC) patient.
Authors: Lisa Marie Ruppert, Howard I. Scher
Journal: Journal of Clinical Oncology (2015)

e16106 Background: Individuals with PC are at risk for skeletal complications and functional impairments secondary to metastatic disease and treatments. Underappreciated is the impact of age related changes and non-skeletal comorbidities that can adversely affect spinal stability and compromise functional status. Methods: Retrospective review of individuals with PC evaluated in a joint medical oncology and physiatry clinic. Data was collected on symptoms, clinical findings, function, imaging and underlying etiology. Results: 78 men of 163 had complaints prompting referral to physiatry. 63% had osseous metastases. 37% had age related spine changes without metastases. Most common symptoms were back pain (52%), musculoskeletal non-spine pain (23%), weakness and decreased endurance (32%), and neurological impairments (26%). Often multiple complaints were reported. Overall, 49% of cases had back pain in the lumbar spine felt to be age related, 39% from metastases, 12% had multifactorial etiology. Musculoskeletal pain was noted during 23% of cases, which was the result of degenerative changes in 78%. Generalized weakness and decreased endurance reported in 32% of encounters was all treatment related. Neurological impairments reported in 26% of encounters, included sensory changes, focal weakness, balance impairments, gait abnormalities and bowel and bladder dysfunction. 50% of neurological impairments were cancer related either from treatment or epidural disease. Recommendations included skilled physical and/or occupational therapies, correction of body mechanics, education on safe exercise and precautions, bracing, and medical management of symptoms. When indicated discussions were held with the treating oncologist regarding ongoing oncologic treatment. Conclusions: Age related changes and non-skeletal comorbidities are prevalent in the PC population. Focused assessment allows for guidance on decision making and rehabilitation interventions improving functional status and potentially preventing negative outcomes. Further study is needed to fully understand the interplay of age related changes, non-skeletal co-morbidities, bone metastases and treatment on the development of symptoms and functional impairments.
Time of referral of patients (pts) with recurrent/metastatic (r/m) head and neck squamous cell cancer (HNSCC) to medical oncology and survival.
Authors: Marco Siano, Vittoria Espeli, Marie-Claire Desax, Martina Anja Broglie, Markus Joerger
Journal: Journal of Clinical Oncology (2015)

e17046 Background: There is no consensus on the adequate time of referral to palliative systemic treatment in patients with r/mHNSCC and it remains unclear whether the time between the diagnosis of metastatic disease and the start of palliative systemic treatment is a prognostic factor for survival in this group of patients. This study was initiated to assess whether the timepoint of referral and start of systemic chemotherapy affects survival in patients with r/mHNSCC. Methods: We performed a retrospective chart review and selecting patients with metastatic HNSCC referred to Medical Oncology between January 2000 and May 2014. We assessed patient characteristics such as performance status, stage at primary diagnosis, number of systemic treatment lines and time points of referral to the Medical Oncologist, confirmation of metastatic disease, start of systemic treatment and death. The primary endpoint was to assess the prognostic effect of the time between diagnosis of metastases to referral (referral time) to survival from the time of metastatic disease (M+-survival) using pairwise correlation analysis and multivariate Cox regression analysis. Results: 110 pts with r/mHNSCC were evaluable for analysis. Systemic regimens applied in first line were mainly carboplatin/paclitaxel in 57%, in combination with cetuximab in 14%, other combinations including cetuximab in 5%, any single agent in 6% and no therapy at all in 14%. As second line treatment, mainly anti-EGFR antibodies as single agent or in combination were applied in 88% of pts. Median M+-survival was 13 months (95%-CI 10.5-15 months), while survival from first-line treatment was 8 months (95%-CI 6.5-12 months). Referal time showed a non-significant, positive correlation with M+-survival (R = 0.17, P = 0.10). Referral time had no significant effect on M+-survival. ECOG performance score was the only prognostic factors with regards to M+-survival (HR 1.59, 95%-CI 1.17-2.15, P = 0.003). Conclusions: Referral time of r/mHNSCC pts to medical oncology for the evaluation of systemic treatment had no prognostic impact. A prospective randomised trial is difficult to be performed in this setting making our analysis pivotal.
Notch expression and bevacizumab efficacy in colorectal cancer patients.
Authors: Francesca Negri, Roberto Sala, Cecilia Bozzetti, Pellegrino Crafa, Costanza Lagrasta, Giuseppe Pedrazzi, Giorgio Gardini, Ione Tamagnini, Alessandra Bisagni, Cinzia Azzoni, Lorena Bottarelli, Ida Romano, Rosa Porzio, Gian Paolo Bacchini, Carlo Paties, Gianluca Tomasello, Francesco Leonardi, Andrea Ardizzoni, Carmine Pinto
Journal: Journal of Clinical Oncology (2015)

612 Background: Antiangiogenic therapies represent a well established additional treatment to standard chemotherapy, nevertheless no markers are available to suggest a successful outcome linked to the use of bevacizumab. To investigate potential mechanisms of resistance to angiogenesis inhibitor bevacizumab, Notch expression was correlated with response and survival in a series of bevacizumab treated advanced colorectal cancer (CRC) patients. Methods: Notch expression was evaluated by immunohistochemistry (IHC) on 65 primary CRC enrolled within 6 randomized clinical trials assessing first-line bevacizumab plus chemotherapy. Notch IHC was conducted using a polyclonal antibody to Cleaved Notch1 (Cell Signaling Technology, Danvers, MA). Notch expression was scored based on intensity of staining (0: none, 1+: weak, 2+: moderate; 3+: strong) and on percentage of immunostained cells. A control series of 21 advanced CRC treated with chemotherapy alone was also examined. Results: Notch positivity was localized to the cytoplasm or nucleus of malignant epithelial cells. In all, 11 of 61 (18%) evaluable primary tumours had a high Notch expression (IHC 3+). Six of the 11 cases (55%) with high Notch expression (IHC 3+) experienced progressive disease compared with 5 of 50 (10%) low Notch expression cases (IHC 0 1+ 2+) (p = 0.003). A high Notch expression also demonstrated an inferior median PFS (4.9 vs. 12.1 months; HR = 2.51; 95% CI, 0.96 to 6.58; p = 0.007) and OS (19.3 vs. 30.4 months; HR = 2.21; 95% CI, 0.79 to 6.15; p = 0.039) compared with low Notch expression cases. When the groups were further analyzed considering VEGF expression, the best outcome was found in low Notch (IHC 0 1 +) and high VEGF expressing tumors (IHC 2+ 3+) (response rate 9 of 11, 82 % vs. 1 of 5, 20%, in patients with high levels of Notch and VEGF expression, respectively). No correlation was found between Notch expression and clinical response in the series of patients treated with chemotherapy without bevacizumab. Conclusions: Notwithstanding the limited power of the present analysis, these data seem to suggest that low Notch expression might be a marker for successful bevacizumab treatment.
A gastric resident drug delivery system for prolonged gram-level dosing of tuberculosis treatment
Authors: Malvika Verma, Karan Vishwanath, Feyisope Eweje, Niclas Roxhed, Tyler Grant, Macy Castaneda, Christoph Steiger, Hormoz Mazdiyasni, Taylor Bensel, Daniel Minahan, Vance Soares, John A. F. Salama, Aaron Lopes, Kaitlyn Hess, Cody Cleveland, Daniel J. Fulop, Alison Hayward, Joy Collins, Siddartha M. Tamang, Tiffany Hua, Chinonyelum Ikeanyi, Gal Zeidman, Elizabeth Mule, Sooraj Boominathan, Ellena Popova, Jonathan B. Miller, Andrew M. Bellinger, David Collins, Dalia Leibowitz, Shelly Batra, Sandeep Ahuja, Manju Bajiya, Sonali Batra, Rohit Sarin, Upasna Agarwal, Sunil D. Khaparde, Neeraj K. Gupta, Deepak Gupta, Anuj K. Bhatnagar, Kamal K. Chopra, Nandini Sharma, Ashwani Khanna, Jayeeta Chowdhury, Robert Stoner, Alexander H. Slocum, Michael J. Cima, Jennifer Furin, Robert Langer, Giovanni Traverso
Journal: Science Translational Medicine (2019)

A retrievable device, compatible with nasogastric tube administration, releases grams of drug over weeks while residing in the stomach.
Correction: The ribosomal RPL10 R98S mutation drives IRES-dependent BCL-2 translation in T-ALL
Authors: Kim R. Kampen, Sergey O. Sulima, Benno Verbelen, Tiziana Girardi, Stijn Vereecke, Laura Fancello, Gianmarco Rinaldi, Jelle Verbeeck, Joyce Op de Beeck, Anne Uyttebroeck, Jules P. P. Meijerink, Anthony V. Moorman, Christine J. Harrison, Pieter Spincemaille, Jan Cools, David Cassiman, Sarah-Maria Fendt, Pieter Vermeersch, Kim De Keersmaecker
Journal: Leukemia (2019)
Increasing isoniazid preventive therapy in people living with HIV in north central Nigeria: outcomes from a quality improvement strategy
Authors: Tongdiyen L Jasper, Iheanyichukwu Onwubiko, Imoiboho Williams, Oriaku Ofem, Uteng Wilson, Hyacinth I Nnaemeka, Iboro E Nta, Young Oluokun, Sunny Phillips, Patrick Dakum
Journal: The Lancet Global Health (2019)

BackgroundIsoniazid preventive therapy (IPT) significantly reduces the incidence of active tuberculosis in people living with HIV. However, despite high tuberculosis morbidity and mortality in people living with HIV, uptake of IPT remains grossly suboptimal, with implementation impeded by several barriers related to health workers and patients. We evaluated the use of a quality improvement approach to improve IPT in a tertiary hospital in north central Nigeria with a high HIV burden.MethodsIn July, 2018, a 4-week quality improvement pilot project was undertaken at the Federal Medical Centre in Keffi, Nigeria. The facility-based continuous quality-improvement committee, comprised of different cadres of staff working in the hospital's antiretroviral therapy clinic, reviewed their HIV quality-of-care indicators and noted that only 3% of eligible HIV clients received IPT between September, 2017, and March, 2018. The committee did a root cause analysis and identified poor knowledge of clinicians on the importance of IPT, fear of drug resistance, frequent stock-outs of isoniazid, and poor medication adherence as the key reasons for low rates of IPT. In response to these findings, the following key change ideas were implemented: IPT orientation for clinicians, incorporation of IPT education into routine health education for people living with HIV, display of IPT information education and communication materials in consulting and patient waiting rooms, and auditing of clients' folders prior to consultation to identify and tag eligible folders with IPT sticky notes.FindingsBetween June 19, 2018, and July 17, 2018, 278 adult clients with a clinic appointment had their folders audited for IPT eligibility and 108 eligible folders (39%) were identified and tagged with an IPT sticker. Of those eligible for IPT, 103 (95%) kept their clinic appointment and all had a 6-month course of isoniazid prescribed. However, of the patients who attended, only 93 (90%) received IPT because stock of the drug had run out.InterpretationA quality improvement strategy for improving IPT in HIV patients was effective, with 86% of eligible patients receiving treatment—an 83% increase from baseline. Quality-improvement principles such as team work and implementation of change ideas targeted at root causes of the problem were pivotal to success. Continued implementation and scale-up of effective change ideas to other hospitals could greatly reduce tuberculosis morbidity and mortality in people living with HIV, while ensuring continued availability of isoniazid.FundingCDC-PEPFAR.
In vivo neuronal gene editing via CRISPR–Cas9 amphiphilic nanocomplexes alleviates deficits in mouse models of Alzheimer’s disease
Authors: Hanseul Park, Jungju Oh, Gayong Shim, Byounggook Cho, Yujung Chang, Siyoung Kim, Soonbong Baek, Hongwon Kim, Jeain Shin, Hwan Choi, Junsang Yoo, Junyeop Kim, Won Jun, Minhyung Lee, Christopher J Lengner, Yu-Kyoung Oh, Jongpil Kim
Journal: Nature Neuroscience (2019)