tbuckley/cabot-search huggingface dataset:
Abstract P445: Pulmonary Function is Associated With the Subendocardial Viability Ratio
Authors: Amena Keshawarz, Martin Cech, Elizabeth Westfeldt, Gregory L Kinney, Janet Snell-bergeon
Journal: Circulation (2020)

Introduction: Pulmonary function is reduced and arterial stiffening is increased in type 1 diabetes. While increased arterial stiffness is associated with greater risk of cardiovascular disease in type 1 diabetes, the association between reduced pulmonary function and health outcomes in this population is less understood. The subendocardial viability ratio (SEVR), a ratio comparing myocardial perfusion to cardiac workload, may provide useful information pulmonary function and myocardial hypoxemia in the context of pulmonary function in type 1 diabetes. Hypothesis: We tested the hypothesis that impaired pulmonary function (i.e., percent predicted forced vital capacity [FVCpp], forced expiratory volume at 1 second [FEV 1 pp], and FEV 1 /FVC), is associated with reduced SEVR in adults with and without type 1 diabetes. Methods: We conducted pulse wave analysis on 208 adults with type 1 diabetes (mean age 52±9 years) and 285 adults without diabetes (mean age 55±8 years) to obtain the outcome measure of SEVR. All participants underwent non-bronchodilated spirometry testing to obtain FVCpp, FEV 1 pp, and FEV 1 /FVC. Independent t-tests were used to test the difference by diabetes status in each pulmonary function measure and the SEVR. Linear regression models were used to test the association between each pulmonary function measure and SEVR after adjustment for age, sex, diabetes status, smoking status, and heart rate. Results: FVCpp and FEV 1 pp were both significantly lower in type 1 diabetes (87.5% and 85.6%, respectively) compared to controls without diabetes (95.6% and 94.9%, respectively; p&lt;0.001 for both). There was no significant difference by diabetes status in FEV 1 /FVC (97.5% vs. 99.0%, p=0.07). SEVR was also significantly lower in type 1 diabetes (137.5 vs. 159.6, p&lt;0.001). In an adjusted linear model, both FVCpp and FEV 1 pp were associated with SEVR. FVCpp was associated with 0.086 greater SEVR per SD (p=0.002), and FEV 1 pp was associated with 0.058 greater SEVR per SD (p=0.04). FEV 1 /FVC was not significantly associated with SEVR (p=0.37). In the model testing FVCpp, type 1 diabetes was associated with 0.18 lower SEVR (p&lt;0.001). Similarly, in the model testing FEV 1 pp, type 1 diabetes was associated with 0.19 lower SEVR (p&lt;0.001). After accounting for FEV 1 /FVC, type 1 diabetes was still associated with 0.20 lower SEVR (p&lt;0.001). Conclusions: In conclusion, reduced pulmonary function was associated with reduced SEVR in cross-sectional analysis, but type 1 diabetes remained independently associated with reduced SEVR after accounting for reduced pulmonary function. The mechanism between pulmonary function and SEVR is unclear, but future research may reveal pathways or shared etiologies in type 1 diabetes.
HLA patterns in pernicious anaemia.
Authors: B Ungar, J D Mathews, B D Tait, D C Cowling
Journal: BMJ (1977)

The pattern of HLA antigens was studied in 127 patients with Addisonian pernicious anaemia. The pattern in the whole group of patients differed significantly from that in 586 controls. But different subgroups of the patients had different HLA antigens. Among 27 patients with anaemia associated with endocrine disease there was an increased frequency of HLA-B8, B18, and BW15. The remaining 100 patients, who did not have endocrine disease, showed increased frequencies of HLA-B7 and B12. The positive association with HLA-B12 among this subgroup was confined to 62 patients with severly impaired vitamin B12 absorption, including 13 patients with vitamin B12 neuromyelopathy, who had the highest frequencies of HLA-B7 and B12. The significant heterogeneity in HLA patterns in different clinical subgroups of these patients indicates genetic heterogeneity in pernicious anaemia and explains previous discrepancies in the associations between HLA antigens and pernicious anaemia.
Oncolytic HSV–Infected Glioma Cells Activate NOTCH in Adjacent Tumor Cells Sensitizing Tumors to Gamma Secretase Inhibition
Authors: Yoshihiro Otani, Ji Young Yoo, Samantha Chao, Joseph Liu, Alena Cristina Jaime-Ramirez, Tae Jin Lee, Brian Hurwitz, Yuanqing Yan, Hongsheng Dai, Joseph C. Glorioso, Michael A. Caligiuri, Jianhua Yu, Balveen Kaur
Journal: Clinical Cancer Research (2020)

To examine the effect of oncolytic herpes simplex virus (oHSV) on NOTCH signaling in central nervous system tumors.Bioluminescence imaging, reverse phase protein array proteomics, fluorescence microscopy, reporter assays, and molecular biology approaches were used to evaluate NOTCH signaling. Orthotopic glioma-mouse models were utilized to evaluate effects in vivo.We have identified that herpes simplex virus-1 (HSV-1; oncolytic and wild-type)-infected glioma cells induce NOTCH signaling, from inside of infected cells into adjacent tumor cells (inside out signaling). This was canonical NOTCH signaling, which resulted in activation of RBPJ-dependent transcriptional activity that could be rescued with dnMAML. High-throughput screening of HSV-1-encoded cDNA and miRNA libraries further uncovered that HSV-1 miR-H16 induced NOTCH signaling. We further identified that factor inhibiting HIF-1 (FIH-1) is a direct target of miR-H16, and that FIH-1 downregulation by virus encoded miR-H16 induces NOTCH activity. FIH-1 binding to Mib1 has been reported, but this is the first report that shows FIH-1 sequester Mib1 to suppress NOTCH activation. We observed that FIH-1 degradation induced NOTCH ligand ubiquitination and NOTCH activity. REMBRANDT and The Cancer Genome Atlas data analysis also uncovered a significant negative regulation between FIH-1 and NOTCH. Furthermore, combination of oHSV with NOTCH-blocking gamma secretase inhibitor (GSI) had a therapeutic advantage in two different intracranial glioma models treated with oncolytic HSV, without affecting safety profile of the virus in vivo.To our knowledge this is the first report to identify impact of HSV-1 on NOTCH signaling and highlights the significance of combining oHSV and GSI for glioblastoma therapy.
Abstract P267: Burden of Disease Among Older Adults With Type 1 and Type 2 Diabetes: Results From the Study of Longevity in Diabetes (SOLID)
Authors: Mary E Lacy, Paola Gilsanz, Chloe Eng, Michal S Beeri, Andrew J Karter, Rachel A Whitmer
Journal: Circulation (2020)

Introduction: Increasing incidence of type 1 diabetes (T1D) coupled with increasing life expectancy have resulted in an unprecedented number of older adults living with T1D. However, little is known about the burden of aging and diabetes-related complications in this unique group. We hypothesized that older adults with T1D would have greater diabetes and aging-related burden compared to an age, sex, race/ethnicity, and education-matched group of older adults with type 2 diabetes (T2D). Methods: We compared the following characteristics by diabetes type among older adults (aged ≥60) with T1D (n=805) and T2D (n=249) from the Study of Longevity in Diabetes (SOLID) using chi-squared tests: diabetes history (age of onset, diabetes duration); diabetes-related complications (retinopathy, neuropathy, nephropathy, severe hypo- and hyperglycemia resulting in hospitalization/emergency department utilization), cardiovascular disease (stroke, MI, coronary bypass), and geriatric syndromes (depression, incontinence, memory problems and functional impairment). Results: Average age at diagnosis and duration of diabetes, respectively, were 28 years old and 40 years duration for T1D and 56 years old and 13 years duration for T2D (Table 1). Compared to T2D, participants with T1D were more likely to report history of retinopathy, neuropathy, nephropathy, lifetime hypo- and hyperglycemic events resulting in hospitalization/emergency department utilization, and history of a coronary bypass. By contrast, those with T2D were more likely to be incontinent and have functional impairment. Conclusions: Our results show that diabetes-related complications are more prevalent in those with T1D than in comparable adults with T2D, while certain geriatric syndromes were more prevalent in those with T2D. Older adults with T1D are a growing population with unique diabetes-specific and aging-related considerations. Additional research is needed to understand the interplay of aging and diabetes in this group to inform patient care .
Adherence to Surveillance for Second Malignant Neoplasms and Cardiac Dysfunction in Childhood Cancer Survivors: A Childhood Cancer Survivor Study
Authors: Adam P. Yan, Yan Chen, Tara O. Henderson, Kevin C. Oeffinger, Melissa M. Hudson, Todd M. Gibson, Joseph P. Neglia, Wendy M. Leisenring, Kirsten K. Ness, Jennifer S. Ford, Leslie L. Robison, Gregory T. Armstrong, Yutaka Yasui, Paul C. Nathan
Journal: Journal of Clinical Oncology (2020)

To evaluate childhood cancer survivors' adherence to surveillance protocols for late effects of treatment and to determine the factors affecting adherence.Between 2014 and 2016, 11,337 survivors and 2,146 siblings in the Childhood Cancer Survivor Study completed a survey ascertaining adherence to Children's Oncology Group (COG) guidelines for survivors at high risk for second malignant neoplasms or cardiac dysfunction and to the American Cancer Society (ACS) cancer screening guidelines for average-risk populations. Adherence rates and factors affecting adherence were analyzed.Median age at diagnosis was 7 years (range, 0-20.9 years), and median time from diagnosis was 29 years (range, 15-47 years). Among high-risk survivors, adherence to COG breast, colorectal, skin, and cardiac surveillance was 12.6% (95% CI, 10.0% to 15.3%), 37.0% (34.1% to 39.9%), 22.3% (21.2% to 23.4%), and 41.4% (40.1% to 42.7%), respectively. Among average-risk survivors, adherence to ACS breast, cervical, and colorectal screening was 57.1% (53.2% to 61.0%), 83.6% (82.7% to 84.5%), and 68.5% (64.7% to 72.2%), respectively. Twenty-seven percent of survivors and 20.0% of primary care providers (PCPs) had a survivorship care plan (SCP). For high-risk survivors, SCP possession was associated with increased adherence to COG breast (22.3% v. 8.1%; prevalence ratio [PR], 2.52; CI, 1.59 to 4.01), skin (34.8% v 23.0%; PR, 1.16; CI, 1.01 to 1.33), and cardiac (67.0% v 33.1%; PR, 1.73; CI, 1.55 to 1.92) surveillance. For high-risk survivors, PCP possession of a SCP was associated only with increased adherence to COG skin cancer surveillance (36.9% v 23.2%; PR, 1.24; CI, 1.08 to 1.43).Guideline adherence is suboptimal. Although survivor SCP possession is associated with better adherence, few survivors and PCPs have one. New strategies to improve adherence are needed.
Bismuth‐Based Nanomaterials: Recent Advances in Tumor Targeting and Synergistic Cancer Therapy Techniques
Authors: Samireh Badrigilan, Jalal Choupani, Hashem Khanbabaei, Mojtaba Hoseini‐Ghahfarokhi, Thomas J. Webster, Lobat Tayebi
Journal: Advanced Healthcare Materials (2020)

Abstract Despite all of the efforts in the field of cancer therapy, the heterogeneous properties of tumor cells induce an insufficient therapeutic outcome when treated with conventional monotherapies, necessitating a shift in cancer treatment from monotherapy to combination therapy for complete cancer treatment. Multifunctional bismuth (Bi)‐based nanomaterials (NMs) with therapeutic functions hold great promise for the fields of cancer diagnosis and therapy based on their low toxicity, X‐ray sensitive capabilities, high atomic number, near‐infrared driven semiconductor properties, and low cost. Herein, a comprehensive review of recent advances in various medicinal aspects of Bi‐based NMs is presented including: evaluation of in‐tumor site accumulation, tumor targeting, and therapeutic performance, as well as the characteristics, benefits, and shortcomings of Bi‐based NM‐mediated major monotherapies. In addition, the cooperative enhancement mechanisms between two or more of these monotherapies are described in detail to address common challenges in cancer therapy, such as multidrug resistance, hypoxia, and metastasis. Finally, this review opens new insights into the design of multimodal synergistic therapies for potential future clinical applications of Bi‐based NMs.
Impact of NCI Clinical Announcement upon use of chemoradiation for women with cervical cancer
Authors: E. L. Trimble, D. Gius, L. C. Harlan
Journal: Journal of Clinical Oncology (2007)

5537 Background: On the basis of 5 NCI-sponsored randomized phase III trials, in 1999 the NCI issued a Clinical Announcement recommending that women with cervical cancer who require radiation also receive concomitant platinum-based chemotherapy. We undertook a population-based cohort study to determine whether the 1999 NCI Clinical Announcement was associated with changes in clinical practice in the United States. Methods: Through the NCI’s SEER program, we identified 973 women with invasive cervical cancer diagnosed in 1997, 773 diagnosed in 2000, and 1370 diagnosed in 2001. Hospital records were re-abstracted and treated physicians were contacted to verify initial therapy provided to each patient. Results: In multivariate analysis, we found a significant increase in the use of chemoradiation between 1997 and 2001/2001 among women with cervical cancer of all stages for which radiation would be appropriate. (see table ). Compared to women with well-differentiated tumors, women with moderately or poorly differentiated tumors were more likely to receive chemoradiation. Women aged 75 years or older were significantly less likely to receive chemoradiation than younger women. We saw no impact of race/ ethnicity or insurance status upon receipt of chemoradiation. Conclusions: Publication of the results from these 5 sutdies, extensive professional educational efforts, and the NCI’s Clinical Announcement were associated with widespread adoption of chemotherapy in the treatment of cervical cancer in the United States. [Table: see text] No significant financial relationships to disclose.
Abstract P339: Association Between Cardiometabolic Syndrome And Cancer: Systematic Review
Authors: Anshul Saxena, Muni Rubens, Venkataraghavan Ramamoorthy, Sankalp Das, Chintan B Bhatt, Joseph A Salami, Peter McGranaghan, Nancy Shehadeh, Emir Veledar
Journal: Circulation (2020)

Introduction: Cardiometabolic syndrome consists of a cluster of metabolic dysfunctions such as impaired glucose tolerance, insulin resistance, dyslipidemia, central adiposity, and hypertension. According to the latest estimates, globally, nearly 25% of all adults have cardiometabolic syndrome. Both cardiometabolic syndrome and cancer pathophysiology commonly involve inflammation and oxidative stress. The objective of this systematic review was to evaluate existing evidences that support the association between cardiometabolic syndrome and risk of developing cancer. Methods: We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and Scopus for relevant articles published from the database inception until October 2019. We followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines for this review. Using the Oxford Center for Evidence-Based Medicine guidelines individual studies were evaluated. A total of 59 articles were included in this study. Results: Our review showed that cardiometabolic syndrome was associated with increased risk for colorectal, hepatic, endometrial, breast, and bladder cancers. These associations showed variations for sex and geographical locations. For example, the associations were stronger for pancreatic and rectal cancers among women. The strength of these associations was also stronger for sex specific cancers such as breast and endometrial cancers. Studies on European populations showed that these associations were stronger for colorectal cancer among women. However, one study showed that presence of cardiometabolic syndrome contributed protective effects to prostate cancer among American men. In general, strongest associations were found for colorectal cancer among both men and women and hepatic cancer among men. Among cardiometabolic factors, impaired glucose tolerance and central adiposity were the greatest contributors towards increased risk for cancers. Conclusion: Given these results, there should be greater focus on primary prevention to identify and treat cardiometabolic risk factors. In addition, patients with greater cardiometabolic risk factors should be screened earlier and more frequently for cancers. A number of gender and geographical gaps identified in this review could be targeted for improvements as per the goals of 2030 sustainable development initiatives. Future studies should consider cardiometabolic syndrome and cancer together and develop effective interventions for decreasing the incidence and morbidity associated with both the conditions.
Long term peripheral neuropathy symptoms in breast cancer survivors.
Authors: Moaath Khader Mustafa Ali, Machelle Moeller, Lisa A. Rybicki, Halle C. F. Moore
Journal: Journal of Clinical Oncology (2017)

e21599 Background: Peripheral neuropathy (PN) is a common complication from chemotherapy (CTX), associated with significant morbidity, and may improve with time. The prevalence of long-term PN symptoms in breast cancer survivors is not well known. We sought to explore PN symptoms and associated risk factors among breast cancer survivors at least 2 years out from diagnosis. Methods: We performed a cross-sectional retrospective study investigating the prevalence of patient-reported numbness/tingling symptoms as a surrogate for PN in breast cancer survivors at our institution. We included patients with stage 0-III breast cancer who completed a questionnaire about symptoms and life-style habits at a survivorship visit that occurred 2 or more years after initial diagnosis. We evaluated the prevalence of PN and associated risk factors using univariable and multivariable logistic regression analysis; results are shown as odds ratio (OR) and 95% confidence interval (CI). Results: 605 patients assessed between April 2009 and October 2016 met eligibility for analysis. Median age was 60 (31-93) years. Median number of years from diagnosis to assessment was 6.3 (2-21). All patients had surgery and 62% had CTX. Twenty-seven percent reported PN. On univariable analysis, obesity, stage II &amp; III, mastectomy, PN before diagnosis, and receipt of taxane CTX were associated with PN (all p &lt; 0.05). Patients who were older, exercised before diagnosis, had ER/PR-positive disease and who received endocrine therapy reported less PN (all p &lt; 0.05). On multivariable analysis, only receipt of docetaxel (OR: 2.18, CI: 1.22- 3.88) or paclitaxel (OR: 4.07, CI: 2.54-6.50) and reporting PN symptoms before diagnosis (OR: 3.28, CI: 1.49-7.21) were associated with PN. Among patients without pre-existing PN symptoms, 15%, 19%, 28% and 43% reported long-term PN after no CTX, non-taxane CTX, docetaxel CTX and paclitaxel CTX respectively. Conclusions: At a median follow-up of 6.3 years from diagnosis, 28% of survivors in our cohort who had received docetaxel and 43% who had received paclitaxel report long-term PN symptoms compared with 15-19% in those who received no or non-taxane CTX. These data can help inform patients and clinicians regarding long-term PN risk following CTX.
Abstract 34: Association of Carotid Intima-Media Thickness and Other Carotid Ultrasound Features With Incident Dementia in The Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS)
Authors: Wendy Wang, Faye L Norby, Kristen M George, Alvaro Alonso, Thomas Mosley, Rebecca F Gottesman, Michelle L Meyer, Pamela L Lutsey
Journal: Circulation (2020)

Background: Increased carotid intima-media thickness (cIMT), a measure of carotid artery thickness, and carotid plaque are predictors of cardiovascular disease and atherosclerosis. Likewise, increased interadventitial diameter (IAD), which references arterial remodeling, and lower carotid distensibility coefficient (DC), which indicates carotid stiffness, are also predictors. These indices likely relate to cerebrovascular disease, and thus may constitute a form of vascular contributions to dementia and Alzheimer’s disease and related dementias. Therefore, we assessed the relationship of carotid measures and distensibility with incident dementia in the Atherosclerosis Risk in Communities (ARIC) study. Methods: 12,459 ARIC participants who had carotid ultrasound measurements in 1990-92 were followed through 2017 for incident dementia. Dementia cases were identified using in-person and phone cognitive status and informant assessments, hospitalization discharge codes, and death certificate codes. Cox proportional hazards models were used to estimate the hazards ratios for incident dementia per 1-SD and per quintile increment in arterial index (cIMT, IAD, and DC) and for presence of carotid plaque. Results: Participants were aged 57±6 at baseline, 57% were female, and 23% were black. Over a median follow-up of 24 years, 2,224 dementia events were ascertained. After multivariable adjustments, the highest quintile of both cIMT and IAD in midlife were associated with increased risk of incident dementia (Table; HRs [95% CIs]: 1.33 [1.15, 1.54]; 1.24 [1.06, 1.46]), while presence of carotid plaque was not (HR [95% CI]: 1.06 [0.97, 1.15]). Additionally, higher distensibility was associated with lower risk of dementia (HR [95% CI] highest vs. lowest quintile: 0.73 [0.61, 0.88]). Conclusion: Increased cIMT, IAD, and lower carotid distensibility are associated with an increased risk of incident dementia. These findings suggest that both atherosclerosis and carotid stiffness may be implicated in dementia risk.
Abstract P505: Real-world Data Validation Of A Novel P-wave Based Automatic Atrial Fibrillation Detection Algorithm
Authors: Åke Olsson, Magnus Samulesson
Journal: Circulation (2020)

Background: Automatic ECG algorithms using only RR-variability in ECG to detect AF have shown high false positive rates. By including P-wave presence in the algorithm, research has shown that it can increase detection accuracy for AF. Methods: A novel RR- and P-wave based automatic detection algorithm implemented in the Coala Heart Monitor ("Coala", Coala Life AB, Sweden) was evaluated for detection accuracy by the comparison to blinded manual ECG interpretation based on real-world data. Evaluation was conducted on 100 consecutive anonymous printouts of chest- and thumb-ECG waveforms, where the algorithm had detected both irregular RR-rhythms and strong P-waves in either chest or thumb recording (non-AF episodes classified by algorithm as Category 12).The recordings, without exclusions, were generated from 5,512 real-world data recordings from actual Coala users in Sweden (both OTC and Rx users) during the period of March 5 to March 22, 2019, with no control or influence by the researchers or any other organization or individual. The prevalence of cardiac conditions in the user population was unknown.The blinded recordings were each manually interpreted by a trained cardiologist. The manual interpretation was compared with the automatic analysis performed by the detection algorithm to determine the number of additional false negative indications for AF as presented to the user. Results: The trained cardiologist manually interpreted 0 of the 100 recordings as AF. Manual interpretation showed that the novel automatic AF algorithm yielded 0 % False Negative error and 100 % Negative Predictive Value (NPV) for detection of AF. Irregular RR-rhythms were detected in 569 recordings (10 % of a total of 5,512 recordings). The 100 non-AF recordings containing both irregular RR-rhythms and strong P-waves constituted 18% of all recordings with irregular RR-rhythms. Respiratory sinus arrhythmia was the single most prevalent condition and was found in 47% of irregular RR-rhythms with strong P-waves. Conclusion: The novel, P-wave based automatic ECG algorithm used in the Coala, showed a zero percent False Negative error rate for AF detection in ECG recordings with RR-variability but presence of P-waves, as compared to manual interpretation by a cardiologist.