tbuckley/cabot-search huggingface dataset:
Serum YKL-40 is elevated in a subgroup of patients after surgery for stage IIb-III melanoma
Authors: M. Jensen, J. S. Johansen, I. J. Christensen, H. Schmidt, P. H. Nørgaard, L. Bastholt
Journal: Journal of Clinical Oncology (2007)

8574 Background: High serum YKL-40 is associated with poor prognosis in patients with adeno- and squamous cell carcinoma, glioblastoma, and stage I-II and IV melanoma. YKL-40 is secreted by cancer cells, macrophages and neutrophils. YKL-40 is a growth and differentiation factor, and plays a role in tissue remodelling and angiogenesis. The aim of our study was to compare serum YKL-40 in patients after surgery for stage IIb-III melanoma with healthy individuals and with clinical and histological prognostic parameters. Methods: YKL-40 was determined by ELISA (Quidel, CA) in serum samples from 231 patients, with stage IIb-III melanoma. The 74 women and 157 men had a median age of 50 (range 22–76 years), and they were enrolled in a Nordic adjuvant protocol, randomizing to observation or interferon therapy (1 or 2 years). Baseline samples were drawn &lt;70 days after primary biopsy, but prior to start of therapy. Results: Serum YKL-40 was increased (p=0.003) in the 231 patients (median 47 μg/l, range 20–1,416 μg/l) compared to healthy individuals (43 μg/l, range: 20–184 μg/l, n=245). Serum YKL-40 was higher than the age-corrected 95 th percentile of s-YKL-40 in healthy individuals in 19% of the patients with melanoma thickness &gt;4 mm and no lymph node metastasis (n=27), in 8% with sentinel lymph node metastasis (n=89) and in 14% with clinical lymph node metastasis at time of surgery or as recurrence in the follow-up period (n=111). Comparison of serum YKL-40 in the 3 groups showed no significant differences (p=0.22). No difference was found comparing serum YKL-40 between the three groups of Breslow thickness (&lt; 1 mm, 1–2 mm, &gt; 2 mm)(p=0.66), and the two groups of Clark′s level (II-III, IV-V)(p=0.88) was found. A weak association (p=0.045) was found between s-YKL-40 and localization of primary tumor, with trunc having the highest median concentration of s-YKL-40. No association between an elevated s-YKL-40 with number of positive lymph nodes (0.36), ulceration (p=0.81), extranodal growth (p=0.56), or histologic subtype of primary tumor (p=0.48) was observed. Conclusion: Serum YKL-40 is elevated in a subgroup of melanoma patients with stage IIb-III and not associated with classical clinical and histological parameters. It is not known if the increased YKL-40 reflects the biological behaviour of the disease. No significant financial relationships to disclose.
Abstract 23: Sexual Dimorphism In Genetic Associations Of Testosterone And Sex-hormone Binding Globulin With Coronary Heart Disease
Authors: Jie Hu, Jun Li, Wonil Chung, Kathryn M Rexrode, Liming Liang
Journal: Circulation (2020)

Introduction: Men have higher prevalence and mortality of coronary heart disease (CHD) than women. Sex differences in associations of testosterone (T) and sex-hormone binding globulin (SHBG) with CHD risk have been recognized. But mechanisms underlying sex differences in CHD are unknown. Hypothesis: Genetic regulations of T and SHBG may differ by sex; such genetic heterogeneity may contribute to sex differences in CHD. Methods: We carried out a sex-stratified genome-wide association study for T, SHBG, and CHD in 187,888 men and 221,014 women from the UK Biobank, to identify sex-specific ( P &lt;5х10 -8 in one sex and P ≥5х10 -8 in the other) and sex-differed ( P &lt;5х10 -8 in both sexes but effects differed significantly by sex) loci for each trait. Plasma T and SHBG were measured by immunoassay. Genetic correlations were estimated using linkage disequilibrium score regressions. We used cross-traits meta-analyses to identify loci that coregulate a biomarker (T or SHBG) and CHD. Results: The median T levels in men were 10-12 times higher than that in women across all age groups. Women had higher SHBG levels. We identified 344 sex-specific/sex-differed loci for T and 89 for SHBG ( Fig. A ). Genetic correlations between sexes were 0.02 for T, suggesting mostly sex-specific genetic regulation, and were 0.86 for SHBG and 0.94 for CHD, suggesting partially sex-differed genetic regulation. We observed a significant inverse genetic correlation between T and CHD in men ( r g =-0.15; P =1.4х10 -5 ) but not in women. The inverse genetic correlation between SHBG and CHD was stronger in women ( r g =-0.33; P =5.2х10 -11 ) than men ( r g =-0.18; P =2.8х10 -7 ). We identified 31 sex-specific loci coregulating T and CHD (26 for men and 5 for women), and 48 sex-specific loci coregulating SHBG and CHD (35 for men and 13 for women) ( Fig. B ). Tissue-specific gene expression regulations at some loci (e.g. LPA ) were also differed by sex ( Fig. C ). Conclusions: The between-sex heterogeneity in genetic coregulations of T and SHBG with CHD may contribute to the sex-differences in CHD etiology.
Abstract P302: Adverse Health Behaviors Identified in Africans Living With Undiagnosed Diabetes in America
Authors: Thomas Hormenu, Arsene F Hobabagabo, Elyssa M Shoup, Christopher W Dubose, Margrethe F Horlyck-Romanovsky, Anne E Sumner
Journal: Circulation (2020)

Background: For African born blacks living in America, lifestyle and food choices may promote or exacerbate diabetes. Objective: Our goal was to determine by OGTT the prevalence of diabetes in 451 self-identified as healthy African-born blacks living in America and then compare social and metabolic characteristics according to whether diabetes was detected. Methods: When the lifestyle questionnaires were administered, neither the participant nor the health care provider knew the results of the OGTT. Waist circumference (WC), inflammatory markers and lipids were obtained. Computerized tomographic scans were done to measure visceral adiposity (VAT). Results: Diabetes was identified in 7% (30/451) of participants. Data provided in the Table. Age and years in the United States were higher in the group with diabetes. After adjusting for age, BMI did not differ by diagnosis, but WC and VAT was higher with diabetes. Homocysteine, hsCRP, and TG were higher and HDL lower in the group with diabetes. The prevalence of both smoking and alcohol intake were higher in the group with diabetes. In addition, the rate of consumption ≥5 servings/day of fruits and vegetables tended to be lower. Education, income, and health insurance did not differ by diagnosis. Conclusions: Africans with undiagnosed diabetes are unhealthier than their counterparts without diabetes. Difficult to address social characteristics such as education, income and health insurance did not differ between groups. Nonetheless, identification of undiagnosed diabetes is important because behavior change in regard to smoking, alcohol, and fiber intake could improve health status.
Fulvestrant in the treatment of HER2-positive advanced breast cancer (ABC)
Authors: J. F. Robertson, G. G. Steger, P. Neven, S. Barni
Journal: Journal of Clinical Oncology (2007)

1061 Background: Patients with HER2-positive (HER2+) disease are regarded as less responsive to endocrine therapy, although there are data to suggest activity in some patients. Fulvestrant is a novel estrogen receptor (ER) antagonist with no agonist effects, and is licensed for the treatment of postmenopausal women with ABC after progression on prior endocrine therapy. Here we pool clinical experience data from HER2+ patients who received fulvestrant. Methods: Postmenopausal women with HER2+ disease were treated with fulvestrant 250 mg/month IM until progression/other reason for discontinuation. Clinical response was assessed monthly using RECIST or UICC criteria, or the clinical judgment of the physician. Clinical benefit (CB) was defined as the proportion of patients experiencing a response (complete or partial response [PR]) or stable disease (SD) lasting =6 months. Results: Fifty-three patients with HER2+ ABC and a median age of 61 years (range 30–85 years) received fulvestrant. Patients received a median of two prior endocrine therapies (range 0–3) and one chemotherapy (range 0–5) for ABC. ER and/or progesterone receptor (PgR) status was assessed in 52 patients. Twenty-two patients experienced CB (4 PR and 18 SD =6 months) with fulvestrant, giving a CB rate of 41.5% (n=53), with activity observed up to 4 th -line endocrine therapy. CB rate was 47.8% amongst ER+/PgR+ patients (n=23) and 45.0% amongst ER+/PgR- patients (n=20). Sixteen adverse events (AEs) were reported (30.2%), with one considered severe (restlessness). No patients discontinued due to AEs. Conclusions: From these data, fulvestrant appears to demonstrate activity in patients with HER2+ ABC. Observed activity was independent of PgR status and is consistent with fulvestrant efficacy demonstrated in the overall ABC population. These are encouraging data, warranting further exploration of the use of fulvestrant in HER2+ disease. No significant financial relationships to disclose.
Abstract P489: Association of Fasting Triglyceride Levels With Long-Term Competing Risks for Cause-Specific Cardiovascular Disease Events Among Middle-aged White and Black Men and Women
Authors: Sadiya S Khan, Hongyan Ning, Norrina B Allen, Mercedes R Carnethon, Donald M Lloyd-jones, John T Wilkins
Journal: Circulation (2020)

Introduction: Hypertriglyceridemia is common and reflects poor metabolic health, but conflicting data exist regarding the independent association of triglycerides (TG) and cardiovascular disease (CVD). In addition, whether elevated TG are associated with differential long-term risks for CVD subtypes and whether this varies by sex and race, is not well-established. Therefore, we sought to examine the incidence of coronary heart disease, stroke, or heart failure in white and black US men and women by baseline TG levels. Methods: We included individual-level pooled data from 5 population-based cohorts and stratified middle-aged participants (index ages 40-59 years) who were free of CVD at baseline by sex and race. We categorized fasting TG levels as optimal (&lt;100 mg/dL), intermediate (100 to 150 mg/dL), or elevated (&gt;150mg/dL). We performed 1) Irwin’s restricted mean to estimate years lived free of and with CVD and 2) competing Cox models (adjusted for age, education, smoking, obesity, hypertension, diabetes, total cholesterol, and HDL-cholesterol) to estimate joint cumulative risks for CVD events (overall and by subtype) and non-CVD death. Results: Among the 20,406 participants, 26% were black and 55% were women. Elevated TG was associated with significantly fewer healthy years lived free of CVD in all race-sex groups (p&lt;0.05 compared with optimal TG). Overall, competing cumulative incidence of CVD as well as non-CVD death was higher in intermediate and elevated TG subgroups compared with the optimal TG group. After adjustment for other risk factors, elevated TG were not associated with risks for any CVD subtype in black adults; among whites, elevated TG were associated with risk for stroke as a first event in men, and with all CVD subtypes in women (TABLE) . Discussion: Using pooled individual-level data from 5 large cohorts of middle-aged individuals, we observed differential competing risks by sex and race group for CVD subtypes associated with elevated TG. White women especially may have independent risk from elevated TG.
WBC changes as a pharmacodynamic marker of outcome in metastatic renal cell carcinoma (mRCC) patients (Pts) receiving sunitinib
Authors: S. George, A. Richmond, P. Elson, T. Jin, L. Wood, J. A. Garcia, B. I. Rini, J. Finke, R. M. Bukowski
Journal: Journal of Clinical Oncology (2007)

5043 Background: Sunitinib is a VEGF, PDGF, c-Kit and FLT-3 inhibitor with significant anti-tumor activity in mRCC. Myelosuppression is a common side effect observed in mRCC pts treated with sunitinib. Thus, the association of myelosuppression with clinical outcome was investigated. Methods: All mRCC pts receiving sunitinib at The Cleveland Clinic Taussig Cancer Center with available data were investigated. White blood cell (WBC) and differential counts at baseline and day 28 of cycle 1 were collected. Peripheral blood mononuclear cell (PBMC) T helper 1 (Th1), T helper 2 (Th2) and T regulatory cell (Treg) numbers at baseline and day 28 of C1 were determined using flow cytometry. Hematologic parameters were analyzed as continuous variables and also dichotomized using a recursive partitioning algorithm. Fisher’s exact test was used to analyze categorical data, the log rank test was used to assess time to progression (TTP) and Spearman’s rank correlation was used to summarize associations between hematologic and immune parameters. Results: Sixty-seven pts were studied (75% male, median age 59 yrs). Objective responses (OR) included 2 complete and 35 partial responses (overall response rate 55%), with a median (m) TTP of 12.4 months. There was a significant reduction (end of C1 vs. baseline) in the absolute neutrophil count (ANC) (m decrease of 46.4%; p &lt;0.001) and absolute monocyte count (m decrease of 41.3%; p&lt;0.001), but not absolute lymphocyte count (m 6.6% decrease; p=0.5). A decrease in the ANC of =2.5K/uL compared to &lt;2.5 K/uL was associated with improved OR (64% vs. 36%; p= .07) and TTP (m 20.6 months vs. 8 months; p=.003). Patients demonstrating a maximum lymphocyte count =1.2 K/uL at anytime during treatment compared to patients with a maximum lymphocyte count &lt;1.2 K/uL also had a greater OR (64% vs. 25%, p=.02) and TTP (m 17.6 months vs. 4.2 months, p=.03). Changes in Treg number and Th1 and Th2 response bias of PBMC did not correlate with ANC/ lymphocyte changes or clinical outcome. Conclusions: Treatment with sunitinib produces significant neutropenia with minimal effects on total lymphocyte numbers. Changes in ANC and maximum lymphocyte count could represent a pharmacodynamic marker of clinical outcome for mRCC patients treated with sunitinib. No significant financial relationships to disclose.
Locusts devastate east African crops
Authors: Tom Moberly
Journal: BMJ (2020)

Dai Kurokawa/EPA-EFE/Shutterstock

Local farmer Theophilus Mwendwa runs through a swarm of desert locusts trying to disperse them in the bush near Enziu, Kitui County, southern Kenya.

Large swarms of desert locusts have been invading Kenya for weeks and have also …
Abstract P428: A Polyexposomic Risk Score for Hypertensive Disorders of Pregnancy Using External Exposome Data
Authors: Hui Hu, Jinying Zhao, Jiang Bian, Yi Zheng, Thomas A Pearson
Journal: Circulation (2020)

Hypertensive disorders of pregnancy (HDP) are one of the most common pregnancy complications that lead to increased maternal and infant morbidity and mortality. While effective prevention of HDP can be attained using low-dose aspirin in high-risk pregnant women, identification of these high-risk women has been ineffective. Existing risk assessment models of HDP predominantly rely on biomarkers such as angiogenesis-related factors which are not routinely tested at the population level. The external environment has been shown to play an important role in the development of HDP, yet no predictive model of HDP has been developed considering the totality of the external environment, or the external exposome. To address this, we developed a polyexposomic risk score of HDP using external exposome-wide data among 6,989 women from the 2007-2012 linked Florida Vital Statistics Birth Records and Pregnancy Risk Assessment Monitoring System data. A total of 5,510 external exposome factors characterizing women’s surrounding natural, built, and social environment during pregnancy (i.e. climate, air pollution, noise, greenness, walkability, food access, socioeconomics, social capital, housing, and safety) were collected, harmonized, integrated, and spatiotemporally linked to pregnant women based on their geocoded residential addresses and pregnancy periods. The data were randomly divided into training (80%) and testing (20%) sets. A gradient boosting decision trees model was trained using the CatBoost library with hyper-parameters tuned by a grid search based on 5-fold cross validations. The model has a test-AUC (areas under curve) of 0.735. The most important features for predictions include neighborhood socioeconomic status, housing characteristics, meteorology factors, and air pollutants. External exposome data can provide important predictive information to identify individuals at high risk of HDP. The model is feasible for implementation at the population level to help guide precision preventions. Future efforts are warranted to integrate external exposome data with electronic health record data to further improve the model performance.
Science and Scientificity
Authors: Zong-Liang Xu
Journal: Genomics Proteomics & Bioinformatics (2005)

A question about scienceWe are now living in a scientific era, in which the theory and practice of science have penetrated into all aspects of society and science is often a hot topic.However, what on earth is science?This question is largely neglected by many people, even researchers focusing on scientific studies may not have a very clear understanding of it.
Impact of BRCA 1/2 testing: Body image, sexual functioning, and quality of life (QOL)
Authors: C. C. Sun, S. N. Westin, K. H. Lu, K. M. Schmeler, K. G. White, M. S. Daniels, B. K. Arun, S. K. Peterson, D. C. Bodurka
Journal: Journal of Clinical Oncology (2007)

1525 Background: Management strategies for women at high risk of breast and ovarian cancer (OVCA) may affect sensitive QOL issues. Methods: As part of a larger study, 540 women who underwent testing for BRCA 1/2 prior to July 2005 were sent follow- up surveys, including FACT-Endocrine Symptom subscale (FACT-ES), Sexual Activity Questionnaire (SAQ), and a modified Body Image Scale. Chi-square, Mann-Whitney and Kruskal-Wallis tests were used to analyze the data. Results: To date, 309 patients (pts) have responded. Pts with previous oophorectomies were excluded (n=68). The final analysis included 241 pts categorized into 4 groups: Group 1=no breast CA, no prophylactic (proph) surgery (n=39); Group 2=no breast CA, + proph surgery (either proph oophorectomy (PO), proph mastectomy (PM), or PO+PM) (n=20); Group 3= + breast CA, no PO or PM (n=90); and Group 4= + breast CA, + proph surgery (n=92). Median age at time of survey = 50 yrs. Median age at time of PO = 46 yrs. Of 65 BRCA + pts, 36 chose PO, while 32/176 BRCA- pts chose PO (p&lt;.001). 155 pts reported being sexually active at time of survey. Women with PO (n=68) had more endocrine symptoms by the FACT-ES vs pts who chose screening (n=173) (p=.005). Women in Group 2 reported more endocrine symptoms compared to all other women (p=.02). The same trend was noted for sexually active women only (p=.06). There were no differences in activity or pleasure measured by the SAQ between women with PO vs screening; pts with PO reported higher levels of pain/discomfort (p=.04). Women in Group 1 reported the lowest level of pain/discomfort (p=.004) and highest level of pleasure. Higher levels of discomfort and less sexual activity were reported by women with breast CA vs those without breast CA (p&lt;.001; p=.05). Women in Group 3 had the most negative body image while Group 2 had the most positive (p=.03). Women who chose screening reported a more negative body image vs women with PO (p=.01). Pts with breast CA had more negative body image scores than women without breast CA (p=.06). Conclusions: Choice of management strategy and personal hx of breast CA appear to influence sexual functioning, endocrine symptoms and body image in women at high risk of breast and OVCA. Baseline assessment of these factors and continued dialogue are critical aspects of comprehensive care for these women. No significant financial relationships to disclose.
Abstract P266: The Association Of Recent Age-specific Growth Of The <u>&gt;</u> 65 Years Population With Heart Disease Mortality In The United States, 2005-2017
Authors: Stephen Sidney, Sadiya S Khan, Yariv Gerber, Donald M Lloyd-jones, Alan S Go, Jamal S Rana
Journal: Circulation (2020)

Introduction: In 2011, the number of deaths with an underlying cause of heart disease (HD) reached its lowest level in 56 years. However, there has subsequently been a steady increase in the annual number of total HD deaths, owing to a rapid increase (23%) in the size of the population ≥65 years of age in the U.S. To understand these trends, we sought to characterize differences between 2005-2011 and 2011-2017 in population and mortality by age subgroups among those ≥65 years. Methods: We determined age-specific population size, HD mortality rate, and absolute number of HD deaths in the ≥65 age group for the time periods 2005-2011 and 2011-2017, as well as for the &lt;65 years age group, using the CDC WONDER online data set. Results: Age-specific population growth was greatest among those 65-74 years between 2005-2011 and 2011-2017, representing 76% of the total population growth among those ≥65 years old in both time periods (Table) and 51% of the growth for the entire population from 2011-2017. From 2005-2011, decreases in the mortality rate of 20% or greater in each of the age subgroups (65-74, 75-84, 85+) resulted in a decline in the number of total HD deaths in each of the age groups in spite of substantial population increases in the 65-74 and 85+ age groups. However, subsequent changes in the age-specific mortality rate among those ≥65 years were lower than population increases from 2011-2017, resulting in an increased number of total HD deaths in all &gt; 65 years age subgroups. This was most notable among those age 65-74 years in whom the 32% population increase with a 1.5% decline in the mortality rate resulted in a 30% increase in the number of HD deaths, representing 61.3% of the increase in number of HD deaths in the 65+ years age group and 53% of the increase of HD deaths in all age groups from 2011-2017. Conclusions: The rapid growth of the 65-74 years age group (baby boomers) accounts for most of the population growth in the ≥65 years age group and more than half the increase in both total population growth and the total number of HD deaths from 2011-2017.
Empagliflozin selected cardiovascular and safety outcomes in routine care: First results from the EMPagliflozin compaRative effectIveness and SafEty (EMPRISE) study
Authors: E. Patorno, A. Pawar, J.M. Franklin, M. Najafzadeh, A. Déruaz-Luyet, K.G. Brodovicz, S. Sambevski, L.G. Bessette, M. Kulldorff, S. Schneeweiss
Journal: Metabolism (2020)