bluuebunny/crossref_metadata_2025_split huggingface dataset:
Birth Rates after Adolescent and Young Adult Cancer in North Carolina, 2000–2014
Authors: Nichols HB , Anderson C , Black KZ , Engel S , Mersereau J 
Published: March 2017

Abstract
Each year, &gt;45,000 U.S. women are diagnosed with cancer during adolescence and young adulthood (AYA), defined by the National Cancer Institute as ages 15–39 years. ASCO first published guidelines on fertility counseling and preservation for cancer patients in 2006. Few studies have assessed birth rates after cancer among AYAs. We identified women with an incident cancer diagnosis at ages 15–39 during 2000–2013 in the North Carolina Cancer Registry. Cancer records were linked with statewide birth certificates through 2014 using a probabilistic algorithm. Hazard ratios (HR) and 95% confidence intervals (CI) for childbirth were calculated using Cox proportional hazards regression, with person-time accrued from cancer diagnosis until death, 46th birthday or December 31, 2014 and adjusted for age at diagnosis. Among 19,507 AYA cancer survivors, 2,343 had ≥1 post-diagnosis birth during 110,216 person-years. The 5- and 10-year cumulative incidence of post-diagnosis birth was 12% and 18%, respectively. The most common cancers were breast (25%), thyroid (14%), gynecologic (10%), melanoma (10%), and lymphoma (7%). The percent with a birth after diagnosis was lowest for breast and gynecologic cancer (6% for both) and highest for Hodgkin lymphoma (23%) and melanoma (24%). Survivors with a birth after diagnosis were more often younger, had not received radiation or chemotherapy, and had lower stage disease. African American women were less likely to have a post-diagnosis birth than white women overall (HR = 0.82; 0.73, 0.92), due in part to a higher proportion of breast cancers (35% vs. 23%). About 30% of births were &lt;2 years from cancer diagnosis and 20% were &gt;5 years after (mean = 3.5 years). Half (48%) were to women who were nulliparous at diagnosis. The 5-year cumulative incidence of post-diagnosis birth was 11.7% for women diagnosed during 2007–2012 (after ASCO's 2006 guidelines), compared to 11.6% during 2000–2005 (HR = 0.98; 0.89, 1.08) and varied little by cancer type. Despite advances in fertility preservation options and recognition of fertility counseling as a part of high quality cancer care, birth rates have remained stable over the last 15 years. Low implementation of fertility counseling and limited access to fertility preservation may be contributing factors.
Explaining Disparities in Ovarian Cancer Incidence Rates between Women of African and European Ancestry: The Role of Genetic Factors
Authors: Mullins M , Mukherjee B , Wu AH , Pike M , Pharoah PDP , Berchuck A , Pearce CL 
Published: March 2017

Abstract
Non-Hispanic White (NHW) women are at higher risk of ovarian cancer than African-American (AA) women. Approximately 30% of the difference in age-adjusted invasive epithelial ovarian cancer incidence rates (AAIR) between the two groups can be explained by differing oophorectomy rates and the prevalence of non-genetic risk and protective factors. Our purpose was to determine how much of the remaining difference in AAIRs could be explained by varying allele frequencies between NHWs and AAs for 18 genome-wide significant common susceptibility variants for ovarian cancer. Using data on 13,385 cases and 24,875 controls from the Ovarian Cancer Association Consortium, a genetic risk score (GRS) was created from 18 single nucleotide polymorphisms (SNPs) associated with ovarian cancer risk following the Collaborative Oncological Gene-environment Study (COGS) effort. Relative risks for each GRS quintile were estimated using conditional logistic regression, adjusting for genetic ancestry and conditioning on study site, age, and race. The population attributable risk percent (PAR) for GRS above the lowest quintile was calculated using the Bruzzi method. Previously reported oophorectomy and non-genetic risk factor (talc, oral contraceptive use, family history of ovarian cancer, endometriosis, parity and tubal ligation) adjusted incidence rates for ovarian cancer in NHWs and AA's were 7.2 and 5.8 per 100,000 respectively. These incidence rates were further adjusted for the contribution of the GRS from this analysis. The subsequent genetic PAR adjusted rate was 5.1 per 100,000 for the European ancestry group and 4.9 for the African ancestry group, after taking into account the different oophorectomy rates and prevalence of non-genetic risk factors. These incidence rates show the unexplained difference in incidence rates between NHWs and AAs is only 3.9%. Future efforts should focus on incorporating novel non-genetic and genetic factors into this analysis to determine whether essentially all of the difference in incidence between these groups can be explained.
Patterns of Multivitamin Use after Colorectal Cancer Diagnosis in Association with Long-term Survival
Authors: Kocarnik JM , Hua X , Lindor N , Gallinger S , Casey G , Jenkins M , Hardikar S , Robinson J , Newcomb PA 
Published: March 2017

Abstract
Multivitamin use has been related to a modest reduced risk of colorectal cancer (CRC), but evidence on its use after diagnosis in relation to survival has been limited. Incident, invasive CRC cases were identified through cancer registries from 1997–2008 and enrolled in four population-based sites of the Colon Cancer Family Registry (Fred Hutchinson Cancer Research Center, Cancer Care Ontario, Mayo Clinic, and the Universities of Queensland and Melbourne). At enrollment, a standardized interview ascertained multivitamin use in the year prior to diagnosis. A follow-up questionnaire was administered approximately 5 years after baseline, with 2,586 participants providing information on their multivitamin use at both time points. Survival outcomes were identified through linkage to national death registries. Delayed-entry Cox regression was used to estimate the association between patterns of multivitamin use and overall or CRC-specific survival (Hazard Ratio (HR) and 95% Confidence Interval (CI)), with survival time beginning at the 5-year follow-up survey. Models were adjusted for age at diagnosis, sex, body mass index, smoking history, stage, study center, and number of days from diagnosis to baseline survey. Over a median 4.8 years after the follow-up survey, 397 participants died (103 from CRC). Multivitamin use was common: at the 5-year follow-up, 37% reported continued use since before diagnosis, 12% had initiated use, 17% had discontinued use, and only 34% participants reported never using multivitamins. Compared to never use of multivitamins, continued use was significantly associated with increased subsequent overall survival (HR = 0.71, 95% CI: 0.55–0.91). However, this association did not reach statistical significance for CRC-specific survival (HR = 0.76, 95% CI: 0.47–1.24). No significant association was observed for discontinuing (HR = 0.92, 95% CI: 0.68–1.25) or initiating (HR = 0.80, 95% CI: 0.55–1.13) multivitamin use from baseline to follow-up, compared to never users, though initiating use trended towards increased survival. These findings suggest that continuing multivitamin use after a CRC diagnosis may increase survival; replication and details on the specific micronutrients included are needed.
Pilot-Testing a Survivorship Needs Assessment Planning Tool for Head and Neck Cancer Survivors and Caregivers
Authors: Sterba KR , Zapka J , Armeson K , Garris TK , Scallion M , Day TD 
Published: March 2017

Abstract
The purpose of this study was to develop and pilot-test a tablet-based survivorship needs assessment planning (SNAP) tool to assess head and neck cancer (HNC) survivor and caregiver needs after treatment and generate tailored care plans. We recruited survivors completing treatment &lt;24 months ago, and their caregivers. Participants completed baseline surveys, a clinic session with SNAP assessments (symptoms, unmet needs, behaviors) and care plan delivery, and 6-week follow-up surveys. We tracked intervention delivery/acceptability and used paired t-tests to explore changes in psychosocial factors over time. We enrolled 25 survivors (65% male, mean age = 63, 65% stage IVA) and their caregivers (73% female, mean age = 56, 77% partners). The average time to complete SNAP assessments was 11 and 6 minutes for survivors and caregivers, respectively. Algorithm-driven care plans included messages (mean = 19), educational materials (mean = 13) and referrals (mean = 4.5). Top referrals included Behavioral Medicine, Nutrition and Physical Therapy (84, 77 and 65% flagged, respectively). In those declining referrals, main reasons included being overwhelmed, seeing local provider or lacking interest. Participants rated SNAP favorably with &gt;80% reporting high comfort using tablets and navigating questions. Dyads strongly agreed that care plans were helpful emotionally (&gt;75%) and provided practical information (&gt;73%). After the session, both survivors and caregivers reported significantly fewer unmet needs (7.7 versus 2.9, P = 0.001 survivors; 7.0 versus 4.1, P = 0.02, caregivers) and higher survivorship preparedness (4.9 versus 5.2 in both, P = 0.02 and P = 0.03). While depression, symptom distress and symptom management abilities were stable in survivors, caregivers had significantly lower depression (P = 0.01) and symptom distress (P = 0.03), and higher ratings of perceived patient symptom management abilities (P = 0.004) at follow-up. Open-ended responses highlighted that SNAP visits helped pull together complex medical information and made families feel supported. Participants desired more information about cancer stage and caregivers preferred earlier intervention. Results support the feasibility of implementing SNAP in the HNC clinic and highlighted needed modifications for system improvement.
Using Global Metabolomics to Identify Novel Biomarkers of Treatment-Associated Cognitive Impairment in Pediatric Acute Lymphoblastic Leukemia
Authors: Brown AL , Rodgers CC , Taylor OA , Moore IM , Hooke MC , Pan W , Hockenberry MJ , Scheurer ME , Lupo PJ 
Published: March 2017

Abstract
Central nervous system-directed chemotherapy is a critical component of pediatric acute lymphoblastic leukemia (ALL) treatment, but is associated with long-term cognitive impairment. Because few strategies exist to identify children who are at risk for this adverse outcome, we employed global metabolomics to identify biomarkers of cognitive impairment using routinely collected, biologically relevant cerebrospinal fluid (CSF) samples from patients undergoing ALL chemotherapy. Methods: CSF samples were collected at 4 months post-induction on pediatric ALL patients enrolled in a multicenter prospective study of symptom toxicity. Metabolomics of CSF detected 314 metabolites by gas chromatography-mass spectrometry (MS) and liquid chromatography-MS/MS. Cognitive performance at 12 months post-induction was assessed with the validated Parent-Perceived Child Cognitive Function scale and categorized using published cut-points: mild (≥50), moderate (41–49), and severe (≤40). Ordinal logistic regression evaluated associations between normalized median-scaled metabolite values and cognitive function, adjusting for patient and treatment factors. A false discovery rate-corrected p-value (q) was calculated to account for multiple comparisons. Results: Among the 96 patients (diagnosed 2012–14), 43% exhibited moderate (n = 25) or severe (n = 16) cognitive impairment. Significant alterations were observed in several biomarkers, including methionine sulfoxide (Log2 Fold Change [FC] = 0.83, P = 5.2e−7, q = 0.001) and citramalate (FC = −0.29, P = 4.6e−5, q = 0.008). A pathway analysis of the top biomarkers (q &lt; 0.3) revealed an enrichment of metabolites involved in methionine (P = 0.0015) and carnitine (P = 0.0052) metabolism. Finally, compared to clinical factors alone, CSF biomarkers significantly improved the ability to predict cognitively impaired patients (area under curve [AUC] = 0.68 vs. AUC = 0.91, P &lt; 0.001). Conclusion: We identified several novel CSF biomarkers of treatment-related cognitive impairment among pediatric ALL patients. These findings may translate to clinical improvements in the management of cognitive outcomes by introducing the opportunity to deliver targeted interventions to high-risk patients prior to detectable or irreversible cognitive impairment.
Cold exposure down-regulates immune response pathways in ferret aortic perivascular adipose tissue
Authors: Reynés Bàrbara , van Schothorst Evert , García-Ruiz Estefanía , Keijer Jaap , Oliver Paula , Palou Andreu 
Published: March 2017

SummaryPerivascular adipose tissue (PVAT) surrounds blood vessels and releases paracrine factors, such as cytokines, which regulate local inflammation. The inflammatory state of PVAT has an important role in vascular disease; a pro-inflammatory state has been related with atherosclerosis development, whereas an anti-inflammatory one is protective. Cold exposure beneficially affects immune responses and, could thus impact the pathogenesis of cardiovascular diseases. In this study, we investigated the effects of one-week of cold exposure at 4°C of ferrets on aortic PVAT (aPVAT) versus subcutaneous adipose tissue. Ferrets were used because of the similarity of their adipose tissues to those of humans. A ferret-specific Agilent microarray was designed to cover the complete ferret genome and global gene expression analysis was performed. The data showed that cold exposure altered gene expression mainly in aPVAT. Most of the regulated genes were associated with cell cycle, immune response and gene expression regulation, and were mainly down-regulated. Regarding the effects on immune response, cold acclimation decreased the expression of genes involved in antigen recognition and presentation, cytokine signalling and immune system maturation and activation. This immunosuppressive gene expression pattern was depot-specific, as it was not observed in the inguinal subcutaneous depot. Interestingly, this depression in immune response related genes was also evident in peripheral blood mononuclear cells (PBMC). In conclusion, these results reveal that cold acclimation produces an inhibition of immune response-related pathways in aPVAT, reflected in PBMC, indicative of an anti-inflammatory response, which can potentially be exploited for the enhancement or maintenance of cardiovascular health.Supplementary Material to this article is available online at www.thrombosis-online.com.
Effect of restrictive versus liberal red cell transfusion strategies on haemostasis: systematic review and meta-analysis
Authors: Colman Katherine , Prick Babette , Duvekot Johannes , Sweeney Connor , Odutayo Ayodele , Jairath Vipul , Doree Carolyn , Trivella Marialena , Hopewell Sally , Estcourt Lise , Stanworth Simon , Desborough Michael 
Published: March 2017

SummaryRed cells play a key role in normal haemostasis in vitro but their importance clinically is less clear. The objective of this meta-analysis was to assess if correction of anaemia by transfusing red cells at a high haemoglobin threshold (liberal transfusion) is superior to transfusion at a lower haemoglobin threshold (restrictive transfusion) for reducing the risk of bleeding or thrombotic events. We searched for randomised controlled trials in any clinical setting that compared two red cell transfusion thresholds and investigated the risk of bleeding. We searched for studies published up to October 19, 2016 in The Cochrane Central Register of Controlled Trials, MEDLINE, PubMed, Embase, and the Transfusion Evidence Library and ISI Web of Science. Relative risks (RR) or Peto Odds Ratios (pOR) were pooled using a random-effect model. Nineteen randomised trials with 9852 participants were eligible for inclusion in this review. Overall there was no difference in the risk of any bleeding between transfusion strategies (RR 0.91, 95 % confidence interval [CI] 0.74 to 1.12). The risk of severe or life-threatening bleeding was lower with a restrictive strategy (RR 0.75, 95 % CI 0.57 to 0.99). There was no difference in the risk of thrombotic events (RR 0.83, 95 % CI 0.61 to 1.13). The risk of any bleeding was not reduced with liberal transfusion and there was no overall difference in the risk of thrombotic events. Data from the included trials do not support aiming for a high haemoglobin threshold to improve haemostasis. PROSPERO registration number CRD42016035519.Supplementary Material to this article is available online at www.thrombosis-online.com.
Sex Differences in Phenotypes of Bicuspid Aortic Valve and Aortopathy
Authors: Kong William K.F. , Regeer Madelien V. , Ng Arnold C.T. , McCormack Louise , Poh Kian Keong , Yeo Tiong Cheng , Shanks Miriam , Parent Sarah , Enache Roxana , Popescu Bogdan A. , Yip James W. , Ma Lawrence , Kamperidis Vasileios , van der Velde Enno T. , Mertens Bart , Ajmone Marsan Nina , Delgado Victoria , Bax Jeroen J. 
Published: March 2017

Background—
This large multicenter, international bicuspid aortic valve (BAV) registry aimed to define the sex differences in prevalence, valve morphology, dysfunction (aortic stenosis/regurgitation), aortopathy, and complications (endocarditis and aortic dissection).

Methods and Results—

Demographic, clinical, and echocardiographic data at first presentation of 1992 patients with BAV (71.5% men) were retrospectively analyzed. BAV morphology and valve function were assessed; aortopathy configuration was defined as isolated dilatation of the sinus of Valsalva or sinotubular junction, isolated dilatation of the ascending aorta distal to the sinotubular junction, or diffuse dilatation of the aortic root and ascending aorta. New cases of endocarditis and aortic dissection were recorded. There were no significant sex differences regarding BAV morphology and frequency of normal valve function. When presenting with moderate/severe aortic valve dysfunction, men had more frequent aortic regurgitation than women (33.8% versus 22.2%,
P
<0.001), whereas women were more likely to have aortic stenosis (34.5% versus 44.1%,
P
<0.001). Men had more frequently isolated dilatation of the sinus of Valsalva or sinotubular junction (14.2% versus 6.7%,
P
<0.001) and diffuse dilatation of the aortic root and ascending aorta (16.2% versus 7.3%,
P
<0.001) than women. Endocarditis (4.5% versus 2.5%,
P
=0.037) and aortic dissections (0.5% versus 0%,
P
<0.001) occurred more frequently in men.

Conclusions—
Although there is a male predominance among patients with BAV, men with BAV had more frequently moderate/severe aortic regurgitation at first presentation compared with women, whereas women presented more often with moderate/severe aortic stenosis compared with men. Furthermore, men had more frequent aortopathy than women.
Pooled Safety Analysis of Evolocumab in Over 6000 Patients From Double-Blind and Open-Label Extension Studies
Authors: Toth Peter P. , Descamps Olivier , Genest Jacques , Sattar Naveed , Preiss David , Dent Ricardo , Djedjos Constantine , Wu Yuna , Geller Michelle , Uhart Magdalena , Somaratne Ransi , Wasserman Scott M. 
Published: March 2017

Background:
Evolocumab, a fully human monoclonal antibody to PCSK9 (proprotein convertase subtilisin/kexin type 9), markedly reduces low-density lipoprotein cholesterol across diverse patient populations. The objective of this study was to assess the safety and tolerability of evolocumab in a pooled safety analysis from phase 2 or 3 randomized and placebo or comparator-controlled trials (integrated parent trials) and the first year of open-label extension (OLE) trials that included a standard-of-care control group.

Methods:
This analysis included adverse event (AE) data from 6026 patients in 12 phase 2 and 3 parent trials, with a median exposure of 2.8 months, and, of those patients, from 4465 patients who continued with a median follow-up of 11.1 months in 2 OLE trials. AEs were analyzed separately for the parent and OLE trials. Overall AE rates, serious AEs, laboratory assessments, and AEs of interest were evaluated.

Results:
Overall AE rates were similar between evolocumab and control in the parent trials (51.1% versus 49.6%) and in year 1 of OLE trials (70.0% versus 66.0%), as were those for serious AEs. Elevations of serum transaminases, bilirubin, and creatine kinase were infrequent and similar between groups. Muscle-related AEs were similar between evolocumab and control. Neurocognitive AEs were infrequent and balanced during the double-blind parent studies (5 events [0.1%], evolocumab groups versus 6 events [0.3%], control groups). In the OLE trials, 27 patients (0.9%) in the evolocumab groups and 5 patients (0.3%) in the control groups reported neurocognitive AEs. No neutralizing antievolocumab antibodies were detected.

Conclusions:
Overall, this integrated safety analysis of 6026 patients pooled across phase 2/3 trials and 4465 patients who continued in OLE trials for 1 year supports a favorable benefit-risk profile for evolocumab.
β
2
-Glycoprotein I/IgA Immune Complexes
Authors: Serrano Manuel , Martínez-Flores José A. , Pérez Dolores , García Florencio , Cabrera Oscar , Pleguezuelo Daniel , Paz-Artal Estela , Morales José M. , González Esther , Serrano Antonio 
Published: March 2017

Background:

Antiphospholipid syndrome is characterized by recurrent thrombosis and gestational morbidity in patients with antiphospholipid autoantibodies (aPLs). Predictive value of the presence of aPLs is low, and new markers are necessary to identify aPL carriers at higher risk and take preventive measures on them. The presence of circulating immune complexes of IgA bound to β
2
-glycoprotein I (B2A-CIC) has been associated with occurrence of acute thrombotic events. In this work we study its possible predictive value for the appearance of acute thrombotic events in patients who are going to undergo transplant surgery, a well-known trigger of acute thrombotic events in aPL carriers.

Methods:

We performed a follow-up study based on the Magnum 12+12 Cohort of patients who received a kidney transplant (n=1339). Three groups were established: group 1 patients who were positive for IgA anti-β
2
-glycoprotein I (aB2GP1) and B2A-CIC (n=125); group 2 patients who were positive only for IgA aB2GP1 (n=240); and control group, patients who were negative for IgA aB2GP1 (n=974). Levels of autoantibodies and B2A-CIC were quantified immediately before the transplant surgery and patients were followed up for 6 months.

Results:

In group 1, 46.4% of patients experienced any type of thrombosis versus 10.4% in group 2 (
P
<0.001) and 8.6% in the control group (
P
<0.001). The incidence of graft thrombosis in group 1 (31.2%) was significantly higher than that observed in group 2 (3.3%,
P
<0.001) and the control group (2.6%,
P
<0.001). In a multivariate analysis, the presence of B2A-CIC was an independent variable to experience any type of posttransplant thrombosis (hazard ratio, 6.72; 95% confidence interval, 4.81–9.37) and, prominently, for graft thrombosis (hazard ratio, 14.75; 95% confidence interval, 9.11–23.89). No significant differences were found between B2A-CIC–negative and control group patients.

Conclusions:
The presence of B2A-CIC is a predictor of acute thrombotic events. Patients who were positive for IgA aB2GP1 only are at risk of experiencing thrombosis if they are B2A-CIC positive. If they are B2A-CIC–negative patients, they have the same risk as the control group. Treatments to prevent acute thrombotic events should focus on B2A-CIC–positive patients.