bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coffee Consumption and Risk of Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma by Sex: The Liver Cancer Pooling Project
Authors: Petrick Jessica L. , Freedman Neal D. , Graubard Barry I. , Sahasrabuddhe Vikrant V. , Lai Gabriel Y. , Alavanja Michael C. , Beane-Freeman Laura E. , Boggs Deborah A. , Buring Julie E. , Chan Andrew T. , Chong Dawn Q. , Fuchs Charles S. , Gapstur Susan M. , Gaziano John Michael , Giovannucci Edward L. , Hollenbeck Albert R. , King Lindsay Y. , Koshiol Jill , Lee I-Min , Linet Martha S. , Palmer Julie R. , Poynter Jenny N. , Purdue Mark P. , Robien Kim , Schairer Catherine , Sesso Howard D. , Sigurdson Alice J. , Zeleniuch-Jacquotte Anne , Wactawski-Wende Jean , Campbell Peter T. , McGlynn Katherine A. 
Published: July 2015

Abstract
Background: Coffee consumption has been reported to be inversely associated with hepatocellular carcinoma (HCC), the most common type of liver cancer. Caffeine has chemopreventive properties, but whether caffeine is responsible for the coffee–HCC association is not well studied. In addition, few studies have examined the relationship by sex, and no studies have examined whether there is an association between coffee and intrahepatic cholangiocarcinoma (ICC), the second most common type of liver cancer.
Methods: In the Liver Cancer Pooling Project, a consortium of U.S.-based cohort studies, data from 1,212,893 individuals (HCC, n = 860; ICC, n = 260) in nine cohorts were pooled. Multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CI) were estimated using proportional hazards regression.
Results: Higher coffee consumption was associated with lower risk of HCC (HR&gt;3 cups/day vs. non-drinker, 0.73; 95% CI, 0.53–0.99; Ptrend cups/day = &lt;0.0001). More notable reduced risk was seen among women than men (Pinteraction = 0.07). Women who consumed more than three cups of coffee per day were at a 54% lower risk of HCC (HR, 0.46; 95% CI, 0.26–0.81), whereas men had more modest reduced risk of HCC (HR, 0.93; 95% CI, 0.63–1.37). The associations were stronger for caffeinated coffee (HR&gt;3 cups/day vs. non-drinker, 0.71; 95% CI, 0.50–1.01) than decaffeinated coffee (HR, 0.92; 95% CI, 0.55–1.54). There was no association between coffee consumption and ICC.
Conclusions: These findings suggest that, in a U.S. population, coffee consumption is associated with reduced risk of HCC.
Impact: Further research into specific coffee compounds and mechanisms that may account for these associations is needed. Cancer Epidemiol Biomarkers Prev; 24(9); 1398–406. ©2015 AACR.
Leisure-Time Spent Sitting and Site-Specific Cancer Incidence in a Large U.S. Cohort
Authors: Patel Alpa V. , Hildebrand Janet S. , Campbell Peter T. , Teras Lauren R. , Craft Lynette L. , McCullough Marjorie L. , Gapstur Susan M. 
Published: July 2015

AbstractBackground: Time spent sitting is distinctly different from accumulating too little physical activity and may have independent deleterious effects. Few studies have examined the association between sitting time and site-specific cancer incidence.Methods: Among 69,260 men and 77,462 women who were cancer-free and enrolled in the American Cancer Society Cancer Prevention Study II Nutrition Cohort, 18,555 men and 12,236 women were diagnosed with cancer between 1992 and 2009. Extended Cox proportional hazards regression was used to estimate multivariable-adjusted relative risks (RR) and 95% confidence intervals (CI) of leisure-time spent sitting with total and site-specific cancer incidence.Results: Longer leisure-time spent sitting, after adjustment for physical activity, BMI, and other factors, was associated with risk of total cancer in women (RR = 1.10; 95% CI, 1.04–1.17 for ≥6 hours vs. &lt;3 hours per day), but not men (RR = 1.00; 95% CI, 0.96–1.05). In women, sitting time was associated with risk of multiple myeloma (RR = 1.65; 95% CI, 1.07–2.54), invasive breast cancer (RR = 1.10; 95% CI, 1.00–1.21), and ovarian cancer (RR = 1.43; 95% CI, 1.10–1.87). There were no associations between sitting time and site-specific cancers in men.Conclusion: Longer leisure-time spent sitting was associated with a higher risk of total cancer risk in women, and specifically with multiple myeloma, breast, and ovarian cancers, but sitting time was not associated with cancer risk in men. Further research is warranted to better understand the differences in associations between men and women.Impact: For women, these findings support American Cancer Society guidelines for cancer prevention to reduce sitting time when possible. Cancer Epidemiol Biomarkers Prev; 24(9); 1350–9. ©2015 AACR.
CCR 20th Anniversary Commentary: Paving the Way for Circulating Tumor Cells
Authors: Allard W. Jeffrey , Terstappen Leon W.M.M. 
Published: July 2015

Abstract
Cancer cells can enter the bloodstream, form distant metastases, and ultimately lead to death. A study by Allard and colleagues, which was published in the October 15, 2004, issue of Clinical Cancer Research, concluded that the CellSearch system could be used as a reliable tool to investigate circulating tumor cells and their clinical utility, and it spurred a still-growing interest in the field. Clin Cancer Res; 21(13); 2883–5. ©2015 AACR.
See related article by Allard et al., Clin Cancer Res 2004;10(20) October 15, 2004;6897–904
Evaluation of Epigenetic Drug Targeting of Heterogenous Tumor Cell Fractions Using Potential Biomarkers of Response in Ovarian Cancer
Authors: Singh Anand Kamal , Chandra Nishi , Bapat Sharmila A. 
Published: July 2015

AbstractPurpose: Resolution of aberrant epigenetic changes leading to altered gene expression during transformation and tumor progression is pertinent for mechanistic understanding of disrupted pathways in cancer. Such changes provide for biomarkers that can be applied in drug screening and improved disease management.Experimental Design: Genome-wide profiling and analyses of promoter DNA methylation, histone modifications, and gene expression of an in vitro progression model of serous ovarian adenocarcinoma were carried out. Similar in silico analyses and comparison of methylation and gene expression of early- and late-grade ovarian cancer samples in The Cancer Genome Atlas assigned a clinical relevance to our study. Candidate biomarkers were evaluated for epigenetic drug treatments in experimental animal models on a background of differing tumor cell responses arising from intratumor heterogeneity.Results: Differentially regulated genes during tumor progression were identified through the previously mentioned analyses as candidate biomarkers. In examining the tumor suppressor PTGIS as a potential biomarker for treatment with either 5-Aza-dC or TSA, 5-Aza-dC effectively stabilized cell cycling, restricted genetic instability, and derepressed PTGIS expression, while TSA led to emergence of drug-resistant progenitors lacking PTGIS expression. Profiling MEST and RXRγ for curcumin and CBB1007, respectively, indicated an inability of curcumin and CBB1007 in restricting residual tumor regenerative capabilities.Conclusions: Our study provides novel insights into epigenetic regulation in ovarian cancer progression and potential biomarkers for evaluating efficacy of epigenetic drugs in restricting residual tumor regeneration. Such approaches may assign a new functional interpretation of drug efficacy and cell tumor responses in ovarian cancer. Clin Cancer Res; 21(22); 5151–63. ©2015 AACR.
A Phase II Randomized, Controlled Trial of S-Adenosylmethionine in Reducing Serum α-Fetoprotein in Patients with Hepatitis C Cirrhosis and Elevated AFP
Authors: Morgan Timothy R. , Osann Kathryn , Bottiglieri Teodoro , Pimstone Neville , Hoefs John C. , Hu Ke-Qin , Hassanein Tarek , Boyer Thomas D. , Kong Lorene , Chen Wen-Pin , Richmond Ellen , Gonzalez Rachel , Rodriguez Luz M. , Meyskens Frank L. 
Published: July 2015

Abstract
In animal models of hepatocellular carcinoma (HCC), deficiency of S-adenosylmethionine (SAMe) increased the risk of HCC whereas administration of SAMe reduced HCC. The aim of this trial was to determine whether oral SAMe administration to patients with hepatitis C cirrhosis would decrease serum α-fetoprotein (AFP) level, a biomarker of HCC risk in hepatitis C. This was a prospective, randomized, placebo-controlled, double-blind trial of SAMe, up to 2.4 g/d, for 24 weeks as compared with placebo among subjects with hepatitis C cirrhosis and a mildly elevated serum AFP. Primary outcome was change in AFP between baseline and week 24. Secondary outcomes included changes in routine tests of liver function and injury, other biomarkers of HCC risk, SAMe metabolites, markers of oxidative stress, and quality of life. One hundred ten subjects were randomized and 87 (44 SAMe and 43 placebo) completed treatment. There was no difference in the change in AFP during 24 weeks among subjects receiving SAMe as compared with placebo. Changes in markers of liver function, liver injury, and hepatitis C viral level were not significantly different between groups. Similarly, SAMe did not change markers of oxidative stress or serum glutathione level. SAMe blood level increased significantly among subjects receiving SAMe. Changes in quality of life did not differ between groups. Overall, this trial did not find that SAMe treatment improved serum AFP in subjects with advanced hepatitis C cirrhosis and a mildly elevated AFP. SAMe did not improve tests of liver function or injury or markers of oxidative stress or antioxidant potential. Cancer Prev Res; 8(9); 864–72. ©2015 AACR.
Functional Characterization of Rare Variants Implicated in Susceptibility to Lone Atrial Fibrillation
Authors: Hayashi Kenshi , Konno Tetsuo , Tada Hayato , Tani Satoyuki , Liu Li , Fujino Noboru , Nohara Atsushi , Hodatsu Akihiko , Tsuda Toyonobu , Tanaka Yoshihiro , Kawashiri Masa-aki , Ino Hidekazu , Makita Naomasa , Yamagishi Masakazu 
Published: July 2015

Background—
Few rare variants in atrial fibrillation (AF)–associated genes have been functionally characterized to identify a causal relationship between these variants and development of AF. We here sought to determine the clinical effect of rare variants in AF-associated genes in patients with lone AF and characterized these variants electrophysiologically and bioinformatically.

Methods and Results—

We screened all coding regions in 12 AF-associated genes in 90 patients with lone AF, with an onset of 47±11 years (66 men; mean age, 56±13 years) by high-resolution melting curve analysis and DNA sequencing. The potassium and sodium currents were analyzed using whole-cell patch clamping. In addition to using 4 individual in silico prediction tools, we extended those predictions to an integrated tool (Combined Annotation Dependent Depletion). We identified 7 rare variants in
KCNA5
,
KCNQ1
,
KCNH2
,
SCN5A
, and
SCN1B
genes in 8 patients: 2 of 8 probands had a family history of AF. Electrophysiological studies revealed that 2 variants showed a loss-of-function, and 4 variants showed a gain-of-function. Five of 6 variants with electrophysiological abnormalities were predicted as pathogenic by Combined Annotation Dependent Depletion scores.

Conclusions—
In our cohort of patients with lone AF, 7 rare variants in cardiac ion channels were identified in 8 probands. A combination of electrophysiological studies and in silico predictions showed that these variants could contribute to the development of lone AF, although further in vivo study is necessary to confirm these results. More than half of AF-associated rare variants showed gain-of-function behavior, which may be targeted using genotype-specific pharmacological therapy.
Monocyte Count and 30-Day Case Fatality in Intracerebral Hemorrhage
Authors: Walsh Kyle B. , Sekar Padmini , Langefeld Carl D. , Moomaw Charles J. , Elkind Mitchell S.V. , Boehme Amelia K. , James Michael L. , Osborne Jennifer , Sheth Kevin N. , Woo Daniel , Adeoye Opeolu 
Published: July 2015

Background and Purpose—
Monocytes may contribute to secondary injury after intracerebral hemorrhage (ICH). We tested the association of absolute monocyte count with 30-day ICH case fatality in a multiethnic cohort.

Methods—
Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study is a prospective, multicenter, case–control study of ICH among white, black, and Hispanic patients. In 240 adults with nontraumatic ICH within 24 hours of symptom onset, we evaluated the influence of ICH score and complete blood count components on 30-day case fatality using generalized linear models.

Results—

Mean age was 62.8 years (SD, 14 years); 61.7% were men, 33.3% black, and 29.6% Hispanic. Median ICH volume was 9.9 mL (interquartile range, 4.4–26.7). After adjusting for patient age and initial hemoglobin, higher total white blood cell count (
P
=0.0011), driven by higher absolute neutrophil count (
P
=0.002), was associated with larger ICH volume, whereas absolute monocyte count was not (
P
=0.15). After adjusting for age, Glasgow Coma Scale, ICH volume, location, and the presence or absence of intraventricular hemorrhage, baseline absolute monocyte count was independently associated with higher 30-day case-fatality (odds ratio, 5.39; 95% confidence interval, 1.87–15.49;
P
=0.0018), whereas absolute neutrophil count (odds ratio, 1.04; 0.46–2.32;
P
=0.93) and white blood cell count (odds ratio, 1.62; 0.58–4.54;
P
=0.36) were not.

Conclusions—
These data support an independent association between higher admission absolute monocyte count and 30-day case-fatality in ICH. Inquiry into monocyte-mediated pathways of inflammation and apoptosis may elucidate the basis for the observed association and may be targets for ICH neuroprotection.
Logit-Based Analysis of Drivers’ Crossing Behavior at Unsignalized Intersections in China
Authors: Lu Guangquan , Liu Miaomiao , Wang Yunpeng , Wan Huasen , Tian Daxin 
Published: July 2015

Objective: This study aims to investigate the crossing behavior of straight-moving drivers when they encounter other straight-moving drivers at unsignalized intersections in China. Background: In China, when two vehicle drivers encounter at an unsignalized intersection, neither driver completely stops his or her vehicle in most cases. Instead, one driver gradually approaches the intersection and dynamically decides to either yield or preempt by gaming with the other vehicle. This process increases the probability of accidents. Method: A total of 305 crossing cases were collected at an unsignalized intersection in Kunming City. Motion parameters were extracted from the video detection program designed by our research group. Based on a logistic regression method, we analyzed decision making moment of straight-moving drivers under crossing conditions, established crossing behavior models, and identified the main factors that affected drivers’ decisions. In all, 68 cases observed at a separate intersection were used to validate the established models. Results: For crossing processes at unsignalized intersections in China, straight-moving drivers from the right side completed preemptive/yielding decisions at 1.3 s before reaching the crossing point. However, the majority of straight-moving drivers from the left side completed decisions at 1.1 s before reaching the crossing point. The most important parameter that influenced the drivers’ decisions was the difference between the speeds of the two vehicles. Conclusion: An effective method for preventing traffic conflict between two straight-moving drivers is to control the speeds of the vehicles before they enter the intersection. Application: This study explores crossing behavior of straight-moving drivers and provides significant insights for controlling driver behavior.
Combined treatment with endovenous laser ablation and compression therapy of incompetent perforating veins for treatment of recalcitrant venous ulcers
Authors: Seren Mustafa , Dumantepe Mert , Fazliogullari Osman , Kucukaksu Suha 
Published: July 2015

Objective Patients with healed venous ulcers often experience recurrence of ulceration, despite the use of long-term compression therapy. This study examines the effect of closing incompetent perforating veins (IPVs) on ulcer recurrence rates in patients with progressive lipodermatosclerosis and impending ulceration. Methods Patients with nonhealing venous ulcers of >2 months’ duration underwent duplex ultrasound to assess their lower extremity venous system for incompetence of superficial, perforating, and deep veins. Endovenous laser ablation (EVLA) of perforating veins was performed on patients with CEAP 6 disease with increasing hyperpigmentation, lipodermatosclerosis, and/or progressive malleolar pain. A minimum of 2 months of compressive therapy was attempted before endovenous ablation of IPVs. Demographic data, risk factors, CEAP classification, procedural details, and postoperative status were all recorded. Results Forty ulcers with 46 associated IPVs were treated with EVLA in 36 patients with CEAP 6 recalcitrant venous ulcers. Treated incompetent perforator veins were located in the medial ankle (85.7%), calf (10.7%), and lateral ankle (3.5%). Endovenous laser ablation was successful in 76% (35/46) with the first laser treatment of incompetent perforator veins and 15.2% (7/46) additional ablation procedures were performed. Of the 46 treated IPVs, 42 (91.3%) were occluded on the duplex examination at 12 months. The average energy administrated per perforating vein treated was 162 joule. Two patients reported localized paresthesia, which subsided spontaneously, but no deep venous thrombosis or skin burn was observed. Conclusion Especially in the case of liposclerotic or ulcerated skin in the affected region, PAP of IPVs is highly effective, safe, and appears to be feasible. Patients with active venous ulcers appear to benefit from EVLA of incompetent perforators in order to reduce the risk of ulcer recurrence.
Role of high sensitivity C-reactive protein and other risk factors in intracranial and extracranial artery occlusion in patients with ischaemic stroke
Authors: Xie Dan , Deng Li , Liu Xiao-dong , Li Ji-mei , Zhang Yong-bo 
Published: July 2015

Objective A retrospective case–control study to identify stroke-associated risk factors and quantify serum C-reactive protein in patients with ischaemic stroke, with or without intracranial and/or extracranial artery occlusion (IEAO). Methods Patients with ischaemic stroke and internal carotid artery occlusion (ICAO), middle cerebral artery occlusion (MCAO), ICAO + MCAO, or no IEAO (control patients) were retrospectively recruited. Data regarding stroke-associated risk factors were retrieved from medical records. High sensitivity (hs)-CRP was quantified within 3 days of hospital admission. Results Patients with ICAO ( n = 89), MCAO ( n = 74) and ICAO + MCAO ( n = 29) had significantly higher serum hs-CRP concentrations, and were significantly more likely to have coronary heart disease, a history of stroke, and more than three stroke-associated risk factors than control patients ( n = 84). Conclusions Coronary heart disease and a history of stroke are risk factors for ischaemic stroke with IEAO. Hs-CRP may be used as a marker for IEAO.
Biomechanical Comparison of External Fixation and Compression Screws for Transverse Tarsal Joint Arthrodesis
Authors: Latt L. Daniel , Glisson Richard R. , Adams Samuel B. , Schuh Reinhard , Narron John A. , Easley Mark E. 
Published: July 2015

Background: Transverse tarsal joint arthrodesis is commonly performed in the operative treatment of hindfoot arthritis and acquired flatfoot deformity. While fixation is typically achieved using screws, failure to obtain and maintain joint compression sometimes occurs, potentially leading to nonunion. External fixation is an alternate method of achieving arthrodesis site compression and has the advantage of allowing postoperative compression adjustment when necessary. However, its performance relative to standard screw fixation has not been quantified in this application. We hypothesized that external fixation could provide transverse tarsal joint compression exceeding that possible with screw fixation. Methods: Transverse tarsal joint fixation was performed sequentially, first with a circular external fixator and then with compression screws, on 9 fresh-frozen cadaveric legs. The external fixator was attached in abutting rings fixed to the tibia and the hindfoot and a third anterior ring parallel to the hindfoot ring using transverse wires and half-pins in the tibial diaphysis, calcaneus, and metatarsals. Screw fixation comprised two 4.3 mm headless compression screws traversing the talonavicular joint and 1 across the calcaneocuboid joint. Compressive forces generated during incremental fixator foot ring displacement to 20 mm and incremental screw tightening were measured using a custom-fabricated instrumented miniature external fixator spanning the transverse tarsal joint. Results: The maximum compressive force generated by the external fixator averaged 186% of that produced by the screws (range, 104%-391%). Fixator compression surpassed that obtainable with screws at 12 mm of ring displacement and decreased when the tibial ring was detached. No correlation was found between bone density and the compressive force achievable by either fusion method. Conclusion: The compression across the transverse tarsal joint that can be obtained with a circular external fixator including a tibial ring exceeds that which can be obtained with 3 headless compression screws. Screw and external fixator performance did not correlate with bone mineral density. This study supports the use of external fixation as an alternative method of generating compression to help stimulate fusion across the transverse tarsal joints. Clinical Relevance: The findings provide biomechanical evidence to support the use of external fixation as a viable option in transverse tarsal joint fusion cases in which screw fixation has failed or is anticipated to be inadequate due to suboptimal bone quality.
Impact of Exposure to Childhood Maltreatment on Transitions to Alcohol Dependence in Women and Men
Authors: Oberleitner Lindsay M. S. , Smith Philip H. , Weinberger Andrea H. , Mazure Carolyn M. , McKee Sherry A. 
Published: July 2015

Background: Childhood maltreatment decreases age of first use and speeds the transition from first use to dependence (i.e., telescoping) for alcohol use, however, it is currently unknown whether this influence is the same for men and women. Method: Analyses were conducted with the National Epidemiologic Survey on Alcohol and Related Conditions ( n = 34,653). Outcome variables included age of alcohol initiation and time to onset of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition alcohol dependence. Predictor variables included gender and childhood maltreatment. Linear and Poisson regression analyses were conducted. Results: Results demonstrated that in regard to age of drinking initiation, individuals who experienced childhood maltreatment initiated 1 year earlier than those without maltreatment, however, there was no interaction of this relationship with gender. Regarding the time to dependence, it was found that women who experienced childhood maltreatment demonstrated telescoping (shorter time between onset and dependence) compared to women without maltreatment and men (both with and without maltreatment). Conclusion: Women with a history of childhood maltreatment are particularly vulnerable to an accelerated time from initiation of alcohol use until dependence, a pattern indicative of increased negative alcohol-related outcomes. Findings highlight the need for development of gender-specific prevention efforts and behavioral treatments to aid in early intervention of problematic alcohol use in women.