bluuebunny/crossref_metadata_2025_split huggingface dataset:
Network-wide oscillations in the parkinsonian state: alterations in neuronal activities occur in the premotor cortex in parkinsonian nonhuman primates
Authors: Wang Jing , Johnson Luke A. , Jensen Alicia L. , Baker Kenneth B. , Molnar Gregory F. , Johnson Matthew D. , Vitek Jerrold L. 
Published: February 2017

A number of studies suggest that Parkinson’s disease (PD) is associated with alterations of neuronal activity patterns in the basal-ganglia-thalamocortical circuit. There are limited electrophysiological data, however, describing how the premotor cortex, which is involved in movement and decision-making, is likely impacted in PD. In this study, spontaneous local field potential (LFP) and single unit neuronal activity were recorded in the dorsal premotor area of nonhuman primates in both the naïve and parkinsonian state using the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of parkinsonism. In both animals, we observed a shift of power in LFP power spectral densities (1−350 Hz) from higher to lower frequency bands; parkinsonism resulted in increased power in frequencies <8 Hz and decreased power at frequencies >30 Hz. A comparable but not identical trend was observed in the power spectral analysis of single unit spike trains: alpha power increased in both animals and gamma power decreased in one; power in other frequency bands remaining unchanged. Although not consistent across animals, we also observed changes in discharge rates and bursting activity. Overall, the LFP and single unit analysis suggest that abnormalities in premotor neural activity are a feature of parkinsonism, although specific details of those abnormalities may differ between subjects. This study further supports the concept that PD is a network disorder that induces abnormal spontaneous neural activities across the basal-ganglia-thalamocortical circuit including the premotor cortex and provides foundational knowledge for future studies regarding the relationship between changes in neuronal activity in this region and the development of motor deficits in PD. NEW & NOTEWORTHY This study begins to fill a gap in knowledge regarding how Parkinson’s disease (PD) may cause abnormal functioning of the premotor cortex. It is novel as the premotor activity is examined in both the naïve and parkinsonian states, in the same subjects, at the single unit and LFP level. It provides foundational knowledge on which to build future studies to explore the relationships between premotor activities and specific parkinsonian motor and cognitive deficits.
Multidigit force control during unconstrained grasping in response to object perturbations
Authors: Naceri Abdeldjallil , Moscatelli Alessandro , Haschke Robert , Ritter Helge , Santello Marco , Ernst Marc O. 
Published: February 2017

Because of the complex anatomy of the human hand, in the absence of external constraints, a large number of postures and force combinations can be used to attain a stable grasp. Motor synergies provide a viable strategy to solve this problem of motor redundancy. In this study, we exploited the technical advantages of an innovative sensorized object to study unconstrained hand grasping within the theoretical framework of motor synergies. Participants were required to grasp, lift, and hold the sensorized object. During the holding phase, we repetitively applied external disturbance forces and torques and recorded the spatiotemporal distribution of grip forces produced by each digit. We found that the time to reach the maximum grip force during each perturbation was roughly equal across fingers, consistent with a synchronous, synergistic stiffening across digits. We further evaluated this hypothesis by comparing the force distribution of human grasping vs. robotic grasping, where the control strategy was set by the experimenter. We controlled the global hand stiffness of the robotic hand and found that this control algorithm produced a force pattern qualitatively similar to human grasping performance. Our results suggest that the nervous system uses a default whole hand synergistic control to maintain a stable grasp regardless of the number of digits involved in the task, their position on the objects, and the type and frequency of external perturbations. NEW & NOTEWORTHY We studied hand grasping using a sensorized object allowing unconstrained finger placement. During object perturbation, the time to reach the peak force was roughly equal across fingers, consistently with a synergistic stiffening across fingers. Force distribution of a robotic grasping hand, where the control algorithm is based on global hand stiffness, was qualitatively similar to human grasping. This suggests that the central nervous system uses a default whole hand synergistic control to maintain a stable grasp.
Cancer Mortality in Hispanic Ethnic Groups
Authors: Pinheiro Paulo S. , Callahan Karen E. , Siegel Rebecca L. , Jin Hongbin , Morris Cyllene R. , Trapido Edward J. , Gomez Scarlett Lin 
Published: February 2017

Abstract
Background: Cancer is the leading cause of death among Hispanics. The burden of cancer mortality within Hispanic groups has not been well quantified.
Methods: Cancer mortality rates for 2008–2012 in Florida were computed on the basis of race, ethnicity, and birthplace, specifically focusing on major Hispanic groups—Mexicans, Puerto Ricans, Cubans, Central Americans, South Americans, and Dominicans. Age-adjusted mortality rate ratios derived from negative binomial regression were used to compare Hispanics, aggregated and by group, to nonHispanic whites (NHW).
Results: A total of 205,369 cancer deaths from 2008–2012 were analyzed, of which 22,042 occurred in Hispanics. Overall cancer mortality rates were lower for Hispanics, 159 and 100 per 100,000 in males and females, respectively, compared with 204 and 145 per 100,000 in NHWs, largely driven by relatively low rates of lung and breast cancers among Hispanics. However, Hispanics had a higher risk of death from stomach and liver cancers, both infection-related. Of all Hispanic groups, Mexicans had the lowest mortality, whereas Cubans had the highest, with significantly higher mortality for colorectal, endometrial, and prostate cancers.
Conclusions: Compared with other Hispanic groups, Cubans and Puerto Ricans had significantly higher rates. For these longer-established populations in the United States, increases in diet and obesity-related cancers are evident. Some groups show excesses that clearly fall out of the common Hispanic patterns, with implications for public health: Cubans for colorectal cancer, Puerto Ricans for liver cancer, and Dominicans for prostate cancer.
Impact: Cancer mortality outcomes in Hispanics vary between ethnic groups. Research and public health strategies should consider this heterogeneity. Cancer Epidemiol Biomarkers Prev; 26(3); 376–82. ©2017 AACR.
Young Adult and Usual Adult Body Mass Index and Multiple Myeloma Risk: A Pooled Analysis in the International Multiple Myeloma Consortium (IMMC)
Authors: Birmann Brenda M. , Andreotti Gabriella , De Roos Anneclaire J. , Camp Nicola J. , Chiu Brian C.H. , Spinelli John J. , Becker Nikolaus , Benhaim-Luzon Véronique , Bhatti Parveen , Boffetta Paolo , Brennan Paul , Brown Elizabeth E. , Cocco Pierluigi , Costas Laura , Cozen Wendy , de Sanjosé Silvia , Foretová Lenka , Giles Graham G. , Maynadié Marc , Moysich Kirsten , Nieters Alexandra , Staines Anthony , Tricot Guido , Weisenburger Dennis , Zhang Yawei , Baris Dalsu , Purdue Mark P. 
Published: February 2017

AbstractBackground: Multiple myeloma risk increases with higher adult body mass index (BMI). Emerging evidence also supports an association of young adult BMI with multiple myeloma. We undertook a pooled analysis of eight case–control studies to further evaluate anthropometric multiple myeloma risk factors, including young adult BMI.Methods: We conducted multivariable logistic regression analysis of usual adult anthropometric measures of 2,318 multiple myeloma cases and 9,609 controls, and of young adult BMI (age 25 or 30 years) for 1,164 cases and 3,629 controls.Results: In the pooled sample, multiple myeloma risk was positively associated with usual adult BMI; risk increased 9% per 5-kg/m2 increase in BMI [OR, 1.09; 95% confidence interval (CI), 1.04–1.14; P = 0.007]. We observed significant heterogeneity by study design (P = 0.04), noting the BMI–multiple myeloma association only for population-based studies (Ptrend = 0.0003). Young adult BMI was also positively associated with multiple myeloma (per 5-kg/m2; OR, 1.2; 95% CI, 1.1–1.3; P = 0.0002). Furthermore, we observed strong evidence of interaction between younger and usual adult BMI (Pinteraction &lt;0.0001); we noted statistically significant associations with multiple myeloma for persons overweight (25–&lt;30 kg/m2) or obese (30+ kg/m2) in both younger and usual adulthood (vs. individuals consistently &lt;25 kg/m2), but not for those overweight or obese at only one time period.Conclusions: BMI-associated increases in multiple myeloma risk were highest for individuals who were overweight or obese throughout adulthood.Impact: These findings provide the strongest evidence to date that earlier and later adult BMI may increase multiple myeloma risk and suggest that healthy BMI maintenance throughout life may confer an added benefit of multiple myeloma prevention. Cancer Epidemiol Biomarkers Prev; 26(6); 876–85. ©2017 AACR.
Global Cancer in Women: Burden and Trends
Authors: Torre Lindsey A. , Islami Farhad , Siegel Rebecca L. , Ward Elizabeth M. , Jemal Ahmedin 
Published: February 2017

AbstractThis review is an abbreviated version of a report prepared for the American Cancer Society Global Health department and EMD Serono, Inc., a subsidiary of Merck KGaA, Darmstadt, Germany, which was released at the Union for International Cancer Control World Cancer Congress in Paris in November 2016. The original report can be found at https://www.cancer.org/health-care-professionals/our-global-health-work/global-cancer-burden/global-burden-of-cancer-in-women.html. Staff in the Intramural Research Department of the American Cancer Society designed and conducted the study, including analysis, interpretation, and presentation of the review. The funding sources had no involvement in the study design, data analysis and interpretation, or preparation of the review.There are striking disparities in the global cancer burden in women, yet few publications highlight cancer occurrence in this population, particularly for cancers that are not sex specific. This article, the first in a series of two, summarizes the current burden, trends, risk factors, prevention, early detection, and survivorship of all cancers combined and seven sites (breast, cervix, uterine corpus, ovary, colorectum, lung, and liver) that account for about 60% of the cancer burden among women worldwide, using data from the International Agency for Research on Cancer. Estimated 2012 overall cancer death rates in general are higher among women in low- and middle-income countries (LMICs) than high-income countries (HICs), despite their lower overall incidence rates, largely due to inadequate access to early detection and treatment. For example, the top mortality rates are in Zimbabwe (147 deaths per 100,000) and Malawi (138). Furthermore, incidence rates of cancers associated with economic development (e.g., lung, breast, colorectum) are rising in several LMICs. The burden of cancer among women could be substantially reduced in both HICs and LMICs through broad and equitable implementation of effective interventions, including tobacco control, HPV and HBV vaccination, and screening (breast, cervix, and colorectum). Cancer Epidemiol Biomarkers Prev; 26(4); 444–57. ©2017 AACR.See related article by Islami et al. in this CEBP Focus section, “Global Cancer in Women.”
Spatial Analysis of Regional Factors and Lung Cancer Mortality in China, 1973–2013
Authors: Shen Xiaoping , Wang Limin , Zhu Li 
Published: February 2017

Abstract
Background: China's lung cancer crude death rate has increased 6.9-fold from 1973 to 2014. During this time, the country experienced extremely rapid economic growth and social change. It is important to understand the effects of risk factors on lung cancer mortality (LCM) for better allocation of limited resources of cancer prevention and control in China.
Methods: Using three nationwide mortality surveys from 1973 to 2005, Global Health Data Exchange data in 2013, three nationwide smoking surveys from 1984 to 2013, four population censuses from 1964 to 2000, and other datasets, we have compiled datasets and developed spatial random effect models to assess the association of various area-level–contributing factors on LCM. Spatial scan statistics are used to detect high-risk clusters of LCM.
Results: LCM is higher in urban and more industrialized areas (RR = 1.17) compared with those in rural areas. The level of industrial development's effect is higher for men, which accounts for about 70% of all LCM. Smoking is positively associated with regional variation of LCM rates, and the effect is higher for women than for men.
Conclusions: The geographic pattern of high LCM in China is different from that of Western countries. LCM is positively associated with higher socioeconomic status, with more urbanized areas at a higher level of industrial development.
Impact: There is a need to further explore additional risk in the high-risk clusters. The study is about China, but this situation may happen in other countries experiencing rapid industrialization and other developing countries. Cancer Epidemiol Biomarkers Prev; 26(4); 569–77. ©2017 AACR.
See all the articles in this CEBP Focus section, “Geospatial Approaches to Cancer Control and Population Sciences.”
Changes in the Glycosylation of Kininogen and the Development of a Kininogen-Based Algorithm for the Early Detection of HCC
Authors: Wang Mengjun , Sanda Miloslav , Comunale Mary Ann , Herrera Harmin , Swindell Charles , Kono Yuko , Singal Amit G. , Marrero Jorge , Block Timothy , Goldman Radoslav , Mehta Anand 
Published: February 2017

Abstract
Background: Hepatocellular carcinoma (HCC) has the greatest increase in mortality among all solids tumors in the United States related to low rates of early tumor detection. Development of noninvasive biomarkers for the early detection of HCC may reduce HCC-related mortality.
Methods: We have developed an algorithm that combines routinely observed clinical values into a single equation that in a study of &gt;3,000 patients from 5 independent sites improved detection of HCC as compared with the currently used biomarker, alpha-fetoprotein (AFP), by 4% to 20%. However, this algorithm had limited benefit in those with AFP &lt;20 ng/mL. To that end, we have developed a secondary algorithm that incorporates a marker, fucosylated kininogen, to improve the detection of HCC, especially in those with AFP &lt;20 ng/mL and early-stage disease.
Results: The ability to detect early-stage AFP-negative (AFP &lt;20 ng/mL) HCC increased from 0% (AFP alone) to 89% (for the new algorithm). Glycan analysis revealed that kininogen has several glycan modifications that have been associated with HCC, but often not with specific proteins, including increased levels of core and outer-arm fucosylation and increased branching.
Conclusions: An algorithm combining fucosylated kininogen, AFP, and clinical characteristics is highly accurate for early HCC detection.
Impact: Our biomarker algorithm could significantly improve early HCC detection and curative treatment eligibility in patients with cirrhosis. Cancer Epidemiol Biomarkers Prev; 26(5); 795–803. ©2017 AACR.
Vascular CXCR4 Expression Promotes Vessel Sprouting and Sensitivity to Sorafenib Treatment in Hepatocellular Carcinoma
Authors: Xu Jing , Liang Jing , Meng Ya-Ming , Yan Jing , Yu Xing-Juan , Liu Chao-Qun , Xu Li , Zhuang Shi-Mei , Zheng Limin 
Published: February 2017

Abstract
Purpose: C-X-C chemokine receptor type 4 (CXCR4) is known to be involved in both developmental and adult angiogenesis; however, its role in tumor angiogenesis remains largely unknown. Here, the role of vascular CXCR4 in regulating vascular structure in hepatocellular carcinoma (HCC) was assessd, and the clinical value of CXCR4 was explored.
Experimental Design: The expression of CXCR4 in HCC was determined by IHC and immunofluorescence. Characteristics of CXCR4+ cells were determined by in vitro and mice experiments. Kaplan–Meier survival analysis was used to determine the correlation of CXCR4 expression with prognosis.
Results: We found that CXCR4 is selectively expressed on a fraction of tumor endothelial cells (TECs) in HCC tissues, but not on the hepatic endothelium in peritumoral area. High levels of CXCR4 on TECs tended to develop a sinusoidal vasculature in tumors and predicted poor prognosis for patients with HCC. CXCR4+ endothelial cells (EC) displayed the functional features of tip cells, with increased expression of tip cell–related markers. Functional studies revealed that CXCR4 could directly promote vessel sprouting in vitro and in vivo. Interestingly, sorafenib treatment reduced the frequency of CXCR4+ ECs in culture and inhibited the formation of sinusoidal vasculature and growth of CXCR4High xenograft tumors. Moreover, high CXCR4 vascular density in resected tumor tissues before sorafenib treatment was associated with prolonged survival in patients with advanced HCC treated with sorafenib.
Conclusions: These data revealed that CXCR4 is a novel HCC vascular marker for vessel sprouting and could serve as a potential therapeutic target and a predictive factor for sorafenib treatment in patients with HCC. Clin Cancer Res; 23(15); 4482–92. ©2017 AACR.
Long-Term Responders on Olaparib Maintenance in High-Grade Serous Ovarian Cancer: Clinical and Molecular Characterization
Authors: Lheureux Stephanie , Lai Zhongwu , Dougherty Brian A. , Runswick Sarah , Hodgson Darren R. , Timms Kirsten M. , Lanchbury Jerry S. , Kaye Stan , Gourley Charlie , Bowtell David , Kohn Elise C. , Scott Claire , Matulonis Ursula , Panzarella Tony , Karakasis Katherine , Burnier Julia V. , Gilks C. Blake , O'Connor Mark J. , Robertson Jane D. , Ledermann Jonathan , Barrett J. Carl , Ho Tony W. , Oza Amit M. 
Published: February 2017

Abstract
Purpose: Maintenance therapy with olaparib has improved progression-free survival in women with high-grade serous ovarian cancer (HGSOC), particularly those harboring BRCA1/2 mutations. The objective of this study was to characterize long-term (LT) versus short-term (ST) responders to olaparib.
Experimental Design: A comparative molecular analysis of Study 19 (NCT00753545), a randomized phase II trial assessing olaparib maintenance after response to platinum-based chemotherapy in HGSOC, was conducted. LT response was defined as response to olaparib/placebo &gt;2 years, ST as &lt;3 months. Molecular analyses included germline BRCA1/2 status, three-biomarker homologous recombination deficiency (HRD) score, BRCA1 methylation, and mutational profiling. Another olaparib maintenance study (Study 41; NCT01081951) was used as an additional cohort.
Results: Thirty-seven LT (32 olaparib) and 61 ST (21 olaparib) patients were identified. Treatment was significantly associated with outcome (P &lt; 0.0001), with more LT patients on olaparib (60.4%) than placebo (11.1%). LT sensitivity to olaparib correlated with complete response to chemotherapy (P &lt; 0.05). In the olaparib LT group, 244 genetic alterations were detected, with TP53, BRCA1, and BRCA2 mutations being most common (90%, 25%, and 35%, respectively). BRCA2 mutations were enriched among the LT responders. BRCA methylation was not associated with response duration. High myriad HRD score (&gt;42) and/or BRCA1/2 mutation was associated with LT response to olaparib. Study 41 confirmed the correlation of LT response with olaparib and BRCA1/2 mutation.
Conclusions: Findings show that LT response to olaparib may be multifactorial and related to homologous recombination repair deficiency, particularly BRCA1/2 defects. The type of BRCA1/2 mutation warrants further investigation. Clin Cancer Res; 23(15); 4086–94. ©2017 AACR.
Modulating Therapeutic Activity and Toxicity of Pyrrolobenzodiazepine Antibody–Drug Conjugates with Self-Immolative Disulfide Linkers
Authors: Pillow Thomas H. , Schutten Melissa , Yu Shang-Fan , Ohri Rachana , Sadowsky Jack , Poon Kirsten Achilles , Solis Willy , Zhong Fiona , Del Rosario Geoffrey , Go Mary Ann T. , Lau Jeffrey , Yee Sharon , He Jintang , Liu Luna , Ng Carl , Xu Keyang , Leipold Douglas D. , Kamath Amrita V. , Zhang Donglu , Masterson Luke , Gregson Stephen J. , Howard Philip W. , Fang Fan , Chen Jinhua , Gunzner-Toste Janet , Kozak Katherine K. , Spencer Susan , Polakis Paul , Polson Andrew G. , Flygare John A. , Junutula Jagath R. 
Published: February 2017

Abstract
A novel disulfide linker was designed to enable a direct connection between cytotoxic pyrrolobenzodiazepine (PBD) drugs and the cysteine on a targeting antibody for use in antibody–drug conjugates (ADCs). ADCs composed of a cysteine-engineered antibody were armed with a PBD using a self-immolative disulfide linker. Both the chemical linker and the antibody site were optimized for this new bioconjugation strategy to provide a highly stable and efficacious ADC. This novel disulfide ADC was compared with a conjugate containing the same PBD drug, but attached to the antibody via a peptide linker. Both ADCs had similar efficacy in mice bearing human tumor xenografts. Safety studies in rats revealed that the disulfide-linked ADC had a higher MTD than the peptide-linked ADC. Overall, these data suggest that the novel self-immolative disulfide linker represents a valuable way to construct ADCs with equivalent efficacy and improved safety. Mol Cancer Ther; 16(5); 871–8. ©2017 AACR.
Resistance Mechanism against Trastuzumab in HER2-Positive Cancer Cells and Its Negation by Src Inhibition
Authors: Jin Mei Hua , Nam Ah-Rong , Park Ji Eun , Bang Ju-Hee , Bang Yung-Jue , Oh Do-Youn 
Published: February 2017

Abstract
Trastuzumab in combination with chemotherapy is the standard of care for patients with human epidermal growth factor receptor 2 (HER2)-positive breast and gastric cancers. Several resistance mechanisms against anti-HER2 therapy have been proposed. Src activation has been suggested to be responsible for the resistance of HER2-positive breast cancer. In our study, we generated four trastuzumab-resistant (HR) cancer cell lines from HER2-amplified gastric and biliary tract cancer cell lines (SNU-216, NCI-N87, SNU-2670, and SNU-2773). Elevated Src phosphorylation was detected in SNU2670HR and NCI-N87HR cell lines, but not in SNU216HR or SNU2773HR cell lines. In SNU216HR and SNU2773HR cell lines, phospho-FAK (focal adhesion kinase) was elevated. Bosutinib as a Src inhibitor suppressed growth, cell-cycle progression, and migration in both parental and HR cell lines. Specifically, Src interacted with FAK to affect downstream molecules such as AKT, ERK, and STAT3. Bosutinib showed more potent antitumor effects in Src-activated HR cell lines than parental cell lines. Taken together, this study suggests that Src inhibition may be an effective measure to overcome trastuzumab resistance in HER2-positive cancer. Mol Cancer Ther; 16(6); 1145–54. ©2017 AACR.