bluuebunny/crossref_metadata_2025_split huggingface dataset:
Leveraging GWAS data to identify metabolic pathways and networks involved in maize lipid biosynthesis
Authors: Li Hui , Thrash Adam , Tang Juliet D. , He Linlin , Yan Jianbing , Warburton Marilyn L. 
Published: February 2019

SummaryMaize (Zea mays mays) oil is a rich source of polyunsaturated fatty acids (FAs) and energy, making it a valuable resource for human food, animal feed, and bio‐energy. Although this trait has been studied via conventional genome‐wide association study (GWAS), the single nucleotide polymorphism (SNP)‐trait associations generated by GWAS may miss the underlying associations when traits are based on many genes, each with small effects that can be overshadowed by genetic background and environmental variation. Detecting these SNPs statistically is also limited by the levels set for false discovery rate. A complementary pathways analysis that emphasizes the cumulative aspects of SNP‐trait associations, rather than just the significance of single SNPs, was performed to understand the balance of lipid metabolism, conversion, and catabolism in this study. This pathway analysis indicated that acyl‐lipid pathways, including biosynthesis of wax esters, sphingolipids, phospholipids and flavonoids, along with FA and triacylglycerol (TAG) biosynthesis, were important for increasing oil and FA content. The allelic variation found among the genes involved in many degradation pathways, and many biosynthesis pathways leading from FAs and carbon partitioning pathways, was critical for determining final FA content, changing FA ratios and, ultimately, to final oil content. The pathways and pathway networks identified in this study, and especially the acyl‐lipid associated pathways identified beyond what had been found with GWAS alone, provide a real opportunity to precisely and efficiently manipulate high‐oil maize genetic improvement.
Hummocks in alpine tundra, northern British Columbia, Canada: distribution, morphology and organic carbon composition
Authors: Verret Marjolaine , Wang Yifeng , Bjornson Jean , Lacelle Denis 
Published: February 2019

Hummocks develop by cryoturbation in fine-grained frost-susceptible soils and their stage of maturity may affect the translocation of organics in Cryosols. This study examines the distribution and morphology of hummocks in the Chuck Creek Trail Valley (northern British Columbia) and determines the quantity, distribution, and composition of organic matter in their soils. Hummocks occupy about 5%–20% of the valley and their morphology is largely affected by their silt content. Cryoturbated intrusions, radiocarbon dated to 2814 and 1648 cal year B.P., suggest that hummock development was initiated during the cooler late Holocene. Hummocks have an average soil organic carbon density of 16.3 kg m−2 in the uppermost 1 m, with 62% stored in the top 25 cm. Organics are mainly present as particulate organic matter in the O-horizon (25%–80%), characterized by degradable alkyl C and O/N-alkyl groups, but occur as mineral-associated organic matter (96%–98%) composed of recalcitrant aromatic and aliphatic C groups in the underlying B and C horizons. Minor differences in organic content and composition occur between hummock tops and troughs, and between hummocks showing different stages of maturity. In the absence of an observed frost table, contemporary hummock activity is attributed to seasonal freezing and thawing.
Mismatching Structures: A New Explanation for the “Unsatisfactory” Labor Conditions in Chinese Mining Companies in the Democratic Republic of Congo
Authors: Wang Duanyong , Zhao Pei 
Published: February 2019

Ever since the Minerals-for-Infrastructure Deal valued at $6 billion was signed between Chinese companies and the Democratic Republic of Congo (DRC) Government in 2008, there have been criticisms on both the agreement itself and the working conditions for Congolese and Chinese workers in Chinese mineral enterprises in the DRC. Based on our fieldwork in Katanga Province of the DRC and interviews with dozens of local Chinese workers and managers in Chinese-run mining companies as well as staff working at the civil society organizations and governmental departments there, this research tries to investigate the real working conditions in Chinese mining companies. This paper concludes with three points. First, the so-called “wage gap” always asserted by the local workers is rather a phenomenon of employment structure than discrimination. In non-English-speaking African countries, a gap has actually emerged between the insufficiency of local human resources and the lack in localization capabilities of the Chinese multinational enterprises. Second, the compliance dynamics and mechanism of Chinese-run mining companies in the field of labor conditions were driven by local pressure groups including legislation, governments and NGOs, rather than by Chinese government or legislative system. What is interesting is that the rigid discipline of local laws and the abuse of discretion in the process of implementing laws have created a special pressuring structure and resulted in some complex consequences. Third, many Chinese-run mining companies in the DRC have quite different business structures from their branches in China. This is because of their financial investment aims and for the ease of enterprises’ transition. Therefore, it has led to their different perspectives of labor conditions and human resources strategy from mature MNCs. In summary, the research cannot draw a conclusion that the labor conditions are really terrible in Chinese-run mining companies in Katanga Province. However, it reveals that the Chinese government and Chinese enterprises are still not fully prepared for direct investment abroad, although “Going-out” strategy was raised 13 years ago.
89Zr-labeled Bispecific T-cell Engager AMG 211 PET Shows AMG 211 Accumulation in CD3-rich Tissues and Clear, Heterogeneous Tumor Uptake
Authors: Moek Kirsten L. , Waaijer Stijn J.H. , Kok Iris C. , Suurs Frans V. , Brouwers Adrienne H. , Menke-van der Houven van Oordt C. Willemien , Wind Thijs T. , Gietema Jourik A. , Schröder Carolien P. , Mahesh Shekar V.K. , Jorritsma-Smit Annelies , Lub-de Hooge Marjolijn N. , Fehrmann Rudolf S.N. , de Groot Derk Jan A. , de Vries Elisabeth G.E. 
Published: February 2019

Abstract

Purpose:
Biodistribution of bispecific antibodies in patients is largely unknown. We therefore performed a feasibility study in 9 patients with advanced gastrointestinal adenocarcinomas to explore AMG 211 biodistribution (also known as MEDI-565), an approximately 55 kDa bispecific T-cell engager (BiTE®) directed against carcinoembryonic antigen (CEA) on tumor cells and cluster of differentiation 3 (CD3) on T-cells.

Experimental Design:
89Zr-labeled AMG 211 as tracer was administered alone or with cold AMG 211, for PET imaging before and/or during AMG 211 treatment.

Results:
Before AMG 211 treatment, the optimal imaging dose was 200-μg 89Zr-AMG 211 + 1,800-μg cold AMG 211. At 3 hours, the highest blood pool standardized uptake value (SUV)mean was 4.0, and tracer serum half-life was 3.3 hours. CD3-mediated uptake was clearly observed in CD3-rich lymphoid tissues including spleen and bone marrow (SUVmean 3.2 and 1.8, respectively), and the SUVmean decreased more slowly than in other healthy tissues. 89Zr-AMG 211 remained intact in plasma and was excreted predominantly via the kidneys in degraded forms. Of 43 visible tumor lesions, 37 were PET quantifiable, with a SUVmax of 4.0 [interquartile range (IQR) 2.7–4.4] at 3 hours using the optimal imaging dose. The tracer uptake differed between tumor lesions 5-fold within and 9-fold between patients. During AMG 211 treatment, tracer was present in the blood pool, whereas tumor lesions were not visualized, possibly reflecting target saturation.

Conclusions:
This first-in-human study shows high, specific 89Zr-AMG 211 accumulation in CD3-rich lymphoid tissues, as well as a clear, inter- and intraindividual heterogeneous tumor uptake.
Evaluation of Salivary Exosomal Chimeric GOLM1-NAA35 RNA as a Potential Biomarker in Esophageal Carcinoma
Authors: Lin Yusheng , Dong Hongmei , Deng Weilun , Lin Wan , Li Kai , Xiong Xiao , Guo Yi , Zhou Fuyou , Ma Changchun , Chen Yuping , Ren Hongzheng , Yang Haijun , Dai Ningtao , Ma Lang , Meltzer Stephen J. , Yeung Sai-Ching J. , Zhang Hao 
Published: February 2019

Abstract

Purpose:
Transcriptionally induced chimeric RNAs are an important emerging area of research into molecular signatures for biomarker and therapeutic target development. Salivary exosomes represent a relatively unexplored, but convenient, and noninvasive area of cancer biomarker discovery. However, the potential of cancer-derived exosomal chimeric RNAs in saliva as biomarkers is unknown. Here, we explore the potential clinical utility of salivary exosomal GOLM1-NAA35 chimeric RNA (seG-NchiRNA) in esophageal squamous cell carcinoma (ESCC).

Experimental Design:
In a retrospective study, the prognostic significance of G-NchiRNA was determined in ESCC tissues. The correlation between seG-NchiRNA and circulating exosomal or tumoral G-NchiRNA was ascertained in cultured cells and mice. In multiple prospective cohorts of patients with ESCC, seG-NchiRNA was measured by qRT-PCR and analyzed for diagnostic accuracy, longitudinal monitoring of treatment response, and prediction of progression-free survival (PFS).

Results:
Exosomal G-NchiRNA was readily detectable in ESCC cells and nude mouse ESCC xenografts. SeG-NchiRNA levels reflected tumor burden in vivo and correlated with tumor G-NchiRNA levels. In prospective studies of a training cohort (n = 220) and a validation cohort (n = 102), seG-NchiRNA levels were substantially reduced after ESCC resection. Moreover, seG-NchiRNA was successfully used to evaluate chemoradiation responsiveness, as well as to detect disease progression earlier than imaging studies. Changes in seG-NchiRNA levels also predicted PFS of patients after chemoradiation.

Conclusions:
SeG-NchiRNA constitutes an effective candidate noninvasive biomarker for the convenient, reliable assessment of therapeutic response, recurrence, and early detection.
Autologous Lymphocyte Infusion Supports Tumor Antigen Vaccine–Induced Immunity in Autologous Stem Cell Transplant for Multiple Myeloma
Authors: Cohen Adam D. , Lendvai Nikoletta , Nataraj Sarah , Imai Naoko , Jungbluth Achim A. , Tsakos Ioanna , Rahman Adeeb , Mei Anna Huo-Chang , Singh Herman , Zarychta Katarzyna , Kim-Schulze Seunghee , Park Andrew , Venhaus Ralph , Alpaugh Katherine , Gnjatic Sacha , Cho Hearn J. 
Published: February 2019

AbstractAutologous stem cell transplant (autoSCT), the standard consolidation therapy for multiple myeloma, improves disease-free survival, but is not curative. This could be an ideal setting for immunologic therapy. However, the immune milieu is impaired after autoSCT. We hypothesized that autologous lymphocyte infusion would restore immune competence, allowing immunotherapies such as cancer vaccines to elicit tumor antigen–specific immunity in the setting of autoSCT. In this pilot study (NCT01380145), we investigated safety, immunologic, and clinical outcomes of autologous lymphocyte infusion combined with peri-autoSCT immunotherapy with recombinant MAGE-A3 (a multiple myeloma–associated antigen) and adjuvant. Thirteen patients with multiple myeloma undergoing autoSCT were enrolled. Autologous lymphocyte infusion and MAGE vaccination were well tolerated. Combination immunotherapy resulted in high-titer humoral immunity and robust, antigen-specific CD4+ T-cell responses in all subjects, and the responses persisted at least one year post-autoSCT. CD4+ T cells were polyfunctional and Th1-biased. CD8+ T-cell responses were elicited in 3 of 13 subjects. These cells recognized naturally processed MAGE-A3 antigen. Median progression-free survival was 27 months, and median overall survival was not reached, suggesting no differences from standard-of-care. In 4 of 8 subjects tested, MAGE-A protein expression was not detected by IHC in multiple myeloma cells at relapse, suggesting therapy-induced immunologic selection against antigen-expressing clones. These results demonstrated that autologous lymphocyte infusion augmentation of autoSCT confers a favorable milieu for immunotherapies such as tumor vaccines. This strategy does not require ex vivo manipulation of autologous lymphocyte products and is an applicable platform for further investigation into combination immunotherapies to treat multiple myeloma.
MG53 Protein Protects Aortic Valve Interstitial Cells From Membrane Injury and Fibrocalcific Remodeling
Authors: Adesanya T. M. Ayodele , Russell Melanie , Park Ki Ho , Zhou Xinyu , Sermersheim Matthew A. , Gumpper Kristyn , Koenig Sara N. , Tan Tao , Whitson Bryan A. , Janssen Paul M. L. , Lincoln Joy , Zhu Hua , Ma Jianjie 
Published: February 2019

Background

The aortic valve of the heart experiences constant mechanical stress under physiological conditions. Maladaptive valve injury responses contribute to the development of valvular heart disease. Here, we test the hypothesis that
MG
53 (mitsugumin 53), an essential cell membrane repair protein, can protect valvular cells from injury and fibrocalcific remodeling processes associated with valvular heart disease.

Methods and Results

We found that
MG
53 is expressed in pig and human patient aortic valves and observed aortic valve disease in aged
Mg53−/−
mice. Aortic valves of
Mg53−/−
mice showed compromised cell membrane integrity. In vitro studies demonstrated that recombinant human
MG
53 protein protects primary valve interstitial cells from mechanical injury and that, in addition to mediating membrane repair, recombinant human
MG
53 can enter valve interstitial cells and suppress transforming growth factor‐β‐dependent activation of fibrocalcific signaling.

Conclusions

Together, our data characterize valve interstitial cell membrane repair as a novel mechanism of protection against valvular remodeling and assess potential in vivo roles of
MG
53 in preventing valvular heart disease.
Living in Food Deserts and Adverse Cardiovascular Outcomes in Patients With Cardiovascular Disease
Authors: Kelli Heval M. , Kim Jeong Hwan , Samman Tahhan Ayman , Liu Chang , Ko Yi‐An , Hammadah Muhammad , Sullivan Samaah , Sandesara Pratik , Alkhoder Ayman A. , Choudhary Fahad K. , Gafeer M. Mazen , Patel Keyur , Qadir Saqib , Lewis Tené T. , Vaccarino Viola , Sperling Laurence S. , Quyyumi Arshed A. 
Published: February 2019

Background

Food deserts (
FDs
), defined as low‐income communities with limited access to healthy food, are a growing public health concern. We evaluated the impact of living in
FDs
on incident cardiovascular events.

Methods and Results

We recruited 4944 subjects (age 64±12, 64% male) undergoing cardiac catheterization into the Emory Cardiovascular Biobank. Using the US Department of Agriculture definition of
FD
, we determined whether their residential addresses had (1) poor access to healthy food, (2) low income, or (3) both (=
FD
). Subjects were prospectively followed for a median of 3.2 years for myocardial infarction (MI) and death. Fine and Gray's subdistribution hazard models for
MI
and Cox proportional hazard models for death/
MI
were used to examine the association between area characteristics (
FD
, poor access, and low income) and the rates of adverse events after adjusting for traditional risk factors. A total of 981 (20%) lived in
FDs
and had a higher adjusted risk of
MI
(subdistribution hazard ratio, 1.44 [95%
CI,
1.06–1.95]) than those living in non‐
FDs
. In a multivariate analysis including both food access and area income, only living in a low‐income area was associated with a higher adjusted risk of
MI
(subdistribution hazard ratio, 1.40 [1.06–1.85]) and death/
MI
(hazard ratio, 1.18 [1.02–1.35]) while living in a poor‐access area was not significantly associated with either (subdistribution hazard ratio, 1.05 [0.80–1.38] and hazard ratio, 0.99 [0.87–1.14], respectively).

Conclusions

Living in an FD is associated with a higher risk of adverse cardiovascular events in those with coronary artery disease. Specifically, low area income of
FDs
, not poor access to food, was significantly associated with worse outcomes.
Role of neutrophil-to-lymphocyte ratio as a prognostic indicator for hemodialysis arteriovenous fistula failure
Authors: Wongmahisorn Yuthapong 
Published: February 2019

Objective: To evaluate the role of preoperative peripheral blood neutrophil-to-lymphocyte ratio in predicting early arteriovenous fistula failure. The impact of postoperative neutrophil-to-lymphocyte ratio on arteriovenous fistula failure was also investigated. Methods: Medical records from 470 patients who underwent first-time arteriovenous fistula creation were studied. Demographic, clinical, and laboratory data were obtained. Receiver operating characteristic curves were constructed to determine the optimal cutoff values of preoperative and postoperative neutrophil-to-lymphocyte ratios for predicting early arteriovenous fistula failure. Univariate and multivariate analyses were performed to evaluate whether the neutrophil-to-lymphocyte ratio parameters were prognostic indicators for arteriovenous fistula failure. Results: Complete data from 396 patients were studied. The prevalence of early arteriovenous fistula failure was 30.6%. The optimal cutoff values of preoperative and postoperative neutrophil-to-lymphocyte ratios for predicting early arteriovenous fistula failure were 2.7 (82.6% sensitivity and 52.0% specificity) and 2.9 (78.5% sensitivity and 73.1% specificity), respectively. By univariate and multivariate analyses, high preoperative and postoperative neutrophil-to-lymphocyte ratios were significantly associated with early arteriovenous fistula failure. The adjusted odds ratios were 5.46 (95% confidence interval: 3.15–9.48) and 7.19 (95% confidence interval: 4.12–12.55), respectively. Conclusions: High preoperative and postoperative neutrophil-to-lymphocyte ratios significantly predict early arteriovenous fistula failure.
Nasal dermoid cyst with intracranial extension in a cat
Authors: Brady Stacey , Bell Erin , Courtman Natalie , Chevoir Matthias Le 
Published: February 2019

Case summary An 11-month-old female neutered Ragdoll cat was presented for focal seizures, aggression and altered behaviour. A diagnosis of a nasal dermoid cyst with intracranial extension was made following MRI, cytology and histopathology. The cyst was surgically excised with a resolution of clinical signs, with the exception of ongoing seizure activity requiring anti-seizure medication. Relevance and novel information To our knowledge, this is the first reported case of a nasal dermoid cyst in a cat, and the first reported case in the veterinary literature of any species with a nasal dermoid cyst presenting with neurological signs.
Patients' perspectives on COPD: findings from a social media listening study
Authors: Cook Nigel S. , Kostikas Konstantinos , Gruenberger Jean-Bernard , Shah Bhavik , Pathak Purnima , Kaur Vinay Preet , Mudumby Alaknanda , Sharma Rajat , Gutzwiller Florian S. 
Published: February 2019

We utilised social media listening (SML) to obtain patients' perspectives on symptoms, diagnosis and comorbidities associated with chronic obstructive pulmonary disease (COPD) and its impact on patients' quality of life (QoL).A comprehensive search on social media platforms was performed for English language content posted between July 2016 and January 2018 using COPD-related terms. Social Studio, a social media data aggregator tool, was used to capture relevant records. The content was manually curated to analyse and map psychological aspects with descriptive statistics applied on aggregated findings.A total of 849 posts from patients or caregivers (“patient insights”) were considered for the analysis, corresponding to postings of 695 unique individuals. Based on 734 mentions of symptoms from 849 posts by potential patients/caregivers, cough (27%), mucus (25%) and shortness of breath (21%) were the most frequent; analysis by perceived COPD severity indicated these to be common across all severities. Difficulty in mucus clearance (24% of 268 mentions) and sadness (40% of 129 mentions) were top among the aspects impacting physical and emotional QoL, respectively.SML from patients with COPD indicated that relief from cough, mucus production and shortness of breath would be the most desirable aspects of disease management from a patient's perspective.
The evolutionary genetics of lactase persistence in seven ethnic groups across the Iranian plateau
Authors: Charati Hadi , Peng Min-Sheng , Chen Wei , Yang Xing-Yan , Jabbari Ori Roghayeh , Aghajanpour-Mir Mohsen , Esmailizadeh Ali , Zhang Ya-Ping 
Published: February 2019

Abstract
Background
The ability to digest dietary lactose is associated with lactase persistence (LP) in the intestinal lumen in human. The genetic basis of LP has been investigated in many populations in the world. Iran has a long history of pastoralism and the daily consumption of dairy products; thus, we aim to assess how LP has evolved in the Iranian population. We recruited 400 adult individuals from seven Iranian ethnic groups, from whom we investigated their lactose tolerance and screened the genetic variants in their lactase gene locus.

Results
The LP frequency distribution ranged from 0 to 29.9% in the seven Iranian ethnic groups with an average value of 9.8%. The variants, − 13910*T and − 22018*A, were significantly associated with LP phenotype in Iranians. We found no evidence of hard selective sweep for − 13910*T and − 22018*A in Persians, the largest ethnic group of Iran. The extremely low frequency of − 13915*G in the Iranian population challenged the view that LP distribution in Iran resulted from the demic diffusion, especially mediated by the spread of Islam, from the Arabian Peninsula.

Conclusions
Our results indicate the distribution of LP in seven ethnic groups across the Iranian plateau. Soft selective sweep rather than hard selective sweep played a substantial role in the evolution of LP in Iranian populations.