bluuebunny/crossref_metadata_2025_split huggingface dataset:
Galactose‐modified duocarmycin prodrugs as senolytics
Authors: Guerrero Ana , Guiho Romain , Herranz Nicolás , Uren Anthony , Withers Dominic J. , Martínez‐Barbera Juan Pedro , Tietze Lutz F. , Gil Jesús 
Published: March 2020

AbstractSenescence is a stable growth arrest that impairs the replication of damaged, old or preneoplastic cells, therefore contributing to tissue homeostasis. Senescent cells accumulate during ageing and are associated with cancer, fibrosis and many age‐related pathologies. Recent evidence suggests that the selective elimination of senescent cells can be effective on the treatment of many of these senescence‐associated diseases. A universal characteristic of senescent cells is that they display elevated activity of the lysosomal β‐galactosidase, and this has been exploited as a marker for senescence (senescence‐associated β‐galactosidase activity). Consequently, we hypothesized that galactose‐modified cytotoxic prodrugs will be preferentially processed by senescent cells, resulting in their selective killing. Here, we show that different galactose‐modified duocarmycin (GMD) derivatives preferentially kill senescent cells. GMD prodrugs induce selective apoptosis of senescent cells in a lysosomal β‐galactosidase (GLB1)‐dependent manner. GMD prodrugs can eliminate a broad range of senescent cells in culture, and treatment with a GMD prodrug enhances the elimination of bystander senescent cells that accumulate upon whole‐body irradiation treatment of mice. Moreover, taking advantage of a mouse model of adamantinomatous craniopharyngioma (ACP), we show that treatment with a GMD prodrug selectively reduced the number of β‐catenin‐positive preneoplastic senescent cells. In summary, the above results make a case for testing the potential of galactose‐modified duocarmycin prodrugs to treat senescence‐related pathologies.
Vitamin D status is associated with muscular strength in a nationally representative sample of US youth
Authors: Laurson Kelly R. , Thomas Jaime N. , Barnes Jennifer L. 
Published: March 2020

AbstractAimTo evaluate the association between serum 25‐hydroxyvitamin D (25OHD) and muscular strength in a nationally representative sample of US youth.MethodsParticipants (n = 3350) were 6‐ to 18‐y‐olds from 2011 to 2014 National Health and Nutrition Examination Survey. Relative handgrip strength was quantified using age‐ and sex‐specific z‐scores. Poor strength was defined as those <25th percentile. Multivariate general linear and logistic models were used to compare strength and poor strength status by clinically relevant groupings of 25OHD.ResultsApproximately 20.2% of youth had 25OHD <50 nmol/L. Mean relative strength was highest for those at ≥75 nmol/L of 25OHD. The percentage of boys/girls with poor strength in the <50 nmol/L, 50‐74.9 nmol/L and ≥75 nmol/L groups was 34.9%/32.3%, 25.8%/28.2% and 14.0%/15.8%, respectively. The odds of boys and girls with <50 nmol/L 25OHD having poor strength were 2.8 (95% CI: 1.4, 5.5) and 3.4 (1.7, 6.8) times higher compared to those with ≥75 nmol/L, respectively.ConclusionHigher levels of circulating vitamin D were associated with higher relative strength, and poor strength was more prevalent when 25OHD was <75 nmol/L. These findings highlight the value of vitamin D for the muscle‐bone unit and potential extraskeletal ramifications.
The concept of skeletal muscle memory: Evidence from animal and human studies
Authors: Snijders Tim , Aussieker Thorben , Holwerda Andy , Parise Gianni , van Loon Luc J. C. , Verdijk Lex B. 
Published: March 2020

AbstractWithin the current paradigm of the myonuclear domain theory, it is postulated that a linear relationship exists between muscle fibre size and myonuclear content. The myonuclear domain is kept (relatively) constant by adding additional nuclei (supplied by muscle satellite cells) during muscle fibre hypertrophy and nuclear loss (by apoptosis) during muscle fibre atrophy. However, data from recent animal studies suggest that myonuclei that are added to support muscle fibre hypertrophy are not lost within various muscle atrophy models. Such myonuclear permanence has been suggested to constitute a mechanism allowing the muscle fibre to (re)grow more efficiently during retraining, a phenomenon referred to as “muscle memory.” The concept of “muscle memory by myonuclear permanence” has mainly been based on data attained from rodent experimental models. Whether the postulated mechanism also holds true in humans remains largely ambiguous. Nevertheless, there are several studies in humans that provide evidence to potentially support or contradict (parts of) the muscle memory hypothesis. The goal of the present review was to discuss the evidence for the existence of “muscle memory” in both animal and human models of muscle fibre hypertrophy as well as atrophy. Furthermore, to provide additional insight in the potential presence of muscle memory by myonuclear permanence in humans, we present new data on previously performed exercise training studies. Finally, suggestions for future research are provided to establish whether muscle memory really exists in humans.
Optimising the selection of candidates for neoadjuvant chemotherapy amongst patients with node‐positive penile squamous cell carcinoma
Authors: Bandini Marco , Albersen Maarten , Chipollini Juan , Pederzoli Filippo , Zhu Yao , Ye Ding‐Wei , Ornellas Antonio A. , Watkin Nick , Ager Michael , Hakenberg Oliver W. , Heidenreich Axel , Raggi Daniele , Catanzaro Mario , Haidl Friederike , Mazzone Elio , Marandino Laura , Briganti Alberto , Montorsi Francesco , Azizi Mounsif , Spiess Philippe E. , Necchi Andrea 
Published: March 2020

ObjectivesTo identify predictors of poor overall survival (OS) amongst patients with penile squamous cell carcinoma (pSCC) with clinical inguinal lymphadenopathy (cN+), in order to define the best candidates for neoadjuvant chemotherapy (NAC).Patients and MethodsUsing an international, multicentre database of 924 patients with pSCC, we identified 334 men who harboured cN+ with available clinical and follow‐up data. Lymph node involvement was defined either by the presence of palpable inguinal node disease or by preoperative computed tomography (CT) assessment. Fluorine‐18 fluorodeoxyglucose positron‐emission tomography (18F‐FDG‐PET)/CT scan was performed based on clinical judgment of the treating physician. Regression‐tree analysis generated a risk stratification tool for prediction of 24‐month overall mortality (OM). Kaplan–Meier explored the OS benefit related to the use of NAC according to the regression‐tree‐stratified subgroups.ResultsOverall, 120 (35.9%), 152 (45.5%), and 62 (18.6%) patients harboured cN1, cN2, and cN3 disease.18F‐FDG‐PET/CT was performed in 48 (14.4%) patients, and 16 (4.8%) had inguinal and pelvic nodal PET detection. The median OS was 107 months, with a 24‐month OS of 66%. At regression‐tree analysis (area under the curve = 70%), patients with cN3 and cN2 with PET/CT‐detected inguinal and pelvic nodal activity had a higher risk of 24‐month OM (>50%). NAC was associated with improved 24‐month OS rates (54% vs 33%) only in this subgroup of patients (P = 0.002), which was also confirmed after multivariable adjustment (hazard ratio 0.28, 95% confidence interval 0.13–0.62;P = 0.002).ConclusionPatients with pSCC with cN3 or cN2 and inguinal and pelvic 18F‐FDG‐PET/CT scan detected disease had higher 24‐month OM rates according to our regression‐tree model. NAC was associated with improved OS only in these subgroups of patients. Our novel decision model may help to stratify cN+ patients, and identify those who most likely will benefit from NAC prior to radical surgical resection.
Is Onodera’s prognostic nutritional index (OPNI) a prognostic factor in small cell lung cancer (SCLC)?
Authors: Yenibertiz Derya , Ozyurek Berna Akinci , Erdogan Yurdanur 
Published: March 2020

AbstractIntroductionWe aimed to evaluate the prognostic value of Onodera’s prognostic nutritional index (OPNI) in patients with Small‐cell lung cancer (SCLC).Materials and methodsThis study retrospectively examined 109 patients diagnosed with SCLC between January 2008 and October 2018 in our hospital. Patients were divided into two groups according to the median of OPNI values.ResultsA significant difference was observed between the groups in terms of neutrophil percentage, lymphocyte count, lymphocyte percentage, C‐reactive protein (CRP), albumin, lactat dehidrogenase (LDH) and neutrophil to lymphocyte ratio (NLR) (P < 0.05). LDH, CRP, neutrophil percentage and NLR (P = 0.008, P < 0.001, P = 0.001, P < 0.001, respectively) were significantly higher and albumin, lymphocyte count and lymphocyte percentage (P < 0.001, P < 0.001, P = 0.001, respectively) were significantly lower in the low OPNI group. Survival analyses have shown that mortality rates and lifespan are similar in the two groups.ConclusionThe OPNI may be a helpful tool for determining the prognosis in SCLC.
On the co‐evolution of surface oxygen levels and animals
Authors: Cole Devon B. , Mills Daniel B. , Erwin Douglas H. , Sperling Erik A. , Porter Susannah M. , Reinhard Christopher T. , Planavsky Noah J. 
Published: March 2020

AbstractFew topics in geobiology have been as extensively debated as the role of Earth's oxygenation in controlling when and why animals emerged and diversified. All currently described animals require oxygen for at least a portion of their life cycle. Therefore, the transition to an oxygenated planet was a prerequisite for the emergence of animals. Yet, our understanding of Earth's oxygenation and the environmental requirements of animal habitability and ecological success is currently limited; estimates for the timing of the appearance of environments sufficiently oxygenated to support ecologically stable populations of animals span a wide range, from billions of years to only a few million years before animals appear in the fossil record. In this light, the extent to which oxygen played an important role in controlling when animals appeared remains a topic of debate. When animals originated and when they diversified are separate questions, meaning either one or both of these phenomena could have been decoupled from oxygenation. Here, we present views from across this interpretive spectrum—in a point–counterpoint format—regarding crucial aspects of the potential links between animals and surface oxygen levels. We highlight areas where the standard discourse on this topic requires a change of course and note that several traditional arguments in this “life versus environment” debate are poorly founded. We also identify a clear need for basic research across a range of fields to disentangle the relationships between oxygen availability and emergence and diversification of animal life.
Long‐term research avoids spurious and misleading trends in sustainability attributes of no‐till
Authors: Cusser Sarah , Bahlai Christie , Swinton Scott M. , Robertson G. Philip , Haddad Nick M. 
Published: March 2020

AbstractAgricultural management recommendations based on short‐term studies can produce findings inconsistent with long‐term reality. Here, we test the long‐term environmental sustainability and profitability of continuous no‐till agriculture on yield, soil water availability, and N2O fluxes. Using a moving window approach, we investigate the development and stability of several attributes of continuous no‐till as compared to conventional till agriculture over a 29‐year period at a site in the upper Midwest, US. Over a decade is needed to detect the consistent effects of no‐till. Both crop yield and soil water availability required 15 years or longer to generate patterns consistent with 29‐year trends. Only marginal trends for N2O fluxes appeared in this period. Relative profitability analysis suggests that after initial implementation, 86% of periods between 10 and 29 years recuperated the initial expense of no‐till implementation, with the probability of higher relative profit increasing with longevity. Importantly, statistically significant but misleading short‐term trends appeared in more than 20% of the periods examined. Results underscore the importance of decadal and longer studies for revealing consistent dynamics and emergent outcomes of no‐till agriculture, shown to be beneficial in the long term.
Logistics: Situating flows in a spatial context
Authors: Hesse Markus 
Published: March 2020

AbstractThe origins of logistics lie in military and imperial methods of expansion and control of geographical space. It is principally associated with the more recent contexts of business management and engineering. Logistics systems are now the conveyor belts of the global system of trade, commerce and production, and its associated techniques and strategies aim at optimizing flows and throughput within discrete units (such as firms), in economic networks and across geographical space. Because flows are important determinants for the development of places, logistics has the power to structure territories. Therefore, it has raised considerable interest in the field of geography, not only with regard to cities and their dense agglomeration of people, buildings, and infrastructure but also in geopolitical terms as it fosters the exploration, control, and surveillance of areas. The paper presents a critical account of logistics operations and their relevance for the making (and unmaking) of territories, related policy dimensions, and future challenges for research.
The evolving borderland of energy geographies
Authors: Baka Jennifer , Vaishnava Saumya 
Published: March 2020

AbstractEnergy geographers have characterized energy as a borderland topic because of its ability to straddle and interconnect different geographic concepts and debates. In this review, we evaluate how the borderland of energy geographies has been emerging in recent years by analyzing scholarship on energy published in top geography journals and a leading energy studies journal, Energy Research & Social Science. In part 1 of our review, we evaluate how the borderland of energy geographies is evolving by mapping the geographic range of empirical studies, the processes and types of energy systems being researched and the key geographic concepts/theories engaged across the four main sub‐fields of geography. We find that energy geographies scholarship has primarily centered on the Global North, remains focused on the extractive and production phase of energy development and is evolving across and within three of the four sub‐fields of geography. Energy transitions, governance, justice, space, and landscape are key topics and concepts examined. Notable underrepresentations include a relative lack of energy geographies scholarship within physical geography, as well as limited studies that engage geographic concepts to study the transportation sector, unconventional energy development and the food‐energy‐water nexus. In part 2, we identify three broad research themes to expand the frontier of energy geographies: (a) geographies of energy knowledge production, particularly indigenous knowledge; (b) materializing energy, especially through engaging political‐industrial ecology; and (c) advancing geographic thought by critically assessing how studying energy advances/challenges/transforms core geographic concepts and debates. Collectively, our review demonstrates that energy geographies have established firm footing within and across geography. Deepening engagement with emerging trends elsewhere in geography and the social sciences will not only help to better conceptualize what a geographic perspective on energy means but will also help to make clearer sense of the rapid economic, social, environmental, and political transformations currently underway within the global energy system.
The optimum seeding and harvesting dates of sorghum–sudangrass hybrid (Sorghum bicolor L.) via optimum moving response surface methodology
Authors: Kim Moonju , Kim Ji Yung , Sung Kyungil 
Published: March 2020

AbstractIn general, determining suitable seeding and harvesting times is important in achieving high yields of forage crops in terms of both physiology and ecology. To determine the optimum point, the response surface methodology (RSM) is well known in agricultural science. This study aimed to establish optimum seeding and harvesting dates and to verify the variation of dry matter yield (DMY) for sorghum–sudangrass hybrid (SSH), by determining what we called the “optimum moving RSM” proposed to optimize the RSM in the metadata. The SSH metadata consist of individual experiments (n = 856) that were performed to check the optimum seeding and harvesting dates using classic RSM. However, the SSH metadata failed to produce a single effective equation to determine the optimum seeding and harvesting dates due to the different characteristics of the experimental design. Therefore, the optimum moving RSM was introduced. As a result, we found that the optimum seeding and harvesting dates were clear, based on a single quadratic function. The maximum DMY at the optimum seeding and harvesting dates (the 4th of May and 23rd of September, respectively) was 25,404.50 and 23,697.01 kg/ha, respectively. SSH yield decreases rapidly from 10 days after the optimum date, and seeding and harvesting should be performed within 5 days to ensure a stable yield. Furthermore, the optimum moving RSM is expected to be useful to establish the optimum point in the metadata.
Enhancing researcher capacity to engage youth in research: Researchers’ engagement experiences, barriers and capacity development priorities
Authors: Hawke Lisa D. , Darnay Karleigh , Relihan Jacqueline , Khaleghi‐Moghaddam Mohammad , Barbic Skye , Lachance Lisa , Ben‐David Shelly , Brown Marion , Iyer Srividya , Chaim Gloria , Soklaridis Sophie , Kidd Sean A. , Halsall Tanya , Mathias Steve , Henderson Joanna 
Published: March 2020

AbstractBackgroundThere is increasing emphasis on engaging youth in research about youth, their needs, experiences and preferences, notably in health services research. By engaging youth as full partners, research becomes more feasible and relevant, and the validity and richness of findings are enhanced. Consequently, researchers need guidance in engaging youth effectively. This study examines the experiences, needs and knowledge gaps of researchers.MethodsEighty‐four researchers interested in youth engagement training were recruited via snowball sampling. They completed a survey regarding their youth engagement experiences, attitudes, perceived barriers and capacity development needs. Data were analysed descriptively, and comparisons were made based on current engagement experience.ResultsParticipants across career stages and disciplines expressed an interest in increased capacity development for youth engagement. They had positive attitudes about the importance and value of youth engagement, but found it to be complex. Participants reported requiring practical guidance to develop their youth engagement practices and interest in a network of youth‐engaged researchers and on‐going training. Those currently engaging youth were more likely to report the need for greater appreciation of youth engagement by funders and institutions.ConclusionsEngaging youth in research has substantial benefits. However, skills in collaborating with youth to design, conduct and implement research have to be learned. Researchers need concrete training and networking opportunities to develop and maximize these skills. They also need mechanisms that formally acknowledge the value of engagement. Researchers and those promoting youth engagement in research are encouraged to consider these findings in their promotion and training endeavours.
Theorizing self‐repairers' worldview–personhood to advance new thinking on extended product lifetimes
Authors: Dermody Janine , Nagase Yoko , Berger Wolfram 
Published: March 2020

AbstractThe ecological and societal problems caused by product obsolescence and consumerism in modern economies constitute a “wicked human‐made problem” of significant magnitude. Current (old) ways of thinking cannot address these problems. Accordingly, in this paper, we critically explore the novel idea of integrated personhood and worldviews to theorize research on self‐repairers and their repair behaviours to extend product lifetimes. We conducted a structured and systematic review of published work (n = 183) to identify the conceptual content of the field to inform our theorization. Our findings highlight three key issues. First, constricted theorization undermines understanding of self‐repairers and their product lifetime extension (and spillover) behaviours. Second, the underlying conceptual complexity is typically underestimated. Third, the dominance of voluntarist and deterministic studies impedes new directions in research. From our review, an integrated worldview–personhood framework emerges that can deepen understanding of avant‐garde self‐repairers’ engagement with product lifetimes.
Role of common ERCC1 polymorphisms in cisplatin‐resistant epithelial ovarian cancer patients: A study in Chinese cohort
Authors: Bao Yuxia , Yang Bin , Zhao Jingjiao , Shen Simin , Gao Jianyuan 
Published: March 2020

AbstractEpithelial ovarian cancer (EOC) contributes the majority of death cases among various ovarian malignancies. Although a standard method of treatment is the surgical removal of malignant tissue followed by platinum‐based chemotherapy, a group of patients does not respond appropriately to cisplatin. An appropriate response to cisplatin has been linked with the nucleotide excision repair mechanism. The present study aims to investigate the role of polymorphisms in DNA repair genes, excision repair cross‐complementation group 1 (ERCC1) with susceptibility to EOC development and tumour response to platinum‐based chemotherapy in Chinese EOC patients. Patients (n = 559) reporting to the Department of Oncology and general surgery, the First Affiliated Hospital of Kunming Medical University, were enrolled in the study. Three hundred twenty‐three healthy controls hailing from similar geographical areas without a history of cancer enrolled as healthy controls. Excision repair cross‐complementation group 1 polymorphisms (rs11615, rs3212986, rs735482, rs2336219, rs3212980, rs3212964, rs3212961 and rs2298881) were genotyped by appropriate methods. Distribution of genotypes and allele for ERCC1 polymorphisms (rs11615, rs3212986, rs735482, rs2336219, rs3212980, rs3212964, rs3212961 and rs2298881) were comparable among healthy controls and EOC patients. Interestingly, homozygous mutant and the minor allele for rs11615 and rs3212986 polymorphisms were significantly higher in nonresponder EOC patients when compared to those with a proper response to cisplatin treatment. The prevalence of other SNPs was comparable among the two treated clinical categories. Furthermore, combined genotype revealed significant association of rs11615: TT/ rs3212986: AA genotype combination with cisplatin nonresponder. Variants of rs11615, rs3212986 polymorphisms are associated with cisplatin resistance in Chinese EOC patients. Combined rs11615 and rs3212986 genotypes can be used as a predictive biomarker for platinum‐based chemotherapy outcomes.