bluuebunny/crossref_metadata_2025_split huggingface dataset:
The TOMMORROW study: Design of an Alzheimer's disease delay‐of‐onset clinical trial
Authors: Burns Daniel K. , Chiang Carl , Welsh‐Bohmer Kathleen A. , Brannan Stephen K. , Culp Meredith , O'Neil Janet , Runyan Grant , Harrigan Patrick , Plassman Brenda L. , Lutz Michael , Lai Eric , Haneline Stephen , Yarnall David , Yarbrough Deborah , Metz Craig , Ponduru Sridevi , Sundseth Scott , Saunders Ann M. ,   TOMMORROW Study Investigators
Published: October 2019

AbstractIntroductionAlzheimer's disease (AD) is a continuum with neuropathologies manifesting years before clinical symptoms; thus, AD research is attempting to identify more disease‐modifying approaches to test treatments administered before full disease expression. Designing such trials in cognitively normal elderly individuals poses unique challenges.MethodsThe TOMMORROW study was a phase 3 double‐blind, parallel‐group study designed to support qualification of a novel genetic biomarker risk assignment algorithm (BRAA) and to assess efficacy and safety of low‐dose pioglitazone to delay onset of mild cognitive impairment due to AD. Eligible participants were stratified based on the BRAA (using TOMM40 rs 10524523 genotype, Apolipoprotein E genotype, and age), with high‐risk individuals receiving low‐dose pioglitazone or placebo and low‐risk individuals receiving placebo. The primary endpoint was time to the event of mild cognitive impairment due to AD. The primary objectives were to compare the primary endpoint between high‐ and low‐risk placebo groups (for BRAA qualification) and between high‐risk pioglitazone and high‐risk placebo groups (for pioglitazone efficacy). Approximately 300 individuals were also asked to participate in a volumetric magnetic resonance imaging substudy at selected sites.ResultsThe focus of this paper is on the design of the study; study results will be presented in a separate paper.DiscussionThe design of the TOMMORROW study addressed many key challenges to conducting a dual‐objective phase 3 pivotal AD clinical trial in presymptomatic individuals. Experiences from planning and executing the TOMMORROW study may benefit future AD prevention/delay‐of‐onset trials.
Effects of iconicity in lexical decision
Authors: SIDHU DAVID M. , VIGLIOCCO GABRIELLA , PEXMAN PENNY M. 
Published: October 2019

abstractIn contrast to arbitrariness, a recent perspective is that words contain both arbitrary and iconic aspects. We investigated iconicity in word recognition, and the possibility that iconic words have special links between phonological and semantic features that may facilitate their processing. In Experiment 1, participants completed a lexical decision task (“Is this letter string a word?”) including words varying in their iconicity. Notably, we manipulated stimulus presentation conditions such that the items were visually degraded for half of the participants; this manipulation has been shown to increase reliance on phonology. Responses to words higher in iconicity were faster and more accurate, but this did not interact with condition. In Experiment 2 we explicitly directed participants’ attention to phonology by using a phonological lexical decision task (“Does this letter string sound like a word?”). Responses to words that were higher in iconicity were once again faster. These results demonstrate facilitatory effects of iconicity in lexical processing, thus showing that the benefits of iconic mappings extend beyond those reported for language learning and those argued for language evolution.
Simultaneous supplementation with iron and folic acid can affect Slc11a2 and Slc46a1 transcription and metabolite concentrations in rats
Authors: Radziejewska A. , Suliburska J. , Kołodziejski P. , Chmurzynska A. 
Published: October 2019

AbstractThe present study aimed at analysing how dietary folic acid (FA) and Fe deficiency, followed by supplementation with these nutrients, affects the expression of folate and Fe transporters in the duodenum, as well as FA and Fe status. After a deficiency period, Wistar rats were randomised to a group fed with a diet deficient in FA and supplemented with Fe (DFE), a diet deficient in Fe and supplemented with FA, a diet supplemented with Fe and FA (FEFOL), a diet deficient in Fe and FA (D) or a control diet (C). Tissue collection was performed after 2, 10 or 21 d of these diets. Group D had higher Slc11a2 mRNA levels than the DFE group at every time point and there were differences in mRNA levels of Slc46a1 between the DFE and the FEFOL groups at the third time point, but we observed no differences in protein levels between the groups. The DFE and D groups not only had lower serum folate concentrations at every time point but also had the highest homocysteine concentrations. Total Fe binding capacity concentrations were the lowest in the DFE group at the first time point and in the DFE and the FEFOL groups at the final time point. Simultaneous supplementation with FA and Fe resulted in significantly higher Hb concentrations than did supplementation with these nutrients alone. Our findings indicate that dietary FA and Fe deficiency, and subsequent supplementation with these nutrients, affects transcription but not the protein levels of FA and Fe transporters in the duodenum.
The reality of at risk mental state services: a response to recent criticisms
Authors: Yung Alison R. , Wood Stephen J. , Malla Ashok , Nelson Barnaby , McGorry Patrick , Shah Jai 
Published: October 2019

AbstractBackgroundIn the 1990s criteria were developed to detect individuals at high and imminent risk of developing a psychotic disorder. These are known as the at risk mental state, ultra high risk or clinical high risk criteria. Individuals meeting these criteria are symptomatic and help-seeking. Services for such individuals are now found worldwide. Recently Psychological Medicine published two articles that criticise these services and suggest that they should be dismantled or restructured. One paper also provides recommendations on how ARMS services should be operate.MethodsIn this paper we draw on the existing literature in the field and present the perspective of some ARMS clinicians and researchers.ResultsMany of the critics' arguments are refuted. Most of the recommendations included in the Moritz et al. paper are already occurring.ConclusionsARMS services provide management of current problems, treatment to reduce risk of onset of psychotic disorder and monitoring of mental state, including attenuated psychotic symptoms. These symptoms are associated with a range of poor outcomes. It is important to assess them and track their trajectory over time. A new approach to detection of ARMS individuals can be considered that harnesses broad youth mental health services, such as headspace in Australia, Jigsaw in Ireland and ACCESS Open Minds in Canada. Attention should also be paid to the physical health of ARMS individuals. Far from needing to be dismantled we feel that the ARMS approach has much to offer to improve the health of young people.
Early adversity and children's regulatory deficits: Does postadoption parenting facilitate recovery in postinstitutionalized children?
Authors: Koss Kalsea J. , Lawler Jamie M. , Gunnar Megan R. 
Published: October 2019

AbstractChildren reared in orphanages typically experience the lack of stable, reliable caregivers and are at increased risk for deficits in regulatory abilities including difficulties in inhibitory control, attention, and emotion regulation. Although adoption results in a radical shift in caregiving quality, there remains variation in postadoption parenting, yet little research has examined postadoption parenting that may promote recovery in children experiencing early life adversity in the form of institutional care. Participants included 93 postinstitutionalized children adopted between 15 and 36 months of age and 52 nonadopted same-aged peers. Parenting was assessed four times during the first 2 years postadoption (at 2, 8, 16, and 24 months postadoption) and children's regulation was assessed at age 5 (Mage = 61.68 months) and during kindergarten (Mage = 71.55 months). Multiple parenting dimensions including sensitivity/responsiveness, structure/limit setting, and consistency in routines were examined. Both parental sensitivity and structure moderated the effect of preadoption adversity on children's emotion regulation while greater consistency was associated with better inhibitory control and fewer attention problems. Results support the notion that postadoption parenting during toddlerhood and the early preschool years promotes better regulation skills following early adversity.
From Neo-Slavism to Internationalism: Interwar Central Europe and the Search for the Lost Mountains
Authors: Roeder Carolin F. 
Published: October 2019

AbstractThis article highlights the contribution of East Central Europe to interwar internationalism by showing how solutions to regional challenges gave birth to theUnion internationale des associations d'alpinisme(UIAA), a permanent international organisation for mountaineering. The territorial fragmentation caused by the dissolution of the Habsburg Empire required alpine clubs to lobby for the softening of new political borders while simultaneously contributing to state building efforts. Successful experiences with bilateral agreements in the Tatras and re-emerging Neo-Slavist ideas led to the founding of the Association of Slavic Tourist Organization in 1924, which in turn motivated the establishment of the UIAA. The leading figures in this process were alpinists with a distinct internationalist profile who navigated seamlessly between their role as agents of the state and private citizens.
Knowledge and skills attractive for the employers of the organic sector: A survey across Europe
Authors: Briz Teresa , von Fragstein und Niemsdorff Peter , Radicetti Emanuele , Moscetti Roberto , Uusitalo Eeva , Iivonen Sari , Mynttinen Ritva , Moudry Jan , Moudry Jan , Konvalina Petr , Kopecky Marek , Średnicka-Tober Dominika , Kazimierczak Renata , Talgre Liina , Matt Darja , Veromann Eve , Mancinelli Roberto , Rembiałkowska Ewa 
Published: October 2019

AbstractIn all countries, the organic sector of the agricultural industry is increasing, with Europe traditionally leading this trend. A survey of different stakeholders (employers) was carried out in 2015 in seven European countries to evaluate the employment market for the organic agricultural industry in Europe. Results indicate the willingness to employ qualified graduates. From the employers' perspective, the most desirable knowledge skills among the graduates of organic agricultural studies include plant production, food quality and plant protection. Further, the study revealed the work skills most desired by the employers are practical expertise, teamwork and problem-solving, and the most important method of learning is cooperation with enterprises (internships/training) in the organic agricultural sector.
Heroic memory and contemporary war
Authors: Holleufer Gilbert 
Published: October 2019

AbstractInter-State wars seem to have come to an end in the late 1990s; ever since, the global reality of collective violence has come down to the chaos of contemporary civil wars and terrorist attacks. In this article, it will be argued that in today's civil wars, as well as in terrorist violence, the traditional warrior ethos is fading, giving way to types of violence governed by a new psychological and social paradigm. In other words, it is assumed that the very set of values that has universally determined the male gender role and the frame of hegemonic masculinity since time immemorial has also informed the waging of war according to a “heroic regime of violence”, and this phenomenon has made war a desirable option for countless generations of young men. On the other hand, the global changes entailed by modernity seem to have undermined this warrior ethos, giving way to a “post-heroic regime” in which extermination-oriented violence, rather than combat-oriented violence, is fostered. In this article, the author will scrutinize the founding psychological and social determinants that have so far upheld the cultural construct of the heroic model, in order to illuminate the ominous consequences of the deculturation of war in today's chaotic conflicts. In such contexts, the men who are fighting1 suffer from a loss of meaning and the impossibility of gaining dignity and social recognition in an ecosystem of humiliation and ubiquitous violence that has little to do with the expectations of pride and dignity conveyed by the past ideals of heroism associated with a certain vision of masculinity. The article will also discuss ways and means of getting the message of international humanitarian law through to men on the front lines caught up in such circumstances.
Changes in nutrient and calorie intake, adipose mass, triglycerides and TNF-α concentrations after non-caloric sweetener intake: A pilot study
Authors: Sánchez-Delgado Marcela , Estrada José Antonio , Paredes-Cervantes Vladimir , Kaufer-Horwitz Martha , Contreras Irazú 
Published: October 2019

Abstract. Establishing the safety of non-caloric sweetener consumption in humans is a difficult task, since many contradictory results have been reported. The objective of this study was to compare the effect of frequent intake of sucrose, sucralose or steviol glycosides, on selected anthropometric, biochemical and immunological parameters in healthy, young adults. 38 individuals with normal body mass index were recruited and randomly divided into three experimental groups. After a washout week (where food with added sweeteners was restricted), each group was supplemented with sucrose (8 × 5 g packets/day), sucralose or steviol glycosides (4 × 1 g packets/day each) for 6 weeks. Selected variables were measured before and after treatment in each group and differences within and among groups were assessed. Our results showed that, compared to baseline, there was a modest but significant increase in weight (p = 0.0293) in the sucralose group, while the steviol glycosides group reduced their fat mass (p = 0.0390). No differences were observed in glycaemia; however, there was a significant increase in serum triglycerides (77.8–110.8 mg/dL) and cholesterol (162.0–172.3 mg/dL) in the sucrose group, whereas the steviol glycosides group presented lower triglycerides (104.7–92.8 mg/dL) and TNF-α concentrations (51.1–47.5 pg/mL). Comparison among groups showed differences in serum triglycerides (p = 0.0226), TNF-α (p = 0.0460) and IL-β (p = 0.0008). Our results suggest that, even in a short time span, frequent intake of steviol glycosides may have positive effects on metabolic parameters that may be relevant for human health.
Dating Deep‐Sea Sediments With 230Th Excess Using a Constant Rate of Supply Model
Authors: Geibert W. , Stimac I. , Rutgers van der Loeff M. M. , Kuhn G. 
Published: October 2019

AbstractWe present a dating method for deep‐sea sediments that uses the natural radionuclide 230Th (half‐life 75,380 years) in analogy to 210Pb with the constant rate of supply (CRS) model. Using an example from the western Indian sector of the Southern Ocean, we demonstrate how sets of values of 230Th, 232Th, and U isotopes activities can supply absolute age information for the last ~450,000 years, given a sufficient precision, resolution, and depth coverage of the analytical data in a suitable core. An assessment of age uncertainties resulting from analytical errors using a Monte Carlo approach and an analytical solution for error propagation shows good agreement. We also investigate errors due to a violation of model assumptions by variable focusing of deep‐sea sediments by means of a simulated core. Finally, we use real examples from independently dated sediment cores containing carbonate, using previously existing 230Th data, to test the approach. The consideration of the systematic errors and the examples suggests that the uncertainties are smallest in the central part of the record and that the variability of focusing conditions controls the accuracy of the 230Th CRS dates. Our own example demonstrates an excellent agreement of the 230Th CRS method with independent age constraints, adding an important tool for dating marine records that does not depend on the presence of carbonate. The obtained values are also suitable to calculate 230Th‐normalized preserved vertical rain rates of various sedimentary compounds, permitting an improved quantitative comparison of marine paleorecords with other archives like ice cores.
Assessment and validation of spot urine in estimating the 24-h urinary sodium, potassium, and sodium/potassium ratio in Chinese adults
Authors: Xu Jianwei , Du Xiaofu , Bai Yamin , Fang Le , Liu Min , Ji Ning , Zhong Jieming , Yu Min , Wu Jing 
Published: October 2019

Abstract
The commonly used methods of estimating the 24-h urinary sodium (UNa) and urinary potassium (UK) from spot urine (SU) are the Kawasaki method (K-method), INTERSALT method (I-method), and Tanaka method (T-method), but the method that is suitable for use in the general Chinese population is still uncertain. We aimed to assess and validate these methods in estimating the 24-h UNa and UK using SU samples in Chinese adults. We studied 1428 individuals aged 18–69 years using SU and 24-h urine samples. For the K-method, I-method, and T-method, the Pearson correlation coefficients of the 24-h UNa were 0.35, 0.35, and 0.33 (all p < 0.01), and the intraclass correlation coefficients (ICC) were 0.34, 0.26, and 0.26 (all p < 0.01), respectively. The estimated 24-h UK using the K-method and T-method had correlation coefficients of 0.36 and 0.39 (all p < 0.01) and ICCs of 0.31 and 0.27 (all p < 0.01). The mean bias for the K-method in estimating the 24-h UNa and UK were the least biased among these methods. The bias between the 24-h urine Na/K ratio and the spot urinary Na/K ratio by the Bland–Altman method was −0.22. These methods for estimating the 24-h UNa and UK from SU were inadequate at the population level in Zhejiang Province, although the K-method showed the least bias among these methods. The spot urine Na/K ratio may be a useful and alternative method for 24-h urine collection for the estimation of the urinary Na/K ratio in the Chinese population.
The reciprocal interaction between tumor cells and activated fibroblasts mediated by TNF-α/IL-33/ST2L signaling promotes gastric cancer metastasis
Authors: Zhou Quan , Wu Xiongyan , Wang Xiaofeng , Yu Zhenjia , Pan Tao , Li Zhen , Chang Xinyu , Jin Zhijian , Li Jianfang , Zhu Zhenggang , Liu Bingya , Su Liping 
Published: October 2019

Abstract
Gastric cancer (GC) is characterized by extensive local invasion, distant metastasis and poor prognosis. In most cases, GC progression is associated with aberrant expression of cytokines or activation of signaling cascades mediated by tumor–stroma interactions. However, the mechanisms by which these interactions contribute to GC progression are poorly understood. In this study, we find that IL-33 and its receptor ST2L are upregulated in the human GC and served as prognostic markers for poor survival of GC patients. In a co-culture model with GC cells and cancer-associated fibroblasts (CAFs), we further demonstrate that CAFs-derived IL-33 enhances the migration and invasion of GC cells by inducing the epithelial–mesenchymal transition (EMT) through activation of the ERK1/2-SP1-ZEB2 pathway in a ST2L-dependent manner. Furthermore, the secretion of IL-33 by CAFs can be induced by the proinflammatory cytokines TNF-α that is released by GC cells via TNFR2-NF-κB-IRF-1 pathway. Additionally, silencing of IL-33 expression in CAFs or ST2L expression in GC cells inhibits the peritoneal dissemination and metastatic potential of GC cells in nude mice. Taken together, these results characterize a critical role of the interaction between epithelial-stroma mediated by the TNF-α/IL-33/ST2L signaling in GC progression, and provide a rationale for targeting this pathway to treat GC metastasis.
Tunneling nanotube-mediated intercellular vesicle and protein transfer in the stroma-provided imatinib resistance in chronic myeloid leukemia cells
Authors: Kolba Marta D. , Dudka Wioleta , Zaręba-Kozioł Monika , Kominek Agata , Ronchi Paolo , Turos Laura , Chroscicki Piotr , Wlodarczyk Jakub , Schwab Yannick , Klejman Agata , Cysewski Dominik , Srpan Katja , Davis Daniel M. , Piwocka Katarzyna 
Published: October 2019

AbstractIntercellular communication within the bone marrow niche significantly promotes leukemogenesis and provides protection of leukemic cells from therapy. Secreted factors, intercellular transfer of mitochondria and the receptor–ligand interactions have been shown as mediators of this protection. Here we report that tunneling nanotubes (TNTs)—long, thin membranous structures, which have been identified as a novel mode of intercellular cross-talk—are formed in the presence of stroma and mediate transfer of cellular vesicles from stroma to leukemic cells. Importantly, transmission of vesicles via TNTs from stromal cells increases resistance of leukemic cells to the tyrosine kinase inhibitor, imatinib. Using correlative light-electron microscopy and electron tomography we show that stromal TNTs contain vesicles, provide membrane continuity with the cell bodies and can be open-ended. Moreover, trans-SILAC studies to reveal the non-autonomous proteome showed that specific sets of proteins are transferred together with cellular vesicles from stromal to leukemic cells, with a potential role in survival and adaptation. Altogether, our findings provide evidence for the biological role of the TNT-mediated vesicle exchange between stromal and leukemic cells, implicating the direct vesicle and protein transfer in the stroma-provided protection of leukemic cells.
Preparation of a new type 2 diabetic miniature pig model via the CRISPR/Cas9 system
Authors: Zou Xiaodong , Ouyang Hongsheng , Yu Tingting , Chen Xue , Pang Daxin , Tang Xiaochun , Chen Chengzhen 
Published: October 2019

AbstractDiabetes has become one of the major noninfectious diseases that seriously endanger public health. The formation of islet amyloid polypeptide (IAPP) affects the normal physiological functions of the body, such as glucose metabolism and lipid metabolism. The mature human IAPP protein (hIAPP) has a strong tendency to misfold and is considered to be one of the major causes of amyloid changes in islets. Deposition of hIAPP is considered to be one of the leading causes of type 2 diabetes mellitus (T2DM). Miniature pigs are experimental animal models that are well suited for research on gene function and human diabetes. In our study, we obtained IAPP gene-humanized miniature pigs via the CRISPR/Cas9 system and somatic cell nuclear transfer (SCNT) technology. The hIAPP pigs can be used to further study the pathogenesis and related complications of T2DM and to lay a solid foundation for the prevention and treatment of T2DM.