bluuebunny/crossref_metadata_2025_split huggingface dataset:
Official advice improves mortgage-holders’ perceptions of switching: experimental evidence
Authors: TIMMONS SHANE , BARJAKOVÁ MARTINA , MCELVANEY TERENCE J. , LUNN PETER D. 
Published: January 2020

AbstractEncouraging consumers to switch to lower-rate mortgages is important both for the individual consumer's finances and for functioning competitive markets, but switching rates are low. Given the complexity of mortgages, one potential regulatory intervention that may increase switching rates is to provide independent advice on how to select good mortgage products and how to navigate the switching process. Working with a government consumer protection agency, we conducted an experiment with mortgage-holders to test whether such advice alters perceptions of switching. The experiment tested how the attributes of the offer, perceptions about the switching process, individual feelings of competence and comprehension of the product affect willingness to switch to better offers, both before and after reading the official advice. The advice made consumers more sensitive to interest rate decreases, especially over longer terms. It also increased consumers’ confidence in their ability to select good offers. Overall, the findings imply that advice from policy-makers can change perceptions and increase switching rates. Moreover, the experiment demonstrates how lab studies can contribute to behaviourally informed policy development.
The 2018 Italian general election: a ‘new Italy’ or a ‘dead end’?
Authors: Pinto Luca 
Published: January 2020

AbstractTo what extent can the 2018 Italian general election be considered as critical? This article examines how the contributors of six volumes published in the aftermath of the election answer this question by focusing on three major dimensions of change in comparison with the 2013 election: changes in the patterns of party competition; changing patterns of voting behaviour in terms of socio-economic characteristics of the electorate; changes in the salience of issue cleavages and in the way new issues affected the electoral outcomes. The picture originating from the volumes under review is not so sharp as that emerging from the literature that flourished after the 2013 election, whereas several contributions stressed the revolutionary traits of that electoral contest. Despite the important changes observed in comparison to 2013, defining the 2018 general election as critical is adequate only to a certain extent.
Prenatal alcohol exposure is associated with early motor, but not language development in a South African cohort
Authors: Hendricks Gaironeesa , Malcolm-Smith Susan , Stein Dan J. , Zar Heather J. , Wedderburn Catherine J. , Nhapi Raymond T. , Chivese Tawanda , Adnams Colleen M. , Donald Kirsten A. 
Published: January 2020

AbstractObjective:To investigate the association of prenatal alcohol exposure (PAE) and early neurodevelopment in the first 2 years of life, adjusting for maternal socio-demographic and psychosocial factors, in the Drakenstein Child Health Study (DCHS), a South African birth cohort study.Methods:The DCHS comprises a population-based birth cohort of 1143 children, of which a subsample completed the Bayley Scales of Infant Development-III (BSID-III) at 6 (n= 260) and 24 months of age (n= 734). A subset of alcohol-exposed and -unexposed children was included in this analysis at age 6 (n= 52 exposed;n= 104 unexposed) and 24 months (n= 92 exposed;n= 184 unexposed). Multiple hierarchical regression was used to explore the associations of PAE with motor and language development.Results:PAE was significantly associated with decreased gross motor [odds ratio (OR) = 0.16, 95% confidence interval (CI) = 0.06–0.44,p= 0.001] or fine motor (OR = 0.16, 95% CI = 0.06–0.46,p= 0.001) functioning after adjusting for maternal socio-demographic and psychosocial factors at 6 months of age only. No significant effects were found in either receptive or expressive communication and cognitive outcomes at either time points.Conclusion:PAE has potentially important consequences for motor development in the first 2 years of life, a period during which the most rapid growth and maturation occur. These findings highlight the importance of identifying high-risk families in order to provide preventive interventions, particularly in antenatal clinics and early intervention services.
Reconstructing Saharan dust transport to the Eastern Mediterranean Sea during the last 180 ka using endmember modelling of grain size data
Authors: Beuscher Sarah , Ehrmann Werner , Krüger Stefan , Schmiedl Gerhard 
Published: January 2020

AbstractEndmember modelling on the terrigenous silt fraction of nine marine sediment cores spanning up to 180,000 years reveals the influx of North African dust into the Eastern Mediterranean Sea. The dust grain size modes decrease with transport distance, from >50 µm off the African coast to ca. 30 µm in the Aegean Sea. The dust signal is strongly influenced by hydrological changes in northern Africa. Changes from arid to humid periods are documented in the grain size data of all cores. The climatic signal gets weaker with growing distance from the source and close to large fluvial sediment sources such as the Nile. Frequency and wavelet analyses show a strong orbital precession signal that is known to trigger the migration of the monsoonal rain belt in northern Africa. The influence of climate changes on suborbital time scales on dust influx is less distinct, but Dansgaard-Oeschger interstadials and Heinrich-like events are documented in some cores. In the sediment core closest to the source, three endmembers represent one or more dust sources in northern Africa. With growing distance from the source, the three modes cannot be separated anymore and appear as one multimodal dust endmember.
Weight loss supplement causing acute heart block in a child
Authors: O’Brien Daniel R. , Szymczuk Vivian , Albaro Cecilia A. 
Published: January 2020

AbstractA 16-year-old male was admitted to the paediatric ICU with acute onset of vomiting, somnolence, and chest pain, and electrocardiogram showing 2nd degree heart block after ingesting an Aleurites moluccana (Candlenut) seed as a herbal weight loss supplement. Electrocardiogram showed progressively worsening heart block with down-sloping of the ST segments, resembling digoxin toxicity. After 2 days of ICU observation, his symptoms began to improve and eventually resolved. The side effects of herbal supplements are often unknown but by analysing cases such as these, physicians can develop a better understanding of these substances to help guide management.
Double-edged sword of federalism: variation in essential health benefits for mental health and substance use disorder coverage in states
Authors: Willison Charley E. , Singer Phillip M. , Grazier Kyle L. 
Published: January 2020

AbstractThe Affordable Care Act requires all insurance plans sold on health insurance marketplaces and individual and small-group plans to cover 10 Essential Health Benefits (EHB), including behavioral health services. Instead of applying a uniform EHB plan design, the Department of Health and Human Services let states define their own EHB plan. This approach was seen as the best balance between flexibility and comprehensiveness, and assumed there would be little state-to-state variation. Limited federal oversight runs the risk of variation in EHB coverage definitions and requirements, as well as potential divergence from standardized medical guidelines. We analyzed 112 EHB documents from all states for behavioral health coverage in effect from 2012 to 2017. We find wide variation among states in their EHB plan required-coverage, and divergence between medical-practice guidelines and EHB plans. These results emphasize consideration of federated regulation over health insurance coverage standards. Federal flexibility in states benefit design nods to state-specific policymaking-processes and population needs. However, flexibility becomes problematic if it leads to inadequate coverage that reduces access to critical health care services. The EHBs demonstrate an incomplete effort to establish appropriate minimum standards of coverage for behavioral health services.
A Global Perspective on Microplastics
Authors: Hale Robert C. , Seeley Meredith E. , La Guardia Mark J. , Mai Lei , Zeng Eddy Y. 
Published: January 2020

AbstractSociety has become increasingly reliant on plastics since commercial production began in about 1950. Their versatility, stability, light weight, and low production costs have fueled global demand. Most plastics are initially used and discarded on land. Nonetheless, the amount of microplastics in some oceanic compartments is predicted to double by 2030. To solve this global problem, we must understand plastic composition, physical forms, uses, transport, and fragmentation into microplastics (and nanoplastics). Plastic debris/microplastics arise from land disposal, wastewater treatment, tire wear, paint failure, textile washing, and at‐sea losses. Riverine and atmospheric transport, storm water, and disasters facilitate releases. In surface waters plastics/microplastics weather, biofoul, aggregate, and sink, are ingested by organisms and redistributed by currents. Ocean sediments are likely the ultimate destination. Plastics release additives, concentrate environmental contaminants, and serve as substrates for biofilms, including exotic and pathogenic species. Microplastic abundance increases as fragment size decreases, as does the proportion of organisms capable of ingesting them. Particles <20 μm may penetrate cell membranes, exacerbating risks. Exposure can compromise feeding, metabolic processes, reproduction, and behavior. But more investigation is required to draw definitive conclusions. Human ingestion of contaminated seafood and water is a concern. Microplastics indoors present yet uncharacterized risks, magnified by the time we spend inside (>90%) and the abundance of polymeric products therein. Scientific challenges include improving microplastic sampling and characterization approaches, understanding long‐term behavior, additive bioavailability, and organismal and ecosystem health risks. Solutions include improving globally based pollution prevention, developing degradable polymers and additives, and reducing consumption/expanding plastic reuse.
Processes Driving Global Interior Ocean pH Distribution
Authors: Lauvset S. K. , Carter B. R. , Pèrez F. F. , Jiang L.‐Q. , Feely R. A. , Velo A. , Olsen A. 
Published: January 2020

AbstractOcean acidification evolves on the background of a natural ocean pH gradient that is the result of the interplay between ocean mixing, biological production and remineralization, calcium carbonate cycling, and temperature and pressure changes across the water column. While previous studies have analyzed these processes and their impacts on ocean carbonate chemistry, none have attempted to quantify their impacts on interior ocean pH globally. Here we evaluate how anthropogenic changes and natural processes collectively act on ocean pH, and how these processes set the vulnerability of regions to future changes in ocean acidification. We use the mapped data product from the Global Ocean Data Analysis Project version 2, a novel method to estimate preformed total alkalinity based on a combination of a total matrix intercomparison and locally interpolated regressions, and a comprehensive uncertainty analysis. We find that the largest contribution to the interior ocean pH gradient comes from organic matter remineralization, with CaCO3 cycling being the second most important process. The estimates of the impact of anthropogenic CO2 changes on pH reaffirm the large and well‐understood anthropogenic impact on pH in the surface ocean, and put it in the context of the natural pH gradient in the interior ocean. We also show that in the depth layer 500–1,500 m natural processes enhance ocean acidification by on average 28 ± 15%, but with large regional gradients.
Applications of genome editing technology in the targeted therapy of human diseases: mechanisms, advances and prospects
Authors: Li Hongyi , Yang Yang , Hong Weiqi , Huang Mengyuan , Wu Min , Zhao Xia 
Published: January 2020

AbstractBased on engineered or bacterial nucleases, the development of genome editing technologies has opened up the possibility of directly targeting and modifying genomic sequences in almost all eukaryotic cells. Genome editing has extended our ability to elucidate the contribution of genetics to disease by promoting the creation of more accurate cellular and animal models of pathological processes and has begun to show extraordinary potential in a variety of fields, ranging from basic research to applied biotechnology and biomedical research. Recent progress in developing programmable nucleases, such as zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and clustered regularly interspaced short palindromic repeat (CRISPR)–Cas-associated nucleases, has greatly expedited the progress of gene editing from concept to clinical practice. Here, we review recent advances of the three major genome editing technologies (ZFNs, TALENs, and CRISPR/Cas9) and discuss the applications of their derivative reagents as gene editing tools in various human diseases and potential future therapies, focusing on eukaryotic cells and animal models. Finally, we provide an overview of the clinical trials applying genome editing platforms for disease treatment and some of the challenges in the implementation of this technology.
Identification of folate receptor α (FRα) binding oligopeptides and their evaluation for targeted virotherapy applications
Authors: Hulin-Curtis Sarah L. , Davies James A. , Nestić Davor , Bates Emily A. , Baker Alexander T. , Cunliffe Tabitha G. , Majhen Dragomira , Chester John D. , Parker Alan L. 
Published: January 2020

AbstractOncolytic virotherapies (OV) based on human adenoviral (HAdV) vectors hold significant promise for the treatment of advanced ovarian cancers where local, intraperitoneal delivery to tumour metastases is feasible, bypassing many complexities associated with intravascular delivery. The efficacy of HAdV-C5-based OV is hampered by a lack of tumour selectivity, where the primary receptor, hCAR, is commonly downregulated during malignant transformation. Conversely, folate receptor alpha (FRα) is highly expressed on ovarian cancer cells, providing a compelling target for tumour selective delivery of virotherapies. Here, we identify high-affinity FRα-binding oligopeptides for genetic incorporation into HAdV-C5 vectors. Biopanning identified a 12-mer linear peptide, DWSSWVYRDPQT, and two 7-mer cysteine-constrained peptides, CIGNSNTLC and CTVRTSAEC that bound FRα in the context of the phage particle. Synthesised lead peptide, CTVRTSAEC, bound specifically to FRα and could be competitively inhibited with folic acid. To assess the capacity of the elucidated FRα-binding oligopeptides to target OV to FRα, we genetically incorporated the peptides into the HAdV-C5 fiber-knob HI loop including in vectors genetically ablated for hCAR interactions. Unfortunately, the recombinant vectors failed to efficiently target transduction via FRα due to defective intracellular trafficking following entry via FRα, indicating that whilst the peptides identified may have potential for applications for targeted drug delivery, they require additional refinement for targeted virotherapy applications.
Coupling of terminal differentiation deficit with neurodegenerative pathology in Vps35-deficient pyramidal neurons
Authors: Tang Fu-Lei , Zhao Lu , Zhao Yang , Sun Dong , Zhu Xiao-Juan , Mei Lin , Xiong Wen-Cheng 
Published: January 2020

AbstractVps35 (vacuolar protein sorting 35) is a key component of retromer that regulates transmembrane protein trafficking. Dysfunctional Vps35 is a risk factor for neurodegenerative diseases, including Parkinson’s and Alzheimer’s diseases. Vps35 is highly expressed in developing pyramidal neurons, and its physiological role in developing neurons remains to be explored. Here, we provide evidence that Vps35 in embryonic neurons is necessary for axonal and dendritic terminal differentiation. Loss of Vps35 in embryonic neurons results in not only terminal differentiation deficits, but also neurodegenerative pathology, such as cortical brain atrophy and reactive glial responses. The atrophy of neocortex appears to be in association with increases in neuronal death, autophagosome proteins (LC3-II and P62), and neurodegeneration associated proteins (TDP43 and ubiquitin-conjugated proteins). Further studies reveal an increase of retromer cargo protein, sortilin1 (Sort1), in lysosomes of Vps35-KO neurons, and lysosomal dysfunction. Suppression of Sort1 diminishes Vps35-KO-induced dendritic defects. Expression of lysosomal Sort1 recapitulates Vps35-KO-induced phenotypes. Together, these results demonstrate embryonic neuronal Vps35’s function in terminal axonal and dendritic differentiation, reveal an association of terminal differentiation deficit with neurodegenerative pathology, and uncover an important lysosomal contribution to both events.
The orphan nuclear receptor Nr4a1 mediates perinatal neuroinflammation in a murine model of preterm labor
Authors: Estrada Sarah M. , Thagard Andrew S. , Dehart Mary J. , Damicis Jennifer R. , Dornisch Elisabeth M. , Ippolito Danielle L. , Burd Irina , Napolitano Peter G. , Ieronimakis Nicholas 
Published: January 2020

AbstractPrematurity is associated with perinatal neuroinflammation and injury. Screening for genetic modulators in an LPS murine model of preterm birth revealed the upregulation of Nr4a1, an orphan nuclear transcription factor that is normally absent or limited in embryonic brains. Concurrently, Nr4a1 was downregulated with magnesium sulfate (MgSO4) and betamethasone (BMTZ) treatments administered to LPS exposed dams. To understand the role of Nr4a1 in perinatal brain injury, we compared the preterm neuroinflammatory response in Nr4a1 knockout (KO) versus wild type (wt) mice. Key inflammatory factors Il1b, Il6 and Tnf, and Iba1+ microglia were significantly lower in Nr4a1 KO versus wt brains exposed to LPS in utero. Treatment with MgSO4/BMTZ mitigated the neuroinflammatory process in wt but not Nr4a1 KO brains. These results correspond with a reduction in cerebral hemorrhage in wt but not mutant embryos from dams given MgSO4/BMTZ. Further analysis with Nr4a1-GFP-Cre × tdTomato loxP reporter mice revealed that the upregulation of Nr4a1 with perinatal neuroinflammation occurs in the cerebral vasculature. Altogether, this study implicates Nr4a1 in the developing vasculature as a potent mediator of neuroinflammatory brain injury that occurs with preterm birth. It is also possible that MgSO4/BMTZ mitigates this process by direct or indirect inhibition of Nr4a1.
Epigenetic priming by Dot1l in lymphatic endothelial progenitors ensures normal lymphatic development and function
Authors: Yoo Hyunjin , Lee Young Jae , Park Chanhyeok , Son Dabin , Choi Dong Yoon , Park Ji-Hyun , Choi Hee-Jin , La Hyun Woo , Choi Yun-Jung , Moon Eun-Hye , Saur Dieter , Chung Hyung Min , Song Hyuk , Do Jeong Tae , Jang Hoon , Lee Dong Ryul , Park Chankyu , Lee Ok-Hee , Cho Ssang-Goo , Hong Seok-Ho , Kong Gu , Kim Jin-Hoi , Choi Youngsok , Hong Kwonho 
Published: January 2020

AbstractProper functioning of the lymphatic system is required for normal immune responses, fluid balance, and lipid reabsorption. Multiple regulatory mechanisms are employed to ensure the correct formation and function of lymphatic vessels; however, the epigenetic modulators and mechanisms involved in this process are poorly understood. Here, we assess the regulatory role of mouse Dot1l, a histone H3 lysine (K) 79 (H3K79) methyltransferase, in lymphatic formation. Genetic ablation of Dot1l in Tie2(+) endothelial cells (ECs), but not in Lyve1(+) or Prox1(+) lymphatic endothelial cells (LECs) or Vav1(+) definitive hematopoietic stem cells, leads to catastrophic lymphatic anomalies, including skin edema, blood–lymphatic mixing, and underdeveloped lymphatic valves and vessels in multiple organs. Remarkably, targeted Dot1l loss in Tie2(+) ECs leads to fully penetrant lymphatic aplasia, whereas Dot1l overexpression in the same cells results in partially hyperplastic lymphatics in the mesentery. Genetic studies reveal that Dot1l functions in c-Kit(+) hemogenic ECs during mesenteric lymphatic formation. Mechanistically, inactivation of Dot1l causes a reduction of both H3K79me2 levels and the expression of genes important for LEC development and function. Thus, our study establishes that Dot1l-mediated epigenetic priming and transcriptional regulation in LEC progenitors safeguard the proper lymphatic development and functioning of lymphatic vessels.
BCL-XL expression is essential for human erythropoiesis and engraftment of hematopoietic stem cells
Authors: Afreen Sehar , Bohler Sheila , Müller Alexandra , Demmerath Eva-Maria , Weiss Julia Miriam , Jutzi Jonas Samuel , Schachtrup Kristina , Kunze Mirjam , Erlacher Miriam 
Published: January 2020

AbstractThe anti-apoptotic BCL-2 proteins (BCL-2, BCL-XL, MCL-1, A1, BCL-W) counteract apoptotic signals emerging during development and under stress conditions, and are thus essential for the survival of every cell. While the “BCL-2 addiction” of different cell types is well described in mouse models, there is only limited information available on the role of different anti-apoptotic BCL-2 proteins in a given human cell type. Here we characterize the role of BCL-XL for survival and function of human hematopoietic cells, with the aim to predict hematological side effects of novel BCL-XL-inhibiting BH3-mimetics and to identify hematological malignancies potentially responsive to such inhibitors. Earlier clinical studies have shown that the combined BCL-2/BCL-XL/BCL-W inhibitor, Navitoclax (ABT-263) induces severe thrombocytopenia caused by direct platelet demise and counteracted by increased megakaryopoiesis. In contrast, murine studies have reported important contribution of BCL-XL to survival of late erythroid cells and megakaryocytes. Using lentiviral knockdown, we show that the roles of BCL-XL for human hematopoietic cells are much more pronounced than expected from murine data and clinical trials. Efficient genetic or chemical BCL-XL inhibition resulted in significant loss of human erythroid cells beginning from very early stages of erythropoiesis, and in a reduction of megakaryocytes. Most importantly, BCL-XL deficient human hematopoietic stem cells and multipotent progenitors were reduced in numbers, and they showed a severely impaired capacity to engraft in mice during xenotransplantation. BCL-XL deficiency was fully compensated by BCL-2 overexpression, however, loss of its antagonist BIM did not result in any rescue of human erythroid or stem and progenitor cells. We thus conclude that novel and specific BCL-XL inhibitors might be efficient to treat malignancies of erythroid or megakaryocytic origin, such as polycythemia vera, acute erythroid leukemia, essential thrombocytosis or acute megakaryocytic leukemia. At the same time, it can be expected that they will have more severe hematological side effects than Navitoclax.