bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of vaccination on children’s learning achievements: findings from the India Human Development Survey
Authors: Arsenault Catherine , Harper Sam , Nandi Arijit 
Published: June 2020

BackgroundBeyond the prevention of illness and death, vaccination may provide additional benefits such as improved educational outcomes. However, there is currently little evidence on this question. Our objective was to estimate the effect of childhood vaccination on learning achievements among primary school children in India.MethodsWe used cohort data from the India Human Development Survey. Vaccination status and confounders were measured among children who were at least 12 months old at baseline in 2004–2005. In 2011–2012, the same children completed basic reading, writing and math tests. We estimated the effect of full vaccination during childhood on learning achievements using inverse probability of treatment-weighted logistic regression models and results reported on the risk difference scale. The propensity score included 33 potential community-, household-, mother- and child-level confounders as well as state fixed effects.ResultsAmong the 4877 children included in our analysis, 54% were fully vaccinated at baseline, and 54% could read by the age of 8–11 years. The estimated effect of full vaccination on learning achievements ranged from 4 to 6 percentage points, representing relative increases ranging from 6% to 12%. Bias analysis suggested that our observed effects could be explained by unmeasured confounding, but only in the case of strong associations with the treatment and outcome.ConclusionThese results support the hypothesis that vaccination has lasting effects on children’s learning achievements. Further work is needed to confirm findings and elucidate the potential mechanisms linking vaccines to educational outcomes.
Simulating future public health benefits of tobacco control interventions: a systematic review of models
Authors: Singh Ankur , Wilson Nick , Blakely Tony 
Published: June 2020

BackgroundTo prioritise tobacco control interventions, simulating their health impacts is valuable. We undertook a systematic review of tobacco intervention simulation models to assess model structure and input variations that may render model outputs non-comparable.MethodsWe applied a Medline search with keywords intersecting modelling and tobacco. Papers were limited to those modelling health outputs (eg, mortality, health-adjusted life years), and at least two of cancer, cardiovascular and respiratory diseases. Data were extracted for each simulation model with ≥3 arising papers, including: model type, untimed or with time steps and trends in business-as-usual (BAU) tobacco prevalence and epidemiology.ResultsOf 1911 papers, 186 met the inclusion criteria, including 13 eligible simulation models. The SimSmoke model had the largest number of publications (n=46), followed by Benefits of Smoking Cessation on Outcomes (n=12) and Tobacco Policy Model (n=10). Two of 13 models only estimated deaths averted, 1 had no time steps, 5 had no future trends in BAU tobacco prevalence, 9 had no future trends in BAU disease epidemiology and 7 had no time lags from quitting tobacco to reversal of health harm.ConclusionsConsiderable heterogeneity exists in simulation models, making outputs substantively non-comparable between models. Ranking of interventions by one model may be valid. However, this may not be true if, for example, interventions that differentially affect age groups (eg, a tobacco-free generation policy vs increased cessation among adults) do not account for plausible future trends. Greater standardisation of model structures and outputs will allow comparison across models and countries, and for comparisons of the impact of tobacco control interventions with other preventive interventions.
Genotypic and allelic frequencies of MDR1 gene in dogs in Italy
Authors: Marelli Stefano Paolo , Polli Michele , Frattini Stefano , Cortellari Matteo , Rizzi Rita , Crepaldi Paola 
Published: June 2020

BackgroundA mutation in the canine multidrug resistance MDR1 gene (also referred as ABCB1), encoding for the multidrug resistance (MDR) P‐glycoprotein (P‐gp) transponder, causes a pathological condition known as ‘ivermectin toxicosis’. The causative mutation, known since 2001, has been described to affects sheep herding breeds related to collie lineage. The present study is a retrospective investigation of the presence of MDR1 mutated allele in Italian dog populations in a 5 years’ time lapse. The aim of the research is to offer a deep knowledge in MDR1 allelic and genotypic frequencies in canine breeds and populations raised in Italy.MethodsGenotype data for the 4‐bp deletion (c296_299del4) in MDR1 gene from 811 dogs belonging to 32 breeds/populations were collected.ResultsThe mutated allele has been found in 9 out of 31 breeds: Rough Collie, Smooth Collie, Border Collie, Bearded Collie, Shetland Sheepdog, Australian Shepherd, White Swiss Shepherd, Old English Sheepdog, Whippet and also in crossbreed. The breeds with the highest allelic mutation frequency are Smooth and Rough Collies with 75 per cent and 66 per cent of mutant MDR1 allele, respectively.ConclusionsThe results support the usefulness of this genetic analysis to optimise medical care in dogs at risk of multidrug resistance and to create an objective basis in breeding programme definition and in the risk evaluation in different breeds.
Lipid droplets are both highly oxidized and Plin2-covered in hepatocytes of diet-induced obese mice
Authors: Nocetti Diego , Espinosa Alejandra , Pino-De la Fuente Francisco , Sacristán Camila , Bucarey José Luis , Ruiz Paulina , Valenzuela Rodrigo , Chouinard-Watkins Raphaël , Pepper Inés , Troncoso Rodrigo , Puente Luis 
Published: June 2020

Chronic high-fat diet feeding is associated with obesity and accumulation of fat in the liver, leading to the development of insulin resistance and nonalcoholic fatty liver disease. This condition is characterized by the presence of a high number of intrahepatic lipid droplets (LDs), with changes in the perilipin pattern covering them. This work aimed to describe the distribution of perilipin (Plin) 2, an LD-associated protein involved in neutral lipid storage, and Plin5, which favors lipid oxidation in LD, and to evaluate lipid peroxidation through live-cell visualization using the lipophilic fluorescent probe C11-BODIPY581/591 in fresh hepatocytes isolated from mice fed a high-fat diet (HFD). Male C57BL/6J adult mice were divided into control and HFD groups and fed with a control diet (10% fat, 20% protein, and 70% carbohydrates) or an HFD (60% fat, 20% protein, and 20% carbohydrates) for 8 weeks. The animals fed the HFD showed a significant increase of Plin2 in LD of hepatocytes. LD from HFD-fed mice have a stronger lipid peroxidation level than control hepatocytes. These data provide evidence that obesity status is accompanied by a higher degree of lipid peroxidation in hepatocytes, both in the cytoplasm and in the fats stored inside the LD. Novelty Our study shows that lipid droplets from isolated hepatocytes in HFD-fed mice have a stronger lipid peroxidation level than control hepatocytes. C11-BODIPY581/591 is a useful tool to measure the initial level of intracellular lipid peroxidation in single isolated hepatocytes. Perilipins pattern changes with HFD feeding, showing an increase of Plin2 covering lipid droplets.
From classical to modern opinion dynamics
Authors: Noorazar Hossein , Vixie Kevin R. , Talebanpour Arghavan , Hu Yunfeng 
Published: June 2020

In this age of Facebook, Instagram, and Twitter, there is rapidly growing interest in understanding network-enabled opinion dynamics in large groups of autonomous agents. The phenomena of opinion polarization, the spread of propaganda and fake news, and the manipulation of sentiment is of interest to large numbers of organizations and people. Whether it is the more nefarious players such as foreign governments that are attempting to sway elections or it is more open and above board, such as researchers who want to make large groups of people aware of helpful innovations, what is at stake is often significant.In this paper, we review opinion dynamics including the extensions of many classical models as well as some new models that deepen understanding. For example, we look at models that track the evolution of an individual’s power, that include noise, and that feature sequentially dependent topics, to name a few.While the first papers studying opinion dynamics appeared over 60 years ago, there is still a great deal of room for innovation and exploration. We believe that the political climate and the extraordinary (even unprecedented) events in the sphere of politics in the last few years will inspire new interest and new ideas.It is our aim to help those interested researchers understand what has already been explored in a significant portion of the field of opinion dynamics. We believe that in doing this, it will become clear that there is still much to be done.
Worldwide examples of global heritage stones: an introduction
Authors: Hannibal Joseph T. , Kramar S. , Cooper B. J. 
Published: June 2020

Abstract
Heritage stones are stones that have special significance in human culture. The papers in this volume discuss a wide variety of such stones, including stones from Europe, Asia, North and South America, Africa and Australia. Igneous (basalt, porphyry and a variety of granites), sedimentary (sandstone, limestone) and metamorphic (marble, quartzite, gneiss, slate, soapstone) stones are featured. These stones have been used over long periods of time for a wide range of uses, including monuments, buildings of architectural note, columns, roofing, tiling and lithography. A number of papers in this book provide information that is essential for eventual approval of stones as a Global Heritage Stone Resource or a group of stones as a Global Heritage Stone Province.
Two for the price of one: Doris Livesey Reynolds (1899–1985)
Authors: Lewis Cherry L. E. 
Published: June 2020

Abstract
Doris Reynolds, known less commonly by her married name Doris Holmes, was an English geologist and petrologist. She is best known for her role in the Granite Controversy that started in the late 1930s and continued throughout the 1940s and 1950s, and particularly for her contribution to the concept of ‘granitization’ in the formation of granites. She was greatly influenced by Catherine Raisin, who introduced her to petrology at Bedford College for Women where Reynolds studied for her first degree. Throughout her career Reynolds worked on igneous intrusions and their associated metamorphism, with particular emphasis on the Newry Igneous Complex in Ireland. In her papers she detailed the sequences of chemical changes that led to granitization which she postulated occurred as a series of ‘fronts’. She argued that these fronts altered the sedimentary rocks through which they passed, eventually turning the sediments into granites or other igneous rocks, depending on the ions carried by the front. In 1939, she married Arthur Holmes; in 1949, she was among the first five women to be elected a Fellow of the Royal Society of Edinburgh, and in 1960 she was awarded the Lyell Medal by the Geological Society of London for her research, her original mind and her refusal to be cowed by the Establishment.
A Pygopus 2-Histone Interaction Is Critical for Cancer Cell Dedifferentiation and Progression in Malignant Breast Cancer
Authors: Saxena Meera , Kalathur Ravi K.R. , Rubinstein Natalia , Vettiger Andrea , Sugiyama Nami , Neutzner Melanie , Coto-Llerena Mairene , Kancherla Venkatesh , Ercan Caner , Piscuoglio Salvatore , Fischer Jonas , Fagiani Ernesta , Cantù Claudio , Basler Konrad , Christofori Gerhard 
Published: June 2020

Abstract

Pygopus 2 (Pygo2) is a coactivator of Wnt/β-catenin signaling that can bind bi- or trimethylated lysine 4 of histone-3 (H3K4me2/3) and participate in chromatin reading and writing. It remains unknown whether the Pygo2–H3K4me2/3 association has a functional relevance in breast cancer progression in vivo. To investigate the functional relevance of histone-binding activity of Pygo2 in malignant progression of breast cancer, we generated a knock-in mouse model where binding of Pygo2 to H3K4me2/3 was rendered ineffective. Loss of Pygo2–histone interaction resulted in smaller, differentiated, and less metastatic tumors, due, in part, to decreased canonical Wnt/β-catenin signaling. RNA- and ATAC-sequencing analyses of tumor-derived cell lines revealed downregulation of TGFβ signaling and upregulation of differentiation pathways such as PDGFR signaling. Increased differentiation correlated with a luminal cell fate that could be reversed by inhibition of PDGFR activity. Mechanistically, the Pygo2–histone interaction potentiated Wnt/β-catenin signaling, in part, by repressing the expression of Wnt signaling antagonists. Furthermore, Pygo2 and β-catenin regulated the expression of miR-29 family members, which, in turn, repressed PDGFR expression to promote dedifferentiation of wild-type Pygo2 mammary epithelial tumor cells. Collectively, these results demonstrate that the histone binding function of Pygo2 is important for driving dedifferentiation and malignancy of breast tumors, and loss of this binding activates various differentiation pathways that attenuate primary tumor growth and metastasis formation. Interfering with the Pygo2–H3K4me2/3 interaction may therefore serve as an attractive therapeutic target for metastatic breast cancer.

Significance:
Pygo2 represents a potential therapeutic target in metastatic breast cancer, as its histone-binding capability promotes β-catenin–mediated Wnt signaling and transcriptional control in breast cancer cell dedifferentiation, EMT, and metastasis.
Platelet-Specific PDGFB Ablation Impairs Tumor Vessel Integrity and Promotes Metastasis
Authors: Zhang Yanyu , Cedervall Jessica , Hamidi Anahita , Herre Melanie , Viitaniemi Kati , D'Amico Gabriela , Miao Zuoxiu , Unnithan Ragaseema Valsala Madhavan , Vaccaro Alessandra , van Hooren Luuk , Georganaki Maria , Thulin Åsa , Qiao Qi , Andrae Johanna , Siegbahn Agneta , Heldin Carl-Henrik , Alitalo Kari , Betsholtz Christer , Dimberg Anna , Olsson Anna-Karin 
Published: June 2020

Abstract

Platelet-derived growth factor B (PDGFB) plays a crucial role in recruitment of PDGF receptor β–positive pericytes to blood vessels. The endothelium is an essential source of PDGFB in this process. Platelets constitute a major reservoir of PDGFB and are continuously activated in the tumor microenvironment, exposing tumors to the plethora of growth factors contained in platelet granules. Here, we show that tumor vascular function, as well as pericyte coverage is significantly impaired in mice with conditional knockout of PDGFB in platelets. A lack of PDGFB in platelets led to enhanced hypoxia and epithelial-to-mesenchymal transition in the primary tumors, elevated levels of circulating tumor cells, and increased spontaneous metastasis to the liver or lungs in two mouse models. These findings establish a previously unknown role for platelet-derived PDGFB, whereby it promotes and maintains vascular integrity in the tumor microenvironment by contributing to the recruitment of pericytes.

Significance:
Conditional knockout of PDGFB in platelets demonstrates its previously unknown role in the maintenance of tumor vascular integrity and host protection against metastasis.
NRASStatus Determines Sensitivity to SHP2 Inhibitor Combination Therapies Targeting the RAS–MAPK Pathway in Neuroblastoma
Authors: Valencia-Sama Ivette , Ladumor Yagnesh , Kee Lynn , Adderley Teresa , Christopher Gabriella , Robinson Claire M. , Kano Yoshihito , Ohh Michael , Irwin Meredith S. 
Published: June 2020

AbstractSurvival for high-risk neuroblastoma remains poor and treatment for relapsed disease rarely leads to long-term cures. Large sequencing studies of neuroblastoma tumors from diagnosis have not identified common targetable driver mutations other than the 10% of tumors that harbor mutations in the anaplastic lymphoma kinase (ALK) gene. However, at neuroblastoma recurrence, more frequent mutations in genes in the RAS–MAPK pathway have been detected. The PTPN11-encoded tyrosine phosphatase SHP2 is an activator of the RAS pathway, and we and others have shown that pharmacologic inhibition of SHP2 suppresses the growth of various tumor types harboring KRAS mutations such as pancreatic and lung cancers. Here we report inhibition of growth and downstream RAS–MAPK signaling in neuroblastoma cells in response to treatment with the SHP2 inhibitors SHP099, II-B08, and RMC-4550. However, neuroblastoma cell lines harboring endogenous NRASQ61K mutation (which is commonly detected at relapse) or isogenic neuroblastoma cells engineered to overexpress NRASQ61K were distinctly resistant to SHP2 inhibitors. Combinations of SHP2 inhibitors with other RAS pathway inhibitors such as trametinib, vemurafenib, and ulixertinib were synergistic and reversed resistance to SHP2 inhibition in neuroblastoma in vitro and in vivo. These results suggest for the first time that combination therapies targeting SHP2 and other components of the RAS–MAPK pathway may be effective against conventional therapy-resistant relapsed neuroblastoma, including those that have acquired NRAS mutations.Significance:These findings suggest that conventional therapy–resistant, relapsed neuroblastoma may be effectively treated via combined inhibition of SHP2 and MEK or ERK of the RAS–MAPK pathway.
Familial Clustering of Aortic Size, Aneurysms, and Dissections in the Community
Authors: Raunsø Jakob , Song Rebecca J. , Vasan Ramachandran S. , Bourdillon Maximillian T. , Nørager Betina , Torp-Pedersen Christian , Gislason Gunnar H. , Xanthakis Vanessa , Andersson Charlotte 
Published: June 2020

Background:
Ruptured aortic aneurysm and aortic dissections are potentially preventable disorders associated with high mortality. Screening of individuals at risk may translate into elective surgical interventions and lowered mortality. It is uncertain if the risk of aortic dilation of varying degrees aggregates within families.

Methods:
We investigated the risk of having thoracic and abdominal aortic sizes in the highest quartile (measured by computed tomography scans and indexed for body size) if at least 1 parent did so in the Framingham Heart Study cohorts, and estimated the incidence rates and hazard ratios of developing aortic aneurysm or dissection among first-degree relatives of those with aortic aneurysm or dissection, in comparison with age- and sex-matched controls (1:10 for aortic aneurysm and 1:100 for aortic dissection) using the Danish nationwide administrative registries.

Results:
In the Framingham Heart Study, offspring (n=235) whose parent(s) had a sex- and age-standardized aortic size in the upper quartile had a multivariable-adjusted ≈3-fold increased odds ratio of belonging to the upper quartile themselves. In Denmark, a total of 68 939 individuals (mean age, 42 years) had a first-degree relative with aortic aneurysm and 7209 persons (mean age, 39 years) had a first-degree relative with aortic dissection. During an average follow-up of 7 years, first-degree relatives of patients with aortic aneurysm and dissection had a hazard ratio of 6.70 (95% CI, 5.96–7.52) for developing aortic aneurysm and a hazard ratio of 9.24 (95% CI, 5.53–15.44) for dissection in comparison with matched controls. These estimates remained unchanged on adjusting for several comorbidities, including prevalent hypertension, bicuspid aortic valve, and the Marfan syndrome. For both aortic aneurysm and dissections, the absolute event rates approached 1 per 1000 person-years for first-degree relatives versus 11 to 13 (aortic aneurysm) and 2 to 3 (aortic dissections) per 100 000 person-years among controls.

Conclusions:
Increased aortic size, a precursor of aortic aneurysm and a risk factor for dissection, clusters in families. The incidence rates of aortic aneurysm and dissections approach the incidence rates of other common cardiovascular conditions in first-degree relatives, supporting the use of systematic screening for these conditions.
Polish Jurisprudence in the 20th Century: A General Overview
Authors: Bekrycht Tomasz , Mańko Rafał 
Published: June 2020

The present paper provides a general overview of the sources of inspiration and main currents in Polish jurisprudence in the 20th century, especially in the post-War and contemporary period. The paper notes that the main sources of inspiration in the early 20th century included Leon Petrażycki, Bronisław Wróblewski, Czesław Znamie-rowski and Jerzy Lande, who exerted a great influence on the first generation of Polish post-War legal theorists. The Lvov-Warsaw school of analytical philosophy also had a huge impact on Polish jurisprudence, as the school to a large extent determined the research questions posed by Polish legal theorists. Indeed, analytical legal theory can be said to have dominated Polish jurisprudence from the 1950s up to the end of the 1980s. After 1989, a broad current of new philosophical approaches to jurisprudence emerged, including legal hermeneutics and philosophies of interpretation, legal ethics, postmodern and critical legal theory, the phenomenology of law as well as an original Polish achievement – the legal theory of ‘juriscentrism’.
The Ecclesiology of Visible Unity at Lambeth 1920: Lost beyond Recovery?
Authors: Worthen Jeremy 
Published: June 2020

According to the ecumenical ecclesiology of the 1920 Lambeth Conference ‘Appeal to All Christian People’, Christians are called to make known to the whole world the fellowship of human persons that is God’s will. They are to do so by means of the visible unity of Christ’s church in faith, sacraments and ministry, which requires the union of churches in each place and the communion of churches in every place, for which universal acceptance of the historic episcopate is pivotal. While this ecumenical ecclesiology faced significant challenges during the following five decades within international Anglican ecumenism, it continued to be widely influential until hopes for the union of churches in each place went into eclipse from the 1970s onwards, with work towards the communion of churches in every place becoming unhinged from it. A re-imagining of the interdependence of local union and universal communion in the contemporary context is needed for the renewal of an ecumenical ecclesiology that holds together unity and mission in a relationship that is not narrowly instrumental but demonstrates the profound inseparability between the communication of Christ and communion in Christ.
Duration of Investor-State Dispute Settlement Proceedings
Authors: Álvarez Zárate José Manuel , Baltag Crina , Behn Daniel , Bonnitcha Jonathan , De Luca Anna , Hestermeyer Holger , Langford Malcolm , Mistelis Loukas , López Rodríguez Clara , Shaffer Gregory , Weber Simon 
Published: June 2020

Abstract
Speed is often touted as an advantage of arbitration. In recent years, however, some have worried that investment arbitration risks losing this advantage. Concerns about the length of investor-State dispute settlement (ISDS) proceedings have also been raised in the discussion about ISDS reform. This article analyses the duration of ISDS proceedings applying a data-centric approach and evaluates the impact of proposed ISDS reforms on the duration of proceedings. After some terminological clarifications on when proceedings are ‘excessively’ long, the article sets out the evidence on the length of proceedings using several data-sets. As a comparator, we present data on the length of World Trade Organization (WTO) proceedings, even though we urge caution as to the usefulness of such a comparator. The article then discusses the impact of various reform proposals on the duration of proceedings, namely improving ISDS, adding an appellate mechanism, establishing a multilateral investment court and abolishing ISDS.