bluuebunny/crossref_metadata_2025_split huggingface dataset:
Loss of PTEN promotes formation of signaling-capable clathrin-coated pits
Authors: Rosselli-Murai Luciana K. , Yates Joel A. , Yoshida Sei , Bourg Julia , Ho Kenneth K. Y. , White Megan , Prisby Julia , Tan Xinyu , Altemus Megan , Bao Liwei , Wu Zhi-Fen , Veatch Sarah L. , Swanson Joel A. , Merajver Sofia D. , Liu Allen P. 
Published: April 2018

ABSTRACT
Defective endocytosis and vesicular trafficking of signaling receptors has recently emerged as a multifaceted hallmark of malignant cells. Clathrin-coated pits (CCPs) display highly heterogeneous dynamics on the plasma membrane where they can take from 20 s to over 1 min to form cytosolic coated vesicles. Despite the large number of cargo molecules that traffic through CCPs, it is not well understood whether signaling receptors activated in cancer, such as epidermal growth factor receptor (EGFR), are regulated through a specific subset of CCPs. The signaling lipid phosphatidylinositol (3,4,5)-trisphosphate [PI(3,4,5)P3], which is dephosphorylated by phosphatase and tensin homolog (PTEN), is a potent tumorigenic signaling lipid. By using total internal reflection fluorescence microscopy and automated tracking and detection of CCPs, we found that EGF-bound EGFR and PTEN are enriched in a distinct subset of short-lived CCPs that correspond with clathrin-dependent EGF-induced signaling. We demonstrated that PTEN plays a role in the regulation of CCP dynamics. Furthermore, increased PI(3,4,5)P3 resulted in higher proportion of short-lived CCPs, an effect that recapitulates PTEN deletion. Altogether, our findings provide evidence for the existence of short-lived ‘signaling-capable’ CCPs.
Multiple roles of epithelial heparan sulfate in stomach morphogenesis
Authors: Huang Meina , He Hua , Belenkaya Tatyana , Lin Xinhua 
Published: April 2018

ABSTRACT
Heparan sulfate proteoglycans (HSPGs) have been shown to regulate various developmental processes. However, the function of heparan sulfate (HS) during the development of mammalian stomach has not been characterized yet. Here, we investigate the role of epithelial HS in embryonic stomach by examining mice deficient in the glycosyltransferase gene Ext1. We show that HS exhibits a specific and dynamic expression pattern in mouse embryonic stomach. Depletion of the epithelial HS leads to stomach hypoplasia, with phenotypic differences in the gastric mucosa between the forestomach and hindstomach. In the posterior stomach, HS depletion disrupts glandular stomach patterning and cytodifferentiation via attenuation of Fgf signaling activity. Inhibition of Fgf signaling in vitro recapitulates the patterning defect. Ligand and carbohydrate engagement assay (LACE) reveals a diminished assembly of Fgf10 and Fgfr2b in the mutant. In the anterior stomach, loss of epithelial HS leads to stratification and differentiation defects of the multilayered squamous epithelium, along with reduced Hh and Bmp signaling activity. Our data demonstrate that epithelial HS plays multiple roles in regulating mammalian stomach morphogenesis in a regional-specific manner.
Non-HDL cholesterol is better than LDL-c at predicting atherosclerotic cardiovascular disease risk factors clustering, even in subjects with near-to-normal triglycerides: A report from a Venezuelan population
Authors: Bermúdez Valmore , Torres Wheeler , Salazar Juan , Martínez María Sofía , Rojas Edward , Olivar Luis Carlos , Lameda Victor , Ortega Ángel , Ramírez Paola , Rojas Milagros , Rastogi Sheena , D’Addosio Rosanna , Hoedebecke Kyle , Graterol Modesto , Graterol Resemily , Wilches Sandra , de Bravo Mayela Cabrera , Rojas-Quintero Joselyn 
Published: April 2018

Background: Non-high density lipoprotein cholesterol (non-HDL-c) has emerged as an important tool in primary prevention of atherosclerotic cardiovascular disease (ASCVD), especially among those at high risk. The main objective of this study was to evaluate the predictive value of non-HDL-c for the coexistence aggregation of multiple ASCVD risk factors and compare this with LDL-c in general subjects with normal or near normal triglycerides from Maracaibo city in Venezuela. Methods: This is a descriptive, cross-sectional study with a randomized multistage sampling. 2026 subjects were selected for this study, all were adults ≥18 years old of both genders and inhabitants of Maracaibo city, Venezuela. A complete history and physical medical assessment was performed. A multivariate logistic regression model was used to determine the odds ratio (CI95%) for the coexistence of multiple risk factors for ASCVD. Results: The median (p25-p75) of non-HDL-c was 143 mg/dL (114-174 mg/dL). 52.1% (n=1056) of the sample were women, with a median of 144 mg/dL (115-174 mg/dL) among women and 143 mg/dL (114-17 4mg/dL) among men; p=0.740. Individuals ≥50 years old, smokers, those with hypertension, obesity, diabetes, high waist circumference and elevated hs-C Reactive Protein, all had higher levels of non-HDL-c. A lower median was observed among those <30 years of age with elevated physical activity levels in their leisure time. Non-HDL-c between 130-159 mg/dL (OR=2.44; CI 95%=1.48-4.02; p<0.001) and ≥160 mg/dL (OR=3.28; CI 95%=1.72-6.23; p<0.001) was associated with greater risk of coexistent multiple risk factors for ASCVD, albeit LDL-c was not significant in the multivariate model. Conclusions: Elevated non-HDL-c was associated with conglomeration of multiple risk factors for ASCVD. This suggests evaluation of non-HDL-c may be of better utility in primary care for early identification of subjects for high risk of ASCVD. Future research might focus on the influence of non-HDL-c in cardiovascular mortality.
TDG regulates cell cycle progression in human neural progenitors
Authors: Germanguz Igal , Park Jenny C. , Cinkornpumin Jessica , Solomon Aryeh , Ohashi Minori , Lowry William E. 
Published: April 2018

Background: As cells divide, they must both replicate their DNA and generate a new set of histone proteins. The newly synthesized daughter strands and histones are unmodified, and must therefore be covalently modified to allow for transmission of important epigenetic marks to daughter cells. Human pluripotent stem cells (hPSCs) display a unique cell cycle profile, and control of the cell cycle is known to be critical for their proper differentiation and survival. A major unresolved question is how hPSCs regulate their DNA methylation status through the cell cycle, namely how passive and active demethylation work to maintain a stable genome. Thymine-DNA glycosylase (TDG), an embryonic essential gene, has been recently implicated as a major enzyme involved in demethylation. Methods: We use human pluripotent stem cells and their derivatives to investigate the role of TDG in differentiation and proliferation. To perform loss of function of TDG, RNA Interference was used. To study the cell cyle, we engineered human pluripotent stem cells to express the FUCCI tool which marks cells at various stages of the cell cycle with distinct patterns of fluorescent proteins. We also used cell cycle profiling by FACS, and DNA methylation analysis to probe a connection between DNA demethylation and cell cycle. Results: Here we present data showing that TDG regulates cell cycle dynamics in human neural progenitors (NPCs) derived from hPSCs, leading to changes in cell cycle related gene expression and neural differentiation capacity. These data show that loss of TDG function can block differentiation by driving proliferation of neural progenitors. We also identify specific cell cycle related genes whose expression changes upon loss of TDG expression. Conclusions: These observations suggest that TDG and active demethylation play an important role in hPSC cell cycle regulation and differentiation.
Preliminary investigation of deoxyoligonucleotide binding to ribonuclease A using mass spectrometry: An attempt to develop a lab experience for undergraduates
Authors: Clark Daniel D. 
Published: April 2018

Deoxyoligonucleotide binding to bovine pancreatic ribonuclease A (RNase A) was investigated using electrospray ionization ion-trap mass spectrometry (ESI-IT-MS). Deoxyoligonucleotides included CCCCC (dC5) and CCACC (dC2AC2). This work was an attempt to develop a biochemistry lab experience that would introduce undergraduates to the use of mass spectrometry for the analysis of protein-ligand interactions. Titration experiments were performed using a fixed RNase A concentration and variable deoxyoligonucleotide concentrations. Samples at equilibrium were infused directly into the mass spectrometer under native conditions. For each deoxyoligonucleotide, mass spectra showed one-to-one binding stoichiometry, with marked increases in the total ion abundance of ligand-bound RNase A complexes as a function of concentration, but the accurate determination of dC5and dC2AC2dissociation constants was problematic.
Pneumococcal Conjugate Vaccine impact assessment in Bangladesh
Authors: Baqui Abdullah H. , McCollum Eric D. , Saha Samir K. , Roy Arun K. , Chowdhury Nabidul H. , Harrison Meagan , Hanif Abu Abdullah Mohammad , Simmons Nicole , Mahmud Arif , Begum Nazma , Ahmed Salahuddin , Khan Ahad M. , Ahmed Zabed Bin , Islam Maksuda , Mitra Dipak , Quaiyum Abdul , Chavez Miguel A. , Pervaiz Farhan , Miele Catherine H. , Schuh Holly B. , Khanam Rasheda , Checkley William , Moulton Lawrence H. , Santosham Mathuram 
Published: April 2018

The study examines the impact of the introduction of 10-valent Pneumococcal Conjugate Vaccine (PCV10) into Bangladesh’s national vaccine program. PCV10 is administered to children under 1 year-old; the scheduled ages of administration are at 6, 10, and 18 weeks.The study is conducted in ~770,000 population containing ~90,000 <5 children in Sylhet, Bangladesh and has five objectives: 1) To collect data on community-based pre-PCV incidence rates of invasive pneumococcal diseases (IPD) in 0-59 month-old children in Sylhet, Bangladesh; 2) To evaluate the effectiveness of PCV10 introduction on Vaccine Type (VT) IPD in 3-59 month-old children using an incident case-control study design. Secondary aims include measuring the effects of PCV10 introduction on all IPD in 3-59 month-old children using case-control study design, and quantifying the emergence of Non Vaccine Type IPD; 3) To evaluate the effectiveness of PCV10 introduction on chest radiograph-confirmed pneumonia in children 3-35 months old using incident case-control study design. We will estimate the incidence trend of clinical and radiologically-confirmed pneumonia in 3-35 month-old children in the study area before and after introduction of PCV10; 4) To determine the feasibility and utility of lung ultrasound for the diagnosis of pediatric pneumonia in a large sample of children in a resource-limited setting. We will also evaluate the effectiveness of PCV10 introduction on ultrasound-confirmed pneumonia in 3-35 month-old children using an incident case-control design and to examine the incidence trend of ultrasound-confirmed pneumonia in 3-35 month-old children in the study area before and after PCV10 introduction; and 5) To determine the direct and indirect effects of vaccination status on nasopharyngeal colonization on VT pneumococci among children with pneumonia. This paper presents the methodology. The study will allow us to conduct a comprehensive and robust assessment of the impact of national introduction of PCV10 on pneumococcal disease in Bangladesh.
Funding global health product R&D: the Portfolio-To-Impact Model (P2I), a new tool for modelling the impact of different research portfolios
Authors: Terry Robert F , Yamey Gavin , Miyazaki-Krause Ryoko , Gunn Alexander , Reeder John C. 
Published: April 2018

Background: the Portfolio-To-Impact (P2I) model is a novel financial model, developed to estimate minimum funding needs to accelerate health product development from late stage preclinical study to phase III clinical trials, and to visualize potential product launches over time (from 2017 to 2040). Methods: The assumptions on development costs at each phase were based on clinical trial costs from Parexel’s research and development (R&D) cost sourcebook. These were further refined and validated by interviews, with a wide variety of stakeholders from Product Development Partnerships, biopharmaceutical and diagnostic companies, and major funders of global health R&D. Results: the tool was used to create seven scenarios describing the impact, in terms of products developed, with different product portfolios of funding ranging from $1 million per annum through to $500 million per annum. These scenarios have been previously presented in a report setting out the potential for a new fund for research and development which would assist in accelerating product development for the diseases of poverty. Conclusion: this article describes the assumptions and methods used in developing the P2I modelling tool. The model is published as open access accompanied with a user guide. The design allows it to be adapted and used for other health R&D portfolio analysis as described in an accompanying publication focussing on the pipeline for neglected diseases in 2017. We aim to continually refine and improve the model and we ask users to provide us with their own inputs that can help us update key parameters and assumptions. We hope to catalyse users to adapt the model in ways that can increase its value, accuracy, and applications.
Collecting family planning intentions and providing reproductive health information using a tablet-based video game in India
Authors: Bertozzi Elena , Bertozzi-Villa Amelia , Kulkarni Praveen , Sridhar Aparna 
Published: April 2018

Background: In response to a Grand Challenges in Global Health call for action to collect data about family planning intentions and increase the uptake of family planning methods in India, our team designed, developed, and piloted the My Future Family video game in Karnataka Province. The game educates adolescents about human sexuality and reproduction while asking players when they would like to achieve five important family planning milestones. Participants were also asked to report who influences them the most when making family planning decisions. Methods: Focus groups were conducted and the resulting data used to design the game which was iteratively tested and then piloted in 11 schools in rural and urban areas of southern India. Data was collected throughout gameplay and cross-checked with paper questionnaires. Results: In August 2018, we successfully piloted the game with 382 adolescents and validated its efficacy both as an educational tool and as an innovative means of accurate data collection. Conclusion: It has historically been problematic to gather accurate data about adolescents in India on this culturally sensitive topic for a variety of reasons. These include difficulties obtaining consent, developing appropriate survey methods, and framing questions in language that young people can understand. Our game met these challenges by working within a single school system with approval from senior administration, delivering information via a game environment, which freed players from societal constraints, and communicating information via images and audio in addition to text in both English and Kannada (the local language).
Self-assessment of executive function and lateralization of brain pathology: What does the DEX-S profile show?
Authors: Szepietowska Ewa , Kuzaka Anna 
Published: April 2018

Cel pracyCelem badań własnych było 1). porównanie ogólnego wyniku oraz profilu DEX-S osób zdrowych i z patologią mózgu, w tym - uwzględnienie lateralizacji patologii mózgowej, oraz 2). określenie związków wyniku DEX-S z poziomem wybranych kompetencji poznawczych. Do badań zakwalifikowano 115 osób, w tym: bez patologii mózgowej (K; N=74), z uszkodzeniem lewej (LP; N=6), prawej (PP; N=12) i obydwu półkul (OP; N=23).MetodaZastosowano DEX-S, podtesty WAIS: Słownik, Cyfry wprost, wspak, test MoCa i skalę Afektu z kwestionariusza ProCog.WynikiWynik ogólny DEX-S nie różnicował grup, jednak najwyższe przeciętne wyniki uzyskały grupy PP i OP. Odnotowano różnice międzygrupowe w wynikach jedynie kilku itemów DEX-S. Osoby z patologią prawej i obu półkul raportowały istotnie wyższe poczucie trudności wykonawczych, głównie w zakresie uwagi, podatności na dystraktory, planowania, sekwencyjnego działania oraz rozwiązywania problemów. Z kolei grupa LP uzyskała najniższy wynik DEX-S. Grupa PP uzyskała niższe wyniki w zadaniach angażujących funkcje poznawcze w porównaniu do innych pacjentów. Wszystkie grupy kliniczne różniły się pod względem wyników w testach/zadaniach do oceny wybranych funkcji poznawczych od osób zdrowych. W każdej grupie odnotowano dodatnie korelacje pomiędzy wynikiem DEX-S a poczuciem niepokoju i brak związku z wiekiem oraz incydentalne z wynikami zadań poznawczych.WnioskiWyniki sugerują zależne od lateralizacji patologii mechanizmy poczucia deficytów wykonawczych. Wysokie poczucie deficytów wykonawczych u osób z patologią prawej półkuli może być zależne od sprawności pamięci odroczonej, i może odzwierciedlać adekwatną samoocenę swoich kompetencji. Niski wynik w DEX-S grupy z patologią lewej półkuli może wynikać z obniżonej, mimo braku afazji, sprawności językowej/semantycznej nie zaś z braku wglądu w ograniczenia wykonawcze.
Sustainable Production and Trade Discrimination: An Analysis of the WTO
Authors: Calle Saldarriaga María Alejandra 
Published: April 2018

This article aims to examine the legality of trade measures addressing environmental conditions of production (PPMs) in the context of non-discrimination provisions under the General Agreement on Tariffs and Trade (GATT) and the Agreement on Technical Barriers to Trade (TBT Agreement). It shows that the notion of de facto discrimination is still a sensitive subject in the analysis of origin-neutral measures, including those based on environmental PPMs. Much of the discussion regarding PPMs focuses on the issue of ‘like products’. The interpretation of ‘likeness’ has also served to classify PPMs into the two categories of product related and non-product related. Such distinction rests on how the PPM affects the final product. However, it is important to analyse to what extent these measures can accord less favourable treatment to like products. The author argues that this requires a competition analysis. This article also elucidates how depending upon the applicable law (the TBT Agreement or the GATT) PPMs are likely to face different legal challenges, particularly in terms of less favourable treatment. The author also assesses the possibility of transposing concepts such as ‘legitimate regulatory distinctions’ stemming from the TBT jurisprudence into GATT cases involving PPMs, and whether there will be an additional ‘test’ for PPMs characterised as TBT measures. This article is based on an extensive literature review and doctrinal legal research
A Bridge Too Far: Divestiture as a Strategic Reaction to Status Inconsistency
Authors: Wang Pengfei , Jensen Michael 
Published: April 2018

This study focuses on the market identities of firms and suggests that identity ambiguity is caused not only by bridging horizontal product categories but also by status inconsistency stemming from bridging vertical status categories. Focusing specifically on how firms reduce status inconsistency by restructuring their business portfolios, we argue that status inconsistency motivates firms to divest business units to present a more coherent vertical market identity. Emphasizing the interplay between horizontal and vertical identity ambiguity, we argue furthermore that status-inconsistent units that are related to the core business units within a firm are more likely to be divested. Using a comprehensive sample of publicly traded U.S. firms from 1998 to 2014, we report that status inconsistency increases the likelihood of divestiture that decreases status inconsistency, particularly for high-status firms. Moreover, although status-inconsistent units are generally more likely to be divested, this effect is stronger for core business units.This paper was accepted by Greta Hsu, organizations.
Hip arthroscopy for femoroacetabular impingement
Authors: Nasser Rima , Domb Benjamin 
Published: April 2018

The purpose of this article is to give a general overview of femoroacetabular impingement (FAI) and how it could be treated arthroscopically, with some details about indications, the procedure itself and some of the complications associated with the surgery. FAI is a dynamic condition of the hip that can be a source of pain and disability and could potentially lead to arthritis. When symptomatic, and if conservative treatment fails, FAI can be addressed surgically. The goal of surgical treatment for FAI is to recreate the spherical contour of the femoral head, improve femoral offset, normalize coverage of the acetabulum, repair/reconstruct chondral damage and repair/reconstruct the labrum to restore normal mechanics and joint sealing. Advances in equipment and technique have contributed to an increase in the number of hip arthroscopy procedures performed worldwide and have made it one of the more common treatment options for symptomatic FAI. Hip arthroscopy is a procedure with an extremely steep and long learning curve.Cite this article: EFORT Open Rev 2018;3:121-129. DOI: 10.1302/2058-5241.3.170041
Closed reduction of distal radius fractures: a systematic review and meta-analysis
Authors: Søsborg-Würtz Hjalte , Corap Gellert Sükriye , Ladeby Erichsen Julie , Viberg Bjarke 
Published: April 2018

Distal radius fractures (DRF) are a common injury, especially in the elderly. Displaced fractures can be reduced by closed reduction through several techniques, two of which are compared in this systematic review and meta-analysis. Closed reduction by finger-trap traction (FTT) seems to offer better correction of radial shortening. Additionally, there may be less pain and fewer complications associated with this technique. Closed reduction by manual traction seems to offer better correction of the dorsal tilt. Further research is needed to fully determine the optimal method of closed reduction. Cite this article: EFORT Open Rev 2018;3:114-120.DOI: 10.1302/2058-5241.3.170063
Mack the Knife and Knife-Black Dorothy Appositional Metaphoric Compounds: A Comparison and Contrast of the Varying Approaches in Sanskrit Treatises on Grammar and Poetics
Authors: Lingorska Mirella 
Published: April 2018

Abstract
The present article focuses on appositional metaphoric compounds karmadhāraya-rūpaka in Sanskrit. A first section addresses some problems of compound typology in Western works, where appositional compounds have often been identified as copulative dvandva. Following this general analysis there is a section on appositional compounds from the perspective of the classical Sanskrit grammar, in particular the Pāṇinian tradition where the metaphorical aspect has not been explored specifically. The final section deals with the contribution of Sanskrit treatises on poetics to the identification of metaphoric compounds and their differentiation from compound similes. The approach suggested in later texts on poetics seems to be based on syntactical criteria, the ambiguity of the double-head topic, i. e. candra-mukha, a moon-face being specified in the comment. According to this, an appositional compound should be analysed as a simile, if the comment refers to the actual part of the compound, i.e. the subject of the simile, or as a metaphor, if the comment refers to the standard of comparison, thus shifting the focus of the sentence from the actual to the imagined entity.