bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tobacco industry’s elaborate attempts to control a global track and trace system and fundamentally undermine the Illicit Trade Protocol
Authors: Gilmore Anna B , Gallagher Allen W A , Rowell Andy 
Published: June 2018

Background
The Illicit Trade Protocol (ITP) requires a global track and trace (T&T) system to reduce tobacco smuggling. Given the tobacco industry’s (TI) historical involvement in tobacco smuggling, it stipulates that T&T ‘shall not be performed by or delegated to the tobacco industry’. This paper explores the rationale for & nature of the TI’s effors to influence the ITP & its T&T system.

Methods
Analysis of leaked TI documents and publicly available data; ,investigation of front groups, trademark and patent ownership.

Findings
Growing & diverse sources of evidence indicate that the TI remains involved in tobacco smuggling and that TI cigarettes account for around two-thirds of the illicit cigarette market. The TI therefore has a vested interest in controlling the global T&T system aimed to curtail this behaviour. To this end, Philip Morris International (PMI) adapted its pack marker system, Codentify, to meet T&T requirements, licensed it for free to its three major competitors who then collectively promoted it to governments using front groups and third parties including companies claiming to be independent despite clear TI links. PMI also sought to suggest Codentify was independent by selling some parts of its intellectual property on Codentify while retaining others, leaving a complex web of shared interests. In Africa, British American Tobacco used payments to obtain data suggesting its smaller competitor companies were evading taxes and secure influence with tax authorities. Regulatory capture has been enhanced by a public relations effort involving TI funding for conferences, training, research, and international police and anti-corruption organisations. Collectively this has created public messaging and a powerful network of organisations supportive of the TI’s misleading postion on illicit.

Conclusions
Governments should assume the TI seeks to control T&T systems in order to avoid scrutiny and minimise excise tax payments and that any T&T system based on Codentify, on intellectual property currently or previously owned by the TI, or being promoted or implemented by companies with TI links, is incompatible with the ITP and would not serve to reduce illicit trade.
Overview of foot‐and‐mouth disease awareness among farmers and veterinarians in France
Authors: Raut Noémie , Rivière Julie , Hosteing Soline , Collin Eric , Philizot Stéphanie , Debaere Olivier , Zanella Gina 
Published: June 2018

Foot‐and‐mouth disease (FMD) is of major concern in most countries including Europe, where no outbreaks have occurred since a decade. Indeed, the risk of FMD introduction from infected countries is not negligible and the awareness of field stakeholders (farmers, veterinarians) is essential to ensure an effective detection of the viral circulation. The French veterinary services launched in 2015 a survey to estimate the awareness of farmers and veterinarians and their knowledge about epidemiological and regulatory aspects of FMD. Official health visits were used to collect information from cattle farmers and veterinarians through two separate questionnaires. The results show that not all cattle farmers were aware of the risk of FMD reintroduction in France and of its routes of infection and speed of dissemination. As for the veterinarians, their promptness to report a suspicion was dependent on the occurrence of FMD cases in European countries. These results highlight key aspectsregarding FMD epidemiology which should be regularly reminded to the field stakeholders in FMD‐free countries to increase their awareness and thus ensure an effective early detection in case of FMD introduction.
Analysis of the microRNA signature driving adaptive right ventricular hypertrophy in an ovine model of congenital heart disease
Authors: Kameny Rebecca Johnson , He Youping , Zhu Terry , Gong Wenhui , Raff Gary W. , Chapin Cheryl J. , Datar Sanjeev A. , Boehme Jason T. , Hata Akiko , Fineman Jeffrey R. 
Published: June 2018

The right ventricular (RV) response to pulmonary arterial hypertension (PAH) is heterogeneous. Most patients have maladaptive changes with RV dilation and RV failure, whereas some, especially patients with PAH secondary to congenital heart disease, have an adaptive response with hypertrophy and preserved systolic function. Mechanisms for RV adaptation to PAH are unknown, despite RV function being a primary determinant of mortality. In our congenital heart disease ovine model with fetally implanted aortopulmonary shunt (shunt lambs), we previously demonstrated an adaptive physiological RV response to increased afterload with hypertrophy. In the present study, we examined small noncoding microRNA (miRNA) expression in shunt RV and characterized downstream effects of a key miRNA. RV tissue was harvested from 4-wk-old shunt and control lambs ( n = 5), and miRNA, mRNA, and protein were quantitated. We found differential expression of 40 cardiovascular-specific miRNAs in shunt RV. Interestingly, this miRNA signature is distinct from models of RV failure, suggesting that miRNAs might contribute to adaptive RV hypertrophy. Among RV miRNAs, miR-199b was decreased in the RV with eventual downregulation of nuclear factor of activated T cells/calcineurin signaling. Furthermore, antifibrotic miR-29a was increased in the shunt RV with a reduction of the miR-29 targets collagen type A1 and type 3A1 and decreased fibrosis. Thus, we conclude that the miRNA signature specific to shunt lambs is distinct from RV failure and drives gene expression required for adaptive RV hypertrophy. We propose that the adaptive RV miRNA signature may serve as a prognostic and therapeutic tool in patients with PAH to attenuate or prevent progression of RV failure and premature death. NEW & NOTEWORTHY This study describes a novel microRNA signature of adaptive right ventricular hypertrophy, with particular attention to miR-199b and miR-29a.
Scleraxis regulates Twist1 and Snai1 expression in the epithelial-to-mesenchymal transition
Authors: Al-Hattab Danah S. , Safi Hamza A. , Nagalingam Raghu S. , Bagchi Rushita A. , Stecy Matthew T. , Czubryt Michael P. 
Published: June 2018

Numerous physiological and pathological events, from organ development to cancer and fibrosis, are characterized by an epithelial-to-mesenchymal transition (EMT), whereby adherent epithelial cells convert to migratory mesenchymal cells. During cardiac development, proepicardial organ epithelial cells undergo EMT to generate fibroblasts. Subsequent stress or damage induces further phenotype conversion of fibroblasts to myofibroblasts, causing fibrosis via synthesis of an excessive extracellular matrix. We have previously shown that the transcription factor scleraxis is both sufficient and necessary for the conversion of cardiac fibroblasts to myofibroblasts and found that scleraxis knockout reduced cardiac fibroblast numbers by 50%, possibly via EMT attenuation. Scleraxis induced expression of the EMT transcriptional regulators Twist1 and Snai1 via an unknown mechanism. Here, we report that scleraxis binds to E-box consensus sequences within the Twist1 and Snai1 promoters to transactivate these genes directly. Scleraxis upregulates expression of both genes in A549 epithelial cells and in cardiac myofibroblasts. Transforming growth factor-β induces EMT, fibrosis, and scleraxis expression, and we found that transforming growth factor-β-mediated upregulation of Twist1 and Snai1 completely depends on the presence of scleraxis. Snai1 knockdown upregulated the epithelial marker E-cadherin; however, this effect was lost after scleraxis overexpression, suggesting that scleraxis may repress E-cadherin expression. Together, these results indicate that scleraxis can regulate EMT via direct transactivation of the Twist1 and Snai1 genes. Given the role of scleraxis in also driving the myofibroblast phenotype, scleraxis appears to be a critical controller of fibroblast genesis and fate in the myocardium and thus may play key roles in wound healing and fibrosis.NEW & NOTEWORTHY The molecular mechanism by which the transcription factor scleraxis mediates Twist1 and Snai1 gene expression was determined. These results reveal a novel means of transcriptional regulation of epithelial-to-mesenchymal transition and demonstrate that transforming growth factor-β-mediated epithelial-to-mesenchymal transition is dependent on scleraxis, providing a potential target for controlling this process.
Changes in cardiac resident fibroblast physiology and phenotype in aging
Authors: Trial JoAnn , Cieslik Katarzyna A. 
Published: June 2018

The cardiac fibroblast plays a central role in tissue homeostasis and in repair after injury. With aging, dysregulated cardiac fibroblasts have a reduced capacity to activate a canonical transforming growth factor-β-Smad pathway and differentiate poorly into contractile myofibroblasts. That results in the formation of an insufficient scar after myocardial infarction. In contrast, in the uninjured aged heart, fibroblasts are activated and acquire a profibrotic phenotype that leads to interstitial fibrosis, ventricular stiffness, and diastolic dysfunction, all conditions that may lead to heart failure. There is an apparent paradox in aging, wherein reparative fibrosis is impaired but interstitial, adverse fibrosis is augmented. This could be explained by analyzing the effectiveness of signaling pathways in resident fibroblasts from young versus aged hearts. Whereas defective signaling by transforming growth factor-β leads to insufficient scar formation by myofibroblasts, enhanced activation of the ERK1/2 pathway may be responsible for interstitial fibrosis mediated by activated fibroblasts.Listen to this article's corresponding podcast at https://ajpheart.podbean.com/e/fibroblast-phenotypic-changes-in-the-aging-heart/ .
Role of endothelial microRNA-23 clusters in angiogenesis in vivo
Authors: Oikawa Satoshi , Wada Shogo , Lee Minjung , Maeda Seiji , Akimoto Takayuki 
Published: June 2018

The capillary network is distributed throughout the body, and its reconstruction is induced under various pathophysiological conditions. MicroRNAs are small noncoding RNAs that regulate gene expression via posttranscriptional mechanisms and are involved in many biological functions, including angiogenesis. Previous studies have shown that each microRNA of miR-23 clusters, composed of the miR-23a cluster (miR-23a~27a~24-2) and miR-23b cluster (miR-23b~27b~24-1), regulates angiogenesis in vitro. However, the role of miR-23 clusters, located within a single transcription unit, in angiogenesis in vivo has not been elucidated. In the present study, we generated vascular endothelial cell (EC)-specific miR-23 cluster double-knockout (DKO) mice and demonstrated sprouting angiogenesis under various conditions, including voluntary running exercise, hindlimb ischemia, skin wound healing, and EC sprouting from aorta explants. Here, we demonstrated that EC-specific miR-23 DKO mice are viable and fertile, with no gross abnormalities observed in pups or adults. The capillary number was normally increased in the muscles of these DKO mice in response to 2 wk of voluntary running and hindlimb ischemia. Furthermore, we did not observe any abnormalities in skin wound closure or EC sprouting from aortic ring explants in EC-specific miR-23 cluster DKO mice. Our results suggest that endothelial miR-23 clusters are dispensable for embryonic development and postnatal angiogenesis in vivo. NEW & NOTEWORTHY We generated vascular endothelial cell (EC)-specific miR-23a/b cluster double-knockout mice and determined sprouting angiogenesis under various conditions, including voluntary running exercise, hindlimb ischemia, skin wound healing, and EC sprouting from aorta explants. We demonstrated that the double-knockout mice were viable and fertile, with no gross abnormalities in exercise- and ischemia-induced angiogenesis and skin wound closure or EC sprouting from aortic ring explants.
Flightless-I Blocks p62-Mediated Recognition of LC3 to Impede Selective Autophagy and Promote Breast Cancer Progression
Authors: He Jian-Ping , Hou Pei-Pei , Chen Qi-Tao , Wang Wei-Jia , Sun Xiao-Yu , Yang Peng-Bo , Li Ying-Ping , Yao Lu-Ming , Li Xiaotong , Jiang Xin-Dong , Chien Kun-Yi , Zhang Zhi-Ming , Wu Qiu-Wan , Cowin Allison J. , Wu Qiao , Chen Hang-Zi 
Published: June 2018

Abstract
p62 is a receptor that facilitates selective autophagy by interacting simultaneously with cargoes and LC3 protein on the autophagosome to maintain cellular homeostasis. However, the regulatory mechanism(s) behind this process and its association with breast cancer remain to be elucidated. Here, we report that Flightless-I (FliI), a novel p62-interacting protein, promotes breast cancer progression by impeding selective autophagy. FliI was highly expressed in clinical breast cancer samples, and heterozygous deletion of FliI retarded the development of mammary tumors in PyVT mice. FliI induced p62-recruited cargoes into Triton X-100 insoluble fractions (TI) to form aggregates, thereby blocking p62 recognition of LC3 and hindering p62-dependent selective autophagy. This function of Flil was reinforced by Akt-mediated phosphorylation at Ser436 and inhibited by phosphorylation of Ulk1 at Ser64. Obstruction of autophagic clearance of p62-recruited cargoes by FliI was associated with the accumulation of oxidative damage on proteins and DNA, which could contribute to the development of cancer. Heterozygous knockout of FliI facilitated selectively autophagic clearance of aggregates, abatement of ROS levels, and protein oxidative damage, ultimately retarding mammary cancer progression. In clinical breast cancer samples, Akt-mediated phosphorylation of FliI at Ser436 negatively correlated with long-term prognosis, while Ulk1-induced FliI phosphorylation at Ser64 positively correlated with clinical outcome. Together, this work demonstrates that FliI functions as a checkpoint protein for selective autophagy in the crosstalk between FliI and p62-recruited cargoes, and its phosphorylation may serve as a prognostic marker for breast cancer.
Significance: Flightless-I functions as a checkpoint protein for selective autophagy by interacting with p62 to block its recognition of LC3, leading to tumorigenesis in breast cancer.Cancer Res; 78(17); 4853–64. ©2018 AACR.
Syntaphilin Ubiquitination Regulates Mitochondrial Dynamics and Tumor Cell Movements
Authors: Seo Jae Ho , Agarwal Ekta , Bryant Kelly G. , Caino M. Cecilia , Kim Eui Tae , Kossenkov Andrew V. , Tang Hsin-Yao , Languino Lucia R. , Gabrilovich Dmitry I. , Cohen Andrew R. , Speicher David W. , Altieri Dario C. 
Published: June 2018

AbstractSyntaphilin (SNPH) inhibits the movement of mitochondria in tumor cells, preventing their accumulation at the cortical cytoskeleton and limiting the bioenergetics of cell motility and invasion. Although this may suppress metastasis, the regulation of the SNPH pathway is not well understood. Using a global proteomics screen, we show that SNPH associates with multiple regulators of ubiquitin-dependent responses and is ubiquitinated by the E3 ligase CHIP (or STUB1) on Lys111 and Lys153 in the microtubule-binding domain. SNPH ubiquitination did not result in protein degradation, but instead anchored SNPH on tubulin to inhibit mitochondrial motility and cycles of organelle fusion and fission, that is dynamics. Expression of ubiquitination-defective SNPH mutant Lys111→Arg or Lys153→Arg increased the speed and distance traveled by mitochondria, repositioned mitochondria to the cortical cytoskeleton, and supported heightened tumor chemotaxis, invasion, and metastasis in vivo. Interference with SNPH ubiquitination activated mitochondrial dynamics, resulting in increased recruitment of the fission regulator dynamin-related protein-1 (Drp1) to mitochondria and Drp1-dependent tumor cell motility. These data uncover nondegradative ubiquitination of SNPH as a key regulator of mitochondrial trafficking and tumor cell motility and invasion. In this way, SNPH may function as a unique, ubiquitination-regulated suppressor of metastasis.Significance: These findings reveal a new mechanism of metastasis suppression by establishing the role of SNPH ubiquitination in inhibiting mitochondrial dynamics, chemotaxis, and metastasis. Cancer Res; 78(15); 4215–28. ©2018 AACR.
Unexpected Benefits of Aging for Favorable Responses to PD-1 Blockade in Melanoma?
Authors: Pawelec Graham 
Published: June 2018

Abstract
Immunosenescence might be expected to reduce the efficacy of checkpoint blockade, which depends on a functionally intact immune system. However, it seems that older patients with melanoma may respond better to anti-PD-1 treatment than younger patients, possibly due to their having fewer regulatory T cells relative to CD8+ T cells within tumor deposits. Clin Cancer Res; 24(21); 5193–4. ©2018 AACR.
See related article by Kugel et al., p. 5347
Is the Awareness of the Aerosol State Useful in Predicting Enhanced Lightning for Lightning-Producing Storms over Northern Alabama?
Authors: Ren Tong , Rapp Anita D. , Nasiri Shaima L. , Mecikalski John R. , Apke Jason 
Published: June 2018

AbstractThe Moderate Resolution Imaging Spectroradiometer (MODIS) aerosol optical depth (AOD) retrievals from theTerraandAquasatellites currently provide the largest satellite aerosol dataset for investigating relationships to meteorological phenomena, such as aerosol impact on electrification in deep convection. The usefulness of polar-orbiting satellite aerosol retrievals in lightning inference is examined by correlating MODIS AOD retrievals with lightning observations of the thunderstorms in the summers during 2002–14 over northern Alabama. Lightning flashes during the 1400–1700 local standard time peak period show weak but positive correlations with the MODIS AOD retrievals 2–4 h earlier. The correlation becomes stronger in particular meteorological conditions, including weak vertical wind shear and prevailing northerly winds over northern Alabama. Results show that the MODIS AOD retrievals are less useful in predicting enhanced lightning flash rate for lightning-producing storms than the forecasts of other meteorological variables that are more closely linked to the intensification of convective storms. However, when relatively weaker convective available potential energy (CAPE) is forecast, the probability of enhanced lightning flash rate increases in a more polluted environment, making the knowledge of aerosols more useful in lightning inference in such CAPE regimes. The aerosol enhancement of lightning, if present, may be associated with enhanced convergence in the boundary layer and secondary convection.
Quasi-Experimental Determination of Turbulent Dispersion Parameters for Different Stability Conditions from a Tall Micrometeorological Tower
Authors: Martins Luís Gustavo N. , Degrazia Gervásio A. , Acevedo Otávio C. , Puhales Franciano S. , de Oliveira Pablo E. S. , Teichrieb Claudio A. , da Silva Samuel M. 
Published: June 2018

AbstractTurbulent wind data measured by sonic anemometers installed at various heights on a 140-m-tall micrometeorological tower located at a coastal site are used to obtain vertical profiles of the velocity standard deviations σi, Lagrangian decorrelation local time scales TLi, and eddy diffusivities Kα for distinct stability conditions. The novelty of the study lies in the use of turbulent data directly measured over the extension of the atmospheric surface layer at a coastal site for that purpose. Furthermore, the approach employs the Hilbert–Huang transform to determine the wind energy spectral peak frequencies. These are applied to the asymptotic spectral equation from Taylor statistical diffusion theory to obtain the turbulent dispersion parameters, which are shown to generally agree well with those provided by a classical autocorrelation approach. For neutral and stable situations the vertical profiles of momentum eddy diffusivities agree well with those derived from the spectral and autocorrelation method. Additionally, the turbulent integral time scales and eddy diffusivities determined by the method at a coastal location are found to overestimate those predicted from analytical expressions based on continental field observations. The turbulence parameters found are suitable to be employed in air pollution dispersion models.
Developing a 3D Gestural Interface for Anesthesia-Related Human-Computer Interaction Tasks Using Both Experts and Novices
Authors: Jurewicz Katherina A. , Neyens David M. , Catchpole Ken , Reeves Scott T. 
Published: June 2018

Objective: The purpose of this research was to compare gesture-function mappings for experts and novices using a 3D, vision-based, gestural input system when exposed to the same context of anesthesia tasks in the operating room (OR). Background: 3D, vision-based, gestural input systems can serve as a natural way to interact with computers and are potentially useful in sterile environments (e.g., ORs) to limit the spread of bacteria. Anesthesia providers’ hands have been linked to bacterial transfer in the OR, but a gestural input system for anesthetic tasks has not been investigated. Methods: A repeated-measures study was conducted with two cohorts: anesthesia providers (i.e., experts) ( N = 16) and students (i.e., novices) ( N = 30). Participants chose gestures for 10 anesthetic functions across three blocks to determine intuitive gesture-function mappings. Reaction time was collected as a complementary measure for understanding the mappings. Results: The two gesture-function mapping sets showed some similarities and differences. The gesture mappings of the anesthesia providers showed a relationship to physical components in the anesthesia environment that were not seen in the students’ gestures. The students also exhibited evidence related to longer reaction times compared to the anesthesia providers. Conclusion: Domain expertise is influential when creating gesture-function mappings. However, both experts and novices should be able to use a gesture system intuitively, so development methods need to be refined for considering the needs of different user groups. Application: The development of a touchless interface for perioperative anesthesia may reduce bacterial contamination and eventually offer a reduced risk of infection to patients.
Three-Dimensional Printing of Personalized Nasal Stents for Patients With Cleft Lip
Authors: Luo Dongyuan , Li Ting , Wang Hongtao , Chen Yiyang 
Published: June 2018

Objective: This report describes the design and printing of personalized nasal stents for cleft lip using 3-dimensional (3D) technology. Materials and Methods: We used silicone rubber to make the impressions, a 3D laser scanner to obtain 3D data, and Dental SG resin cartridges as printing material. We printed the personalized nasal stents using a photosensitive resin printer. Results: We placed the stents in patients after cleft lip surgery. They enabled personalized adjustment and good anastomosis, with a low probability of slipping from the nasal cavity. Conclusion: With this technique, we can provide good nasal support for patients with cleft lip.