bluuebunny/crossref_metadata_2025 huggingface dataset:
Examining Opportunities for Goal-Directed Self-Tracking to Support Chronic Condition Management
Authors: Schroeder Jessica , Karkar Ravi , Murinova Natalia , Fogarty James , Munson Sean A.
Published: December 2019

Although self-tracking offers potential for a more complete, accurate, and longer-term understanding of personal health, many people struggle with or fail to achieve their goals for health-related self-tracking. This paper investigates how to address challenges that result from current self-tracking tools leaving a person's goals for their data unstated and lacking explicit support. We examine supporting people and health providers in expressing and pursuing their tracking-related goals via goal-directed self-tracking, a novel method to represent relationships between tracking goals and underlying data. Informed by a reanalysis of data from a prior study of migraine tracking goals, we created a paper prototype to explore whether and how goal-directed self-tracking could address current disconnects between the goals people have for data in their chronic condition management and the tools they use to support such goals. We examined this prototype in interviews with 14 people with migraine and 5 health providers. Our findings indicate the potential for scaffolding goal-directed self-tracking to: 1) elicit different types and hierarchies of management and tracking goals; 2) help people prepare for all stages of self-tracking towards a specific goal; and 3) contribute additional expertise in patient-provider collaboration. Based on our findings, we present implications for the design of tools that explicitly represent and support an individual's specific self-tracking goals.
Scheduling Content in Pervasive Display Systems
Authors: Clinch Sarah , Mikusz Mateusz , Elhart Ivan , Davies Nigel , Langheinrich Marc
Published: December 2019

Digital displays are a ubiquitous feature of public spaces; London recently deployed a whole network of new displays in its Underground stations, and the screens on One Time Square (New York) allow for presentation of over 16,000 square feet of digital media. However, despite decades of research into pervasive displays, the problem of scheduling content is under-served and there is little forward momentum in addressing the challenges brought with large-scale and open display networks. This paper presents the first comprehensive architectural model for scheduling in current and anticipated pervasive display systems. In contrast to prior work, our three-stage model separates out the process of high level goal setting from content filtering and selection. Our architecture is motivated by an extensive review of the literature and a detailed consideration of requirements. The architecture is realised with an implementation designed to serve the world's largest and longest-running research testbed of pervasive displays. A mixed-methods evaluation confirms the viability of the architecture from three angles: demonstrating capability to meet the articulated requirements, performance that comfortably fits within the demands of typical display deployments, and evidence of its ability to serve as the day-to-day scheduling platform for the previously described research testbed. Based on our evaluation and a reflection on paper as a whole, we identify ten implications that will shape future research and development in pervasive display scheduling.
Probing Sucrose Contents in Everyday Drinks Using Miniaturized Near-Infrared Spectroscopy Scanners
Authors: Jiang Weiwei , Marini Gabriele , van Berkel Niels , Sarsenbayeva Zhanna , Tan Zheyu , Luo Chu , He Xin , Dingler Tilman , Goncalves Jorge , Kawahara Yoshihiro , Kostakos Vassilis
Published: December 2019

Near-Infrared Spectroscopy (NIRS) is a non-invasive sensing technique which can be used to acquire information on an object's chemical composition. Although NIRS is conventionally used in dedicated laboratories, the recent introduction of miniaturized NIRS scanners has greatly expanded the use cases of this technology. Previous work from the UbiComp community shows that miniaturized NIRS can be successfully adapted to identify medical pills and alcohol concentration. In this paper, we further extend this technology to identify sugar (sucrose) contents in everyday drinks. We developed a standalone mobile device which includes inter alia a NIRS scanner and a 3D printed clamp. The clamp can be attached to a straw-like tube to sense a liquid's sucrose content. Through a series of studies, we show that our technique can accurately measure sucrose levels in both lab-made samples and commercially available drinks, as well as classify commercial drinks. Furthermore, we show that our method is robust to variations in the ambient temperature and lighting conditions. Overall, our system can estimate the concentration of sugar with ±0.29 g/100ml error in lab-made samples and < 2.0 g/100ml error in 18 commercial drinks, and can identify everyday drinks with > 99% accuracy. Furthermore, in our analysis, we are able to discern three characteristic wavelengths in the near-infrared region (1055 nm, 1235 nm and 1545 nm) with acute responses to sugar (sucrose). Our proposed protocol contributes to the development of everyday "food scanners" consumers.
Skeletal muscle transcriptional networks linked to type I myofiber grouping in Parkinson’s disease
Authors: Lavin Kaleen M. , Sealfon Stuart C. , McDonald Merry-Lynn N. , Roberts Brandon M. , Wilk Katarzyna , Nair Venugopalan D. , Ge Yongchao , Lakshman Kumar Preeti , Windham Samuel T. , Bamman Marcas M.
Published: December 2019

Parkinson’s disease (PD) is a common neurodegenerative disorder impacting cognition, movement, and quality of life in >10 million individuals worldwide. We recently characterized and quantified a skeletal muscle pathology in PD represented by exaggerated type I myofiber grouping presumed to result from denervation-reinnervation processes. Our previous findings indicated that impaired neuromuscular junction integrity may be involved in type I grouping, which is associated with excessive motor unit activation during weight-bearing tasks. In this study, we performed transcriptional profiling to test the hypothesis that type I grouping severity would link to distinct gene expression networks. We generated transcriptome-wide poly(A) RNA-Seq data from skeletal muscle of individuals with PD [ n = 12 (9 men, 3 women); 67 ± 2 yr], age- and sex-matched older adults ( n = 12; 68 ± 2 yr), and sex-matched young adults ( n = 12; 30 ± 1 yr). Differentially expressed genes were evaluated across cohorts. Weighted gene correlation network analysis (WGCNA) was performed to identify gene networks most correlated with indicators of abnormal type I grouping. Among coexpression networks mapping to phenotypes pathologically increased in PD muscle, one network was highly significantly correlated to type I myofiber group size and another to percentage of type I myofibers found in groups. Annotation of coexpressed networks revealed that type I grouping is associated with altered expression of genes involved in neural development, postsynaptic signaling, cell cycle regulation and cell survival, protein and energy metabolism, inflammation/immunity, and posttranscriptional regulation (microRNAs). These transcriptomic findings suggest that skeletal muscle may play an active role in signaling to promote myofiber survival, reinnervation, and remodeling, perhaps to an extreme in PD.

NEW & NOTEWORTHY Despite our awareness of the impact of Parkinson’s disease (PD) on motor function for over two centuries, limited attention has focused on skeletal muscle. We previously identified type I myofiber grouping, a novel indicator of muscle dysfunction in PD, presumably a result of heightened rates of denervation/reinnervation. Using transcriptional profiling to identify networks associated with this phenotype, we provide insight into potential mechanistic roles of skeletal muscle in signaling to promote its survival in PD.
Laparoscopic Vessel Endometriosis Resection Surgery: A Case Report and Review of Literature
Authors: Rezai Shadi , Giovane Richard A. , Mann Tiffanie , Patil Ninad M. , Bardawil Elise , Henderson Cassandra E. , Guan Xiaoming
Published: December 2019

Background. Endometriosis usually occurs in the pelvis and often involves the ovaries, the uterosacral and broad ligaments, and the pelvic peritoneum. In rare instances, it can occur in the vasculature of the pelvis. Patients with endometriosis present with abnormal pain, menstrual cycle disruption and infertility. Management of endometriosis is usually surgical with excision of the tissue via laparoscopic means. Case. A 42-year-old Gravida 5, Para 2-0-3-2 patient with a 22 year history of endometriosis, who had had multiple laparoscopic endometriosis resections, total abdominal hysterectomy, and an exploratory laparotomy with bilateral salpingo-oophorectomy, presented with left pelvic pain when standing, dyspareunia, and a 3.7 cm cyst on ultrasound. The patient underwent laparoscopic vessel endometriosis resection and excision of endometriotic nodules from external iliac vessels. Final pathology report showed evidence of old endometriosis in all locations. On interval follow-up, the patient reported sustained relief from pain. Conclusion. Complete resection of endometriosis from large vessels can be successfully achieved laparoscopically by a well-experienced surgeon with delicate, proper techniques.
Risedronate Effects on the In Vivo Bioactive Glass Behavior: Nuclear Magnetic Resonance and Histopathological Studies
Authors: Mosbahi Siwar , Oudadesse Hassane , Roiland Claire , Lefeuvre Bertrand , Slimani Lotfi , Keskes Hassib
Published: December 2019

The present study aimed to enhance the anti-osteoporotic performance of bioactive glass (46S6) through its association with bisphosphonate such as risedronate with amounts of 8, 12, and 20%. Obtained composites have been called 46S6-8RIS, 46S6-12RIS, and 46S6-20RIS, respectively. In vitro and in vivo explorations have been carried out. Bioactive glass and risedronate association has been performed by adsorption process. Structure analyses have been carried out to evaluate and to understand their chemical interactions. Solid Nuclear Magnetic Resonance (NMR) has been employed to study the structural properties of obtained biocomposite. The spectra deconvolution showed the appearance of a species (Q4) in the biocomposites 46S6-8RIS, 46S6-12RIS, and 46S6-20RIS indicating their successful chemical association. In vitro experiments showed the enhancement of the chemical reactivity of the composites 46S6-xRIS compared to the pure bioactive glass. In fact, the silicon liberation after 30 days of immersion was 50 ppm for pure bioactive glass 46S6, and 41, 64, and 62 from 46S6-8RIS, 46S6-12RIS, and 46S6-20RIS, respectively. Based on the in vitro results, 46S6-8RIS was implanted in the femoral condyle of an ovariectomized rat and compared with implanted pure glass in the goal to highlight its anti-osteoporotic performance. After 60 days, implanted group with 46S6-8RIS showed the increase in bone mineral density (BMD with 10%) and bone volume fraction (BV/TV with 80%) and the decrease in trabecular separation (Tb/Sp with 74%) when compared to that of 46S6 group. These results are confirmed by the histopathological analyses, which showed the bone trabeculae reconnection after the 46S6-8RIS implantation. Chemical analyses showed the reduction in silicon (Si) and sodium (Na) ion concentrations, and the rise in calcium (Ca) and phosphorus (P) ion levels, which was explained by the dissolution of biocomposite matrix and the deposition of hydroxyapatite layer. Histomorphometric results highlighted the risedronate effect on the antiosteoporotic phenomenon. Obtained results showed good behavior with only 8% of introduced risedronate in the glass matrix.
Experimental Research on the Vibration of Ship Propulsion Shaft under Hull Deformation Excitations on Bearings
Authors: Zhang Cong , Xie Dongchen , Huang Qianwen , Wang Zhihua
Published: December 2019

With the development of ship enlargement, the problems of coupling vibration between hull and propulsion system and vibration transmission via bearings are more and more prominent. Based on the theory of shaft vibration and the experimental system for dynamic characteristics of the shaft, an experiment plan about propulsion shaft vibration under dynamic excitations is designed in this paper. The performance of propulsion shaft vibration under hull deformation excitations applied on intermediate and stern bearings is studied. Hydraulic excitations in horizontal and vertical directions on the intermediate bearing and stern bearing of the experimental model of propulsion shaft are considered in this paper to simulate hull deformation on bearings of the ship. Vibration characteristics of the shaft under different excitations are gained and coupling effects are discussed. Moreover, the influences of amplitude and direction of excitations on bearings and the shaft rotation speed on the vibration of propulsion are studied. The results show that aiming at improving the safety and reliability of navigation, the hull deformation, especially the horizontal hull deformation excitation on the intermediate bearing, is not neglectable and should be considered during primary design. Also, rotation speed and resonant frequency are needed to be well designed with the frequencies of hull deformation excitations.
New Insights for Cellular and Molecular Mechanisms of Aging and Aging-Related Diseases: Herbal Medicine as Potential Therapeutic Approach
Authors: Liu Yanfei , Weng Weiliang , Gao Rui , Liu Yue
Published: December 2019

Aging is a progressive disease affecting around 900 million people worldwide, and in recent years, the mechanism of aging and aging-related diseases has been well studied. Treatments for aging-related diseases have also made progress. For the long-term treatment of aging-related diseases, herbal medicine is particularly suitable for drug discovery. In this review, we discuss cellular and molecular mechanisms of aging and aging-related diseases, including oxidative stress, inflammatory response, autophagy and exosome interactions, mitochondrial injury, and telomerase damage, and summarize commonly used herbals and compounds concerned with the development of aging-related diseases, including Ginkgo biloba, ginseng, Panax notoginseng, Radix astragali, Lycium barbarum, Rhodiola rosea, Angelica sinensis, Ligusticum chuanxiong, resveratrol, curcumin, and flavonoids. We also summarize key randomized controlled trials of herbal medicine for aging-related diseases during the past ten years. Adverse reactions of herbs were also described. It is expected to provide new insights for slowing aging and treating aging-related diseases with herbal medicine.
Development and Characterization of PEGylated Chromatographic Monoliths as a Novel Platform for the Separation of PEGylated RNase a Isomers
Authors: Sánchez-Trasviña Calef , Rito-Palomares Marco , González-Valdez José
Published: December 2019

PEGylated or polyethylene glycol-modified proteins have been used as therapeutic agents in different diseases. However, the major drawback in their procurement is the purification process to separate unreacted proteins and the PEGylated species. Several efforts have been done to separate PEGylation reactions by chromatography using different stationary phases and modified supports. In this context, this study presents the use of chromatographic monoliths modified with polyethylene glycol (PEG) to separate PEGylated Ribonuclease A (RNase A). To do this, Convective Interaction Media (CIM) Ethylenediamine (EDA) monolithic disks were PEGylated using three PEG molecular weights (1, 10, and 20 kDa). The PEGylated monoliths were used to separate PEGylated RNase A modified, as well, with three PEG molecular weights (5, 20, and 40 kDa) by hydrophobic interaction chromatography. Performance results showed that Bovine Serum Albumin (BSA) can bind to PEGylated monoliths and the amount of bound BSA increases when ammonium sulfate concentration and flow rate increase. Furthermore, when PEGylated RNase A was loaded into the PEGylated monoliths, PEG-PEG interactions predominated in the separation of the different PEGylated species (i.e., mono and di-PEGylated). It was also observed that the molecular weight of grafted PEG chains to the monolith impacts strongly in the operation resolution. Interestingly, it was possible to separate, for the first time, isomers of 40 kDa PEGylated RNase A by hydrophobic interaction chromatography. This technology, based on PEGylated monoliths, represents a new methodology to efficiently separate proteins and PEGylated proteins. Besides, it could be used to separate other PEGylated molecules of biopharmaceutical or biotechnological interest.
SVR-EEMD: An Improved EEMD Method Based on Support Vector Regression Extension in PPG Signal Denoising
Authors: Liu Guangda , Hu Xinlei , Wang Enhui , Zhou Ge , Cai Jing , Zhang Shang
Published: December 2019

Photoplethysmography (PPG) has been widely used in noninvasive blood volume and blood flow detection since its first appearance. However, its noninvasiveness also makes the PPG signals vulnerable to noise interference and thus exhibits nonlinear and nonstationary characteristics, which have brought difficulties for the denoising of PPG signals. Ensemble empirical mode decomposition known as EEMD, which has made great progress in noise processing, is a noise-assisted nonlinear and nonstationary time series analysis method based on empirical mode decomposition (EMD). The EEMD method solves the “mode mixing” problem in EMD effectively, but it can do nothing about the “end effect,” another problem in the decomposition process. In response to this problem, an improved EEMD method based on support vector regression extension (SVR-EEMD) is proposed and verified by simulated data and real-world PPG data. Experiments show that the SVR-EEMD method can solve the “end effect” efficiently to get a better decomposition performance than the traditional EEMD method and bring more benefits to the noise processing of PPG signals.
Efficient Localization Algorithm for Near‐Field Noncircular Sources via Dual‐Polarization Sensor Array
Authors: Song Jiaqi , Tao Haihong
Published: December 2019

Noncircular signals are widely used in the area of radar, sonar, and wireless communication array systems, which can offer more accurate estimates and detect more sources. In this paper, the noncircular signals are employed to improve source localization accuracy and identifiability. Firstly, an extended real‐valued covariance matrix is constructed to transform complex‐valued computation into real‐valued computation. Based on the property of noncircular signals and symmetric uniform linear array (SULA) which consist of dual‐polarization sensors, the array steering vectors can be separated into the source position parameters and the nuisance parameter. Therefore, the rank reduction (RARE) estimators are adopted to estimate the source localization parameters in sequence. By utilizing polarization information of sources and real‐valued computation, the maximum number of resolvable sources, estimation accuracy, and resolution can be improved. Numerical simulations demonstrate that the proposed method outperforms the existing methods in both resolution and estimation accuracy.
Cardiac Murmur in a Boy with Normal Paternal Prenatal Carrier Screening for Pompe Disease
Authors: Jay Allison M. , Anne Premchand , Stockton David
Published: December 2019

Introduction. Pompe disease is an autosomal recessive lysosomal storage disorder with marked morbidity and mortality, if untreated. With the advent of enzyme replacement therapy, it is essential to identify the infantile-type as early as possible to mitigate the effects of the enzyme deficiency. Identification is possible prenatally with testing of both parents. More recently, many states have instituted newborn screening for this condition. Case. We report a patient with infantile-onset Pompe disease with a normal paternal carrier genetic test, born prior to newborn screening for Pompe disease in the state of Michigan. The infant’s father was retested once the infant was diagnosed with Pompe disease postnatally and noted to have a mutation conducive to Pompe disease. Conclusion. Providers should have a strong clinical suspicion for disorders even if prenatal parental carrier screening is normal. A normal parental prenatal test does not exclude the possibility that the fetus may be diagnosed with a disorder postnatally, and pediatricians may be faced with limitations in accuracy of parents’ recollection of parental testing results.
Efficacy of Using Probiotics with Antagonistic Activity against Pathogens of Wound Infections: An Integrative Review of Literature
Authors: Fijan Sabina , Frauwallner Anita , Langerholc Tomaž , Krebs Bojan , ter Haar (née Younes) Jessica A. , Heschl Adolf , Mičetić Turk Dušanka , Rogelj Irena
Published: December 2019

The skin and its microbiota serve as physical barriers to prevent invasion of pathogens. Skin damage can be a consequence of illness, surgery, and burns. The most effective wound management strategy is to prevent infections, promote healing, and prevent excess scarring. It is well established that probiotics can aid in skin healing by stimulating the production of immune cells, and they also exhibit antagonistic effects against pathogens via competitive exclusion of pathogens. Our aim was to conduct a review of recent literature on the efficacy of using probiotics against pathogens that cause wound infections. In this integrative review, we searched through the literature published in the international following databases: PubMed, ScienceDirect, Web of Science, and Scopus using the search terms “probiotic” AND “wound infection.” During a comprehensive review and critique of the selected research, fourteenin vitrostudies, 8 animal studies, and 19 clinical studies were found. Two of thesein vitrostudies also included animal studies, yielding a total of 39 articles for inclusion in the review. The most commonly used probiotics for all studies were well-known strains of the speciesLactobacillus plantarum,Lactobacillus casei,Lactobacillus acidophilus, andLactobacillus rhamnosus.Allin vitrostudies showed successful inhibition of chosen skin or wound pathogens by the selected probiotics. Within the animal studies on mice, rats, and rabbits, probiotics showed strong opportunities for counteracting wound infections. Most clinical studies showed slight or statistically significant lower incidence of surgical site infections, foot ulcer infection, or burn infections for patients using probiotics. Several of these studies also indicated a statistically significant wound healing effect for the probiotic groups. This review indicates that exogenous and oral application of probiotics has shown reduction in wound infections, especially when used as an adjuvant to antibiotic therapy, and therefore the potential use of probiotics in this field remains worthy of further studies, perhaps focused more on typical skin inhabitants as next-generation probiotics with high potential.
Advances in Organocatalyzed Atom Transfer Radical Polymerization
Authors: Hu Xin , Zhu Ning , Guo Kai
Published: December 2019

Atom transfer radical polymerization (ATRP) is one of the most robust tools to prepare well-defined polymers with precise topologies and architectures. Although series of improved ATRP methods have been developed to decrease the metal catalyst loading to parts per million, metal residue is the key limiting factor for variety of applications, especially in microelectronic and biomedical area. The feasible solution to this challenge would be the establishment of metal-free ATRP. Since 2014, organocatalyzed ATRP (O-ATRP) or metal free ATRP has achieved significant progress by developing kinds of organic photoredox catalysts. This review highlights the advances in organocatalyzed atom transfer radical polymerization as well as the potential future directions.
Current Landscape of Epigenetics in Lung Cancer: Focus on the Mechanism and Application
Authors: Shi Yuan-Xiang , Sheng De-Qiao , Cheng Lin , Song Xin-Yu
Published: December 2019

Lung cancer is the leading cause of cancer-related mortality worldwide. Tumorigenesis involves a multistep process resulting from the interactions of genetic, epigenetic, and environmental factors. Genome-wide association studies and sequencing studies have identified many epigenetic alterations associated with the development of lung cancer. Epigenetic mechanisms, mainly including DNA methylation, histone modification, and noncoding RNAs (ncRNAs), are heritable and reversible modifications that are involved in some important biological processes and affect cancer hallmarks. We summarize the major epigenetic modifications in lung cancer, focusing on DNA methylation and ncRNAs, their roles in tumorigenesis, and their effects on key signaling pathways. In addition, we describe the clinical application of epigenetic biomarkers in the early diagnosis, prognosis prediction, and oncotherapy of lung cancer. Understanding the epigenetic regulation mechanism of lung cancer can provide a new explanation for tumorigenesis and a new target for the precise treatment of lung cancer.
Crystallinity and Reinforcement in Poly-L-Lactic Acid Scaffold Induced by Carbon Nanotubes
Authors: Wang Guoyong , Qi Fangwei , Yang Wenjing , Yang Youwen , He Chongxian , Peng Shuping , Shuai Cijun
Published: December 2019

Poly-L-Lactic Acid (PLLA) is a bioabsorbable implant material due to its favorable biocompatibility and inherent degradability, while the insufficient mechanical strength hinders its further bone repair application. In present work, carbon nanotubes (CNTs) were introduced into PLLA scaffolds fabricated via selective laser sintering. It was found that the crystallinity of PLLA increased considerably since CNTs could promote the orderly stacking of its molecular chains, thereby improving the mechanical strength of PLLA scaffold. Furthermore, the fracture surface analysis revealed that CNTs acted as a bridge across the cracks and hindered their further expansion. Moreover, CNTs pulled out from the matrix to consume a large amount of fracture energy, which enhanced the resistance to external forces. As a consequence, the compressive strength, Vickers hardness and tensile strength of the scaffold were enhanced by 22.7%, 58.8% and 17.6%, respectively. Besides, the cells exhibited good attachment, spreading and proliferation on the scaffold. This study demonstrated that PLLA/CNTs scaffold was a promising candidate as bone implant.
Yield and Physicochemical Properties of Soluble Dietary Fiber Extracted from Untreated and Steam Explosion-Treated Black Soybean Hull
Authors: Shen Meng , Ge Yunfei , Kang Ziyue , Quan Zhigang , Wang Juan , Xiao Jinling , Wang Weihao , Cao Longkui
Published: December 2019

Black soybean hull was subjected to steam explosion (SE) treatment under different conditions to improve the yield and properties of soluble dietary fiber (SDF) extract. Optimal conditions for SE treatment were found to be moisture content of 15%, pressure level of 1.0 MPa, and treatment time of 80 s. Under these conditions, the yield of SDF increased from 10.20% to 17.49%. In addition, structural and functional properties of SDF from untreated and SE-treated black soybean hull were investigated. Soluble dietary fiber extracted from SE-treated hull exhibited lower molecular weight and improved functional properties, such as cholesterol-binding capacity, when compared to SDF extracted from untreated soybean hull. In addition, SDF extracted from SE-treated black soybean hull showed a rough surface structure, while a smooth surface structure was found for SDF extracted from the untreated hull. The obtained results indicate that SE treatment can be successfully used to enhance the yield and the property of yolk cholesterol absorption of SDF adsorption of yolk cholesterol functional properties of SDF from black soybean hull.
Impact of TCR Diversity on the Development of Transplanted or Chemically Induced Tumors
Authors: Schreiber Karin , Karrison Theodore G. , Wolf Steven P. , Kiyotani Kazuma , Steiner Madeline , Littmann Eric R. , Pamer Eric G. , Kammertoens Thomas , Schreiber Hans , Leisegang Matthias
Published: December 2019

Burnet postulated that the diversity of T-cell receptors (TCR) allows T cells to protect against the development of cancers that display antigens with a similar, seemingly endless diversity. To test this hypothesis, we developed a strategy in which a single breeding pair of mice gives rise to four groups of sibling mice. Three of the four groups had a similar number of CD8+ T cells, but TCR diversity was either broad, significantly reduced, or absent when expressing only one type of TCR. The fourth group had no T cells. All mice shared the same housing, and, therefore, their microbial environment was similar. Only slight differences in the intestinal flora were observed under these conditions. An undisturbed broad TCR repertoire was required for the rejection of inoculated cancers displaying the natural antigenic heterogeneity of primary tumors, whereas even one type of TCR was sufficient to protect against artificial cancers stably expressing cognate antigens. The three groups of mice with limited or no TCR repertoire showed an increased risk of developing primary tumors after chemical induction. However, the risk of early death or morbidity in these cohorts of mice was significantly higher than in mice with a diverse TCR repertoire, and it remains unknown whether mice with reduced TCR diversity, who died early without cancer, would have developed tumors with higher, lower, or equal probability after induction. Together, TCR diversity seems crucial to overcome the natural genetic instability of cancers and their antigenic heterogeneity, which impacts the design of cellular therapies.
The Prognostic Value of Soluble ST2 in Maintenance Hemodialysis Patients: A Meta-Analysis
Authors: Wang Shuang , Wei Fang , Chen Haiyan , Wang Zhe , Zhang Ruining , Jiang Aili
Published: December 2019

Background: Much controversy remains in the literature with respect to whether soluble suppression of tumorigenicity 2 (sST2) can serve to predict all-cause death in patients undergoing maintenance hemodialysis (MHD). This meta-analysis therefore sought to analyze extant datasets exploring the association between these 2 variables in MHD patients in order to draw relevant conclusions. Methods: Articles published through December 2018 in PubMed and Embase were independently reviewed by 2 authors to identify relevant articles, and STATA 12.0 was used for statistical analyses of relevant results and study parameters. Results: In total, we identified 4 relevant studies that were incorporated into this meta-analysis. These studies included a total of 1,924 participants (60% male, mean follow-up 911 days). The combined study results suggested that increased levels of sST2 were significantly linked to a 2.23 fold rise in all-cause mortality (hazard ratio [HR] 2.23, 95% CI 1.81–2.75). Subgroup analyses confirmed that this same association was true in patients undergoing hemodialysis (HR 2.17, 95% CI 1.74–2.71), which indicated that the increased levels of sST2 were significantly linked to a 2.17 fold rise in all-cause mortality. Conclusions: This analysis suggests that there is a significant link between elevated levels of sST2 and death in patients undergoing MHD. Further large-scale trials, however, will be needed to fully validate these findings and their clinical relevance.
Idiopathic Pulmonary Fibrosis: Best Practice in Monitoring and Managing a Relentless Fibrotic Disease
Authors: Wuyts Wim A. , Wijsenbeek Marlies , Bondue Benjamin , Bouros Demosthenes , Bresser Paul , Robalo Cordeiro Carlos  , Hilberg Ole , Magnusson Jesper , Manali Effrosyni D. , Morais António , Papiris Spyridon , Shaker Saher , Veltkamp Marcel , Bendstrup Elisabeth
Published: December 2019

Idiopathic pulmonary fibrosis (IPF) is a fibrosing interstitial lung disease that is, by definition, progressive. Progression of IPF is reflected by a decline in lung function, worsening of dyspnea and exercise capacity, and deterioration in health-related quality of life. In the short term, the course of disease for an individual patient is impossible to predict. A period of relative stability in forced vital capacity (FVC) does not mean that FVC will remain stable in the near future. Frequent monitoring using multiple assessments, not limited to pulmonary function tests, is important to evaluate disease progression in individual patients and ensure that patients are offered appropriate care. Optimal management of IPF requires a multidimensional approach, including both pharmacological therapy to slow decline in lung function and supportive care to preserve patients’ quality of life.
An Unconventional Diagnostic Method for Cryptosporidial Enteritis in a Healthy Host: Never Call It Quits!
Authors: Amarnath Shivantha , El Imad Cheikh Talal , Ebare Kingsley , Wu Hueizhi , Mulrooney Stephen
Published: December 2019

Cryptosporidial enteritis has a rising incidence in the USA, mostly affecting immunocompromised individuals and children. It has a self-limiting course in healthy hosts. Herein, we present a unique case of a healthy middle-aged female who presented with a 1-month history of voluminous watery diarrhea and acute blood loss anemia. Cryptosporidial enteritis was diagnosed based on endoscopy with biopsy-proven evidence of 2 jejunal peptic ulcers infected with Cryptosporidiumspp. that was originally missed on routine stool culture, ova and parasite tests. The patient was successfully treated with nitazoxanide,and eradication of the protozoan was also confirmed on repeat endoscopic biopsies of the ulcer that were carried out 6 months later. To our knowledge, this is the first case to be reported in the literature with infective colonization of peptic ulcers with Cryptosporidiumspp.with consequent systemic symptoms.
EAGEN and UEG: A Long-Term Partnership with a Focus on Education
Authors: Hammer Heinz F.
Published: December 2019

EAGEN is one of the 7 founding sisters and an ordinary member society of UEG. EAGEN members have contributed significantly to the development of UEG in leading positions within UEG. The significant impact of UEG board members on science, education, and organization of European gastroenterology is demonstrated by the remarkable list of EAGEN board members who have received major UEG awards or prizes. The focus of EAGEN within UEG has been on postgraduate education. In this function, EAGEN has developed educational formats which after their establishment were handed over to UEG. EAGEN has established itself as an important provider of education in gastroenterology including pancreatic-biliary diseases, GI oncology, endoscopic procedures, nutrition, and intestinal microbiology. EAGEN has the goal to identify educational needs, fill existing gaps in medical education, and advance the quality of education. To fulfill these tasks, EAGEN is in close cooperation with the UEG education committee and UEG member societies. EAGEN puts a focus on reduction of pan-European health inequalities, provision of equal opportunity, promotion of young talent, and improvement of clinical standards and guidelines.
Intercellular Conduction Optimizes Arterial Network Function and Conserves Blood Flow Homeostasis During Cerebrovascular Challenges
Authors: Zechariah Anil , Tran Cam Ha T. , Hald Bjorn O. , Sandow Shaun L. , Sancho Maria , Kim Michelle Sun Mi , Fabris Sergio , Tuor Ursula I. , Gordon Grant R.J. , Welsh Donald G.
Published: December 2019

Objective:

Cerebral arterial networks match blood flow delivery with neural activity. Neurovascular response begins with a stimulus and a focal change in vessel diameter, which by themselves is inconsequential to blood flow magnitude, until they spread and alter the contractile status of neighboring arterial segments. We sought to define the mechanisms underlying integrated vascular behavior and considered the role of intercellular electrical signaling in this phenomenon.

Approach and Results:

Electron microscopic and histochemical analysis revealed the structural coupling of cerebrovascular cells and the expression of gap junctional subunits at the cell interfaces, enabling intercellular signaling among vascular cells. Indeed, robust vasomotor conduction was detected in human and mice cerebral arteries after focal vessel stimulation: a response attributed to endothelial gap junctional communication, as its genetic alteration attenuated this behavior. Conducted responses were observed to ascend from the penetrating arterioles, influencing the contractile status of cortical surface vessels, in a simulated model of cerebral arterial network. Ascending responses recognized in vivo after whisker stimulation were significantly attenuated in mice with altered endothelial gap junctional signaling confirming that gap junctional communication drives integrated vessel responses. The diminishment in vascular communication also impaired the critical ability of the cerebral vasculature to maintain blood flow homeostasis and hence tissue viability after stroke.

Conclusions:

Our findings highlight the integral role of intercellular electrical signaling in transcribing focal stimuli into coordinated changes in cerebrovascular contractile activity and expose, a hitherto unknown mechanism for flow regulation after stroke.
Shear Stress Regulation of Endothelial Glycocalyx Structure Is Determined by Glucobiosynthesis
Authors: Wang Gangqi , Kostidis Sarantos , Tiemeier Gesa L. , Sol Wendy M.P.J. , de Vries Margreet R. , Giera Martin , Carmeliet Peter , van den Berg Bernard M. , Rabelink Ton J.
Published: December 2019

Objective:

Endothelial cells exposed to laminar shear stress express a thick glycocalyx on their surface that plays an important role in reducing vascular permeability and endothelial anti-inflammatory, antithrombotic, and antiangiogenic properties. Production and maintenance of this glycocalyx layer is dependent on cellular carbohydrate synthesis, but its regulation is still unknown.

Approach and Results:

Here, we show that biosynthesis of the major structural component of the endothelial glycocalyx, hyaluronan, is regulated by shear. Both in vitro as well as in in vivo, hyaluronan expression on the endothelial surface is increased on laminar shear and reduced when exposed to oscillatory flow, which is regulated by KLF2 (Krüppel-like Factor 2). Using a CRISPR-CAS9 edited small tetracysteine tag to endogenous HAS2 (hyaluronan synthase 2), we demonstrated increased translocation of HAS2 to the endothelial cell membrane during laminar shear. Hyaluronan production by HAS2 was shown to be further driven by availability of the hyaluronan substrates UDP-glucosamine and UDP-glucuronic acid. KLF2 inhibits endothelial glycolysis and allows for glucose intermediates to shuttle into the hexosamine- and glucuronic acid biosynthesis pathways, as measured using nuclear magnetic resonance analysis in combination with
13
C-labeled glucose.

Conclusions:

These data demonstrate how endothelial glycocalyx function and functional adaptation to shear is coupled to KLF2-mediated regulation of endothelial glycolysis.
Hybrid Coronary Revascularization Versus Off‐Pump Coronary Artery Bypass Grafting: Comparative Effectiveness Analysis With Long‐Term Follow‐up
Authors: Hage Ali , Giambruno Vincenzo , Jones Philip , Chu Michael W. , Fox Stephanie , Teefy Patrick , Lavi Shahar , Bainbridge Daniel , Harle Christopher , Iglesias Ivan , Dobkowski Woijtecj , Kiaii Bob
Published: December 2019

Background

Hybrid coronary revascularization (
HCR
) involves the integration of coronary artery bypass grafting (
CABG
) and percutaneous coronary intervention to treat multivessel coronary artery disease. Our objective was to perform a comparative analysis with long‐term follow‐up between
HCR
and conventional off‐pump
CABG
.

Methods and Results

We compared all double off‐pump
CABG
(n=216) and
HCR
(n=147; robotic‐assisted minimally invasive direct
CABG
of the left internal thoracic artery to the left anterior descending artery and percutaneous coronary intervention to one of the non–left anterior descending vessels) performed at a single institution between March 2004 and November 2015. To adjust for the selection bias of receiving either off‐pump
CABG
or
HCR
, we performed a propensity score analysis using inverse‐probability weighting. Both groups had similar results in terms of re‐exploration for bleeding, perioperative myocardial infarction, stroke, blood transfusion, in‐hospital mortality, and intensive care unit length of stay.
HCR
was associated with a higher in‐hospital reintervention rate (
CABG
0% versus
HCR
3.4%;
P
=0.03), lower prolonged mechanical ventilation (>24 hours) rate (4% versus 0.7%;
P
=0.02), and shorter hospital length of stay (8.1±5.8  versus 4.5±2.1 days;
P
<0.001). After a median follow‐up of 81 (48–113) months for the off‐pump
CABG
and 96 (53–115) months for
HCR
, the
HCR
group of patients had a trend toward improved survival (85% versus 96%;
P
=0.054). Freedom from any form of revascularization was similar between the 2 groups (92% versus 91%;
P
=0.80). Freedom from angina was better in the
HCR
group (73% versus 90%;
P
<0.001).

Conclusions

HCR
seems to provide, in selected patients, a shorter postoperative recovery, with similar excellent short‐ and long‐term outcomes when compared with standard off‐pump
CABG
.
Intravenously Transplanted Human Multilineage-Differentiating Stress-Enduring Cells Afford Brain Repair in a Mouse Lacunar Stroke Model
Authors: Abe Takatsugu , Aburakawa Daiki , Niizuma Kuniyasu , Iwabuchi Naoya , Kajitani Takumi , Wakao Shohei , Kushida Yoshihiro , Dezawa Mari , Borlongan Cesar V. , Tominaga Teiji
Published: December 2019

Background and Purpose—

Multilineage-differentiating stress-enduring cells are endogenous nontumorigenic reparative pluripotent-like stem cells found in bone marrow, peripheral blood, and connective tissues. Topically administered human multilineage-differentiating stress-enduring cells into rat/mouse stroke models differentiated into neural cells and promoted clinically relevant functional recovery. However, critical questions on the appropriate timing and dose, and safety of the less invasive intravenous administration of clinical-grade multilineage-differentiating stress-enduring cell–based product CL2020 remain unanswered.

Methods—

Using an immunodeficient mouse lacunar model, CL2020 was administered via the cervical vein in different doses (high dose=5×10
4
cells/body; medium dose=1×10
4
cells/body; low dose=5×10
3
cells/body) at subacute phase (≈9 days after onset) and chronic phase (≈30 days). Cylinder test, depletion of human cells by diphtheria toxin administration, immunohistochemistry, and human specific-genome detection were performed.

Results—

Tumorigenesis and adverse effects were not detected for up to 22 weeks. The high-dose group displayed significant functional recovery compared with the vehicle group in cylinder test in subacute-phase–treated and chronic-phase–treated animals after 6 weeks and 8 weeks post-injection, respectively. In the high-dose group of subacute-phase–treated animals, robust and stable recovery in cylinder test persisted up to 22 weeks compared with the vehicle group. In both groups, intraperitoneal injection of diphtheria toxin abrogated the functional recovery. Anti-human mitochondria revealed CL2020 distributed mainly in the peri-infarct area at 1, 10, and 22 weeks and expressed NeuN (neuronal nuclei)- and MAP-2 (microtubule-associated protein-2)-immunoreactivity.

Conclusions—

Intravenously administered CL2020 was safe, migrated to the peri-infarct area, and afforded functional recovery in experimental stroke.
External Performance of the HAVOC Score for the Prediction of New Incident Atrial Fibrillation
Authors: Ntaios George , Perlepe Kalliopi , Lambrou Dimitrios , Sirimarco Gaia , Strambo Davide , Eskandari Ashraf , Karagkiozi Efstathia , Vemmou Anastasia , Koroboki Eleni , Manios Efstathios , Makaritsis Konstantinos , Vemmos Konstantinos , Michel Patrik
Published: December 2019

Background and Purpose—

The HAVOC score (hypertension, age, valvular heart disease, peripheral vascular disease, obesity, congestive heart failure, coronary artery disease) was proposed for the prediction of atrial fibrillation (AF) after cryptogenic stroke. It showed good model discrimination (area under the curve, 0.77). Only 2.5% of patients with a low-risk HAVOC score (ie, 0–4) were diagnosed with new incident AF. We aimed to assess its performance in an external cohort of patients with embolic stroke of undetermined source.

Methods—

In the AF-embolic stroke of undetermined source dataset, we assessed the discriminatory power, calibration, specificity, negative predictive value, and accuracy of the HAVOC score to predict new incident AF. Patients with a HAVOC score of 0 to 4 were considered as low-risk, as proposed in its original publication.

Results—

In 658 embolic stroke of undetermined source patients (median age, 67 years; 44% women), the median HAVOC score was 2 (interquartile range, 3). There were 540 (82%) patients with a HAVOC score of 0 to 4 and 118 (18%) with a score of ≥5. New incident AF was diagnosed in 95 (14.4%) patients (28.8% among patients with HAVOC score ≥5 and 11.3% among patients with HAVOC score 0–4 [age- and sex-adjusted odds ratio, 2.29 (95% CI, 1.37–3.82)]). The specificity of low-risk HAVOC score to identify patients without new incident AF was 88.7%. The negative predictive value of low-risk HAVOC score was 85.1%. The accuracy was 78.0%, and the area under the curve was 68.7% (95% CI, 62.1%–73.3%).

Conclusions—

The previously reported low rate of AF among embolic stroke of undetermined source patients with low-risk HAVOC score was not confirmed in our cohort. Further assessment of the HAVOC score is warranted before it is routinely implemented in clinical practice.
Herodian and the Crisis of Emperorship, 235-238 AD
Authors: Davenport Caillan , Mallan Christopher
Published: December 2019

This article examines Herodian’s portrayal of the rise and fall of Roman emperors and usurpers in Books 7 and 8 of his History (covering the years 235-238 AD). Herodian’s narrative provides its readers with a perceptive account of the challenges faced by Rome’s rulers during the middle decades of the third century AD. Emperors had to defend the frontiers while cultivating the support of the army, the senate, and the people of Rome and the provinces. The historian explores how potential candidates for the purple were likely to succeed or fail based on the support, or lack thereof, of these key constituencies. He shows how even theoretically promising experiments in imperial rule, such as the joint reign of Pupienus and Balbinus, were ultimately doomed to fail because the emperors did not possess a deep and broad consensus among all elements of the Roman state.
Metal Mirrors from Altai Sites of the Xiongnu Time
Authors: Tishkin Alexey A. , Seregin Nikolay N.
Published: December 2019

Metal mirrors are important indicators when reconstructing the history of the ancient peoples of Altai on the basis of archaeological materials. Among the latter there are imported products, recorded in the mounds of the Xiongnu time (2nd century BC – 1st century AD). The article gives an overview of the results of a comprehensive study of the mirrors. Only one mirror was found intact, and the rest are represented by fragments. This collection of 19 archaeological items is divided into two groups, reflecting the direction of contacts of the Altai population in this period. The first demonstrates Chinese products that could have entered the region indirectly from the Xiongnu who dominated Inner Asia. Some of them were made in the previous period, but were used for a long time. The analyses of metal alloys from the Yaloman-II site supplements the conclusions made during the visual examination. The second group, through its origin, is associated with the cultures of the so-called Sarmatian circle, whose sites were located to the west of the Altai. A separate section of the article is devoted to a discussion of reconstruction of some aspects of the social history of the nomads and their world.