bluuebunny/crossref_metadata_2025 huggingface dataset:
Microbial Contribution to the Human Metabolome: Implications for Health and Disease
Authors: Van Treuren William , Dodd Dylan
Published: October 2019

The human gastrointestinal tract is home to an incredibly dense population of microbes. These microbes employ unique strategies to capture energy in this largely anaerobic environment. In the process of breaking down dietary- and host-derived substrates, the gut microbiota produce a broad range of metabolic products that accumulate to high levels in the gut. Increasingly, studies are revealing that these chemicals impact host biology, either by acting on cells within the gastrointestinal tract or entering circulation and exerting their effects at distal sites within the body. Given the high level of functional diversity in the gut microbiome and the varied diets that we consume, the repertoire of microbiota-derived molecules within our bodies varies dramatically across individuals. Thus, the microbes in our gut and the metabolic end products they produce represent a phenotypic lever that we can potentially control to develop new therapeutics for personalized medicine. Here, we review current understanding of how microbes in the gastrointestinal tract contribute to the molecules within our gut and those that circulate within our bodies. We also highlight examples of how these molecules affect host physiology and discuss potential strategies for controlling their production to promote human health and to treat disease.
Molecular Pathogenesis of Membranous Nephropathy
Authors: Ronco Pierre , Debiec Hanna
Published: October 2019

Membranous nephropathy is a noninflammatory autoimmune disease of the kidney glomerulus, characterized by the formation of immune deposits, complement-mediated proteinuria, and risk of renal failure. Considerable advances in understanding the molecular pathogenesis have occurred with the identification of several antigens [neutral endopeptidase, phospholipase A2 receptor (PLA2R), thrombospondin domain-containing 7A (THSD7A)] in cases arising from the neonatal period to adulthood and the characterization of antibody-binding domains (that is, epitopes). Immunization against PLA2R occurs in 70% to 80% of adult cases. The development of highly specific and sensitive assays of circulating antibodies has induced a paradigm shift in diagnosis and treatment monitoring. In addition, several interacting loci in HLA-DQ, HLA-DR, and PLA2R1, as well as classical human leukocyte antigen (HLA)-D alleles have been identified as being risk factors, depending on a patient's ethnicity. Additionally, mechanisms of antibody pathogenicity and pathways of complement activation are now better understood. Further research is mandatory for designing new therapeutic strategies, including the identifying triggering events, the molecular bases of remission and progression, and the T cell epitopes involved.
Comparative molecular analysis of endurance exercise in vivo with electrically stimulated in vitro myotube contraction
Authors: Son Young Hoon , Lee Seung-Min , Lee Seol Hee , Yoon Jong Hyeon , Kang Jae Sook , Yang Yong Ryoul , Kwon Ki-Sun
Published: October 2019

Exercise has positive effects on health and improves a variety of disease conditions. An in vitro model of exercise has been developed to better understand its molecular mechanisms. While various conditions have been used to mimic in vivo exercise, no specific conditions have matched a specific type of in vivo exercise. Here, we screened various electrical pulse stimulation (EPS) conditions and compared the molecular events under each condition in myotube culture with that obtained under voluntary wheel running (VWR), a mild endurance exercise, in mice. Both EPS and VWR upregulated the mRNA levels of genes involved in the slow-type twitch ( Myh7 and Myh2) and myogenesis ( Myod and Myog) and increased the protein expression of peroxisome proliferator-activated receptor-γ coactivator-1α, which is involved in mitochondrial biogenesis. These changes were accompanied by activation of p38 and AMPK. However, neither condition induced the expression of muscle-specific E3 ligases such as MAFbx and MuRF1. Both EPS and VWR consistently induced antioxidant genes such as Sod3 and Gpx4 but did not cause similar changes in the expression levels of the calcium channel/pump-related genes Ryr and Serca. Furthermore, both EPS and VWR reduced glycogen levels but not lactate levels as assessed in post-EPS culture medium and post-VWR serum, respectively. Thus we identified an in vitro EPS condition that effectively mimics VWR in mice, which can facilitate further studies of the detailed molecular mechanisms of endurance exercise in the absence of interference from multiple tissues and organs.

NEW & NOTEWORTHY This study establishes an optimal condition for electrical pulse stimulation (EPS) in myotubes that shows a similar molecular signature as voluntary wheel running. The specific EPS condition 1) upregulates the mRNA of slow-twitch muscle components and myogenic transcription factors, 2) induces antioxidant genes without any muscle damage, and 3) promotes peroxisome proliferator-activated receptor-γ coactivator-1α and its upstream regulators involved in mitochondrial biogenesis.
Effect of β-alanine supplementation during high-intensity interval training on repeated sprint ability performance and neuromuscular fatigue
Authors: Milioni Fabio , de Poli Rodrigo Araújo Bonetti , Saunders Bryan , Gualano Bruno , da Rocha Alisson L. , Sanchez Ramos da Silva Adelino , Muller Paulo de Tarso Guerrero , Zagatto Alessandro Moura
Published: October 2019

The study investigated the influence of β-alanine supplementation during a high-intensity interval training (HIIT) program on repeated sprint ability (RSA) performance. This study was randomized, double-blinded, and placebo controlled. Eighteen men performed an incremental running test until exhaustion (TINC) at baseline and followed by 4-wk HIIT (10 × 1-min runs 90% maximal TINCvelocity [1-min recovery]). Then, participants were randomized into two groups and performed a 6-wk HIIT associated with supplementation of 6.4 g/day of β-alanine (Gβ) or dextrose (placebo group; GP). Pre- and post-6-wk HIIT + supplementation, participants performed the following tests: 1) TINC; 2) supramaximal running test; and 3) 2 × 6 × 35-m sprints (RSA). Before and immediately after RSA, neuromuscular function was assessed by vertical jumps, maximal isometric voluntary contractions of knee extension, and neuromuscular electrical stimulations. Muscle biopsies were performed to determine muscle carnosine content, muscle buffering capacity in vitro (βmin vitro), and content of phosphofructokinase (PFK), monocarboxylate transporter 4 (MCT4), and hypoxia-inducible factor-1α (HIF-1α). Both groups showed a significant time effect for maximal oxygen uptake (Gβ: 6.2 ± 3.6% and GP: 6.5 ± 4.2%; P > 0.01); only Gβ showed a time effect for total (−3.0 ± 2.0%; P = 0.001) and best (−3.3 ± 3.0%; P = 0.03) RSA times. A group-by-time interaction was shown after HIIT + Supplementation for muscle carnosine (Gβ: 34.4 ± 2.3 mmol·kg−1·dm−1and GP: 20.7 ± 3.0 mmol·kg−1·dm−1; P = 0.003) and neuromuscular voluntary activation after RSA (Gβ: 87.2 ± 3.3% and GP: 78.9 ± 12.4%; P = 0.02). No time effect or group-by-time interaction was shown for supramaximal running test performance, βm, and content of PFK, MCT4, and HIF-1α. In summary, β-alanine supplementation during HIIT increased muscle carnosine and attenuated neuromuscular fatigue, which may contribute to an enhancement of RSA performance.

NEW & NOTEWORTHY β-Alanine supplementation during a high-intensity interval training program increased repeated sprint performance. The improvement of muscle carnosine content induced by β-alanine supplementation may have contributed to an attenuation of central fatigue during repeated sprint. Overall, β-alanine supplementation may be a useful dietary intervention to prevent fatigue.
Descending octopaminergic neurons modulate sensory-evoked activity of thoracic motor neurons in stick insects
Authors: Stolz Thomas , Diesner Max , Neupert Susanne , Hess Martin E. , Delgado-Betancourt Estefania , Pflüger Hans-Joachim , Schmidt Joachim
Published: October 2019

Neuromodulatory neurons located in the brain can influence activity in locomotor networks residing in the spinal cord or ventral nerve cords of invertebrates. How inputs to and outputs of neuromodulatory descending neurons affect walking activity is largely unknown. With the use of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and immunohistochemistry, we show that a population of dorsal unpaired median (DUM) neurons descending from the gnathal ganglion to thoracic ganglia of the stick insect Carausius morosus contains the neuromodulatory amine octopamine. These neurons receive excitatory input coupled to the legs’ stance phases during treadmill walking. Inputs did not result from connections with thoracic central pattern-generating networks, but, instead, most are derived from leg load sensors. In excitatory and inhibitory retractor coxae motor neurons, spike activity in the descending DUM (desDUM) neurons increased depolarizing reflexlike responses to stimulation of leg load sensors. In these motor neurons, descending octopaminergic neurons apparently functioned as components of a positive feedback network mainly driven by load-detecting sense organs. Reflexlike responses in excitatory extensor tibiae motor neurons evoked by stimulations of a femur-tibia movement sensor either are increased or decreased or were not affected by the activity of the descending neurons, indicating different functions of desDUM neurons. The increase in motor neuron activity is often accompanied by a reflex reversal, which is characteristic for actively moving animals. Our findings indicate that some descending octopaminergic neurons can facilitate motor activity during walking and support a sensory-motor state necessary for active leg movements.

NEW & NOTEWORTHY We investigated the role of descending octopaminergic neurons in the gnathal ganglion of stick insects. The neurons become active during walking, mainly triggered by input from load sensors in the legs rather than pattern-generating networks. This report provides novel evidence that octopamine released by descending neurons on stimulation of leg sense organs contributes to the modulation of leg sensory-evoked activity in a leg motor control system.
A Blockchain-Based Platform for Consent Management of Personal Data Processing in the IoT Ecosystem
Authors: Rantos Konstantinos , Drosatos George , Kritsas Antonios , Ilioudis Christos , Papanikolaou Alexandros , Filippidis Adam P.
Published: October 2019

In the Internet of Things (IoT) ecosystem, the volume of data generated by devices in the user’s environment is continually increasing and becoming of particular value. In such an environment the average user is bound to face considerable difficulties in understanding the size and scope of his/her collected data. However, the provisions of the European General Data Protection Regulation (GDPR) require data subjects to be able to control their personal data, be informed, and consent to its processing in an intelligible manner. This paper proposes ADVOCATE platform, a user-centric solution that allows data subjects to easily manage consents regarding access to their personal data in the IoT ecosystem. The proposed platform also assists data controllers to meet GDPR requirements, such as informing data subjects in a transparent and unambiguous manner about the data they will manage, the processing purposes, and periods. The integrity of personal data processing consents and the immutable versioning control of them are protected by a blockchain infrastructure. Finally, the paper provides a prototype implementation of the proposed platform that supports the main consents management functionality.
Provably Secure Identity-Based Encryption and Signature over Cyclotomic Fields
Authors: Wang Yang , Wang Mingqiang , Zou Jingdan , Xu Jin , Wang Jing
Published: October 2019

Identity-based cryptography is a type of public key cryptography with simple key management procedures. To our knowledge, till now, the existing identity-based cryptography based on NTRU is all over power-of-2 cyclotomic rings. Whether there is provably secure identity-based cryptography over more general fields is still open. In this paper, with the help of the results of collision resistance preimage sampleable functions (CRPSF) over cyclotomic fields, we give concrete constructions of provably secure identity-based encryption schemes (IBE) and identity-based signature schemes (IBS) based on NTRU over any cyclotomic field. Our IBE schemes are provably secure under adaptive chosen-plaintext and adaptive chosen-identity attacks, meanwhile, our IBS schemes are existentially unforgeable against adaptively chosen message and adaptively chosen identity attacks for any probabilistic polynomial time (PPT) adversary in the random oracle model. The securities of both schemes are based on the worst-case approximate shortest independent vectors problem (SIVPγ) over corresponding ideal lattices. The secret key size of our IBE (IBS) scheme is short—only one (two) ring element(s). The ciphertext (signature) is also short—only two (three) ring elements. Meanwhile, as the case of NTRUEncrypt, our IBE scheme could encrypt n bits in each encryption process. These properties may make our schemes have more advantages for some IoT applications over postquantum world in theory.
Healthcare Data Security Technology: HIPAA Compliance
Authors: Mbonihankuye Scholas , Nkunzimana Athanase , Ndagijimana Ange
Published: October 2019

Information technology (IT) plays an increasingly important and prominent role in the health sector. Data security is more important than ever to the healthcare industry and in world in general. The number of data breaches compromising confidential healthcare data is on the rise. For data security, cloud computing is very useful for securing data. Due to data storage issue, there is a need to use the electronic communication, and a number of methods have been developed for data security technology. Health Insurance Portability and Accountability Act (HIPAA) is one of the methods that can help in healthcare research. On stored database of patient in hospital or clinic, we can develop a conservational and analytical method so as to keep the medical records of the patients in a well-preserved and adequate environment. The method includes the improvement of working possibilities by delivering all the details necessary for the patient. All the information must be identified clearly. The protection of the privacy of the patients and the security of their information are the most imperative obstacles to obtain their intakes when considering the adoption of useful health data in the electronic field of healthcare industries.
Properties of Asphalt Mixtures Using Reclaimed Asphalt Containing Polymer-Modified Binder and Technicoeconomical Considerations of Their Use
Authors: Mikolaj Jan , Schlosser Frantisek , Remek Lubos , Pitoňák Martin , Šrámek Juraj
Published: October 2019

The article summarises findings from laboratory testing of asphalt mixtures using reclaimed asphalt containing polymer-modified binder and subsequent technicoeconomical considerations of their use in pavement management system. Tested mixtures had 0%, 15%, and 40% content of reclaimed asphalt (RA) containing polymer-modified bitumen (PMB) obtained by milling from surfacing layers of existing PA, AC11, and SMA11 pavement layers. A complete description of these mixtures is given, and testing methods used are described. The mixtures were tested for air void content, ITSR water sensitivity test, plastic deformation wheel tracking test, stiffness of the tested mixtures, and two-point bending test to ascertain fatigue. Concise and succinct conclusions from laboratory testing are derived and used as an input in the second part of the article. It is found that the addition of RA containing PMB increased stiffness modulus of the final mixture, which increases resistance to plastic deformation and leads to higher brittleness at low temperatures. It is found that virgin PMB also increases fatigue resistance as opposed to PMB content from reclaimed materials. In the second part of the article, findings from laboratory testing are addressed in the context of their practical use in pavement management. The key element identified, having a direct impact on pavement performance models, was the stiffness modulus for mixtures with different PMB-reclaimed asphalt contents. A method is described to evaluate pavement construction properties related to wearing course materials via the pavement performance model. Practical use of this method is described and applied in a case study. In this case study, the proposed method is used to evaluate the issues regarding practical use of asphalt mixtures with different ratios of reclaimed asphalt containing PMB and economic implications of their use. It is found that pavement performance of surfacing mixtures with reclaimed asphalt containing PMB is significantly better for plastic deformation at the cost of earlier initiation and progression of surface distress due to cracking and potholing. This paper suggests that due to cracking and potholing, periodic maintenance costs increase for pavements with reclaimed asphalt material containing PMB; however, they are outweighed by lower procurement cost and longer life expectancy due to slower plastic deformation of the pavement.
A Case of a Spinal Extradural Arachnoid Cyst
Authors: Kojimahara Yousuke , Tsuge Shintaro , Hasegawa Keiji , Fukutake Katsunori , Nakamura Kazumasa , Wada Akihito , Takahashi Hiroshi
Published: October 2019

The patient was a 49-year-old woman with a chief complaint of hip and buttock pain that had persisted for 3 years. She visited our hospital for aggravation of the pain. Percussion tenderness of the spinous process was observed and a T1-low, T2-high cystic lesion was detected on the dorsal side of the dural canal at the 12th thoracic vertebral level on MRI performed by a previous physician. Plane CT showed severe scalloping at the same level. During laminectomy for the 11th and 12th thoracic vertebrae, a cystic lesion of about 60×25 mm was noted on the dorsal side of the dural canal, with a communication pathway with the cyst present near the left 12th nerve root bifurcation. This pathway was ligated and the cyst was excised. The histopathological diagnosis was an arachnoid cyst. Pain improved after surgery, and as of 10 months after surgery, the cystic lesion has not recurred. A spinal extradural arachnoid cyst (SEAC) is a relatively rare disease. This case shows that surgical ligation of a communicating tract and cystectomy are necessary and contrast-enhanced CT was useful for the identification of the position of the communication pathway before surgery.
Plasma Betatrophin Levels and Carotid Atherosclerosis
Authors: Niki Hanako , Kishimoto Yoshimi , Saita Emi , Ohmori Reiko , Kondo Kazuo , Momiyama Yukihiko
Published: October 2019

Aims. Betatrophin is a recently identified circulating adipokine that may affect lipid and glucose metabolism. However, the association between plasma betatrophin levels and carotid atherosclerosis has not been elucidated. Methods. We investigated plasma betatrophin levels in 153 subjects undergoing carotid ultrasonography. The severity of plaque was evaluated as plaque score. Results. Of the 153 subjects, plaque was found in 63 (41%). Plasma betatrophin levels were higher in 63 subjects with plaque than in 90 without plaque (median 906 vs. 729 pg/mL, P<0.025). A stepwise increase in betatrophin levels was found depending on the plaque score: 729 pg/mL in score=0 (n=90), 802 pg/mL in score=1 (n=31), and 978 pg/mL in score≥2 (n=32) (P<0.01). In particular, betatrophin levels in subjects with score≥2 were higher than in those with score=0 (P<0.05). Moreover, betatrophin levels correlated with plaque score (r=0.23, P<0.01), but no significant correlation was found between betatrophin levels and triglyceride or HbA1c levels. The percentage of subjects with betatrophin>800 pg/mL was higher in subjects with plaque than in those without plaque (65% vs. 44%) and was highest in score≥2 (78%) (P<0.005). In the multivariate analysis, betatrophin level was not a significant factor for the presence of plaque but was a significant factor for plaque score≥2, independent of atherosclerotic risk factors. The odds ratio for score≥2 was 4.9 (95% CI=1.9-12.8) for betatrophin>800 pg/mL. Conclusions. Plasma betatrophin levels were found to be high in subjects with carotid plaque and to be associated with the severity of plaque. Betatrophin may play a role in the progression of carotid atherosclerosis.
Tuberculosis Presenting as Isolated Wrist Swelling: A Case Report and Review of Literature
Authors: Basnayake Oshan , Nihaj Ahamed , Pitagampalage Ranji , Mendis Harsha
Published: October 2019

Background. Tuberculosis is a common disease entity in South East Asian countries with a significant global burden. An extra skeletal manifestation such as monoarticular TB is common, but isolated involvement of the wrist is rare. Case Summary. A 53-year-old Sri Lankan male with long-standing diabetes presented with an isolated hand swelling for a 7-month duration. His initial imaging and MRI showed multiple destructive lesions in the carpal bones, surrounding focal fluid collections and found to have caseous material intraoperatively. His histology and microbiological studies were positive for TB with no other concurrent evidence of TB elsewhere. Conclusion. Different presentations of tuberculosis should be considered when patients are presenting with atypical clinical and initial basic investigation findings in relation to monoarticular pathologies.
Antiplasmodial Activity Assay of 3-Chloro-4-(4-chlorophenoxy) Aniline Combinations with Artesunate or Chloroquine In Vitro and in a Mouse Model
Authors: Wekesa Sifuna Martin , Wambui Milka , Kang’ethe Nganga Joseph , Wainaina Kariuki Daniel , Kimani Francis Thuo , Muregi Francis Wamakima
Published: October 2019

Malaria is the eighth highest contributor to global disease burden with 212 million cases and 429,000 deaths reported in 2015. There is an urgent need to develop multiple target drug to curb growing resistance by Plasmodia due to use of single target drugs and lack of vaccines. Based on a previous study, 3-chloro-4-(4-chlorophenoxy) aniline (ANI) inhibits Plasmodia enoyl acyl carrier protein reductase. This study aimed at evaluating the antiplasmodial activity of ANI combinations with artesunate (AS) or chloroquine (CQ) against P. falciparum in vitro based on the semiautomated microdilution assay and P. berghei in vivo based on Peters’ 4-day test. Data were analysed by linear regression using version 5.5 of Statistica, 2000. From the results, on the one hand, a combination of 1.1 ng/ml AS and 3.3 μg/ml of ANI inhibited 50% growth of W2, while a combination of 0.8 ng/ml of AS and 2.6 μg/ml of ANI inhibited 50% growth of 3D7. On the other hand, a combination of 22 ng/ml CQ and 3.7 μg/ml of ANI inhibited 50% growth of W2, while a combination of 4.6 ng/ml CQ and 3.1 μg/ml of ANI inhibited 50% growth of 3D7. In in vivo assays, a combination of ED50 concentrations of AS and ANI cleared all parasites, while 1/2 and 1/4 ED50 combinations inhibited 67.0% and 35.4% parasite growth, respectively. ED50 combinations of CQ and ANI inhibited 81.0% growth of parasites, while 1/2 and 1/4 ED50 combinations inhibited 27.3% and 10.2% parasite growth. Assuming a linear relationship between percentage chemosuppression and combination ratios, only 0.88 mg/kg of AS combined with 1.68 mg/kg of ANI or 1.78 mg/kg of CQ with 3.15 mg/kg of ANI inhibited 50% parasite growth in vivo. ANI combinations with AS or CQ are thus potential antimalarial drug combinations if their clinical efficacy and safety are ascertained.
Free Vibration Analysis of Arbitrary‐Shaped Plates Based on the Improved Rayleigh–Ritz Method
Authors: Guo Wenjie , Feng Qingsong
Published: October 2019

In this investigation, an improved Rayleigh–Ritz method is put forward to analyze the free vibration characteristics of arbitrary‐shaped plates for the traditional Rayleigh–Ritz method which is difficult to solve. By expanding the domain of admissible functions out of the structural domain to form a rectangular domain, the admissible functions of arbitrary‐shaped plates can be described conveniently by selecting the appropriate admissible functions. Adopting the spring model to simulate the general boundary conditions, the problems of vibration of the arbitrary plate domain can be solved perfectly. Then, a numerical method is introduced to figure out the structure strain energy, kinetic energy, and elastic potential energy of the boundary. Finally, comparing the result with the simulation results and reference examples, the accuracy and convergence of this method are testified. Therefore, an effective new method is proposed for the guidance of the related research and practical engineering problems.
Comparison of Outcomes of Colorectal Polypectomy Using Traditional Snare and Rotary Snare: A Prospective Randomized Controlled Trial
Authors: Xu Lu , Zhang Zhixing , Xie Jiarong , Xu Lei , Wang Weihong
Published: October 2019

Background and Objective. The aim of the current study was to compare the efficacy and safety of polypectomy by using rotary snare vs. traditional snare during colonoscopy. Methods. A single-center randomized controlled trial, which included consecutive participants who were ≥18 years old and detected with polyp(s) during routine colonoscopy between July and September 2018, was conducted. Participants with colorectal polyps were randomized to receive polypectomy using rotary snares or traditional snares. The primary outcome measure was the comparison of the average time of removing a polyp between those two groups. The secondary outcome measure was to compare the polyp resection time by using SMSA (size, morphology, site, and access) scores. Results. A total of two hundred participants were included in this study. Of them, 100 participants were randomly assigned to the rotary snare group (214 polyps) and the other 100 participants were randomly assigned to the traditional group (232 polyps). The mean resection time was significantly shorter in the rotary snare group than in the traditional snare group (24.41±18.14 seconds vs. 29.53±25.74 seconds, P=0.021). In the subgroup analysis, the resection time was also shorter in the rotary snare group than in the traditional snare group in SMSA level 1 (18.51±8.26 seconds vs.23.84±15.07 seconds, P=0.013) and in SMSA level 2 (25.03±15.32 seconds vs.29.15±24.82 seconds, P=0.009), respectively. Conclusion. Colorectal polyps could be removed more efficient by using rotary snares than by using traditional snares in SMSA level 1 and SMSA level 2.
CD200 Checkpoint Reversal: A Novel Approach to Immunotherapy
Authors: Xiong Zhengming , Ampudia Mesias Elisabet , Pluhar G. Elizabeth , Rathe Susan K. , Largaespada David A. , Sham Yuk Y. , Moertel Christopher L. , Olin Michael R.
Published: October 2019

Purpose:

Advances in immunotherapy have revolutionized care for some patients with cancer. However, current checkpoint inhibitors are associated with significant toxicity and yield poor responses for patients with central nervous system tumors, calling into question whether cancer immunotherapy can be applied to glioblastoma multiforme. We determined that targeting the CD200 activation receptors (CD200AR) of the CD200 checkpoint with a peptide inhibitor (CD200AR-L) overcomes tumor-induced immunosuppression. We have shown the clinical efficacy of the CD200AR-L in a trial in companion dogs with spontaneous high-grade glioma. Addition of the peptide to autologous tumor lysate vaccines significantly increased the median overall survival to 12.7 months relative to tumor lysate vaccines alone, 6.36 months.

Experimental Design:

This study was developed to elucidate the mechanism of the CD200ARs and develop a humanized peptide inhibitor. We developed macrophage cell lines with each of four CD200ARs knocked out to determine their binding specificity and functional response. Using proteomics, we developed humanized CD200AR-L to explore their effects on cytokine/chemokine response, dendritic cell maturation and CMV pp65 antigen response in human CD14+ cells. GMP-grade peptide was further validated for activity.

Results:

We demonstrated that the CD200AR-L specifically targets a CD200AR complex. Moreover, we developed and validated a humanized CD200AR-L for inducing chemokine response, stimulating immature dendritic cell differentiation and significantly enhanced an antigen-specific response, and determined that the use of the CD200AR-L downregulated the expression of CD200 inhibitory and PD-1 receptors.

Conclusions:

These results support consideration of a CD200AR-L as a novel platform for immunotherapy against multiple cancers including glioblastoma multiforme.
Prediction of Preeclampsia in Nulliparous Women according to First Trimester Maternal Factors and Serum Markers
Authors: Pihl Kasper , Sørensen Steen , Stener Jørgensen Finn
Published: October 2019

Objective: To evaluate the performance of maternal risk factors (BMI and mean arterial pressure [MAP]) and first-trimester maternal serum markers in the early prediction of preeclampsia (PE) in nulliparous women. Material and Methods: This was a case-cohort study based on a cohort of 14,207 nulliparous women. A total of 213 cases with term PE (from 37 weeks + 0 days) and 55 cases with preterm PE (before 37 weeks + 0 days) were identified and validated. Randomly, 449 controls were selected. Serum samples previously collected for the double test (pregnancy-associated plasma protein A [PAPP-A] and free β human chorionic gonadotrophin [hCGβ]) as part of the first-trimester screening program were retrieved and analyzed for placental growth factor (PlGF), soluble fms-like tyrosine kinase 1 (sFlt-1), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and neutrophil gelatinase-associated lipocalin (NGAL). Concentrations were transformed to multiples of the median (MoM). Multivariate regression analysis was used for prediction models. Receiver-operating characteristics (ROC) curves were used for evaluation of the screening performance. Results: In preterm PE, the PlGF (0.79 MoM), sFlt-1 (0.86 MoM), NGAL (1.15 MoM), and PAPP-A (0.89 MoM) medians were significantly altered. In term PE, PlGF (0.90 MoM) and NT-proBNP (0.86 MoM) medians were significantly reduced. The combination of MAP and PlGF yielded a 39% detection rate of preterm PE for a 10% false-positive rate. The combination of MAP, BMI, and PlGF yielded a 33% detection rate of term PE with a 10% false-positive rate. Conclusion: First-trimester MAP, maternal serum PlGF, and NGAL are markers of preterm PE. Maternal serum sFlt-1 is a significant marker of preterm PE, but only early in the first trimester. First-trimester maternal serum NT-proBNP is not a predictor of PE. Screening performance for PE with these markers individually or in combination is modest.
Replacing Saturated Fat With Unsaturated Fat in Western Diet Reduces Foamy Monocytes and Atherosclerosis in Male
Ldlr

–/–

Mice
Authors: Lian Zeqin , Perrard Xiao-yuan Dai , Peng Xueying , Raya Joe L. , Hernandez Alfredo A. , Johnson Collin G. , Lagor William R. , Pownall Henry J. , Hoogeveen Ron C. , Simon Scott I. , Sacks Frank M. , Ballantyne Christie M. , Wu Huaizhu
Published: October 2019

Objective:

A Mediterranean diet supplemented with olive oil and nuts prevents cardiovascular disease in clinical studies, but the underlying mechanisms are incompletely understood. We investigated whether the preventive effect of the diet could be due to inhibition of atherosclerosis and foamy monocyte formation in
Ldlr

–/–

mice fed with a diet in which milkfat in a Western diet (WD) was replaced with extra-virgin olive oil and nuts (EVOND).

Approach and Results:

Ldlr

–/–

mice were fed EVOND or a Western diet for 3 (or 6) months. Compared with the Western diet, EVOND decreased triglyceride and cholesterol levels but increased unsaturated fatty acid concentrations in plasma. EVOND also lowered intracellular lipid accumulation in circulating monocytes, indicating less formation of foamy monocytes, compared with the Western diet. In addition, compared with the Western diet, EVOND reduced monocyte expression of inflammatory cytokines, CD36, and CD11c, with decreased monocyte uptake of oxLDL (oxidized LDL [low-density lipoprotein]) ex vivo and reduced CD11c
+
foamy monocyte firm arrest on vascular cell adhesion molecule-1 and E-selectin–coated slides in an ex vivo shear flow assay. Along with these changes, EVOND compared with the Western diet reduced the number of CD11c
+
macrophages in atherosclerotic lesions and lowered atherosclerotic lesion area of the whole aorta and aortic sinus.

Conclusions:

A diet enriched in extra-virgin olive oil and nuts, compared with a Western diet high in saturated fat, lowered plasma cholesterol and triglyceride levels, inhibited foamy monocyte formation, inflammation, and adhesion, and reduced atherosclerosis in
Ldlr

–/–

mice.
Failure to Rescue as an Outcome Metric for Pediatric and Congenital Cardiac Catheterization Laboratory Programs: Analysis of Data From the IMPACT Registry
Authors: O'Byrne Michael L. , Kennedy Kevin F. , Jayaram Natalie , Bergersen Lisa J. , Gillespie Matthew J. , Dori Yoav , Silber Jeffrey H. , Kawut Steven M. , Rome Jonathan J. , Glatz Andrew C
Published: October 2019

Background

Risk‐adjusted adverse event (
AE
) rates have been used to measure the quality of pediatric and congenital cardiac catheterization laboratories. In other settings, failure to rescue (
FTR
) has demonstrated utility as a quality metric.

Methods and Results

A multicenter retrospective cohort study was performed using data from the IMPACT (Improving Adult and Congenital Treatment) Registry between January 2010 and December 2016. A modified
FTR
metric was developed for pediatric and congenital cardiac catheterization laboratories and then compared with pooled
AEs
. The associations between patient‐ and hospital‐level factors and outcomes were evaluated using hierarchical logistic regression models. Hospital risk standardized ratios were then calculated. Rankings of risk standardized ratios for each outcome were compared to determine whether
AEs
and
FTR
identified the same high‐ and low‐performing centers. During the study period, 77 580 catheterizations were performed at 91 hospitals. Higher annual hospital catheterization volume was associated with lower odds of
FTR
(odds ratio: 0.68 per 300 cases;
P
=0.0003). No association was seen between catheterization volume and odds of
AEs
. Odds of
AEs
were instead associated with patient‐ and procedure‐level factors. There was no correlation between risk standardized ratio ranks for
FTR
and pooled
AEs
(
P
=0.46). Hospital ranks by catheterization volume and
FTR
were associated (
r
=−0.28,
P
=0.01) with the largest volume hospitals having the lowest risk of
FTR
.

Conclusions

In contrast to
AEs
,
FTR
was not strongly associated with patient‐ and procedure‐level factors and was significantly associated with pediatric and congenital cardiac catheterization laboratory volume. Hospital rankings based on
FTR
and
AEs
were not significantly correlated. We conclude that
FTR
is a complementary measure of catheterization laboratory quality and should be included in future research and quality‐improvement projects.
Posttraumatic Stress Disorder and Risk for Stroke in Young and Middle-Aged Adults
Authors: Rosman Lindsey , Sico Jason J. , Lampert Rachel , Gaffey Allison E. , Ramsey Christine M. , Dziura James , Chui Philip W. , Cavanagh Casey E. , Brandt Cynthia , Haskell Sally , Burg Matthew M.
Published: October 2019

Background and Purpose—

In older populations, transient ischemic attack (TIA) and ischemic stroke have been linked to psychological factors, including posttraumatic stress disorder (PTSD). Whether PTSD also increases risk for early incident stroke in young adults is unknown.

Methods—

We prospectively assessed the incidence of TIA and ischemic stroke in a cohort of 987 855 young and middle-aged Veterans (mean age of 30.29±9.19 years; 87.8% men, 64.4% white) who first accessed care through the Veterans Health Administration from October 2001 to November 2014 and were free of TIA and ischemic stroke at baseline. For each outcome, time-varying multivariate Cox models were constructed to examine the effect of PTSD on incident stroke. We also assessed for effect modification by sex. Additional sensitivity analyses controlled for healthcare utilization.

Results—

Over a 13-year period, TIA and ischemic stroke were diagnosed in 766 and 1877 patients, respectively. PTSD was diagnosed in 28.6% of the sample during follow-up. In unadjusted analyses, PTSD was significantly associated with new-onset TIA (hazard ratio [HR], 2.02; 95% CI, 1.62–2.52) and ischemic stroke (HR, 1.62; 95% CI, 1.47–1.79). In fully adjusted models, the association between PTSD and incident TIA (HR, 1.61; 95% CI, 1.27–2.04) and ischemic stroke (HR, 1.36; 95% CI, 1.22–1.52) remained significant. The effect of PTSD on ischemic stroke risk was stronger in men than in women (HR, 0.63; 95% CI, 0.47–0.86;
P
=0.003), but no effect of sex was found for TIA.

Conclusions—

PTSD is associated with a significant increase in risk of early incident TIA and ischemic stroke independent of established stroke risk factors, coexisting psychiatric disorders, and healthcare utilization. Sex moderated the relationship for adults with ischemic stroke but not TIA. These findings suggest that psychological factors, including PTSD, may be important targets for future age-specific prevention strategies for young adults.
Participation and Superfluity
Authors: Wieland Jan Willem , van Oeveren Rutger
Published: October 2019

Why act when the effects of one’s act are negligible? For example, why boycott sweatshop or animal products if doing so makes no difference for the better? According to recent proposals, one may still have a reason to boycott in order to avoid complicity or participation in harm. Julia Nefsky has argued that accounts of this kind suffer from the so-called “superfluity problem,” basically the question of why agents can be said to participate in harm if they make no difference to it. This paper develops and responds to Nefsky’s challenge.
The Reluctant Martyr: John Hart’s English Mission
Authors: Feingold Mordechai
Published: October 2019

In chronicles of early Catholic missions to England, John Hart (d.1586) comes across as something of an embarrassment. Slated to be executed alongside Edmund Campion on December 1, 1581, at the last moment Hart chose life over martyrdom. In exchange for his freedom he volunteered to spy on William Allen, president of the English College in Rheims. Equally embarrassing, in the context of the charged religious and political atmosphere of the early 1580s, when put to the test as a scholar, Hart revealed weakness instead of strength in his conference with John Rainolds. Though this basic story line is known and often summarily retold, few scholars have delved into the intricacies of the affair—an omission this article seeks to remedy.
New Approach for Bias Correction and Stochastic Downscaling of Future Projections for Daily Mean Temperatures to a High-Resolution Grid
Authors: Yuan Qifen , Thorarinsdottir Thordis L. , Beldring Stein , Wong Wai Kwok , Huang Shaochun , Xu Chong-Yu
Published: October 2019

In applications of climate information, coarse-resolution climate projections commonly need to be downscaled to a finer grid. One challenge of this requirement is the modeling of subgrid variability and the spatial and temporal dependence at the finer scale. Here, a postprocessing procedure for temperature projections is proposed that addresses this challenge. The procedure employs statistical bias correction and stochastic downscaling in two steps. In the first step, errors that are related to spatial and temporal features of the first two moments of the temperature distribution at model scale are identified and corrected. Second, residual space–time dependence at the finer scale is analyzed using a statistical model, from which realizations are generated and then combined with an appropriate climate change signal to form the downscaled projection fields. Using a high-resolution observational gridded data product, the proposed approach is applied in a case study in which projections of two regional climate models from the Coordinated Downscaling Experiment–European Domain (EURO-CORDEX) ensemble are bias corrected and downscaled to a 1 km × 1 km grid in the Trøndelag area of Norway. A cross-validation study shows that the proposed procedure generates results that better reflect the marginal distributional properties of the data product and have better consistency in space and time when compared with empirical quantile mapping.
Postprocessing Next-Day Ensemble Probabilistic Precipitation Forecasts Using Random Forests
Authors: Loken Eric D. , Clark Adam J. , McGovern Amy , Flora Montgomery , Knopfmeier Kent
Published: October 2019

Most ensembles suffer from underdispersion and systematic biases. One way to correct for these shortcomings is via machine learning (ML), which is advantageous due to its ability to identify and correct nonlinear biases. This study uses a single random forest (RF) to calibrate next-day (i.e., 12–36-h lead time) probabilistic precipitation forecasts over the contiguous United States (CONUS) from the Short-Range Ensemble Forecast System (SREF) with 16-km grid spacing and the High-Resolution Ensemble Forecast version 2 (HREFv2) with 3-km grid spacing. Random forest forecast probabilities (RFFPs) from each ensemble are compared against raw ensemble probabilities over 496 days from April 2017 to November 2018 using 16-fold cross validation. RFFPs are also compared against spatially smoothed ensemble probabilities since the raw SREF and HREFv2 probabilities are overconfident and undersample the true forecast probability density function. Probabilistic precipitation forecasts are evaluated at four precipitation thresholds ranging from 0.1 to 3 in. In general, RFFPs are found to have better forecast reliability and resolution, fewer spatial biases, and significantly greater Brier skill scores and areas under the relative operating characteristic curve compared to corresponding raw and spatially smoothed ensemble probabilities. The RFFPs perform best at the lower thresholds, which have a greater observed climatological frequency. Additionally, the RF-based postprocessing technique benefits the SREF more than the HREFv2, likely because the raw SREF forecasts contain more systematic biases than those from the raw HREFv2. It is concluded that the RFFPs provide a convenient, skillful summary of calibrated ensemble output and are computationally feasible to implement in real time. Advantages and disadvantages of ML-based postprocessing techniques are discussed.
Workshop Report: Tracing Legacies of Violence in French Equatorial Africa
Authors: de Vries Lotje , Mangarella Joseph
Published: October 2019

This report offers an account of an international workshop held at the Omar Bongo University in Libreville, Gabon, from 23 November to 27 November 2018. Bringing together specialists on and from Cameroon, Central African Republic, Chad, Congo, Equatorial Guinea, and Gabon, participants reflected on the ways in which different forms of violence have historically had – and continue to have – an impact on social fabrics and several dimensions of politics. The workshop also sought to relate these legacies of violence to the region’s economies of extraction. The region is confronted with social and political turmoil that receives little international attention. The combination of simmering and open instability and the relatively marginal position of the region vis-à-vis the wider continent risks propelling several countries into outright political strife with regional repercussions. The debates concluded that further thinking on how violence permeates every aspect of social and political life is much needed.
Preserving the (right kind of) city: The urban politics of the middle classes in Belo Horizonte, Brazil
Authors: Nogueira Mara
Published: October 2019

Since re-democratisation, Brazil has experienced a slow but continuous process of urban reform, with the introduction of legal and institutional developments that favour participatory democracy in urban policy. Legal innovations such as the City Statute have been celebrated for expanding the ‘right to the city’ to marginalised populations. While most studies examine the struggles of the urban poor, I focus on middle-class citizens, showing how such legal developments have unevenly affected the ways in which different social groups are able to impact the production of urban space. The two cases explored in this study concern residents’ struggles to preserve their middle-class neighbourhoods against change triggered by projects related to the hosting of the 2014 World Cup in Belo Horizonte, Brazil. The first looks at the Musas Street residents’ fight against the construction of a luxury hotel in their neighbourhood, while the second examines the Pampulha residents’ struggle against the presence of street vendors and football fans in their streets. My findings show that through the articulation of legal discourses, middle-class claims on the need for preserving the environment and the city’s cultural heritage are legitimised by the actions of the local state. The article thus looks beyond neoliberalism, showing that socio-spatial segregation and inequality should not be regarded solely as the product of state–capital alliances for engendering capital accumulation through spatial restructuring, but also as the result of the uneven capacities of those living in the city to access the state resources and legitimise certain forms of inhabitance of urban space.
The classroom culture of a middle school music technology class
Authors: Albert Daniel J.
Published: October 2019

The purpose of this study was to examine the culture of an American middle school music technology classroom based in musical composition. Research questions explored students’ perceptions of how they co-create the classroom culture with the teacher and how the classroom culture influences participation in musical composition activities, if at all. Data sources for this ethnographic case study included field notes from multiple class observations, audio- and video-recordings, and semi-structured interviews. Findings determined that teacher and students’ mutual use of constructive feedback in their discourse, the teacher’s role as co-learner, his facilitation of “messiness” as part of the learning process, and his pedagogical style helped to create an affirming classroom culture that motivated students to compose. Implications for teaching practice include critical examination of classroom cultures and thoughtful inclusion of technology in music education courses.