bluuebunny/crossref_metadata_2025 huggingface dataset:
A Rare Presentation of Cardiac Tamponade from Metastatic Urothelial Carcinoma of the Bladder
Authors: Palam Sowmya , Kapoor Ridhima , Kulinski Jacquelyn
Published: June 2018

A 62-year-old man presented with 2 weeks of progressive dyspnea and chest pain. He was previously diagnosed with high-grade invasive urothelial carcinoma (UC) of the bladder and underwent neoadjuvant chemotherapy followed by radical cystectomy 10 months earlier, resulting in pathologic complete remission. Clinical evaluation and echocardiographic imaging was consistent with a diagnosis of cardiac tamponade. Due to a history of malignancy, the patient was referred for a surgical pericardial window, to include biopsy of the pericardium. Pericardial fluid and pericardial biopsy specimens were consistent with metastatic UC. Cardiac tamponade due to metastatic UC is a rare presentation, and, to our knowledge, there have been only 5 cases reported in the English literature. We report a rare case of cardiac tamponade due to isolated pericardial metastases from high grade UC of the bladder and discuss the symptoms, treatment, and prognosis of this pathologic condition. We also present a brief review of previously published literature. Through this discussion, we would like to emphasize the (1) consideration of cardiac metastases in the differential diagnosis for patients with a history of UC presenting with cardiac or pulmonary symptoms and (2) improved diagnostics with pericardial biopsy and pericardiocentesis over pericardiocentesis alone.
The Antibacterial Effect In Vitro of Honey Derived from Various Danish Flora
Authors: Matzen Reem Dina , Zinck Leth-Espensen Julie , Jansson Therese , Nielsen Dennis Sandris , Lund Marianne N. , Matzen Steen
Published: June 2018

The mechanism behind the biologic actions of honey as a wound remedy has been intensively studied; however, there is no published data regarding any antibacterial effect of honey derived from Danish flora. We surveyed 11 honeys of various Danish floral sources for their antibacterial activity and compared them to a culinary processed commercial honey (Jakobsens) and a raw and a medical grade Manuka (Leptospermum scoparium) honey using the agar-well diffusion method. We tested the effect on three gram-positive bacteria (two strains of Staphylococcus aureus and one strain of Staphylococcus epidermidis) and two gram-negative bacteria (Pseudomonas aeruginosa and Escherichia coli). All samples, except the commercial honey, exhibited antibacterial activity, and samples derived from Water Mint (Mentha aquatica), Organic 2 (mixed organic flora), and Linden (Tilia cordata) honey had consistent effects on all bacteria tested and showed greater effect than medical grade and raw Manuka (L. scoparium) honey. The content of methylglyoxal was low in the Danish honey (< 2 μg/mL) and significantly (p<0.05) higher in both the raw and the medical grade Manuka (L. scoparium) honey, where the concentrations were, respectively, 6.29 μg/mL and 54.33 μg/mL. The antibacterial effect of Danish honeys was mostly due to hydrogen peroxide. We conclude that honeys derived from Danish flora possess antibacterial effect, probably by a hurdle effect of viscosity, osmolality, acidity, bioactive peptides, and most importantly the content of hydrogen peroxide. These findings indicate that honeys of various Danish floral sources may have clinical potential, although further studies are necessary to elucidate this in order to determine whether the results of our in vitro experiments also apply to a clinical setting.
A Preferable Airborne Integrated Navigation Method Based on INS and GPS
Authors: Zhang Xiaoyue , Ning Kaiwen
Published: June 2018

An integrated navigation method based on INS and GPS was proposed for airborne navigation. The influence of scale factor error and misalignment error of gyroscope and accelerometer on navigation accuracy was analyzed. Compared with traditional INS/GPS integrated navigation method, scale factor error and misalignment error were added to the state model of the integrated navigation system. The observability of scale factor error and misalignment error was analyzed combined with typical airborne movement. Then the integrated system was optimized, and the new navigation model of the integrated system was obtained. The optimized INS/GPS integrated model was validated by numerical simulation and turntable test. Comparing the proposed model with traditional integrated model (integrated system error states do not include scale factor error and misalignment error), the results showed that the proposed integrated navigation method can improve the accuracy from 8% to 28% of the east, north, and upward positions.
Activation, Inhibition, or Something Else: An Exploratory Study on Response Priming Using Moving Dots as Primes in Middle-Aged and Old Adults
Authors: Bermeitinger Christina , Kappes Cathleen
Published: June 2018

Response priming refers to the finding that a prime stimulus preceding a target stimulus influences the response to the following target stimulus. With young subjects, using moving dot stimuli as primes indicated faster responses to compatible targets (i.e., prime and target are associated with the same response) with short stimulus onset asynchronies (SOAs). In contrast, with longer SOAs, participants responded faster to incompatible targets. In the present study, we extended the evidence by comparing middle-aged (50–65 years) and old (66–87 years) adults. With two different motion types, the result found in young participants was replicated in the middle-aged adults. In contrast, old adults showed large positive compatibility effects with the short SOA but neither activation nor inhibition effects with the longer SOA. We discuss our findings in light of several theoretical accounts (i.e., inhibitory deficit, deautomatization, evaluation window account, attention, rapid decay).
Adaptive Output Feedback Tracking Controller Design of Stochastic Nonlinear Systems with Parameter Uncertainty for Polynomial Function Growth Conditions
Authors: Guo Long-Chuan
Published: June 2018

This paper mainly focuses on output feedback practical tracking controller design for stochastic nonlinear systems with polynomial function growth conditions. Mostly, there are some studies on output feedback tracking control problem for general nonlinear systems with parametric certainty in existing achievements. Moreover, we extend it to stochastic nonlinear systems with parametric uncertainty and system nonlinear terms are assumed to satisfy polynomial function growth conditions which are more relaxed than linear growth conditions or power growth conditions. Due to the presence of unknown parametric uncertainty, an output feedback practical tracking controller with dynamically updated gains is constructed explicitly so that all the states of the closed-loop systems are globally bounded and the tracking error belongs to arbitrarily small interval after some positive finite time. An example illustrates the efficiency of the theoretical results.
Overcoming Therapeutic Resistance of Triple Positive Breast Cancer with CDK4/6 Inhibition
Authors: Schedin Troy B. , Borges Virginia F. , Shagisultanova Elena
Published: June 2018

Triple positive breast cancers overexpress both the human epidermal growth factor receptor 2 (HER2) oncogene and the hormonal receptors (HR) to estrogen and progesterone. These cancers represent a unique therapeutic challenge because of a bidirectional cross-talk between the estrogen receptor alpha (ERα) and HER2 pathways leading to tumor progression and resistance to targeted therapy. Attempts to combine standard of care HER2-targeted drugs with antihormonal agents for the treatment of HR+/HER2+ breast cancer yielded encouraging results in preclinical experiments but did improve overall survival in clinical trial. In this review, we dissect multiple mechanisms of therapeutic resistance typical of HR+/HER2+ breast cancer, summarize prior clinical trials of targeted agents, and describe novel rational drug combinations that include antihormonal agents, HER2-targeted drugs, and CDK4/6 inhibitors for treatment of the HR+/HER2+ breast cancer subtype.
A New Approach to the Existence of Quasiperiodic Solutions for Second-Order Asymmetric p-Laplacian Differential Equations
Authors: Wang Xiaoming , Wang Lixia
Published: June 2018

For p≥2 and ϕp(s):=sp-2s, we propose a new estimate approach to study the existence of Aubry-Mather sets and quasiperiodic solutions for the second-order asymmetric p-Laplacian differential equations ϕpx′′+λϕp(x+)-μϕp(x-)=ψ(t,x), where λ and μ are two positive constants satisfying λ-1/p+μ-1/p=2/ω with ω∈R+, ψ(t,x)∈C0,1(Sp×R) is a continuous function, 2πp-periodic in the first argument and continuously differentiable in the second one, x±=max⁡{±x,0}, πp=2π(p-1)1/p/psin⁡π/p, and Sp=R/2πpZ. Using the Aubry-Mather theorem given by Pei, we obtain the existence of Aubry-Mather sets and quasiperiodic solutions under some reasonable conditions. Particularly, the advantage of our approach is that it not only gives a simpler estimation procedure, but also weakens the smoothness assumption on the function ψ(t,x) in the existing literature.
Recycling of Waste Sludge: Preparation and Application of Sludge-Based Activated Carbon
Authors: Bian Yongning , Yuan Qian , Zhu Guocheng , Ren Bozhi , Hursthouse Andrew , Zhang Peng
Published: June 2018

With the rapidly increasing industrial and agricultural development, a large amount of sludge has been produced from much water treatment. Sludge treatment has become one of the most important environmental issues. Resource utilization of sludge is one of the important efficient methods for solving this issue. Sludge-based activated carbon (SBAC) materials have high adsorption performance and can effectively remove environmental pollutants including typical organic matter and heavy metals through physical and chemical processes. Therefore, developing efficient SBAC materials is important and valuable. At present, preparation, modification, and application of SBAC materials have gained widespread attention. This paper provides a review of the research on SBAC preparation and modification and its utilization in removing environmental pollutants. It included the following topics present in this review: conventional and new methods for preparation of SBAC were clearly present; the effective methods for improving SBAC performance via physical and chemical modification were reviewed; and the correlation of their physic-chemical properties of SBAC with pollutants’ removal efficiencies as well as the removal mechanisms was revealed. SBAC has a better adsorption performance than commercial activated carbon in some aspects. Furthermore, it is a cost-effective technique and has a wide range of raw materials. However, there are still some drawbacks to its research; thus, some suggestions for further research were given in this review.
Reaction Force Compensator for High‐Speed Precision Stage of Laser Direct Imaging Process
Authors: Seo Chang-hoon , Jeon Yong ho , Lee Hyung-ku , Kim Hyo-young , Lee Moon G.
Published: June 2018

Recently, laser direct imaging (LDI) process has become popular as a substitute for lithography in flexible printed circuit board (FPCB) manufacturing industry. However, repeated motion of the process equipment causes residual vibration in a transient state when the stage accelerates or decelerates. The supporting structure for the laser head is complex and heavy in order to increase the resonant frequency, because the residual vibration must be controlled below a certain level for the LDI process precision. If the vibration cannot be rejected, the controller needs longer settling time; therefore, the productivity is reduced. In this study, a reaction force compensator (RFC) for the granite of a precision stage in the equipment is proposed to minimize the detrimental vibration and steady state error. First, displacement is measured with a laser Doppler vibrometer (LDV) to identify the dynamic characteristics of a pneumatic isolator for the stage. Second, the compensator’s mechanism design is proposed by using a voice coil motor and capacitive displacement sensor. Third, a hybrid control algorithm combining the RFC and PID is applied to reduce the vibration. Finally, the RFC is evaluated in terms of vibration peak and steady state error. The LDI apparatus is stabilized more rapidly, because the proposed method cancels the impulsive reaction force of linear motion module immediately.
Arthroscopic Osteosynthesis for the Treatment of Coronoid Process Fractures: A Case Series
Authors: Shimada Noriaki , ShirakiIt Katsuhiko , Saita Kazuo
Published: June 2018

The treatment strategy and surgical indication for coronoid process fractures are not clear. Many methods of surgery have been described. We report on the use of arthroscopic osteosynthesis for this type of fracture. This method is minimally invasive and effective for confirming the reduction, and it is advantageous for postoperative pain and early recovery after surgery.
Reliability Analysis for Multipath Communications in Mobile Cloud Computing Architectures
Authors: Li Shiyong , Sun Wei , Zhang Yaming , Liu Haiou
Published: June 2018

Mobile cloud computing (MCC) has gained much attention from both academia and industry in recent years. It can support new types of services, such as m‐commerce, m‐learning, and mobile healthcare, and enrich mobile users’ experience and satisfaction by taking full advantage of cloud computing. In MCC architectures multipath communications can be achieved with multihomed mobile devices, so as to utilize multiple paths for data transmission in parallel. They can achieve better utilization of bandwidth resource, split traffic for load balancing, and enhance reliability, fault tolerance, and robustness for applications. However, little attention has been paid to model the reliability of multipath communications in case of path failure. In this paper we investigate the reliability of concurrent multipath communications in MCC architectures and propose two reliability models when paths are failure. One is for static path failure where the failed paths cannot recover for communication in some delay time. The other is for dynamic path failure where the failed paths can recover in some delay time. Finally, numerical results are given to illustrate the reliability of multipath communications.
Self-Reported Occupational Injuries and Perceived Occupational Health Problems among Latino Immigrant Swine Confinement Workers in Missouri
Authors: Ramos Athena K. , Fuentes Axel , Carvajal-Suarez Marcela
Published: June 2018

Swine production has changed dramatically, and in the United States production often takes place in concentrated animal feeding operations (CAFOs). Because of the size and density of these types of facilities, workers may be exposed to serious occupational health risks such as noxious gases, agricultural dusts, elevated noise levels, and zoonotic diseases. This descriptive study examines self-reported occupational injuries and perceived occupational health problems among a convenience sample of 40 Latino immigrant swine confinement workers (92.5% male; M age = 36.1 years; SD = 10.0) in Missouri. Results indicated that seventeen workers (42.5%) rated their health as fair or poor, thirteen (32.5%) had experienced an occupational injury, and eleven (28.2%) reported occupational health problems such as burning eyes, muscular pain, headaches, coughing, nausea, nasal congestion, and sneezing. The majority of workers did not perceive their job to be dangerous. Clearly, more must be done to protect workers, especially immigrant workers, who may not have the same access to information, training, or other protections. Health and safety should be a priority for both farmworkers and farm employers. Practical and policy-based implications and recommendations are discussed.
Systemic Administration of Curcumin Affect Anxiety‐Related Behaviors in a Rat Model of Posttraumatic Stress Disorder via Activation of Serotonergic Systems
Authors: Lee Bombi , Lee Hyejung
Published: June 2018

Posttraumatic stress disorder (PTSD) is a trauma‐induced psychiatric disease characterized by impaired hyperarousal, fear extermination, depression, anxiety, and amnesic symptoms that may include the release of monoamines in the dread circuit. Curcumin (CUR), a major diarylheptanoid and polyphenolic component of Curcuma longa, reportedly possesses several pharmacological features, including antidiabetic, antiatherosclerotic, anticancer, and neuropsychiatric actions. But the anxiolytic‐like effects of CUR and its mechanism of action in PTSD are unclear. The current research measured some anxiety‐related behavioral responses to examine the effects of CUR on symptoms of anxiety in rats after single prolonged stress (SPS) exposure by reversing the serotonin (5‐HT) dysfunction. Rats received CUR (20, 50, or 100 mg/kg, i.p., once daily) for 14 days after SPS exposure. Administration of CUR significantly increased the number of central zone crossings in the open field test and reduced grooming behavior in the elevated plus maze (EPM) test and increased the number of open‐arm visits on the EPM test. CUR administration significantly reduced freezing response to contextual fear conditioning. CUR recovered neurochemical abnormalities and SPS‐induced decreased 5‐HT tissue levels in the hippocampus, amygdala, and striatum. These results suggested that CUR has anxiolytic‐like effects on biochemical and behavioral symptoms associated with anxiety. Thus, CUR may be a useful agent to alleviate or treat psychiatric disorders similar to those observed in patients with PTSD.
Effect of the Dynamic Load on Stresses in a Deck Pavement with an Interlayer Contact Model
Authors: Wang Xuntao , Feng Jianhu , Wang Hu , Hong Shidi , Cheng Xiaohan , Zheng Supei
Published: June 2018

Random surface roughness of bridge deck pavement just like random road surface roughness was simulated by the harmony superposition method in this paper. The dynamic load of vehicle was calculated by the random surface roughness of the deck pavement and the quarter‐car model. A finite element model of a box girder bridge and its deck pavement was established, and the bonding condition between the adjacent layers was assumed to be contact bonding condition. The stress values of the asphalt concrete layer were calculated and analyzed when surface roughness condition, vehicle speed, and disengaging area changed. Results show that random surface roughness of deck pavement affected the stress trend of the asphalt concrete layer obviously. The appearance of disengaging area would increase the stress values of the asphalt concrete layer and the normal tensile stress value between the asphalt concrete layer and the waterproof layer. This would speed up the damage of the asphalt concrete layer and enlarge further the disengaging area.
Identification and Characterization of Families That Are Positively Deviant for Childhood Obesity in a Latino Population: A Case-Control Study
Authors: Foster Byron A. , Aquino Christian A. , Mejia Sharol , Turner Barbara J. , Singhal Arvind
Published: June 2018

Background. Childhood obesity is a complex public health challenge that requires innovative, sustainable solutions. Positive deviance, inspired by the science of complexity, is an approach that examines what allows certain individuals to succeed despite being predicted to fail. This study is aimed at identifying and defining positive deviants for early childhood obesity. Methods. This case-control study used medical record data to identify Latino children aged 2–5 and classify them using their longitudinal weight change. Parents of children with trajectories toward a healthy weight from an obese weight (cases) and parents of children with stable obese weight trajectories over time (controls) were recruited. Mixed-methods analyses were used including a semistructured interview and quantitative surveys evaluating diet, physical activity, sleep, feeding practices, and self-efficacy. Qualitative description was applied to the qualitative data; quantitative data were analyzed using descriptive statistics and logistic regression modeling. Results. Of eligible Latino children identified from the overall data set (n=1,621), 257 (16%) had trajectories toward a healthy weight, and among these, 21 positively deviant cases completed the study with 23 matched controls. Positive deviant families were characterized by lower education, higher self-efficacy, and a more Mexican cultural orientation. Findings suggest that effective engagement of other caregivers and creating healthy food environments were important determinants of healthy weight outcomes. Conclusions. Positive deviants (cases) were distinct from controls in several parenting strategies such as creating healthy food environments and engaging caregivers. They had higher self-efficacy despite lower education. There were fewer differences in diet and physical activity than expected.
The Kinetoplast of Trypanosomatids: From Early Studies of Electron Microscopy to Recent Advances in Atomic Force Microscopy
Authors: Cavalcanti Danielle Pereira , de Souza Wanderley
Published: June 2018

The kinetoplast is a specialized region of the mitochondria of trypanosomatids that harbors the most complex and unusual mitochondrial DNA found in nature. Kinetoplast DNA (kDNA) is composed of thousands of circular molecules topologically interlocked to form a single network. Two types of DNA circles are present in the kinetoplast: minicircles (0.5–10 kb) and maxicircles (20–40 kb). Knowledge of kinetoplast architecture is crucial to understanding the replication and segregation of kDNA circles because the molecules involved in these processes are precisely positioned in functional domains throughout the kinetoplast. The fine structure of the kinetoplast was revealed in early electron microscopy (EM) studies. However, an understanding of the topological organization of kDNA was only demonstrated after the development of protocols to separate kDNA from nuclear DNA, followed by EM observations. Electron microscopy analysis of thin sections of trypanosomatids, spreading of isolated kDNA networks onto EM grids, deep-etching studies, and cytochemical and immunocytochemical approaches are examples of techniques that were useful for elucidating the structure and replication of the kinetoplast. Recently, atomic force microscopy has joined this set of techniques and improved our knowledge about the kDNA network and revealed new details about kDNA topology in trypanosomatids.
Fracture of a Femoral Revision Stem following a Technical Failure
Authors: Herold Falko , Eijer Henk
Published: June 2018

We report about a fracture of a modular, uncemented femoral revision stem (Zimmer, Revitan®) due to a not previously described intraoperative technical problem. During implantation, a small ring, part of the proximal part of the trial stem, was left on the distal part of the definite stem. Following this, the top screwcap of the proximal part of the definite stem could not be tightened properly. However, the stem was thought to be stable, and the situation left. Two and a half years later, the proximal part of the stem fractured and the situation became unstable. It is very useful to know about this ring and that it should always be removed, otherwise, there is possibility that it may be left on the definite distal part of the stem with the possibility of a later fracture.
Pyogenic Liver Abscess Caused by Methicillin-Susceptible Staphylococcus aureus in a 21-Year-Old Male
Authors: Igbinedion Samuel , Mavuram Meher S. , Boktor Moheb , Bienvenu John
Published: June 2018

Liver abscesses are the most common types of visceral abscesses. Pyogenic liver abscesses, a particular type of liver abscesses, are uncommonly encountered. We present a rare case of pyogenic liver abscess caused by methicillin-susceptible Staphylococcus aureus in a young man. A 21-year- old man presented from prison to the hospital with fever, nausea, vomiting, diarrhea, and abdominal pain for five days. Labs were significant for leukocytosis with predominant neutrophilia and elevated liver enzymes. CT abdomen with contrast revealed an 8.4 cm multiloculated right hepatic mass extending to the kidney. Patient was started on broad spectrum antibiotics, given septic presentation. Peripheral blood cultures returned positive for methicillin-susceptible Staphylococcus aureus (MSSA). The culture from percutaneous drainage also revealed MSSA. He received a total of four weeks of IV Nafcillin therapy along with drainage of his abscess via percutaneous catheter. Follow-up revealed clinical resolution. This case highlights the importance of obtaining an aspirate from the liver abscess to better guide treatment strategy. Clinicians must consider broadening antibiotic coverage to include gram-positive organisms if the patient presents with severe illness and risk factors for Staphylococcus aureus infections.
Transcription Factor YY1 Promotes Cell Proliferation by Directly Activating the Pentose Phosphate Pathway
Authors: Wu Shourong , Wang Huimin , Li Yanjun , Xie Yudan , Huang Can , Zhao Hezhao , Miyagishi Makoto , Kasim Vivi
Published: June 2018

Tumor cells alter their metabolism to meet their demand for macromolecules and support a high rate of proliferation as well as cope with oxidative stress. The transcription factor yin yang 1 (YY1) is upregulated in various types of tumors and is crucial for tumor cell proliferation and metastasis. However, its role in tumor cell metabolic reprogramming is poorly understood. Here, we show that YY1 alters tumor cell metabolism by activating glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme in the pentose phosphate pathway. By stimulating the pentose phosphate pathway, YY1 enhanced production of nucleotides and DNA synthesis, decreased intracellular reactive oxygen species levels, and promoted antioxidant defense by supplying increased reducing power in the form of NADPH. Importantly, YY1-mediated regulation of the pentose phosphate pathway in tumor cells occurred not through p53, but rather through direct activation of G6PD transcription by YY1. Regulation of pentose phosphate pathway activity through G6PD was strongly related to YY1-induced proliferation of tumor cells and tumorigenesis. Together, our results describe a novel role for YY1 in regulating G6PD in a p53-independent manner, which links its function in tumorigenesis to metabolic reprogramming in tumor cells.

Significance: This study reveals a novel role for YY1 in regulating G6PD and activating the pentose phosphate pathway, linking its function in tumorigenesis to metabolic reprogramming. Cancer Res; 78(16); 4549–62. ©2018 AACR.
DDX3 Activates CBC-eIF3–Mediated Translation of uORF-Containing Oncogenic mRNAs to Promote Metastasis in HNSCC
Authors: Chen Hung-Hsi , Yu Hsin-I , Yang Muh-Hwa , Tarn Woan-Yuh
Published: June 2018

Mutated or dysregulated DDX3 participates in the progression and metastasis of cancer via its multiple roles in regulating gene expression and cellular signaling. Here, we show that the high expression levels of DDX3 in head and neck squamous cell carcinoma (HNSCC) correlate with lymph node metastasis and poor prognosis and demonstrate that DDX3 is essential for the proliferation, invasion, and metastasis of oral squamous cell carcinoma (OSCC) cells. Microarray analyses revealed that DDX3 is required for the expression of a set of pro-metastatic genes, including ATF4-modulated genes in an aggressive OSCC cell line. DDX3 activated translation of ATF4 and a set of its downstream targets, all of which contain upstream open reading frames (uORF). DDX3 promoted translation of these targets, likely by skipping the inhibitory uORF. DDX3 specifically enhanced the association of the cap-binding complex (CBC) with uORF-containing mRNAs and facilitated recruitment of the eukaryotic initiation factor 3 (eIF3). CBC and certain eIF3 subunits contributed to the expression of metastatic-related gene expression. Taken together, our results indicate a role for the novel DDX3–CBC–eIF3 translational complex in promoting metastasis.

Significance: The discovery of DDX3-mediated expression of oncogenic uORF-containing genes expands knowledge on translational control mechanisms and provides potential targets for cancer therapy.

Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/16/4512/F1.large.jpg Cancer Res; 78(16); 4512–23. ©2018 AACR.
Experimental Lung Metastases in Mice Are More Effectively Inhibited by Blockade of IL23R than IL23
Authors: Yan Juming , Allen Stacey , Vijayan Dipti , Li Xian-Yang , Harjunpää Heidi , Takeda Kazuyoshi , Liu Jing , Cua Daniel J. , Smyth Mark J. , Teng Michele W.L.
Published: June 2018

Tumor-induced immunosuppression is mediated through various mechanisms including engagement of immune checkpoint receptors on effector cells, function of immunoregulatory cells such as regulatory T cells and myeloid-derived suppressor cells, and deployment of immunosuppressive cytokines such as TGFβ and IL10. IL23 is a cytokine that negatively affects antitumor immunity. In this study, we investigated whether IL23-deficient (IL23p19−/−) and IL23R-deficient (IL23R−/−) mice phenocopied each other, with respect to their tumor control. We found that IL23R−/− mice had significantly fewer lung metastases compared with IL23p19−/− mice across three different experimental lung metastasis models (B16F10, LWT1, and RM-1). Similarly, IL23R blocking antibodies were more effective than antibodies neutralizing IL23 in suppressing experimental lung metastases. The antimetastatic activity of anti-IL23R was dependent on NK cells and IFNγ but independent of CD8+ T cells, CD4+ T cells, activating Fc receptors, and IL12. Furthermore, our data suggest this increased antitumor efficacy was due to an increase in the proportion of IFNγ-producing NK cells in the lungs of B16F10 tumor-bearing mice. Anti-IL23R, but not anti-IL23p19, partially suppressed lung metastases in tumor-bearing mice neutralized for IL12p40. Collectively, our data imply that IL23R has tumor-promoting effects that are partially independent of IL23p19. Blocking IL23R may be more effective than neutralizing IL23 in the suppression of tumor metastases. Cancer Immunol Res; 6(8); 978–87. ©2018 AACR.
Minimally Invasive Surgical Device for Precise Application of Bioadhesives to Prevent iPPROM
Authors: Devaud Yannick Robert , Züger Silvia , Zimmermann Roland , Ehrbar Martin , Ochsenbein-Kölble Nicole
Published: June 2018

Introduction: The benefits of endoscopic fetal surgery are deteriorated by the high risk of iatrogenic preterm prelabor rupture of fetal membranes (iPPROM). While previous studies have reported good sealing candidates to prevent membrane rupture, the delivery of these materials to the location of membrane puncture remains unsolved. Materials and Methods: We describe an approach to apply sealing materials onto the amnion through the fetoscopy port. We developed a device composed of an umbrella-shaped polyester coated nitinol mesh and an applicator. The spontaneously unfolding umbrella is pushed through the port, pulled against the amnion, and glued onto the amnion defect site. We tested the adhesion strength of multiple glues and tested the feasibility and reproducibility of this fetal membrane sealing approach in an ex vivo model. Results: The umbrella unfolded and was well positioned in all tests (n = 18). When applied via the fetoscopy port, umbrellas were successfully glued onto the fetal membrane, and all of them completely covered the defect (n = 5). The mean time needed for the whole procedure was 3 min. Discussion: This study is a proof of concept presenting a potential future solution for the precise local application of bioadhesives for the prevention of iPPROM.
Long Survival and Preservation of Good Visual Acuity in a Patient with Bilateral Diffuse Uveal Melanocytic Proliferation
Authors: van Noort Baudine C. , Keunen Jan E.E. , Schlingemann Reinier O. , Marinkovic Marina
Published: June 2018

Purpose: To report a patient with bilateral diffuse uveal melanocytic proliferation (BDUMP) due to a lung carcinoma, who survived 9.5 years with preservation of good visual acuity after cataract surgery and curative chemotherapy with neoadjuvant radiation therapy. Methods: Clinical review of a patient with BDUMP. Results: We report the case of a 64-year-old man presenting with bilateral visual deterioration. Ophthalmological examination showed bilateral cataract, a small elevated non-pigmented tumor in the iris and multiple elevated, diffuse round pigmented choroidal lesions. Based on the clinical presentation, the diagnosis of BDUMP was suspected. After referral to an internal medicine specialist, a poorly differentiated non-small cell lung carcinoma was diagnosed and treated with chemotherapy followed by irradiation. After 3 years, spontaneous depigmentation of the choroidal lesions occurred. According to the literature, the mean survival of patients with BDUMP is 11.6 months. Our patient, however, survived for 9.5 years with preservation of good visual acuity after cataract extraction. Conclusion: This case illustrates that prolonged survival and preservation of useful visual acuity is possible in BDUMP. Cataract surgery should be considered in selected patients, and depigmentation of the lesions may occur during long-term follow-up.
Does Sample Attrition Affect the Assessment of Frailty Trajectories Among Older Adults? A Joint Model Approach
Authors: Stolz Erwin , Mayerl Hannes , Rásky Éva , Freidl Wolfgang
Published: June 2018

Background: Frailty constitutes an important risk factor for adverse outcomes among older adults. In longitudinal studies on frailty, selective sample attrition may threaten the validity of results. Objective: To assess the impact of sample attrition on frailty index trajectories and gaps related to socio-economic status (education) therein among older adults in Europe. Methods: A total of 64,143 observations from 21,044 respondents (50+) from the Survey of Health, Ageing and Retirement in Europe across 12 years of follow-up (2004–2015) and subject to substantial sample attrition (59%) were analysed. We compared results of a standard linear mixed model assuming missing at random (MAR) sample attrition with a joint model assuming missing not at random sample attrition. Results: Estimated frailty trajectories of both the mixed and joint models were identical up to an age of 80 years, above which modest underestimation occurred when a standard linear mixed model was used rather than a joint model. The latter effect was larger for men than women. Substantial education-based inequality in frailty continued throughout old age in both the mixed and joint models. Conclusion: Linear mixed models assuming MAR sample attrition provided good estimates of frailty trajectories up until high age. Thus, the validity of existing studies estimating frailty trajectories based on standard linear mixed models seems not threatened by substantial sample attrition.
Distinct Gene Expression Patterns between Nasal Mucosal Cells and Blood Collected from Allergic Rhinitis Sufferers
Authors: Watts Annabelle M. , West Nicholas P. , Cripps Allan W. , Smith Pete K. , Cox Amanda J.
Published: June 2018

Background: Investigations of gene expression in allergic rhinitis (AR) typically rely on invasive nasal biopsies (site of inflammation) or blood samples (systemic immunity) to obtain sufficient genetic material for analysis. New methodologies to circumvent the need for invasive sample collection offer promise to further the understanding of local immune mechanisms relevant in AR. Methods: A within-subject design was employed to compare immune gene expression profiles obtained from nasal washing/brushing and whole blood samples collected during peak pollen season. Twelve adults (age: 46.3 ± 12.3 years) with more than a 2-year history of AR and a confirmed grass pollen allergy participated in the study. Gene expression analysis was performed using a panel of 760 immune genes with the NanoString nCounter platform on nasal lavage/brushing cell lysates and compared to RNA extracted from blood. Results: A total of 355 genes were significantly differentially expressed between sample types (9.87 to –9.71 log2 fold change). The top 3 genes significantly upregulated in nasal lysate samples were Mucin 1 (MUC1), Tight Junction Protein 1 (TJP1), and Lipocalin-2 (LCN2). The top 3 genes significantly upregulated in blood samples were cluster of differentiation 3e (CD3E), FYN Proto-Oncogene Src Family Tyrosine Kinase (FYN) and cluster of differentiation 3d (CD3D). Conclusions: Overall, the blood and nasal lavage samples showed vastly distinct gene expression profiles and functional gene pathways which reflect their anatomical and functional origins. Evaluating immune gene expression of the nasal mucosa in addition to blood samples may be beneficial in understanding AR pathophysiology and response to allergen challenge.
Association of Brain-Derived Neurotrophic Factor and Vitamin D with Depression and Obesity: A Population-Based Study
Authors: Goltz Annemarie , Janowitz Deborah , Hannemann Anke , Nauck Matthias , Hoffmann Johanna , Seyfart Tom , Völzke Henry , Terock Jan , Grabe Hans Jörgen
Published: June 2018

Background: Depression and obesity are widespread and closely linked. Brain-derived neurotrophic factor (BDNF) and vitamin D are both assumed to be associated with depression and obesity. Little is known about the interplay between vitamin D and BDNF. We explored the putative associations and interactions between serum BDNF and vitamin D levels with depressive symptoms and abdominal obesity in a large population-based cohort. Methods: Data were obtained from the population-based Study of Health in Pomerania (SHIP)-Trend (n = 3,926). The associations of serum BDNF and vitamin D levels with depressive symptoms (measured using the Patient Health Questionnaire) were assessed with binary and multinomial logistic regression models. The associations of serum BDNF and vitamin D levels with obesity (measured by the waist-to-hip ratio [WHR]) were assessed with binary logistic and linear regression models with restricted cubic splines. Results: Logistic regression models revealed inverse associations of vitamin D with depression (OR = 0.966; 95% CI 0.951–0.981) and obesity (OR = 0.976; 95% CI 0.967–0.985). No linear association of serum BDNF with depression or obesity was found. However, linear regression models revealed a U-shaped association of BDNF with WHR (p < 0.001). Conclusion: Vitamin D was inversely associated with depression and obesity. BDNF was associated with abdominal obesity, but not with depression. At the population level, our results support the relevant roles of vitamin D and BDNF in mental and physical health-related outcomes.
Locally Advanced Cervical Cancer: Is a Trimodality Treatment a Safe and Effective Approach?
Authors: Lorusso Domenica , Martinelli Fabio , Maltese Giuseppa , Fontanella Caterina , Sabatucci Ilaria , Ditto Antonino , Signorelli Mauro , Bogani Giorgio , Lepori Stefano , Tripodi Elisa , Pappalardi Brigida , Scaffa Cono , Cerrotta Annamaria , Rapagliesi Francesco
Published: June 2018

Background: Chemoradiotherapy (CRT) is the standard of care for locally advanced cervical cancer (LACC). Pre-treatment lymph nodes (LN) assessment may have an important therapeutic role. CRT followed by adjuvant chemotherapy increased progression free survival (PFS) and overall survival (OS). Our study evaluated the feasibility and the effectiveness of a trimodality strategy in patients with LACC and positive LN. Methods: Consecutive patients with LACC treated at the National Cancer Institute of Milan were enrolled. All patients underwent pelvic and para-aortic extraperitoneal laparoscopic lymphadenectomy to assess the nodal status. After surgery, patients received radiotherapy followed by chemotherapy according to the stage of disease. Results: Between April 2012 and October 2013, 19 cervical cancer patients were enrolled. Overall, 10 (52.6%) patients presented with positive LN: 6 in the pelvic area and 4 both in the pelvic and para-aortic area. No perioperative major complications occurred. The most common surgical-related adverse events were bleeding (26%), respiratory distress (5%), infection (5%) and the development of lymphoceles (25%). Overall, 15 (78.9%) complete responses and 2 (10.5%) partial responses were registered. After a median follow-up of 43.3 months, 89.5% of patients were alive at the last visit, and 3-year PFS was 63%. Conclusions: Trimodality treatment appears feasible, well tolerated and promising in terms of oncologic outcome.
Transplanted Mesenchymal Stem Cells Reduce Autophagic Flux in Infarcted Hearts via the Exosomal Transfer of miR-125b
Authors: Xiao Changchen , Wang Kan , Xu Yinchuan , Hu Hengxun , Zhang Na , Wang Yingchao , Zhong Zhiwei , Zhao Jing , Li Qingju , Zhu Dan , Ke Changle , Zhong Shuhan , Wu Xianpeng , Yu Hong , Zhu Wei , Chen Jinghai , Zhang Jianyi , Wang Jian’an , Hu Xinyang
Published: June 2018

Rationale
:

Autophagy can preserve cell viability under conditions of mild ischemic stress by degrading damaged organelles for ATP production, but under conditions of severe ischemia, it can promote cell death and worsen cardiac performance. Mesenchymal stem cells (MSCs) are cardioprotective when tested in animal models of myocardial infarction, but whether these benefits occur through the regulation of autophagy is unknown.

Objective:

To determine whether transplanted MSCs reduce the rate of autophagic degradation (autophagic flux) in infarcted hearts and if so, to characterize the mechanisms involved.

Methods and Results:

Treatment with transplanted MSCs improved cardiac function and infarct size while reducing apoptosis and measures of autophagic flux (bafilomycin A1-induced LC3-II [microtubule-associated protein 1 light chain 3] accumulation and autophagosome/autolysosome prevalence) in infarcted mouse hearts. In hypoxia and serum deprivation–cultured neonatal mouse cardiomyocytes, autophagic flux and cell death, as well as p53-Bnip3 (B-cell lymphoma 2–interacting protein 3) signaling, declined when the cells were cultured with MSCs or MSC-secreted exosomes (MSC-exo), but the changes associated with MSC-exo were largely abolished by pretreatment with the exosomal inhibitor GW4869. Furthermore, a mimic of the exosomal oligonucleotide miR-125b reduced, whereas an anti-miR-125b oligonucleotide increased, autophagic flux and cell death, via modulating p53-Bnip3 signaling in hypoxia and serum deprivation–cultured neonatal mouse cardiomyocytes. In the in vivo mouse myocardial infarction model, MSC-exo, but not the exosomes obtained from MSCs pretreated with the anti-miR-125b oligonucleotide (MSC-exo
anti-miR-125b
), recapitulated the same results as the in vitro experiments. Moreover, measurements of infarct size and cardiac function were significantly better in groups that were treated with MSC-exo than the MSC-exo
anti-miR-125b
group.

Conclusions:

The beneficial effects offered by MSC transplantation after myocardial infarction are at least partially because of improved autophagic flux through excreted exosome containing mainly miR-125b-5p.
Economic Growth in the Governance of the Cold War Divide: Mikoyan's Encounter with Japan, Summer 1961
Authors: Sanchez-Sibony Oscar
Published: June 2018

Using recently declassified documents from Moscow, this article recounts Anastas Mikoyan's trip to Japan in the summer of 1961. The trip served as an inflection point in the commercial relationship between the Soviet Union and Japan—a relationship that by the end of the decade had become the most extensive between the Soviet Union and a country of the “free world.” The article indicates that narratives focusing on ideologies of great-power rivalry during the Cold War tend to miss the kinds of global ideological currents that shaped many states’ behavior after 1945. Mikoyan's discussions with political and business elites in Japan suggest that an ideology of economic growth increasingly underlay concepts of political governance on both sides and ultimately allowed for the kind of cooperation that characterized Soviet-Japanese relations.
The Enemy of My Enemy: The Soviet Union, East Germany, and the Iranian Tudeh Party's Support for Ayatollah Khomeini
Authors: Friedman Jeremy
Published: June 2018

This article examines the strategy of the Iranian Tudeh Party in concert with its Soviet and East German patrons and allies during and after the Iranian revolution of 1979. The article assesses the thinking behind the Tudeh's strategy of unwavering support for Ayatollah Ruhollah Khomeini and his Islamist allies, even after other major leftist parties had begun fighting the new Islamic regime. This strategy was a product of the international Communist movement's model of revolution in the developing world that envisioned new states following a “non-capitalist path of development.” In Iran, this was compounded by the use of Allende-era Chile as a model for the politics of revolutionary Iran, as well as a deep conviction that Islamism could not provide an effective model of governance in the twentieth century and therefore would collapse of its own accord within months after the Islamists seized power.
The Challenge of Western Neutralism during the Cold War: Britain and the Buildup of a Nigerian Air Force
Authors: Wyss Marco
Published: June 2018

In the wake of decolonization, Britain wanted to maintain its strategic interests in Nigeria and to keep the newly independent African country in the Western orbit. Having abrogated a defense agreement in reaction to Nigerian domestic opposition, the British government counted on military assistance to secure its postcolonial security role. The British thus hoped to gain responsibility for the buildup of a Nigerian air force, which the authorities in Lagos wished to establish for national prestige and protection against potential enemies such as Ghana. The Nigerians, however, first tried to secure the requisite assistance from Commonwealth countries other than Britain before opting for a West German air force mission. The Nigerian government aimed to reduce its dependence on Britain and thereby burnish its neutralist credentials. Yet London was challenged by a Western version of neutralism, similar to Western neutrality, because the Nigerians never attempted to approach the Soviet bloc about military assistance.
Neuronal Population Responses in the Human Ventral Temporal and Lateral Parietal Cortex during Arithmetic Processing with Digits and Number Words
Authors: Baek Sori , Daitch Amy L. , Pinheiro-Chagas Pedro , Parvizi Josef
Published: June 2018

Past research has identified anatomically specific sites within the posterior inferior temporal gyrus (PITG) and the intraparietal sulcus (IPS) areas that are engaged during arithmetic processing. Although a small region of the PITG (known as the number form area) is selectively engaged in the processing of numerals, its surrounding area is activated during both digit and number word processing. In eight participants with intracranial electrodes, we compared the timing and selectivity of electrophysiological responses in the number form area-surround and IPS regions during arithmetic processing with digits and number words. Our recordings revealed stronger electrophysiological responses in the high-frequency broadband range in both regions to digits than number words, with the difference that number words elicited delayed activity in the IPS but not PITG. Our findings of distinct profiles of responses in the PITG and the IPS to digits compared with number words provide novel information that is relevant to existing theoretical models of mathematical cognition.