bluuebunny/crossref_metadata_2025 huggingface dataset:
Herb Formula ZhenRongDan Balances Sex Hormones, Modulates Organ Atrophy, and Restores ERα and ERβ Expressions in Ovariectomized Rats
Authors: Zhang Xuan , Chen Qian , Chen Bo , Wang Fangqin , Chen Xiao-Hong
Published: June 2018

Herb mixtures are widely used for treatment of the menopausal syndrome long before the hormonal therapy. However, there is insufficient data for herb remedies in treating menopausal syndromes. Here we aim to investigate the effect of ZhenRongDan (ZRD) in balancing female hormones, regulating expression of estrogen receptors (ERs), and preventing organ atrophy in menopausal rats. Rats that underwent bilateral ovariectomy were used in the experiments; the effects of ZRD on serum follicle‐stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), and estradiol (E2) levels were observed. Histology of vagina and ERs expression in vagina, uterus, and adrenal gland were also examined. ELISAs were used to analyze the changes of FSH, LH, PRL, and E2 in serum, and the morphological changes of the cervical epithelium cells were observed by Hematoxylin & Eosin (H&E) staining. Immunohistochemistry and western blot were applied to detect estrogen receptors subtypes alpha (ERα) and beta (ERβ) expression in vagina, uterus, and adrenal gland. We found that ZRD could significantly reduce the weight of the adrenal gland and increase the weight of the uterus. It could decrease the release of FSH and LH as well as increasing E2 and PRL levels. Furthermore, ZRD could improve the number of cervical vaginal epithelial cells and increase the thickness of the vaginal wall. And the altered expressions of ERα and ERβ are also restored by ZRD. ZRD could obviously relieve the endocrine disorders, modulate organ atrophy, and restore ERα and ERβ expression in the ovariectomized rat model.
Scanning Techniques for Nanobioconjugates of Carbon Nanotubes
Authors: Umemura Kazuo , Sato Shizuma
Published: June 2018

Nanobioconjugates using carbon nanotubes (CNTs) are attractive and promising hybrid materials. Various biological applications using the CNT nanobioconjugates, for example, drug delivery systems and nanobiosensors, have been proposed by many authors. Scanning techniques such as scanning electron microscopy (SEM) and scanning probe microscopy (SPM) have advantages to characterize the CNT nanobioconjugates under various conditions, for example, isolated conjugates, conjugates in thin films, and conjugates in living cells. In this review article, almost 300 papers are categorized based on types of CNT applications, and various scanning data are introduced to illuminate merits of scanning techniques.
Slant Angle and Its Influence on Rock Cutting Performance
Authors: Sun Yong , Li Xingsheng
Published: June 2018

Rock cutting is an important aspect of the civil engineering, for example, tunnelling. To improve cutting efficiency, it is important to understand the rock failure (fracture) mechanisms and the influences of cutting parameters on rock fracture behaviour. This study identified that the relative position of a pick (rock cutting tool) to the rock surface is critical to the cutting performance of the pick during rock cutting process. However, the pick tilt angle commonly used by the industries is not sufficient to describe this relative position. To address this issue, a new angle named “slant angle” is introduced. The slant angle of a pick is determined by its tilt angle and the inclination angle of the rock surface. The calculation of the slant angle is presented. A series of laboratory rock cutting experiments were conducted to investigate the influence of the slant angle on cutting force and rock fracture pattern, and two new findings were made: (1) the rotational angle of the groove cut by a tilted pick was possibly different from the tilt angle and (2) all forces on a pick increased significantly with the increase of the slant angle. The findings of this study can help improve the rock cutting efficiency.
Comparison of Modular Control during Smash Shot between Advanced and Beginner Badminton Players
Authors: Matsunaga Naoto , Kaneoka Koji
Published: June 2018

This study investigated muscle synergy during smash shot in badminton and compared synergies of advanced players (more than 7 years experience) and beginner players (less than 3 years experience). The dominant hand of all players was the right side. Muscle activities were recorded on both sides of the rectus abdominis, external oblique (EO), internal oblique/transversus abdominis (IO/TrA), and erector spinae. Additionally, the right side of the biceps brachii, triceps brachii, flexor carpi radialis, flexor carpi ulnaris, and flexor digitorum profundus muscle activities were recorded. All data was obtained using surface electromyography. Synergy was extracted from electromyography signals using nonnegative matrix factorization. Extracted synergies in each group were compared using scalar product (SP) which is the similarity index. As a result, two synergies were extracted in the beginner players and three synergies were extracted in advanced players. Beginner and advanced players had one synergy in common (SP = 0.86) that was mainly on the left side of the EO. It activated in the early stroke and had a role of side bending from the left to hit the shuttlecock at a higher point. Another synergy that had coactivation of the IO/TrA and forearm muscles at impact was extracted only for advanced players and it may enhance the smash shot performance in badminton.
Evaluation of Skin and Soft Tissue Infection Outcomes and Admission Decisions in Emergency Department Patients
Authors: Black Nicholas , Schrock Jon W.
Published: June 2018

Background. Skin and soft tissue infections are common presenting complaints for Emergency Department (ED) patients. Although they are common, there remain no definitive guidelines on decisions of admission for these patients. Objectives. To determine the influence of demographic and clinical information of those presenting with skin and soft tissue infection(s) (SSTI) on both disposition and treatment failure. Methods. We prospectively enrolled adults with SSTI seen at a large urban ED. Secondary outcome was treatment failure. Statistics utilized t-tests and multivariate logistic regression. Results. We enrolled 125 subjects and 32 were admitted. 15.2% of patients failed treatment with both increasing age and infection area correlating with admission. IV drug use (IVDU) (OR: 10.2; 95% confidence interval [CI]: 1.9 to 50.0) and recent antibiotic use (OR: 2.9; 95% CI 1.003 to 8.333) independently predicted admission. Age and recent surgery in the area of infection (OR: 6.4; 95% CI 1.3 to 30.8) showed positive association with treatment failure. IV antibiotics (OR: 22.3; 95% CI 2.8 to 179.4) and admission (OR: 12.1; 95% CI 2.9 to 50.4) strongly predicted treatment failure. Conclusions. Age, infection size, IVDU, and recent antibiotics predicted admission. Age, recent surgery at infection site, IV antibiotics, and admission correlated with treatment failure.
Non-Fickian Solute Transport in a Single Fracture of Marble Parallel Plate
Authors: Yan Xiaosan , Qian Jiazhong , Ma Lei , Wang Mu , Hu Aofeng
Published: June 2018

Accurate prediction of solute transport processes in a fracture aquifer is an important task not only for proper management of the groundwater but also for pollution control. A key issue of this task is how to accurately obtain the experimental data and to analyze the solute transport in fracture in subsurface hydrology, which would greatly help us to understand the releasing mechanism and transport of the solute in a fracture. In this study, a fracture experiment is conducted in a laboratory based on previous studies. The fracture used with a length of 60 cm and a width of 10 cm is sealed with glass glue to avoid leakage of tracer due to uneven fracture walls. The sodium chloride (NaCl) solute is injected from the left of the fracture. And an electrical conductivity monitoring system is installed on the right of the fracture. Then breakthrough curves (BTCs) of solute transport are fitted using the classical advection-dispersion equation (ADE) and the truncation power-law function (TPL) model in the package of the continuous time random walk (CTRW). The results show that the flow satisfies non-Darcian law in the experimental conditions, which can be better fitted using the Forchheimer equation and Izbash equation. The solute transport presents non-Fickian phenomena and shows a long tailing. The fitting results of the TPL model are far better than ADE in fitting the long tailing at three different flow velocities. Furthermore, electrical conductivity monitoring method not only is effective but also has an advantage of no disturbance to water and concentration fields in a fracture.
The Role of Autoimmunity in the Pathogenesis of Sudden Sensorineural Hearing Loss
Authors: Li Guangfei , You Dan , Ma Jiaoyao , Li Wen , Li Huawei , Sun Shan
Published: June 2018

Sudden sensorineural hearing loss (SSHL) is a clinically common acute symptom in otolaryngology. Although the incidence of SSHL has increased around the world in recent years, the etiology of the disease is still unclear. It has been reported that infections, ototoxic drugs, membrane labyrinth rupture, carcinomas, circulatory system diseases, autoimmune diseases, brain lesions, mental diseases, congenital or inherited diseases, and so on, are all risk factors for SSHL. Here, we discuss the autoimmune mechanisms behind SSHL, which might be induced by type II–IV allergic reactions. We also introduce the main immunosuppressive medications that have been used to treat SSHL, which will help us to identify potential targets for immune therapy.
An Effective Classification Approach for Big Data Security Based on GMPLS/MPLS Networks
Authors: Alouneh Sahel , Al-Hawari Feras , Hababeh Ismail , Ghinea Gheorghita
Published: June 2018

The need for effective approaches to handle big data that is characterized by its large volume, different types, and high velocity is vital and hence has recently attracted the attention of several research groups. This is especially the case when traditional data processing techniques and capabilities proved to be insufficient in that regard. Another aspect that is equally important while processing big data is its security, as emphasized in this paper. Accordingly, we propose to process big data in two different tiers. The first tier classifies the data based on its structure and on whether security is required or not. In contrast, the second tier analyzes and processes the data based on volume, variety, and velocity factors. Simulation results demonstrated that using classification feedback from a MPLS/GMPLS core network proved to be key in reducing the data evaluation and processing time.
Tobacco Use and Associated Factors in Patients Presenting to a Psychiatric Emergency Room
Authors: Collins Ashely , Ajayi Oluwadamilare , Diamond Savannah , Diamond William , Holroyd Suzanne
Published: June 2018

Background. Rates of cigarette smoking among the public and individuals with mental illness have been well documented. Studies have demonstrated that prevalence of smoking among individuals with mental illness remains elevated compared to the general population and as a distinct subgroup, individuals with mental illness consume more than a third of cigarettes sold in the U.S. However, information on rates of smoking among patients presenting to a psychiatric emergency room (ER) is lacking. This study assesses this understudied population for smoking prevalence and associated factors.Methods. A retrospective chart review of 203 distinct psychiatric ER patients was conducted. Demographics, tobacco use, substance use, psychiatric diagnoses, and family history were noted and analyzed with SPSS.Result. Tobacco use rates were noted to be nearly fifty percent and significant associations were found with active suicidal ideation, alcohol use disorders, illicit drug use disorders, and history of prior psychiatric hospitalization.Conclusion. Tobacco use among psychiatric ER patients is much higher than that of the general population and associated with active suicidal ideations, alcohol use disorders, and illicit substance use disorders. These findings should be considered in the evaluation and expectant management of these patients by their clinicians and healthcare providers.
Endoscopic Surgery under Fluoroscopic Guidance Is Useful for Diagnosing and Treating Epiphyseal Osteomyelitis Caused by Mycobacterium Species
Authors: Ochi Hironori , Taira Katsuaki , Nemoto Naho , Oikawa Noboru , Nagao Soya , Takano Tadamasa , Kaneko Kazuo
Published: June 2018

Osteomyelitis caused by Mycobacterium species may be difficult to diagnose and treat. We report a case of treatment for osteomyelitis caused by Mycobacterium species in the epiphysis of the right proximal tibia. A 28-month-old boy presented to a hospital with symptoms of fever and right knee pain. He had been vaccinated with Mycobacterium bovis Bacille Calmette-Guérin (BCG) at five months of age. The epiphyseal radiolucent lesion had increased in size and extended to the metaphysis through the physis on a plain radiograph of the right proximal tibia. Surgical drainage and curettage of the lesion were performed with an endoscope under C-arm fluoroscopy. The intraoperative histopathological examination revealed granulation tissue composed of caseous necrosis and Langerhans giant cells, revealing Mycobacterium species to be the causative pathogen. Because of suspected osteomyelitis caused by BCG, the antituberculosis drugs were administered orally from an early postoperative stage. A plain radiograph taken eight months postoperatively showed bone regeneration in the area of curettage and a slight physeal bridge, in addition to normalization of the inflammatory response on blood sampling. It was possible to perform accurate diagnosis and rapid treatment for epiphyseal osteomyelitis caused by Mycobacterium species using endoscopic surgery under fluoroscopic guidance.
Potential of Gene and Cell Therapy for Inner Ear Hair Cells
Authors: Lee Min Yong , Park Yong-Ho
Published: June 2018

Sensorineural hearing loss is caused by the loss of sensory hair cells (HCs) or a damaged afferent nerve pathway to the auditory cortex. The most common option for the treatment of sensorineural hearing loss is hearing rehabilitation using hearing devices. Various kinds of hearing devices are available but, despite recent advancements, their perceived sound quality does not mimic that of the “naïve” cochlea. Damage to crucial cochlear structures is mostly irreversible and results in permanent hearing loss. Cochlear HC regeneration has long been an important goal in the field of hearing research. However, it remains challenging because, thus far, no medical treatment has successfully regenerated cochlear HCs. Recent advances in genetic modulation and developmental techniques have led to novel approaches to generating HCs or protecting against HC loss, to preserve hearing. In this review, we present and review the current status of two different approaches to restoring or protecting hearing, gene therapy, including the newly introduced CRISPR/Cas9 genome editing, and stem cell therapy, and suggest the future direction.
Online Structural Health Monitoring of Rotating Machinery via Ultrasonic Guided Waves
Authors: Li Ming , Meng Guang , Li Hongguang , Qiu Jianxi , Li Fucai
Published: June 2018

This paper focuses on the establishment of the online structural health monitoring strategy for rotating shafts using ultrasonic guided waves. The dispersion of cylindrical shaft is investigated and a conclusion that the longitudinal ultrasonic wave propagating along the cylindrical shaft can hardly be interfered by the rotation is obtained. The experimental system and the numerical simulation model have been constructed, based on the fact that the experimental research and the numerical verification have been conducted intensively. The strategy can be concluded no matter the cracked rotor is at rest or rotating. Comparing with the same rotor without crack, the amplitudes of the guided wave packages descend along the transmission path and the symmetric path where crack exists; however, the amplitude of the wave packages will ascend along the other transmission paths.
SERPINA1 mRNA as a Treatment for Alpha-1 Antitrypsin Deficiency
Authors: Connolly Brendan , Isaacs Cleo , Cheng Lei , Asrani Kirtika H. , Subramanian Romesh R.
Published: June 2018

Alpha-1-antitrypsin (AAT) deficiency is a genetic disorder that produces inactive/defective AAT due to mutations in the SERPINA1 gene encoding AAT. This disease is associated with decreased activity of AAT in the lungs and deposition of excessive defective AAT protein in the liver. Currently there is no specific treatment for liver disease associated with AAT deficiency. AAT lung disease is often treated with one of several serum protein replacement products; however, long-term studies of the effectiveness of SerpinA1 replacement therapy are not available, and it does not reduce liver damage in AAT deficiency. mRNA therapy could potentially target both the liver and lungs of AAT deficient patients. AAT patient fibroblasts and AAT patient fibroblast-derived hepatocytes were transfected with SERPINA1-encoding mRNA and cell culture media were tested for SerpinA1 expression. Our data demonstrates increased SerpinA1 protein in culture media from treated AAT patient fibroblasts and AAT patient fibroblast-derived hepatocytes. In vivo studies in wild type mice demonstrate SERPINA1 mRNA biodistribution in liver and lungs, as well as SerpinA1 protein expression in these two target organs which are critically affected in AAT deficiency. Taken together, our data suggests that SerpinA1 mRNA therapy has the potential to benefit patients suffering from AAT deficiency.
A Threat Assessment Method for Unmanned Aerial Vehicle Based on Bayesian Networks under the Condition of Small Data Sets
Authors: Di Ruohai , Gao Xiaoguang , Guo Zhigao , Wan Kaifang
Published: June 2018

The autonomous decision-making of a UAV is based on rapid and accurate threat assessment of the target. Accordingly, modeling of threat assessment under the condition of a small data set is studied in this paper. First, the operational scenario of a manned/unmanned aerial vehicle is constructed, and feature selection and data preprocessing are performed. Second, to obtain the structure, a modeling method for threat assessment is proposed based on an improved BIC score. Finally, the obtained model is applied to compute the threat probability using the junction tree algorithm. The experimental results show that the method proposed in this paper is an available method for threat assessment under the condition of small data sets.
A Laser-Based Noncontact Vibration Technique for Health Monitoring of Structural Cables: Background, Success, and New Developments
Authors: Mehrabi Armin B. , Farhangdoust Saman
Published: June 2018

Structural cables are susceptible to the effects of high stress concentrations, corrosion, and wind-induced and other vibrations. Cables are normally the most critical elements in a cable-supported structure and their well-being is very important in the health of the structure. The laser-based vibration technique discussed in this paper is a means for health monitoring of cables and therefore the entire cable-supported structure. This technique uses a noncontact remote sensing laser vibrometer for collecting cable vibration data from distances of up to several hundreds of feet and determines its dynamic characteristics including vibration frequencies and damping ratios. A formulation specifically developed for structural cables capable of accounting for important cable parameters is then used to calculate the cable force. Estimated forces in the cables are compared to previously measured forces or designer’s prediction to detect patterns associated with damage to the cable itself and/or changes to the structure elsewhere. The estimated damping ratios are also compared against predefined criteria to infer about susceptibility against wind-induced vibrations and other vibrations. The technique provides rapid, effective, and accurate means for health monitoring of cable-supported structures. It determines the locations and elements with potential damage and the need for detailed and hands on inspection. To date, the technique has been used successfully for evaluation of twenty-five major bridges in the US and abroad. Though originally devised for condition assessment of stay cables, it has been developed further to include a variety of systems and conditions among them structural hanger ropes in suspension, truss, and arch supported bridges, ungrouted stay cables, cables with cross-ties, and external posttensioning tendons in segmental bridge construction. It has also found a valuable place in construction-phase activities for verification of forces in tension elements with minimal efforts. Future endeavors for automation and aerial delivery are being considered for this technique.
Intramural Bowel Hematoma Presenting as Small Bowel Obstruction in a Patient on Low-Molecular-Weight Heparin
Authors: Choi Beatrix Hyemin , Koeckert Michael , Tomita Sandra
Published: June 2018

There is increasing use of low-molecular-weight heparin (LMWH) for treatment of pediatric thromboembolic disease as it has been shown to be safe and effective. It has several advantages over unfractionated heparin, such as reduced need for monitoring, easier route of administration, decreased risk of heparin-induced thrombocytopenia, and lack of drug-drug interactions. Nevertheless, LMWH still poses a bleeding risk as with any anticoagulant therapy. We present the case of a 4-year-old boy who was placed on LMWH for a catheter-related deep venous thrombosis in the setting of intractable seizures and subsequently developed a small bowel obstruction secondary to a suspected intussusception. He underwent exploratory laparotomy and was found to have an intramural bowel hematoma. Prior to this bleed, the patient had been monitored daily, and his anti-Xa levels were found to be in the therapeutic range. This case highlights the need for a high index of suspicion for spontaneous bleeding even in the setting of therapeutic anti-Xa levels.
Bone Response to Titanium Implants Coated with Double- or Single-Stranded DNA
Authors: Miyamoto Nagahiro , Yamachika Rina , Sakurai Toshitsugu , Hayakawa Tohru , Hosoya Noriyasu
Published: June 2018

We aimed to evaluate in vivo bone response and in vitro apatite formation to titanium (Ti) implants, coated with double-stranded DNA (DNA-d) or single-stranded DNA (DNA-s), and to compare the influence in different structure of DNA, double strand and single strand on bone response and apatite formation. The bone responses to multilayered DNA-d/protamine or DNA-s/protamine coating implants were evaluated after implantation into the extracted sockets of rat maxillary molars. Apatite formation on either coating surface after immersion in simulated body fluid (SBF) was evaluated using the quartz crystal microbalance (QCM) method. DNA-d/protamine and DNA-s/protamine coatings produced more roughened and hydrophilic surfaces than untreated Ti. Animal experiments showed that higher bone-to-implant ratios were achieved 3 and 6 weeks after implantation using DNA-d/protamine and DNA-s/protamine coatings compared with Ti. QCM measurements revealed that each coating contributed to significant earlier apatite formation in SBF. We conclude that both DNA-d/protamine and DNA-s/protamine coatings enhanced early bone formation. We suggest that a DNA-multilayer coating is useful for the surface modification of a Ti implant.
Gender Dysphoria: Bioethical Aspects of Medical Treatment
Authors: Bizic Marta R. , Jeftovic Milos , Pusica Slavica , Stojanovic Borko , Duisin Dragana , Vujovic Svetlana , Rakic Vojin , Djordjevic Miroslav L.
Published: June 2018

Gender affirmation surgery remains one of the greatest challenges in transgender medicine. In recent years, there have been continuous discussions on bioethical aspects in the treatment of persons with gender dysphoria. Gender reassignment is a difficult process, including not only hormonal treatment with possible surgery but also social discrimination and stigma. There is a great variety between countries in specified tasks involved in gender reassignment, and a complex combination of medical treatment and legal paperwork is required in most cases. The most frequent bioethical questions in transgender medicine pertain to the optimal treatment of adolescents, sterilization as a requirement for legal recognition, role of fertility and parenthood, and regret after gender reassignment. We review the recent literature with respect to any new information on bioethical aspects related to medical treatment of people with gender dysphoria.
Direct Intrahepatic Portocaval Shunt for Sinusoidal Obstruction Syndrome Associated with Hepatotoxicity of Pyrrolizidine Alkaloids
Authors: Luo Shihua , Chu Jianguo , Huang He , Yao Kechun
Published: June 2018

We retrospectively identified 89 consecutive patients from January 2004 to January 2012 to investigate efficacy of direct intrahepatic portocaval shunt (DIPS) combined with inferior vena cava (IVC) stenting for sinusoidal obstruction syndrome (SOS) associated with hepatotoxicity of pyrrolizidine alkaloids. Indications for treatment were variceal hemorrhage and/or refractory ascites. Patients were treated with DIPS plus IVC stenting (group A, n=68) or DIPS alone (group B, n=21). A technical success rate of 100% was obtained in all 89 patients, and there were no early procedure-related adverse events or 30-day mortality. Mean portosystemic gradient decreased in both groups. Changes in aspartate and alanine aminotransferases and total bilirubin did not differ between the groups. Ascites disappeared in group A but was not obvious in group B until IVC stenting. During follow-up, recurrent bleeding and ascites and incidence of hepatic encephalopathy did not differ between the groups. The 1-, 3-, and 5-year survival rate was 98, 89.59, and 80%, respectively. Satisfactory clinical results were obtained for combined DIPS and IVC stenting for SOS associated with pyrrolizidine-alkaloid-related decompensated cirrhosis.
Age Correlates with Response to Anti-PD1, Reflecting Age-Related Differences in Intratumoral Effector and Regulatory T-Cell Populations
Authors: Kugel Curtis H. , Douglass Stephen M. , Webster Marie R. , Kaur Amanpreet , Liu Qin , Yin Xiangfan , Weiss Sarah A. , Darvishian Farbod , Al-Rohil Rami N. , Ndoye Abibatou , Behera Reeti , Alicea Gretchen M. , Ecker Brett L. , Fane Mitchell , Allegrezza Michael J. , Svoronos Nikolaos , Kumar Vinit , Wang Daniel Y. , Somasundaram Rajasekharan , Hu-Lieskovan Siwen , Ozgun Alpaslan , Herlyn Meenhard , Conejo-Garcia Jose R. , Gabrilovich Dmitry , Stone Erica L. , Nowicki Theodore S. , Sosman Jeffrey , Rai Rajat , Carlino Matteo S. , Long Georgina V. , Marais Richard , Ribas Antoni , Eroglu Zeynep , Davies Michael A. , Schilling Bastian , Schadendorf Dirk , Xu Wei , Amaravadi Ravi K. , Menzies Alexander M. , McQuade Jennifer L. , Johnson Douglas B. , Osman Iman , Weeraratna Ashani T.
Published: June 2018

Purpose: We have shown that the aged microenvironment increases melanoma metastasis, and decreases response to targeted therapy, and here we queried response to anti-PD1.

Experimental Design: We analyzed the relationship between age, response to anti-PD1, and prior therapy in 538 patients. We used mouse models of melanoma, to analyze the intratumoral immune microenvironment in young versus aged mice and confirmed our findings in human melanoma biopsies.

Results: Patients over the age of 60 responded more efficiently to anti-PD-1, and likelihood of response to anti-PD-1 increased with age, even when we controlled for prior MAPKi therapy. Placing genetically identical tumors in aged mice (52 weeks) significantly increased their response to anti-PD1 as compared with the same tumors in young mice (8 weeks). These data suggest that this increased response in aged patients occurs even in the absence of a more complex mutational landscape. Next, we found that young mice had a significantly higher population of regulatory T cells (Tregs), skewing the CD8+:Treg ratio. FOXP3 staining of human melanoma biopsies revealed similar increases in Tregs in young patients. Depletion of Tregs using anti-CD25 increased the response to anti-PD1 in young mice.

Conclusions: While there are obvious limitations to our study, including our inability to conduct a meta-analysis due to a lack of available data, and our inability to control for mutational burden, there is a remarkable consistency in these data from over 500 patients across 8 different institutes worldwide. These results stress the importance of considering age as a factor for immunotherapy response. Clin Cancer Res; 24(21); 5347–56. ©2018 AACR.

See related commentary by Pawelec, p. 5193
Nuclear PTEN Localization Contributes to DNA Damage Response in Endometrial Adenocarcinoma and Could Have a Diagnostic Benefit for Therapeutic Management of the Disease
Authors: Mukherjee Ananda , Patterson Amanda L. , George Jitu W. , Carpenter Tyler J. , Madaj Zachary B. , Hostetter Galen , Risinger John I. , Teixeira Jose M.
Published: June 2018

Endometrial adenocarcinoma (EndoCA) is the most common gynecologic cancer type in the United States, and its incidence is increasing. The majority of patients are disease-free after surgical resection of stage I tumors, which is often followed by radiotherapy, but most patients with advanced disease recur and have a poor prognosis, largely because the tumors become refractory to cytotoxic chemotherapies. PTEN, a commonly mutated tumor suppressor in EndoCAs, is well known for its ability to inhibit the AKT/mTOR signaling pathway. Nuclear functions for PTEN have been proposed as well, but whether those affect EndoCA development, progression, or outcomes is not well understood. Using immunohistochemistry, nuclear PTEN expression was observed in approximately half of EndoCA patient tumors, independent of grade and cytoplasmic PTEN expression. Higher levels of the DNA damage response (DDR) marker, γH2AX, were observed by immunohistochemistry and immunofluorescence in human EndoCA tumor sections that were PTEN-negative, in murine EndoCA tissues that were genetically modified to be PTEN-null, and in Ishikawa EndoCA cells, which do not express endogenous PTEN. Overexpression of exogenous PTEN-WT or PTEN-NLS, a modified PTEN with an added nuclear localization signal, significantly improved both DDR and G2–M transition in Ishikawa cells treated with a DNA-damaging agent. Whereas PARP inhibition with Olaparib was not as effective in Ishikawa cells expressing native or PTEN-NLS, inhibition with Talazoparib was not affected by PTEN overexpression. These results suggest that nuclear PTEN subcellular localization in human EndoCA could be diagnostic when considering DDR therapeutic intervention. Mol Cancer Ther; 17(9); 1995–2003. ©2018 AACR.
Endotracheal Intubation and In-Hospital Mortality after Intracerebral Hemorrhage
Authors: Lioutas Vasileios-Arsenios , Marchina Sarah , Caplan Louis R. , Selim Magdy , Tarsia Joseph , Catanese Luciana , Edlow Jonathan , Kumar Sandeep
Published: June 2018

Background: Many patients with acute intracerebral hemorrhages (ICHs) undergo endotracheal intubation with subsequent mechanical ventilation (MV) for “airway protection” with the intent to prevent aspiration, pneumonias, and its related mortality. Conversely, these procedures may independently promote pneumonia, laryngeal trauma, dysphagia, and adversely affect patient outcomes. The net benefit of intubation and MV in this patient cohort has not been systematically investigated. Methods: We conducted a large single-center observational cohort study to examine the independent association between endotracheal intubation and MV, hospital-acquired pneumonia (HAP), and in-hospital mortality (HM) in patients with ICH. All consecutive patients admitted with a primary diagnosis of a spontaneous ICH to a tertiary care hospital in Boston, Massachusetts, from June 2000 through January 2014, who were ≥18 years of age and hospitalized for ≥2 days were eligible for inclusion. Patients with pneumonia on admission, or those having brain or lung neoplasms were excluded. Our exposure of interest was endotracheal intubation and MV during hospitalization; our primary outcomes were incidence of HAP and HM, ascertained using International Classification of Diseases-9 and administrative discharge disposition codes, respectively, in patients who underwent endotracheal intubation and MV versus those who did not. Multivariable logistic regression was used to control for confounders. Results: Of the 2,386 hospital admissions screened, 1,384 patients fulfilled study criteria and were included in the final analysis. A total of 507 (36.6%) patients were intubated. Overall 133 (26.23%) patients in the intubated group developed HAP versus 41 (4.67%) patients in the non-intubated group (p < 0.0001); 195 (38.5%) intubated patients died during hospitalization compared to 48 (5.5%) non-intubated patients (p < 0.0001). After confounder adjustments, OR for HAP and HM, were 4.23 (95% CI 2.48–7.22; p < 0.0001) and 4.32 (95% CI 2.5–7.49; p < 0.0001) with c-statistics of 0.79 and 0.89, in the intubated versus non-intubated patients, respectively. Conclusion: In this large hospital-based cohort of patients presenting with an acute spontaneous ICH, endotracheal intubation and MV were associated with increased odds of HAP and HM. These findings urge further examination of the practice of intubation in prospective studies.
Statin Eligibility, Coronary Artery Calcium, and Subsequent Cardiovascular Events According to the 2016 United States Preventive Services Task Force (USPSTF) Statin Guidelines: MESA (Multi‐Ethnic Study of Atherosclerosis)
Authors: Miedema Michael D. , Dardari Zeina A. , Kianoush Sina , Virani Salim S. , Yeboah Joseph , Knickelbine Thomas , Sandfort Veit , Rodriguez Carlos J. , Nasir Khurram , Blaha Michael J.
Published: June 2018

Background

The potential impact of the 2016 United States Preventive Services Task Force (
USPSTF
) guidelines on statins for primary prevention of atherosclerotic cardiovascular disease (
ASCVD)
warrants further analysis.

Methods and Results

We studied participants from MESA (Multi‐Ethnic Study of Atherosclerosis) aged 40 to 75 years and not on statins. We compared statin eligibility at baseline (2000–2002) and over follow‐up between
USPSTF
and the 2013 American College of Cardiology/American Heart Association (
ACC
/
AHA
) guidelines. Coronary artery calcium (
CAC
) was measured at baseline. Absolute
ASCVD
event rates were calculated according to eligibility categories for each guideline. Among 4962
MESA
participants (aged 59.3±8.8 years, 47.2% female), compared with
ACC
/
AHA
guidelines, baseline statin eligibility by
USPSTF
was significantly lower (34.4% versus 49.1%) and increased less over time (39.1% versus 59.1%) at examination 5 [years 2010–2012]). Compared with
ACC
/
AHA
, participants eligible by
USPSTF
were less likely to have zero
CAC
at baseline (36.6% versus 41.2%) and had higher rates of hard
ASCVD
events per 1000 person‐years (11.6 [95% confidence interval, 10.2–13.3] versus 10.0 [8.9–11.3]). The hard
ASCVD
event rate in those eligible by
ACC
/
AHA
but not
USPSTF
was 6.5 (4.9–8.5) events per 1000 person‐years, with the rate varying significantly according to baseline
CAC
(4.2 [2.7–6.7] events in those with
CAC
=0, 12.8 [8.3–19.9] events in those with
CAC
>100).

Conclusions

In
MESA
, compared with
ACC
/
AHA
, the
USPSTF
statin guidelines resulted in a 15% absolute decrease in eligibility. Participants with discordant eligibility had
ASCVD
rates that varied significantly according to baseline
CAC
, suggesting
CAC
could aid clinical decision making for statins in these individuals.
Morpho-molecular characterization of Peroneutypa (Diatrypaceae, Xylariales) with two novel species from Thailand
Authors: SHANG QIU-JU , HYDE KEVIN D. , JEEWON RAJESH , KHAN SEHROON , PROMPUTTHA ITTHAYAKORN , PHOOKAMSAK RUNGTIWA
Published: June 2018

Three species of Peroneutypa were collected from dead wood in Thailand. Two new taxa P. diminutiasca and P. rubiformis are herein described, illustrated and compared with related taxa, based on the evidence from morphology and phylogenetic analyses. Details for the holomorphs of P. rubiformis and the third species P. scoparia are provided. Phylogenetic analyses of a combined ITS and TUB2 DNA sequence dataset support their placement in the genus Peroneutypa  (Diatrypaceae, Xylariales). An updated key to Peroneutypa species is also provided.
Two new combinations of the Philippine Orchidaceae
Authors: NAIVE MARK ARCEBAL K. , ALEJANDRO GRECEBIO JONATHAN D.
Published: June 2018

Recent studies (Schuiteman 2011, Xiang et al. 2013, Pridgeon et al. 2014) have proposed that Euphlebium (Kräenzlin) Brieger (1981: 722) and Grastidium Blume (1825: 333) should be congeneric with Dendrobium Swartz (1799: 82). Most names in Euphlebium and Grastidium have combinations in Dendrobium already. However, Euphlebium papilionaceum Cootes & M.A. Clem. (Cootes & Clements 2017) and Grastidium ginalopeziae Cootes, M.D. De Leon & Naive (Cootes et al. 2017) has not yet been formally transferred. Here we propose the new combination of these two species to merge under the genus Dendrobium.
The genus Cryptotendipes Beck et Beck in Florida, with the description of a new species (Diptera: Chironomidae: Chironominae)
Authors: EPLER J.H.
Published: June 2018

Species of the genus Cryptotendipes Beck et Beck in Florida are reviewed. Previous Florida records of C. casuarius (Townes) are shown to be misidentifications of C. emorsus (Townes). One species new for the state, C. pseudotener (Goetghebuer), is recorded and a new species, C. rutteri Epler, is described from pharate pupae and associated larval exuviae. Thus, a total of three species are known from the state. Keys are provided for adult males, pupae and larvae of these three species.
Two new species of the genus Loboschiza Diakonoff, 1968 (Lepidoptera: Tortricidae: Olethreutinae) from Thailand
Authors: PINKAEW NANTASAK , PHOSRITHONG NETNAPA
Published: June 2018

Two new species of Loboschiza Diakonoff, 1968 are described and illustrated from Thailand: L. bispina Phosrithong and Pinkaew, n.sp., L. rectanguluma Phosrithong and Pinkaew, n.sp. The two new species brings to 20 the number of described species in the genus, which is distributed from India to Australia.
Revising the generic characters of Lobogonodes Bastelberger, 1909, with description of a new species from Taiwan (Lepidoptera: Geometridae: Larentiinae)
Authors: WU SHIPHER , CHANG WEI-CHUN
Published: June 2018

The present study re-assesses the characters of the Oriental genus Lobogonodes Bastelberger, 1909 based on all 8 species, including the newly described L. shiushioui sp. nov. and the distinct species L. dactylotypa Prout, 1940 stat. rev.. Three synapomorphic characters based on the male genitalia are proposed: the presence of a sclerotized subscaphium, the U-shaped connection between the juxta and anellus lobe and the saccus process pointed anteriorly. A new key to the species in this genus is provided.
Revision of the Agrilus gratiosus species-group (Coleoptera, Buprestidae, Agrilinae)
Authors: JENDEK EDUARD
Published: June 2018

The newly defined Agrilus gratiosus species–group comprising ten species from the Oriental region is revised. A key to species is provided and complemented with illustrations of habitus, genitalia and type specimens. The following seven new species are described: Agrilus cultus sp. nov. (Laos); A. oudomxai sp. nov. (Laos); A. pergratus sp. nov. (Malaysia); A. pluridens sp. nov. (Laos, Thailand); A. pubinotus sp. nov. (Indonesia: Sumba Island); A. siberuticola sp. nov. (Indonesia: Siberut Island) and A. signipes sp. nov. (Vietnam). Agrilus makiharai Tôyama, 1987 is considered conspecific with A. bacchus Kerremans, 1913 and therefore the name makiharai syn. nov. is a junior subjective synonym of the name bacchus.
Dynamical Insights into Extreme Short-Term Precipitation Associated with Supercells and Mesovortices
Authors: Nielsen Erik R. , Schumacher Russ S.
Published: June 2018

In some prominent extreme precipitation and flash flood events, radar and rain gauge observations have suggested that the heaviest short-term rainfall accumulations (up to 177 mm h−1) were associated with supercells or mesovortices embedded within larger convective systems. In this research, we aim to identify the influence that rotation has on the storm-scale processes associated with heavy precipitation. Numerical model simulations conducted herein were inspired by a rainfall event that occurred in central Texas in October 2015 where the most extreme rainfall accumulations were collocated with meso-β-scale vortices. Five total simulations were performed to test the sensitivity of precipitation processes to rotation. A control simulation, based on a wind profile from the aforementioned event, was compared with two experiments with successively weaker low-level shear. With greater environmental low-level shear, more precipitation fell, in both a point-maximum and an area-averaged sense. Intense, rotationally induced low-level vertical accelerations associated with the dynamic nonlinear perturbation vertical pressure gradient force were found to enhance the low- to midlevel updraft strength and total vertical mass flux and allowed access to otherwise inhibited sources of moisture and CAPE in the higher-shear simulations. The dynamical accelerations, which increased with the intensity of the low-level shear, dominated over buoyant accelerations in the low levels and were responsible for inducing more intense low-level updrafts that were sustained despite a stable boundary layer.
Impact of the South China Sea Summer Monsoon on the Indian Ocean Dipole
Authors: Zhang Yazhou , Li Jianping , Xue Jiaqing , Feng Juan , Wang Qiuyun , Xu Yidan , Wang Yuehong , Zheng Fei
Published: June 2018

This paper investigates the impact of the South China Sea summer monsoon (SCSSM) on the Indian Ocean dipole (IOD). The results show that the SCSSM has a significant positive relationship with the IOD over the boreal summer [June–August (JJA)] and fall [September–November (SON)]. When the SCSSM is strong, the enhanced southwesterly winds that bring more water vapor to the western North Pacific (WNP) lead to surplus precipitation in the WNP, inducing anomalous ascending there. Consequently, the anomalous descending branch of the SCSSM Hadley circulation (SCSSMHC) develops over the Maritime Continent (MC), favoring deficit precipitation in situ. The precipitation dipole over the WNP and MC as well as the enhanced SCSSMHC leads to intensification of the southeasterly anomalies off Sumatra and Java, which then contributes to the negative sea surface temperature (SST) anomalies through the positive wind–evaporation–SST and wind–thermocline–SST (Bjerknes) feedbacks. Consequently, a positive IOD develops because of the increased zonal gradient of the tropical Indian Ocean SST anomalies and vice versa. The SCSSM has a peak correlation with the IOD when the former leads the latter by three months. This implies that a positive IOD can persist from JJA to SON and reach its mature phase within the frame of the positive Bjerknes feedback in SON. In addition, the local and remote SST anomalies in the tropical Indian and Pacific Oceans have a slight influence on the relationship between the SCSSM and precipitation dipole over the WNP and MC.
The Nature of the Stochastic Wind Forcing of ENSO
Authors: Capotondi Antonietta , Sardeshmukh Prashant D. , Ricciardulli Lucrezia
Published: June 2018

El Niño–Southern Oscillation (ENSO) is commonly viewed as a low-frequency tropical mode of coupled atmosphere–ocean variability energized by stochastic wind forcing. Despite many studies, however, the nature of this broadband stochastic forcing and the relative roles of its high- and low-frequency components in ENSO development remain unclear. In one view, the high-frequency forcing associated with the subseasonal Madden–Julian oscillation (MJO) and westerly wind events (WWEs) excites oceanic Kelvin waves leading to ENSO. An alternative view emphasizes the role of the low-frequency stochastic wind components in directly forcing the low-frequency ENSO modes. These apparently distinct roles of the wind forcing are clarified here using a recently released high-resolution wind dataset for 1990–2015. A spectral analysis shows that although the high-frequency winds do excite high-frequency Kelvin waves, they are much weaker than their interannual counterparts and are a minor contributor to ENSO development. The analysis also suggests that WWEs should be viewed more as short-correlation events with a flat spectrum at low frequencies that can efficiently excite ENSO modes than as strictly high-frequency events that would be highly inefficient in this regard. Interestingly, the low-frequency power of the rapid wind forcing is found to be higher during El Niño than La Niña events, suggesting a role also for state-dependent (i.e., multiplicative) noise forcing in ENSO dynamics.
A Coupled System for Investigating the Physics of Wave–Ice Interactions
Authors: Orzech Mark D. , Shi Fengyan , Veeramony Jayaram , Bateman Samuel , Calantoni Joseph , Kirby James T.
Published: June 2018

A coupled model system has been developed to investigate the physics of wave attenuation and ice edge retreat in the marginal ice zone (MIZ) at small scales [O(m)]. A phase-dependent finite-volume/finite-difference fluid dynamics model is used to simulate waves and currents, and a discrete element software package is employed to represent ice floes as bonded collections of individually tracked smaller particles. We first review the development of the coupled system, with an emphasis on the coupling software and the representation of wave–ice shear stress. Then we describe a series of simulations that were conducted to evaluate and qualitatively validate the performance of the coupled models. The system produced reasonable results for cases of a vertically oscillating ice block and a free-floating ice floe in monochromatic waves. In larger-scale simulations involving multiple ice floes and pancake ice, estimated transmission and reflection coefficients were similar to those obtained from alternate models and/or data, although numerical dissipation may have reduced estimates of transmitted wave energy in longer wave flumes. Challenges and limitations involving relative length scales in the coupled wave and ice domains are explained and discussed.
Jock McCulloch (1945–2018): A Tribute
Authors: Tweedale Geoffrey , Castleman Barry
Published: June 2018

Jock William McCulloch, who died at Melbourne, Australia, in January 2018, was one of the foremost historians of occupational health of his generation. This tribute reviews his career and oeuvre, which was tragically ended by his death from mesothelioma.
Antecedents and Correlates of Adolescent Employment: Race as a Moderator of Psychological Predictors
Authors: McLoyd Vonnie C. , Hallman Samantha K.
Published: June 2018

Adolescent employment during high school has become the norm in the United States, but studies of associated outcomes have yielded mixed results. These discrepant findings may be partly attributable to study methods, including differences in how adolescent employment is measured and how selection factors are taken into account. The present study, based on data from the Child Development Supplement of the Panel Study of Income Dynamics, aims to continue untangling these complexities by (a) examining whether the strength of theoretical predictors varies when predictors are assessed in a comprehensive model that simultaneously controls several psychological, family, and community factors; (b) determining whether the strength of predictors varies depending on how adolescent employment is measured (work status, work duration, and work intensity); and (c) assessing whether race moderates some of these relationships. Results indicate differences in how each predictor is related to each dimension of adolescent employment, as well as a moderating effect of race on the relationship between educational expectations and number of hours adolescents worked each week.