bluuebunny/crossref_metadata_2025 huggingface dataset:
Lesbians achieving pregnancy: The intersections of social location and the heteronormative medicalization of infertility
Authors: Rogalin Christabel L. , Brooks Jane E.
Published: September 2018

Few sociological studies address the relationship between social location and other intersecting influences on lesbian's experiences achieving pregnancy. Other disciplines examine the experiences of lesbians seeking infertility interventions, whether low‐tech (self‐insemination at home) or high‐tech (paying for medical interventions within a medical institution). Recently, as lesbians seek to achieve pregnancy, many are increasingly coming into contact with the heteronormative medical world. In this review, we discuss the intersecting factors of race/ethnicity, social class and sexuality, and how these factors influence and shape lesbian experiences regarding the heteronormative medicalization of infertility.
Cancer stem cell populations in lymphoma in dogs and impact of cytotoxic chemotherapy
Authors: Hartley Genevieve , Elmslie Robyn , Murphy Brent , Hopkins Leone , Guth Amanda , Dow Steven
Published: September 2018

Cancer relapse following chemotherapy has been attributed in part to the presence of cancer stem cells (CSC), which drive tumour growth and metastasis and are highly resistant to the effects of cytotoxic chemotherapy. As a result, treatment with cytotoxic chemotherapy selects for drug‐resistant CSC populations that eventually drive tumour recurrence. Little is known currently regarding the role of CSC in dogs with lymphoma, nor the impact of chemotherapy on CSC populations. Therefore, we prospectively quantitated CSC populations in dogs with B‐cell (BCL) and T‐cell lymphoma (TCL), using tumour aspirates and flow cytometric analysis with a panel of CSC markers. In addition, in vitro studies were carried out to determine the impact of chemotherapy resistance on the stem cell phenotype and stem cell properties of lymphoma cells. We found that the percentages of tumour cells expressing CSC markers were significantly increased in dogs with BCL, compared with B cells from normal lymph nodes. Similar findings were observed in dogs with TCL. In vitro studies revealed that lymphoma cells selected for resistance to CHOP chemotherapy had significantly upregulated expression of CSC markers, formed spheroids in culture more readily, and expressed significantly greater aldehyde dehydrogenase activity compared with chemotherapy‐sensitive tumour cells. Similar results were observed in tumour samples dogs with relapsed BCL. These findings suggest that cytotoxic chemotherapy can lead to a relative enrichment of tumour cells with CSC properties, which may be associated with lymphoma recurrence.
Intra‐operative imaging of surgical margins of canine soft tissue sarcoma using optical coherence tomography
Authors: Selmic Laura E. , Samuelson Jonathan , Reagan Jennifer K. , Mesa Kelly J. , Driskell Elizabeth , Li Joanne , Marjanovic Marina , Boppart Stephen A.
Published: September 2018

Optical coherence tomography (OCT) is a rapid non‐invasive imaging technique that has shown high sensitivity for intra‐operative surgical margin assessment in human breast cancer clinical trials. This promising technology has not been evaluated in veterinary medicine. The objective of this study was to correlate normal and abnormal histological features with OCT images for surgical margins from excised canine soft tissue sarcoma (STS) and to establish image evaluation criteria for identifying positive surgical margins. Fourteen client‐owned dogs underwent surgical resection of a STS and OCT imaging of 2 to 4 areas of interest on the resected specimen were performed. Following imaging these areas were marked with surgical ink and trimmed for histopathology evaluation. Results showed that different tissue types had distinct characteristic appearances on OCT imaging. Adipose tissue exhibited a relatively low scattering and a honey‐comb texture pattern. Skeletal muscle and sarcoma tissue were both dense and highly scattering. While sarcoma tissue was highly scattering, it did not have organized recognizable structure in contrast to muscle which showed clear fibre alignment patterns. In this investigation, we showed different tissue types had different and characteristic scattering and image texture appearances on OCT, which closely correlate with low‐power histology images. Given the differentiation between tissue types the results support that OCT could be used to identify positive surgical margins immediately following resection of STS. Further research is needed to assess the diagnostic accuracy of this method for surgical margin assessment.
Behavioral measurements of auditory streaming and build-up by budgerigars (Melopsittacus undulatus)
Authors: Cai Huaizhen , Screven Laurel A. , Dent Micheal L.
Published: September 2018

The perception of the build-up of auditory streaming has been widely investigated in humans, while it is unknown whether animals experience a similar perception when hearing high (H) and low (L) tonal pattern sequences. The paradigm previously used in European starlings (Sturnus vulgaris) was adopted in two experiments to address the build-up of auditory streaming in budgerigars (Melopsittacus undulatus). In experiment 1, different numbers of repetitions of low-high-low triplets were used in five conditions to study the build-up process. In experiment 2, 5 and 15 repetitions of high-low-high triplets were used to investigate the effects of repetition rate, frequency separation, and frequency range of the two tones on the birds' streaming perception. Similar to humans, budgerigars subjectively experienced the build-up process in auditory streaming; faster repetition rates and larger frequency separations enhanced the streaming perception, and these results were consistent across the two frequency ranges. Response latency analysis indicated that the budgerigars needed a longer amount of time to respond to stimuli that elicited a salient streaming perception. These results indicate, for the first time using a behavioral paradigm, that budgerigars experience a build-up of auditory streaming in a manner similar to humans.
In Vitro
Activity of LYS228, a Novel Monobactam Antibiotic, against Multidrug-Resistant Enterobacteriaceae
Authors: Blais Johanne , Lopez Sara , Li Cindy , Ruzin Alexey , Ranjitkar Srijan , Dean Charles R. , Leeds Jennifer A. , Casarez Anthony , Simmons Robert L. , Reck Folkert
Published: September 2018

LYS228 is a novel monobactam with potent activity against
Enterobacteriaceae
. LYS228 is stable to metallo-β-lactamases (MBLs) and serine carbapenemases, including
Klebsiella pneumoniae
carbapenemases (KPCs), resulting in potency against the majority of extended-spectrum β-lactamase (ESBL)-producing and carbapenem-resistant
Enterobacteriaceae
strains tested.
In Silico
Investigation of the Decline in Clinical Efficacy of Artemisinin Combination Therapies Due to Increasing Artemisinin and Partner Drug Resistance
Authors: Zaloumis Sophie G. , Cao Pengxing , Dini Saber , Davenport Miles P. , Cromer Deborah , Khoury David S. , Fowkes Freya J. I. , McCaw James M. , Simpson Julie A.
Published: September 2018

Antimalarial treatment currently relies on an artemisinin derivative and a longer-acting partner drug. With the emergence of resistance to the artemisinin derivatives and the potential pressure this exerts on the partner drugs, the impact of resistance to each drug on efficacy needs to be investigated.
Coenzyme F
420
-Dependent Glucose-6-Phosphate Dehydrogenase-Coupled Polyglutamylation of Coenzyme F
420
in Mycobacteria
Authors: Purwantini Endang , Loganathan Usha , Mukhopadhyay Biswarup
Published: September 2018

Coenzyme F
420
-dependent reactions of
Mycobacterium tuberculosis
, which causes tuberculosis, potentially contributes to the virulence of this bacterium. The coenzyme carries a glutamic acid-derived tail, the length of which influences the metabolism of
M. tuberculosis
. Mutations that eliminate the production of F
420
with longer tails make
M. tuberculosis
resistant to two new tuberculosis drugs. This report describes that the synthesis of longer glutamyl tails of F
420
requires concerted actions of two enzymes, one of which reduces the coenzyme prior to the action of the other, which catalyzes polyglutamylation. This knowledge will help to develop more effective tuberculosis (TB) drugs. Remarkably, the introduction of multiple glutamate residues into the sidechain of folate (vitamin B
9
) requires similar concerted actions, where one enzyme reduces the vitamin to tetrahydrofolate and the other catalyzes polyglutamylation; folate is required for DNA and amino acid synthesis. Thus, the reported research has also revealed a key similarity between two important cellular systems.
Specificity of QuantiFERON-TB Plus, a New-Generation Interferon Gamma Release Assay
Authors: Siegel S. A. R. , Cavanaugh M. , Ku J. H. , Kawamura L. M. , Winthrop K. L.
Published: September 2018

Interferon gamma release assays (IGRAs) are important tools in identifying prior tuberculosis exposure. The new-generation QuantiFERON-TB Gold Plus (QFT-Plus) assay, recently approved for use in the United States, differs from the current-generation QFT Gold-In-Tube (QFT-GIT) assay with the addition of a second antigen tube that also contains novel CD8
+
T-cell-stimulating peptides.
Structure-Guided Identification of a Nonhuman Morbillivirus with Zoonotic Potential
Authors: Abdullah Nurshariza , Kelly James T. , Graham Stephen C. , Birch Jamie , Gonçalves-Carneiro Daniel , Mitchell Tim , Thompson Robin N. , Lythgoe Katrina A. , Logan Nicola , Hosie Margaret J. , Bavro Vassiliy N. , Willett Brian J. , Heaton Michael P. , Bailey Dalan
Published: September 2018

A significant proportion of viral pandemics occur following zoonotic transmission events, where animal-associated viruses jump species into human populations. In order to provide forewarnings of the emergence of these viruses, it is necessary to develop a better understanding of what determines virus host range, often at the genetic and structural levels. In this study, we demonstrated that the small-ruminant morbillivirus, a close relative of measles, is unable to use human receptors to enter cells; however, a change of a single amino acid in the virus is sufficient to overcome this restriction. This information will be important for monitoring this virus’s evolution in the field. Of note, this study was undertaken
in vitro
, without generation of a fully infectious virus with this phenotype.
Robust Human and Murine Hepatocyte Culture Models of Hepatitis B Virus Infection and Replication
Authors: Qiao Luhua , Sui Jianhua , Luo Guangxiang
Published: September 2018

HBV research has been greatly hampered by the lack of robust cell culture and small animal models of HBV infection and propagation. The discovery of NTCP as an HBV receptor has greatly impacted the field of HBV research. Although HBV infection of NTCP-expressing human and murine hepatocyte cell lines has been demonstrated, its replication in cell culture appeared inefficient. To further improve cell culture systems of HBV infection and replication, we constructed NTCP-expressing HepG2 and AML12 cell lines that are highly permissive to HBV infection. More significantly, we found that DMSO and hydrocortisone markedly enhanced HBV transcription and replication in human and murine hepatocytes when added to the cell culture medium. These new cell culture models of HBV infection and replication will facilitate HBV research and antiviral drug discovery towards the ultimate elimination of chronic hepatitis B virus infection.
Cellular Protein Kinase D Modulators Play a Role during Multiple Steps of Herpes Simplex Virus 1 Egress
Authors: Roussel Élisabeth , Lippé Roger
Published: September 2018

Viruses are obligatory parasites that highjack numerous cellular functions. This is certainly true when it comes to transporting viral particles within the cell. Herpesviruses share the unique property of traveling through the two nuclear membranes by subsequent budding and fusion and acquiring their final envelope from a cellular organelle. Albeit disputed, the overall evidence from many laboratories points to the
trans
-Golgi network (TGN) as the source of that membrane. Moreover, past findings revealed that the host protein kinase D (PKD) plays an important role at that stage, which is significant given the known implication of that protein in vesicular transport. The present findings suggest that the PKD machinery not only affects the late stages of herpes simplex virus I egress but also modulates earlier steps, such as nuclear egress. This opens up new means to control these viruses.
Influence of myocardial scar on the response to frequent premature ventricular complex ablation
Authors: Penela Diego , Martínez Mikel , Fernández-Armenta Juan , Aguinaga Luis , Tercedor Luis , Ordóñez Augusto , Acosta Juan , Martí-Almor Julio , Bisbal Felipe , Rossi Luca , Borràs Roger , Linhart Markus , Soto-Iglesias David , Jáuregui Beatriz , Ortiz-Pérez José T , Perea Rosario J , Bosch Xavier , Mont Lluis , Berruezo Antonio
Published: September 2018

Objective

This study aims to evaluate the influence of myocardial scar after premature ventricular complexes (PVC) ablation in patients with left ventricular (LV) dysfunction.

Methods

70 consecutive patients (58±11 years, 58 (83%) men, 23% (18–32) mean PVC burden) with LV dysfunction and frequent PVCs submitted for ablation were included. A late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) was performed prior to the ablation and a quantitative and qualitative analysis of the scar was done.

Results

Left ventricular ejection fraction progressively improved from 34.3%±9% at baseline to 44.4%±12% at 12 months (p<0.01) and 48 (69%) patients were echocardiographic responders. New York Heart Association class improved from 1.96±0.9 points at baseline to 1.36±0.6 at 12 months (p<0.001). Brain natriuretic peptide decreased from 120 (60–284) to 46 (23–81) pg/mL (p=0.04). Twenty-nine (41%) patients showed scar in the preprocedural LGE-CMR with a mean scar mass of 10.4 (5–20) g. Mean scar mass was significantly smaller in responders than in non-responders (0 (0–4.7) g vs 2 (0–14) g, respectively, p=0.017). PVC burden reduction (OR 1.09 (1.01–1.16), p=0.02) and scar mass (OR 0.9 (0.81–0.99), p=0.04) were independent predictors of response, but the former showed a higher accuracy.

Conclusions

Presence of myocardial scar modulates, but does not preclude, the probability of response to PVC ablation in patients with LV dysfunction.
Fourteen-year-old boy with decreased appetite and pedal swelling
Authors: Ghosh Gopal Chandra , S Aparna , George Oomen K
Published: September 2018

Clinical introduction

A 14-year-old boy presented with history of decreased appetite and bilateral swelling of feet for 6 months. He did not give any associated history of orthopnoea or paroxysmal nocturnal dyspnoea. He was born by a normal delivery after a non-consanguineous marriage. He had an unremarkable birth and childhood health history. There was no family history of significant cardiovascular illness or sudden death. Clinical examination showed an average built boy with elevated jugular venous pressure with prominent v wave and bilateral pitting pedal oedema. Cardiovascular examination showed normal first (S1) and second (S2) heart sounds and a short early systolic murmur over tricuspid region. Other systems examination was remarkable for soft tender hepatomegaly.

ECG showed sinus rhythm with tall, peaked p waves. Chest X-ray revealed enlargement along the right cardiac border. Transthoracic echocardiographic images are shown in figure 1A (apical four-chamber view) and figure 1B (tricuspid inflow Doppler). There was no colour Doppler evidence of interatrial shunt.

Question

What is the most likely diagnosis of his condition?

Endomyocardial fibrosis (EMF)

Ebstein’s anomaly

Arrhythmogenic right ventricular dysplasia (ARVD)

Idiopathic dilatation of right atrium

Restrictive cardiomyopathy
Systematic review and evidence synthesis of non-cervical human papillomavirus-related disease health system costs and quality of life estimates
Authors: Ong Koh Jun , Checchi Marta , Burns Lorna , Pavitt Charlotte , Postma Maarten J , Jit Mark
Published: September 2018

Background

Many economic evaluations of human papillomavirus vaccination should ideally consider multiple disease outcomes, including anogenital warts, respiratory papillomatosis and non-cervical cancers (eg, anal, oropharyngeal, penile, vulvar and vaginal cancers). However, published economic evaluations largely relied on estimates from single studies or informal rapid literature reviews.

Methods

We conducted a systematic review of articles up to June 2016 to identify costs and utility estimates admissible for an economic evaluation from a single-payer healthcare provider’s perspective. Meta-analyses were performed for studies that used same utility elicitation tools for similar diseases. Costs were adjusted to 2016/2017 US$.

Results

Sixty-one papers (35 costs; 24 utilities; 2 costs and utilities) were selected from 10 742 initial records. Cost per case ranges were US$124–US$883 (anogenital warts), US$6912–US$52 579 (head and neck cancers), US$12 936–US$51 571 (anal cancer), US$17 524–34 258 (vaginal cancer), US$14 686–US$28 502 (vulvar cancer) and US$9975–US$27 629 (penile cancer). The total cost for 14 adult patients with recurrent respiratory papillomatosis was US$137 601 (one paper).

Utility per warts episode ranged from 0.651 to 1 (12 papers, various utility elicitation methods), with pooled mean EQ-5D and EQ-VAS of 0.86 (95% CI 0.85 to 0.87) and 0.74 (95% CI 0.74 to 0.75), respectively. Fifteen papers reported utilities in head and neck cancers with range 0.29 (95% CI 0.0 to 0.76) to 0.94 (95% CI 0.3 to 1.0). Mean utility reported ranged from 0.5 (95% CI 0.4 to 0.61) to 0.65 (95% CI 0.45 to 0.75) (anal cancer), 0.59 (95% CI 0.54 to 0.64) (vaginal cancer), 0.65 (95% CI 0.60 to 0.70) (vulvar cancer) and 0.79 (95% CI 0.74 to 0.84) (penile cancer).

Conclusions

Differences in values reported from each paper reflect variations in cancer site, disease stages, study population, treatment modality/setting and utility elicitation methods used. As patient management changes over time, corresponding effects on both costs and utility need to be considered to ensure health economic assumptions are up-to-date and closely reflect the case mix of patients.
Philip Morris International-funded ‘Foundation for a Smoke-Free World’: analysing its claims of independence
Authors: van der Eijk Yvette , Bero Lisa A , Malone Ruth E
Published: September 2018

The Foundation for a Smoke-Free World was launched in September 2017 with an announced 12-year funding commitment of $1 billion from Philip Morris International (PMI). The Foundation claims that its governing documents (certificate of incorporation, bylaws and a pledge agreement) ensure that it has an independent research agenda and stringent protections from conflicts of interest. We analysed the text of these governing documents. Their provisions have multiple loopholes, particularly regarding conflicts of interest. Further, these documents cannot substitute for other important documentation such as information about PMI’s internal business case for investing $1 billion in the Foundation, an unwaivable conflict of interest policy, annual disclosure statements, copies of pre-Foundation establishment correspondence between key individuals, all signed contracts or salary information, none of which, as of July 2018, the Foundation has made publicly available. Even if these were released, however, it is problematic that the Foundation’s fundamental purpose was decided on and its leader selected following a tobacco company-paid, privately negotiated arrangement with the Foundation’s president. It cannot be regarded as independent.
Use of stable isotopes in benthic organic material as a baseline for estimating fish trophic positions in lakes
Authors: Lake James L. , Serbst Jonathan R. , Kuhn Anne , Smucker Nathan J. , Edwards Phillip , Libby Alan , Charpentier Michael , Miller Kenneth
Published: September 2018

Estimating the trophic position of predators in food webs using stable isotopes requires establishing a “baseline”, typically served by bivalves or snails. However, the frequent absence of such organisms in lakes leaves researchers in a difficult situation. Here we test the hypothesis that trophic position (TP) of largemouth bass (LB; Micropterus salmoides) in lakes can be estimated from δ15N of benthic organic material (BOM) in littoral surficial sediment. δ15NLB as a function of δ15NBOM was significant across 51 lakes with an R2 of 0.84, supporting our hypothesis. In a subset of six lakes, the mean TPLB did not differ significantly when calculated using baselines of δ15N in BOM, unionid mussels (UN), gastropods (SN), or from a stable isotope mixing model. In a subset of 26 lakes, mean TPLB calculated from δ15NBOM and δ15NUN baselines were not significantly different, but TPLB calculated using δ15NBOM was not significantly correlated with TPLB calculated using δ15NUN. Although δ15NBOM should not be used interchangeably with δ15NUN as a baseline for estimating TPLB, δ15NBOM can be useful as a separate baseline where estimates of fish TP are needed in all study lakes given that mussels are frequently absent and BOM is always available for collection.
Multiscale modeling of thermal properties of silicene using molecular dynamics
Authors: Das D. K. , Sarkar Jit
Published: September 2018

Silicene sheet is prepared by atomistic multiscale modeling using molecular dynamics (MD) simulations to evaluate thermal properties of silicene at different temperatures and variable sample sizes. In this paper, by MD simulation study, we have estimated coefficient of linear and surface expansion between a temperature range from 318 K to 398 K, specific heat at constant volume and pressure, melting point, heat of fusion and thermal conductivity of silicene at different sample sizes by both equilibrium molecular dynamics (EMD) and non-equilibrium molecular dynamics (NEMD) approaches. The presented multiscale modeling approaches could guide experimental studies to design silicene sheet with required thermal properties for operation under specific conditions.
Power-law entropies for continuous systems and generalized operations
Authors: Creaco Anthony J. , Kalogeropoulos Nikolaos
Published: September 2018

We present our view in a standing debate about the definition and meaning of power-law entropies for continuous systems. Our suggestion is that such arguments should take into account the generalized operations of addition and multiplication induced by the power-law entropies’ composition properties. To be concrete, we highlight our view using the case of the “q-”, also known as “Tsallis”, entropic functionals.
Semi-Active Fluid Viscous Dampers for Seismic Mitigation of RC Elevated Liquid Storage Tanks
Authors: Waghmare Manisha V. , Madhekar Suhasini N. , Matsagar Vasant A.
Published: September 2018

The effectiveness of the semi-active control strategies using fluid viscous dampers (SAFVDs) for seismic mitigation of reinforced concrete (RC) elevated liquid storage tanks is investigated. Three control algorithms are employed for regulating the damping coefficient of the SAFVDs: (1) Passive-OFF, (2) Passive-ON, and (3) Clipped Optimal Control (COC). The uncontrolled response of the tank is compared with those installed with SAFVD of different control algorithms. Focus is also placed on various positions of the dampers, viz., dampers installed at alternate levels (Configurations I, II, IV, and V) and at all levels (Configurations III and VI) of the staging. A discrete two-mass model for the liquid and multi-degree-of-freedom system for the staging, installed with the dampers, is developed for the RC elevated liquid storage tanks. The response of the broad and slender tanks is studied, for which the ratios of the height of the liquid to the radius of the container are 0.5 and 2.0, respectively. The time-history response of the elevated tank is evaluated for eight different earthquake ground motions, including near- and far-field earthquakes. A MATLAB code was developed to solve the coupled differential equations of motion of the system using the state-space approach. Key parameters, viz., convective displacement, rigid mass displacement, base shear, overturning moment, and damper force, are evaluated. The results show that all the control systems considered herein are beneficial in reducing the seismic responses. The frequency response function for the uncontrolled and semi-actively controlled liquid storage tank in frequency domain exhibits significant response reduction, highlighting the effectiveness of the SAFVDs. The structural response is effectively controlled using the SAFVDs with Passive-OFF (valve closed) and COC algorithms. The COC algorithm employed in this study is a promising candidate for the seismic mitigation of RC elevated liquid storage tanks using the semi-active control.
Assessment of Percussive Music Performances with Feature Learning
Authors: Wu Chih-Wei , Lerch Alexander
Published: September 2018

The automatic assessment of (student) music performance involves the characterization of the audio recordings and the modeling of human judgments. To build a computational model that provides a reliable assessment, the system must take into account various aspects of a performance including technical correctness and aesthetic standards. While some progress has been made in recent years, the search for an effective feature representation remains open-ended. In this study, we explore the possibility of using learned features from sparse coding. Specifically, we investigate three sets of features, namely a baseline set, a set of designed features, and a feature set learned with sparse coding. In addition, we compare the impact of two different input representations on the effectiveness of the learned features. The evaluation is performed on a dataset of annotated recordings of students playing snare exercises. The results imply the general viability of feature learning in the context of automatic assessment of music performances.
Advanced Authentication Protocol for Software-Defined Networks
Authors: Allouzi Maha Ali , Khan Javed I.
Published: September 2018

Software-Defined Networking (SDN) is being widely implemented by critical infrastructure networks, however providing security features still a challenge. In this work, we present SafeFlow an Automatic Trust Negotiation Protocol for SDN, a first line of defense and fine-grained authentication protocol, in order to deny the access of OpenFlow switches without valid digital credentials. Traditional security approaches based on identity or capabilities do not solve the problem of establishing trust between strangers. One alternative approach to mutual trust establishment is Trust Negotiation, the bilateral exchange of digital credentials to establish trust gradually. The proposed protocol describes Trust Negotiation in OpenFlow protocol, probable extension to the OpenFlow handshake protocol. In this paper, we describe the implementation of SafeFlow. The proposed protocol ensures the security of the infrastructure itself, as there are also other proposals for developing security application on OpenFlow network infrastructure.
Moderate-intensity exercise reduces activated and apoptotic endothelial microparticles in healthy midlife women
Authors: Serviente Corinna , Burnside Amy , Witkowski Sarah
Published: September 2018

Endothelial microparticles (EMPs) are related to cardiovascular disease (CVD) risk. Risk factors for CVD increase with menopause, and greater cardiorespiratory fitness is generally expected to reduce CVD risk. The effects of habitual physical activity on endothelial health may be due in part to the effect of acute exercise on circulating EMPs. This study was performed to evaluate the effect of an acute bout of exercise on CD62E+and CD31+/42b−EMPs in healthy fit midlife women at different menopausal stages. Healthy, active premenopausal (PRE), perimenopausal (PERI), and postmenopausal (POST) women completed a single bout of moderate-intensity treadmill exercise. Activated (CD62E+) and apoptotic (CD31+/42b−) EMPs were evaluated before and 30 min after exercise by using fluorescent activated cell sorting. In an exploratory analysis, these results were compared with data from low-fit peri- and postmenopausal women. Differences by group and time point were evaluated with repeated-measure ANOVAs. There was a reduction in the number of total microparticles ( P < 0.001), CD62E+( P = 0.003), and CD31+/42b−( P < 0.001) EMPs/μl plasma following acute exercise. The percentage of CD62E+EMPs increased with acute exercise ( P < 0.001), whereas the percentage of CD31+/42b−EMPs did not change ( P = 0.40). There was no effect of menopausal status on CD62E+or CD31+/42b−EMPs, or on total microparticles (all P > 0.05). The exploratory analysis revealed that low-fit women had similar changes in EMPs with acute exercise. We concluded that acute moderate-intensity exercise reduces CD62E+and CD31+/42b−EMPs, as well as total microparticles, in healthy midlife women. These effects occurred despite differences in menopausal status and fitness.

NEW & NOTEWORTHY This study demonstrates that acute moderate-intensity exercise reduces activated and apoptotic endothelial microparticles in healthy midlife women.
Effects of stroke injury on the shear modulus of the lower leg muscle during passive dorsiflexion
Authors: Le Sant Guillaume , Nordez Antoine , Hug François , Andrade Ricardo , Lecharte Thomas , McNair Peter J. , Gross Raphaël
Published: September 2018

Contractures are common complications of a stroke. The spatial location of the increased stiffness among plantar flexors and its variability among survivors remain unknown. This study assessed the mechanical properties of the lower leg muscles in stroke survivors during passive dorsiflexions. Stiffness was estimated through the measurement of the shear modulus. Two experiments were independently conducted, in which participants lay supine: with the knee extended ( experiment 1, n = 13 stroke survivors and n = 13 controls), or with the knee flexed at 90° ( experiment 2, n = 14 stroke survivors and n = 14 controls). The shear modulus of plantar flexors [gastrocnemius medialis (three locations), gastrocnemius lateralis (three locations), soleus (two locations), flexor digitorum longus, flexor hallucis longus), peroneus longus] and dorsiflexors (tibialis anterior and extensor digitorum longus) was measured using ultrasound shear wave elastography during passive dorsiflexions (2°/s). At the same ankle angle, stroke survivors displayed higher shear modulus than controls for gastrocnemius medialis and gastrocnemius lateralis (knee extended) and soleus (knee flexed). Very low shear modulus was found for the other muscles. The adjustment for muscle slack angle suggested that the increased shear modulus was arising from consequences of contractures. The stiffness distribution between muscles was consistent across participants with the highest shear modulus reported for the most distal regions of gastrocnemius medialis (knee extended) and soleus (knee flexed). These results provide a better appreciation of stiffness locations among plantar flexors of stroke survivors and can provide evidence for the implementation of clinical trials to evaluate targeted interventions applied on these specific muscle regions.

NEW & NOTEWORTHY The shear modulus of 13 muscle regions was assessed in stroke patients using elastography. When compared with controls, shear modulus was increased in the gastrocnemius muscle (GM) when the knee was extended and in the soleus (SOL) when the knee was flexed. The distal regions of GM and SOL were the most affected. These changes were consistent in all the stroke patients, suggesting that the regions are a potential source of the increase in joint stiffness.
Adverse early life environment induces anxiety-like behavior and increases expression of FKBP5 mRNA splice variants in mouse brain
Authors: Ke Xingrao , Fu Qi , Majnik Amber , Cohen Susan , Liu Qiuli , Lane Robert
Published: September 2018

Adverse early life environment (AELE) predisposes adult offspring toward anxiety disorders. Anxiety disorders are associated with prenatal injuries in key regions of the brain including prefrontal cortex (PFC), hippocampus (HP), and hypothalamus (HT). Injuries in these brain regions result in an impaired hypothalamus-pituitary-adrenal axis (HPA axis) and stress response. An important regulator of the stress response is FK506-binding protein 5 (FKBP5). FKBP5 is a cochaperone of the glucocorticoid receptor (GR) and inhibits GR-mediated regulatory feed-back on the HPA axis in response to stress. Human studies have shown that polymorphisms of FKBP5 are associated with higher FKBP5 levels. Increased FKBP5 leads to GR resistance and impaired negative feedback, which is associated with anxiety disorders. FKBP5 and its mRNA splice variants in the aforementioned brain regions have not been reported. We hypothesized that AELE will increase expression of FKBP5 and its mRNA splice variants in PFC, HP, and HT as well as increase anxiety in adult mice. AELE increased expression of FKBP5 and its mRNA variants in PFC, HP and HT at postnatal day 21. Additionally, AELE caused anxiety and increased GR abundance in association with these changes in FKBP5 expression. We speculate that these changes in FKBP5 mRNA variants affect HPA axis function and contributes to subsequent anxiety-like behavior later in life in AELE mice.
Downregulation ofDipeptidyl Peptidase 4Accelerates Progression to Castration-Resistant Prostate Cancer
Authors: Russo Joshua W. , Gao Ce , Bhasin Swati S. , Voznesensky Olga S. , Calagua Carla , Arai Seiji , Nelson Peter S. , Montgomery Bruce , Mostaghel Elahe A. , Corey Eva , Taplin Mary-Ellen , Ye Huihui , Bhasin Manoj , Balk Steven P.
Published: September 2018

The standard treatment for metastatic prostate cancer, androgen deprivation therapy (ADT), is designed to suppress androgen receptor (AR) activity. However, men invariably progress to castration-resistant prostate cancer (CRPC), and AR reactivation contributes to progression in most cases. To identify mechanisms that may drive CRPC, we examined a VCaP prostate cancer xenograft model as tumors progressed from initial androgen sensitivity prior to castration to castration resistance and then on to relapse after combined therapy with further AR-targeted drugs (abiraterone plus enzalutamide). AR activity persisted in castration-resistant and abiraterone/enzalutamide–resistant xenografts and was associated with increased expression of the AR gene and the AR-V7 splice variant. We then assessed expression of individual AR-regulated genes to identify those that persisted, thereby contributing to tumor growth, versus those that decreased and may therefore exhibit tumor suppressor activities. The most significantly decreased AR target gene was dipeptidyl peptidase 4 (DPP4), which encodes a membrane-anchored protein that cleaves dipeptides from multiple growth factors, resulting in their increased degradation. DPP4 mRNA and protein were also decreased in clinical CRPC cases, and inhibition of DPP4 with sitagliptin enhanced the growth of prostate cancer xenografts following castration. Significantly, DPP4 inhibitors are frequently used to treat type 2 diabetes as they increase insulin secretion. Together, these results implicate DPP4 as an AR-regulated tumor suppressor gene whose loss enhances growth factor activity and suggest that treatment with DPP4 inhibitors may accelerate emergence of resistance to ADT.

Significance: These findings identify DPP4 as an AR-stimulated tumor suppressor gene that is downregulated during progression to castration-resistant prostate cancer, warning that treatment with DPP4 inhibitors, commonly used to treat type 2 diabetes, may accelerate prostate cancer progression following androgen deprivation therapy. Cancer Res; 78(22); 6354–62. ©2018 AACR.
Nano-delivery of RAD6/Translesion Synthesis Inhibitor SMI#9 for Triple-negative Breast Cancer Therapy
Authors: Saadat Nadia , Liu Fangchao , Haynes Brittany , Nangia-Makker Pratima , Bao Xun , Li Jing , Polin Lisa A. , Gupta Smiti , Mao Guangzhao , Shekhar Malathy P.
Published: September 2018

The triple-negative breast cancer (TNBC) subtype, regardless of their BRCA1 status, has the poorest outcome compared with other breast cancer subtypes, and currently there are no approved targeted therapies for TNBC. We have previously demonstrated the importance of RAD6-mediated translesion synthesis pathway in TNBC development/progression and chemoresistance, and the potential therapeutic benefit of targeting RAD6 with a RAD6-selective small-molecule inhibitor, SMI#9. To overcome SMI#9 solubility limitations, we recently developed a gold nanoparticle (GNP)-based platform for conjugation and intracellular release of SMI#9, and demonstrated its in vitro cytotoxic activity toward TNBC cells. Here, we characterized the in vivo pharmacokinetic and therapeutic properties of PEGylated GNP-conjugated SMI#9 in BRCA1 wild-type and BRCA1-mutant TNBC xenograft models, and investigated the impact of RAD6 inhibition on TNBC metabolism by 1H-NMR spectroscopy. GNP conjugation allowed the released SMI#9 to achieve higher systemic exposure and longer retention as compared with the unconjugated drug. Systemically administered SMI#9-GNP inhibited the TNBC growth as effectively as intratumorally injected unconjugated SMI#9. Inductively coupled mass spectrometry analysis showed highest GNP concentrations in tumors and liver of SMI#9-GNP and blank-GNP–treated mice; however, tumor growth inhibition occurred only in the SMI#9-GNP–treated group. SMI#9-GNP was tolerated without overt signs of toxicity. SMI#9-induced sensitization was associated with perturbation of a common set of glycolytic pathways in BRCA1 wild-type and BRCA1-mutant TNBC cells. These data reveal novel SMI#9 sensitive markers of metabolic vulnerability for TNBC management and suggest that nanotherapy-mediated RAD6 inhibition offers a promising strategy for TNBC treatment.
Allergen Immunization Induces Major Changes in Microbiota Composition and Short-Chain Fatty Acid Production in Different Gut Segments in a Mouse Model of Lupine Food Allergy
Authors: Andreassen Monica , Rudi Knut , Angell Inga Leena , Dirven Hubert , Nygaard Unni C.
Published: September 2018

Background: The incidence of food allergies in western countries has increased in recent decades. Objectives: To study the association between gut bacterial microbiota composition, short-chain fatty acids (SCFAs) and food allergy in a mouse model. Methods: After oral immunizations with the human food allergen lupine with the adjuvant cholera toxin (CT) (or buffer in controls), sensitization and anaphylactic responses were determined. Gastrointestinal content was collected from the distal ileum, cecum, colon, and fecal pellets, and the bacterial diversity and composition was determined by deep sequencing of the 16S rRNA gene. SCFAs in gastrointestinal content supernatants were determined by gas chromatography. Results: The microbiota signatures were profoundly affected by allergen immunization. Ten operational taxonomic units (OTUs) were significantly different between immunized and control animals for at least one of the intestinal segments; eight of these OTUs belonged to the Clostridia class. Although consistent across all four gut segments, the colon showed the highest number of OTUs significantly associated with allergic immunization. SCFA levels in the cecum were also altered by immunization. Conclusions: Allergen immunization with CT in the present food allergy model induced profound changes in the microbiome composition and SCFA production. The result suggests that the colon may be the most sensitive gut segment for investigating changes in the gut microbiome.
The Digital Outcome Measure
Authors: Cohen Adam B. , Mathews Simon C.
Published: September 2018

Improving clinical outcomes remains the gold standard in advancing healthcare. Focusing on outcomes holds the potential to unite all clinical stakeholders including payers, industry, providers, and patients. Yet, the dominant ways in which outcomes are captured, provider-collected or patient-reported, have significant limitations. The emerging field of biosensors and wearables, which aims to capture many types of health data, holds promise to specifically capture outcomes while complementing existing outcome collection methods. A digital outcome measure, unlike a traditional provider-collected or patient-reported outcome measure, depends less on active patient or provider participation. Thus, digital outcome measures may be more amenable to standardization as well as greater collection consistency, frequency, and accuracy.
The Consequences of Leaving School Early: The Effects of Within-Year and End-of-Year Teacher Turnover
Authors: Henry Gary T. , Redding Christopher
Published: September 2018

Using unique administrative data from North Carolina that allow us to separate classroom teacher turnover during the school year from end-of-year turnover, we find students who lose their teacher during the school year have significantly lower test score gains (on average −7.5 percent of a standard deviation unit) than those students whose teachers stay. Moreover, the turnover of other teachers during the year lowers achievement gains, whereas end-of-year teacher turnover appears to have little effect on achievement. The harmful effects of within-year turnover cannot be explained by other extraneous shocks or the quality of departing teachers. Teachers who depart from December through April have the most harmful effects on achievement, although these vary somewhat by level of schooling and subject.
Subgoal- and Goal-related Reward Prediction Errors in Medial Prefrontal Cortex
Authors: Ribas-Fernandes José J. F. , Shahnazian Danesh , Holroyd Clay B. , Botvinick Matthew M.
Published: September 2018

A longstanding view of the organization of human and animal behavior holds that behavior is hierarchically organized—in other words, directed toward achieving superordinate goals through the achievement of subordinate goals or subgoals. However, most research in neuroscience has focused on tasks without hierarchical structure. In past work, we have shown that negative reward prediction error (RPE) signals in medial prefrontal cortex (mPFC) can be linked not only to superordinate goals but also to subgoals. This suggests that mPFC tracks impediments in the progression toward subgoals. Using fMRI of human participants engaged in a hierarchical navigation task, here we found that mPFC also processes positive prediction errors at the level of subgoals, indicating that this brain region is sensitive to advances in subgoal completion. However, when subgoal RPEs were elicited alongside with goal-related RPEs, mPFC responses reflected only the goal-related RPEs. These findings suggest that information from different levels of hierarchy is processed selectively, depending on the task context.
Parallels Between Tyrant and Philosopher in Plato’s Republic
Authors: Connell Sophia M.
Published: September 2018

The Republic presents the characters of the philosopher and the tyrant as similar. Strongly focused by indiscriminate erotic motivation, both defy convention and lack familiar emotional responses, which make them appear to be mad. This essay argues that Plato put forward these parallels partly in order to defend Socrates from the charge of corrupting the young, partly to present a possible way to overthrow the current regime and partly to show the ineffectiveness of democracy. The very best leaders may look like tyrants; it is only through proper philosophical education that their true natures can be discerned.
Xenophon’s Hipparchikos and the Athenian Embrace of Citizen Philotimia
Authors: Keim Benjamin
Published: September 2018

Although negotiations over the competing claims of honour (timê) and awards of instantiated honours (timai) were central features of Athenian democracy, the dangerous ambiguities of philotimia meant that only from the 340s BC were the Athenians explicitly embracing this love of honour and celebrating its display by citizens and non-citizens alike. Here I argue that a close reading of Xenophon’s treatise on cavalry command, Hipparchikos, advances our understanding of this embrace of public-spirited honour in three ways. First, Xenophon founds the success of the cavalry on the training of knowledgeable officers who are able to harness the Athenians’ extraordinary love of honour, on display and on campaign. Second, he reveals the diverse roles played by timê and philotimia throughout the entire institution of the Athenian cavalry, fostering competitive excellence as well as community amongst cavalry, polis, and gods. Third, Xenophon’s arguments about the nature and negotiation of Athenian honour anticipate the ideological and institutional embrace of citizen honour that, amply attested by epigraphic and literary records, was central to Athenian flourishing during the Lycurgan and Hellenistic eras.
Thucydides’ Assessments of Pericles and Alcibiades as a Lesson in Leadership Ethics
Authors: Mantzouranis Kleanthis
Published: September 2018

The present study examines Thucydides’ assessments of Pericles (2.65) and Alcibiades (6.15) drawing on advances from Leadership Studies. Moving away from conceptions of leadership as a quality of individuals, modern leadership theory views leadership as a relational process between leaders and followers. Thucydides’ assessments of Pericles and Alcibiades examine not only their effectiveness (i.e., their success or failure in conducting the war), but more importantly, the impact of their personal ethics on their relationship with followers. For Thucydides, both leaders displayed administrative competence, but their diverse adherence to ethical principles had a grave impact on their interaction with followers and consequently on their position as leaders. The comparative study of the two passages highlights how Thucydides’ understanding of leadership as a relational process anticipates an important strand of modern leadership theory according to which both effectiveness and ethics are inextricably intertwined in the concept of good leadership.
A new species of Deamia (Cactaceae) from the Mesoamerican region
Authors: CERÉN GABRIEL , CRUZ MIGUEL ÁNGEL , MENJÍVAR JENNY , ARIAS SALVADOR
Published: September 2018

Deamia montalvoae sp. nov. (Cactaceae) from the Mesoamerican region (El Salvador, Guatemala, and Mexico) is described and illustrated based on morphological and molecular evidences. The new species is morphologically characterized by stems up to 2 cm in diameter, 7−8-ribbed, flowers (23−)27−30 cm long, with pericarpel covered by bristles and trichomes, but without spines; fruit 5−6 cm long and pale-red, covered by bristles and trichomes, with white flesh; seeds 3.1−3.5 mm long, dark brown, with a smooth microrelief. The phylogenetic analysis using two introns, rpl16 and trnL-trnF, and a spacer, psbA-trnH, shows that D. testudo is the sister species of D. montalvoae and D. chontalensis.