bluuebunny/crossref_metadata_2025 huggingface dataset:
The GAS6-AXL signaling network is a mesenchymal (Mes) molecular subtype–specific therapeutic target for ovarian cancer
Authors: Antony Jane , Tan Tuan Zea , Kelly Zoe , Low Jeffrey , Choolani Mahesh , Recchi Chiara , Gabra Hani , Thiery Jean Paul , Huang Ruby Yun-Ju
Published: October 2016

AXL inhibitors may prolong survival in a subset of patients with advanced ovarian cancer.
New twists in the AXL(e) of tumor progression
Authors: Halmos Balazs , Haura Eric B.
Published: October 2016

AXL inhibitors may slow tumor progression in patients with a mesenchymal subtype of ovarian cancer (Antony
et al.
, in 4 October 2016 issue).
Papers of note in
Science
Authors: VanHook Annalisa M.
Published: October 2016

This week’s articles describe a mechanism for the propagation of protein aggregates associated with Parkinson’s disease, crosstalk between fat cells and the brain that controls the growth of fruit flies, a histone brake on tumor growth, the coordination of DNA repair with the cell cycle, and a role for the innate immune response in liver damage caused by hepatitis A infection.
A uniquely human susceptibility to bacterial infection
Authors: VanHook Annalisa M.
Published: October 2016

A sialic acid that is abundant in human mucus enhances
Streptococcus pneumoniae
virulence.
High-Dose Micafungin for Preterm Neonates and Infants with Invasive and Central Nervous System Candidiasis
Authors: Auriti Cinzia , Falcone Marco , Ronchetti Maria Paola , Goffredo Bianca Maria , Cairoli Sara , Crisafulli Rosamaria , Piersigilli Fiammetta , Corsetti Tiziana , Dotta Andrea , Pai Manjunath P.
Published: October 2016

High doses of micafungin are advocated in neonates with systemic candidiasis, but limited pharmacokinetic (PK) and safety data are available to support their use. Eighteen preterm neonates and infants with systemic candidiasis, three of whom had meningitis, were treated for at least 14 days with 8 to 15 mg/kg of body weight/day of intravenous micafungin. Plasma micafungin concentrations (four measurements for each patient) were determined after the third dose, and the cerebrospinal fluid (CSF) micafungin concentrations in three patients were also obtained. Population PK analyses were used to identify the optimal model, and the model was further validated using external data (
n
= 5). The safety of micafungin was assessed by measurement of the levels of liver and kidney function biomarkers. The mean age and weight at the initiation of treatment were 2.33 months (standard deviation [SD], 1.98 months) and 3.24 kg (SD, 1.61 kg), respectively. The optimal PK model was one that scaled plasma clearance to weight and the transaminase concentration ratio. The CSF of three patients was sampled, and the observed concentrations were between 0.80 and 1.80 mg/liter. The model-predicted mean micafungin area under the concentration-time curve over 24 h was 336 mg · h/liter (SD, 165 mg · h/liter) with the 10-mg/kg/day dosage. Eighteen of the 23 subjects (78.2%) had clinical resolution of their infection, but 5 had neurologic impairments. Among the transaminases, alkaline phosphatase measurements were significantly higher posttreatment, with a geometric mean ratio of 1.17 (90% confidence interval, 1.01, 1.37). Furthermore, marked elevations in the gamma-glutamyltransferase (GGT) level were observed in three patients treated with 10- to 15-mg/kg/day doses, and improvement of the GGT level was noted after a dose reduction. Higher weight-based doses of micafungin were generally well tolerated in neonates and infants and achieved pharmacokinetic profiles predictive of an effect.
Tropical circulation intensification and tectonic extension recorded by Neogene terrestrial δ18O records of the western United States
Authors: Feng Ran , Poulsen Christopher J. , Werner Martin
Published: October 2016

Terrestrial water isotope records preserve a history of hydrological cycling that is influenced by past climate and surface topography. δ18O and δD records from authigenic minerals of the western United States display a long-term increase during the Neogene in the vicinity of the Sierra Nevada and the central Rocky Mountains (Rockies), but a smaller increase or decrease in the northern Great Basin. Interpretations of these isotopic trends require quantitative estimates of the influence of climatic and environmental changes on δ18O and δD of soil water. Here we use a coupled atmosphere-land model with water-isotopologue tracking capabilities, ECHAM5-JSBACH-wiso, to simulate precipitation and δ18O responses to elevation-independent changes in Neogene geography, equator to pole temperature gradient (EPGRAD), grassland expansion, and tropical Pacific sea surface temperatures. Both precipitation and soil water δ18O (δ18Osw) respond strongly to Neogene strengthening of the EPGRAD, but weakly to other forcings. An increase in EPGRAD leads to significant drying and 18O enrichment (3‰–5‰) of soil water over the northern Sierra Nevada and central Rockies as a result of Hadley circulation strengthening and enhanced coastal subtropical subsidence. These large-scale circulation changes reduce inland moisture transport from the Pacific Ocean and Gulf of Mexico. Our simulated δ18Osw responses could explain 50%–100% of the proxy δ18O increases over the Sierra Nevada and central Rockies, suggesting that climate change rather than surface subsidence may have been the dominant climate signal in δ18O records in these regions. On the contrary, δ18O responses to climate changes are small in the Great Basin, indicating that the observed δ18O increase over this region was likely a direct response to surface subsidence with elevation losses of 1–1.5 km. Adding this elevation loss to current Great Basin elevations reveals the former existence of a uniformly high plateau extending from the Sierra Nevada to the central Rockies prior to Neogene extension. This revised elevation history brings Neogene δ18O and δD paleoaltimetry of the western United States in accordance with independent lines of structural evidence and early Cenozoic elevation reconstructions.
Giant landslides and highstands of the Caspian Sea
Authors: Pánek Tomáš , Korup Oliver , Minár Jozef , Hradecký Jan
Published: October 2016

The history of Quaternary sea-level changes in the Caspian Sea, the world’s largest lake, is partly enigmatic, and so is the geomorphic response of its coasts. Late Pleistocene transgressions during the Early Khvalynian (ca. 40–25 ka) inundated extensive portions of the flat, low-lying semi-desert of western Kazakhstan. Cliffs cut during these highstands form a prominent escarpment tens of kilometers to several hundred kilometers from the present coast of the Caspian Sea. Satellite images, digital terrain analysis, and field mapping reveal that >300 giant landslides intersect with this escarpment. More than 100 of these slope failures mobilized volumes >108 m3 along basal failure planes with gradients as low as ∼5°. All landslides share characteristics of lateral rock spreads involving competent limestones overlying weak and plastic claystones. From relative stratigraphy and new 14C data, we infer that catastrophic slope failure of over 41 km3 occurred mostly during Pleistocene Caspian sea-level highstands, while several landslides may have been reactivated or entirely originated during the Holocene. This largest cluster of terrestrial mass wasting in a tectonically quiescent setting offers an opportunity to understand how landslides erode low-relief landscapes subject to oscillating sea levels.
Integrated geochemical-petrographic insights from component-selective δ238U of Cryogenian marine carbonates
Authors: Hood Ashleigh v.S. , Planavsky Noah J. , Wallace Malcolm W. , Wang Xiangli , Bellefroid Eric J. , Gueguen Bleuenn , Cole Devon B.
Published: October 2016

Emerging geochemical proxies have improved our understanding of the broad-scale history of Earth’s oxygenation. However, paleoredox work does not always include extensive consideration of sample preservation and paleoenvironmental setting. This is particularly an issue with marine carbonates, which although being potentially ideal ocean redox archives, are commonly altered during diagenesis. Here we provide new insight into the robustness of uranium isotopes (238U/235U ratios: δ238U values) as paleoredox tracers by determining texture-specific δ238U values from a well-described Cryogenian (Balcanoona) reef complex in South Australia. We found high variability in δ238U values between different carbonate components, even within a single sample. Petrographically, the best-preserved components from the Balcanoona reef are marine cements, which have a mean δ238U value of −0.23‰, essentially unfractionated from riverine inputs. These values are interpreted as reflecting a marine system with widespread anoxic and iron-rich settings. Less-well-preserved phases have δ238U values spanning almost the entire extent of the documented isotopic range. This integrated petrographic-geochemical work demonstrates the need for petrographic analysis and careful sample selection on a case-by-case basis in future carbonate metal isotope geochemistry.
Unraveling alteration histories in serpentinites and associated ultramafic rocks with magnetite (U-Th)/He geochronology
Authors: Cooperdock Emily H.G. , Stockli Daniel F.
Published: October 2016

Serpentinization is a widespread process that affects large-scale geodynamic processes along plate boundaries, including continental breakup, seafloor spreading, and subduction. Documenting the timing of serpentinization is critical for our understanding of these processes, but direct dating of serpentinites has been challenging or impossible. We present the first application of magnetite (U-Th)/He chronometry to date stages of alteration and cooling in ultramafic rocks. In order to demonstrate the viability of magnetite He dating in these lithologies, magnetite ages were obtained from two ultramafic lithologies of the Kampos mélange belt, a high-pressure–low-temperature subduction complex on the island of Syros, Greece. Magnetite (U-Th)/He measurements of internal fragments from large grains within a chlorite schist and a serpentinite record Miocene exhumation-related cooling ages, whereas smaller grains from the serpentinite record mineral growth associated with hydrothermal fluid flow along Pliocene normal faults. These age results with magnetite trace element geochemistry reveal evidence for multiple episodes of fluid-rock alteration, which has implications for the cooling history and local geochemical exchanges of this high-pressure–low-temperature terrane. This method provides a new tool that may be expanded to investigate the processes and time scales of serpentinization from a variety of tectonic settings.
Effects of Myofascial Trigger Point Dry Needling in Patients with Sleep Bruxism and Temporomandibular Disorders: A Prospective Case Series
Authors: Blasco-Bonora Paloma María , Martín-Pintado-Zugasti Aitor
Published: October 2016

Objectives

To investigate the effects of deep dry needling (DN) of myofascial trigger points (MTrPs) of the masseter and temporalis on pain, pressure pain threshold (PPT), pain-free maximal jaw opening and temporomandibular disorder (TMD)-related disability in patients with sleep bruxism (SB) and myofascial TMD.

Methods

Seventeen subjects (11 women, 6 men) aged 39±13 years (range 23–66) diagnosed with SB and myofascial TMD were invited to participate in this prospective case series study. Each subject received a deep DN intervention in the masseter and temporalis MTrPs. Pain intensity, PPT, pain-free maximal jaw opening and TMD-related disability were assessed before treatment, immediately after treatment and at 1-week follow-up. Jaw disability was assessed using the jaw disability checklist (JDC) at baseline and 1 week post-treatment only.

Results

One-way analyses of variance showed significant improvements in pain intensity, PPT and jaw opening (p<0.001). Post-hoc analysis revealed significant differences between baseline and post-intervention follow-up time points in pain (immediate: Cohen's d=1.72, p<0.001; 1 week: d=3.24, p<0.001), jaw opening (immediate: d=0.77, p<0.001; 1 week: d=1.02, p<0.001) and PPT in the masseter (immediate: d=1.02, p<0.001; 1 week: d=1.64, p<0.001) and temporalis (immediate: d=0.91, p=0.006; 1 week: d=1.8, p<0.001). A dependent t-test showed a significant improvement in jaw functioning, reflected by a large reduction in 1-week JDC scores relative to baseline (d=3.15, p<0.001).

Conclusions

Deep DN of active MTrPs in the masseter and temporalis in patients with myofascial TMD and SB was associated with immediate and 1-week improvements in pain, sensitivity, jaw opening and TMD-related disability.

Trial registration number

Results.
Rare presentation of a localised malignant pleural mesothelioma with cranial metastasis
Authors: Ertan Gulhan , Eren Abdulkadir , Ulus Sila
Published: October 2016

Mesothelioma is an uncommon malignant neoplasm and a localised form of the pleura is especially very rare. Diagnosis of localised malignant pleural mesothelioma (LMPM) is very challenging. Histopathological verification is the gold standard, and studies such as CT, positron emission tomography (PET) and thoracoscopy are very valuable tools in assisting diagnosis. We report a case of histopathologically proven LMPM, which was discovered as a well circumscribed solitary subpleural nodule on PET-CT after presentation with cranial metastasis. This case shows that LMPM can present with uncommon radiological and clinical appearances, and imaging tools such as PET-CT have a very important role in diagnosis.
The relationships between golf and health: a scoping review
Authors: Murray A D , Daines L , Archibald D , Hawkes R A , Schiphorst C , Kelly P , Grant L , Mutrie N
Published: October 2016

Objective

To assess the relationships between golf and health.

Design

Scoping review.

Data sources

Published and unpublished reports of any age or language, identified by searching electronic databases, platforms, reference lists, websites and from consulting experts.

Review methods

A 3-step search strategy identified relevant published primary and secondary studies as well as grey literature. Identified studies were screened for final inclusion. Data were extracted using a standardised tool, to form (1) a descriptive analysis and (2) a thematic summary.

Results and discussion

4944 records were identified with an initial search. 301 studies met criteria for the scoping review. Golf can provide moderate intensity physical activity and is associated with physical health benefits that include improved cardiovascular, respiratory and metabolic profiles, and improved wellness. There is limited evidence related to golf and mental health. The incidence of golfing injury is moderate, with back injuries the most frequent. Accidental head injuries are rare, but can have serious consequences.

Conclusions

Practitioners and policymakers can be encouraged to support more people to play golf, due to associated improved physical health and mental well-being, and a potential contribution to increased life expectancy. Injuries and illnesses associated with golf have been identified, and risk reduction strategies are warranted. Further research priorities include systematic reviews to further explore the cause and effect nature of the relationships described. Research characterising golf's contribution to muscular strengthening, balance and falls prevention as well as further assessing the associations and effects between golf and mental health are also indicated.
Large-scale survey of rates of achieving targets for blood glucose, blood pressure, and lipids and prevalence of complications in type 2 diabetes (JDDM 40)
Authors: Yokoyama Hiroki , Oishi Mariko , Takamura Hiroshi , Yamasaki Katsuya , Shirabe Shin-ichiro , Uchida Daigaku , Sugimoto Hidekatsu , Kurihara Yoshio , Araki Shin-ichi , Maegawa Hiroshi
Published: October 2016

Objective

The fact that population with type 2 diabetes mellitus and bodyweight of patients are increasing but diabetes care is improving makes it important to explore the up-to-date rates of achieving treatment targets and prevalence of complications. We investigated the prevalence of microvascular/macrovascular complications and rates of achieving treatment targets through a large-scale multicenter-based cohort.

Research design and methods

A cross-sectional nationwide survey was performed on 9956 subjects with type 2 diabetes mellitus who consecutively attended primary care clinics. The prevalence of nephropathy, retinopathy, neuropathy, and macrovascular complications and rates of achieving targets of glycated hemoglobin (HbA1c) <7.0%, blood pressure <130/80 mm Hg, and lipids of low-density/high-density lipoprotein cholesterol <3.1/≥1.0 mmol/L and non-high-density lipoprotein cholesterol <3.8 mmol/L were investigated.

Results

The rates of achieving targets for HbA1c, blood pressure, and lipids were 52.9%, 46.8% and 65.5%, respectively. The prevalence of microvascular complications was ∼28% each, 6.4% of which had all microvascular complications, while that of macrovascular complications was 12.6%. With an increasing duration of diabetes, the rate of achieving target HbA1c decreased and the prevalence of each complication increased despite increased use of diabetes medication. The prevalence of each complication decreased according to the number achieving the 3 treatment targets and was lower in subjects without macrovascular complications than those with. Adjustments for considerable covariates exhibited that each complication was closely inter-related, and the achievement of each target was significantly associated with being free of each complication.

Conclusions

Almost half of the subjects examined did not meet the recommended targets. The risk of each complication was significantly affected by 1 on-target treatment (inversely) and the concomitance of another complication (directly). Total diabetes care including one-by-one management of modifiable risk factors and complications may be important for high-quality care. The future studies including more subjects and clinics with precise complication status are needed.
Improving the well-being of men by Evaluating and Addressing the Gastrointestinal Late Effects (EAGLE) of radical treatment for prostate cancer: study protocol for a mixed-method implementation project
Authors: Taylor Sophia , Demeyin Weyinmi , Muls Ann , Ferguson Catherine , Farnell Damian J J , Cohen David , Andreyev Jervoise , Green John , Smith Lesley , Ahmedzai Sam , Pickett Sara , Nelson Annmarie , Staffurth John
Published: October 2016

Introduction

Radiotherapy treatment for prostate cancer can cause bowel problems, which may lead to severe difficulties for cancer survivors including limiting travel, work or socialising. These symptoms can appear at any time following radiotherapy. This study focuses on the early identification and protocol-based management of effects known to cause long-term, or even permanent, changes to the well-being of prostate cancer survivors. The rationale of this study is to improve the care offered to men and their families following pelvic radiotherapy for prostate cancer.

Method and analysis

Implementation research methodology will be used to adopt a multicomponent intervention at three UK centres. The intervention package comprises a standardised clinical assessment of relevant symptoms in oncology outpatient clinics and rapid referral to an enhanced gastroenterological service for patients identified with bowel problems. Gastroenterology staff will be trained to use an expert-practice algorithm of targeted gastroenterology investigations and treatments. The evaluation of the intervention and its embedding within local practices will be conducted using a mixed-methods design. The effect of the new service will be measured in terms of the following outcomes: acceptability to staff and patients; quality of life; symptom control and cost-effectiveness. Data collection will take place at baseline, 6 months (±2 months), and 12 months (±2 months) after entry into the study.

Ethics and dissemination

The study has ethical approval from the North West-Liverpool East Research Ethics Committee and the appropriate NHS governance clearance. All participants provide written informed consent. The study team aim to publish the results of the study in peer-reviewed journals as well as at national and international conferences.

Trial registration number

UKCRN16974
Stability of gas measures under perturbations and discretizations
Authors: Fernández Roberto , Groisman Pablo , Saglietti Santiago
Published: October 2016

For a general class of gas models — which includes discrete and continuous Gibbsian models as well as contour or polymer ensembles — we determine a diluteness condition that implies: (1) uniqueness of the infinite-volume equilibrium measure; (2) stability of this measure under perturbations of parameters and discretization schemes, and (3) existence of a coupled perfect-simulation scheme for the infinite-volume measure together with its perturbations and discretizations. Some of these results have previously been obtained through methods based on cluster expansions. In contrast, our treatment is purely probabilistic and its diluteness condition is weaker than existing convergence conditions for cluster expansions.
COST-EFFECTIVENESS ANALYSIS OF ELECTRIC VEHICLES IN SINGAPORE
Authors: YUEN KAH-HUNG
Published: October 2016

As a compact city-state with a modern electricity grid and relatively clean energy sources, Singapore seems ideal for the deployment of the battery electric vehicle (BEV). A fleet of 89 BEVs were deployed in a test-bed that was concluded in 2013. The paper conducts a cost-effectiveness analysis and financial analysis of the Renault Fluence ZE and its comparable gasoline model to assess the economics of BEVs. It concludes that BEV adoption in Singapore is both undesirable (due to higher social costs) and unlikely (due to higher private costs) in the immediate and near future. Where 94% of the population live in high-rise apartments, there will be a heavy reliance on costlier communal charging stations, thereby mitigating the operating savings that BEVs could have offered if home chargers were used. Lifetime costs are not as sensitive to changes in oil prices as expected. For the BEV to be socially viable, the breakeven carbon price amounts to S$9,700 per tonne of CO2, which suggests that BEVs are not a cost-effective means of reducing carbon emissions in Singapore, or battery prices would need to be halved. Nevertheless, the study demonstrates that exempting the BEV batteries from taxation could support BEV adoption if that were to be a government objective.
A Note on 1.5 Sigma Shift in Performance Evaluation
Authors: Raval Neha , Muralidharan K.
Published: October 2016

Understanding variation is critical to quality (CTQ) of product or service delivery, which is the key to success. Six Sigma is the business process improvement strategy that extensively focuses on variation reduction thereby reducing number of defects. One of the major constituents of Six Sigma definitions is 1.5 sigma shift, which is attributable to random error. It is not possible to understand Six Sigma thoroughly by overlooking the concept of 1.5 sigma shift. A conventional 3.4 defect per million opportunity (DPMO) capability of Six Sigma process is based on 1.5 sigma shift. This paper aimed at explaining ancestry of 1.5 sigma shift in connection with quality engineering methods. Origin of 1.5 sigma shift factor with reference to producibility analysis, worst-case sampling error and other quality engineering methods has been discussed in this paper.
An Application of Reliability Centered Maintenance Using RPN Mean and Range on Conventional Lathe Machine
Authors: Gupta G. , Mishra R. P. , Singhvi P.
Published: October 2016

RCM provides a structured and practical approach for arriving at an acceptable maintenance strategy for each component of a given system. In this paper, a study on reliability centered maintenance (RCM) has been conducted to reduce the total number of failures and its effects on the conventional lathe machine. The risk priority number (RPN) is, one of the key factors in determining the critical ranking of a failure mode of the mechanical equipment but there is a drawback in determining the critical ranking from RPN. There might be more than one failure modes which can share the same RPN number and therefore critical ranking cannot be assigned to those failure modes. Initially, the Severity, Occurrence and Detection rating integrating with failure mode and effect analysis (FMEA) is taken from several experts and then RPN is calculated for each of those experts. Then the criticality of the failure mode of the functionally significant items of conventional lathe machine is judged on the basis of mean RPN value as well as using the range. Overall the risk or criticality level of each failure mode is identified. After that, RCM logic is used for selection of a proper maintenance strategy for each failure mode.
Arithmetic properties of 5-regular bipartitions
Authors: Naika M. S. Mahadeva , Hemanthkumar B.
Published: October 2016

Let [Formula: see text] denote the number of [Formula: see text]-regular bipartitions of [Formula: see text]. In this work, we establish several infinite families of congruences modulo powers of 2 and 5 for [Formula: see text]. For example, we find that for all nonnegative integers [Formula: see text], [Formula: see text] and [Formula: see text] and [Formula: see text], [Formula: see text]
The McCoy condition on skew monoid rings
Authors: Paykan Kamal , Moussavi Ahmad
Published: October 2016

Let [Formula: see text] be an associative ring with identity, [Formula: see text] a monoid and [Formula: see text] a monoid homomorphism. When [Formula: see text] is a u.p.-monoid and [Formula: see text] is a reversible [Formula: see text]-compatible ring, then we observe that [Formula: see text] satisfies a McCoy-type property, in the context of skew monoid ring [Formula: see text]. We introduce and study the [Formula: see text]-McCoy condition on [Formula: see text], a generalization of the standard McCoy condition from polynomial rings to skew monoid rings. Several examples of reversible [Formula: see text]-compatible rings and also various examples of [Formula: see text]-McCoy rings are provided. As an application of [Formula: see text]-McCoy rings, we investigate the interplay between the ring-theoretical properties of a general skew monoid ring [Formula: see text] and the graph-theoretical properties of its zero-divisor graph [Formula: see text].
Caspase-1 deficiency promotes high-fat diet-induced adipose tissue inflammation and the development of obesity
Authors: Kimura Hiroaki , Karasawa Tadayoshi , Usui Fumitake , Kawashima Akira , Endo Yuka , Kobayashi Motoi , Sadatomo Ai , Nakamura Jun , Iwasaki Yusaku , Yada Toshihiko , Tsutsui Hiroko , Kasahara Tadashi , Takahashi Masafumi
Published: October 2016

Caspase-1 is a cysteine protease responsible for the processing of the proinflammatory cytokine interleukin-1β and activated by the formation of inflammasome complexes. Although several investigations have found a link between diet-induced obesity and caspase-1, the relationship remains controversial. Here, we found that mice deficient in caspase-1 were susceptible to high-fat diet-induced obesity with increased adiposity as well as normal lipid and glucose metabolism. Caspase-1 deficiency clearly promoted the infiltration of inflammatory macrophages and increased the production of C-C motif chemokine ligand 2 (CCL2) in the adipose tissue. The dominant cellular source of CCL2 was stromal vascular fraction rather than adipocytes in the adipose tissue. These findings demonstrate a critical role of caspase-1 in macrophage-driven inflammation in the adipose tissue and the development of obesity. These data provide novel insights into the mechanisms underlying inflammation in the pathophysiology of obesity.
Prolonged sitting negatively affects the postprandial plasma triglyceride-lowering effect of acute exercise
Authors: Kim Il-Young , Park Sanghee , Chou Ting-Heng , Trombold Justin R. , Coyle Edward F.
Published: October 2016

The interaction of prolonged sitting with physical exercise for maintaining health is unclear. We tested the hypothesis that prolonged siting would have a deleterious effect on postprandial plasma lipemia (PPL, postprandial plasma triglycerides) and reduce the ability of an acute exercise bout to attenuate PPL. Seven healthy young men performed three, 5-day interventions [ days 1–5 (D1–D5)] in a randomized crossover design with >1 wk between interventions: 1) sitting > 14 h/day with hypercaloric energy balance (SH), 2) sitting >14 h/day with net energy balance (SB), and 3) active walking/standing with net energy balance (WB) and sitting 8.4 h/day. The first high-fat tolerance test (HFTT1) was performed on D3 following 2 days of respective interventions. On the evening of D4 subjects ran on a treadmill for 1 h at ~67% V̇o2max, followed by the second HFTT (HFTT2) on D5. Two days of prolonged sitting increased TG AUCI (i.e., incremental area under the curve for TG), irrespective of energy balance, compared with WB (27% in SH, P = 0.003 and 26% in SB, P = 0.046). Surprisingly, after 4 days of prolonged sitting (i.e.; SH and SB), the acute exercise on D4 failed to attenuate TG AUCI or increase relative fat oxidation in HFTT2, compared with HFTT1, regardless of energy balance. In conclusion, prolonged sitting over 2–4 days was sufficient to amplify PPL, which was not attenuated by acute exercise, regardless of energy balance. This underscores the importance of limiting sitting time even in people who have exercised.
Inositol Treatment and ART Outcomes in Women with PCOS
Authors: Garg Deepika , Tal Reshef
Published: October 2016

Polycystic ovary syndrome (PCOS) affects 5–10% of women in reproductive age and is characterized by oligo/amenorrhea, androgen excess, insulin resistance, and typical polycystic ovarian morphology. It is the most common cause of infertility secondary to ovulatory dysfunction. The underlying etiology is still unknown but is believed to be multifactorial. Insulin-sensitizing compounds such as inositol, a B-complex vitamin, and its stereoisomers (myo-inositol and D-chiro-inositol) have been studied as an effective treatment of PCOS. Administration of inositol in PCOS has been shown to improve not only the metabolic and hormonal parameters but also ovarian function and the response to assisted-reproductive technology (ART). Accumulating evidence suggests that it is also capable of improving folliculogenesis and embryo quality and increasing the mature oocyte yield following ovarian stimulation for ART in women with PCOS. In the current review, we collate the evidence and summarize our current knowledge on ovarian stimulation and ART outcomes following inositol treatment in women with PCOS undergoing in vitro fertilization (IVF) and/or intracytoplasmic sperm injection (ICSI).
Radix Astragali‐Based Chinese Herbal Medicine for Oxaliplatin‐Induced Peripheral Neuropathy: A Systematic Review and Meta‐Analysis
Authors: Deng Bo , Jia Liqun , Cheng Zhiqiang
Published: October 2016

Background. Treatment of chemotherapy‐induced peripheral neuropathy (CIPN) remains a big challenge for oncologists. The aim of this study is to evaluate the effects of Radix Astragali‐ (RA‐) based Chinese herbal medicine in the prevention and treatment of oxaliplatin‐induced peripheral neuropathy, including the incidence and grading of neurotoxicity, effective percentage, and nerve conduction velocity. Methods. All randomized controlled trials (RCTs) were found using PubMed, Cochrane, Springer, China National Knowledge Infrastructure (CNKI), and Wanfang Database of China Science Periodical Database (CSPD) by keyword search. Meta‐analysis was conducted using RevMan 5.0. Results. A total of 1552 participants were included in 24 trials. Meta‐analysis showed the incidence of all‐grade neurotoxicity was significantly lower in experimental groups and high‐grade neurotoxicity was also significantly less. Effective percentage was significantly higher and sensory nerve conduction velocity was improved significantly, but changes in motor nerve conduction velocity were not statistically significant. No adverse events associated with RA‐based intervention were reported. Conclusion. RA‐based intervention may be beneficial in relieving oxaliplatin‐induced peripheral neuropathy. However, more double‐blind, multicenter, large‐scale RCTs are needed to support this theory. Trial Registration. PROSPERO International prospective register of systematic reviews has registration number  CRD42015019903.
Profile of Trace Elements in Selected Medicinal Plants Used for the Treatment of Diabetes in Eritrea
Authors: Sium Mussie , Kareru Patrick , Keriko Joseph , Girmay Berhane , Medhanie Ghebrehiwet , Debretsion Semere
Published: October 2016

This study was designed to investigate the profile of certain trace elements having therapeutic properties related to diabetes mellitus. The investigated plants wereAloe camperi,Meriandra dianthera,Lepidium sativum,Brassica nigra, and Nigella sativa. These plants are traditionally used in the management of diabetes in Eritrea. The elemental analysis was conducted using inductively coupled plasma optical emission spectrometry (ICP-OES) and flame atomic absorption spectroscopy (FAAS) techniques. The accuracy of the methods was verified using in-house reference materials (CRMs) and no significant differences were observed between the measured and certified values. The analysis displayed variable concentrations of the different trace elements including Zn, Cr, V, Mn, and Se in the plants. Moreover, the levels of major elements, such as Mg, Ca, K, Na, and Ba, and heavy metals, such as Fe, Cu, Ni, Co, As, and Pb, were determined and found to be in the permissible limit defined by WHO. Among the plants,Meriandra diantherashowed the highest levels of Mn, Cr, V, and other elements and the values were significantly different (P<0.05).
CCR9 Is a Key Regulator of Early Phases of Allergic Airway Inflammation
Authors: López-Pacheco C. , Soldevila G. , Du Pont G. , Hernández-Pando R. , García-Zepeda E. A.
Published: October 2016

Airway inflammation is the most common hallmark of allergic asthma. Chemokine receptors involved in leukocyte recruitment are closely related to the pathology in asthma. CCR9 has been described as a homeostatic and inflammatory chemokine receptor, but its role and that of its ligand CCL25 during lung inflammation remain unknown. To investigate the role of CCR9 as a modulator of airway inflammation, we established an OVA-induced allergic inflammation model in CCR9-deficient mice. Here, we report the expression of CCR9 and CCL25 as early as 6 hours post-OVA challenge in eosinophils and T-lymphocytes. Moreover, in challenged CCR9-deficient mice, cell recruitment was impaired at peribronchial and perivenular levels. OVA-administration in CCR9-deficient mice leads to a less inflammatory cell recruitment, which modifies the expression of IL-10, CCL11, and CCL25 at 24 hours after OVA challenge. In contrast, the secretion of IL-4 and IL-5 was not affected in CCR9-deficient mice compared to WT mice. These results demonstrate for the first time that CCR9 and CCL25 expressions are induced in the early stages of airway inflammation and they have an important role modulating eosinophils and lymphocytes recruitment at the first stages of inflammatory process, suggesting that they might be a potential target to regulate inflammation in asthma.
Two Cases of Solitary Fibrous Tumor Involving Urinary Bladder and a Review of the Literature
Authors: Tanaka Eduardo Yukio , Buonfiglio Vitor Bonadia , Manzano Joao Padua , Filippi Renée Zon , Sadi Marcus Vinicius
Published: October 2016

Solitary fibrous tumor (SFT) is a rare neoplasia of mesenchymal origin, initially described in visceral pleura and lately discovered to have ubiquitous distribution. SFT of the urogenital tract is uncommon and appears to have similar morphologic features and biologic behaviors as SFTs found elsewhere. We present two new cases of SFT of the bladder and review 22 similar cases published in the literature. Due to the general indolent behavior of these lesions, a complete but organ sparing surgical excision should be considered when technically feasible. Therefore, proper identification and characterization of SFT through morphological and immunohistochemical criteria on biopsy specimens are mandatory in the differential diagnosis from other more aggressive spindle-cell tumors, thus avoiding unnecessary radical surgery.
Does Physical Fitness Buffer the Relationship between Psychosocial Stress, Retinal Vessel Diameters, and Blood Pressure among Primary Schoolchildren?
Authors: Gerber Markus , Endes Katharina , Herrmann Christian , Colledge Flora , Brand Serge , Donath Lars , Faude Oliver , Pühse Uwe , Hanssen Henner , Zahner Lukas
Published: October 2016

Background. Strong evidence exists showing that psychosocial stress plays an important part in the development of cardiovascular diseases. Because physical inactivity is associated with less favourable retinal vessel diameter and blood pressure profiles, this study explores whether physical fitness is able to buffer the negative effects of psychosocial stress on retinal vessel diameters and blood pressure in young children.Methods. 325 primary schoolchildren (51% girls,Mage=7.28years) took part in this cross-sectional research project. Retinal arteriolar diameters, retinal venular diameters, arteriolar to venular ratio, and systolic and diastolic blood pressure were assessed in all children. Interactions terms between physical fitness (performance in the 20 m shuttle run test) and four indicators of psychosocial stress (parental reports of critical life events, family, peer and school stress) were tested in a series of hierarchical regression analyses.Results. Critical life events and family, peer, and school-related stress were only weakly associated with retinal vessel diameters and blood pressure. No support was found for a stress-buffering effect of physical fitness.Conclusion. More research is needed with different age groups to find out if and from what age physical fitness can protect against arteriolar vessel narrowing and the occurrence of other cardiovascular disease risk factors.
Effect of Gender on the Knowledge of Medicinal Plants: Systematic Review and Meta‐Analysis
Authors: Torres-Avilez Wendy , Medeiros Patrícia Muniz de , Albuquerque Ulysses Paulino
Published: October 2016

Knowledge of medicinal plants is not only one of the main components in the structure of knowledge in local medical systems but also one of the most studied resources. This study uses a systematic review and meta‐analysis of a compilation of ethnobiological studies with a medicinal plant component and the variable of gender to evaluate whether there is a gender‐based pattern in medicinal plant knowledge on different scales (national, continental, and global). In this study, three types of meta‐analysis are conducted on different scales. We detect no significant differences on the global level; women and men have the same rich knowledge. On the national and continental levels, significant differences are observed in both directions (significant for men and for women), and a lack of significant differences in the knowledge of the genders is also observed. This finding demonstrates that there is no gender‐based pattern for knowledge on different scales.
Solidification/Stabilization of Fly Ash from a Municipal Solid Waste Incineration Facility Using Portland Cement
Authors: Tang Qiang , Liu Yang , Gu Fan , Zhou Ting
Published: October 2016

This study investigated the solidification/stabilization of fly ash containing heavy metals using the Portland cement as a binder. It is found that both the cement/fly ash ratio and curing time have significant effects on the mechanical (i.e., compressive strength) and leaching behaviors of the stabilized fly ash mixtures. When the cement/fly ash ratio increases from 4 : 6 to 8 : 2, the increase of compressive strength ratio raises from 42.24% to 80.36%; meanwhile, the leaching amount of heavy metals decreases by 2.33% to 85.23%. When the curing time increases from 3 days to 56 days, the compressive strength ratio of mixtures raises from 240.00% to 414.29%; meanwhile, the leaching amount of heavy metals decreases by 16.49% to 88.70%. The decrease of compressive strength with the lower cement/fly ash ratios and less curing time can be attributed to the increase of fly ash loading, which hinders the formation of ettringite and destroys the structure of hydration products, thereby resulting in the pozzolanic reaction and fixation of water molecules. Furthermore, the presence of cement causes the decrease of leaching, which results from the formation of ettringite and the restriction of heavy metal ion migration in many forms, such as C-S-H gel and adsorption.
The Dual Syk/JAK Inhibitor Cerdulatinib Antagonizes B-cell Receptor and Microenvironmental Signaling in Chronic Lymphocytic Leukemia
Authors: Blunt Matthew D. , Koehrer Stefan , Dobson Rachel C. , Larrayoz Marta , Wilmore Sarah , Hayman Alice , Parnell Jack , Smith Lindsay D. , Davies Andrew , Johnson Peter W.M. , Conley Pamela B. , Pandey Anjali , Strefford Jonathan C. , Stevenson Freda K. , Packham Graham , Forconi Francesco , Coffey Greg P. , Burger Jan A. , Steele Andrew J.
Published: October 2016

Purpose: B-cell receptor (BCR)–associated kinase inhibitors, such as ibrutinib, have revolutionized the treatment of chronic lymphocytic leukemia (CLL). However, these agents are not curative, and resistance is already emerging in a proportion of patients. IL4, expressed in CLL lymph nodes, can augment BCR signaling and reduce the effectiveness of BCR kinase inhibitors. Therefore, simultaneous targeting of the IL4- and BCR signaling pathways by cerdulatinib, a novel dual Syk/JAK inhibitor currently in clinical trials (NCT01994382), may improve treatment responses in patients.

Experimental Design: PBMCs from patients with CLL were treated in vitro with cerdulatinib alone or in combination with venetoclax. Cell death, chemokine, and cell signaling assay were performed and analyzed by flow cytometry, immunoblotting, q-PCR, and ELISA as indicated.

Results: At concentrations achievable in patients, cerdulatinib inhibited BCR- and IL4-induced downstream signaling in CLL cells using multiple readouts and prevented anti-IgM- and nurse-like cell (NLC)–mediated CCL3/CCL4 production. Cerdulatinib induced apoptosis of CLL cells, in a time- and concentration-dependent manner, and particularly in IGHV-unmutated samples with greater BCR signaling capacity and response to IL4, or samples expressing higher levels of sIgM, CD49d+, or ZAP70+. Cerdulatinib overcame anti-IgM, IL4/CD40L, or NLC-mediated protection by preventing upregulation of MCL-1 and BCL-XL; however, BCL-2 expression was unaffected. Furthermore, in samples treated with IL4/CD40L, cerdulatinib synergized with venetoclax in vitro to induce greater apoptosis than either drug alone.

Conclusions: Cerdulatinib is a promising therapeutic for the treatment of CLL either alone or in combination with venetoclax, with the potential to target critical survival pathways in this currently incurable disease. Clin Cancer Res; 23(9); 2313–24. ©2016 AACR.
Electrospun Fibers for Drug Delivery after Spinal Cord Injury and the Effects of Drug Incorporation on Fiber Properties
Authors: Johnson Christopher D.L. , D'Amato Anthony R. , Gilbert Ryan J.
Published: October 2016

There is currently no cure for individuals with spinal cord injury (SCI). While many promising approaches are being tested in clinical trials, the complexity of SCI limits several of these approaches from aiding complete functional recovery. Several different categories of biomaterials are investigated for their ability to guide axonal regeneration, to deliver proteins or small molecules locally, or to improve the viability of transplanted stem cells. The purpose of this study is to provide a brief overview of SCI, present the different categories of biomaterial scaffolds that direct and guide axonal regeneration, and then focus specifically on electrospun fiber guidance scaffolds. Much like other polymer guidance approaches, electrospun fibers can retain and deliver therapeutic drugs. The experimental section presents new data showing the incorporation of two therapeutic drugs into electrospun poly-L-lactic acid fibers. Two different concentrations of either riluzole or neurotrophin-3 were loaded into the electrospun fibers to examine the effect of drug concentration on the physical characteristics of the fibers (fiber alignment and fiber diameter). Overall, the drugs were successfully incorporated into the fibers and the release was related to the loading concentration. The fiber diameter decreased with the inclusion of the drug, and the decreased diameter was correlated with a decrease in fiber alignment. Subsequently, the study includes considerations for successful incorporation of a therapeutic drug without changing the physical properties of the fibers.
Metabolic and Hormonal Determinants of Glomerular Filtration Rate and Renal Hemodynamics in Severely Obese Individuals
Authors: Vitolo Edoardo , Santini Eleonora , Salvati Antonio , Volterrani Duccio , Duce Valerio , Bruno Rosa Maria , Solini Anna
Published: October 2016

Objective: Renal function is often compromised in severe obesity. A true measurement of glomerular filtration rate (GFR) is unusual, and how estimation formulae (EstForm) perform in such individuals is unclear. We characterized renal function and hemodynamics in severely obese individuals, assessing the reliability of EstForm. Methods: We measured GFR (mGFR) by iohexol plasma clearance, renal plasma flow (RPF) by 123I-ortho-iodo-hippurate, basal and stimulated vascular renal indices, endothelium-dependent and -independent vasodilation using flow-mediated dilation (FMD) as well as metabolic and hormonal profile in morbid, otherwise healthy, obese subjects. Results: Compared with mGFR, the better performing EstForm was CKD-EPI (5.3 ml/min/1.73 m2 bias by Bland-Altman analysis). mGFR was directly related with RPF, total and incremental glucose AUC, and inversely with PTH and h8 cortisol. Patients with mGFR below the median shown significantly higher PTH and lower vitamin D3. Basal or dynamic renal resistive index, FMD, pulse wave velocity were not related with mGFR. In an adjusted regression model, renal diameter and plasma flow remained related with mGFR (R2 = 0.67), accounting for 15% and 21% of mGFR variance, respectively. Conclusions: CKD-EPI formula should be preferred in morbid obesity; glucose increments during oral glucose tolerance test correlate with hyperfiltration; RPF and diameter are independent determinants of mGFR; slightly high PTH values, frequent in obesity, might influence mGFR.