bluuebunny/crossref_metadata_2025 huggingface dataset:
Loss of Bacitracin Resistance Due to a Large Genomic Deletion among
Bacillus anthracis
Strains
Authors: Furuta Yoshikazu , Harima Hayato , Ito Emiko , Maruyama Fumito , Ohnishi Naomi , Osaki Ken , Ogawa Hirohito , Squarre David , Hang'ombe Bernard Mudenda , Higashi Hideaki
Published: October 2018

Anthrax is caused by
Bacillus anthracis
, an endospore-forming soil bacterium. The genetic diversity of
B. anthracis
is known to be low compared with that of
Bacillus
species. In this study, we performed whole-genome sequencing of Zambian isolates of
B. anthracis
to understand the genetic diversity between closely related strains. Comparison of genomic sequences revealed that closely related strains were separated into three groups based on single nucleotide polymorphisms distributed throughout the genome. A large genomic deletion was detected in the region containing a bacitracin resistance gene cluster flanked by rRNA operons, resulting in the loss of bacitracin resistance. The structure of the deleted region, which was also conserved among species of the
Bacillus cereus
group, has the potential for both deletion and amplification and thus might be enabling the species to flexibly control the level of bacitracin resistance for adaptive evolution.
Using patient-reported outcome measures (PROMs) to promote quality of care in the management of patients with established kidney disease requiring treatment with haemodialysis in the UK (PROM-HD): a qualitative study protocol
Authors: Anderson Nicola Elzabeth , Calvert Melanie , Cockwell Paul , Dutton Mary , Aiyegbusi Olalekan Lee , Kyte Derek
Published: October 2018

Introduction

Patients undergoing haemodialysis (HD) for end-stage kidney disease often report a poor quality of life (QoL) and identify that improving QoL has a higher priority for them than improvements in long-term survival. Research suggests that regular collection and usage of patient-reported outcome measures (PROMs) in patients with chronic conditions may reduce hospitalisation, improve QoL and overall survival. In the UK, despite increased use within research settings, PROMs have not been introduced into the routine clinical care for patients undergoing HD.

We report the protocol for ‘Using patient reported outcome measures (PROMs) to promote quality of care in the management of patients with established kidney disease requiring treatment with haemodialysis in the UK—PROM-HD’. The study aim is to investigate the methodological basis for the use of routine PROMs assessment, particularly using electronic formats (ePROMs) within clinical and research settings, to maximise the potential of PROM use in the management of the care of this patient group.

Methods and analysis

The project will use qualitative methodology to explore, by thematic analysis, the views, perceptions and experiences of patients receiving HD and members of the HD multidisciplinary team regarding the collection and use of PROMs in routine clinical care, particularly ePROMs. This will involve interviews with up to 30 patients or until saturation is achieved and three focus group sessions with approximately 18 members of the clinical team delivering care to this patient group, which will be interpreted broadly to include both professional and non-professional staff.
Clinical features, management and outcomes of severe ischaemic stroke in tertiary hospitals in China: protocol for a prospective multicentre registry-based observational study
Authors: Wu Simiao , Yuan Ruozhen , Xiong Yao , Zhang Shihong , Wu Bo , Liu Ming
Published: October 2018

Introduction

Severe ischaemic stroke is a devastating condition with high mortality and morbidity; however, there is insufficient evidence on its management. The aim of this study is to investigate causes, risk factors, clinical course, management and outcomes of severe ischaemic stroke in a real-world setting in tertiary hospitals in China.

Methods and analysis

This is a prospective, multicentre, registry-based observational study. We will recruit 2500 patients with acute ischaemic stroke from nine tertiary hospitals in Western China. Patients with acute ischaemic stroke admitted to the Department of Neurology within 30 days of stroke onset will be included. Patients will be visited within 24 hours after admission, on day 3, day 7 and at discharge, to collect data on their clinical state, blood biomarkers and brain imaging. Severe stroke is defined as severe neurological deficits (National Institute of Health Stroke Scale (NIHSS) ≥15 or in coma) on admission or clinical worsening (NIHSS increased by ≥4 scores) during hospitalisation. Patients will be followed up by structured telephone interviews at 3 months and 1 year after stroke onset. In-hospital outcomes include symptomatic haemorrhagic transformation and brain oedema by day 7 of admission, and survival status (death or survival) by discharge; follow-up outcomes will include survival status and functional outcome (assessed by modified Rankin Scale) at 3 months and 1 year. The current study will improve our knowledge about the development of severe ischaemic stroke at acute phase and factors influencing its outcomes, which will eventually facilitate optimisation of individualised interventions for its prevention and treatment.

Ethics and dissemination

Ethics approval is obtained from The Biomedical Research Ethics Committee of West China Hospital, Sichuan University (Reference No. 2017(130)). We will present our findings at the national and international conferences and peer-reviewed journals in stroke and neurology.

Trial registration number

NCT03222024; Pre-results.
BET 2: Ability of a normal gait examination to rule out cerebellar stroke in acute vertigo
Authors: Greer Alisha , Hewitt Mark
Published: October 2018

A short-cut review was carried out to establish whether a normal gait examination can rule out cerebellar stroke in patients with acute vertigo. 16 studies were relevant to the question. The author, year and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these papers are tabulated. The clinical bottom line is that a normal gait examination cannot rule out a cerebellar stroke but the presence of an abnormal gait can be associated.
The transferability of airborne laser scanning based tree-level models between different inventory areas
Authors: Karjalainen Tomi , Korhonen Lauri , Packalen Petteri , Maltamo Matti
Published: October 2018

In this paper, we examine the transferability of airborne laser scanning (ALS) based models for individual-tree detection (ITD) from one ALS inventory area (A1) to two other areas (A2 and A3). All areas were located in eastern Finland less than 100 km from each other and were scanned using different ALS devices and parameters. The tree attributes of interest were diameter at breast height (Dbh), height (H), crown base height (Cbh), stem volume (V), and theoretical sawlog volume (Vlog) of Scots pine (Pinus sylvestris L.) with Dbh ≥ 16 cm. All trees were first segmented from the canopy height models, and various ALS metrics were derived for each segment. Then only the segments covering correctly detected pines were chosen for further inspection. The tree attributes were predicted using the k-nearest neighbor (k-NN) imputation. The results showed that the relative root mean square error (RMSE%) values increased for each attribute after the transfers. The RMSE% values were, for A1, A2, and A3, respectively: Dbh, 13.5%, 14.8%, and 18.1%; H, 3.2%, 5.9%, and 6.2%; Cbh, 13.3%, 15.3%, and 18.3%; V, 29.3%, 35.4%, and 39.1%; and Vlog, 38.2%, 54.4% and 51.8%. The observed values indicate that it may be possible to employ ALS-based tree-level k-NN models over different inventory areas without excessive reduction in accuracy, assuming that the tree species are known to be similar.
Combined effects of elevated ozone, temperature, and nitrogen on stem phenolic concentrations of Scots pine (Pinus sylvestris) seedlings
Authors: Ghimire Rajendra P. , Kasurinen Anne , Häikiö Elina , Holopainen Jarmo K. , Julkunen-Tiitto Riitta , Holopainen Toini , Kivimäenpää Minna
Published: October 2018

Phenolic metabolites in forest trees play a key role in the defence against biotic and abiotic stressors, yet we lack information about the effects of combined abiotic factors on phenolic compounds in conifers. We studied the effects of combined abiotic factors (ozone × temperature, ozone × nitrogen, temperature × nitrogen, and ozone × temperature × nitrogen) on phenolic concentrations in stems of Scots pine (Pinus sylvestris L.) seedlings in a 3-year-long field experiment in central Finland. In current-year stems, elevated ozone increased the concentrations of total phenolics, soluble proanthocyanidins, and total proanthocyanidins, while warming reduced the concentrations of piceatannol glucoside, pinosylvin, isorhamnetin + kaempferol-3-rhamnoside, and monocoumaroyl isoquercitrin 1. Complex interaction effects on current-year stems showed that nitrogen addition increased the concentrations of some flavonoids in ambient ozone and temperature levels. In the stems from the previous years, ozone decreased the concentrations of total phenolics, total proanthocyanidins, and several flavonoids in ambient temperature, while warming increased their concentrations in combination with elevated ozone. Our results suggest that phenolic defence responses in Scots pine seedlings are affected by all three factors, but that the level of phenolics in the stems from previous years may increase under the combined exposure to elevated temperature and ozone — an expected climate trend in the Northern Hemisphere.
Lateral Inhibition Organizes Beta Attentional Modulation in the Primary Visual Cortex
Authors: Gajewska-Dendek Elżbieta , Wróbel Andrzej , Bekisz Marek , Suffczynski Piotr
Published: October 2018

We have previously shown that during top-down attentional modulation (stimulus expectation) correlations of the beta signals across the primary visual cortex were uniform, while during bottom-up attentional processing (visual stimulation) their values were heterogeneous. These different patterns of attentional beta modulation may be caused by feed-forward lateral inhibitory interactions in the visual cortex, activated solely during stimulus processing. To test this hypothesis, we developed a large-scale computational model of the cortical network. We first identified the parameter range needed to support beta rhythm generation, and next, simulated the different activity states corresponding to experimental paradigms. The model matched our experimental data in terms of spatial organization of beta correlations during different attentional states and provided a computational confirmation of the hypothesis that the paradigm-specific beta activation spatial maps depend on the lateral inhibitory mechanism. The model also generated testable predictions that cross-correlation values depend on the distance between the activated columns and on their spatial position with respect to the location of the sensory inputs from the thalamus.
FLC and PWM SMC for KY Boost Converter
Authors: Ramash Kumar K.
Published: October 2018

This paper presents a design and implementation of fuzzy logic controller (FLC) plus PWM sliding mode controller (SMC) for 2nd order-d KY positive output voltage boost converter (KYPOVBC) operated in continuous inductor current mode (CICM). It is more suitable for steady power source in liquid crystal display (LCD), I-pad, CCTV camera, computer parts, light emitting diode (LED), renewable energy and industrial application. The 2nd order-d KYPOVBC always works in CICM and replica of synchronous rectification characteristics. The ON/OFF nature of the 2nd order-d KYPOVBC is nonlinear and their dynamic performance becomes poor. The classical linear controllers are noncapable of output voltage regulation of this converter during the high input supply voltage and load disparities. With the purpose of improving dynamic performance, an output voltage and inductor current regulation of the 2nd order-d KYPOVBC, a SMC plus FLC is designed. The state-space equations of the 2nd order-d KYPOVBC are arrived and then, SMC parameters are calculated. The FLC rules are framed according to the working nature of the 2nd order-d KYPOVBC without mathematical modeling, which is one of the major advantages of the FLC. The SMC acts as an inside loop of this converter to regulate the inductor current, whereas the FLC and proportional integral (PI) controllers act as an outside loop of the same converter for controlling the output voltage. The performance of the designed model is investigated at various operating regions by developing both the experimental and matrix laboratory (MATLAB)/simulation link (Simulink) models in comparison with the SMC plus PI controller. The results are presented to show the best performance of the designed model.
New α-coupled fixed point theorem for 𝜃-contraction and its application to a class of systems of functional equations arising in dynamic programming
Authors: Dhivya P. , Marudai M.
Published: October 2018

We introduce [Formula: see text]-coupled fixed point for [Formula: see text]-contractions in the space of bounded functions on a set [Formula: see text]. As an application of our result, we prove the existence and uniqueness of solutions for a class of systems of functional equations arising in dynamic programming.
Morphological characterization of landforms produced by springtime seasonal activity on Russell Crater megadune, Mars
Authors: Jouannic Gwenaël , Conway Susan J. , Gargani Julien , Costard François , Massé Marion , Bourgeois Olivier , Carter John , Schmidt Frédéric , Marmo Chiara , Ori Gian G. , Nachon Marion , Pasquon Kelly
Published: October 2018

We describe in detail an annual seasonal process that occurs on the surface of the Russell Crater megadune on Mars. We give these features the name ‘perennial rills’, because their surface topographical expression persists from year-to-year and they form a distinctive, downstream-branching network of small channels, or rills. We used time-series images, elevation data from stereophotogrammetry and spectral data to characterize the evolution of these features over 6 Mars years. Growth and modification of these networks occurs abruptly in spring (at a solar longitude of
c.
200°) after most of the seasonal CO
2
ice has sublimated. We find that the peculiar morphology of perennial rills seems to be the only aspect that sets them apart from active linear dune gullies. By comparison to terrestrial analogues, we identified two conditions favouring the production of such a network: (a) the presence of an impermeable layer; and (b) the repeated formation of obstacles in front of propagating channels. We find that the most plausible formation mechanisms that can explain the formation of both the perennial rills and the active linear dune gullies are levitating CO
2
blocks or liquid debris flows of water/brine, but neither can completely satisfy all the observational evidence.
Ordovician conulariids (Scyphozoa) from the Upper Tiouririne Formation (Katian), eastern Anti-Atlas Mountains, southern Morocco
Authors: Van Iten Heyo , Gutiérrez-Marco Juan Carlos , Muir Lucy A. , Simões Marcello G. , Leme Juliana M.
Published: October 2018

Storm-dominated siliciclastic shelf deposits in the upper half of the Upper Tiouririne Formation (Upper Ordovician, upper Berounian–
c.
Katian 1–2) of southern Morocco contain large specimens of at least two species of
Archaeoconularia
(
A
. aff.
consobrina
and
A
. cf.
imperialis
).
Pseudoconularia
cf.
grandissima
occurs in basal beds of the formation, but is far less abundant than
Archaeoconularia
. The large size of the
Archaeoconularia
(>500 mm long in some cases) suggests gigantism induced by cold, nutrient-rich waters. Specimens preserving the apical end terminate in a schott, indicating that the conulariids were severed near the apex prior to final burial. Many of the
Archaeoconularia
occur in monospecific aggregations in which the component specimens exhibit preferential alignment, probably owing to entrainment and burial by storm currents or flows. Some
Archaeoconularia
are encrusted by edrioasteroids and/or craniid brachiopods, which in certain cases are so closely spaced as to interfere with growth. The edrioasteroids and brachiopods were probably epibionts attached to living, erect or semi-erect conulariids that were partially infaunal. More generally, Late Ordovician conulariid assemblages of South Polar Gondwana and adjacent terranes exhibit low generic diversity relative to those of low- to mid-latitude terranes (Baltica and Laurentia), and are dominated numerically by
Archaeoconularia
.
Exposing Memory Access Patterns to Improve Instruction and Memory Efficiency in GPUs
Authors: Crago Neal C. , Stephenson Mark , Keckler Stephen W.
Published: October 2018

Modern computing workloads often have high memory intensity, requiring high bandwidth access to memory. The memory request patterns of these workloads vary and include regular strided accesses and indirect (pointer-based) accesses. Such applications require a large number of address generation instructions and a high degree of memory-level parallelism. This article proposes new memory instructions that exploit strided and indirect memory request patterns and improve efficiency in GPU architectures. The new instructions reduce address calculation instructions by offloading addressing to dedicated hardware, and reduce destructive memory request interference by grouping related requests together. Our results show that we can eliminate 33% of dynamic instructions across 16 GPU benchmarks. These improvements result in an overall runtime improvement of 26%, an energy reduction of 18%, and a reduction in energy-delay product of 32%.
Anacardium microcarpum Promotes Neuroprotection Dependently of AKT and ERK Phosphorylation but Does Not Prevent Mitochondrial Damage by 6‐OHDA
Authors: Martins Illana Kemmerich , de Carvalho Nélson Rodrigues , Macedo Giulianna Echeverria , Rodrigues Nathane Rosa , Ziech Cynthia Camila , Vinadé Lúcia , Filho Valter Menezes Barbosa , Menezes Irwin Alencar , Franco Jeferson , Posser Thaís
Published: October 2018

Parkinson’s disease is a degenerative and progressive illness characterized by the degeneration of dopaminergic neurons. 6‐hydroxydopamine (6‐OHDA) is a widespread model for induction of molecular and behavioral alterations similar to Parkinson and has contributed for testing of compounds with neuroprotective potential. The Brazilian plant Anacardium microcarpum is used in folk medicine for treatment of several illnesses; however, the knowledge about toxicology and biological effects for this plant is very rare. The neuroprotective effect from hydroalcoholic extract and methanolic and acetate fraction of A. microcarpum on 6‐OHDA‐induced damage on chicken brain slices was investigated in this study. 6‐OHDA decreased cellular viability measured by MTT reduction assay, induced lipid peroxidation by HPLC, stimulated Glutathione‐S‐Transferase and Thioredoxin Reductase activity, and decreased Glutathione Peroxidase activity and the total content of thiols containing compounds. The methanolic fraction of A. microcarpum presented the better neuroprotective effects in 6‐OHDA‐induced damage in relation with hydroalcoholic and acetate fraction. The presence of AKT and ERK1/2 pharmacological inhibitors blocked the protective effect of methanolic fraction suggesting the involvement of survival pathways in the neuroprotection by the plant. The plant did not prevent 6‐OHDA autoxidation or 6‐OHDA‐induced mitochondrial dysfunction. Thus, the neuroprotective effect of the methanolic fraction of A. microcarpum appears to be attributed in part to chelating properties of extract toward reactive species and is dependent on ERK1/2 and AKT phosphorylation. This study contributes to the understanding of biochemical mechanisms implied in neuroprotective effects of the vegetal species A. microcarpum.
Analysis of the Patient Information Quality and Readability on Esophagogastroduodenoscopy (EGD) on the Internet
Authors: Priyanka P. , Hadi Yousaf B. , Reynolds G. J.
Published: October 2018

Objective. Patients are increasingly using the Internet to inform themselves of health-related topics and procedures, including EGD. We analyzed the quality of information and readability of websites after a search on 3 different search engines. Methods. We used an assessment tool for website quality analysis that we developed in addition to using validated instruments for website quality, Global Quality Score (GQS) and Health on Net (HON) certification. The readability was assessed using Flesch-Kincaid Reading Ease (FRE) and Flesch-Kincaid Grade level (FKG). 30 results of each search terms ‘EGD’ and ‘Upper Endoscopy’ from Google and 15 each from Bing and Yahoo were analyzed. A total of 45 websites were included from 100 URLs after removing duplicates, video links, and journal articles. Results. Only 3 websites were found to have good quality and comprehensive and authentic information. These websites were https://www.healthline.com, https://www.uptodate.com, and https://www.emedicine.medscape.com. There were additional 13 sites with moderate quality of information. The mean Flesch-Kincaid Reading Ease (FRE) score was 46.92 (range 81.6-6.5). The mean Flesch-Kincaid Grade level (FKG) was 11th grade, with a range of 6th grade to 12th grade and above making them difficult to read. Conclusions. Our study shows that there are quite a few websites with moderate quality content. We recommend 3 comprehensive and authentic websites out of 45 URLs analyzed for information on Internet for EGD. In addition, the readability of the websites was consistently at a higher level than recommended by AMA at 11th grade level. In addition, we identified 3 websites with moderate quality content written at 8th grade and below readability level. We feel that gastroenterologists can help their patients better understand this procedure by directing them to these comprehensive websites.
Safety Analysis for Icing Aircraft during Landing Phase Based on Reachability Analysis
Authors: Zhou Chi , Li Yinghui , Zheng Wuji , Wu Pengwei , Dong Zehong
Published: October 2018

Icing is one of the leading causes of fatal aircraft accidents worldwide. Encountering icing conditions, dynamic characteristics of the aircraft will be damaged, thereby greatly affecting flight safety. Research on real-time estimations of the safety envelope under icing conditions is critical to improve flight safety. In order to determine the safety envelope, the reachability analysis based on the level set method is presented. The reachable set is obtained via computing the Hamilton-Jacobi partial differential equation (HJPDE), which is based on optimal control and is used in the landing phase of an aircraft. The results show that icing will shrink the safety envelope. Particularly under severe icing conditions, the stall speed of the aircraft will increase, and dynamic behavior will be more sensitive. A slight change of command by the pilot may contribute to the flight state moving outside the safety envelope. Furthermore, the effect of flap deflection was considered, which positively impacts the expanding safety envelope during the landing phase. Finally, a maneuvering coping strategy based on safety envelope is proposed. Examples are provided using the NASA’s generic transport model (GTM), and the results can be applied to flight safety risk assessment, providing theoretical guidance for the design of envelope protection systems.
Repeated Autologous Bone Marrow Transfusion through Portal Vein for Treating Decompensated Liver Cirrhosis after Splenectomy
Authors: Zhang Weiwei , Teng Mujian , Liu Baochi , Liu Qiling , Liu Xin , Si Yanhui , Li Lei
Published: October 2018

Objective. This study is aimed at examining the impact of repeated intraportal autologous bone marrow transfusion (ABMT) in patients with decompensated liver cirrhosis after splenectomy. Methods. A total of 25 patients with decompensated liver cirrhosis undergoing splenectomy were divided into ABMT and control groups. The portal vein was cannulated intraoperatively using Celsite Implantofix through the right gastroomental vein. Both groups were given a routine medical treatment. Then, 18 mL of autologous bone marrow was transfused through the port in the patients of the ABMT group 1 week, 1 month, and 3 months after laminectomy, while nothing was given to the control group. All patients were monitored for adverse events. Liver function tests, including serum albumin (ALB), alanine aminotransferase (ALT), total bilirubin (TB), prothrombin activity (PTA), cholinesterase (CHE), α-fetoprotein (AFP), and liver stiffness measurement (LSM), were conducted before surgery and 1, 3, and 6 months after surgery. Results. Significant improvements in ALB, ALT, and CHE levels and decreased LSM were observed in the ABMT group compared with those in the control group (P<0.05). TB and PTA improved in both groups but with no significant differences between the groups. No significant changes were observed in AFP in the control group, but it decreased in the ABMT group. No major adverse effects were noted during the follow-up period in the patients of either group. Conclusions. Repeated intraportal ABMT was clinically safe, and liver function of patients significantly improved. Therefore, this therapy has the potential to treat patients with decompensated liver cirrhosis after splenectomy. This trial was registered with the identification number of ChiCTR-ONC-17012592.
Evaluation of Accuracy of Episiotomy Incision in a Governmental Maternity Unit in Palestine: An Observational Study
Authors: Ali-Masri Hadil Y. , Hassan Sahar J. , Zimmo Kaled M. , Zimmo Mohammed W. , Ismail Khaled M. K. , Fosse Erik , Alsalman Hasan , Vikanes Åse , Laine Katariina
Published: October 2018

Episiotomy should be cut at certain internationally set criteria to minimize risk of obstetric anal sphincter injuries (OASIS) and anal incontinence. The aim of this study was to assess the accuracy of cutting right mediolateral episiotomy (RMLE). An institution-based prospective cohort study was undertaken in a Palestinian maternity unit from February 1, to December 31, 2016. Women having vaginal birth at gestational weeks ≥24 or birthweight ≥1000 g and with intended RMLE were eligible (n=240). Transparent plastic films were used to trace sutured episiotomy in relation to the midline within 24-hour postpartum. These were used to measure incisions’ distance from midline, and suture angles were used to classify the incisions into RMLE, lateral, and midline episiotomy groups. Clinical characteristics and association with OASIS were compared between episiotomy groups. A subanalysis by profession (midwife or trainee doctor) was done. Less than 30% were RMLE of which 59% had a suture angle of <40° (equivalent to an incision angle of <60°). There was a trend of higher OASIS rate, but not statistically significant, in the midline (16%, OR: 1.7, CI: 0.61–4.5) and unclassified groups (16.5%, OR: 1.8, CI: 0.8–4.3) than RMLE and lateral groups (10%). No significant differences were observed between episiotomies cut by doctors and midwives. Most of the assessed episiotomies lacked the agreed criteria for RMLE and had less than optimal incision angle which increases risk of severe complications. A well-structured training program on how to cut episiotomy is recommended.
Brief Report: Exercise and Blood Pressure in Older Adults—An Updated Look
Authors: Kelley George A. , Kelley Kristi S.
Published: October 2018

Background/Objectives. Raised blood pressure is a major problem in older adults. Using a random-effects model, a recent meta-analysis reported statistically significant reductions in both resting systolic blood pressure (SBP) and diastolic blood pressure (DBP) as a result of aerobic, resistance, and combined aerobic and resistance exercise in adults ≥65 years. To provide more objective information regarding this nonpharmacologic approach, this study applied more robust methods to this data. Design. Meta-analysis of 41 randomized controlled trials representing 96 groups (52 exercise; 44 control). Setting. Any location where a randomized controlled trial could be conducted. Participants. Adults ≥65 years. Intervention. Trials ≥2 weeks that included aerobic, resistance, and/or combined aerobic and resistance exercise as the intervention. Measurements. The recently developed inverse heterogeneity model (IVhet) was used to pool findings and the Doi plot was used to examine for small-study effects. Absolute and relative differences between the IVhet and random-effects model were also calculated. Data were reported using the mean difference (exercise minus control) with nonoverlapping 95% confidence intervals considered statistically significant. Results. Statistically significant reductions in resting blood pressure were found as a result of aerobic exercise (SBP, -4.7 mmHg, 95% CI, -7.7 to -1.8; DBP, -2.0 mmHg, 95% CI -3.13 to -0.9), SBP but not DBP for resistance training (SBP, -7.0 mmHg, 95% CI, -10.5 to -3.4; DBP, -1.2 mmHg, 95% CI -2.7 to 0.3), and both SBP and DBP for combined aerobic and resistance training (SBP, -5.5 mmHg, 95% CI, -8.3 to -2.7; DBP, -3.7 mmHg, 95% CI -4.8 to -2.7). Conclusions. Exclusive of changes in DBP congruent with resistance training, exercise (aerobic, resistance, and combined aerobic and resistance) reduces resting SBP and DBP in older adults. These findings have practical implications when considering exercise for the prevention and treatment of raised blood pressure in older adults.
Angiotensin II Attenuates the Bioactivities of Human Endothelial Progenitor Cells via Downregulation of β2-Adrenergic Receptor
Authors: Lee Seon Jin , Kim Da Yeon , Yun Jisoo , Choi Sung Hyun , Jung Seok Yun , Kang Songhwa , Park Ji Hye , Kim Yeon Ju , Ha Jong Seong , Ji Seung Taek , Jang Woong Bi , Lee Dong Hyung , Lee Dongjun , Kwon Sang-Mo
Published: October 2018

Cross talks between the renin-angiotensin system (RAS), sympathetic nervous system, and vascular homeostasis are tightly coordinated in hypertension. Angiotensin II (Ang II), a key factor in RAS, when abnormally activated, affects the number and bioactivity of circulating human endothelial progenitor cells (hEPCs) in hypertensive patients. In this study, we investigated how the augmentation of Ang II regulates adrenergic receptor-mediated signaling and angiogenic bioactivities of hEPCs. Interestingly, the short-term treatment of hEPCs with Ang II drastically attenuated the expression of beta-2 adrenergic receptor (ADRB2), but did not alter the expression of beta-1 adrenergic receptor (ADRB1) and Ang II type 1 receptor (AT1R). EPC functional assay clearly demonstrated that the treatment with ADRB2 agonists significantly increased EPC bioactivities including cell proliferation, migration, and tube formation abilities. However, EPC bioactivities were decreased dramatically when treated with Ang II. Importantly, the attenuation of EPC bioactivities by Ang II was restored by treatment with an AT1R antagonist (telmisartan; TERT). We found that AT1R binds to ADRB2 in physiological conditions, but this binding is significantly decreased in the presence of Ang II. Furthermore, TERT, an Ang II-AT1R interaction blocker, restored the interaction between AT1R and ADRB2, suggesting that Ang II might induce the dysfunction of EPCs via downregulation of ADRB2, and an AT1R blocker could prevent Ang II-mediated ADRB2 depletion in EPCs. Taken together, our report provides novel insights into potential therapeutic approaches for hypertension-related cardiovascular diseases.
One-Pot Synthesis of Ru-Doped ZnO Oxides for Photodegradation of 4-Chlorophenol
Authors: Manríquez Maria E. , Noreña Luis Enrique , Wang Jin An , Chen Lifang , Salmones Jose , González-García Julio , Reza Carmen , Tzompantzi Francisco , Hernández Cortez José G. , Ye Liqun , Xie Haiquan
Published: October 2018

The photocatalytic degradation of 4-chlorophenol in water using Ru-doped ZnO mixed oxides (0, 0.5, 1, and 3 wt% RuO2) synthesized by the one-pot homogeneous coprecipitation method is reported. ZnO with wurtzite structure was present in the mixed oxide as corroborated by Raman spectroscopy and X-ray diffraction analysis. All the samples showed nanorod morphological features. The presence of Ru6+/Ru4+ couples on ZnO modified the band gap of the mixed oxides and led to a shift of the band gap energy from 3.20 eV to 3.07 eV. Ru addition increased the surface area and significantly promoted the formation of active surface oxygen species such as hydroradicals evidenced by the fluorescence spectroscopy measurement. In the photodegradation of 4-chlorophenol solution under UV irradiation, a notable increase in photoactivity was obtained as the amount of RuO2 in the mixed oxides increased to 3 wt%. The charge transfer between Ru6+/Ru4+ couples and ZnO nanoparticles together with the formation of free radical oxidant species effectively inhibits electron-hole recombination rate, thus favoring the photodegradation of 4-chlorophenol.
Numerical Study of Flame Propagation Morphology for Deflagration in the Pipeline Using Proper Orthogonal Decomposition
Authors: Wu Weimin , Yao Jianyao , Liu Jingcheng , Wu Zejun , Liu Jiawen
Published: October 2018

A multilevel independent spatial modal analysis of flame propagation characteristics of a deflagration in a specific pipeline was performed using the proper orthogonal decomposition (POD) method, in order to research the evolution process of the explosion which is closely related to flame propagation speed and front rupture pressure. The CFD results indicated that the full‐order calculation results well agreed with the normal combustion propagation characteristics of premixed methane‐air for the flame propagation with the unbroken thin layer. The POD analysis results showed that the static temperature gradient of the 1st order mode of initial and subsequent stages both exhibited a range of continuity change from left to right, and the frontal curvature of the cooling area decreased as the flame propagated in all stages. The number of the low‐temperature interval regions displayed an expanding form of a staircase with the increase of the mode order, especially for subsequent flame in which the interval areas became more and more slender. Moreover, the level of information content in the multilevel modal space was mostly concentrated in the first 3 modes, especially in the 1st order mode, and the flame propagation pattern at the initial stage was more complicated than the subsequent based on the relational information content features.
Hip Mobilization at Preterm Age May Accelerate Developmental Dysplasia Recovery
Authors: Voos Mariana Callil , Maria Clara Drummond Soares de Moura , Hasue Renata Hydee
Published: October 2018

Purpose. Few studies have described mobilization approaches in developmental dysplasia of the hip (DDH). The present study describes the hip mobilization of a preterm infant (born at 33 6/7 weeks of gestational age) diagnosed with DDH. Design and Methods. During the 43-day hospital stay, the infant was seen twice a week (ten sessions, 20 minutes each). All sessions included hip approximation maneuvers, with the hip positioned in abduction, lateral rotation and flexion, and lower limbs passive mobilization, which were taught to the mother. Early intervention with auditory, tactile, visual, and vestibular stimulations was also performed. The infant was assessed with hip ultrasound before and after treatment. Results. At 34 2/7 weeks of gestational age, she was classified as Graf IIa (left: alpha: 55°, beta: 68°; right: alpha: 59°, beta: 64°). At 40 5/7 weeks, she was classified as Graf I for left (alpha: 67°; beta: 42°) and right (alpha: 66°; beta: 42°) hips. Practical Implications. The intervention seemed to accelerate the acquisition of stability of dysplasic hips in a preterm infant. The outcome supports further investigation of hip approximation maneuvers as part of early stimulation in preterm infants with DDH during hospital stay.
The Microbiomes of Pancreatic and Duodenum Tissue Overlap and Are Highly Subject Specific but Differ between Pancreatic Cancer and Noncancer Subjects
Authors: del Castillo Erika , Meier Richard , Chung Mei , Koestler Devin C. , Chen Tsute , Paster Bruce J. , Charpentier Kevin P. , Kelsey Karl T. , Izard Jacques , Michaud Dominique S.
Published: October 2018

Background:

In mice, bacteria from the mouth can translocate to the pancreas and impact pancreatic cancer progression. In humans, oral bacteria associated with periodontal disease have been linked to pancreatic cancer risk. It is not known if DNA bacterial profiles in the pancreas and duodenum are similar within individuals.

Methods:

Tissue samples were obtained from 50 subjects with pancreatic cancer or other conditions requiring foregut surgery at the Rhode Island Hospital (RIH), and from 34 organs obtained from the National Disease Research Interchange. 16S rRNA gene sequencing was performed on 189 tissue samples (pancreatic duct, duodenum, pancreas), 57 swabs (bile duct, jejunum, stomach), and 12 stool samples.

Results:

Pancreatic tissue samples from both sources (RIH and National Disease Research Interchange) had diverse bacterial DNA, including taxa typically identified in the oral cavity. Bacterial DNA across different sites in the pancreas and duodenum were highly subject specific in both cancer and noncancer subjects. Presence of genus Lactobacillus was significantly higher in noncancer subjects compared with cancer subjects and the relative abundance of Fusobacterium spp., previously associated with colorectal cancer, was higher in cancer subjects compared with noncancer subjects.

Conclusions:

Bacterial DNA profiles in the pancreas were similar to those in the duodenum tissue of the same subjects, regardless of disease state, suggesting that bacteria may be migrating from the gut into the pancreas. Whether bacteria play a causal role in human pancreatic cancer needs to be further examined.

Impact:

Identifying bacterial taxa that differ in cancer patients can provide new leads on etiologically relevant bacteria.
Ibrutinib Therapy Releases Leukemic Surface IgM from Antigen Drive in Chronic Lymphocytic Leukemia Patients
Authors: Drennan Samantha , Chiodin Giorgia , D'Avola Annalisa , Tracy Ian , Johnson Peter W. , Trentin Livio , Steele Andrew J. , Packham Graham , Stevenson Freda K. , Forconi Francesco
Published: October 2018

Purpose:

In chronic lymphocytic leukemia (CLL), disease progression associates with surface IgM (sIgM) levels and signaling capacity. These are variably downmodulated in vivo and recover in vitro, suggesting a reversible influence of tissue-located antigen. Therapeutic targeting of sIgM function via ibrutinib, an inhibitor of Bruton tyrosine kinase (BTK), causes inhibition and tumor cell redistribution into the blood, with significant clinical benefit. Circulating CLL cells persist in an inhibited state, offering a tool to investigate the effects of drug on BTK-inhibited sIgM.

Experimental Design:

We investigated the consequences of ibrutinib therapy on levels and function of sIgM in circulating leukemic cells of patients with CLL.

Results:

At week 1, there was a significant increase of sIgM expression (64% increase from pretherapy) on CLL cells either recently released from tissue or persisting in blood. In contrast, surface IgD (sIgD) and a range of other receptors did not change. SIgM levels remained higher than pretherapy in the following 3 months despite gradual cell size reduction and ongoing autophagy and apoptotic activity. Conversely, IgD and other receptors did not increase and gradually declined. Recovered sIgM was fully N-glycosylated, another feature of escape from antigen, and expression did not increase further during culture in vitro. The sIgM was fully capable of mediating phosphorylation of SYK, which lies upstream of BTK in the B-cell receptor pathway.

Conclusions:

This specific IgM increase in patients underpins the key role of tissue-based engagement with antigen in CLL, confirms the inhibitory action of ibrutinib, and reveals dynamic adaptability of CLL cells to precision monotherapy.

See related commentary by Burger, p. 2372
Prospective Genotyping of Hepatocellular Carcinoma: Clinical Implications of Next-Generation Sequencing for Matching Patients to Targeted and Immune Therapies
Authors: Harding James J. , Nandakumar Subhiksha , Armenia Joshua , Khalil Danny N. , Albano Melanie , Ly Michele , Shia Jinru , Hechtman Jaclyn F. , Kundra Ritika , El Dika Imane , Do Richard K. , Sun Yichao , Kingham T. Peter , D'Angelica Michael I. , Berger Michael F. , Hyman David M. , Jarnagin William , Klimstra David S. , Janjigian Yelena Y. , Solit David B. , Schultz Nikolaus , Abou-Alfa Ghassan K.
Published: October 2018

Purpose:

Prior molecular profiling of hepatocellular carcinoma (HCC) has identified actionable findings that may have a role in guiding therapeutic decision-making and clinical trial enrollment. We implemented prospective next-generation sequencing (NGS) in the clinic to determine whether such analyses provide predictive and/or prognostic information for HCC patients treated with contemporary systemic therapies.

Experimental Design:

Matched tumor/normal DNA from patients with HCC (N = 127) were analyzed using a hybridization capture–based NGS assay designed to target 341 or more cancer-associated genes. Demographic and treatment data were prospectively collected with the goal of correlating treatment outcomes and drug response with molecular profiles.

Results:

WNT/β-catenin pathway (45%) and TP53 (33%) alterations were frequent and represented mutually exclusive molecular subsets. In sorafenib-treated patients (n = 81), oncogenic PI3K–mTOR pathway alterations were associated with lower disease control rates (DCR, 8.3% vs. 40.2%), shorter median progression-free survival (PFS; 1.9 vs. 5.3 months), and shorter median overall survival (OS; 10.4 vs. 17.9 months). For patients treated with immune checkpoint inhibitors (n = 31), activating alteration WNT/β-catenin signaling were associated with lower DCR (0% vs. 53%), shorter median PFS (2.0 vs. 7.4 months), and shorter median OS (9.1 vs. 15.2 months). Twenty-four percent of patients harbored potentially actionable alterations including TSC1/2 (8.5%) inactivating/truncating mutations, FGF19 (6.3%) and MET (1.5%) amplifications, and IDH1 missense mutations (<1%). Six percent of patients treated with systemic therapy were matched to targeted therapeutics.

Conclusions:

Linking NGS to routine clinical care has the potential to identify those patients with HCC likely to benefit from standard systemic therapies and can be used in an investigational context to match patients to genome-directed targeted therapies.

See related commentary by Pinyol et al., p. 2021
TRAF2 Cooperates with Focal Adhesion Signaling to Regulate Cancer Cell Susceptibility to Anoikis
Authors: da Silva Sabrina Daniela , Xu Bin , Maschietto Mariana , Marchi Fabio Albuquerque , Alkailani Maisa I. , Bijian Krikor , Xiao Dingzhang , Alaoui-Jamali Moulay A.
Published: October 2018

TRAF2, a RING finger adaptor protein, plays an important function in tumor necrosis factor (TNF)- and TNF-like weak inducer of apoptosis (TWEAK)-dependent signaling, in particular during inflammatory and immune responses. We identified a functional interaction of TRAF2 with focal adhesion (FA) signaling involving the focal adhesion kinase (FAK) in the regulation of cell susceptibility to anoikis. Comparison of TRAF2-proficient (TRAF2+/+) versus TRAF2-deficient (TRAF2−/−), and FAK-proficient (FAK+/+) versus FAK-deficient (FAK−/−) mouse embryonic fibroblasts and their matched reconstituted cells demonstrated that TRAF2 interacts physically with the N-terminal portion of FAK and colocalizes to cell membrane protrusions. This interaction was found to be critical for promoting resistance to cell anoikis. Similar results were confirmed in the human breast cancer cell line MDA-MB-231, where TRAF2 and FAK downregulation promoted cell susceptibility to anoikis. In human breast cancer tissues, genomic analysis of The Cancer Genome Atlas database revealed coamplification of TRAF2 and FAK in breast cancer tissues with a predictive value for shorter survival, further supporting a potential role of TRAF2–FAK cooperative signaling in cancer progression.
Octadecyloxyethyl Adefovir Exhibits Potent in vitro and in vivo Cytotoxic Activity and Has Synergistic Effects with Ara-C in Acute Myeloid Leukemia
Authors: Khoury Haytham , He Ruijuan , Schimmer Aaron , Beadle James R. , Hostetler Karl Y. , Minden Mark D.
Published: October 2018

Acute myeloid leukemia (AML) continues to be a deadly disease, with only 50–70% of patients achieving complete remission and less than 30% of adults having sustained long-term remissions. In order to address these unmet medical needs, we carried out a high-throughput screen of an in-house library of on- and off-patent drugs with the OCI/AML-2 cell line. Through this screen, we discovered adefovir dipi­voxil (adefovir-DP) as being active against human AML. In addition to adefovir-DP, there are second-generation formulations of adefovir, including octadecyloxyethyl adefovir (ODE-adefovir) and hexadecyloxypropyl adefovir (HDP-adefovir), which were designed to overcome the pharmacokinetic problems of the parent compound adefovir. Given the known clinical benefit of nucleoside analogs for the treatment of AML, we undertook studies to evaluate the potential benefit of adefovir-based molecules. In AML cell lines and patient samples, adefovir-DP and ODE-adefovir were highly potent, whereas HDP-adefovir was significantly less active. Interestingly, ODE-adefovir was remarkably less toxic than adefovir-DP towards normal hematopoietic cells. In addition, ODE-adefovir at a dose of 15 mg/kg/day showed potent activity against human AML in a NOD/SCID mouse model, with a reduction of human leukemia in mouse bone marrow of > 40% in all mice tested within 20 days of treatment. Based on its chemical structure, we hypothesized that the cytotoxicity of ODE-adefovir toward AML was through cell cycle arrest and DNA damage. Indeed, ODE-adefovir treatment induced cell cycle arrest in the S phase and increased levels of pH2Ax, indicating the induction of DNA damage. Furthermore, there was an increase in phospho-p53, transactivation of proapoptotic genes and activation of the intrinsic apoptotic pathway. Subsequent investigation unveiled strong synergism between ODE-adefovir and ara-C, making their coadministration of potential clinical benefit. Expression of MRP4, a nucleoside transporter, appeared to influence the response of AML cells to ODE-adefovir, as its inhibition potentiated ODE-adefovir killing. Taken together, our findings indicate that clinical development of ODE-adefovir or related compounds for the treatment of AML is warranted.