bluuebunny/crossref_metadata_2025 huggingface dataset:
Effectiveness of Simulated Horseback Riding for Patients With Chronic Low Back Pain: A Randomized Controlled Trial
Authors: Kim TaeYeong , Lee JaeHyuk , Oh SeJun , Kim Seungmin , Yoon BumChul
Published: January 2019

Context: A simulated horseback riding (SHR) exercise is effective for improvement of pain and functional disability, but its comparative effectiveness with the other is unknown. Objective: The authors aimed to demonstrate the effect of a SHR exercise in people with chronic low back pain. Design: A randomized controlled trial. Settings: Community and university campus. Participants: A total of 48 participants with chronic low back pain were divided into 2 groups, and SHR exercises (n = 24) or stabilization (STB) exercises (n = 24) were performed. Interventions: The exercises were performed for 30 minutes, 2 days per week for 8 weeks. Main Outcome Measures: Numeric rating scale, functional disabilities (Oswestry disability index and Roland–Morris disability), and fear-avoidance beliefs questionnaire (FABQ) scores were measured at baseline and at 4 weeks, 8 weeks, and 6 months. Results: A 2-way repeated analysis of variance identified that between-group comparisons showed significant differences in the FABQ related to work scale (F = 21.422; P = .01). There were no significant differences in the numeric rating scale (F = 1.696; P = .21), Oswestry disability index (F = 1.848; P = .20), Roland–Morris disability (F = 0.069; P = .80), and FABQ related to physical scale (F = 1.579; P = .24). In within-group comparisons, both groups presented significant differences in numeric rating scale (both SHR and STB after 4 wk), Oswestry disability index (both SHR and STB after 6 mo), and Roland–Morris disability (SHR after 6 mo and STB after 8 wk) compared with baseline values. In FABQ-related physical (SHR after 4 wk) and work scales (SHR after 6 mo), there were only significant differences in the SHR compared with baseline values. Conclusions: SHR exercise for 8 weeks had a greater effect than STB exercise for reducing work-related FABQ. The SHR exercise performed in a seated position could substantially decrease pain-related fear disability in young adults with chronic low back pain.
Cold Water Immersion as a Strategy for Muscle Recovery in Professional Basketball Players During the Competitive Season
Authors: Seco-Calvo Jesús , Mielgo-Ayuso Juan , Calvo-Lobo César , Córdova Alfredo
Published: January 2019

Context:Despite prior studies that have addressed the recovery effects of cold-water immersion (CWI) in different sports, there is a lack of knowledge about longitudinal studies across a full season of competition assessing these effects.Objective:To analyze the CWI effects, as a muscle recovery strategy, in professional basketball players throughout a competitive season.Design:A prospective cohort design.Setting:Elite basketball teams.Participants:A total of 28 professional male basketball players divided into 2 groups: CWI (n = 12) and control (n = 16) groups.Main Outcome Measures:Muscle metabolism serum markers were measured during the season in September—T1, November—T2, March—T3, and April—T4. Isokinetic peak torque strength and ratings of perceived exertion were measured at the beginning and at the end of the season. CWI was applied immediately after every match and after every training session before matches.Results:All serum muscular markers, except myoglobin, were higher in the CWI group than the control group (P < .05). The time course of changes in muscle markers over the season also differed between the groups (P < .05). In the CWI group, ratings of perceived exertion decreased significantly from the beginning (T1–T2) to the end (T3–T4). Isokinetic torque differed between groups at the end of the season (60°/s peak torque:P < .001 and; and 180°/s peak torque:P < .001 and) and had changed significantly over the season in the CWI group (P < .05).Conclusions:CWI may improve recovery from muscle damage in professional basketball players during a regular season.
The Effect of Total Body Resistance Exercise on Mobility, Proprioception, and Muscle Strength of the Knee in People With Multiple Sclerosis
Authors: Moghadasi Afshin , Ghasemi Gholamali , Sadeghi-Demneh Ebrahim , Etemadifar Masoud
Published: January 2019

Context: Muscle weakness and sensory deficits cause impaired balance and walking abilities that are prerequisites for independent activity of daily living in people with multiple sclerosis (MS). Recent physical exercises tailored to improve the activity of daily living people with MS have focused on the functional training. Objective: To investigate the effect of total body resistance exercise suspension training on mobility, proprioception, and muscle strength of the knee in people with MS. Design: Single-blind pretest and posttest control group design. Setting: Referral Center of Multiple Sclerosis Society. Participants: Thirty-four women with relapsing–remitting MS were participated in this study. The mean (SD) of their age was 36.44 (4.88) years, and the Expanded Disability Status Scale was 2.35 (0.94). The participants were divided into 2 groups: control group (n = 15) and training group (n = 19). Intervention: The training group performed the total body resistance exercise program for 8 weeks, 3 sessions per week. The control group received their usual care and daily activities. Outcomes were measured presessions and postsessions. Main Outcome Measures: Mobility was assessed with Timed Up and Go test, 10-m walk maximum test, 2 minute walk test, and 5-time sit-to-stand test. Knee proprioception absolute error and isometric strength of knee flexor and extensor muscles were measured by using a biodex isokinetic dynamometer. Results: In the training group, mobility (P = .001), maximal voluntary isometric contraction of knee flexor and extensor muscles in both legs (P > .05), and the knee proprioception absolute error in nondominant leg at 60° knee flexion (P = .02) improved significantly compared with the control group. Conclusion: Total body resistance exercise is a functional and safe intervention that can improve the mobility and muscles strength of the knee in a short period in people with MS.
Late Cretaceous subduction-related magmatism on the southern edge of Sabzevar basin, NE Iran
Authors: Kazemi Zakie , Ghasemi Habibollah , Tilhac Romain , Griffin William , Moghadam Hadi Shafaii , O'Reilly Suzanne , Mousivand Fardin
Published: January 2019

Despite detailed geological studies on the Late Cretaceous Sabzevar ophiolites, the non-ophiolitic, subduction-related igneous rocks of NE Iran are still enigmatic. This paper focuses on the Late Cretaceous, non-ophiolitic Sabzevar magmatic rocks, and presents both precise U–Pb ages and a tectonomagmatic scenario for the genesis of these igneous rocks. A thick sequence of Late Cretaceous acidic volcanic rocks associated with sandstones, shales and pelagic limestones dominates the northern parts of the Lut block. This sequence is intruded by a series of shallow mafic to felsic intrusions. New zircon U–Pb results on the intrusive and extrusive rocks show ages of 75–101 Ma. These ages show a pulsed magmatism in NE Iran, which lasted for
c.
25 myr. The whole-rock geochemistry of the igneous rocks shows suprasubduction-zone-related geochemical signatures, represented by negative anomalies in high field strength elements and enrichment in large ion lithophile elements. The initial
87
Sr/
86
Sr ratios and εNd(
t
) values of the extrusive rocks range from 0.70411 to 0.70628 and from +5.9 to +7.4 respectively, and for intrusive rocks are in the range of 0.70423–0.70579 and +5.8 to +7.2. High εNd(
t
) values for these rocks confirm that their melts were derived from a depleted-mantle source. Both geochemical and isotopic data indicate that the genesis of these rocks was related to the partial melting of mid-ocean ridge basalt-type slab or depleted-mantle wedge sources during the northward movement of the Sabzevar oceanic slab beneath the southern edge of Eurasia (Turan block) in Late Cretaceous time.
Evaluation of shark tooth diagenesis-screening methods and the application of their stable oxygen isotope data for palaeoenvironmental reconstructions
Authors: Hättig K. , Stevens K. , Thies D. , Schweigert G. , Mutterlose J.
Published: January 2019

The δ
18
O
(PO4)
of shark teeth can be used as a geochemical proxy for the palaeoenvironment during tooth mineralization. A well-preserved state of the teeth is necessary for this approach. We used polarization, cathodoluminescence (CL) and scanning electron microscopy to investigate two fossil shark teeth (
Sphenodus nitidus
) from the Late Jurassic Nusplingen Plattenkalk. The data are compared with those for two recent shark teeth (
Hemipristis elongata
,
Lamiopsis temminckii
). δ
18
O
(PO4)
of six further Jurassic shark teeth was measured and is compared with δ
18
O data from co-occurring belemnite rostra and carbonate sediments. The enameloid of both the fossil and the recent shark teeth shows orange–red CL, which is due to incorporation of Mn during biomineralization. The δ
18
O
(PO4)
values of the fossil enameloid are constant around 21.50‰ V-SMOW whereas those of the fossil dentine are more negative with values around 20‰ V-SMOW, which indicates that the enameloid is well preserved. Palaeotemperatures calculated from the enameloid are like those derived from belemnites. We demonstrate that CL microscopy should only be used cautiously as a diagenesis-screening method for fossil biophosphates. Geochemical and microstructural analyses of tissue types with different susceptibility to diagenetic alteration on the other hand provide an effective way to identify well-preserved tissues.

Supplementary material:
Polarization microscopy images, energy-dispersive X-ray data and cathodoluminescence spectra are available at
https://doi.org/10.6084/m9.figshare.c.4373720
A resistivity-based approach to determining the rates of groundwater seepage into buffer materials
Authors: Ishii T. , Kawakubo M. , Asano H. , Kobayashi I. , Sellin P. , Luterkort D. , Eriksson P.
Published: January 2019

Bentonite-based buffer materials play an important safety role in engineered barriers planned for use in geological disposal repositories for radioactive high-level waste (HLW) in Japan. The effectiveness of buffer materials is dependent on the status of groundwater saturation during resaturation of the repository. Accordingly, it is important to determine the behaviour of buffer materials during saturation and predict post-saturation conditions such as the distribution of residual dry density and chemical alteration.

In this study, the rate of groundwater uptake into a buffer material was determined to clarify the behaviour of the material during the saturation process. As mechanical changes and chemical alteration of buffer materials are generated by groundwater permeation, knowledge of the water uptake rate is necessary for the prediction of post-permeation conditions. In the experiment reported here, one-dimensional permeation by distilled water and a NaCl water solution at a constant rate was monitored over a period of more than seven years. The results indicated that the seepage and saturation front moved in proportion to the square root of the seepage time. The coefficient of the relationships between the seepage and the saturation fronts with time of the reference bentonite used in Japan was determined.
Site screening of clay formations in NW China as host rocks for a high-level radioactive waste disposal repository
Authors: Liu Xiaodong , Liu Pinghui , Dai Chaocheng , Liu Shuai , Deng Juzhi , Zhang Weimin , Yu Zheng
Published: January 2019

Deep geological disposal of high-level radioactive waste (HLW) in a repository with a system of engineered and natural barriers has been recognized as an appropriate disposal concept by Chinese authorities since 2003, and both crystalline rocks and argillaceous rocks are considered as the candidate host rocks for HLW disposal repository. The 1:200 000 regional survey indicated that there are potential clay formations in Mesozoic–Cenozoic sedimentary basins in NW China. Five candidate areas have been suggested with potential clay formations including the Tamusu and Suhongtu areas with upper K
1
Bayingebi clay formations in the east Bayingebi Basin, in the Inner Mongolia Autonomous Region. On the basis of a detailed ground geological, hydrological and geophysical surveys, two test boreholes drilled to a depth of 800 m in the Tamusu area revealed that there are three lacustrine-facies clay formations (K
1
b
2-3
, K
1
b
2-2
and K
1
b
2-1
). The thickness of the K
1
b
2-3
and K
1
b
2-2
clay formations is about 300–600 m with sandstone and siltstone interbeds, while the thickness of the K
1
b
2-1
homogeneous clay formation is more than 200 m with the depth of 450 m below the surface. The spatial extension of the clay formations could meet the fundamental criteria to ensure the long-term safety of the repository. Initial mineralogical studies on core samples indicated that the mineral assemblage is dominated by analcite, kaolinite, illite and dolomite. The homogeneous argillaceous rocks rich in analcite in Tamusu area could be a new type of host rock for a HLW disposal repository.
Topographical plots of esophageal distension and contraction: effects of posture on esophageal peristalsis and bolus transport
Authors: Zifan Ali , Song Hyun Joo , Youn Young-Hoon , Qiu Xinhuan , Ledgerwood-Lee Melissa , Mittal Ravinder K.
Published: January 2019

Each swallow induces a wave of inhibition followed by contraction in the esophagus. Unlike contraction, which can easily be measured in humans using high-resolution manometry (HRM), inhibition is difficult to measure. Luminal distension is a surrogate of the esophageal inhibition. The aim of this study was to determine the effect of posture on the temporal and quantitative relationship between distension and contraction along the entire length of the esophagus in normal healthy subjects by using concurrent HRM, HRM impedance (HRMZ), and intraluminal ultrasound (US). Studies were conducted in 15 normal healthy subjects in the supine and Trendelenburg positions. Both manual and automated methods were used to extract quantitative pressure and impedance-derived features from the HRMZ recordings. Topographical plots of distension and contraction were visualized along the entire length of the esophagus. Distension was also measured from the US images during 10-ml swallows at 5 cm above the lower esophageal sphincter. Each swallow was associated with luminal distension followed by contraction, both of which traversed the esophagus in a sequential/peristaltic fashion. Luminal distension (US) and esophageal contraction amplitude were greater in the Trendelenburg compared with the supine position. Length of esophageal breaks (in the transition zone) were reduced in the Trendelenburg position. Change in posture altered the temporal relationship between distension and contraction, and bolus traveled closer to the esophageal contraction in the Trendelenburg position. Topographical contraction-distension plots derived from HRMZ recordings is a novel way to visualize esophageal peristalsis. Future studies should investigate if abnormalities of esophageal distension are the cause of functional dysphagia.

NEW & NOTEWORTHY Ascending contraction and descending inhibition are two important components of peristalsis. High-resolution manometry only measures the contraction phase of peristalsis. We measured esophageal distension from intraluminal impedance recordings and developed novel contraction-distension topographical plots to prove that similar to contraction, distension also travels in a peristaltic fashion. Change in posture from the supine to the Trendelenburg position also increased the amplitude of esophageal distension and contraction and altered the temporal relationship between distension and contraction.
Accumulation of intramyocyte TRPV1-mediated calcium during heat stress is inhibited by concomitant muscle contractions
Authors: Ikegami Ryo , Eshima Hiroaki , Mashio Takuro , Ishiguro Tomosada , Hoshino Daisuke , Poole David C. , Kano Yutaka
Published: January 2019

Heat stress promotes intramyocyte calcium concentration ([Ca2+]i) accumulation via transient receptor potential vanilloid 1 (TRPV1) channels. We tested the hypothesis that muscle contractile activity concomitant with heat stress would accelerate the increase in [Ca2+]ivia TRPV1, further impairing [Ca2+]ihomeostasis. Spinotrapezius muscles of adult Wistar rats were exteriorized in vivo and loaded with the fluorescent Ca2+probe fura 2-AM. Heat stress (muscle surface temperature 40°C) was used as TRPV1 activator. An isometric contraction (100 Hz, 5–10 V, 30 s) was induced electrically concomitant with heat stress. [Ca2+]iwas determined for 20 min using in vivo fluorescence microscopy, and the phosphorylation response of TRPV1 was determined by Western blotting. Heat stress induced a significant [Ca2+]iincrease of 18.5 ± 8.1% at 20 min and TRPV1 phosphorylation (+231%), which was inhibited by addition of the TRPV1 inhibitor (capsazepine). However, contrary to expectations, the heat stress and isometric contraction condition almost completely inhibited TRPV1 phosphorylation and the consequent [Ca2+]ielevation (<2.8% accumulation during heat stress, P > 0.05). In conclusion, this in vivo physiological model demonstrated that isometric muscle contraction(s) can suppress the phosphorylation response of TRPV1 and maintain [Ca2+]ihomeostasis during heat stress.

NEW & NOTEWORTHY This investigation is the first document the dynamics of intramyocyte calcium concentration ([Ca2+]i) increase in the myoplasm of skeletal muscle fibers in response to heat stress where the muscle blood flow is preserved. Heat stress at 40°C drives a myoplasmic [Ca2+]iaccumulation in concert with transient receptor potential vanilloid 1 (TRPV1) phosphorylation. However, muscle contraction caused TRPV1 channel deactivation by dephosphorylation of TRPV1. TRPV1 inactivation via isometric contraction(s) permits maintenance of [Ca2+]ihomeostasis even under high imposed muscle temperature.
Tensiomyography detects early hallmarks of bed-rest-induced atrophy before changes in muscle architecture
Authors: Šimunič Boštjan , Koren Katja , Rittweger Jörn , Lazzer Stefano , Reggiani Carlo , Rejc Enrico , Pišot Rado , Narici Marco , Degens Hans
Published: January 2019

In young and older people, skeletal muscle mass is reduced after as little as 7 days of disuse. The declines in muscle mass after such short periods are of high clinical relevance, particularly in older people who show a higher atrophy rate and a slower or even a complete lack of muscle mass recovery after disuse. Ten men (24.3 yr; SD 2.6) underwent 35 days of 6° head-down tilt bed rest, followed by 30 days of recovery. During bed rest, a neutral energy balance was maintained, with three weekly passive physiotherapy sessions to minimize muscle soreness and joint stiffness. All measurements were performed in a hospital at days 1–10, 16, 28, and 35 of bed rest (BR1–BR10, BR16, BR28, and BR35, respectively) and days 1, 3, and 30 after reambulation (R + 1, R + 3, and R + 30, respectively). Vastus medialis obliquus (VMO), vastus medialis longus (VML), and biceps femoris (BF) thickness (d) and pennation angle (Θ) were assessed by ultrasonography, whereas twitch muscle belly displacement (Dm) and contraction time (Tc) were assessed with tensiomyography (TMG). After bed rest, d and Θ decreased by 13–17% in all muscles ( P < 0.001) and had recovered at R + 30. Dm was increased by 42.3–84.4% ( P < 0.001) at BR35 and preceded the decrease in d by 7, 5, and 3 days in VMO, VML, and BF, respectively. Tc increased only in BF (32.1%; P < 0.001) and was not recovered at R + 30. TMG can detect early bed-rest-induced changes in muscle with higher sensitivity before overt architectural changes, and atrophy can be detected.

NEW & NOTEWORTHY Detection of early atrophic processes and irreversible adaptation to disuse are of high clinical relevance. With the use of tensiomyography (TMG), we detected early atrophic processes before overt architectural changes, and atrophy can be detected using imaging technique. Furthermore, TMG detected irreversible changes of biceps femoris contraction time.
Quadriceps miR-542-3p and -5p are elevated in COPD and reduce function by inhibiting ribosomal and protein synthesis
Authors: Farre-Garros Roser , Lee Jen Y. , Natanek S. Amanda , Connolly Martin , Sayer Avan A. , Patel Harnish , Cooper Cyrus , Polkey Michael I. , Kemp Paul R.
Published: January 2019

Reduced physical performance reduces quality of life in patients with chronic obstructive pulmonary disease (COPD). Impaired physical performance is, in part, a consequence of reduced muscle mass and function, which is accompanied by mitochondrial dysfunction. We recently showed that miR-542-3p and miR-542-5p were elevated in a small cohort of COPD patients and more markedly in critical care patients. In mice, these microRNAs (miRNAs) promoted mitochondrial dysfunction suggesting that they would affect physical performance in patients with COPD, but we did not explore the association of these miRNAs with disease severity or physical performance further. We therefore quantified miR-542-3p/5p and mitochondrial rRNA expression in RNA extracted from quadriceps muscle of patients with COPD and determined their association with physical performance. As miR-542-3p inhibits ribosomal protein synthesis its ability to inhibit protein synthesis was also determined in vitro. Both miR-542-3p expression and -5p expression were elevated in patients with COPD (5-fold P < 0.001) and the degree of elevation associated with impaired lung function (transfer capacity of the lung for CO in % and forced expiratory volume in 1 s in %) and physical performance (6-min walk distance in %). In COPD patients, the ratio of 12S rRNA to 16S rRNA was suppressed suggesting mitochondrial ribosomal stress and mitochondrial dysfunction and miR-542-3p/5p expression was inversely associated with mitochondrial gene expression and positively associated with p53 activity. miR-542-3p suppressed RPS23 expression and maximal protein synthesis in vitro. Our data show that miR-542-3p and -5p expression is elevated in COPD patients and may suppress physical performance at least in part by inhibiting mitochondrial and cytoplasmic ribosome synthesis and suppressing protein synthesis.

NEW & NOTEWORTHY miR-542-3p and -5p are elevated in the quadriceps muscle of patients with chronic obstructive pulmonary disease (COPD) in proportion to the severity of their lung disease. These microRNAs inhibit mitochondrial and cytoplasmic protein synthesis suggesting that they contribute to impaired exercise performance in COPD.
Patient-specific targeted bronchial thermoplasty: predictions of improved outcomes with structure-guided treatment
Authors: Donovan Graham M. , Elliot John G. , Boser Stacey R , Green Francis H. Y. , James Alan L. , Noble Peter B.
Published: January 2019

Bronchial thermoplasty is a recent treatment for asthma in which ablative thermal energy is delivered to specific large airways according to clinical guidelines. Therefore, current practice is effectively “blind,” as it is not informed by patient-specific data. The present study seeks to establish whether a patient-specific approach based on structural or functional patient data can improve outcomes and/or reduce the number of procedures required for clinical efficacy. We employed a combination of extensive human lung specimens and novel computational methods to predict bronchial thermoplasty outcomes guided by structural or functional data compared with current clinical practice. Response to bronchial thermoplasty was determined from changes in airway responses to strong bronchoconstrictor simulations and flow heterogeneity after one or three simulated thermoplasty procedures. Structure-guided treatment showed significant improvement over current unguided clinical practice, with a single session of structure-guided treatment producing improvements comparable with three sessions of unguided treatment. In comparison, function-guided treatment did not produce a significant improvement over current practice. Structure-guided targeting of bronchial thermoplasty is a promising avenue for improving therapy and reinforces the need for advanced imaging technologies. The functional imaging-guided approach is predicted to be less effective presently, and we make recommendations on how this approach could be improved.

NEW & NOTEWORTHY Bronchial thermoplasty is a recent treatment for asthma in which thermal energy is delivered via bronchoscope to specific airways in an effort to directly target airway smooth muscle. Current practice involves the treatment of a standard set of airways, unguided by patient-specific data. We consider the potential for guided treatments, either by functional or structural data from the lung, and show that treatment guided by structural data has the potential to improve clinical practice.
Research on Online Capacity Estimation of Power Battery Based on EKF-GPR Model
Authors: Zhou Di , Yin Hongtao , Xie Wei , Fu Ping , Lu Wenbin
Published: January 2019

Capacity degrading over repeated charge/discharge cycles is a main parameter for evaluating battery performance, which is commonly used for determining the state of health. However, it is difficult to measure the available capacity because it requires the normal operation to be terminated and a long time-consuming detection process. This study presents an online available-capacity estimation method by combining extended Kalman filter (EKF) with Gaussian process regression (GPR) for the daily partial charge data of lithium-ion batteries. First, GPR is used to establish an empirical model of the time-voltage curve in the constant current charge cases. Second, by analyzing the characteristics of the charge curve, the daily piecewise partially charge data are registered with the piecewise complete charge data to update GPR model and preestimate the equivalent complete charge time. On this basis, the equivalent complete charge time is refined by EKF. Furthermore, the available capacity estimation of the battery with constant current charge processes under different aging conditions is achieved. It is verified by experiments that the estimated error can be controlled within 5% when the actual available capacity is greater than 90% of the initial capacity.
Stiffness Calculation Model of Thread Connection Considering Friction Factors
Authors: Lu Shi-kun , Hua Deng-xin , Li Yan , Cui Fang-yuan , Li Peng-yang
Published: January 2019

In order to design a reasonable thread connection structure, it is necessary to understand the axial force distribution of threaded connections. For the application of bolted connection in mechanical design, it is necessary to estimate the stiffness of threaded connections. A calculation model for the distribution of axial force and stiffness considering the friction factor of the threaded connection is established in this paper. The method regards the thread as a tapered cantilever beam. Under the action of the thread axial force, in the consideration of friction, the two cantilever beams interact and the beam will be deformed, these deformations include bending deformation, shear deformation, inclination deformation of cantilever beam root, shear deformation of cantilever beam root, radial expansion deformation and radial shrinkage deformation, etc.; calculate each deformation of the thread, respectively, and sum them, that is, the total deformation of the thread. In this paper, on the one hand, the threaded connection stiffness was measured by experiments; on the other hand, the finite element models were established to calculate the thread stiffness; the calculation results of the method of this paper, the test results, and the finite element analysis (FEA) results were compared, respectively; the results were found to be in a reasonable range; therefore, the validity of the calculation of the method of this paper is verified.
Modeling a Risk-Based Dynamic Bus Schedule Problem under No-Notice Evacuation Incorporated with Dynamics of Disaster, Supply, and Demand Conditions
Authors: Li Menghui , Xu Jinliang , Wei Leyu , Jia Xingli , Sun Chao
Published: January 2019

Apart from private traffic, the evacuation of transit-dependent population is also an essential component of emergency preparedness, especially under no-notice evacuation scenarios with limit evacuation horizon. In literature, most bus-based evacuation models for no-notice evacuation are established under implicit assumptions of uniform evacuation horizon among different pick-up locations or fixed bus fleet in the evacuation area. These constraints will distance their models from real-world situations, where evacuation horizon is various due to spatial distribution of pick-up locations and fleet size of bus available for allocation will increase over time in no-notice evacuation. This research presents a risk-based bus schedule model which is differentiated from the vehicle routing problem (VRP) and bus evacuation problem (BEP) in literature, including the objective and the time-dependent parameters. A quantified definition of evacuation risk for pick-up location with concerns of disaster dynamics and time-varying supply-demand conditions is proposed in this paper as a criterion for bus allocation, also acting as a reflection of social equity to some extent. A notion of time-evolving disadvantageous evacuation units (DEU) is introduced to represent the pick-up locations selected for bus allocation with limited resource. The binary integer linear programming (BILP) named risk-based bus schedule model incorporated with DEU notion can provide a reference for resource allocation in stage of both evacuation planning and operation for transit-dependent population. The proposed model structure can effectively capture the changes of evacuation risk among pick-up locations over time to realize real-time bus schedule. Numerical experiments are conducted using the transportation network of the city of Xi’an, China, to test the performance of the model. The applicability and comparison of different bus evacuation models are also discussed in this paper. This research provides insights into dealing with disaster dynamics and time-varying supply conditions in realistic bus-based no-notice evacuation operations.
A Blazing Landscape: Neuroinflammation Shapes Brain Metastasis
Authors: Doron Hila , Pukrop Tobias , Erez Neta
Published: January 2019

Brain metastases are more common than primary CNS tumors and confer grave prognosis on patients, as existing treatments have very limited efficacy. The tumor microenvironment has a central role in facilitating tumorigenesis and metastasis. In recent years, there has been much progress in our understanding of the functional role of the brain metastatic microenvironment. In this review, we discuss the latest advances in brain metastasis research, with special emphasis on the role of the brain microenvironment and neuroinflammation, integrating insights from comparable findings in neuropathologies and primary CNS tumors. In addition, we overview findings on the formation of a hospitable metastatic niche and point out the major gaps in knowledge toward developing new therapeutics that will cotarget the stromal compartment in an effort to improve the treatment and prevention of brain metastases.
First-in-Human Phase I Study of an Oral HSP90 Inhibitor, TAS-116, in Patients with Advanced Solid Tumors
Authors: Shimomura Akihiko , Yamamoto Noboru , Kondo Shunsuke , Fujiwara Yutaka , Suzuki Shigenobu , Yanagitani Noriko , Horiike Atsushi , Kitazono Satoru , Ohyanagi Fumiyoshi , Doi Toshihiko , Kuboki Yasutoshi , Kawazoe Akihito , Shitara Kohei , Ohno Izumi , Banerji Udai , Sundar Raghav , Ohkubo Shuichi , Calleja Elizabeth M. , Nishio Makoto
Published: January 2019

HSP90 is involved in stability and function of cancer-related proteins. This study was conducted to define the MTD, safety, pharmacokinetics, pharmacodynamics, and preliminary antitumor efficacy of TAS-116, a novel class, orally available, highly selective inhibitor of HSP90. Patients with advanced solid tumors received TAS-116 orally once daily (QD, step 1) or every other day (QOD, step 2) in 21-day cycles. Each step comprised a dose escalation phase to determine MTD and an expansion phase at the MTD. In the dose escalation phase, an accelerated dose-titration design and a “3+3” design were used. Sixty-one patients were enrolled in Japan and the United Kingdom. MTD was determined to be 107.5 mg/m2/day for QD, and 210.7 mg/m2/day for QOD. In the expansion phase of step 1, TAS-116 was administered 5 days on/2 days off per week (QD × 5). The most common treatment-related adverse events included gastrointestinal disorders, creatinine increases, AST increases, ALT increases, and eye disorders. Eye disorders have been reported with HSP90 inhibitors; however, those observed with TAS-116 in the expansion phases were limited to grade 1. The systemic exposure of TAS-116 increased dose-proportionally with QD and QOD regimens. Two patients with non–small cell lung cancer and one patient with gastrointestinal stromal tumor (GIST) achieved a confirmed partial response. TAS-116 had an acceptable safety profile with some antitumor activity, supporting further development of this HSP90 inhibitor.

This is a result from a first-in-human study, in which the HSP90 inhibitor TAS-116 demonstrated preliminary antitumor efficacy in patients with advanced solid tumors, including those with heavily pretreated GIST.
Efficacy of a Novel Intranasal Formulation of Azelastine Hydrochloride and Fluticasone Propionate, Delivered in a Single Spray, for the Treatment of Seasonal Allergic Rhinitis: Results from Russia
Authors: Ilyina Natalia I. , Edin Anton S. , Astafieva Natalia G. , Lopatin Andrey S. , Sidorenko Irina V. , Ukhanova Olga P. , Khanova Fatimat M.
Published: January 2019

Background: The novel intranasal formulation of azelastine hydrochloride (AZE) and fluticasone propionate (FP) in a single spray (MP-AzeFlu) was compared with a first-line intranasal antihistamine spray (AZE) in Russian seasonal allergic rhinitis (SAR) patients. Methods: Moderate-to-severe SAR/rhinoconjunctivitis patients (n = 149; aged 18–65 years) were randomized to receive MP-AzeFlu (137/50 μg AZE/FP per spray) or AZE (137 μg/spray), both as 1 spray/nostril twice daily, in a multicenter, open-label, 14-day, parallel-group trial. The primary outcome was change from baseline in morning and evening reflective total nasal symptom score (rTNSS). Secondary end points included: change from baseline in reflective total ocular symptom score (rTOSS), reflective total of 7 symptom scores (rT7SS), 28-item Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) overall score, and EuroQol-5D (EQ-5D) questionnaire score. Results: When compared with AZE-treated patients, those treated with MP-AzeFlu experienced significantly greater reductions in rTNSS (difference: –2.47; 95% confidence interval [CI] –3.65 to –1.30; p < 0.001), rTOSS (difference: –1.62; 95% CI –2.32 to –0.92; p < 0.001), and rT7SS (difference: –4.34; 95% CI –5.98 to –2.70; p < 0.001). Superior relief observed on day 2 with MP-AzeFlu versus AZE was sustained throughout the study. MP-AzeFlu-treated patients experienced a greater improvement in QoL than AZE-treated patients as measured by overall RQLQ score (mean ± SD 2.91 ± 1.08 vs. 2.05 ± 1.15) and EQ-5D score (mean ± SD 87.4 ± 10.3 vs. 83.0 ± 12.8). MP-AzeFlu was well tolerated. Conclusions: MP-AzeFlu was superior to AZE in reducing moderate-to-severe SAR symptoms, providing earlier and more complete symptom relief.
Hard Tissue Augmentation of Aged Bone by Means of a Tin-Free PLLA-PCL Co-Polymer Exhibiting in vivo Anergy and Long-Term Structural Stability
Authors: Schimke Magdalena M. , Paul Swaraj , Tillmann Katharina , Lepperdinger Günter , Stigler Robert G.
Published: January 2019

Background: Due to aging, tissue regeneration gradually declines. Contemporary strategies to promote tissue-specific regeneration, in particular in elderly patients, often include synthetic material apt for implantation primarily aiming at upholding body functions and regaining appropriate anatomical and functional integrity. Objective: Biomaterials suitable for complex reconstruction surgical procedures have to exert high physicochemical stability and biocompatibility. Method: A polymer made of poly-L-lactic acid and poly-ε-caprolactone was synthesized by means of a novel tin-free catalytic process. The material was tested in a bioreactor-assisted perfusion culture and implanted in a sheep model for lateral augmentation of the mandible. Histological and volumetric evaluation was performed 3 and 6 months post-implantation. Results: After synthesis the material could be further refined by cryogrinding and sintering, thus yielding differently porous scaffolds that exhibited a firm and stable appearance. In perfusion culture, no disintegration was observed for extended periods of up to 7 weeks, while mesenchymal stromal cells readily attached to the material, steadily proliferated, and deposited extracellular calcium. The material was tested in vivo together with autologous bone marrow-derived stromal cells. Up to 6 months post-implantation, the material hardly changed in shape with composition also refraining from foreign body reactions. Conclusion: Given the long-term shape stability in vivo, featuring imperceptible degradation and little scarring as well as exerting good compatibility to cells and surrounding tissues, this novel biomaterial is suitable as a space filler in large anatomical defects.
Male Meiotic Recombination in the Steppe Agama, Trapelus sanguinolentus (Agamidae, Iguania, Reptilia)
Authors: Lisachov Artem P. , Tishakova Katerina V. , Tsepilov Yakov A. , Borodin Pavel M.
Published: January 2019

Meiotic recombination rates and patterns of crossover distributions along the chromosomes vary considerably even between closely related species. The adaptive significance of these differences is still unclear due to the paucity of empirical data. Most data on recombination come from mammalian species, while other vertebrate clades are poorly explored. Using immunolocalization of the protein of the lateral element of the synaptonemal complex (SYCP3) and the mismatch-repair protein MLH1, which marks mature recombination nodules, we analyzed recombination rates and crossover distribution in meiotic prophase chromosomes of the steppe agama (Trapelus sanguinolentus, Agamidae, Acrodonta, Iguania) and compared them with data obtained for the genus Anolis (Dactyloidae, Pleurodonta, Iguania). We found that, despite a smaller genome size, the total SC length and the MLH1 focus number per cell are much higher in the agama than in the anoles. The distributions of the MLH1 foci in the agama are multimodal in larger chromosomes and bimodal in smaller chromosomes without a significant centromere effect, resembling the patterns known for birds. A possible relationship between karyotype remodeling and the evolution of recombination in Iguania is discussed.
Roles of 12-Lipoxygenase and Its Interaction with Angiotensin II on p21 and p27 Expression in Diabetic Nephropathy
Authors: Zhang Yuan-yuan , Wang Wan-ning , Su Sen-sen , Chen Bin , Sun Wei-xia , Wu Hao , Cheng Yan-li , Xu Zhong-gao
Published: January 2019

Background: 12-Lipoxygenase (12-LO) and angiotensin II (Ang II) are involved in the development of diabetic renal hypertrophy, in which cyclin-kinase inhibitors, p21 and p27 play pivotal roles. Here, we study the effects of 12-LO and its interaction with Ang II on glomerular p21 and p27 expression in diabetic conditions. Methods: Models used in the current study include glomerular mesangial cells (MCs); and glomeruli from (1) type 2 diabetic db/db mice; (2) type 2 diabetic rats induced by high-fat diet feeding followed by streptozotocin injection; (3) 12-LO knockout (12-LOKO) mice; and (4) normal rats infused with Ang II or 12(S)-hydroxyeicosatetraenoic acid (12[S]-HETE, arachidonic acid metabolite of 12-LO). Results: The protein expression levels of p21 and p27 were increased in high glucose-stimulated MCs and in glomeruli isolated from db/db mice. In type 2 diabetic rats, cinnamyl-3,4-dihydroxy-α-cynanocinnamate (inhibitor of 12-LO) attenuated the increases in glomerular p21 and p27 protein expression, while in normal rats, 12(S)-HETE injection increased glomerular p21 and p27 expression. 12(S)-HETE and Ang II were mutually stimulated in glomeruli. Glomerular p21 and p27 expression were decreased in 12-LOKO mice compared to levels in control mice, and Ang II stimulation increased the protein expression of p27 in control but not 12-LOKO mice. Ang II stimulation had no effect on p21 protein expression in 12-LOKO mice. Conclusion: 12-LO is involved in diabetic renal hypertrophy via the induction of p21 and p27 protein expression and interacts with Ang II to induce p27 upregulation in diabetes. The current results suggest a potential amplifying loop in the pathogenesis of diabetic nephropathy.
GENETIC VARIATION OF WILD Musa acuminata COLLA FROM INDONESIA
Authors: Poerba Yuyu Suryasari , Martanti Diyah , Ahmad Fajarudin
Published: January 2019

Indonesia is the center of origin and diversity of Musa acuminata Colla, one of the progenitors of cultivated bananas today. However, the genetic variation of wild M. acuminata has not been studied extensively, thus this study aimed to assess the genetic variation of the Indonesian wild M. acuminata based on 10 RAPD (Random Amplified Polymorphic DNA) and 10 ISSR (Inter Simple Sequence Repeats) markers. The genetic properties of 17 populations of wild M. acuminata were analyzed by Popgene 1.32 based on Neiâ€™s unbiased measures of genetic identity and genetic distance. Of the 443 DNA bands produced, 425 (95.94%) were polymorphic. Cluster analysis of the combined data of RAPD and ISSR produced a dendrogram which separated the population of M. acuminata (A genome) from M. balbisiana (B genome), but not from M. schizocarpa (S genome).Â  Neiâ€™s genetic distance of the 17 populations of wild M. acuminata ranged from 0.3676 to 0.1634.Â  The highest genetic distance was observed between M. acuminata var rutilifes (from East Java) and M. acuminata var sumatrana (from West Sumatra). The percentages of polymorphic loci among the 17 populations of M. acuminata ranged from 9.93% to 39.73%. Neiâ€™s gene diversity (h) ranged from 0.041 to 0.1418. M. acuminata var malaccensis population was the most diverse among the researched 17 M. acuminata. The high level of genetic diversity of the wild M. acuminata from Indonesia emphasizes the need for conservation and preservation of the natural population and its use in the banana breeding program.
Call to Action: Urgent Challenges in Cardiovascular Disease: A Presidential Advisory From the American Heart Association
Authors: McClellan Mark , Brown Nancy , Califf Robert M. , Warner John J.
Published: January 2019

Although advances in care have spurred improvements in cardiovascular outcomes, cardiovascular disease remains the leading cause of death in the United States and around the world. Previous declines in cardiovascular disease mortality have slowed and even reversed for certain demographics. Further concerns exist with regard to cardiovascular drug innovation, quality of care, and healthcare costs. The Value in Healthcare Initiative–Transforming Cardiovascular Care, a collaboration of the American Heart Association and Duke University, Robert J. Margolis, MD, Center for Health Policy, aims to increase access to and affordability of cardiovascular treatment and to decrease barriers to care. The following Call to Action describes trends in cardiovascular care, identifies gaps in areas of cardiovascular disease prevention and treatment, highlights challenges with medical product innovation, and finally, outlines a series of learning collaboratives that will aid in the development of road maps for transforming cardiovascular care.
The genus Terthrothrips Karny (Thysanoptera: Phlaeothripidae) from China with one new species
Authors: WANG JUN , TONG XIAOLI
Published: January 2019

The Phlaeothripinae genus Terthrothrips is recorded from China for the first time, with a key to the three species here recorded, including one new species, T. palmatus. This differs from the known species of the genus by the pronotal anteromarginal setae being well developed and broadly expanded at the apex. New distribution information is provided for T. apterus Kudô and T. parvus Okajima, described originally from Japan.
On the identity of Microananteris, with a discussion on pectinal morphology, and description of a new Ananteris from Brazil (Scorpiones, Buthidae)
Authors: BOTERO-TRUJILLO RICARDO , NORIEGA JORGE ARI
Published: January 2019

The characters originally used to define the monotypic genus Microananteris Lourenço, 2003 are reanalyzed from the point of view of their usefulness to justify its recognition as a genus apart from Ananteris Thorell, 1891. A study of pectinal morphology conducted with Scanning Electron Microscopy (SEM) in six species of Ananteris, along with the results presented by Lourenço (2003) and other authors, demonstrate that both genera cannot be separated based on the shape of the peg sensillae but demonstrate this character’s (and the presence of seta-like structures) immediate usefulness at the species level instead. Such analysis of the morphological attributes of Microananteris as defined by Lourenço (2003) reveals there is no evidence in support of its validity. Therefore, Microananteris is synonymized with Ananteris and Microananteris minor Lourenço, 2003 transferred to this genus. A new species of Ananteris is also described from the Natural Reserve Palmari in the Brazilian Amazon.
A new genus, Krameragallia, a segregate from the Neogeic genus Agalliopsis (Hemiptera: Cicadellidae: Megophthalminae)
Authors: GONÇALVES ANA CLARA , NIELSON MERVIN WILLIAM
Published: January 2019

A new genus, Krameragallia, type-species Agalliopsis rex gen. nov. Kramer, is described and illustrated. Krameragallia gen. nov. can be distinguished from all other known genera of Neotropical Agalliini by morphological features such as the following: largest size (7.4–9mm) among known species in the New World representatives of the subfamily; strong contrasting scarlet and black color pattern; aedeagus shaft very long, almost ribbon-like with ventral process; aedeagal apex bearing one pair of lateral slender processes on each side and first valvifer of female genitalia very well developed and hook-shaped. Female genitalia are described for the first time, including a highly unusual, well developed first valvifer. Notes on the genus as well as on the distinction between Krameragallia gen. nov., Agalliopsis Kirkaldy, Brasa Oman, and Chromagallia Linnavuori are given.
On the identity of Ashlockobius Slater & Slater and Villalobosothignus Brailovsky (Hemiptera: Heteroptera: Rhyparochromidae: Myodochini), with the description of a new arboreal species from Ecuador
Authors: DELLAPÉ PABLO MATÍAS , MONTEMAYOR SARA ITZEL
Published: January 2019

The genus Villalobosothignus Brailovsky, 1984 is diagnosed, and Ashlockobius Slater & Slater, 1999 is synonymized with it. A new arboreal species of Villalobosothignus from Ecuador is described, and photographs of the adult and male genitalia are provided together with illustrations of certain diagnostic characters to facilitate identification.