bluuebunny/crossref_metadata_2025 huggingface dataset:
Systematic client feedback to brief therapy in basic mental healthcare: study protocol for a four-centre clinical trial
Authors: Bovendeerd Bram , de Jong Kim , Colijn Sjoerd , de Groot Erik , Hafkenscheid Anton , Moerbeek Mirjam , de Keijser Jos
Published: May 2019

Introduction

The Partners for Change Outcome Management System (PCOMS) is a client feedback-system built on two brief visual analogue self-report scales. Prior studies of PCOMS have found effects varying from significant positive to negative. Aims of present study are; to test the predicted beneficial impact of PCOMS, while accounting for methodological flaws in prior studies and to clarify under which circumstances the addition of PCOMS to therapy has a beneficial effect.

Methods and analysis

This study focuses on patients applying for brief, time-limited treatments. Four centres will be randomised to either treatment as usual (TAU) or TAU with PCOMS. All participating patients will be assessed four times. The full staff in the experimental condition will be trained in PCOMS. In the second part of this study, all therapists in the PCOMS condition will fill in a questionnaire concerning the influence of regulatory focus, self-efficacy, external or internal feedback orientation and perceived feedback validity of PCOMS. Finally, patients in the PCOMS condition will be asked to give feedback through a structured interview.

The primary outcome measure is the Outcome Questionnaire over the period from beginning to end of therapy. The Mental Health Continuum-Short Form and Consumer Quality Index are also completed. In the primary analysis, outcomes of the two treatment conditions on treatment outcome, patient satisfaction, costs, drop-out and duration will be examined with a three-level (within patient, between patients and between therapists) multilevel analysis. The DSM-classification, sex, education level, age of each patient and therapist factors will be included as covariates.

Ethics and dissemination

The Medical Ethics Committee of the University of Twente approved this study (K15-11, METC Twente). Data will be included from 1 January 2016 to 1 July 2019. Study results will be disseminated through peer-reviewed journals and conferences.

Trial registration number

NTR5466; Pre-results.
Evaluating antibiotic stewardship in a tertiary care hospital in Kerala, India: a qualitative interview study
Authors: Baubie Kelsey , Shaughnessy Catherine , Kostiuk Lia , Varsha Joseph Mariam , Safdar Nasia , Singh Sanjeev K , Siraj Dawd , Sethi Ajay , Keating Julie
Published: May 2019

Objectives

To determine what barriers and facilitators to antibiotic stewardship exist within a healthcare facility.

Setting

1300-bed tertiary care private hospital located in the state of Kerala, India.

Participants

31 semistructured interviews and 4 focus groups with hospital staff ranging from physicians, nurses, pharmacists and a clinical microbiologist.

Results

Key facilitators of antibiotic stewardship (AS) at the hospital included a dedicated committee overseeing appropriate inpatient antibiotic use, a prompt microbiology laboratory, a high level of AS understanding among staff, established guidelines for empiric prescribing and an easily accessible antibiogram. We identified the following barriers: limited access to clinical pharmacists, physician immunity to change regarding stewardship policies, infrequent antibiotic de-escalation, high physician workload, an incomplete electronic medical record (EMR), inadequate AS programme (ASP) physical visibility and high antibiotic use in the community.

Conclusions

Opportunities for improvement at this institution include increasing accessibility to clinical pharmacists, implementing strategies to overcome physician immunity to change and establishing a more accessible and complete EMR. Our findings are likely to be of use to institutions developing ASPs in lower resource settings.
Multinational comparison of new antidepressant use in older adults: a cohort study
Authors: Tamblyn Robyn , Bates David Westfall , Buckeridge David L , Dixon Will , Forster Alan J , Girard Nadyne , Haas Jennifer , Habib Bettina , Kurteva Siyana , Li Jack , Sheppard Therese
Published: May 2019

Objectives

We used an international pharmacosurveillance network to estimate the rate and characteristics of antidepressant use in older adults in countries with more conservative (UK) and liberal depression guidelines (Canada, USA).

Setting

Electronic health records and population-based administrative data from six jurisdictions in four countries (UK, Taiwan, USA and Canada).

Participants

A historical cohort of older adults (≥65 years) who had a new episode of antidepressant use between 2009 and 2014.

Outcome measures

The age and sex-standardised cumulative incidence of new episodes of antidepressant use in older adults was measured. Descriptive statistics were used to compare the proportion of new users by the antidepressant prescribed, therapeutic class, potential treatment indication and country, as well as the characteristics of the first treatment episode (standardised daily doses, duration and changes).

Results

The incidence of antidepressant use between 2009 and 2014 varied from 4.7% (Montreal and Quebec City) to 18.6% (Taiwan). Tricyclic antidepressants (TCAs) were the most commonly used class in the UK (48.8%) and Taiwan (52.4%) compared with selective serotonin reuptake inhibitors (SSRIs) in North American jurisdictions (42.3%–53.3%). Chronic pain was the most common potential treatment indication (41.2%–68.2%). Among users with chronic pain, TCAs were used most frequently in the UK and Taiwan (55.2%–60.4%), whereas SSRIs were used most frequently in North America (33.5%–46.4%). Treatment was longer (252–525 vs 169–437 days), standardised doses were higher (0.7–1.3 vs 0.5–1.0) and treatment was more likely to be changed (31%–46% vs 21%–34%) among patients with depression (9.1%–43%) than those with chronic pain.

Conclusion

Antidepressant use in older adults varied 24-fold by country, with the UK, which has the most conservative treatment guidelines, being among the lowest. Chronic pain was the most common potential treatment indication. Evaluation of real-world risks of TCAs is a priority for future research, given high rates of use and the potential for increased toxicity in older adults because of potent anticholinergic effects.
Altered K+ current profiles underlie cardiac action potential shortening in hyperkalemia and β-adrenergic stimulation
Authors: Hegyi Bence , Chen-Izu Ye , Izu Leighton T. , Bányász Tamás
Published: May 2019

Hyperkalemia is known to develop in various conditions including vigorous physical exercise. In the heart, hyperkalemia is associated with action potential (AP) shortening that was attributed to altered gating of K+ channels. However, it remains unknown how hyperkalemia changes the profiles of each K+ current under a cardiac AP. Therefore, we recorded the major K+ currents (inward rectifier K+ current, IK1; rapid and slow delayed rectifier K+ currents, IKr and IKs, respectively) using AP-clamp in rabbit ventricular myocytes. As K+ may accumulate at rapid heart rates during sympathetic stimulation, we also examined the effect of isoproterenol on these K+ currents. We found that IK1 was significantly increased in hyperkalemia, whereas the reduction of driving force for K+ efflux dominated over the altered channel gating in case of IKr and IKs. Overall, the markedly increased IK1 in hyperkalemia overcame the relative decreases of IKr and IKs during AP, resulting in an increased net repolarizing current during AP phase 3. β-Adrenergic stimulation of IKs also provided further repolarizing power during sympathetic activation, although hyperkalemia limited IKs upregulation. These results indicate that facilitation of IK1 in hyperkalemia and β-adrenergic stimulation of IKs represent important compensatory mechanisms against AP prolongation and arrhythmia susceptibility.
The effect of the nuclear motion on harmonic spectral structure
Authors: Zhang Cai-Ping , Xia Chang-Long , Miao Xiang-Yang
Published: May 2019

The harmonic emissions from hydrogen molecular ion at different initial vibrational states have been simulated by numerically solving the time-dependent Schrödinger equation. The results show that the nuclear motion exhibits different effects on the spectral structure for different vibrational states. For lower vibrational state, the odd harmonics experience obvious harmonic shifting; however, for higher vibrational state, the even harmonics are emitted from the symmetric system due to the asymmetric electronic distribution in the coupling region of two lowest electronic states.
Light deflection by a quantum improved Kerr black hole pierced by a cosmic string
Authors: Jusufi Kimet , Övgün Ali
Published: May 2019

In this work, we calculate the quantum correction effects on the deflection of light in the space-time geometry of a quantum improved Kerr black hole pierced by an infinitely long cosmic string. More precisely, we calculate the deflection angle by applying the Gauss–Bonnet theorem (GBT) to the osculating optical geometries related to the quantum improved rotating black hole in the weak limit approximation. We find that the deflection angle of light is affected by the quantum effects as well as the global topology due to the presence of the cosmic string. Besides, we have managed to find the same expression for the deflection angle in leading order terms using the geodesic equations.
Degradation of fracture porosity in sandstone by carbonate cement, Piceance Basin, Colorado, USA
Authors: Weisenberger Tobias B. , Eichhubl Peter , Laubach Stephen E. , Fall András
Published: May 2019

Cretaceous Mesaverde Group sandstones contain opening-mode fractures lined or filled by quartz and, locally, calcite cement. Fracture occlusion by quartz is controlled primarily by fracture size, age and thermal history. Fracture occlusion by calcite is highly heterogeneous, with open and calcite-sealed fractures found at adjacent depths. In the Piceance and in other basins, processes that control the distribution of these calcite cements have been uncertain. Using pore and fracture cement petrography, fluid inclusions, and isotopic and elemental analysis, we show that host-rock calcite distribution and remobilization govern porosity degradation and occlusion of fractures >1 mm wide by calcite. Fluid-inclusion analyses indicate calcite cement precipitation at 135–165°C.
87
Sr/
86
Sr ratios of calcite and the presence of porous albite suggest that detrital feldspar albitization released Ca
2+
, driving carbonate cement precipitation. In host rock, both albite and calcite content decreases with depth along with greater fracture porosity preservation. Although the cement sequence Fe-dolomite → ankerite → calcite is widespread, Fe-dolomite and ankerite occur as host-rock cements only, with detrital dolomite as preferred precipitation substrate. We find that the rock-mass calcite cement content correlates with fracture degradation and occlusion, and can be used to accurately predict where wide fractures are sealed or open.

Thematic collection:
This article is part of the Naturally Fractured Reservoirs collection available at:
https://www.lyellcollection.org/cc/naturally-fractured-reservoirs
Seismic pore pressure prediction at the Halten Terrace in the Norwegian Sea
Authors: Aker Eyvind , Tveiten Ole G. , Wynn Tim
Published: May 2019

Pre-drill pore pressure prediction is essential for safe and efficient drilling, and is a key element in the risk-reducing toolbox when designing a well. On the Norwegian Continental Shelf, pore pressure prediction commonly relies on traditional 1D offset well analysis, whereas velocity data from seismic surveys are often not considered. Our work with seismic interval velocities shows that the velocity field can provide an important basis for pressure prediction and enable the construction of regional 3D pressure cubes. This may increase the confidence in the pore pressure models and aid the pre-drill geohazard screening process. We demonstrate how a 3D velocity field can be converted to a 3D pore pressure cube using reported pressures in offset wells as calibration points. The method is applied to a regional dataset at the Halten Terrace in the Norwegian Sea; an area with a complex pattern of pore pressure anomalies which traditionally has been difficult to predict. The algorithm is searching for a velocity to pore pressure transform that best matches the reported pressures. The 3D velocity field is a proxy of rock velocity and is derived from seismic surveys, and is verified to checkshot velocities and sonic data in the offset wells.
The Decline of the Judicial Override
Authors: Radelet Michael L. , Cohen G. Ben
Published: May 2019

Since 1972, the Supreme Court has experimented with regulation of the death penalty, seeking the illusive goals of consistency, reliability, and fairness. In this century, the court held that the Sixth Amendment prohibited judges from making findings necessary to impose a death sentence. Separately, the court held that the Eighth Amendment safeguarded evolving standards of decency as measured by national consensus. In this article, we discuss the role of judges in death determinations, identifying jurisdictions that initially (post 1972) allowed judge sentencing and naming the individuals who today remain under judge-imposed death sentences. The decisions guaranteeing a jury determination have so far been applied only to cases that have not undergone initial review in state courts. Key questions remain unresolved, including whether the evolving standards of decency permit the execution of more than 100 individuals who were condemned to death by judges without a jury's death verdict before implementation of the rules that now require unanimous jury votes.
Analyzing Age-Period-Cohort Data: A Review and Critique
Authors: Fosse Ethan , Winship Christopher
Published: May 2019

Age-period-cohort (APC) analysis has a long, controversial history in sociology and related fields. Despite the existence of hundreds, if not thousands, of articles and dozens of books, there is little agreement on how to adequately analyze APC data. This article begins with a brief overview of APC analysis, discussing how one can interpret APC effects in a causal way. Next, we review methods that obtain point identification of APC effects, such as the equality constraints model, Moore-Penrose estimators, and multilevel models. We then outline techniques that entail point identification using measured causes, such as the proxy variables approach and mechanism-based models. Next, we discuss a general framework for APC analysis grounded in partial identification using bounds and sensitivity analyses. We conclude by outlining a general step-by-step procedure for conducting APC analyses, presenting an empirical example examining temporal shifts in verbal ability.
Novel swine model of colonic diverticulosis
Authors: Guo Xiaomei , Patel Bhavesh , Han Ling , Al-Dulaimi Hiba , Van Alstine William G. , Noblet Jillian N. , Chambers Sean , Kassab Ghassan S
Published: May 2019

The pathophysiology of colonic diverticulosis has not been completely understood. The development of appropriate animal models is essential to study diverticular disease. To date, no large animal models are available for this disease condition. The objective of this study was to develop a swine model by damaging the colon wall, combined with or without a low-fiber diet to mimic the pathogenesis of diverticulosis. To create a weakness on the colon wall, collagenase was applied in vivo to degrade the collagen in the colon wall. Three groups of Yucatan minipigs were included. Group 1 ( n = 12) underwent collagenase injection (CI) with a low-fiber diet for 6 mo, group 2 ( n = 8) underwent CI alone with a standard swine diet for 6 mo, and group 3 ( n = 12) received a low-fiber diet alone for 6 mo. We found that diverticulosis occurred in 91.7% (11 of 12) of pigs in the CI + diet group and 100% (8 of 8) in CI-alone group. Moreover, around 30–75% of colon CI spots for each pig developed diverticular lesions. Diet alone for 6 mo did not induce diverticulosis. The endoscopic and histological examinations revealed the formation of multiple wide-mouthed diverticular lesions along the descending colon. Our results provide convincing evidence of the high efficacy of the reduced colon wall strength caused by CI in the development of a swine model of diverticulosis. Low-fiber diet consumption for 6 mo had no influence on the generation time or incidence rate of diverticulosis. In this model, digestion of the collagen in the colonic wall is sufficient to cause diverticulosis.

NEW & NOTEWORTHY Effective large animal models of diverticulosis are currently lacking for the study of diverticular disease. This study marks the first time that a swine model of diverticulosis was developed by damaging colon wall structure, combined with or without a low-fiber diet. We found that a defect of colon wall could result in colon diverticular lesions within 6 mo in swine. This animal model mimicking the pathological process of diverticulosis is of great clinical value.
Sex differences and the role of ovarian hormones in site-specific nociception of SHR
Authors: M. Santos Bruna , Nascimento Glauce C. , Capel Camila P. , Borges Gabriela S. , Rosolen Thales , Sabino João P. J. , Leite-Panissi Christie R. A. , Branco Luiz G. S.
Published: May 2019

Accurate diagnosis and treatment of pain is dependent on knowledge of the variables that might alter this response. Some of these variables are the locality of the noxious stimulus, the sex of the individual, and the presence of chronic diseases. Among these chronic diseases, hypertension is considered a serious and silent disease that has been associated with hypoalgesia. The main goal of this study was to evaluate the potential nociceptive differences in spontaneously hypertensive rats (SHR) regarding the locality of the stimulus, i.e., the temporomandibular joint or paw, the sex, and the role of ovarian hormones in a model of mechanical nociception (Von Frey test) or formalin-induced inflammatory nociception. Our results indicate that SHR had lower orofacial mechanical nociception beyond the lower mechanical nociception in the paw compared with WKY rats. In a model of formalin-induced inflammatory nociception, SHR also had decreased nociception compared with normotensive rats. We also sought to evaluate the influence of sex and ovarian hormones on orofacial mechanical nociception in SHR. We observed that female SHR had higher mechanical nociception than male SHR only in the paw, but it had higher formalin-induced orofacial nociception than male SHR. Moreover, the absence of ovarian hormones caused an increase in mean arterial pressure and a decrease in paw nociception in female SHR.
DCLK1 Plays a Metastatic-Promoting Role in Human Breast Cancer Cells
Authors: Liu Heshu , Wen Tao , Zhou Ying , Fan Xiaona , Du Tan , Gao Tianbo , Li Lina , Liu Jian , Yang Lei , Yao Jiannan , Ge Yang , An Guangyu
Published: May 2019

Background. Doublecortin-like kinase 1 (DCLK1) has been universally identified as a cancer stem cell (CSC) marker and is found to be overexpressed in many types of cancers including breast cancer. However, there is little data regarding the functional role of DCLK1 in breast cancer metastasis. In the present study, we sought to investigate whether and how DCLK1 plays a metastatic-promoting role in human breast cancer cells.Methods. We used Crispr/Cas9 technology to knock out DCLK1 in breast cancer cell line BT474, which basically possesses DCLK1 at a higher level, and stably overexpressed DCLK1 in another breast cancer cell line, T47D, that basically expresses DCLK1 at a lower level. We further analyzed the alterations of metastatic characteristics and the underlying mechanisms in these cells.Results. It was shown that, compared with the corresponding control cells, DCLK1 overexpression led to an increase in metastatic behaviors including enhanced migration and invasion of T47D cells. By contrast, forced depletion of DCLK1 drastically inhibited these metastatic characteristics in BT474 cells. Mechanistically, the epithelial-mesenchymal transition (EMT) program, which is critical for cancer metastasis, was prominently activated in DCLK1-overexpressing cancer cells, evidenced by a decrease in an epithelial marker ZO-1 and an enhancement in several mesenchymal markers including ZEB1 and Vimentin. In addition, DCLK1 overexpression induced the ERK MAPK pathway, which resultantly enhanced the expression of MT1-MMP that is also involved in cancer metastasis. Knockout of DCLK1 could reverse these events, further supporting a metastatic-promoting role for DCLK1.Conclusions. Collectively, our data suggested that DCLK1 overexpression may be responsible for the increased metastatic features in breast cancer cells. Targeting DCLK1 may become a therapeutic option for breast cancer metastasis.
Numerical Simulation for Engine/Airframe Interaction Effects of the BWB300 on Aerodynamic Performances
Authors: Yu Gang , Li Dong , Shu Yue , Zhang Zeyu
Published: May 2019

The engine/airframe interaction effects of the BWB300 on aerodynamic performances were analyzed by using the numerical simulation method. The BWB300 is a 300-seat Blended Wing Body airplane designed by the Airplane Concept Design Institute of Northwestern Polytechnical University. The engine model used for simulation was simplified as a powered nacelle. The results indicated the following: at high speed, although the engine/airframe interaction effects on the aerodynamic forces were not significant, the airframe’s upper surface flow was greatly changed; at low speed, the airframe’s aerodynamic forces (of the airplane with/without the engine) were greatly different, especially at high attack angles, i.e., the effect of the engine suction caused the engine configuration aerodynamic forces of the airframe to be bigger than those without the engine; and the engine’s installation resulting in the different development of flow separation at the airframe’s upper surface caused greater obvious differences between the 2 configurations at high angles and low speed. Moreover, at low-speed high attack angles, the separated flow from the blended area caused serious distortion at the fan inlet of the engine.
High‐Precision Extraction of Segment Points of 2D Profiles Based on a Dynamic Grid Method
Authors: Zhang Xu , Zhang Haibo , Zhang Liqiang , Shen Jie
Published: May 2019

In order to improve the reconstruction precision and performance of 2D profiles, this paper presents a new high‐precision extraction method of segment points of 2D profile features. Firstly, we extract the intervals which include initial segment points based on the curvature information of data points. Secondly, a grid is dynamically constructed in the interval and all the nodes of the grid are considered as candidate segment points for an optimization process. Thirdly, the optimization model of each feature curve is constructed on the basis of boundary constraints. Selection of the optimal segment point is related to two factors: the number of control points of B‐spline and the total approximation error of all collected points to the fitted curves. Numerical experiments were conducted and the results demonstrate the efficacy of our method in capturing design intent and in industrial applications, compared to existing methods.
Electroacupuncture Mitigates Hippocampal Cognitive Impairments by Reducing BACE1 Deposition and Activating PKA in APP/PS1 Double Transgenic Mice
Authors: Tang Yinshan , Shao Shujun , Guo Yu , Zhou You , Cao Jin , Xu Anping , Wu Jihong , Li Zhigang , Xiang Dulian
Published: May 2019

Increased amyloid-β (Aβ) plaque deposition is thought to be the main cause of Alzheimer’s disease (AD). β-Site amyloid precursor protein cleaving enzyme 1 (BACE1) is the key protein involved in Aβ peptide generation. Excessive expression of BACE1 might cause overproduction of neurotoxins in the central nervous system. Previous studies indicated that BACE1 initially cleaves the amyloid precursor protein (APP) and may subsequently interfere with physiological functions of proteins such as PKA, which is recognized to be closely associated with long-term potentiation (LTP) level and can effectively ameliorate cognitive impairments. Therefore, revealing the underlying mechanism of BACE1 in the pathogenesis of AD might have a significant impact on the future development of therapeutic agents targeting dementia. This study examined the effects of electroacupuncture (EA) stimulation on BACE1, APP, and p-PKA protein levels in hippocampal tissue samples. Memory and learning abilities were assessed using the Morris water maze test after EA intervention. Immunofluorescence, immunohistochemistry, and western blot were employed to assess the distribution patterns and expression levels of BACE1, APP, and p-PKA, respectively. The results showed the downregulation of BACE1 and APP and the activation of PKA by EA. In summary, EA treatment might reduce BACE1 deposition in APP/PS1 transgenic mice and regulate PKA and its associated substrates, such as LTP to change memory and learning abilities.
Rho-Kinase II Inhibitory Potential of Eurycoma longifolia New Isolate for the Management of Erectile Dysfunction
Authors: Ezzat Shahira M. , Okba Mona M. , Ezzat Marwa I. , Aborehab Nora M. , Mohamed Shanaz O.
Published: May 2019

Background. Eurycoma longifolia Jack (Fam.: Simaroubaceae), known as Tongkat Ali (TA), has been known as a symbol of virility and sexual power. The aim of the study was to screen E. longifolia aqueous extract (AE) and isolates for ROCK-II inhibition. Results. The AE (1-10 μg/ml) showed a significant inhibition for ROCK-II activity (62.8-81%) at P < 0.001 with an IC50 (651.1 ± 32.9 ng/ml) compared to Y-27632 ([(+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl)cyclohexanecarboxamide dihydrochloride]) (68.15-89.9 %) at same concentrations with an IC50 (192 ± 8.37 ng/ml). Chromatographic purification of the aqueous extract (AE) allowed the isolation of eight compounds; stigmasterol T1, trans-coniferyl aldehyde T2, scopoletin T3, eurycomalactone T4, 6α- hydroxyeurycomalactone T5, eurycomanone T6, eurycomanol T7, and eurycomanol-2-O-β-D-glucopyranoside T8. This is the first report for the isolation of T1 and T3 from E. longifolia and for the isolation of T2 from genus Eurycoma. The isolates (at 10 μg/ml) exhibited maximum inhibition % of ROCK-II 82.1 ± 0.63 (T2), 78.3 ± 0.38 (T6), 77.1 ± 0.11 (T3), 76.2 ± 3.53 (T4), 74.5 ± 1.27 (T5), 74.1 ± 2.97 (T7), 71.4 ± 2.54 (T8), and 60.3 ± 0.14 (T1), where the newly isolated compound trans-coniferyl aldehyde T2 showed the highest inhibitory activity among the tested isolated compounds and even higher than the total extract AE. The standard Y-27632 (10 μg/ml) showed 89.9 ± 0.42 % inhibition for ROCK-II activity when compared to control at P < 0.0001. Conclusion. The traditional use of E. longifolia as aphrodisiac and for male sexual disorders might be in part due to the ROCK-II inhibitory potential.
The Effect of Supplementation with Some Essential Oils on the Mobility and the Vitality of Human Sperm
Authors: Mbaye Modou M. , El Khalfi Bouchra , Addoum Boutaina , Mar Papa D. , Saadani Brahim , Louanjli Noureddine , Soukri Abdelaziz
Published: May 2019

The objective of this work is to study the improvement effect of some essential oils of sage (Salvia officinalis), oregano (Origanum vulgare), and eucalyptus (eucalyptus globulus) on the physiological parameters characterizing the quality of human sperm (mobility and vitality). We find natural biomolecules to improve sperm quality to increase the chances of success of very low in vitro fertilization (IVF) that stagnate around 20%. Sperm samples were mixed with different concentrations of essential oils. The effect of these essential oils on the motility and vitality of spermatozoa has been analyzed. The mobility was determined using a Computer Assisted Sperm Analysis (CASA). In the other side, the evaluation of sperm vitality was performed by staining eosin 2% and the microscopic examination is carried out via optical microscope. A drop of sperm will be mixed with a drop of eosin solution 2%, spread between the slip and coverslip, then allowed to air dry, and examined under a microscope. A significant improvement in the mobility and vitality of human spermatozoa has been noted with oregano. Eucalyptus after 10 min of exposure also significantly improves the mobility and vitality of the spermatozoa. Sage does not improve mobility for these incubation times but significantly improves vitality.
Experimental Study on Dynamic Performance of Self‐Compacting Lightweight Aggregate Concrete under Compression
Authors: Li Furong , Yu Zhenpeng , Hu Yanli
Published: May 2019

In order to study the dynamic characteristics of the self‐compacting lightweight aggregate concrete (SCLC) under uniaxial compression, 10 different strain rates (10−5–10−1/s) were set up to examine the uniaxial compressive dynamic performance of ordinary concrete, lightweight aggregate concrete, and SCLC, respectively. The failure modes and stress‐strain curves of the samples under different loading conditions were obtained through experiment. The dynamic characteristics of the SCLC were analyzed by comparing the failure modes and testing data under different loading conditions. The following conclusions are drawn: the failure modes of the SCLC belong to destruction of shale ceramsite, which are similar to that of the lightweight aggregate concrete. The peak stress and elastic modulus of the self‐compacting lightweight aggregate gradually increase with the increase of the loading strain rate, but the extent of increase of the peak stress is lower than that of the ordinary concrete and lightweight aggregate concrete. Affected by the loading strain rate and the random coupling of concrete, the peak strain of the self‐compacting lightweight aggregate shows a relatively discrete changing trend. At the same time, the compressive dynamic performance of the SCLC was analyzed from the perspective of failure mechanism with a quantitative point of view.
HNF1α Controls Liver Lipid Metabolism and Insulin Resistance via Negatively Regulating the SOCS-3-STAT3 Signaling Pathway
Authors: Tan Jiaorong , Xu Jiahong , Wei Guohua , Zhang Lijuan , Sun Long’e , Wang Guangyu , Li Fei , Jiang Fengxiang
Published: May 2019

This study is aimed at evaluating the effects, functions, and mechanism of HNF1α on hepatic glycolipid metabolism. In this study, free fatty acid- (FFA-) induced steatosis of hepatocyte liver cell LO2 was used as an in vitro model. The methods of Oil Red O staining, RT-qPCR, western blot, and immunofluorescence staining were used to detect LO2-regulated HNF1α expression and its effects on FFA-induced LO2 cell steatosis, the insulin signaling and SOCS-3-STAT3 signaling pathways, the expression of lipid metabolism-related regulators, and phosphorylation. With increased FFA induction time, the expression of HNF1α in the LO2 fatty degeneration hepatic cells gradually decreased. Downregulation of HNF1α expression aggravated FFA-induced steatosis of LO2 hepatocytes. HNF1α promotes activation of the insulin pathway and oxidative breakdown of fat and inhibits lipid anabolism. Inhibitors of STAT3 can reverse the regulation of decreased HNF1α expression on the insulin signaling pathway and fat metabolism. We also confirmed this pathway using HNF1α-/- mice combining treatment with STAT3 inhibitor NSC 74859 in vivo. HNF1α regulates hepatic lipid metabolism by promoting the expression of SOCS-3 and negatively regulating the STAT3 signaling pathway.
Follicular Helper T Cell Derived Exosomes Promote B Cell Proliferation and Differentiation in Antibody-Mediated Rejection after Renal Transplantation
Authors: Yang Jintao , Bi Lili , He Xiuyun , Wang Zhen , Qian Yeyong , Xiao Li , Shi Bingyi
Published: May 2019

Follicular helper T cells (Tfh cells) are closely related to the occurrence and development of antibody-mediated rejection (AMR) after renal transplantation. Exosomes play a key role in the rejection after organ transplantation. However, whether Tfh-derived exosomes are involved in AMR has not been reported. We collected peripheral blood from 42 kidney transplant patients and found no significant differences in CD4+CXCR5+ and CD4+CXCR5+CXCR3+CCR6-exosomes between AMR and non-AMR groups, whereas the proportion of CD4+CXCR5+CXCR3-exosomes was significantly higher in AMR group than that in non-AMR group; CTLA-4 expression of CD4+CXCR5+exosomes was significantly lower in AMR group than that in non-AMR group. HLA-G expression was not significantly different between two groups. We further separated CD4+CXCR5+cells from patients by magnetic beads. Coculture experiments showed that Tfh cell-derived exosomes in AMR patients significantly promoted B cell proliferation and differentiation, compared with non-AMR group, the percentage of B cells and plasma cells increased by 87.52% and 110.2%, respectively. In conclusion, our study found that Tfh cell-derived exosomes could promote the proliferation and differentiation of B cells and they may play an important role in the development of AMR after renal transplantation.
Compensatory Plasticity in the Lateral Extrastriate Visual Cortex Preserves Audiovisual Temporal Processing following Adult-Onset Hearing Loss
Authors: Schormans Ashley L. , Allman Brian L.
Published: May 2019

Partial hearing loss can cause neurons in the auditory and audiovisual cortices to increase their responsiveness to visual stimuli; however, behavioral studies in hearing-impaired humans and rats have found that the perceptual ability to accurately judge the relative timing of auditory and visual stimuli is largely unaffected. To investigate the neurophysiological basis of how audiovisual temporal acuity may be preserved in the presence of hearing loss-induced crossmodal plasticity, we exposed adult rats to loud noise and two weeks later performed in vivo electrophysiological recordings in two neighboring regions within the lateral extrastriate visual (V2L) cortex—a multisensory zone known to be responsive to audiovisual stimuli (V2L-Mz) and a predominantly auditory zone (V2L-Az). To examine the cortical layer-specific effects at the level of postsynaptic potentials, a current source density (CSD) analysis was applied to the local field potential (LFP) data recorded in response to auditory and visual stimuli presented at various stimulus onset asynchronies (SOAs). As predicted, differential effects were observed in the neighboring cortical regions’ postnoise exposure. Most notably, an analysis of the strength of multisensory response interactions revealed that V2L-Mz lost its sensitivity to the relative timing of the auditory and visual stimuli, due to an increased responsiveness to visual stimulation that produced a prominent audiovisual response irrespective of the SOA. In contrast, not only did the V2L-Az in noise-exposed rats become more responsive to visual stimuli but neurons in this region also inherited the capacity to process audiovisual stimuli with the temporal precision and specificity that was previously restricted to the V2L-Mz. Thus, the present study provides the first demonstration that audiovisual temporal processing can be preserved following moderate hearing loss via compensatory plasticity in the higher-order sensory cortices that is ultimately characterized by a functional transition in the cortical region capable of temporal sensitivity.
Predictable Behavior of GFRP-Reinforced Bridge Decks: Formulation of a Strain-Based Capacity Model
Authors: Kim Young Hoon , Kim Yeesock , Park Yeonho
Published: May 2019

This paper proposes a reliability analysis framework for glass fiber-reinforced polymer- (GFRP-) reinforced concrete systems with uncertain capacities and demands over time. Unfortunately, there has been limited discussion or research done related to the potential change of failure modes over time. Therefore, a rational approach is needed to integrate multiple failure modes in a single analysis framework, considering uncertainties of time-variant demands and capacities. To account for multiple failure modes, this study proposes the limit state function to estimate the safety margin, based on strain values of GFRP-reinforcing bars. A proposed limit state function can capture the likelihood of both shear and flexural failure modes, simultaneously. In this study, seven typical bridge deck configurations (e.g., varied deck thickness, girder spacing, and bar size) were exposed to various ambient temperatures. Simulation results show that reliability indices of 100-year exposure exhibit significant variance, ranging from 2.35 to 0.93, with exposure temperatures ranging from 13 to 33°C. Exposure temperature and time are the dominant factors influencing the reliability indices, so are the ones that need to be changed. As exposure time and/or exposure temperature increase, the flexural capacity model plays an important role to determine the reliability indices. When flexural and shear failure modes are equally dominant, reliability indices can capture risks of both failures, using the proposed strain-based approach.
Related Results to Hybrid Pair of Mappings and Applications in Bipolar Metric Spaces
Authors: Kishore G. N. V. , Rao K. P. R. , Sombabu A. , Rao R. V. N. S.
Published: May 2019

In this paper, we introduce the concept of multivalued contraction mappings in partially ordered bipolar metric spaces and establish the existence of unique coupled fixed point results for multivalued contractive mapping by using mixed monotone property in partially ordered bipolar metric spaces. Some interesting consequences of our results are obtained.
Analysis of a Late-Autumn Rainstorm in the Sichuan Basin on the Eastern Side of the Tibetan Plateau
Authors: Chen Yongren , Li Yueqing
Published: May 2019

An abnormal heavy rainfall that occurred on 27 October 2014 in the Sichuan Basin (SB), China, is analyzed. An inverted trough at 850 hPa evolved into a Southwest China Vortex (SWCV), and strong upward motion caused by interaction between the low-level jet (LLJ) at 850 hPa and the upper-level jet (ULJ) at 200 hPa triggered the rainstorm process. Under a large-scale circulation system featuring a westerly trough and subtropical high, there were two cloud bands over the northeast side and south side of the Tibetan Plateau, respectively. Influenced by the eastward-moving trough, the inverted trough, LLJ, and the SWCV, a Mesoscale Convective System (MCS) was generated near the intersection of the two cloud bands, and it was the direct rainstorm system. The MCS strengthened under the situation of the 850 hPa inverted trough, but weakened when the inverted trough evolved to into the SWCV. Eventually, it formed the phenomenon known as “existing vortex without cloud.” Through analysis of the possible reasons why precipitation strengthened (weakened) under the situation of the inverted trough (SWCV), it was found that the strengthening of precipitation was due to a strong tilting updraft in the area of the ULJ and LLJ intersection. On one hand, the upward motion was related to the vorticity advection variation with height and the low-level warm advection forcing; while on the other hand, the dew-point front near the LLJ also played a lifting role in the upward flow of the lower-layer vertical circulation. Meanwhile, the LLJ “head” was a high-value area of water vapor convergence, which provided sufficient water vapor for the rainstorm. During the SWCV, the weakening of precipitation was due to the SWCV weakening gradually; plus, the ULJ was interrupted over the SB, the upper airflow presented downdrafts, and its superposition with the ascending branch of low-level vertical circulation. This airflow structure inhibited the development of strong upward motion, whilst at the same time, the LLJ retreated toward the south and the dew-point front ultimately weakened and disappeared. Subsequently, water vapor convergence weakened and no longer supported the occurrence of heavy rainfall. Therefore, the strong upward motion caused by the ULJ-LLJ intersection and the lower-level dew-point front were the key reasons for the occurrence of this late-autumn rainstorm.
Prevalence of Hypertension and Associated Factors in Dire Dawa City, Eastern Ethiopia: A Community-Based Cross-Sectional Study
Authors: Roba Hirbo Shore , Beyene Addisu Shunu , Mengesha Melkamu Merid , Ayele Behailu Hawulte
Published: May 2019

Background. Hypertension is a major cardiovascular risk factor that is linked with fatal complications and is an overwhelming global challenge. Primary prevention is a key to control hypertension with identification of major risk factors. This study was aimed at assessing the prevalence and factors associated with hypertension. Methods. Community-based cross-sectional study was conducted among 903 adults aged 25 to 64 years in Dire Dawa City, East Ethiopia. Data were collected using World Health Organization (WHO) STEPwise approach to Surveillance (STEPS) for non-communicable disease (NCD) standard survey tool. Multivariate logistic regression models were used to identify relative effects of distal, proximal, and immediate risk factors of hypertension, and all statistical tests were declared significantly at P-value<0.05. Results. The average SBP and DBP were 124.98±17.18 mmHg and 78.92±10.13 mmHg, respectively. The prevalence of hypertension was 24.43% (95% CI: 21.57, 27.28). Majority (51.64%) of adults were not aware of their elevated blood pressure status. hypertension was significantly associated with the age group 30-44 (aOR 3.61, 95% CI: 2.0, 6.55), 45-54 (aOR 5.36, 95% CI: 2.62, 10.91), and 55-64 (aOR 9.38, 95% CI: 4.73, 18.59), being unemployed (aOR 1.68, 95%CI: 1.03, 2.77), ever smoking (aOR 1.89, 95% CI: 1.04, 2.23), having abdominal obesity (aOR 1.72, 95% CI: 1.13, 2.64), and BMI≥25 kg/m2 (aOR 1.48, 95%CI: 1.01, 2.15). Conclusion. Moderately high prevalence of hypertension was observed among adults in study setting demonstrating a major public health problem. Majority of adults with hypertension in study setting were not aware of their elevated BP status highlighting the burden of the hidden morbidity and subsequent complications. Community level intervention and routine assessment of sociodemographic, behavioral, and biophysiological risk factors, screening, and diagnosis of NCDs should be institutionalized to address the occult burden.
Inhibition of Pyruvate Dehydrogenase Kinase Enhances the Antitumor Efficacy of Oncolytic Reovirus
Authors: Kennedy Barry E. , Murphy John Patrick , Clements Derek R. , Konda Prathyusha , Holay Namit , Kim Youra , Pathak Gopal P. , Giacomantonio Michael A. , Hiani Yassine El , Gujar Shashi
Published: May 2019

Oncolytic viruses (OV) such as reovirus preferentially infect and kill cancer cells. Thus, the mechanisms that dictate the susceptibility of cancer cells to OV-induced cytotoxicity hold the key to their success in clinics. Here, we investigated whether cancer cell metabolism defines its susceptibility to OV and if OV-induced metabolic perturbations can be therapeutically targeted. Using mass spectrometry–based metabolomics and extracellular flux analysis on a panel of cancer cell lines with varying degrees of susceptibility to reovirus, we found that OV-induced changes in central energy metabolism, pyruvate metabolism, and oxidative stress correlate with their susceptibility to reovirus. In particular, reovirus infection accentuated Warburg-like metabolic perturbations in cell lines relatively resistant to oncolysis. These metabolic changes were facilitated by oxidative stress–induced inhibitory phosphorylation of pyruvate dehydrogenase (PDH) that impaired the routing of pyruvate into the tricarboxylic acid cycle and established a metabolic state unsupportive of OV replication. From the therapeutic perspective, reactivation of PDH in cancer cells that were weakly sensitive for reovirus, either through PDH kinase (PDK) inhibitors dichloroacetate and AZD7545 or short hairpin RNA–specific depletion of PDK1, enhanced the efficacy of reovirus-induced oncolysis in vitro and in vivo. These findings identify targeted metabolic reprogramming as a possible combination strategy to enhance the antitumor effects of OV in clinics.

Significance:

This study proposes targeted metabolic reprogramming as a valid combinatorial strategy to enhance the translational efficacy of oncolytic virus–based cancer therapies.
Magnetic Resonance Imaging Is More Sensitive Than PET for Detecting Treatment-Induced Cell Death–Dependent Changes in Glycolysis
Authors: Hesketh Richard L. , Wang Jiazheng , Wright Alan J. , Lewis David Y. , Denton Alice E. , Grenfell Richard , Miller Jodi L. , Bielik Robert , Gehrung Marcel , Fala Maria , Ros Susana , Xie Bangwen , Hu De-en , Brindle Kevin M.
Published: May 2019

Metabolic imaging has been widely used to measure the early responses of tumors to treatment. Here, we assess the abilities of PET measurement of [18F]FDG uptake and MRI measurement of hyperpolarized [1-13C]pyruvate metabolism to detect early changes in glycolysis following treatment-induced cell death in human colorectal (Colo205) and breast adenocarcinoma (MDA-MB-231) xenografts in mice. A TRAIL agonist that binds to human but not mouse cells induced tumor-selective cell death. Tumor glycolysis was assessed by injecting [1,6-13C2]glucose and measuring 13C-labeled metabolites in tumor extracts. Injection of hyperpolarized [1-13C]pyruvate induced rapid reduction in lactate labeling. This decrease, which correlated with an increase in histologic markers of cell death and preceded decrease in tumor volume, reflected reduced flux from glucose to lactate and decreased lactate concentration. However, [18F]FDG uptake and phosphorylation were maintained following treatment, which has been attributed previously to increased [18F]FDG uptake by infiltrating immune cells. Quantification of [18F]FDG uptake in flow-sorted tumor and immune cells from disaggregated tumors identified CD11b+/CD45+ macrophages as the most [18F]FDG-avid cell type present, yet they represented <5% of the cells present in the tumors and could not explain the failure of [18F]FDG-PET to detect treatment response. MRI measurement of hyperpolarized [1-13C]pyruvate metabolism is therefore a more sensitive marker of the early decreases in glycolytic flux that occur following cell death than PET measurements of [18F]FDG uptake.

Significance:

These findings demonstrate superior sensitivity of MRI measurement of hyperpolarized [1-13C]pyruvate metabolism versus PET measurement of 18F-FDG uptake for detecting early changes in glycolysis following treatment-induced tumor cell death.
Progress in Understanding Complexity and Determinants of Immune-Related Prognostic Subsets in Primary Melanoma
Authors: Anichini Andrea
Published: May 2019

Gene signatures are increasingly being used to infer the immune composition of the tumor microenvironment. This strategy holds the promise for earlier detection, identification of patients at higher risk of progression, and for understanding therapeutic response and resistance to immunotherapy. This gene signature approach is now being integrated with information from genomic changes, gene networks, and master immunoregulatory genes, and this development can lead to identify the main determinants shaping the tumor immune landscape. A study in this issue of Cancer Research indicates a way forward to discover prognostic immune-related subsets in primary melanoma and to understand major determinants impairing protective immunity in early stage of disease.

See related article by Poźniak et al., p. 2684