bluuebunny/crossref_metadata_2025 huggingface dataset:
An exploration of the prevalence and experience of cardiac cachexia: protocol for a mixed methods cross-sectional study
Authors: Carson Matthew A. , Reid Joanne , Hill Loreena , Dixon Lana , Donnelly Patrick , Slater Paul , Hill Alyson , Fitzsimons Donna
Published: October 2019

Background

Cachexia is a complex and multifactorial syndrome defined as severe weight loss and muscle wasting which frequently goes unrecognised in clinical practice [1]. It is a debilitating syndrome, resulting in patients experiencing decreased quality of life and an increased risk of premature death; with cancer cachexia alone resulting in 2 million deaths per annum [2]. Most work in this field has focused on cancer cachexia, with cardiac cachexia being relatively understudied – despite its potential prevalence and impact in patients who have advanced heart failure. We report here the protocol for an exploratory study which will: 1. focus on determining the prevalence and clinical implications of cardiac cachexia within advanced heart failure patients; and 2. explore the experience of cachexia from patients’ and caregivers’ perspectives.

Methods

A mixed methods cross-sectional study. Phase 1: A purposive sample of 362 patients with moderate to severe heart failure from two Trusts within the United Kingdom will be assessed for known characteristics of cachexia (loss of weight, loss of muscle, muscle mass/strength, anorexia, fatigue and selected biomarkers), through basic measurements (i.e. mid-upper arm circumference) and use of three validated questionnaires; focusing on fatigue, quality of life and appetite. Phase 2: Qualitative semi-structured interviews with patients (n = 12) that meet criteria for cachexia, and their caregivers (n = 12), will explore their experience of this syndrome and its impact on daily life. Interviews will be digitally recorded and transcribed verbatim, prior to qualitative thematic and content analysis. Phase 3: Workshops with key stakeholders (patients, caregivers, healthcare professionals and policy makers) will be used to discuss study findings and identify practice implications to be tested in further research.

Discussion

Data collected as part of this study will allow the prevalence of cardiac cachexia in a group of patients with moderate to severe heart failure to be determined. It will also provide a unique insight into the implications and personal experience of cardiac cachexia for both patients and carers. It is hoped that robust quantitative data and rich qualitative perspectives will promote crucial clinical discussions on implications for practice, including targeted interventions to improve patients’ quality of life where appropriate.
Pathogenicity of egg-type duck-origin isolate of Tembusu virus in Pekin ducklings
Authors: Liang Te , Liu Xiaoxiao , Qu Shenghua , Lv Junfeng , Yang Lixin , Zhang Dabing
Published: October 2019

Background

Tembusu virus (TMUV) usually affects adult ducks, causing a severe drop of egg production. It has also been shown to be pathogenic in commercial Pekin ducklings below 7 weeks of age. Here, we report a TMUV-caused neurological disease in young egg-type ducklings and the pathogenicity of the egg-type duck-origin TMUV isolates in meat-type Pekin ducklings.

Results

The disease occurred in 25 to 40-day-old Jinding ducklings in China, and was characterized by paralysis. Gross lesions were lacking and microscopic lesions appeared chiefly in brain and spleen. Inoculation in embryonated duck eggs resulted in isolation of TMUV Y and GL. The clinical signs and microscopic lesions observed in the spontaneously infected egg-type ducks were repeated in Pekin ducklings by experimental infection. Notably, both Y and GL strains caused 100% mortality in the case of 2-day-old inoculation by intracerebral route. High mortalities (80 and 70%) also occurred following infection of the Y virus at 2 days of age by intramuscular route and at 9 days of age by intracerebral route.

Conclusions

These findings demonstrate that the egg-type duck-origin TMUVs exhibit high pathogenicity in Pekin ducklings, and that the severity of the disease in ducklings is dependent on the infection route and the age of birds at the time of infection. The availability of the highly pathogenic TMUV strains provides a useful material with which to begin investigations into the molecular basis of TMUV pathogenicity in ducks.
Yy1 regulates Senp1 contributing to AMPA receptor GluR1 expression following neuronal depolarization
Authors: Wu Tao , Donohoe Mary E.
Published: October 2019

Background

Neuronal activity-induced changes in gene expression patterns are important mediators of neuronal plasticity. Many neuronal genes can be activated or inactivated in response to neuronal depolarization. Mechanisms that activate gene transcription are well established, but activity-dependent mechanisms that silence transcription are less understood. It is also not clear what is the significance of inhibiting these genes during neuronal activity.

Methods

Quantitative Real Time-PCR, western blot and immunofluorescence staining were performed to examine the expression of Senp1 and GluR1 in mouse cortical neurons. The alterations of Yy1 phosphorylation upon neuronal depolarization and the interaction of Yy1 with Brd4 were studied by protein co-immunoprecipitation. The regulators of Yy1 phosphorylation were identified by phosphatase inhibitors. Chromatin immunoprecipitation, in vitro DNA binding assay, luciferase assay and gene knockdown experiments were used to validate the roles of Yy1 and its phosphorylation as well as Brd4 in regulating Senp1 expression.

Results

We report that neuronal depolarization deactivates the transcription of the SUMO protease Senp1, an important component regulating synaptic transmission, scaling, and plasticity, through Yy1. In un-stimulated neurons, Senp1 transcription is activated by a Yy1-Brd4 transcription factor protein complex assembled on the Senp1 promoter. Upon membrane depolarization, however, Yy1 is dephosphorylated and the Yy1-Brd4 complex is evicted from the Senp1 promoter, reducing Senp1 transcription levels. Both Yy1 and Senp1 promote the expression of AMPA receptor subunit GluR1, a pivotal component in learning and memory.

Conclusions

These results reveal an axis of Yy1/Brd4-Senp1 which regulates the expression of GluR1 during neuronal depolarization. This implicates a regulation mechanism in silencing gene expression upon neuronal activity.
Evaluation of left ventricular remodelling in young Afro-Caribbean athletes
Authors: Galanti Giorgio , Toncelli Loira , Tosi Benedetta , Orlandi Melissa , Giannelli Chiara , Stefani Laura , Mascherini Gabriele , Modesti Pietro A.
Published: October 2019

Background

Cardiac adaptation to intense physical training is determined by many factors including age, gender, body size, load training and ethnicity. Despite the wide availability of ECG analysis, with a higher presence of abnormalities in different races, echocardiographic studies on young Afro-Caribean (AA) and Caucasian athletes (CA) are lacking in literature. We aimed to assess the effect in the secondary LV remodelling of load training in young AA players compared to matched CA players.

Method

Seventy-seven AA and 53 CA matched soccer players (mean age 17.35 ± 0.50 and 18.25 ± 0.77 y) were enrolled. They were evaluated with echocardiography. A subgroup of 30 AA and 27 CA were followed up for a period of 4 years. The myocardial contractile function was evaluated by speckle-tracking echocardiographic global longitudinal strain (GLS).

Results

No significant differences were found in weight and height and in blood pressure response to maximal ergometer test in either group. In AA a higher level of LV remodelling, consisting in higher LV wall thickness, higher interventricular septum (IVS) and posterior wall (PW) thickness were found (IVS: 10.04 ± 0.14 and 9.35 ± 0.10 in AA and CA respectively, p < 0.001. PW: 9.70 ± 0.20 and 9.19 ± 0.10 mm in AA and CA respectively, p < 0.05). Strain data showed no significant differences between the two groups (22.35 ± 0.48 and 23.38 ± 0.69 in AA (n = 27) and CA (n = 25), respectively). At the beginning of the follow-up study AA showed a significantly higher left ventricular remodelling (IVS = 9.29 ± 0.3 and 8.53 ± 0.12 mm in AA and CA respectively, p < 0.002. PW = 9.01 ± 0.2 and 8.40 ± 0.20 in AA and CA respectively, p = 0.1). During the next four years of follow-up we observed a regular parallel increase in LV wall thickness and chamber diameters in both groups, proportionally to the increase in body size and LV mass. (IVS = 10.52 ± 0.17 and 9.03 ± 0.22 mm in AA and CA respectively, p < 0.001. PW: 10.06 ± 0.17 and 8.26 ± 0.19 mm in AA and CA respectively, p < 0.001).

Conclusion

The study shows that the ventricular remodelling observed in AA appears to be a specific phenotype already present in pre-adolescence. These data also suggest that genetic/ethnic factors play a central role in left ventricular remodelling during the first years of life in elite athletes.
Activated spinal astrocytes contribute to the later phase of carrageenan-induced prostatitis pain
Authors: Deng Guo-Chuang , Lu Ming , Zhao Ya-Yu , Yuan Ying , Chen Gang
Published: October 2019

Background

Prostatodynia is the main symptom of chronic prostatitis and the main reason that patients go to the hospital for treatment. Although a variety of factors, including inflammatory immune response, nervous system sensitization, and psychological factors, have been shown to play important roles in the induction and development of chronic pain in prostatitis, the underlying cause of chronic prostatodynia maintenance in prostatitis patients remains unclear.

Methods

A mouse model of chronic prostatitis induced by carrageenan injection was used. The von Frey test was used to measure pain behavior. The microglial and astrocyte activations were immunohistochemically demonstrated with antibodies against Iba1 and GFAP. The expression of cytokine or signaling pathway was detected by enzyme-linked immunosorbent assay (ELISA) and Western blotting.

Results

In this study, we provide several lines of evidence to demonstrate that activated spinal astrocytes contribute to the later phase (5 weeks after carrageenan injection) of carrageenan-induced prostatitis pain. First, activation of spinal astrocytes but not microglia was found in the spinal cord dorsal horn at 5 weeks. Second, intrathecal injection of the astroglial toxin L-2-Aminoadipate acid (L-AA) but not microglial inhibitor minocycline reduced mechanical allodynia at 5 weeks. Third, chronic prostatitis induced a profound and persistent upregulation of connexin-43 hemichannels in spinal astrocytes, and spinal injection of the connexin-43 inhibitor carbenoxolone (CBX) effectively reduced pain symptoms. Fourth, increased expression and release of chemokine C-X-C motif ligand 1 (CXCL1) in the spinal dorsal horn and intrathecal injection of a CXCL1 neutralizing antibody or the CXCR2 (a major receptor of CXCL1) antagonist SB225002 significantly reduced mechanical allodynia at 5 weeks.

Conclusions

In this study, we found that a novel mechanism of activated spinal astrocytes plays a crucial role in maintaining chronic prostatitis-induced persistent pain via connexin-43-regulated CXCL1 production and secretion.
Traumatic injury in female Drosophila melanogaster affects the development and induces behavioral abnormalities in the offspring
Authors: Chauhan Ved , Chauhan Abha
Published: October 2019

Traumatic injury (TI) during pregnancy increases the risk for developing neurological disorders in the infants. These disorders are a major concern for the well-being of children born after TI during pregnancy. TI during pregnancy may result in preterm labor and delivery, abruptio placentae, and/or fetomaternal hemorrhage. Drosophila melanogaster (fruit fly) is a widely used model to study brain and behavioral disorders in humans. In this study, we analyzed the effects of TI to female fruit flies on the development timing of larvae, social interaction and the behavior of offspring flies. TI to the female flies was found to affect the development of larvae and the behavior of offspring flies. There was a significant increase in the length of larvae delivered by traumatically injured maternal flies as compared to larvae from control maternal flies (without TI). The pupae formation from larvae, and the metamorphosis of pupae to the first generation of flies were faster in the TI group than the control group. Negative geotaxis and distance of the fly to its nearest neighbor are parameters of behavioral assessment in fruit flies. Negative geotaxis significantly decreased in the first generation of both male (p = 0.0021) and female (p = 0.0426) flies. The distance between the first generation of flies to its nearest neighbor was shorter in both male and female offspring flies in the TI group as compared to control group flies. These results indicate that TI to the female flies affected the development of larvae and resulted in early delivery, impaired social interaction and behavioral alterations in the offspring.
Positive drug test trends in fatally-injured drivers in the United States from 2007 to 2017
Authors: Azagba Sunday , Latham Keely , Shan Lingpeng , Qeadan Fares
Published: October 2019

Background

The last two decades have seen tremendous changes in the U.S. environment surrounding drugs. Driving under the influence of drugs is a growing public health hazard. The present study examined trends in drug involvement in fatally-injured drivers in the U.S.

Methods

Data were drawn from the 2007–2017 Fatality Analysis Reporting System. Cochran–Armitage tests were performed to assess the statistical significance of changes in the yearly prevalence of positive drug tests in fatally-injured drivers over time. In addition, analyses were stratified by sex, race, and age.

Results

The yearly prevalence of positive drug tests in fatally-injured drivers increased significantly from 20.7% in 2007 to 30.7% in 2017, with results showing a higher prevalence among males, those aged 21–44, and Whites. The gap between Blacks and Whites narrowed in 2017. There was a decline in the yearly prevalence in all age groups between 2016 and 2017, although the decrease in the 21–44 age group was much smaller than other age groups. Among drivers who tested positive for drugs, 34.6% had a blood alcohol concentration (BAC) above the threshold of per se evidence for impaired driving, and 63% had a BAC below the threshold.

Conclusions

Our results indicate that the overall yearly prevalence of fatally-injured drivers who tested positive for drugs increased significantly from 2007 to 2017, with similar results found for subgroups. Findings further highlight that drugged driving remains a public health priority, and more action is needed to stem this disturbing trend.
Effects of the Bragg peak degradation due to lung tissue in proton therapy of lung cancer patients
Authors: Baumann Kilian-Simon , Flatten Veronika , Weber Uli , Lautenschläger Stefan , Eberle Fabian , Zink Klemens , Engenhart-Cabillic Rita
Published: October 2019

Purpose

To quantify the effects of the Bragg peak degradation due to lung tissue on treatment plans of lung cancer patients with spot scanning proton therapy and to give a conservative approximation of these effects.

Methods and materials

Treatment plans of five lung cancer patients (tumors of sizes 2.7–46.4 cm3 at different depths in the lung) were optimized without consideration of the Bragg peak degradation. These treatment plans were recalculated with the Monte Carlo code TOPAS in two scenarios: in a first scenario, the treatment plans were calculated without including the Bragg peak degradation to reproduce the dose distribution predicted by the treatment-planning system (TPS). In a second scenario, the treatment plans were calculated while including the Bragg peak degradation. Subsequently, the plans were compared by means of Dmean, D98% and D2% in the clinical target volume (CTV) and organs at risk (OAR). Furthermore, isodose lines were investigated and a gamma index analysis was performed.

Results

The Bragg peak degradation leads to a lower dose in the CTV and higher doses in OARs distal to the CTV compared to the prediction from the TPS. The reduction of the mean dose in the CTV was − 5% at maximum and − 2% on average. The deeper a tumor was located in the lung and the smaller its volume the bigger was the effect on the CTV. The enhancement of the mean dose in OARs distal to the CTV was negligible for the cases investigated.

Conclusions

Effects of the Bragg peak degradation due to lung tissue were investigated for lung cancer treatment plans in proton therapy. This study confirms that these effects are clinically tolerable to a certain degree in the current clinical context considering the various more critical dose uncertainties due to motion and range uncertainties in proton therapy.
Sahaj Samadhi meditation vs a Health Enhancement Program in improving late-life depression severity and executive function: study protocol for a two-site, randomized controlled trial
Authors: Peckham Stephen Benjamin , Ionson Emily , Nassim Marouane , Ojha Kevin , Palaniyappan Lena , Gati Joe , Thebérge Jean , Lazosky Andrea , Speechley Mark , Barušs Imants , Rej Soham , Vasudev Akshya
Published: October 2019

Background

Recent estimates suggest an 11% prevalence of current late-life depression (LLD) and a lifetime prevalence of 16–20%. LLD leads to cognitive disturbance as well as a nearly two to three times increased risk of dementia. We conducted a recent randomized controlled trial (RCT) which demonstrated that Sahaj Samadhi meditation (SSM), an easy-to-implement, meditation-based augmentation strategy, led to higher rates of symptom remission when compared to treatment as usual (40.0 vs 16.3%; odds ratio, 3.36; 95% CI 1.06–10.64; p = 0.040). Here we present a protocol describing a two-site, blinded, RCT, comparing an SSM arm to an active-control arm – a Health Enhancement Program (HEP) intervention – in their ability to reduce depressive symptoms and improve executive functioning, among several other exploratory outcomes.

Methods/design

One hundred and ninety-two (n = 192) participants with LLD will be recruited at two sites (London, ON, Canada, and Montreal, QC, Canada). Participants will undergo stratified randomization with regards to site and the presence of treatment-resistant-LLD (TR-LLD) or not, to either SSM or HEP. We will assess change in (1) depression severity using the Hamilton Depression Rating Scale (HAM-D), (2) executive functioning, and (3) other exploratory physiological and mood-based measures, at baseline (0 weeks), post intervention (12 weeks), and 26 weeks after baseline. Raters, clinicians, and care providers will be blinded to group allocation while participants will be blinded to the study hypotheses.

Discussion

This study should more definitively assess whether SSM can be used as an augmentation strategy in routine clinical care for patients suffering from LLD and TR-LLD. If the effects of SSM are significantly better than HEP, it will offer support for the routine use of this intervention to manage LLD/TR-LLD and comorbid declines in executive dysfunction. The results of this study could also inform whether SSM can improve/prevent cognitive decline in LLD.

Trial registration

ClinicalTrials.gov, ID: NCT03564041. Registered on 20 June 2018.
Midlife physical activity is associated with lower incidence of vascular dementia but not Alzheimer’s disease
Authors: Hansson Oskar , Svensson Martina , Gustavsson Anna-Märta , Andersson Emelie , Yang Yiyi , Nägga Katarina , Hållmarker Ulf , James Stefan , Deierborg Tomas
Published: October 2019

Background

Physical activity might reduce the risk of developing dementia. However, it is still unclear whether the protective effect differs depending on the subtype of dementia. We aimed to investigate if midlife physical activity affects the development of vascular dementia (VaD) and Alzheimer’s disease (AD) differently in two large study populations with different designs.

Methods

Using a prospective observational design, we studied whether long-distance skiers of the Swedish Vasaloppet (n = 197,685) exhibited reduced incidence of VaD or AD compared to matched individuals from the general population (n = 197,684) during 21 years of follow-up (median 10, interquartile range (IQR) 5–15 years). Next, we studied the association between self-reported physical activity, stated twice 5 years apart, and incident VaD and AD in 20,639 participants in the Swedish population-based Malmo Diet and Cancer Study during 18 years of follow-up (median 15, IQR 14–17 years). Finally, we used a mouse model of AD and studied brain levels of amyloid-β, synaptic proteins, and cognitive function following 6 months of voluntary wheel running.

Results

Vasaloppet skiers (median age 36.0 years [IQR 29.0–46.0], 38% women) had lower incidence of all-cause dementia (adjusted hazard ratio (HR) 0.63, 95% CI 0.52–0.75) and VaD (adjusted HR 0.49, 95% CI 0.33–0.73), but not AD, compared to non-skiers. Further, faster skiers exhibited a reduced incidence of VaD (adjusted HR 0.38, 95% CI 0.16–0.95), but not AD or all-cause dementia compared to slower skiers. In the Malmo Diet and Cancer Study (median age 57.5 years [IQR 51.0–63.8], 60% women), higher physical activity was associated with reduced incidence of VaD (adjusted HR 0.65, 95% CI 0.49-0.87), but not AD nor all-cause dementia. These findings were also independent ofAPOE-ε4 genotype. In AD mice, voluntary running did not improve memory, amyloid-β, or synaptic proteins.

Conclusions

Our results indicate that physical activity in midlife is associated with lower incidence of VaD. Using three different study designs, we found no significant association between physical activity and subsequent development of AD.
Spatial time-frequency distribution of cross term-based direction-of-arrival estimation for weak non-stationary signal
Authors: Shao Shuai , Liu Aijun , Yu Changjun , Yang Hongjuan , Li Yong , Li Bo
Published: October 2019

In the radar array signal processing direction of arrival (DOA), the estimation of weak non-stationary signal is an important and difficult problem when both strong and weak signals are coexisting particularly because the weak non-stationary signals are often submerged in noise. In this paper, we proposed a novelty method to estimate the direction of arrival (DOA) of weak non-stationary signal in scenario for strong non-stationary interference signals and Gaussian white noise. The method utilizes spatial time-frequency distribution (STFD) of cross terms rather than suppressing cross terms in time-frequency analysis. The STFD of cross terms are introduced as an alternative matrix, which is similar to data covariance matrix in multiple signal classification (MUSIC), for the DOA estimation of a weak non-stationary signal. The cross-term amplitude of the strong and weak signals is usually above the noise and is easier to use than the auto-term of the weak signal. In the cross term, the information of the weak signal is included, and the auto-term of these weak signals is difficult to extract directly. The ability to incorporate the STFD of cross terms empowers information about a weak non-stationary signal for DOA estimation, leading to improved signal estimates for direction finding. The method based on the STFD of cross terms for DOA estimation of the weak non-stationary signal is revealed to outperform the time-frequency MUSIC and traditional MUSIC algorithm by simulation, respectively. This method has the advantages of the time-frequency direction finding method and also deals with the situation of weak signals. When the strong and weak signals exist at the same time and the two angles are similar, the cross-terms can be used to perform DOA estimation on the weak signal.
Green’s function homotopy perturbation method for the initial-boundary value problems
Authors: Sawangtong Wannika , Sawangtong Panumart
Published: October 2019

This article deals with the novel method for finding solutions for the initial-boundary value problems (IBVPs), which is called the Sawangtong’s Green function homotopy perturbation method, shortly called SGHPM. The SGHPM is a method which combines the homotopy perturbation method with Green’s function method. The convergence analysis for the SGHPM is shown. Furthermore, some examples are presented to illustrate the validity of the proposed method and to ensure that SGHPM is a technique which is powerful and efficient for finding approximate analytic solutions of IBVPs.
Multispectral coherence: Which decomposition should we use?
Authors: Lyu Bin , Qi Jie , Li Fangyu , Hu Ying , Zhao Tao , Verma Sumit , Marfurt Kurt J.
Published: October 2019

Seismic coherence is commonly used to delineate structural and stratigraphic discontinuities. We generally use full-bandwidth seismic data to calculate coherence. However, some seismic stratigraphic features may be buried in this full-bandwidth data but can be highlighted by certain spectral components. Due to thin-bed tuning phenomena, discontinuities in a thicker stratigraphic feature may be tuned and thus better delineated at a lower frequency, whereas discontinuities in the thinner units may be tuned and thus better delineated at a higher frequency. Additionally, whether due to the seismic data quality or underlying geology, certain spectral components exhibit higher quality over other components, resulting in correspondingly higher quality coherence images. Multispectral coherence provides an effective tool to exploit these observations. We have developed the performance of multispectral coherence using different spectral decomposition methods: the continuous wavelet transform (CWT), maximum entropy, amplitude volume technique (AVT), and spectral probe. Applications to a 3D seismic data volume indicate that multispectral coherence images are superior to full-bandwidth coherence, providing better delineation of incised channels with less noise. From the CWT experiments, we find that providing exponentially spaced CWT components provides better coherence images than equally spaced components for the same computation cost. The multispectral coherence image computed using maximum entropy spectral voices further improves the resolution of the thinner channels and small-scale features. The coherence from AVT data set provides continuous images of thicker channel boundaries but poor images of the small-scale features inside the thicker channels. Additionally, multispectral coherence computed using the nonlinear spectral probes exhibits more balanced and reveals clear small-scale geologic features inside the thicker channel. However, because amplitudes are not preserved in the nonlinear spectral probe decomposition, noise in the noisier shorter period components has an equal weight when building the covariance matrix, resulting in increased noise in the generated multispectral coherence images.
Gluco-Metabolic Effects of Pharmacotherapy-Induced Modulation of Bile Acid Physiology
Authors: Brønden Andreas , Knop Filip K
Published: October 2019

Context

The discovery and characterization of the bile acid specific receptors farnesoid X receptor (FXR) and Takeda G protein-coupled receptor 5 (TGR5) have facilitated a wealth of research focusing on the link between bile acid physiology and glucose metabolism. Modulation of FXR and TGR5 activation have been demonstrated to affect the secretion of glucagon-like peptide 1, insulin, and glucagon as well as energy expenditure and gut microbiota composition, with potential beneficial effects on glucose metabolism.

Evidence Acquisition

A search strategy based on literature searches in on PubMed with various combinations of the key words FXR, TGR5, agonist, apical sodium-dependent bile acid transporter (ASBT), bile acid sequestrant, metformin, and glucose metabolism has been applied to obtain material for the present review. Furthermore, manual searches including scanning of reference lists in relevant papers and conference proceedings have been performed.

Evidence Synthesis

This review provides an outline of the link between bile acid and glucose metabolism, with a special focus on the gluco-metabolic impact of treatment modalities with modulating effects on bile acid physiology; including FXR agonists, TGR5 agonists, ASBT inhibitors, bile acid sequestrants, and metformin.

Conclusions

Any potential beneficial gluco-metabolic effects of FXR agonists remain to be established, whereas the clinical relevance of TGR5-based treatment modalities seems limited because of substantial safety concerns of TGR5 agonists observed in animal models. The glucose-lowering effects of ASBT inhibitors, bile acid sequestrants, and metformin are at least partly mediated by modulation of bile acid circulation, which might allow an optimization of these bile acid–modulating treatment modalities. (J Clin Endocrinol Metab 106: 362–373, 2020)
Elagolix Suppresses Ovulation in a Dose-Dependent Manner: Results From a 3-Month, Randomized Study in Ovulatory Women
Authors: Archer David F , Ng Juki , Chwalisz Kristof , Chiu Yi-Lin , Feinberg Eve C , Miller Charles E , Feldman Robert A , Klein Cheri E
Published: October 2019

Context

Elagolix is an oral gonadotropin-releasing hormone (GnRH) antagonist recently approved for the treatment of endometriosis-associated pain and being developed for heavy menstrual bleeding associated with uterine fibroids.

Objective

The objective was to evaluate the effects of elagolix on ovulation and ovarian sex hormones.

Design and Setting

This was a randomized, open-label, multicenter study.

Participants

Participants were healthy ovulatory women aged 18 to 40 years.

Interventions

Elagolix was administered orally for 3 continuous 28-day dosing intervals at 100 to 200 mg once daily (QD), 100 to 300 mg twice daily (BID), and 300 mg BID plus estradiol/norethindrone acetate (E2/NETA) 1/0.5 mg QD.

Main Outcome Measures

The main outcomes measures were ovulation rates measured by transvaginal ultrasound, progesterone concentrations, and hormone suppression.

Results

Elagolix suppressed ovulation in a dose-dependent manner. The percentage of women who ovulated was highest at 100 mg QD (78%), intermediate at 150 and 200 mg QD and 100 mg BID (47%–57%), and lowest at 200 and 300 mg BID (32% and 27%, respectively). Addition of E2/NETA to elagolix 300 mg BID further suppressed the ovulation rate to 10%. Elagolix also suppressed luteinizing hormone and follicle stimulating hormone in a dose-dependent manner, leading to dose-dependent suppression of estradiol and progesterone. Elagolix had no effect on serum biomarker of ovarian reserve, and reduced endometrial thickness compared to the screening cycle.

Conclusion

Women being treated with elagolix may ovulate and should use effective methods of contraception. The rate of ovulation was lowest with elagolix 300 mg BID plus E2/NETA 1/0.5 mg QD.
Point-of-Care Thromboelastography for Intrathecal Drain Management in Patients With Coagulopathy and Thoracic Aorta Surgery: A Case Report
Authors: Bortman Jeffrey , Chaudhry Omar , Sharkey Aidan , Sohail Mahad , Bose Ruma , Matyal Robina
Published: October 2019

Spinal drain placement to prevent spinal cord ischemia during thoracic aorta surgery is a necessary yet complex undertaking in patients with coagulopathies. Thromboelastography (TEG) can be used as a point-of-care management tool to monitor coagulation status before drain placement and removal. We present 2 cases: a case of a patient with factor VII deficiency and a case of a patient with thrombocytopenia for whom TEG was an important procedural adjunct during coagulopathy reversal. TEG parameters are also discussed to encourage more frequent TEG use as an adjunct during these complex cases.
Condensin II protein dysfunction impacts mitochondrial respiration and stress response
Authors: Deutschman Emily , Ward Jacqueline R. , Kumar Avinash , Ray Greeshma , Welch Nicole , Lemieux Madeleine E. , Dasarathy Srinivisan , Longworth Michelle S.
Published: October 2019

The maintenance of mitochondrial respiratory function and homeostasis is essential to human health. Here, we identify Condensin II subunits as novel regulators of mitochondrial respiration and stress response. Condensin II is present in the nucleus and cytoplasm. While the effects of Condensin II depletion on nuclear genome organization are well-studied, effects on essential cytoplasmic and metabolic processes are not as well understood. Excitingly, we observe that Condensin II Chromosome Associated Protein (CAP) subunits individually localize to different regions of mitochondria, suggesting possible mitochondrial-specific functions independent from the canonical Condensin II holocomplex. Changes in cellular ATP levels and mitochondrial respiration are observed in Condensin II CAP subunit-deficient cells. Surprisingly, we find that loss of NCAPD3 also sensitizes cells to oxidative stress. Together, these studies identify new, and possibly independent, roles for Condensin II CAP subunits in preventing mitochondrial damage and dysfunction. These findings reveal a new area of Condensin protein research that could contribute to the identification of targets to treat diseases where aberrant function of Condensin II proteins is implicated.
Exercise and Executive Function during Follicular and Luteal Menstrual Cycle Phases
Authors: DIRK KENNEDY LAINE , BELFRY GLEN ROBERT , HEATH MATTHEW
Published: October 2019

Purpose

A single bout of aerobic or resistance exercise improves executive function. We sought to determine whether menstrual cycle variations in ovarian hormone concentrations differentially influence the expression and/or magnitude of a postexercise executive benefit.

Methods

Eumenorrheic female participants completed 20-min single bouts of aerobic exercise (via cycle ergometer) at a moderate intensity (i.e., 80% of estimated lactate threshold) during the early follicular and midluteal phases of their menstrual cycle. Pre- and postexercise executive function was examined via antisaccades—an executive task requiring a saccade mirror-symmetrical to a visual stimulus. Antisaccades are an ideal tool for examining postexercise executive changes because the task is mediated via the same frontoparietal networks as modified following single-bout and chronic exercise.

Results

Antisaccade reaction times decreased from the pre- to postexercise assessments by an average of 22 ms (P = 0.003), and this benefit was independent of changes in directional errors or end point accuracy (P’s > 0.26). In other words, participants did not decrease their postexercise reaction times at the cost of increased planning times or execution errors. Most notably, the postexercise antisaccade benefit did not vary in magnitude across follicular or luteal phases (P = 0.33) and a two one-sided test statistic (i.e., equivalence testing) provided support for the null hypothesis (P = 0.008).

Conclusions

A postexercise executive benefit is independent of hormonal variations in the menstrual cycle. Further, our results evince that the phase of a female participant’s menstrual cycle should not be a limiting factor in determining their inclusion in exercise neuroscience research.
DETERMINANTS OF TRANSPORT COMPANY VALUE AND THE SELECTION OF VALUATION METHODS
Authors: Adámiková Eva , Čorejová Tatiana , Môcová Lenka
Published: October 2019

The development of a company significantly influences its final value. The value of a transport company can be determined for various legal acts, which also influence the selection of valuation methods. The view of the transport company may differ, depending on whether it is seen by investors or the company owners. Methods of evaluating a transport company, but also of all companies in expert practice, usually follow methodological procedures outlined in the legal standards. These methods are based on basic principles, namely the asset principle, the yield principle, the combined principle, and the market principle. These principles also include other methods of determining the company's value. Each method has its own specifics, a modification of only one model parameter changes the entire company value. The aim of this paper is to analyze the input data and their impact on the value of the transport company from the perspective of various methods. The paper shows the impact of the change in the rate of capitalization and g - the sustainable growth rate and the significant impact of the continuing value on the general value of the company.
THE INTERRELATION AND INTERACTION OF FINANCIAL MARKETS WITH FINANCIAL CYCLES OF THE NATIONAL ECONOMY OF RUSSIA
Authors: Barkhatov Viktor , Lymar Ekaterina , Koptelov Ivan
Published: October 2019

A market economy assumes the circularity of economic development. Many scholars have speculated on the existing relationship between economic and financial cycles. The emergence of financial markets in the early 20th century gave impetus to the development of the theory of financial cycles which account for financial ups and downs similarly with economic cycles. One of the most impactful areas of research of current trends in financial cycles is the study of how these are influenced by contemporary financial market tools, as this will help determine whether the basic phases of financial cycles can be reconciled.

This article aims at analyzing various aspects of the relationship and the interaction of financial markets with the financial cycles of the national economy in the context of the Russian Federation. We also give consideration to the behavior of the contemporary financial system’s chief players––large corporations, credit institutions, facilitating agencies, and state authorities acting as regulators of financial and economic cycles.
PROJECT MANAGEMENT AND ITS STRATEGIES IN GLOBAL ORGANISATION: CASE STUDY
Authors: Bočková Kateřina , Škoda Miroslav , Lengyelfalusy Tomáš
Published: October 2019

The goal of the presented paper is to compare the different approaches of the Novartis Global IT project management in its four divisions. The basics of the project management with the focus on the global or international project management are described in the theoretical part. There are highlighted the ways of projects´ monitoring and evaluation. The history and the evolution of the project management in the context of used methods and approaches in various time periods in the particular divisions of the Novartis Global group are described in the analytical part. The comparison is used through the identification of positives and negatives of the analysed IT project management parameters. Currently we underline the importance of the communication within and outside of the projects with emphasis on the cultural differences in global project management. The results of the comparison are becoming essential for the recommendation for future project management plans in the Novartis Global group.
PRICE–VOLUME DEPENDENCE OF BITCOIN AND ITS FRACTAL ANALYSIS
Authors: Bohdalová Mária , Greguš Michal
Published: October 2019

Nowadays Bitcoin as cryptocurrency takes a significant place on the global financial markets. This paper analyzes the Bitcoin closing prices and traded volume during the period from December 28, 2013 to January 22, 2019. This period is known as a period with rapid increasing of the Bitcoin closing prices, mainly in the second half of the year 2017. The aim of this paper is twofold. First, we compute the Hurst coefficient to discover the close price dynamics and traded volume using a fractal point of view. We have discovered an anti-persistent behavior in the traded volume and random character of bitcoin closing prices. Second, we propose an analysis of the relationship between the close prices and traded volume. Our findings show how changes in the high-price period differ from changes in the low-price period. We also found that high prices caused investors to be afraid to trade due to possible rapid decrease in bitcoin closing prices.
KNOWLEDGE SHARING IN BUSINESS NETWORKS FROM THE BUILDING INDUSTRY
Authors: Czapla Alina
Published: October 2019

Introduction: Both networking and knowledge management can give a company a competitive advantage. But the combination of these two approaches is particularly interesting. Knowledge sharing is crucial in the building industry, because it is changing all the time nowadays. The knowledge of new technologies and environmentally friendly building materials is especially important for companies from the construction industry. Also an average investor, who plans on building a house, has a very low level of knowledge about building materials and  modern building technologies. So it is not surprising, that there are some business networks in building industry, which use knowledge sharing in their strategy.

Objectives: The objective of this study is to explore the knowledge sharing in business networks from the building industry. Our research question is: what forms of knowledge sharing take place in the construction industry and what is the scale of this phenomenon.

Methods: The case study method was used to analyze one of the largest and fastest growing Polish business networks of small and medium-sized enterprises (SMEs) -  Grupa Polskie Składy Budowlane (PSB). The survey among the owners and managers was carried out, interviews, document studies and observations were used.

Results: Both the sharing of date and a large number of educational activities were observed in the studied business network. The vast majority of network members are engaged in these actions. Knowledge sharing in the building industry is implemented not only in relation to network partners and their employees but also in relation to customers.

Conclusions: A business network can use knowledge management to achieve its business goals. The educational aspects of this approach are especially interesting. The scale of this phenomenon in the building industry is much bigger than it might seem. The range of these educational actions can go beyond the formal boundaries of the network.
ENHANCING THE DESTINATION IMAGE THROUGH PROMOTING POPULAR RIVER CRUISE DESTINATIONS
Authors: Dimitrov Maksym , Zlatkova Stankova Mariya
Published: October 2019

The sector of cruise tourism is growing in both subdivisions: river and ocean cruises. The most popular river cruise destinations in Europe are connected with historical places around big rivers such as the Danube, Rhine, Volga and others. One cruise itinerary consists of several tourist destinations, well-known and unknown for the cruise tourist, and creates one tourist destination combined with different ports of call. The well-known ports of call such as Paris, Vienna, St. Petersburg are the main attraction for the tourists.

Among them there are some ports of calls which the tourist is not familiar with before visiting them. River cruise tourists have the opportunity to discover smaller cities in the chosen country or visit a new country as a tourist destination. For the areas where tourism is in a very early developing stage it is crucial to create a unique destination image which could influence the future choice of the tourists and bring them back.

The study focuses on the main objective of exploring the attitudes of tourists traveling on two European river cruise routes, their experience and satisfaction within the visited destinations. Тhe research has a scientifically applied character, outlining certain attitudes that would be of interest to the business operating on river cruise destinations. Research results show that popular cities are a pull factor for river cruise tourism. Integrating them into the tourism offer as part of the long-term tourism planning would bring benefits to the destination by contributing to the creation of a unique and attractive destination image and growing popularity.
MONETARY DISCRETION BY FISCAL MEANS: THE CASE OF BULGARIA
Authors: Dimitrov Preslav , Todorov Ivan , Tanchev Stoyan , Yurukov Petar
Published: October 2019

The specific design of the Bulgarian currency board arrangement (CBA), which provides an opportunity for the Bulgarian government to conduct discretionary monetary policy by changes in the fiscal reserve, was analyzed. The impact of government deposit fluctuations on the dynamics of reserve money and interbank interest rates was investigated. The hypotheses of an automatic adjustment mechanism and a liquidity effect under the Bulgarian currency board arrangement were tested. The methodology employed was a vector autoregression, which included the following variables: MB – monetary base; BP – the balance of payments; GD – government deposit on the balance sheet of the Issue Department of the Bulgarian National Bank; MRR – minimum required reserve ratio of commercial banks. The target variable was MB. Monthly data for the period of January 1998 - December 2018 were used. The study results did not provide evidence of a statistically significant impact of changes in government deposit on reserve money and interbank interest rates. The hypotheses for the existence of an automatic adjustment mechanism and a liquidity effect did not find an empirical confirmation.
OPTIMIZATION OF THE LOGISTICS NETWORK OF THE SELECTED ONLINE STORE
Authors: Dobroselskyi Mykhailo , Madleňák Radovan
Published: October 2019

The Internet serves as the main infrastructure for global shopping. For this purpose, the construction of an e-commerce logistics network is the main aspect of a successful existence in the virtual environment.

This paper analyses the logistics system of a company located in Ukraine. The core business of the company is selling diagnostic equipment for cars through an online store. The structure of the company consists of one warehouse and five branches. The company does not have its own fleet for the transportation of products from warehouse to branches or to end customers and it outsources the services of another logistics company.

The main goal of the paper is to optimize the existing logistics system of the product flow between the warehouse, branches and the final buyers of the online store.

At the end of the article, after optimizing the warehouse localization, we received a reduction in shipping costs by 23%. Also, an existing and optimized logistics network is compared in terms of speed and cost of transportation between warehouse, affiliates and end users.
DETERMINANTS AND DIRECTIONS OF THE TRANSITION FROM TRADITIONAL TO SUSTAINABLE AGRICULTURE: THE BULGARIAN CASE
Authors: Doitchinova Julia , Miteva Albena , Zaimova Darina
Published: October 2019

On the basis of a literature review, the directions for transition of agriculture from the productive to the post-productive model are presented. A methodological framework has been developed, including the directions of the transition and the indicators on which it can be assessed. On the basis of this implementation, the passage from quantity to production quality, to the sustainability of agriculture, to new business models based on multifunctionality are assessed. It turns out that the changes in Bulgarian agriculture cannot be assessed unambiguously. The transition to sustainability is accompanied by continued mechanization and digitization of technological processes. There is a simultaneous development of both the productive and the post-productive model of agriculture. Together with the increasing interest in organic production, the implementation of environmentally friendly practices and the implementation of ecosystem services, modernization based on computerization and chemisation continues.

The results are part of scientific project DN 15/8 2017 Sustainable multifunctional rural areas: reconsidering agricultural models and systems with increased demands and limited resources funded by the Bulgarian research fund.