bluuebunny/crossref_metadata_2025 huggingface dataset:
Combinatorial effect of nicotine and black tea on heart rate variability: Useful or harmful?
Authors: Joukar S. , Sheibani M.
Published: August 2017

The effect of nicotine on heart rate variability (HRV) is controversial. Autonomic nervous system is the main regulator of heart rhythm, and heart rate variability is an appropriate index to assessment of the effects of the autonomic system on heart.

In this study, the combination effect of nicotine and black tea consumption on sympatho‐vagal balance and heart rate variability was investigated in rats.

Male Wistar rats were randomized into four groups as control, tea (2.5 g/100 cc, daily), nicotine (2 mg/kg/d) and tea plus nicotine groups which treated for 28 days, and in the 29th day, their electrocardiograms (lead II) were recorded.

The mean of high‐frequency power (HF) in tea, nicotine and tea plus nicotine groups was significantly more than control group (P < .05), and low‐frequency power/high‐frequency power (LF/HF) ratio in the nicotine and tea + nicotine groups was significantly less than control group (P < .05). LF values did not differ significantly among groups. Mean of standard deviation of normal RR intervals (SDNN) and square root of the mean squared differences of successive RR intervals (RMSSD) increased significantly in tea, nicotine and tea + nicotine groups in comparison with control group (P < .05)

Overall, 4‐week administration of black tea, nicotine or their combination with dosages used in this study can increase the heart rate variability and improve the sympatho‐vagal balance in rat.
A multimethod computational simulation approach for investigating mitochondrial dynamics and dysfunction in degenerative aging
Authors: Hoffman Timothy E. , Barnett Katherine J. , Wallis Lyle , Hanneman William H.
Published: August 2017

Research in biogerontology has largely focused on the complex relationship between mitochondrial dysfunction and biological aging. In particular, the mitochondrial free radical theory of aging (MFRTA) has been well accepted. However, this theory has been challenged by recent studies showing minimal increases in reactive oxygen species (ROS) as not entirely deleterious in nature, and even beneficial under the appropriate cellular circumstances. To assess these significant and nonintuitive observations in the context of a functional system, we have taken an in silico approach to expand the focus of the MFRTA by including other key mitochondrial stress response pathways, as they have been observed in the nematode Caenorhabditis elegans. These include the mitochondrial unfolded protein response (UPRmt), mitochondrial biogenesis and autophagy dynamics, the relevant DAF‐16 and SKN‐1 axes, and NAD+‐dependent deacetylase activities. To integrate these pathways, we have developed a multilevel hybrid‐modeling paradigm, containing agent‐based elements among stochastic system‐dynamics environments of logically derived ordinary differential equations, to simulate aging mitochondrial phenotypes within a population of energetically demanding cells. The simulation experiments resulted in accurate predictions of physiological parameters over time that accompany normal aging, such as the declines in both NAD+ and ATP and an increase in ROS. Additionally, the in silico system was virtually perturbed using a variety of pharmacological (e.g., rapamycin, pterostilbene, paraquat) and genetic (e.g., skn‐1, daf‐16, sod‐2) schemes to quantitate the temporal alterations of specific mechanistic targets, supporting insights into molecular determinants of aging as well as cytoprotective agents that may improve neurological or muscular healthspan.
Cost‐effectiveness of emergency department‐initiated treatment for opioid dependence
Authors: Busch Susan H. , Fiellin David A. , Chawarski Marek C. , Owens Patricia H. , Pantalon Michael V. , Hawk Kathryn , Bernstein Steven L. , O'Connor Patrick G. , D'Onofrio Gail
Published: August 2017

Background and Aims

In a recent randomized trial, patients with opioid dependence receiving brief intervention, emergency department (ED)‐initiated buprenorphine and ongoing follow‐up in primary care with buprenorphine (buprenorphine) were twice as likely to be engaged in addiction treatment compared with referral to community‐based treatment (referral) or brief intervention and referral (brief intervention). Our aim was to evaluate the relative cost‐effectiveness of these three methods of intervening on opioid dependence in the ED.

Design

Measured health‐care use was converted to dollar values. We considered a health‐care system perspective and constructed cost‐effectiveness acceptability curves that indicate the probability each treatment is cost‐effective under different thresholds of willingness‐to‐pay for outcomes studied.

Setting

An urban ED in the United States.

Participants

Opioid‐dependent patients aged 18 years or older.

Measurements

Self‐reported 30‐day assessment data were used to construct cost‐effectiveness acceptability curves for patient engagement in formal addiction treatment at 30 days and the number of days illicit opioid‐free in the past week.

Findings

Considering only health‐care system costs, cost‐effectiveness acceptability curves indicate that at all positive willingness‐to‐pay values, ED‐initiated buprenorphine treatment was more cost‐effective than brief intervention or referral. For example, at a willingness‐to‐pay threshold of $1000 for 30‐day treatment engagement, we are 79% certain ED‐initiated buprenorphine is most cost‐effective compared with other studied treatments. Similar results were found for days illicit opioid‐free in the past week. Results were robust to secondary analyses that included patients with missing cost data, included crime and patient time costs in the numerator, and to changes in unit price estimates.

Conclusion

In the United States, emergency department‐initiated buprenorphine intervention for patients with opioid dependence provides high value compared with referral to community‐based treatment or combined brief intervention and referral.
Caledopsalta gen. nov., a new genus for the New Caledonian cicadas previously assigned to Pauropsalta Goding & Froggatt, plus the description of four new species (Hemiptera: Cicadoidea: Cicadidae)
Authors: Delorme Quentin
Published: August 2017

Species currently assigned to Pauropsalta Goding & Froggatt in New Caledonia are reviewed. Molecular and morphological studies indicate that New Caledonian cicadas placed in this genus belong in a different genus. The genus Caledopsalta gen. nov. is therefore erected to accommodate Caledopsalta johanae comb. nov., and Caledopsalta judithae. comb. nov., as well as the following four new species: Caledopsalta ouitchamboensis sp. nov., C. canteminvantum sp. nov., C. garrula sp. nov. and C. sciaphila sp. nov. Male calling songs of all species are analysed and described from field recordings. A key to the species of Caledopsalta gen. nov. is provided. This new genus is included within the tribe Cicadettini, with Pauropsalta johanae designated as the type species.
Atypical fibroxanthoma management: Recurrence, metastasis and disease‐specific death
Authors: Polcz Margit Marisa , Sebaratnam Deshan Frank , Fernández‐Peñas Pablo
Published: August 2017

Atypical fibroxanthoma (AFX) is a rare spindle cell neoplasm predominantly found on the head and neck of elderly individuals with sun‐damaged skin, with no evidence‐based guidelines for their management. A systematic retrospective review of the literature focusing on treatment modality found a recurrence and metastasis rate of 8.0% (5.6% when adjusted for incomplete excisions) and 0.5% for local excision and 4.6% and 3.2% for Mohs micrographic surgery, respectively. Our results suggest that with clear surgical margins, AFX is unlikely to recur and metastases are rare, with significantly higher rates in the immunosuppressed population.
Chinko/Mbari drainage basin represents a conservation hotspot for Eastern Derby eland in Central Africa
Authors: Brandlová Karolína , Gloneková Markéta , Hejcmanová Pavla , Jůnková Vymyslická Pavla , Aebischer Thierry , Hickisch Raffael , Mallon David
Published: August 2017

One of the largest of antelopes, Derby eland (Taurotragus derbianus), is an important ecosystem component of African savannah. While the western subspecies is Critically Endangered, the eastern subspecies is classified as least concern. Our study presents the first investigation of population dynamics of the Derby eland in the Chinko/Mbari Drainage Basin, Central African Republic, and assesses the conservation role of this population. We analysed data from 63 camera traps installed in 2012. The number of individuals captured within a single camera event ranged from one to 41. Herds were mostly mixed by age and sex, mean group size was 5.61, larger during the dry season. Adult (AD) males constituted only 20% of solitary individuals. The overall sex ratio (M:F) was 1:1.33, while the AD sex ratio shifted to 1:1.52, reflecting selective hunting pressure. Mean density ranged from 0.04 to 0.16 individuals/km2, giving an estimated population size of 445–1,760 individuals. Chinko harbours one of the largest documented populations of Derby eland in Central Africa, making Chinko one of its potential conservation hotspots.
Health professional students' rural placement satisfaction and rural practice intentions: A national cross‐sectional survey
Authors: Smith Tony , Sutton Keith , Pit Sabrina , Muyambi Kuda , Terry Daniel , Farthing Annie , Courtney Claire , Cross Merylin
Published: August 2017

Objective

The aim of this study was to profile students undertaking placements at University Departments of Rural Health (UDRHs) and investigate factors affecting students' satisfaction and intention to enter rural practice.

Design

Cross‐sectional survey comprising 21 core questions used by all UDRHs.

Setting

Eleven UDRHs across Australia that support students' placements in regional, rural and remote locations.

Participants

Medical, nursing and allied health students who participated in UDRH placements between July 2014 and November 2015 and completed the questionnaire.

Main outcome measures

Key dependent variables were placement satisfaction and rural practice intention. Descriptive variables were age, gender, Aboriginal or Torres Strait Islander (ATSI) background, location of placement, healthcare discipline, year of study and type and length of placement.

Results

A total of 3328 students responded. The sample was predominantly female (79%), the mean age was 26.0 years and 1.8% identified as ATSI. Most placements (69%) were >2 but ≤12 weeks, 80% were in Modified Monash 3, 4 or 5 geographical locations. Public hospitals and community health made up 63% of placements. Students satisfied with their placement had 2.33 higher odds of rural practice intention. Those satisfied with Indigenous cultural training, workplace supervision, access to education resources and accommodation had higher odds of overall satisfaction and post‐placement rural practice intention.

Conclusions

The majority of students were highly satisfied with their placement and the support provided by rural clinicians and the UDRHs. UDRHs are well placed to provide health professional students with highly satisfactory placements that foster rural practice intention.
Fertility preservation in women with borderline ovarian tumors – how does it impact disease outcome? A cohort study
Authors: Helpman Limor , Yaniv Assaf , Beiner Mario E. , Aviel‐Ronen Sarit , Perri Tamar , Ben‐Baruch Gilad , Hogen Ben‐David Liat , Jakobson‐Setton Ariella , Korach Jacob
Published: August 2017

Introduction

Borderline ovarian tumors are typically indolent neoplasms. Since many are diagnosed in younger women, fertility conservation is an important consideration and has been advocated based on retrospective data. The objective of this study was to identify features impacting on recurrence and survival in a series of borderline ovarian tumors, and to assess the safety of a fertility‐sparing approach.

Material and methods

A historical cohort study of consecutive borderline ovarian tumors cases treated at a single institution over 30 years (1981–2011). Data on surgical approach (fertility‐sparing or otherwise), disease stage, CA125 levels, histological features, adjuvant treatment and follow‐up data were collected. Recurrence and survival were assessed using the Kaplan–Meier method and associations with the variables of interest were evaluated using a multivariate Cox proportional hazards model.

Results

213 patients were included. Of 132 women age 40 years and below at diagnosis, 112 (85%) had a fertility‐sparing procedure and 60 (46%) had conservation of an involved ovary. Fifty patients (24%) developed recurrences; fertility preservation (hazard ratio = 2.57; 95% confidence interval 1.1–6; p = 0.029) and advanced stage (hazard ratio = 4.15; 95% confidence interval 2.3–7.6; p < 0.001) were independently associated with recurrence on multivariate analysis. Eleven (5%) patients died of their disease. Fertility preservation was not associated with compromised survival.

Conclusions

Borderline ovarian tumors carry a good prognosis overall. Fertility preservation is associated with a higher risk of disease relapse; however, as most relapses are localized and may be salvaged with surgical treatment, overall survival is not compromised.
Clusters of week‐specific maternal gestational weight gain pattern and their association with birthweight: an observational cohort study
Authors: Liang Huan , Yin Chuanmin , Dong Xinran , Acharya Ganesh , Li Xiaotian
Published: August 2017

Introduction

Gestational weight gain varies widely among different populations, and an inappropriate gestational weight gain is associated with adverse pregnancy outcomes. We aimed to investigate week‐specific serial changes in gestational weight gain in an urban Chinese population to derive clusters of gestational weight gain patterns and explore the impact of gestational weight gain patterns on birthweight.

Material and methods

This was an observational cohort study of 6130 women delivered at a university hospital in Shanghai, China. Pre‐pregnancy bodyweight, height, week‐specific and total gestational weight gain, pregnancy outcome and birthweight were extracted using electronic medical records. The association between gestational weight gain and gestational age was tested using linear regression, and week‐specific reference percentiles for gestational weight gain were calculated. Hierarchical clustering was used to derive gestational weight gain clusters. Mean birthweight among the clusters was compared using Dunnet's test.

Results

We found a significant linear association between gestational weight gain and gestational age (r = 0.56; p < 0.00001). Seven distinct clusters of gestational weight gain pattern were identified. The birthweight significantly correlated with gestational weight gain (r = 0.28; p < 0.00001). Compared with the cluster that had normal gestational weight gain throughout the pregnancy, the mean birthweight among the clusters that had abnormal gestational weight gain (inadequate or excessive) in the third trimester was significantly different (p < 0.001), but those who achieved normal gestational weight gain (between 5 and 95 percentile) in the third‐trimester had similar mean birthweight.

Conclusion

Women with abnormal gestational weight gain before the third‐trimester still had a fair chance of delivering a normal birthweight baby if their gestational weight gain was normal in the third‐trimester, suggesting that interventions started even late in pregnancy may have a positive effect on fetal growth.
Systematic review with meta‐analysis: enteral nutrition therapy for the induction of remission in paediatric Crohn's disease
Authors: Swaminath A. , Feathers A. , Ananthakrishnan A. N. , Falzon L. , Li Ferry S.
Published: August 2017

Background

Despite potential adverse‐events in a paediatric population, corticosteroids are used to induce remission in paediatric Crohn's disease. Exclusive enteral nutrition also induces remission, but is infrequently used in the USA because corticosteroids are considered the superior therapy. New data have become available since the publication of the most recent meta‐analysis in 2007.

Aim

To see if current literature supports the use of EEN versus CS in paediatric populations.

Methods

All studies with comparator arms of exclusive enteral nutrition and an exclusive corticosteroids, with remission clearly defined were identified by searching eight online databases.

Results

Of 2795 identified sources, nine studies met our inclusion criteria. Eight of these (n = 451), had data that could be abstracted into our meta‐analysis. Exclusive enteral nutrition was as effective as corticosteroids in inducing remission (OR = 1.26 [95% CI 0.77, 2.05]) in paediatric Crohn's disease. There was no difference between Exclusive enteral nutrition and corticosteroids efficacy when comparing newly diagnosed Crohn's (OR = 1.61 [95% CI .87, 2.98]) or relapsed (OR = 0.76 [95% CI .29‐1.98]). Intestinal healing was significantly more likely among patients receiving Exclusive enteral nutrition compared to corticosteroids (OR = 4.5 [95% CI 1.64, 12.32]). There was no difference in the frequency of biomarker normalisation including CRP (OR = 0.85 [95% CI .44, 1.67]) and faecal calprotectin (OR 2.79 [95% CI .79‐10.90]).

Conclusions

There is no difference in efficacy between exclusive enteral nutrition and corticosteroids in induction of remission in Crohn's disease in a paediatric population. Exploratory analyses suggest that a greater proportion of patients treated with exclusive enteral nutrition achieved mucosal healing.
Lenalidomide as second‐line therapy for advanced hepatocellular carcinoma: exploration of biomarkers for treatment efficacy
Authors: Shao Y.‐Y. , Chen B.‐B. , Ou D.‐L. , Lin Z.‐Z. , Hsu C.‐H. , Wang M.‐J. , Cheng A.‐L. , Hsu C.
Published: August 2017

Background

Lenalidomide has immunomodulatory and anti‐angiogenic effects and showed moderate anti‐tumour efficacy in patients with. advanced hepatocellular carcinoma (HCC)

Aim

To explore potential biomarkers of lenalidomide efficacy as second‐line therapy for HCC.

Methods

Eligible patients were diagnosed with advanced HCC, documented progression on sorafenib, and Child‐Pugh class A liver function. Patients received 25 mg/day lenalidomide orally on days 1‐21 every 4 weeks. The primary endpoint was 6 month progression‐free survival rate. Early α‐fetoprotein response was defined as a > 20% decline of α‐fetoprotein levels from baseline within the first 4 weeks of treatment. Vascular response, evaluated using dynamic contrast‐enhanced magnetic resonance imaging, was defined as a > 40% decline in Ktrans after 2 weeks of treatment. The percentage of peripheral blood lymphocyte subsets were also analysed.

Results

Fifty‐five patients were enrolled. The response rate was 13%, and the disease‐control rate was 53%. The 6 month progression‐free survival rate was 9.1%. The median progression‐free and overall survival was 1.8 months and 8.9 months respectively. Early α‐fetoprotein response was significantly associated with higher disease‐control rate (76% vs 22%, P = .001) and longer progression‐free survival (P = .020). Vascular response was not associated with any treatment outcomes. Patients with a high pre‐treatment B cell percentage were more likely to have disease control (70% vs 36%, P = .010) and exhibited longer progression‐free survival (P < .001) and overall survival (P = .042).

Conclusions

Lenalidomide exhibited moderate activity as second‐line therapy for advanced HCC. Its immunomodulatory effects should be further explored (www.clinicaltrials.gov NCT01545804).
Thinning affects understorey tree community assembly in monoculture plantations by facilitating stochastic immigration from the landscape
Authors: Kitagawa Ryo , Ueno Mitsuru , Masaki Takashi
Published: August 2017

Aim

To maintain biodiversity in plantation forest ecosystems it is important to understand the community assembly process. Canopy thinning effectively increases understorey diversity in plantation forests. However, the process of understorey community assembly after canopy thinning remains unclear. We compared the relative importance of two mechanisms that could affect the assembly of understorey woody communities after thinning: (1) environmental filtering due to competition from canopy trees, and (2) stochastic immigration. If the latter is dominant, the effectiveness of local treatment might be unpredictable because of the variable probability of immigration at each location.

Location

Yamagata Prefecture, Japan.

Methods

We censused the understorey tree communities in 18 quadrats (each 1 m × 1 m) in each of 49 stands of Japanese cedar plantations. The mean species richness of the 18 quadrats (alpha‐diversity), variation in community composition among them (beta‐diversity), deviation of beta‐diversity from that of a random community (beta‐deviation) and total species richness of the plots (gamma‐diversity) were compared among censuses (before thinning, 2 and 5 yr after thinning). The relative contributions of two explanatory variables to the various diversities were examined: (1) basal area of canopy trees (overstorey BA, an index of environmental filtering), and (2) available seed source in the surrounding landscape (landscape effect; an index of the probability of immigration).

Results

Although neither beta‐diversity nor gamma‐diversity changed throughout the censuses, the alpha‐diversity, stem abundance and beta‐deviation were affected by thinning. beta‐deviation increased after thinning. Overstorey BA limited alpha‐ and gamma‐diversity throughout the censuses. The landscape effect was more significant in terms of beta‐deviation after than before thinning. In addition, the effective scale of the landscape effect increased after thinning.

Conclusion

Our results indicate that both processes are important: thinning brought about an increase in the relative importance of stochastic immigration as well as a reduction in competitive pressure from canopy trees. These results suggest that while local treatment can increase understorey diversity, stochastic immigration from seed sources is the direct driver after thinning. Although local treatment is effective, its efficiency depends on the seed source availability in the surrounding landscape.
Medication adherence in patients with apparent resistant hypertension: findings from the SYMPATHY trial
Authors: de Jager Rosa L. , van Maarseveen Erik M. , Bots Michiel L. , Blankestijn Peter J. ,   on behalf of the SYMPATHY investigators
Published: August 2017

Aims

Hypertension is only controlled in approximately 35% of the patients, which could be partially due to nonadherence. Recently, bioanalytical assessment of adherence to blood pressure (BP) lowering drugs has gaining interest. Our aim was to explore possible determinants of nonadherence in treatment resistant hypertension, assessed by objective screening for antihypertensive agents in serum. The secondary aim was to study the effect of adherence on the change in BP.

Methods

This project was a substudy of SYMPATHY; an open‐label randomized‐controlled trial to assess the effect of renal denervation on BP 6 months after treatment compared to usual care in patients with resistant hypertension. Stored serum samples were screened for antihypertensive agents to assess adherence at baseline and 6 months after intervention, using liquid chromatography–tandem mass spectrometry. Office and 24‐h BP were measured on the same day as blood was sampled. Patients and physicians were unaware of adherence measurements.

Results

Ninety‐eight baseline and 83 6‐month samples were available for analysis. Sixty‐eight percent [95% confidence interval (CI) 59–78%] of the patients was nonadherent (n = 67). For every onw pill more prescribed, 0.785 [95%CI 0.529–0.891] prescribed pill was less detected in blood. A decrease of one pill in adherence between baseline and 6 months was associated with a significant rise in office systolic BP of 4 (95%CI 0.230–8.932) mmHg.

Conclusion

Objective measurement of BP lowering drugs in serum, as a tool to assess adherence, showed that nonadherence was very common in patients with apparent resistant hypertension. Furthermore, the assessment results were related to (changes in) blood pressure. Our findings provide direct and objective methodology to help the physician to understand and to improve the condition of apparent resistant hypertension.
Protective Effect of Atazanavir Sulphate Against Pulmonary FibrosisIn VivoandIn Vitro
Authors: Song Shina , Ji Yunxia , Zhang Guanghua , Zhang Xue , Li Bin , Li Defang , Jiang Wanglin
Published: August 2017

Atazanavir sulphate, an antiretroviral protease inhibitor, has been used to treatHIV/AIDS, but its ability to serve as an antipulmonary fibrosis (PF) agent remains unknown. In this study, the effects of atazanavir sulphate on various aspects ofPFwere examined and CoCl2was used to induce the hypoxia‐mimicking conditionin vitro, including epithelial–mesenchymal transition (EMT) in A549 cells, endothelial–mesenchymal transition (EndMT) in human pulmonary microvascular endothelial cells (HPMECs), proliferation in human lung fibroblasts (HLF‐1) and potential protective effects in human type I alveolar epithelial cells (ATI). Additionally, the effects of atazanavir sulphate were examined using a bleomycin (BLM)‐induced pulmonary fibrosis model. After atazanavir sulphate treatment, in A549 cells andHPMECs, the expression of vimentin,HMGB1, Toll‐like receptor 4 (TLR‐4) and p‐NF‐κB decreased, while the expression of E‐cadherin andVE‐cadherin increased. InATI cells, the expression of aquaporin 5 andRAGEwere increased after atazanavir treatment. Proliferation ofHLF‐1 was reduced after atazanavir treatment, meanwhile the expression of hypoxia‐inducible factor‐1α (HIF‐1α), prolyl hydroxylase domain protein 2 (PHD‐2),HMGB1,TLR‐9, p‐NF‐κB, collagen I and collagenIIIwas decreased. In theBLM‐induced pulmonary fibrosis rat model, atazanavir sulphate amelioratedPFby reducing pathological score, collagen deposition and the expression of α‐SMA,HIF‐1α,PHD‐2,HMGB1,TLR‐4,TLR‐9 and p‐NF‐κB. In summary, our study supports the proposal that atazanavir sulphate may have a therapeutic potential in reducing the progression of pulmonary fibrosis by suppressingHMGB1/TLRsignalling.
Shifting intra‐ and inter‐organizational innovation processes towards digital business: An empirical analysis of SMEs
Authors: Scuotto Veronica , Santoro Gabriele , Bresciani Stefano , Del Giudice Manlio
Published: August 2017

The literature suggests that increasing investments in information and communication technologies (ICTs), knowledge exchange and sharing help SMEs tackle the current global and dynamic environment. Given that much of the useful knowledge resides outside the enterprises’ boundaries, these technological tools foster the gathering of big data and information. Despite these premises, few studies have considered the role of ICTs and big data in intra‐ and inter‐organizational ties and the consequent effects on enterprises’ innovation performance. The paper investigates whether ICTs oriented to intra‐organizational (in‐house research and development [R&D]) and inter‐organizational (open innovation) processes improve SMEs’ innovation performance. Therefore, via structural equation modelling (SEM), the study analyses a sample of 239 knowledge‐intensive SMEs located in Italy. The noteworthy results are that ICTs oriented to intra‐ and inter‐organizational innovation processes improve both these processes in generating new products and/or services. On this basis, managerial and academic implications are provided, along with avenues for further research.
Fostering creativity through critical thinking: The case of business start‐up simulations
Authors: Eggers Fabian , Lovelace Kathi J. , Kraft Frederik
Published: August 2017

Research suggests a positive link between critical thinking and creativity. However, this relationship has not been measured in an empirical study. This study aims to explore whether critical thinking can serve to enhance creativity and whether creativity positively mediates the relationship between critical thinking and business performance. In this study, we analyse these relationships within the entrepreneurial context of a web‐based business start‐up simulation. We examined data from 26 teams of three to four senior business students and found partial support for our hypotheses. Critical thinking positively influenced creativity, measured as the total number of unique product designs. Creativity (unique product designs) also positively mediated the link between critical thinking and performance. This effect, however, did not exist when creativity was assessed through advertisement designs. This research contributes to entrepreneurship and innovation management by demonstrating the importance of critical thinking as a basis for creativity and testing this relationship in a business start‐up simulation context.
Comparative in vitro study on cytotoxicity of recombinant β‐hairpin peptides
Authors: Kuzmin Denis V. , Emelianova Anna A. , Kalashnikova Mariana B. , Panteleev Pavel V. , Balandin Sergey V. , Serebrovskaya Ekaterina O. , Belogurova‐Ovchinnikova Oksana Y. , Ovchinnikova Tatiana V.
Published: August 2017

Natural antimicrobial peptides (AMPs) are important components of the innate immune system with a wide spectrum of biological activity. In this study, we investigated the cytotoxic effect of three recombinant β‐hairpin cationic AMPs: arenicin‐1 from the polychaeta Arenicola marina, tachyplesin I from the horseshoe crab Tachypleus tridentatus, and gomesin from the spider Acanthoscurria gomesiana. All the three β‐hairpin AMPs were overexpressed in Escherichia coli. Different cell lines were incubated with various concentrations of the investigated AMPs in order to evaluate their cytotoxic activity. Double staining with subsequent flow cytometric analysis was used to determine the predominant way of cell death mediated by each AMP. Hemolytic activity of the peptides was tested against fresh human red blood cells. Our results indicated that all the three AMPs exhibited significant cytotoxic effect against cancer cells that varied depending on the cell line type and, in most cases, on the presence of serum components. Flow cytometric analysis implicitly indicated that tachyplesin I mostly promoted late apoptosis/necrosis, while arenicin‐1 and gomesin induced early apoptosis under the same conditions. Tachyplesin I proved to be the most promising therapeutic candidate as it displayed the highest specific cytotoxicity against cancer cell lines, independent of the serum presence.
Aromatic interactions at the ligand–protein interface: Implications for the development of docking scoring functions
Authors: Brylinski Michal
Published: August 2017

The ability to design and fine‐tune non‐covalent interactions between organic ligands and proteins is indispensable to rational drug development. Aromatic stacking has long been recognized as one of the key constituents of ligand–protein interfaces. In this communication, we employ a two‐parameter geometric model to conduct a large‐scale statistical analysis of aromatic contacts in the experimental and computer‐generated structures of ligand–protein complexes, considering various combinations of aromatic amino acid residues and ligand rings. The geometry of interfacial π–π stacking in crystal structures accords with experimental and theoretical data collected for simple systems, such as the benzene dimer. Many contemporary ligand docking programs implicitly treat aromatic stacking with van der Waals and Coulombic potentials. Although this approach generally provides a sufficient specificity to model aromatic interactions, the geometry of π–π contacts in high‐scoring docking conformations could still be improved. The comprehensive analysis of aromatic geometries at ligand–protein interfaces lies the foundation for the development of type‐specific statistical potentials to more accurately describe aromatic interactions in molecular docking. A Perl script to detect and calculate the geometric parameters of aromatic interactions in ligand–protein complexes is available at https://github.com/michal-brylinski/earomatic. The dataset comprising experimental complex structures and computer‐generated models is available at https://osf.io/rztha/.
Discovery of naphthyl‐N‐acylhydrazone p38α MAPK inhibitors with in vivo anti‐inflammatory and anti‐TNF‐α activity
Authors: Freitas Rosana H. C. N. , Cordeiro Natália M. , Carvalho Patrícia R. , Alves Marina A. , Guedes Isabella A. , Valerio Tayna S. , Dardenne Laurent E. , Lima Lídia M. , Barreiro Eliezer J. , Fernandes Patrícia D. , Fraga Carlos A. M.
Published: August 2017

Protein kinases constitute attractive therapeutic targets for development of new prototypes to treat different chronic diseases. Several available drugs, like tinibs, are tyrosine kinase inhibitors; meanwhile, inhibitors of serine/threonine kinases, such as mitogen‐activated protein kinase (MAPK), are still trying to overcome some problems in one of the steps of clinical development to become drugs. So, here we reported the synthesis, the in vitro kinase inhibitory profile, docking studies, and the evaluation of anti‐inflammatory profile of new naphthyl‐N‐acylhydrazone derivatives using animal models. Although all tested compounds (3a–d) have been characterized as p38α MAPK inhibitors and have showed in vivo anti‐inflammatory action, LASSBio‐1824 (3b) presented the best performance as p38α MAPK inhibitor, with IC50 = 4.45 μm, and also demonstrated to be the most promising anti‐inflammatory prototype, with good in vivo anti‐TNF‐α profile after oral administration.
Docking field‐based QSAR and pharmacophore studies on the substituted pyrimidine derivatives targeting HIV‐1 reverse transcriptase
Authors: Fan Ningning , Zhang Shuang , Sheng Tao , Zhao Liang , Liu Zhenming , Liu Junyi , Wang Xiaowei
Published: August 2017

HIV‐1 reverse transcriptase (RT) is one of the most important enzymes required for viral replication, thus acting as an attractive target for antiretroviral therapy. Pyrimidine analogues reportedly have selective inhibition on HIV‐1 RT with favorable antiviral activities in our previous study. To further explore the relationship between inhibitory activity and pharmacophoric characteristics, field‐based QSAR models were generated and validated using Schrodinger Suite (correlation coefficient of .8078, cross‐validated value of 0.5397 for training set and Q2 of 0.4669, Pearson's r of .7357 for test set). Docking, pocket surfaces, and pharmacophore study were also investigated to define the binding pattern and pharmacophoric features, including (i) π–π interaction with residue Tyr181, Tyr188, and Trp229 and p–π interaction with His235 and (ii) hydrogen bond with residue Lys101 and halogen bond with residue Tyr188. The pharmacophore features of six‐point hypothesis AADRRR.184, AAADRR.38, and AADRRR.26 further complimented to the docking and QSAR results. We also found that the protein‐ligand complex exhibited high relative binding free energy. These observations could be potentially utilized to guide the rational design and optimization of novel HIV‐1 RT inhibitors.
Effectiveness of oral health education on oral hygiene and dental caries in schoolchildren: Systematic review and meta‐analysis
Authors: Stein Caroline , Santos Nathália Maria Lopes , Hilgert Juliana Balbinot , Hugo Fernando Neves
Published: August 2017

Objectives

The objective of this study was to evaluate the effectiveness of oral health educational actions in the school context in improving oral hygiene and dental caries in schoolchildren through systematic review and meta‐analysis.

Methods

Clinical trials with schoolchildren between 5 and 18 years old were included. Eligible studies were those which had as outcomes caries, plaque accumulation, gingivitis, toothache or tooth loss and which had been published from 1995 to 2015, in any language. The risk of bias was assessed in specific domains according to the Cochrane Handbook. A meta‐analysis was carried out using fixed‐effects models.

Results

A total of 4417 references were found, from which 93 full texts were evaluated and 12 included in this meta‐analysis. Five studies showed a reduction in plaque levels, and two studies with gingivitis as the outcome found no effect. There was not enough evidence on the effectiveness of the interventions in reducing dental caries.

Conclusions

Traditional oral health educational actions were effective in reducing plaque, but not gingivitis. There is no long‐term evidence in respect of the effectiveness of these interventions in preventing plaque accumulation, gingivitis and dental caries in the school environment.
Tree Growth Modelling Constrained by Growth Equations
Authors: Yi Lei , Li Hongjun , Guo Jianwei , Deussen Oliver , Zhang Xiaopeng
Published: August 2017

Modelling and simulation of tree growth that is faithful to the living environment and numerically consistent to botanic knowledge are important topics for realistic modelling in computer graphics. The realism factors concerned include the effects of complex environment on tree growth and the reliability of the simulation in botanical research, such as horticulture and agriculture. This paper proposes a new approach, namely, integrated growth modelling, to model virtual trees and simulate their growth by enforcing constraints of environmental resources and tree morphological properties. Morphological properties are integrated into a growth equation with different parameters specified in the simulation, including its sensitivity to light, allocation and usage of received resources and effects on its environment. The growth equation guarantees that the simulation procedure numerically matches the natural growth phenomenon of trees. With this technique, the growth procedures of diverse and realistic trees can also be modelled in different environments, such as resource competition among multiple trees.
Traps and transformations influencing the financial viability of tourism on private‐land conservation areas
Authors: Clements Hayley S. , Cumming Graeme S.
Published: August 2017

The ability of private conservation organizations to remain financially viable is a key factor influencing their effectiveness. One‐third of financially motivated private‐land conservation areas (PLCAs) surveyed in South Africa are unprofitable, raising questions about landowners’ abilities to effectively adapt their business models to the socioeconomic environment. In any complex system, options for later adaptation can be constrained by starting conditions (path dependence). We tested 3 hypothesized drivers of path dependence in PLCA ecotourism and hunting business models: (H1) the initial size of a PLCA limits the number of mammalian game and thereby predators that can be sustained; (H2) initial investments in infrastructure limit the ability to introduce predators; and (H3) rainfall limits game and predator abundance. We further assessed how managing for financial stability (optimized game stocking) or ecological sustainability (allowing game to fluctuate with environmental conditions) influenced the ability to overcome path dependence. A mechanistic PLCA model based on simple ecological and financial rules was run for different initial conditions and management strategies, simulating landowner options for adapting their business model annually. Despite attempts by simulated landowners to increase profits, adopted business models after 13 years were differentiated by initial land and infrastructural assets, supporting H1 and H2. A conservation organization's initial assets can cause it to become locked into a financially vulnerable business model. In our 50‐year simulation, path dependence was overcome by fewer of the landowners who facilitated natural ecological variability than those who maintained constant hunting rates and predator numbers, but the latter experienced unsustainably high game densities in low rainfall years. Management for natural variability supported long‐term ecological sustainability but not shorter term socioeconomic sustainability for PLCAs. Our findings highlight trade‐offs between ecological and economic sustainability and suggest a role for governmental support of the private conservation industry.
The study of colour fastness of commercial microencapsulated photoresponsive dye applied on cotton, cotton/polyester and polyester fabric using a pad‐dry‐cure process
Authors: Kert Mateja , Gorjanc Marija
Published: August 2017

Commercial microencapsulated photoresponsive dye was applied on cotton, polyester/cotton and polyester fabric using a pad‐dry‐cure process. Colour fastness of the photoresponsive fabrics to washing, wet cleaning, dry cleaning, rubbing and light was investigated. The CIELAB colour values of the fabrics before and after testing were measured using a reflectance spectrophotometer, and the colour differences were calculated to evaluate the fastness properties. The fabrics had better colour fastness to wet cleaning and washing than to dry cleaning. The fabrics showed higher colour fastness to wet than to dry rubbing. The photoresponsiveness of the fabrics decreased with prolonged exposure time to artificial light due to low photostability of the microcapsules.
Rise and fall of island butterfly diversity: Understanding genetic differentiation and extinction in a highly diverse archipelago
Authors: Dapporto Leonardo , Cini Alessandro , Menchetti Mattia , Vodă Raluca , Bonelli Simona , Casacci Luca P. , Dincă Vlad , Scalercio Stefano , Hinojosa Joan C. , Biermann Heinrich , Forbicioni Leonardo , Mazzantini Umberto , Venturi Lucia , Zanichelli Franca , Balletto Emilio , Shreeve Tim G. , Dennis Roger L. H. , Vila Roger
Published: August 2017

Aim

We describe fine‐scale diversity patterns of the entire butterfly fauna occurring on the Tuscan Archipelago. By assessing the traits associated with population diversification, haplotype uniqueness and extinction, we aim to identify the factors determining the origin and maintenance of genetic diversity, and population vulnerability to environmental changes.

Location

Tuscan Archipelago, Sardinia, Tuscany (Italy) and Corsica (France).

Methods

We built a mtDNA dataset (1,303 COI sequences) for the 52 butterfly species reported in the Archipelago, also including specimens from neighbouring areas, and compiled data on 12 species traits and on the apparent extinction of species from the main islands. We calculated indices that measure genetic differentiation, and using phylogenetic regressions we evaluated the relationships between these indices and species traits. Finally, we inferred which traits are associated with disappearance of species on individual islands using phylogenetic regression.

Results

The overall spatial pattern of genetic diversity corresponded with the proximity of the areas, but strong contrasts were also identified between geographically close areas. Together with the island endemics, several common and widespread species had a high genetic diversification among islands and mainland. Phylogenetic regressions revealed that smaller‐sized, more specialized species, with a preference for drier regions, displayed greater genetic structure and/or haplotype uniqueness. Species that disappeared from islands had a higher population diversification. Capraia has experienced a notable loss of diversity, which significantly affected species with shorter flight periods.

Main conclusions

Tuscan island butterflies are characterized by strong genetic contrasts and species differ in their contribution to the overall genetic diversity. By ranking the species for their contribution to genetic diversity and identifying the traits linked to the emergence and maintenance of diversity, we have developed a valuable tool for prioritizing populations as targets for monitoring and conservation action. The dataset constructed also represents a valuable resource for testing biogeographical hypotheses.
Synergistic effects of climate and land use on avian beta‐diversity
Authors: Ferger Stefan W. , Peters Marcell K. , Appelhans Tim , Detsch Florian , Hemp Andreas , Nauss Thomas , Otte Insa , Böhning‐Gaese Katrin , Schleuning Matthias
Published: August 2017

Aim

Gradients in climate and land use occur simultaneously in many of the Earth's ecosystems and thus collectively impact most ecological communities. Albeit climate and land use have potentially interacting effects on ecological communities that may exacerbate or ameliorate their individual effects, little is known about the effect of the climate–land use interaction on community composition. A better understanding of the interaction between climate and land use is essential to predict the impacts of environmental change on ecological communities.

Location

Mt. Kilimanjaro, Tanzania.

Methods

We quantified the community composition of bird species and feeding guilds on 64 study plots of 13 different habitat types along an elevational gradient from 870 to 4550 m a.s.l. We partitioned the variation in pairwise beta‐diversity (βcc) of birds and its two additive components, abundance differences (βabu) and replacement (β−3), among the effects of temperature, land‐use intensity and their interaction.

Results

Temperature and land use had synergistic effects on beta‐diversity (βcc) of birds; that is, the combination of high temperature and high land‐use intensity led to higher beta‐diversity than expected from the sum of both individual effects. While temperature explained more of the variation in abundance differences (βabu), land use explained more of the variation in the replacement of individuals between species and feeding guilds (β−3), indicating that different processes drove avian beta‐diversity along the temperature and land‐use gradients.

Main Conclusions

Our results challenge previous studies that investigated the effects of climate and land use in isolation because disregarding their synergistic interaction underestimates the joint effect of climate and land use on biodiversity. A consideration of the synergy between climate and land use is essential for adequate predictions of the impact of global change on biodiversity.
Endoscopic diagnosis and treatment of superficial pharyngeal cancer
Authors: Katada Chikatoshi , Okamoto Tabito , Kano Koichi
Published: August 2017

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Early segregation of the adrenal cortex and gonad in chicken embryos
Authors: Saito Daisuke , Tamura Koji , Takahashi Yoshiko
Published: August 2017

The adrenal gland is an endocrine organ that plays essential roles in stress responses. This organ consists of two types of tissues, adrenomedulla and adrenocortex, deriving from different embryonic origins. Whereas it is well accepted that the adrenomedulla derives from neural crest cells, the origin of the adrenocortex remains elusive. In addition, the adrenocortex and gonads, two major steroid hormone‐producing tissues, have been thought to share the same origin, although the experimental evidence is lacking. In this study, to identify the origin of adrenocortex and to compare it to that of gonads, we scrutinized the medial portion of the coelomic epithelium (CE) after the lateral plate mesoderm has split into two CE components with a concomitant opening of the coelomic cavity in between them. We found that early medial CE consists of a two‐cell layer‐thick band of epithelial‐like cells, the outer and inner CEs. The outer CE faces the coelomic cavity, whereas the inner CE is juxtaposed to nascent blood vessels. Combining direct cell labeling with early molecular markers, we found that outer CE was the origin of the gonad but not the adrenocortex. The adrenocortex, instead, appears to derive from inner CE. Thus, the adrenocortical and gonadal progenitors are already segregated from each other when the coelomic cavity has opened. This study provides a new basis for understanding how the adrenal gland forms and how steroid hormone‐producing tissues arise during development.
Validation of the Scale for Assessment and Rating of Ataxia: testing a test (and failing it)
Authors: Streiner David L
Published: August 2017

This commentary is on the original article by Lawerman et al. on pages 1077–1082 of this issue.