Beyond bone biology: Lessons from team science

Today, research in biomedicine often requires the knowledge and technologies in diverse fields. Therefore, there is an increasing need for collaborative team science that crosses traditional disciplines. Here, we discuss our own lessons from both interdisciplinary and transdisciplinary teams, which ultimately ushered us to expand our research realm beyond bone biology. This article is protected by copyright. All rights reserved

Testing the paradox of enrichment along a land use gradient in a multitrophic aboveground and belowground community

In the light of ongoing land use changes, it is important to understand how multitrophic communities perform at different land use intensities. The paradox of enrichment predicts that fertilization leads to destabilization and extinction of predator-prey systems. We tested this prediction for a land use intensity gradient from natural to highly fertilized agricultural ecosystems. We included multiple aboveground and belowground trophic levels and land use-dependent searching efficiencies of insects. To overcome logistic constraints of field experiments, we used a successfully validated simulation model to investigate plant responses to removal of herbivores and their enemies. Consistent with our predictions, instability measured by herbivore-induced plant mortality increased with increasing land use intensity. Simultaneously, the balance between herbivores and natural enemies turned increasingly towards herbivore dominance and natural enemy failure. Under natural conditions, there were more frequently significant effects of belowground herbivores and their natural enemies on plant performance, whereas there were more aboveground effects in agroecosystems. This result was partly due to the “boom-bust” behavior of the shoot herbivore population. Plant responses to herbivore or natural enemy removal were much more abrupt than the imposed smooth land use intensity gradient. This may be due to the presence of multiple trophic levels aboveground and belowground. Our model suggests that destabilization and extinction are more likely to occur in agroecosystems than in natural communities, but the shape of the relationship is nonlinear under the influence of multiple trophic interactions.

Experiences of patients and health care professionals on the quality of telephone follow-up care during the COVID-19 pandemic:a large qualitative study in a multidisciplinary academic setting

OBJECTIVE: To evaluate the perceived quality of follow-up telephone consultations (TCs) from the perspective of patients and healthcare professionals (HCPs) of multiple medical disciplines during the COVID-19 pandemic. DESIGN: A qualitative study using semi-structured interviews and reflexive thematic analysis. SETTING: Seven medical disciplines (general dermatology, dermato-oncology, head and neck oncology, internal medicine, medical oncology, gynaecological oncology and surgical oncology) at a large university hospital in the Netherlands. PARTICIPANTS: Patients who received and HCPs who provided TCs as a substitute for outpatient follow-up appointments during the COVID-19 pandemic. RESULTS: Eighty-two patients and 58 HCPs were interviewed. Predominantly, patients and HCPs were satisfied with the quality of care by TCs. They regarded TCs as efficient, accessible and of acceptable quality, provided there was an established patient-HCP relationship, medical complaints were absent and physical examination was not indicated. However, most patients were worried about the accuracy of their health assessment in the absence of physical examination and non-verbal communication. Both patients and HCPs wish to use TCs in the future alternatively with face-to-face consultations. CONCLUSION: This study concludes that TCs seem a valuable contribution to the context of follow-up care and could partially replace face-to-face consultations. TCs can be performed in stable, chronic patients with whom a doctor-patient relationship has already been established. Face-to-face consultations are considered more appropriate in the case of new patients, challenging or emotionally charged consultations and when clinically relevant physical examination is indicated. Due to the context-dependent nature of experiences of patients and HCPs, TCs should be used with an individually customised approach based on patient and disease specifics, in which shared decision-making plays an extensive role. Before major implementation is considered, sufficient data on the safety regarding missed diagnoses or cancer recurrences should be assembled first

Effects of combined treatment with rapamycin and cotylenin A, a novel differentiation-inducing agent, on human breast carcinoma MCF-7 cells and xenografts

INTRODUCTION: Rapamycin, an inhibitor of the serine/threonine kinase target of rapamycin, induces G(1 )arrest and/or apoptosis. Although rapamycin and its analogues are attractive candidates for cancer therapy, their sensitivities with respect to growth inhibition differ markedly among various cancer cells. Using human breast carcinoma cell line MCF-7 as an experimental model system, we examined the growth-inhibitory effects of combinations of various agents and rapamycin to find the agent that most potently enhances the growth-inhibitory effect of rapamycin. METHOD: We evaluated the growth-inhibitory effect of rapamycin plus various agents, including cotylenin A (a novel inducer of differentiation of myeloid leukaemia cells) to MCF-7 cells, using either MTT assay or trypan blue dye exclusion test. The cell cycle was analyzed using propidium iodide-stained nuclei. Expressions of several genes in MCF-7 cells with rapamycin plus cotylenin A were studied using cDNA microarray analysis and RT-PCR. The in vitro results of MCF-7 cells treated with rapamycin plus cotylenin A were further confirmed in vivo in a mouse xenograft model. RESULTS: We found that the sensitivity of rapamycin to MCF-7 cells was markedly affected by cotylenin A. This treatment induced growth arrest of the cells at the G(1 )phase, rather than apoptosis, and induced senescence-associated β-galactosidase activity. We examined the gene expression profiles associated with exposure to rapamycin and cotylenin A using cDNA microarrays. We found that expressions of cyclin G(2), transforming growth factor-β-induced 68 kDa protein, BCL2-interacting killer, and growth factor receptor-bound 7 were markedly induced in MCF-7 cells treated with rapamycin plus cotylenin A. Furthermore, combined treatment with rapamycin and cotylenin A significantly inhibited the growth of MCF-7 cells as xenografts, without apparent adverse effects. CONCLUSION: Rapamycin and cotylenin A cooperatively induced growth arrest in breast carcinoma MCF-7 cells in vitro, and treatment with rapamycin and cotylenin A combined more strongly inhibited the growth of MCF-7 cells as xenografts in vivo than treatment with rapamycin or cotylenin A alone, suggesting that this combination may have therapeutic value in treating breast cancer. We also identified several genes that were markedly modulated in MCF-7 cells treated with rapamycin plus cotylenin A

Validation of Serum Neurofilament Light Chain as a Biomarker of Parkinson's Disease Progression

Background: The objective of this study was to assess neurofilament light chain as a Parkinson’s disease biomarker. Methods: We quantified neurofilament light chain in 2 independent cohorts: (1) longitudinal cerebrospinal fluid samples from the longitudinal de novo Parkinson’s disease cohort and (2) a large longitudinal cohort with serum samples from Parkinson’s disease, other cognate/neurodegenerative disorders, healthy controls, prodromal conditions, and mutation carriers. Results: In the Parkinson’s Progression Marker Initiative cohort, mean baseline serum neurofilament light chain was higher in Parkinson’s disease patients (13 � 7.2 pg/mL) than in controls (12 � 6.7 pg/mL), P = 0.0336. Serum neurofilament light chain increased longitudinally in Parkinson’s disease patients versus controls (P < 0.01). Motor scores were positively associated with neurofilament light chain, whereas some cognitive scores showed a negative association. Conclusions: Neurofilament light chain in serum samples is increased in Parkinson’s disease patients versus healthy controls, increases over time and with age, and correlates with clinical measures of Parkinson’s disease severity. Although the specificity of neurofilament light chain for Parkinson’s disease is low, it is the first blood-based biomarker candidate that could support disease stratification of Parkinson’s disease versus other cognate/neurodegenerative disorders, track clinical progression, and possibly assess responsiveness to neuroprotective treatments. However, use of neurofilament light chain as a biomarker of response to neuroprotective interventions remains to be assessed

First-in-class humanized FSH blocking antibody targets bone and fat

Blocking the action of FSH genetically or pharmacologically in mice reduces body fat, lowers serum cholesterol, and increases bone mass, making an anti-FSH agent a potential therapeutic for three global epidemics: obesity, osteoporosis, and hypercholesterolemia. Here, we report the generation, structure, and function of a first-in-class, fully humanized, epitope-specific FSH blocking antibody with a KD of 7 nM. Protein thermal shift, molecular dynamics, and fine mapping of the FSH-FSH receptor interface confirm stable binding of the Fab domain to two of five receptor-interacting residues of the FSHβ subunit, which is sufficient to block its interaction with the FSH receptor. In doing so, the humanized antibody profoundly inhibited FSH action in cell-based assays, a prelude to further preclinical and clinical testing

Non-smoking adolescents' perceptions of dissuasive cigarettes

Introduction Dissuasive cigarettes, cigarettes with an unappealing colour or displaying a health warning label, may deter young people from smoking uptake. Methods Two online surveys were conducted with non-smokers aged 12–17 to explore perceptions of cigarette appeal, harm and product trial. Study 1 was a within-subject study which examined perceptions of four cigarettes with different coloured paper, and four cigarettes displaying a warning. Study 2 was a between-subject study (with limited power), in which respondents were randomized to one of four cigarettes: (1) regular cigarette; (2) least favourable warning from Study 1; (3) least favourable colour from Study 1; or (4) a combination of the least favourable warning and colour from Study 1. Warnings or colours were considered least favourable when they had lower scores on appeal, harm, and product trial. Results In Study 1, a cigarette featuring the warning ‘cancer, heart disease, stroke’ and a drab dark brown cigarette were rated lowest on appeal and trial intentions, and highest on perceived harm. In Study 2, there were no significant differences in perceptions of appeal, harm or trial intentions between the regular and dissuasive cigarettes. Conclusions Findings from our within-subject study suggest that a cigarette displaying the text ‘cancer, heart disease, stroke’ and a drab dark brown coloured cigarette are most dissuasive for Dutch non-smoking adolescents. Whether dissuasive cigarettes reduce appeal, reduce product trial, or increase perceptions of harm compared to a regular cigarette should be further examined in larger between-subject studies

Exploring the potential of phone call data to characterize the relationship between social network and travel behavior

[EN] Social network contacts have significant influence on individual travel behavior. However, transport models rarely consider social interaction. One of the reasons is the difficulty to properly model social influence based on the limited data available. Non-conventional, passively collected data sources, such as Twitter, Facebook or mobile phones, provide large amounts of data containing both social interaction and spatiotemporal information. The analysis of such data opens an opportunity to better understand the influence of social networks on travel behavior. The main objective of this paper is to examine the relationship between travel behavior and social networks using mobile phone data. A huge dataset containing billions of registers has been used for this study. The paper analyzes the nature of co-location events and frequent locations shared by social network contacts, aiming not only to provide understanding on why users share certain locations, but also to quantify the degree in which the different types of locations are shared. Locations have been classified as frequent (home, work and other) and non-frequent. A novel approach to identify co-location events based on the intersection of users' mobility models has been proposed. Results show that other locations different from home and work are frequently associated to social interaction. Additionally, the importance of non-frequent locations in co-location events is shown. Finally, the potential application of the data analysis results to improve activity-based transport models and assess transport policies is discussed.The authors would like to thank the anonymous reviewers for their valuable comments and suggestions to improve the quality of the paper. The research leading to these results has received funding from the European Union Seventh Framework Programme FP7/2007-2013 under grant agreement no 318367 (EUNOIA project) and no 611307 (INSIGHT project). The work of ML has been funded under the PD/004/2013 project, from the Conselleria de Educacion, Cultura y Universidades of the Government of the Balearic Islands and from the European Social Fund through the Balearic Islands ESF operational program for 2013-2017.Picornell Tronch, M.; Ruiz Sánchez, T.; Lenormand, M.; Ramasco, JJ.; Dubernet, T.; Frías-Martínez, E. (2015). Exploring the potential of phone call data to characterize the relationship between social network and travel behavior. Transportation. 42(4):647-668. https://doi.org/10.1007/s11116-015-9594-1S647668424Ahas, R., Aasa, A., Silm, S., Tiru, M.: Daily rhythms of suburban commuters’ movements in the tallinn metropolitan area: case study with mobile positioning data. Transp. Res. 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Is web interviewing a good alternative to telephone interviewing? Findings from the International Tobacco Control (ITC) Netherlands Survey

<p>Abstract</p> <p>Background</p> <p>Web interviewing is becoming increasingly popular worldwide, because it has several advantages over telephone interviewing such as lower costs and shorter fieldwork periods. However, there are also concerns about data quality of web surveys. The aim of this study was to compare the International Tobacco Control (ITC) Netherlands web and telephone samples on demographic and smoking related variables to assess differences in data quality.</p> <p>Methods</p> <p>Wave 1 of the ITC Netherlands Survey was completed by 1,668 web respondents and 404 telephone respondents of 18 years and older. The two surveys were conducted in parallel among adults who reported smoking at least monthly and had smoked at least 100 cigarettes over their lifetime.</p> <p>Results</p> <p>Both the web and telephone survey had a cooperation rate of 78%. Web respondents with a fixed line telephone were significantly more often married, had a lower educational level, and were older than web respondents without a fixed line telephone. Telephone respondents with internet access were significantly more often married, had a higher educational level, and were younger than telephone respondents without internet. Web respondents were significantly less often married and lower educated than the Dutch population of smokers. Telephone respondents were significantly less often married and higher educated than the Dutch population of smokers. Web respondents used the "don't know" options more often than telephone respondents. Telephone respondents were somewhat more negative about smoking, had less intention to quit smoking, and had more self efficacy for quitting. The known association between educational level and self efficacy was present only in the web survey.</p> <p>Conclusions</p> <p>Differences between the web and telephone sample were present, but the differences were small and not consistently favourable for either web or telephone interviewing. Our study findings suggested sometimes a better data quality in the web than in the telephone survey. Therefore, web interviewing can be a good alternative to telephone interviewing.</p