Scientific activity by medical students: the relationship between academic publishing during medical school and publication careers after graduation.

INTRODUCTION: Engagement of clinicians in research is important for the integration of science and clinical practice. However, at this moment, there is a shortage of clinician-scientists. Success experiences can stimulate student interest in a research career. Conducting actual research leading to publication is a potential method to gain success experience. This study assessed whether publication as a medical student is associated with publication after graduation. We determined whether medical students in the Netherlands who are involved in research, as measured by publication in international journals before graduation: 1) are more likely to publish, 2) publish a greater number of papers, and 3) have higher citation impact scores after graduation. METHODS: We matched 2005-2008 MD graduates (with rare names, n = 4145 in total) from all eight Dutch university medical centres to their publications indexed in the Web of Science and published between 6 years before and 6 years after graduation. For sensitivity analysis we performed both automatic assignment on the whole group and manual assignment on a 10% random sample. RESULTS: Students who had published before graduation: 1) were 1.9 times as likely to publish, 2) published more papers, and 3) had a slightly higher citation impact after graduation. DISCUSSION: Medical students who conducted research leading to a publication before graduation were more likely to be scientifically active after graduation. While this is not a causal relationship per se, these results cautiously suggest that successful early involvement in research could influence the long-term scientific activity of clinicians.

Future physician-scientists: could we catch them young? Factors influencing intrinsic and extrinsic motivation for research among first-year medical students.

INTRODUCTION: The medical field is currently facing a physician-scientist shortage. One possible solution is to direct medical students towards a research oriented career. To do so, knowledge is needed on how to motivate medical students to do research. Therefore, this study examines motivation for research and identifies factors influencing intrinsic and extrinsic motivation for research among first-year medical students. METHODS: First-year medical students were surveyed at the beginning of their bachelor's program in 2016. On a 7-point Likert scale, students reported their motivation for research, self-efficacy, perceptions of research, curiosity, and need for challenge. Regression analyses were used to examine the influence of these factors on students' motivation for research. RESULTS: Out of 316 approached students, 315 participated (99.7%). On average, students scored 5.49 on intrinsic, and 5.66 on extrinsic motivation for research. All factors measured influenced intrinsic and extrinsic motivation for research significantly and positively, also after adjusting for gender and age. Cumulative regression showed that these factors explained 39.6% of the variance in intrinsic, and 14% in extrinsic motivation for research. DISCUSSION: All factors play an important role in intrinsic and, to a lesser extent, extrinsic motivation for research. First-year medical students' motivation for research could be enhanced by stimulating positive self-efficacy beliefs, positive perceptions of research, and curiosity. Also, it is important to fulfil students' needs for challenge by stimulating them to actively conduct research. Thus, to catch students young and cultivate physician-scientists, students should be stimulated to engage in research from the beginning of medical training.

The Role of Gender in the Employment, Career Perception and Research Performance of Recent PhD Graduates from Dutch Universities.

Recent decades have seen a sharp increase in the number of female PhD graduates in the Netherlands. Currently, the share of females among newly graduated PhDs is almost on par with that of males. A considerable body of scientific studies has investigated the role of gender in the academic workplace. However, the role of gender in the careers of all PhD graduates, including those outside academia, has been studied less. In this study, we investigate gender differences in type of job, occupation, career perception and research performance of recent PhDs. The study is based on a survey of persons who obtained a PhD from one of five Dutch universities between 2008 and early 2012. We show that gender differences in post-PhD careers are non-existent in some aspects studied, but there are small differences in other aspects, such as sector of employment, type of contract, involvement in teaching and management, and career perception. In contrast, male and female PhDs differ sharply on two factors. The first is field of PhD, females being heavily underrepresented in engineering and the natural sciences. The second is part-time employment, females being much more likely to work part-time than males, especially if they work in the Netherlands. In later career stages, the combination of the small and large differences can be presumed to affect the career progression of female PhDs through cumulative disadvantage.

Scientific workflows for bibliometrics.

Scientific workflows organize the assembly of specialized software into an overall data flow and are particularly well suited for multi-step analyses using different types of software tools. They are also favorable in terms of reusability, as previously designed workflows could be made publicly available through the myExperiment community and then used in other workflows. We here illustrate how scientific workflows and the Taverna workbench in particular can be used in bibliometrics. We discuss the specific capabilities of Taverna that makes this software a powerful tool in this field, such as automated data import via Web services, data extraction from XML by XPaths, and statistical analysis and visualization with R. The support of the latter is particularly relevant, as it allows integration of a number of recently developed R packages specifically for bibliometrics. Examples are used to illustrate the possibilities of Taverna in the fields of bibliometrics and scientometrics.

Stability and Longevity in the Publication Careers of U.S. Doctorate Recipients.

Since the 1950s, the number of doctorate recipients has risen dramatically in the United States. In this paper, we investigate whether the longevity of doctorate recipients' publication careers has changed. This is achieved by matching 1951-2010 doctorate recipients with rare names in astrophysics, chemistry, economics, genetics and psychology in the dissertation database ProQuest to their publications in the publication database Web of Science. Our study shows that pre-PhD publication careers have changed: the median year of first publication has shifted from after the PhD to several years before PhD in most of the studied fields. In contrast, post-PhD publication career spans have not changed much in most fields. The share of doctorate recipients who have published for more than twenty years has remained stable over time; the shares of doctorate recipients publishing for shorter periods also remained almost unchanged. Thus, though there have been changes in pre-PhD publication careers, post-PhD career spans remained quite stable.

Inhibition of mutant IDH1 decreases D-2-HG levels without affecting tumorigenic properties of chondrosarcoma cell lines.

Mutations in isocitrate dehydrogenase 1 (IDH1) and IDH2 are found in a subset of benign and malignant cartilage tumors, gliomas and leukaemias. The mutant enzyme causes the production of D-2-hydroxyglutarate (D-2-HG), affecting CpG island and histone methylation. While mutations in IDH1/2 are early events in benign cartilage tumors, we evaluated whether these mutations play a role in malignant chondrosarcomas. Compared to IDH1/2 wildtype cell lines, chondrosarcoma cell lines harboring an endogenous IDH1 (n=3) or IDH2 mutation (n=2) showed up to a 100-fold increase in intracellular and extracellular D-2-HG levels. Specific inhibition of mutant IDH1 using AGI-5198 decreased levels of D-2-HG in a dose dependent manner. After 72 hours of treatment one out of three mutant IDH1 cell lines showed a moderate decrease in viability , while D-2-HG levels decreased >90%. Likewise, prolonged treatment (up to 20 passages) did not affect proliferation and migration. Furthermore, global gene expression, CpG island methylation as well as histone H3K4, -9, and -27 trimethylation levels remained unchanged. Thus, while IDH1/2 mutations cause enchondroma, malignant progression towards central chondrosarcoma renders chondrosarcoma growth independent of these mutations. Thus, monotherapy based on inhibition of mutant IDH1 appears insufficient for treatment of inoperable or metastasized chondrosarcoma patients.

Bibliometric mapping: eight decades of analytical chemistry, with special focus on the use of mass spectrometry.

In this Feature we use automatic bibliometric mapping tools to visualize the history of analytical chemistry from the 1920s until the present. In particular, we have focused on the application of mass spectrometry in different fields. The analysis shows major shifts in research focus and use of mass spectrometry. We conclude by discussing the application of bibliometric mapping and visualization tools in analytical chemists' research.

Imaging mass spectrometry-based molecular histology differentiates microscopically identical and heterogeneous tumors.

Many tumors display significant cellular heterogeneity as well as molecular heterogeneity. Sensitive biomarkers that differentiate between diagnostically challenging tumors must contend with this heterogeneity. Mass spectrometry-based molecular histology of a patient series of heterogeneous, microscopically identical bone tumors highlighted the tumor cell types that could be characterized by a single profile and led to the identification of specific peptides that differentiate between the tumors.

Intronic deletion and duplication proximal of the EXT1 gene: a novel causative mechanism for multiple osteochondromas.

Multiple osteochondromas (MO) is a syndrome in which benign cartilage-capped neoplasms develop at the surface of the long bones. Most cases are caused by exonic changes in EXT1 or EXT2, but 15% are negative for these changes. Here we report for the first time a family of MO patients with germline genomic alterations at the EXT1 locus without detectable mutations or copy number alterations of EXT exonic sequences. Array-CGH showed an 80.7 kb deletion of Intron 1 of EXT1 and a 68.9 kb duplication proximal of EXT1. We identified a breakpoint between the distal end of the duplicated region and a sequence distal of the deleted region in the first intron. This breakpoint was absent in non-affected family members. The configuration of the breakpoint indicates a direct insertion of the duplicated region into the deletion. However, no other breakpoint was found, which suggests a more complex genomic rearrangement has occurred within the duplicated region. Our results reveal intronic deletion and duplication as a new causative mechanism for MO not detected by conventional diagnostic methods.

Cartilage tumour progression is characterized by an increased expression of heparan sulphate 6O-sulphation-modifying enzymes.

Chondrosarcomas are malignant cartilage-forming tumours that can arise centrally (in the medulla) or peripherally (at the surface) of the bone. They are classified into three histological grades which correspond to the clinical severity. Previous studies by our group have shown altered signal transduction of the fibroblast growth factor and Wnt signalling pathways during peripheral chondrosarcoma progression. Heparan sulphate (HS) is a glycosaminoglycan that facilitates receptor binding of multiple growth factors, in which the sulphation of 6O position plays a pivotal role. 6O-Sulphation occurs through three HS 6O-sulphotransferases (HS6ST1-3) and is fine-tuned by two endosulphatases (SULF1-2) that remove 6O-sulphate groups. We have investigated whether the expression of HS6STs and SULFs changes during chondrosarcoma progression and have determined 6O-sulphation levels in two chondrosarcoma cell lines. Immunohistochemistry on tissue microarrays of chondrosarcomas showed that HS6ST3 and SULF1 were highly expressed in most chondrosarcomas, whereas SULF2 expression was absent in most cases. HS6ST1 and HS6ST2 expression are significantly increased during chondrosarcoma progression, which suggest that 6O-sulphation is increased during progression. This was confirmed in one grade III chondrosarcoma cell line, which showed a dramatically increased 6O-sulphation compared to an articular chondrocyte cell line by HPLC; another cell line showed an increased expression of one 6O-sulphated HS disaccharide. In conclusion, our results show increased HS6ST1 and HS6ST2 expression during chondrosarcoma progression and increased HS 6O-sulphation in vitro. As 6O-sulphation plays an important role in signal transduction, altered HS6ST expression might be associated with changes in signal transduction pathways in chondrosarcoma progression.

On the map: Nature and Science editorials.

Bibliometric mapping of scientific articles based on keywords and technical terms in abstracts is now frequently used to chart scientific fields. In contrast, no significant mapping has been applied to the full texts of non-specialist documents. Editorials in Nature and Science are such non-specialist documents, reflecting the views of the two most read scientific journals on science, technology and policy issues. We use the VOSviewer mapping software to chart the topics of these editorials. A term map and a document map are constructed and clusters are distinguished in both of them. The validity of the document clustering is verified by a manual analysis of a sample of the editorials. This analysis confirms the homogeneity of the clusters obtained by mapping and augments the latter with further detail. As a result, the analysis provides reliable information on the distribution of the editorials over topics, and on differences between the journals. The most striking difference is that Nature devotes more attention to internal science policy issues and Science more to the political influence of scientists. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11192-010-0205-9) contains supplementary material, which is available to authorized users.

No haploinsufficiency but loss of heterozygosity for EXT in multiple osteochondromas.

Multiple osteochondromas (MO) is an autosomal dominant disorder caused by germline mutations in EXT1 and/or EXT2. In contrast, solitary osteochondroma (SO) is nonhereditary. Products of the EXT gene are involved in heparan sulfate (HS) biosynthesis. In this study, we investigated whether osteochondromas arise via either loss of heterozygosity (2 hits) or haploinsufficiency. An in vitro three-dimensional chondrogenic pellet model was used to compare heterozygous bone marrow-derived mesenchymal stem cells (MSCs EXT(wt/-)) of MO patients with normal MSCs and the corresponding tumor specimens (presumed EXT(-/-)). We demonstrated a second hit in EXT in five of eight osteochondromas. HS chain length and structure, in vitro chondrogenesis, and EXT expression levels were identical in both EXT(wt/-) and normal MSCs. Immunohistochemistry for HS, HS proteoglycans, and HS-dependent signaling pathways (eg, TGF-ß/BMP, Wnt, and PTHLH) also showed no differences. The cartilaginous cap of osteochondroma contained a mixture of HS-positive and HS-negative cells. Because a heterozygous EXT mutation does not affect chondrogenesis, EXT, HS, or downstream signaling pathways in MSCs, our results refute the haploinsufficiency theory. We found a second hit in 63% of analyzed osteochondromas, supporting the hypothesis that osteochondromas arise via loss of heterozygosity. The detection of the second hit may depend on the ratio of HS-positive (normal) versus HS-negative (mutated) cells in the cartilaginous cap of the osteochondroma.