New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

TRY plant trait database – enhanced coverage and open access

Plant traits - the morphological, anatomical, physiological, biochemical and phenological characteristics of plants - determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait‐based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits - almost complete coverage for ‘plant growth form’. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait–environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Autistic adults and adults with sub-clinical autistic traits differ from non-autistic adults in social-pragmatic inferencing and narrative discourse

Abstract Since prior research has mostly focused on children, less is known about how autistic adults and adults with sub-clinical autistic traits interpret pragmatically complex social situations and the kind of narrative discourse they produce. 32 autistic young adults, 18 young adults with sub-clinical autistic traits and 34 non-autistic young adults participated this study. They were shown videos of social interactions which required complex pragmatic processing and were asked to freely narrate what they thought was occurring in each video. Their narratives were coded for aspects of social-pragmatic and narrative discourse. The results indicate that the autistic and sub-clinical groups differed from the comparison group in what they inferred as relevant video content. The narratives of the autistic group also differed from the comparison group in meaning, focus and emphasis on details. In addition, the comparison group produced more holistic narratives whereas the autistic and sub-clinical groups produced more atomistic narratives. Correlational findings indicated that perceptual reasoning has stronger associations with pragmatic inferencing in the autistic and sub-clinical groups than in the comparison group. This study suggests that autistic adults and adults with sub-clinical autistic traits differ from non-autistic adults in what they perceive to be relevant in their social world

The effect of fascin 1 inhibition on head and neck squamous cell carcinoma cells

Abstract Fascin 1 plays important pro-metastatic roles in head and neck carcinoma (HNSCC) migration, invasion, and metastasis. However, limited advancement in targeting metastasis remains a major obstacle in improving HNSCC patients’ survival. Therefore, we assessed the therapeutic potential of fascin 1 targeted inhibition and its potential prognostic value in HNSCC patients. Using in vitro and in vivo approaches, we investigated the effect of compound G2, a novel fascin 1 inhibitor, on HNSCC cells migration, invasion, and metastasis. High-throughput screening (HTS) was used to assess cytotoxic activity of compound G2 alone or combined with irradiation. We also evaluated the prognostic potential of fascin 1 in HNSCC patients. Interestingly, compound G2 reduced carcinoma cells migration and invasion in vitro and inhibited metastasis in vivo. Moreover, HTS revealed a modest cytotoxic activity of the compound G2 on HNSCC cell lines. Irradiation did not synergistically enhance the compound G2-mediated cytotoxic activity. Survival analyses showed that high fascin 1 immunoexpression, at the tumor invasive front, was associated with cancer-specific mortality in the advanced stages of HNSCC. Collectively, our findings suggest that fascin 1 represents a promising anti-metastatic therapeutic target and a useful prognostic marker in patients with HNSCC. Novel anti-metastatic agents could provide a valuable addition to cancer therapy

Seasonal regulation of metabolism:the effect of wintertime fasting and autumnal fattening on key central regulators of metabolism and the metabolic profile of the raccoon dog (Nyctereutes Procyonoides)

Abstract Investigations into the mechanisms regulating obesity are frantic and novel translational approaches are needed. The raccoon dog (Nyctereutes procyonoides) is a canid species representing a promising model to study metabolic regulation in a species undergoing cycles of seasonal obesity and fasting. To understand the molecular mechanisms of metabolic regulation in seasonal adaptation, we analyzed key central nervous system and peripheral signals regulating food intake and metabolism from raccoon dogs after autumnal fattening and winter fasting. Expressions of neuropeptide Y (NPY), orexin-2 receptor (OX2R), pro-opiomelanocortin (POMC) and leptin receptor (ObRb) were analyzed as examples of orexigenic and anorexigenic signals using qRT-PCR from raccoon dog hypothalamus samples. Plasma metabolic profiles were measured with ¹H NMR-spectroscopy and LC-MS. Circulating hormones and cytokines were determined with canine specific antibody assays. Surprisingly, NPY and POMC were not affected by the winter fasting nor autumn fattening and the metabolic profiles showed a remarkable equilibrium, indicating conserved homeostasis. However, OX2R and ObRb expression changes suggested seasonal regulation. Circulating cytokine levels were not increased, demonstrating that the autumn fattening did not induce subacute inflammation. Thus, the raccoon dog developed seasonal regulatory mechanisms to accommodate the autumnal fattening and prolonged fasting making the species unique in coping with the extreme environmental challenges

Non-linguistic comprehension, social inference and empathizing skills in autistic young adults, young adults with autistic traits and control young adults:group differences and interrelatedness of skills

Abstract Background: Despite increasing knowledge of social communication skills of autistic peole, the interrelatedness of different skills such as non-linguistic comprehension, social inference and empathizing skills is not much known about. A better understanding of the complex interplay between different domains of social communication helps us to develop assessment protocols for individuals with social communication difficulties. Aims: To compare the performances of autistic young adults, young adults with autistic traits identified in childhood and control young adults in social communication tasks measuring non-linguistic comprehension, social inference and empathizing skills. In addition, to examine associations between the different social communication measures. Methods &amp; Procedures: Autistic young adults (n = 34), young adults with autistic traits (n = 19) and control young adults (n = 36) completed the extra- and paralinguistic scales of the Assessment Battery for Communication (ABaCo), the Faux Pas Recognition Test, Social–Pragmatic Questions (SoPra) and the Empathy Quotient (EQ). Outcomes &amp; Results: Group differences were found in the performance in the ABaCo, SoPra and EQ scores. Compared with the control young adults, autistic young adults scored lower. The performance of the young adults in the autistic traits group fell in between the other two groups. There were no group differences in the Faux Pas Recognition Test. The variability within the groups was large in all measurements. In the control group, there was a significant correlation between EQ and SoPra scores and between the Faux Pas and SoPra scores. In the autistic group, a significant correlation was found between Faux Pas and SoPra scores. Also, other patterns were observed but these were not statistically significant. Conclusions &amp; Implications: The young adults with autistic traits fell in between the control and autistic young adults, highlighting the presence of the continuum in the terms of features of social communication. The results support other current research that suggests that theory of mind and other social communication skills may not be universally or widely impaired in all autistic individuals without cognitive deficits. Although all tasks examined social communication skills, only a small number of significant correlations were found between test scores. This highlights that clinical conclusions about a person’s social communication should be based on the outcomes of different types of methods measuring different aspects of social communication. It is clear that the interrelatedness of different social communication skills needs further research. What This Paper Adds What is already known on this subject: For successful communication, the ability to infer others’ emotions, intentions and mental states is crucial. Autistic people have difficulty with many aspects of social communication. However, the associations between different aspects of social communication need to be better understood. What this paper adds to existing knowledge: The unique contribution of this study is to compare the performance of autistic people not only with that of a control group but also with people with childhood autistic traits. This provides an understanding of the interrelatedness of different social communication skills in people with varying degrees of autistic traits. This study used four assessment methods focusing on three different social communication elements (non-linguistic comprehension, social inference and empathizing skills). These elements have complex relationships to one another, some being closely overlapping, some more distally related and some reflect more complex multifactorial elements. This study shows that although groups differ from each other in most of the assessments, the performance of different groups overlapped showing that many autistic young adults can perform well in non-linguistic and social inference tasks in structured assessment contexts. What are the potential or actual clinical implications of this work? Our findings suggest that in the assessment of social communication, self-reports and clinical assessments can be used effectively together. They can complement each other, pointing out the strengths and weaknesses of a person, leading to more personalized therapeutic interventions

Short interruptions of TNF-inhibitor treatment can be associated with treatment failure in patients with immune-mediated diseases

Abstract Introduction: The prevalence of immune-mediated diseases has increased in the past decades and despite the use of biological treatments all patients do not achieve remission. The aim of this study was to characterise the reasons for short interruptions during treatment with two commonly used TNF-inhibitors infliximab and adalimumab and to analyse the possible effects of the interruptions on immunisation and switching the treatment. Material and methods: This case-control study was based on retrospective analyses of patient records and a questionnaire survey to clinicians. A total of 370 patients (194 immunised cases and 172 non-immunised controls, 4 excluded) were enrolled from eight hospitals around Finland. Eleven different diagnoses were represented, and the largest patient groups were those with inflammatory bowel or rheumatic diseases. Results: Treatment interruptions were associated with immunisation in patients using infliximab (p &lt; .001) or adalimumab (p &lt; .000001). Patients with treatment interruptions were more likely to have been treated with more than one biological agent compared to those without treatment interruptions. This was particularly prominent among patients with a rheumatic disease (p &lt; .00001). The most frequent reason for a treatment interruption among the cases was an infection, whereas among the control patients it was remission. The median length of one interruption was one month (interquartile range 1–3 months). Conclusion: Our results suggest that the interruptions of the treatment with TNF-inhibitors expose patients to immunisation and increase the need for drug switching. These findings stress the importance of careful judgement of the need for a short interruption in the biological treatment in clinical work, especially during non-severe infections

Small oral tongue cancers (≤ 4 cm in diameter) with clinically negative neck:from the 7th to the 8th edition of the American Joint Committee on Cancer

Abstract One of the main changes in the 8th edition of the American Joint Committee on Cancer (AJCC) for staging of oral cancer is the inclusion of depth of invasion (DOI) in the T category. However, cancers in different oral subsites have variable behavior, with oral tongue squamous cell carcinoma (OTSCC) being the most aggressive one even at early stage. Thus, it is necessary to evaluate the performance of this new T category in homogenous cohort of early OTSCC. Therefore, we analyzed a large cohort of patients with a small (≤ 4 cm) OTSCC to demonstrate the differences in T stage between the AJCC 7th and 8th editions. A total of 311 early-stage cases (AJCC 7th) of OTSCC were analyzed. We used 5 mm and 10 mm DOI for upstaging from T1 to T2 and from T2 to T3 respectively, as in the AJCC 8th. We further reclassified the cases according to our own proposal suggesting 2 mm to upstage to T2 and 4 mm to upstage to T3. According to AJCC 7th, there were no significant differences in the survival analysis. When we applied the 8th edition, many cases were upstaged to T3 and thus associated with worse disease-specific survival (HR 2.37, 95% CI 1.12–4.99) and disease-free survival (HR 2.12, 95% CI 1.09–4.08). Based on our proposal, T3 cases were associated with even worse disease-specific survival (HR 4.19, 95% CI 2.27–7.74). The 8th edition provides better survival prediction for OTSCC than the 7th and can be further optimized by lowering the DOI cutoffs

Prognostic impact of tumour–stroma ratio in early‐stage oral tongue cancers

Abstract Aims: Oral tongue squamous cell carcinoma (OTSCC) has a relatively poor outcome, and there is a need to identify better prognostic factors. Recently, tumour–stroma ratio (TSR) has been associated with prognosis in several cancers. The aim of this multi‐institutional study was to evaluate the prognostic value of TSR from original haematoxylin and eosin (HE)‐stained tumour‐resection slides in a series of early‐stage (cT1‐2N0) OTSCC patients. Methods and results: A TSR cutoff value of 50% was used to divide the patients into stroma‐rich (≥50%) and stroma‐poor (&lt;50%) groups. The relationships between TSR and clinicopathological characteristics of 311 early‐stage OTSCC cases were analysed. The prognostic value of TSR in OTSCC was calculated separately and in combination with a previously published cancer cell budding and depth of invasion (BD) prognostic model. A total of 89 cases (28.6%) belonged to the stroma‐rich group. In a multivariate analysis, the stroma‐rich group had worse disease‐free survival, with a hazard ratio (HR) of 1.81 [95% confidence interval (CI) 1.17–2.79, P = 0.008], and higher cancer‐related mortality (HR 1.71, 95% CI 1.02–2.86, P = 0.03). The combination of the highest‐risk parameter scores of TSR and the BD model showed significant correlations with recurrence rate (HR 3.42, 95% CI 1.71–6.82, P = 0.004) and cancer‐related mortality (HR 11.63, 95% CI 3.83–35.31, P &lt; 0.001). Conclusions: We conclude that TSR is a simple histopathological feature that is useful for prognostication of early‐stage OTSCC, and suggest that TSR analyses in association with BD score could be included in routine clinical pathology reports for HE‐stained slides