Cytopathology of non‐invasive follicular thyroid neoplasm with papillary‐like nuclear features: A comparative study with similar patterned papillary thyroid carcinoma variants

Objective

Noninvasive follicular thyroid neoplasm with papillary‐like nuclear features (NIFTP) is a recently described, indolent thyroid tumor, with well‐defined histopathological diagnostic criteria. Cytology features are not well documented. We reviewed cytology of histologically proven cases of NIFTP and some of its common differentials to look for salient diagnostic features.

Methods

Cases reported on histopathology as follicular variant of papillary thyroid carcinoma (FVPTC), or NIFTP between July 2015 and April 2017 having available cytology smears were retrieved and reclassified as NIFTP, FVPTC, and classical papillary thyroid carcinoma with predominant follicular pattern (PTC‐FP). Cytological features were assessed, classified as per The Bethesda System for Reporting Cytopathology and compared.

Results

There were 23 NIFTP cases, 18 FVPTC and 8 PTC‐FP. A microfollicle‐predominant pattern was seen in all. Nuclear score was 2 in most NIFTP cases (61%). Pseudoinclusions were absent. NIFTP showed features of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) (III) in 61%, follicular neoplasm/suspicious for a follicular neoplasm (FN/SFN) (IV) in 35% and suspicious for malignancy (SFM) (V) in 4%. Most of the FVPTCs were also called FN/SFN (IV) (56%) or AUS/FLUS (III) (22%). Nuclear features did not statistically differ from NIFTP. PTC‐FP showed high‐grade cytology in 75%, and higher nuclear score (3 in 75%) in contrast to NIFTP (P = .003).

Conclusion

NIFTP and FVPTC show a similar distribution among the Bethesda categories hence precluding conclusive distinction on cytology. PTC‐FP, in contrast, was found to have a statistically significant higher nuclear score and more commonly showed malignant cytology.

     

The impact of the non‐invasive follicular thyroid neoplasm with papillary‐like nuclear feature terminology in the routine diagnosis of thyroid tumours

Background

Due to the recent proposal of the non‐invasive follicular thyroid neoplasm with papillary‐like nuclear feature (NIFTP) category, the authors analyse the state of the art in the challenging diagnosis of follicular thyroid neoplasms in routine practice.

Methods and results

A consecutive series of 200 histological diagnoses, with complete cytological correlation, was analysed following the introduction of the NIFTP definition. The study was conducted in a general hospital with a high prevalence of thyroid benign nodules that accounted for approximately 60% of surgically‐treated nodules. The significant incidence of the new NIFTP category was 7%. Concurrently, a gradual decrease of the follicular variant of papillary thyroid carcinoma (fvPTC) was observed (3.5%). When evaluating the FNA biopsies within the NIFTP group, despite the systematic evaluation of nuclear crowding, enlargement, irregularities and clearing, the final cytological class was often indeterminate for malignancy (Thy3/III‐IV, 71%). At histology, the application of the semiquantitative NIFTP score for the evaluation of the PTC‐like nuclear features was able to discriminate benign lesions (score 0/1) from fvPTC (score 2/3). A certain degree of overlapping still persisted between NIFTP and fvPTC (score 2) or between NIFTP and benign lesions (score 1).

Conclusions

In the routine evaluation of FNA biopsies, the presence of subtle and questionable PTC‐like nuclear features still remains a controversial aspect of the diagnostic workflow. Given that the NIFTP category was introduced to stratify the low‐risk group of thyroid tumours more precisely, pathologists should force themselves to apply the nuclear score rigorously and to classify cases assigned a score of 1 as benign proliferations.

     

Pre‐operative features of non‐invasive follicular thyroid neoplasms with papillary‐like nuclear features: An analysis of their cytological,Gene Expression Classifier and sonographic findings

Objective

To investigate the corresponding cytological diagnoses, Gene Expression Classifier (GEC) results and ultrasound features of thyroid nodules diagnosed as non‐invasive follicular thyroid neoplasms with papillary‐like nuclear features (NIFTP), as well as any coexisting pathology.

Methods

We performed a retrospective review of thyroid nodules histologically diagnosed as NIFTP at our institution between 1^st April 2016 and 1^st April 2017. The following data points were collected: demographics, nodule size, ultrasound features, cytological diagnosis, GEC results, origin of sample (in‐house vs outside hospital) and any additional pathology identified in the resection specimen.

Results

The case cohort included 87 nodules diagnosed as NIFTP (size range: 1‐7 cm, mean: 2.5 cm) from 82 patients (age range: 22‐82, mean age: 50.4, M:F—1:4.1). Corresponding FNA results were available for 72 nodules (82.8%) and were categorised as follows: benign (n = 5, 6.9%), atypia of unknown significance/follicular lesion of undetermined significance (n = 29, 40.3%), follicular neoplasm/suspicious for follicular neoplasm/follicular neoplasm with oncocytic features (n = 27, 37.5%), suspicious for papillary thyroid carcinoma (n = 6, 8.3%) and malignant (n = 5, 6.9%). GEC results were available for 32 (44.4%) nodules, with the majority of cases classified as suspicious (81.3%). On ultrasound, most of the nodules were predominantly solid (81.8%), vascular (93.8%), non‐calcified (86.5%), and either hypoechoic (44.9%) or isoechoic (38.8%). In addition to NIFTP and other benign findings in the background thyroid, 75 separate malignant tumours were identified in 38 (46.3%) patients, many of which were papillary thyroid microcarcinomas (86.5%) with lymph node metastases present in two cases.

Conclusions

The majority of thyroid nodules histologically diagnosed as NIFTP have indeterminate cytology (77.8%) and are classified as suspicious (81.3%) by GEC testing. Taken together, these findings can guide clinicians toward a more conservative therapeutic approach.

     

Species traits suggest European mammals facing the greatest climate change are also least able to colonize new locations

Aim

The risk climate change poses to biodiversity is often estimated by forecasting the areas that will be climatically suitable for species in the future and measuring the distance of the “range shifts” species would have to make to reach these areas. Species’ traits could indicate their capacity to undergo range shifts. However, it is not clear how range‐shift capacity influences risk. We used traits from a recent evidence review to measure the relative potential of species to track changing climatic conditions.

Location

Europe.

Time period

Baseline period (1961–1990) and forecast period (2035–2064).

Major taxa studied

62 mammal species.

Methods

We modelled species distributions using two general circulation models and two representative concentration pathways (RCPs) to calculate three metrics of “exposure” to climate change: range area gained, range area lost and distance moved by the range margin. We identified traits that could inform species’ range‐shift capacity (i.e., potential to establish new populations and proliferate, and thus undertake range shifts), from a recent evidence‐based framework. The traits represent ecological generalization and reproductive strategy. We ranked species according to each metric of exposure and range‐shift capacity, calculating sensitivity to ranking methods, and synthesized both exposure and range‐shift capacity into “risk syndromes.”

Results

Many species studied whose survival depends on colonizing new areas were relatively unlikely to undergo range shifts. Under the worst‐case scenario, 62% of species studied were relatively highly exposed. 47% were highly exposed and had relatively low range‐shift capacity. Only 14% of species faced both low exposure and high range‐shift capacity. Both range‐shift and exposure metrics had a greater effect on risk assessments than climate models.

Main conclusions

The degree to which species’ potential ranges will be altered by climate change often does not correspond to species’ range‐shift capacities. Both exposure and range‐shift capacity should be considered when evaluating biodiversity risk from climate change.

     

Mesenchymal‐like stem cells in canine ovary show high differentiation potential

Objectives

Recent studies have reported the existence of stem cells in ovarian tissue that show enhanced proliferative and differentiation potential compared to other adult tissues. Based on this evidence, we hypothesized that ovarian tissue contained mesenchymal‐like stem cells (MSC) that could be isolated using a novel rapid plastic adhesion technique.

Materials and methods

We established MSC lines derived from ovarian and adipose tissue based on their ability to rapidly adhere to plastic culture dishes in the first 3 hours after plating and studied their potentiality in terms of molecular markers and differentiation capacity.

Results

Morphological and kinetic properties of in vitro cultured ovarian MSC were similar to adipose‐derived MSC, and both reached senescence after similar passage numbers. Ovarian‐derived MSC expressed mesenchymal (CD90 and CD44) but not haematopoietic markers (CD34 and CD45), indicating similarity to adipose‐derived MSC. Moreover, ovarian‐derived MSC expressed NANOG, TERT, SOX2, OCT4 and showed extensive capacity to differentiate not only into adipogenic, osteogenic and chondrogenic tissue but also towards neurogenic and endodermal lineages and even precursors of primordial germ cells.

Conclusion

These results show for the first time the derivation of ovarian cells with the molecular properties of MSC as well as wide differentiation potential. Canine ovarian tissue is accessible, expandable, multipotent and has high plasticity, holding promise for applications in regenerative medicine.

     

Ocean current connectivity propelling the secondary spread of a marine invasive comb jelly across western Eurasia

Aim

Invasive species are of increasing global concern. Nevertheless, the mechanisms driving further distribution after the initial establishment of non‐native species remain largely unresolved, especially in marine systems. Ocean currents can be a major driver governing range occupancy, but this has not been accounted for in most invasion ecology studies so far. We investigate how well initial establishment areas are interconnected to later occupancy regions to test for the potential role of ocean currents driving secondary spread dynamics in order to infer invasion corridors and the source–sink dynamics of a non‐native holoplanktonic biological probe species on a continental scale.

Location

Western Eurasia.

Time period

1980s–2016.

Major taxa studied

‘Comb jelly’ Mnemiopsis leidyi.

Methods

Based on 12,400 geo‐referenced occurrence data, we reconstruct the invasion history of M. leidyi in western Eurasia. We model ocean currents and calculate their stability to match the temporal and spatial spread dynamics with large‐scale connectivity patterns via ocean currents. Additionally, genetic markers are used to test the predicted connectivity between subpopulations.

Results

Ocean currents can explain secondary spread dynamics, matching observed range expansions and the timing of first occurrence of our holoplanktonic non‐native biological probe species, leading to invasion corridors in western Eurasia. In northern Europe, regional extinctions after cold winters were followed by rapid recolonizations at a speed of up to 2,000 km per season. Source areas hosting year‐round populations in highly interconnected regions can re‐seed genotypes over large distances after local extinctions.

Main conclusions

Although the release of ballast water from container ships may contribute to the dispersal of non‐native species, our results highlight the importance of ocean currents driving secondary spread dynamics. Highly interconnected areas hosting invasive species are crucial for secondary spread dynamics on a continental scale. Invasion risk assessments should consider large‐scale connectivity patterns and the potential source regions of non‐native marine species.

     

Factors influencing above‐ground and soil seed bank vegetation diversity at different scales in a quasi‐Mediterranean ecosystem

Questions

Are factors influencing plant diversity in a fire‐prone Mediterranean ecosystem of southeast Australia scale‐dependent?

Location

Heathy woodland, Otways region, Victoria, southeast Australia

Methods

We measured patterns of above‐ground and soil seed bank vegetation diversity and associated them with climatic, biotic, edaphic, topographic, spatial and disturbance factors at multiple scales (macro to micro) using linear mixed effect and generalized dissimilarity modelling.

Results

At the macro‐scale, we found species richness above‐ground best described by climatic factors and in the soil seed bank by disturbance factors. At the micro‐scale we found species richness best described above‐ground and in the soil seed bank by disturbance factors, in particular time‐since‐last‐fire. We found variance in macro‐scale β‐diversity (species turnover) best explained above‐ground by climatic and disturbance factors and in the soil seed bank by climatic and biotic factors.

Conclusions

Regional climatic gradients interact with edaphic factors and fire disturbance history at small spatial scales to influence species richness and turnover in the studied ecosystem. Current fire management regimes need to incorporate key climatic–disturbance–diversity interactions to maintain floristic diversity in the studied system.

     

Body Composition Percentiles in Urban South Indian Children and Adolescents

Objective

This study aimed to generate age‐ and sex‐specific percentiles for body composition indices in children and to assess the variability in these indices, in relation to BMI.

Methods

Anthropometry and body fat were measured with the BOD POD (Cosmed; Rome, Italy) in 9,702 children from Bangalore, India. Smoothed percentile curves using the lambda‐mu‐sigma method were obtained for BMI, fat‐free mass index (FFMI), fat mass index (FMI), and body fat percentage (% BF).

Results

Percentile curves for % BF and FMI in boys increased from 6 to 12 years and declined from 13 years on, while in girls, it increased until 15 years. The FFMI percentile curves increased with age in both sexes. The mean FMI declined from 12 years on in boys, corresponding to a large increase in FFMI from that age, while in girls, both FMI and FFMI continued to increase. The 75th percentile of % BF and FMI had greater sensitivity to identify children with obesity.

Conclusions

This study developed smoothed percentile curves for body composition in Indian children and suggests FMI and FFMI as good indicators of growth in children.

     

Low‐intensity pulsed ultrasound induced enhanced adipogenesis of adipose‐derived stem cells

Objective

The aim of this study was to investigate effects of low‐intensity pulsed ultrasound (LIPUS) on differentiation of adipose‐derived stem cells (ASCs), in vitro.

Materials and methods

Murine ASCs were treated with LIPUS for either three or five days, immediately after adipogenic induction, or delayed for 2 days. Expression of adipogenic genes PPAR‐γ1, and APN, was examined by real‐time PCR. Immunofluorescence (IF) staining was performed to test for PPAR‐γ at the protein level.

Results

Our data revealed that specific patterns of LIPUS up‐regulated levels of both PPAR‐γ1 and APN mRNA, and PPAR‐γ protein.

Conclusions

In culture medium containing adipogenic reagents, LIPUS enhanced ASC adipogenesis.

     

Mesenchymal stem cell transfusion for desensitization of positive lymphocyte cross‐match before kidney transplantation: outcome of 3 cases

Objectives

Donor specific antibodies (DSA) and a positive cross‐match are contraindications for kidney transplantation. Trials of allograft transplantation across the HLA barrier have employed desensitization strategies, including the use of plasmapheresis, intravenous immunoglobulins, anti‐B‐cell monoclonal antibodies and splenectomy, associated with high‐intensity immunosuppressive regimens. Our case 1 report suffered from repeatedly positive lymphocyte cross match after 1st renal transplantation. Graft nephrectomy could not correct the state of sensitization. Splenectomy was done in a trial to get rid of the antibody producing clone. Furthermore plasmapheresis with low dose IVIG could not as well revert the state of sensitization for the patient.

Material and methods

About 50 millions donor specific MSCs were injected to the patient.

Results

MSCs transfusion proved to be the only procedure which could achieve successful desensitization before performing the second transplantation owing to their immunosuppressive properties.

Conclusion

This case indicates that DS‐MSCs is a potential option for anti‐HLA desensitization. In cases 2 and 3 IV DS‐MSCs transfusion was selected from the start as a successful line of treatment for pre renal transplantation desensitization to save other unnecessary lines of treatment that were tried in case 1.

     

BioTIME: A database of biodiversity time series for the Anthropocene

Motivation

The BioTIME database contains raw data on species identities and abundances in ecological assemblages through time. These data enable users to calculate temporal trends in biodiversity within and amongst assemblages using a broad range of metrics. BioTIME is being developed as a community‐led open‐source database of biodiversity time series. Our goal is to accelerate and facilitate quantitative analysis of temporal patterns of biodiversity in the Anthropocene.

Main types of variables included

The database contains 8,777,413 species abundance records, from assemblages consistently sampled for a minimum of 2 years, which need not necessarily be consecutive. In addition, the database contains metadata relating to sampling methodology and contextual information about each record.

Spatial location and grain

BioTIME is a global database of 547,161 unique sampling locations spanning the marine, freshwater and terrestrial realms. Grain size varies across datasets from 0.0000000158 km² (158 cm²) to 100 km² (1,000,000,000,000 cm²).

Time period and grain

BioTIME records span from 1874 to 2016. The minimal temporal grain across all datasets in BioTIME is a year.

Major taxa and level of measurement

BioTIME includes data from 44,440 species across the plant and animal kingdoms, ranging from plants, plankton and terrestrial invertebrates to small and large vertebrates.

Software format

.csv and .SQL.

     

Effects of simvastatin and rosuvastatin on RAS protein,matrix metalloproteinases and NF‐κB in lung cancer and in normal pulmonary tissues

Objectives

In this study, we have evaluated effects of 24‐hour treatments with simvastatin or rosuvastatin on RAS protein, NF‐κB and MMP expression in LC tissues obtained from 12 patients undergoing thoracic surgery.

Materials and methods

Normal and lung tumour tissues obtained from each sample were exposed to simvastatin (2.5–30 μm ) or rosuvastatin (1.25–30 μm ) and western blot analysis was then performed.

Results

We documented increased expression of proteins, MMP‐2, MMP‐9 and NF‐κB‐p65 in LC tissues, with respect to normal tissues (P < 0.01). In the malignant tissues, simvastatin and rosuvastatin significantly (P < 0.01) and dose‐dependently reduced RAS protein, MMP‐2/9 and NF‐κB‐p65 expression.

Conclusions

In conclusion, our results suggest that simvastatin and rosuvastatin could play a role in LC treatment by modulation of RAS protein, MMP‐2/9 and NF‐κB‐p65.

     

Critical role of inflammatory mast cell in fibrosis: Potential therapeutic effect of IL‐37

Background

Fibrosis involves the activation of inflammatory cells, leading to a decrease in physiological function of the affected organ or tissue.

Aims

To update and synthesize relevant information concerning fibrosis into a new hypothesis to explain the pathogenesis of fibrosis and propose potential novel therapeutic approaches.

Materials and Methods

Literature was reviewed and relevant information is discussed in the context of the pathogenesis of fibrosis.

Results

A number of cytokines and their mRNA are involved in the circulatory system and in organs of patients with fibrotic tissues. The profibrotic cytokines are generated by several activated immune cells, including fibroblasts and mast cells (MCs), which are important for tissue inflammatory responses to different types of injury. MC‐derived TNF, IL‐1, and IL‐33 contribute crucially to the initiation of a cascade of the host defence mechanism(s), leading to the fibrosis process. Inhibition of TNF and inflammatory cytokines may slow the progression of fibrosis and improve the pathological status of the affected subject. IL‐37 is generated by various types of immune cells and is an IL‐1 family member protein. IL‐37 is not a receptor antagonist; it binds IL‐18 receptor alpha (IL‐18Rα) and delivers the inhibitory signal by using TIR8. It has been shown that IL‐37 can be protective in inflammation and injury, and inhibits both innate and adaptive immunity.

Discussion

IL‐37 may be useful for suppression of inflammatory diseases induced by inhibiting MyD88‐dependent TLR signalling. In addition, IL‐37 downregulates NF‐κB induced by TLR2 or TLR4 through a mechanism dependent on IL‐18Rα.

Conclusion

This review summarizes current knowledge on the role of MC in inflammation and tissue/organ fibrosis, with a focus on the therapeutic potential of IL‐37‐targeting cytokines.

     

Identifying the factors that determine the severity and type of alien bird impacts

Aim

To identify traits related to the severity and type of environmental impacts generated by alien bird species, in order to improve our ability to predict which species may have the most damaging impacts.

Location

Global.

Methods

Information on traits hypothesized to influence the severity and type of alien bird impacts was collated for 113 bird species. These data were analysed using mixed effects models accounting for phylogenetic non‐independence of species.

Results

The severity and type of impacts generated by alien bird species are not randomly distributed with respect to their traits. Alien range size and habitat breadth were strongly associated with impact severity. Predation impacts were strongly associated with dietary preference, but also with alien range size, relative brain size and residence time. Impacts mediated by interactions with other alien species were related to alien range size and diet breadth.

Main conclusions

Widely distributed generalist alien birds have the most severe environmental impacts. This may be because these species have greater opportunity to cause environmental impacts through their sheer number and ubiquity, but this could also be because they are more likely to be identified and studied. Our study found little evidence for an effect of per capita impact on impact severity.

     

Comprehensive molecular profiling of the B7 family in gastrointestinal cancer

Objectives

B7 family has been identified as co‐stimulatory or co‐inhibitory molecules on T‐cell response and plays an important role in tumour mortality and malignancy. In this study, the expression pattern of B7 family in gastrointestinal (GI) cancer was examined. Its upstream regulating mechanism, downstream targets and association with clinical parameters were also studied.

Materials and methods

The expression level of B7 members was analysed by FIREHOUSE. The gene mutation, DNA methylation, association with clinical parameters and downstream network of B7 members were analysed in cBioportal. The mutation frequency was analysed by Catalogue of Somatic Mutations in Cancer (COSMIC) analysis. The phylogenetic tree was constructed in MEGA7. The interaction protein domain analysis was performed by Pfam 31.0.

Results

Differential expression of B7 family molecules was detected in different kinds of GI cancer. High‐frequency gene alteration was found in tumour samples. There was negative correlation of promoter methylation and mRNA expression of B7 family members in tumour samples, suggesting the epigenetic basis of B7 family gene deregulation in GI cancer. The overexpression of B7‐H1 in pancreatic cancer, B7‐H5 in oesophageal cancer and B7‐H6 in liver cancer were significantly associated with worse overall survival. Finally, by network analysis, we identified some potential interacting proteins for B7‐1/2 and B7‐H1/DC.

Conclusions

Overall, our study suggested that B7 member deregulation was strongly involved in GI cancer tumorigenesis.

     

Effect of substrate stiffness on proliferation and differentiation of periodontal ligament stem cells

Objectives

The aim of this study was to understand the effect of substrate stiffness (a mechanical factor of the extracellular matrix) on periodontal ligament stem cells (PDLSCs) and its underlying mechanism.

Materials and methods

Elastic substrates were fabricated by mixing 2 components, a base and curing agent in proportions of 10:1, 20:1, 30:1 or 40:1. PDLSC morphology was observed using scanning electron microscopy (SEM). Cell proliferation and differentiation were assessed after PDLSCs was cultured on various elastic substrates. Data were analysed using one‐way ANOVA.

Results

SEM revealed variations in the morphology of PDLSCs cultured on elastic substrates. PDLSC proliferation increased with substrate stiffness (P < .05). Osteogenic differentiation of PDLSCs was higher on stiff substrates. Notch pathway markers were up‐regulated in PDLSCs cultured on stiff substrates.

Conclusions

Results suggested that the osteogenic differentiation of PDLSCs might be promoted by culturing them in a stiffness‐dependent manner, which regulates the Notch pathway. This might provide a new method of enhancing osteogenesis in PDLSCs.

     

Resistance Training Reduces Skeletal Muscle Work Efficiency in Weight‐Reduced and Non–Weight‐Reduced Subjects

Objective

The objective of this study is to determine whether resistance training is similarly effective in reducing skeletal muscle efficiency and increasing strength in weight‐reduced and maximal weight subjects.

Methods

This study examined the effects of supervised resistance exercise on skeletal muscle in 14 individuals with overweight and obesity sustaining a 10% or greater weight loss for over 6 months and a phenotypically similar group of 15 subjects who had not reduced weight and were weight stable at their maximal lifetime body weight. We assessed skeletal muscle work efficiency and fuel utilization (bicycle ergometry), strength (dynamometry), body composition (dual energy x‐ray absorptiometry), and resting energy expenditure (indirect calorimetry) before and after 12 weeks of thrice‐weekly resistance training.

Results

Non–weight‐reduced subjects were significantly (10%‐20%) stronger before and after the intervention than reduced‐weight subjects and gained significantly more fat‐free mass with a greater decline in percentage of body fat than weight‐reduced subjects. Resistance training resulted in similar significant decreases (~10%) in skeletal muscle work efficiency at low‐level exercise and ~10% to 20% increases in leg strength in both weight‐reduced and non–weight‐reduced subjects.

Conclusions

Resistance training similarly increases muscle strength and decreases efficiency regardless of weight loss history. Increased resistance training could be an effective adjunct to reduced‐weight maintenance therapy.