Editorial: Controversies in the Local Management of Lung Cancer

At the time we agreed to edit this special edition of Frontiers in early 2017, the immunotherapy revolution was already established in the second-line treatment of metastatic non-small cell lung cancer (NSCLC) and even to a select group of patients (those whose tumor cells expressed PD-L1 of ≥50%) in the first-line treatment of metastatic disease. We felt that the summarization and understanding of the strengths and benefits of our local modalities were needed prior to the possible integration of immunotherapy into the treatment paradigms of Stages I–III NSCLC and small cell lung cancer (SCLC)

Multiple primary melanomas: Is there a correlation between dermoscopic features and germline mutations?

No abstract availabl

A Toolbox for Functional Analysis and the Systematic Identification of Diagnostic and Prognostic Gene Expression Signatures Combining Meta-Analysis and Machine Learning

The identification of biomarker signatures is important for cancer diagnosis and prognosis. However, the detection of clinical reliable signatures is influenced by limited data availability, which may restrict statistical power. Moreover, methods for integration of large sample cohorts and signature identification are limited. We present a step-by-step computational protocol for functional gene expression analysis and the identification of diagnostic and prognostic signatures by combining meta-analysis with machine learning and survival analysis. The novelty of the toolbox lies in its all-in-one functionality, generic design, and modularity. It is exemplified for lung cancer, including a comprehensive evaluation using different validation strategies. However, the protocol is not restricted to specific disease types and can therefore be used by a broad community. The accompanying R package vignette runs in ~1 h and describes the workflow in detail for use by researchers with limited bioinformatics training

DOPAL derived alpha-synuclein oligomers impair synaptic vesicles physiological function

Parkinson's disease is a neurodegenerative disorder characterized by the death of dopaminergic neurons and by accumulation of alpha-synuclein (aS) aggregates in the surviving neurons. The dopamine catabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL) is a highly reactive and toxic molecule that leads to aS oligomerization by covalent modifications to lysine residues. Here we show that DOPAL-induced aS oligomer formation in neurons is associated with damage of synaptic vesicles, and with alterations in the synaptic vesicles pools. To investigate the molecular mechanism that leads to synaptic impairment, we first aimed to characterize the biochemical and biophysical properties of the aS-DOPAL oligomers; heterogeneous ensembles of macromolecules able to permeabilise cholesterol-containing lipid membranes. aS-DOPAL oligomers can induce dopamine leak in an in vitro model of synaptic vesicles and in cellular models. The dopamine released, after conversion to DOPAL in the cytoplasm, could trigger a noxious cycle that further fuels the formation of aS-DOPAL oligomers, inducing neurodegeneration

Efficacy of milbemycin oxime/afoxolaner chewable tablets (NEXGARD SPECTRA®) against Capillaria aerophila and Capillaria boehmi in naturally infected dogs

BACKGROUND: Capillaria aerophila and Capillaria boehmi parasitize the respiratory system of wild and domestic carnivores. Capillaria aerophila inhabits the trachea and bronchi of dogs and cats, while C. boehmi affects the nasal cavities and sinuses of dogs. In dogs the infection may be subclinical or characterized by varying respiratory distress.METHODS: The present study evaluated the efficacyof an oral formulation containing milbemycin oxime and afoxolaner (NEXGARD SPECTRA) in dogs naturally infected with C. aerophila and/or C. boehmi from three enzootic areas of Italy. Dogs were enrolled pending fecal examination and molecular confirmation of respiratory capillarioses. Dogs were allocated in two groups: Group 1 (G1, 25 dogs), treated with a negative control product with no anthelmintic activity (afoxolaner, NEXGARD), and Group 2 (G2, 26 dogs), treated with NEXGARD SPECTRA. At the day of treatment administration (Day 0), all dogs were clinically examined. Dogs were again subjected to clinical and fecal examinations at Days 28 (±4) and 56 (±2). The primary criterion for treatment efficacy was the reduction of fecal Capillaria egg counts in G2 compared with G1. The regression of/recovery from baseline clinical signs was considered as a further efficacy criterion.RESULTS: Percentage reduction of fecal Capillaria egg counts in the NEXGARD SPECTRA group compared to the control group was >97% on Day 28 and 100% on Day 56, respectively (p<0.05 for both time points). Twelve of the 13 dogs in the NEXGARD SPECTRA group with respiratory signs prior to treatment were free of clinical signs at the end of the study. Conversely, the six control group dogs with respiratory signs prior to treatment remained symptomatic.CONCLUSIONS: Results of the present study showed that NEXGARD SPECTRA was safe and highly efficacious in the reduction of C. aerophila and C. boehmi eggs after one treatment with a complete reduction of the egg output after the second administration associated with a recovery from respiratory signs

Positron emission tomography in the diagnostic work-up of screening-detected lung nodules

Low-dose computed tomography (CT) screening for lung cancer can reduce lung cancer mortality, but overdiagnosis, false positives and invasive procedures for benign nodules are worrying. We evaluated the utility of positron emission tomography (PET)-CT in characterising indeterminate screeningdetected lung nodules. 383 nodules, examined by PET-CT over the first 6 years of the COSMOS (Continuous Observation of Smoking Subjects) study to diagnose primary lung cancer, were reviewed and compared with pathological findings (surgically-treated patients) or follow-up (negative CT for â\u89¥2 years, considered negative); 196 nodules were malignant. The sensitivity, specificity and accuracy of PET-CT for differentially diagnosing malignant nodules were, respectively, 64%, 89% and 76% overall, and 82%, 92% and 88% for baseline-detected nodules. Performance was lower for nodules found at repeat annual scans, with sensitivity ranging from 22% for nonsolid to 79% for solid nodules (p=0.0001). Sensitivity (87%) and specificity (73%) were high for nodules â\u89¥15 mm, better (sensitivity 98%) for solid nodules â\u89¥15 mm. PET-CT was highly sensitive for the differential diagnosis of indeterminate nodules detected at baseline, nodules â\u89¥15 mm and solid nodules. Sensitivity was low for sub-solid nodules and nodules discovered after baseline for which other methods, e.g. volume doubling time, should be used

Passive smoking outdoors is harmful: it is time to take a step forward!

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Absence of Viable Toxoplasma gondii in Artisanal Raw-Milk Ewe Cheese Derived from Naturally Infected Animals

The presence of viable Toxoplasma gondii was investigated in artisanal cheeses made from milk of naturally infected ewes. Ewe milk was analyzed beforehand for the presence and vitality of T. gondii by loop-mediated isothermal amplification (LAMP) and reverse-transcriptase PCR (RT-PCR), respectively. Cheeses were prepared from raw milk following a traditional cheesemaking process. The cheese obtained from T. gondii-positive milk was analyzed by LAMP to detect Toxoplasma DNA-positive samples. RT-PCR was then carried out to assess the viability of the parasites in T. gondii-positive milk samples and fresh cheese, after 5 and 15 days of ripening. Physical-chemical parameters of cheeses were also investigated. All cheese samples derived from T. gondii-positive milk were positive according to LAMP, at both 5 and 15 days of ripening, while none of the samples were positive according to RT-PCR. Thus, while the presence of the parasite was demonstrated by the detection of specific DNA, the absence of detectable T. gondii RNA supports the hypothesis that changes in the chemical and physical characteristics occurring during the cheesemaking process and ripening period, could be sufficient to inactivate viable T. gondii in milk, minimizing the risk of human infection through consumption of raw sheep milk cheese

Women in thoracic surgery: European perspectives

During the last decades, women have been discouraged from entering the medical career and in particular in the surgical specialties. This situation is changing across continents and national and international initiatives are supporting aspiring female surgeons in pursuing the surgical career through mentorship and fellowship programmes. Due to the differences in training programmes, Health Care systems and cultural backgrounds, it's not easy to describe unanimously the pathways and obstacles that junior female thoracic surgeons are experiencing in Europe. The development of female surgical associations, mentorship programmes and national initiatives will further champion the gender equality in this specialty across Europe. During the recent years, the European Society of Thoracic Surgeons (ESTS) has established initiatives like the first ESTS Women in Thoracic Surgery Scientific Session or the annual Women in Thoracic ESTS Reception during the Annual Conference, which are done in an effort to encourage all female colleagues to join this specialty and increase the opportunity to share their experience and meet potential mentors. In this article we will depict the situation in some of the European countries whose female thoracic surgeons have led their way. We aim to give the next generation the examples that can influence women's choice of surgical career, and the possible strategies and initiatives to reduce the gender discrimination within healthcare