Recent Advances in Time-resolved Nir Spectroscopy for Nondestructive Assessment of Fruit Quality

Non-destructive monitoring of food internal attributes by near infrared spectroscopy (NIRS) is typically performed by the continuous wave (CW) technique, where steady state light sources (e.g. lamp or LED with constant intensity in time) and photodetectors (e.g. photodiode or charge coupled device camera) are used to measure light attenuation. Indeed light scattering can largely affect light attenuation resulting in the need of calibration for each new batch of samples. To tackle this effect time-resolved NIRS (TRS) has been proposed to improve the classical CW approach to NIRS. The main feature of TRS is its ability to retrieve information on photon path-length in a diffusive medium (generally much larger than the geometrical distance between source and detector). The use of TRS in combination with proper physical models for photon migration allows for the complete optical characterisation with the simultaneous non-destructive measurement of the optical properties (absorption and scattering) of a diffusive medium. This can be of special interest for most fruits and vegetables as well as for other foods (e.g. meat, fish, and cheese), because information derived by TRS refers to the internal properties of the medium, and is not so much affected by surface features as is the case for CW spectroscopy. In the past TRS measurements were possible only with complex laboratory instrumentation consisting of picosecond pulsed lasers, water cooled photomultiplier tubes, and electronic chain for timecorrelated single photon counting. In this work we present the recent advances in TRS technology (laser, detectors and acquisition electronics) that allow the design of portable instrumentation for use in the preharvest (i.e. in the field) and post-harvest

A Preliminary Clinical Study

Background. Telangiectasia is the dilation of dermal capillaries mainly due to hypertension and vein insufficiency. Treatments of choice for this condition are sclerotherapy with foam liquid or intradermal fiber optic laser energy delivery. Aim. The aim of this study was to assess the efficacy of a new therapeutic approach consisting in the use of polymerized hyaluronic acid mesotherapic injections following sclerotherapy in the areas of the skin affected by telangiectasia in patients without major vein insufficiency. Materials and Methods. A total of 20 women, aged between 19 and 64 years, affected by recurrent lower leg telangiectasia, were included in this study. Patients were preliminarily submitted to echo color Doppler sonography to rule out severe saphenofemoral valve and lower limb major vein insufficiency. All patients underwent 3 sessions a month of polidocanol 1% capillary injections for 2 months. This was followed by 0.1 ml cross-linked hyaluronic acid introduction in the polidocanol 1% needle track. A total of 50 mesotherapic injections (0.05 ml each) were performed on the skin surface where an ice pack was previously applied for 4 to 5 minutes. A follow-up visit was performed at 3 months. The results, based on photographic examination, were rated as follows: poor improvement (0%-50%), good improvement (51%-75%), and very good improvement (76%-100%). The side effects of the clinical procedure, in terms of pain, itching, paresthesia, ecchymosis, and relapse of telangiectasia over the treated skin surface, as well as a persisting pigmentation in the injection spots and induced benefits related to leg heaviness and comfort, were recorded. Results. In total, 6 patients displayed a slight venous insufficiency, 3 patients displayed patent venous insufficiency, and 11 patients did not show any venous insufficiency. Before treatment, itching was present in 18 out of 20 patients, paresthesia in 15 out of 20 patients, ecchymosis in 16 out of 20 patients, and leg heaviness in 15 out of 20 patients. At the 3-month follow-up, an improvement of 0% to 50% was observed in 4 patients who had a relapse in telangiectasia. A 51% to 75% improvement was observed in 3 patients and a 76% to 100% improvement occurred in 13 patients. At the 3-month follow-up, itching persisted only in 4 patients; paresthesia was absent in 12 patients, while 3 patients still presented this symptom; ecchymosis was absent in 16 patients; 15 patients reported a feeling of lightweight legs. Among the patients with relapsing telangiectasia, 2 patients reported pigmentation due to hemosiderin deposit in the skin at the 3-month follow-up. The slight venous insufficiency, observed at the beginning of the study, improved in 5 out of 6 patients. The patients' compliance with the procedure was high and 16 out of 20 patients declared their willingness to repeat the whole clinical procedure, if necessary. Conclusions. This pilot clinical study supports the use of hyaluronic acid mesotherapic injections following sclerotherapy for treatment of lower leg telangiectasia without major venous insufficiency. We propose that the prolonged persistence of cross-linked hyaluronic acid, across the microvascular venous areas, is able to induce a stronger stromal tissue, thus preventing relapse. Further clinical studies, comparing this new approach with existing clinical procedures, are needed in a larger number of patients

Combination Therapy of Hyaluronic Acid Mesotherapic Injections and Sclerotherapy for Treatment of Lower Leg Telangiectasia Without Major Venous Insufficiency: A Preliminary Clinical Study

Background. Telangiectasia is the dilation of dermal capillaries mainly due to hypertension and vein insufficiency. Treatments of choice for this condition are sclerotherapy with foam liquid or intradermal fiber optic laser energy delivery. Aim. The aim of this study was to assess the efficacy of a new therapeutic approach consisting in the use of polymerized hyaluronic acid mesotherapicinjections following sclerotherapy in the areas of the skin affected by telangiectasia in patients without major vein insufficiency. Materials and Methods. A total of 20 women, aged between 19 and 64 years, affected by recurrent lower leg telangiectasia, were included in this study. Patients were preliminarily submitted to echo color Doppler sonography to rule out severe saphenofemoral valve and lower limb major vein insufficiency. All patients underwent 3 sessions a month of polidocanol 1% capillary injections for 2 months. This was followed by 0.1 ml cross-linked hyaluronic acid introduction in the polidocanol 1% needle track. A total of 50 mesotherapic injections (0.05 ml each) were performed on the skin surface where an ice pack was previously applied for 4 to 5 minutes. A follow-up visit was performed at 3 months. The results, based on photographic examination, were rated as follows: poor improvement (0%-50%), good improvement (51%-75%), and very good improvement (76%-100%). The side effects of the clinical procedure, in terms of pain, itching, paresthesia, ecchymosis, and relapse of telangiectasia over the treated skin surface, as well as a persisting pigmentation in the injection spots and induced benefits related to leg heaviness and comfort, were recorded. Results. In total, 6 patients displayed a slight venous insufficiency, 3 patients displayed patent venous insufficiency, and 11 patients did not show any venous insufficiency. Before treatment, itching was present in 18 out of 20 patients, paresthesia in 15 out of 20 patients, ecchymosis in 16 out of 20 patients, and leg heaviness in 15 out of 20 patients. At the 3-month follow-up, an improvement of 0% to 50% was observed in 4 patients who had a relapse in telangiectasia. A 51% to 75% improvement was observed in 3 patients and a 76% to 100% improvement occurred in 13 patients. At the 3-month follow-up, itching persisted only in 4 patients; paresthesia was absent in 12 patients, while 3 patients still presented this symptom; ecchymosis was absent in 16 patients; 15 patients reported a feeling of lightweight legs. Among the patients with relapsing telangiectasia, 2 patients reported pigmentation due to hemosiderin deposit in the skin at the 3-month follow-up. The slight venous insufficiency, observed at the beginning of the study, improved in 5 out of 6 patients. The patients’ compliance with the procedure was high and 16 out of 20 patients declared their willingness to repeat the whole clinical procedure, if necessary. Conclusions. This pilot clinical study supports the use of hyaluronic acid mesotherapic injections following sclerotherapy for treatment of lower leg telangiectasia without major venous insufficiency. We propose that the prolonged persistence of cross-linked hyaluronic acid, across the microvascular venous areas, is able to induce a stronger stromal tissue, thus preventing relapse. Further clinical studies, comparing this new approach with existing clinical procedures, are needed in a larger number of patients

MUG-Mel2, a novel highly pigmented and well characterized NRAS mutated human melanoma cell line

NRAS mutation in melanoma has been associated with aggressive tumor biology and poor prognosis. Although targeted therapy has been tested for NRAS mutated melanoma, response rates still appear much weaker, than in BRAF mutated melanoma. While plenty of cell lines exist, however, only few melanogenic cell lines retain their in vivo characteristics. In this work we present an intensively pigmented and well-characterized cell line derived from a highly aggressive NRAS mutated cutaneous melanoma, named MUG-Mel2. We present the clinical course, unique morphology, angiogenic properties, growth characteristics using in vivo experiments and 3D cell culture, and results of the exome gene sequencing of an intensively pigmented melanogenic cell line MUG-Mel2, derived from a cutaneous metastasis of an aggressive NRAS p. Q61R mutated melanoma. Amongst several genetic alterations, mutations in GRIN2A, CREBP, PIK3C2G, ATM, and ATR were present. These mutations, known to reinforce DNA repair problems in melanoma, might serve as potential treatment targets. The aggressive and fast growing behavior in animal models and the obtained phenotype in 3D culture reveal a perfect model for research in the field of NRAS mutated melanoma.Peer reviewe

HNF1B polymorphism influences the prognosis of endometrial cancer patients: A cohort study

Background: HNF1B (formerly known as TCF2) gene encodes for a transcription factor that regulates gene expression involved in normal mesodermal and endodermal developments. A close association between rs4430796 polymorphism of HNF1B gene and decreased endometrial cancer (EC) risk has been demonstrated. The aim of the current study was to test the hypothesis that rs4430796 polymorphism can influence the prognosis of EC patients. Methods: Retrospective cohort study. Clinical and pathological data were extrapolated and genotypes were assessed on formalin-fixed and paraffin-embedded non-tumour tissues. The influence of patients' genotype on overall survival and progression free survival were our main outcome measures. Results: A total of 191 EC patients were included in the final analysis. Overall survival differed significantly (P = 0.003) among genotypes. At multivariate analysis, a significant (P < 0.05) effect on overall survival was detected for FIGO stage, and rs4430796 polymorphism of HNF1B gene. After grouping EC patients according to adjuvant treatment, rs4430796 polymorphism resulted significantly (P < 0.001) related to overall survival only in subjects who received radiotherapy plus chemotherapy. A significant (P = 0.014) interaction between rs4430796 polymorphism and chemo-radiotherapy was also detected. Finally, only a trend (P = 0.090) towards significance was observed for rs4430796 polymorphism effect on progression free survival. Conclusions: rs4430796 polymorphism of HNF1B gene influences independently the prognosis of EC patients with a potential effect on tumor chemo-sensitivity

Imaging features of uterine and ovarian fibromatosis in Nevoid Basal Cell Carcinoma Syndrome

Gorlin-Goltz Syndrome also known as Nevoid Basal Cell Carcinoma Syndrome is an autosomal dominant multisystem disorder. It is characterized by basal cell carcinomas, odontogenic keratocysts, skeletal abnormalities and in a minority of female patients bilateral calcified ovarian fibromas. It is challenging to radiologically assess ovarian fibromas as they have similar imaging patterns to some malignant ovarian lesions. However, it is vitally important to differentiate between benign and malignant lesions to determine patients' suitability for fertility-sparing surgery. This report describes a case of a 25 year-old patient with Gorlin-Goltz Syndrome and bilateral ovarian fibromas

Expression of NOTCH1 in thyroid cancer is mostly restricted to papillary carcinoma

The NOTCH signaling is an evolutionarily conserved signaling pathway that regulates cell-cell interactions. NOTCH family members play a fundamental role in a variety of processes during development in particular in cell fate decisions. As other crucial factors during embryogenesis, NOTCH signaling is aberrantly reactivated in cancer where it has been linked to context-dependent effects. In thyroid cancer, NOTCH1 expression has been associated to aggressive features even if its in vivo expression within the entire spectrum of thyroid tumors has not definitively established. A series of 106 thyroid specimens including non-neoplastic lesions, benign and malignant tumors of common and rare histotypes, were investigated by immunohistochemistry to assess NOTCH1 expression. Extent of positivity and protein localization were investigated and correlated with clinical and morphological parameters. NOTCH1 positivity was predominantly associated with papillary carcinomas and only occasionally found in follicular carcinomas. Poorly differentiated and undifferentiated thyroid carcinomas showed only a partial positivity. NOTCH1 expression pattern also seemed differently distributed according to histotype. Our data confirm a role of NOTCH1 in thyroid cancer and highlight for the first time the specific involvement of this pathway in papillary carcinomas. Our data also indicate that other thyroid malignancies do not rely on NOTCH1 signaling for development and progression

The DNA-helicase HELLS drives ALK - ALCL proliferation by the transcriptional control of a cytokinesis-related program.

Deregulation of chromatin modifiers, including DNA helicases, is emerging as one of the mechanisms underlying the transformation of anaplastic lymphoma kinase negative (ALK-) anaplastic large cell lymphoma (ALCL). We recently identified the DNA-helicase HELLS as central for proficient ALK-ALCL proliferation and progression. Here we assessed in detail its function by performing RNA-sequencing profiling coupled with bioinformatic prediction to identify HELLS targets and transcriptional cooperators. We demonstrated that HELLS, together with the transcription factor YY1, contributes to an appropriate cytokinesis via the transcriptional regulation of genes involved in cleavage furrow regulation. Binding target promoters, HELLS primes YY1 recruitment and transcriptional activation of cytoskeleton genes including the small GTPases RhoA and RhoU and their effector kinase Pak2. Single or multiple knockdowns of these genes reveal that RhoA and RhoU mediate HELLS effects on cell proliferation and cell division of ALK-ALCLs. Collectively, our work demonstrates the transcriptional role of HELLS in orchestrating a complex transcriptional program sustaining neoplastic features of ALK-ALCL

Expression levels of NONO, a nuclear protein primarily involved in paraspeckles function, are associated with several deregulated molecular pathways and poor clinical outcome in multiple myeloma

Purpose The NONO protein belongs to the multifunctional family of proteins that can bind DNA, RNA and proteins. It is located in the nucleus of most mammalian cells and can affect almost every step of gene regulation. Dysregulation of NONO has been found in many types of cancer; however, data regarding its expression and relevance in Multiple Myeloma (MM) are virtually absent. Methods We took advantage of a large cohort of MM patients enrolled in the Multiple Myeloma Research Foundation CoMMpass study to elucidate better the clinical and biological relevance of NONO expression in the context of the MM genomic landscape and transcriptome. Results NONO is overexpressed in pathological samples compared to normal controls. In addition, higher NONO expression levels are significant independent prognostic markers of worse clinical outcome in MM. Our results indicate that NONO deregulation may play a pathogenetic role in MM by affecting cell cycle, DNA repair mechanisms, and influencing translation by regulating ribosome biogenesis and assembly. Furthermore, our data suggest NONO involvement in the metabolic reprogramming of glucose metabolism from respiration to aerobic glycolysis, a phenomenon known as the 'Warburg Effect' that supports rapid cancer cell growth, survival, and invasion. Conclusion These findings strongly support the need of future investigations for the understanding of the mechanisms of deregulation and the biological role and activity of NONO in MM

Ex vivo mapping of enhancer networks that define the transcriptional program driving melanoma metastasis

: Mortality from vmelanoma is associated with metastatic disease, but the mechanisms leading to spreading of the cancer cells remain obscure. Spatial profiling revealed that melanoma is characterized by a high degree of heterogeneity, which is established by the ability of melanoma cells to switch between different phenotypical stages. This plasticity, likely a heritage from embryonic pathways, accounts for a relevant part of the metastatic potential of these lesions, and requires the rapid and efficient reorganization of the transcriptional landscape of melanoma cells. A large part of the non-coding genome cooperates to control gene expression, specifically through the activity of enhancers (ENHs). In this study, we aimed to identify ex vivo the network of active ENHs and to outline their cooperative interactions in supporting transcriptional adaptation during melanoma metastatic progression. We conducted a genome-wide analysis to map active ENHs distribution in a retrospective cohort of 39 melanoma patients, comparing the profiles obtained in primary (N = 19) and metastatic (N = 20) melanoma lesions. Unsupervised clustering showed that the profile for acetylated histone H3 at lysine 27 (H3K27ac) efficiently segregates lesions into three different clusters corresponding to progressive stages of the disease. We reconstructed the map of super-ENHs (SEs) and cooperative ENHs that associate with metastatic progression in melanoma, which showed that cooperation among regulatory elements is a mandatory requirement for transcriptional plasticity. We also showed that these elements carry out specialized and non-redundant functions, and indicated the existence of a hierarchical organization, with SEs on top as masterminds of the entire transcriptional program and classical ENHs as executors. By providing an innovative vision of how the chromatin landscape of melanoma works during metastatic spreading, our data also point out the need to integrate functional profiling in the analysis of cancer lesions to increase definition and improve interpretation of tumor heterogeneity