Mapping Brain Clusterings to Reproduce Missing MRI Scans

Machine learning has become an essential part of medical imaging research. For example, convolutional neural networks (CNNs) are used to perform brain tumor segmentation, which is the process of distinguishing between tumoral and healthy cells. This task is often carried out using four different magnetic resonance imaging (MRI) scans of the patient. Due to the cost and effort required to produce the scans, oftentimes one of the four scans is missing, making the segmentation process more tedious. To obviate this problem, we propose two MRI-to-MRI translation approaches that synthesize an approximation of the missing image from an existing one. In particular, we focus on creating the missing T2 Weighted sequence from a given T1 Weighted sequence. We investigate clustering as a solution to this problem and propose BrainClustering, a learning method that creates approximation tables that can be queried to retrieve the missing image. The images are clustered with hierarchical clustering methods to identify the main tissues of the brain, but also to capture the different signal intensities in local areas. We compare this method to the general image-to-image translation tool Pix2Pix, which we extend to fit our purposes. Finally, we assess the quality of the approximated solutions by evaluating the tumor segmentations that can be achieved using the synthesized outputs. Pix2Pix achieves the most realistic approximations, but the tumor areas are too generalized to compute optimal tumor segmentations. BrainClustering obtains transformations that deviate more from the original image but still provide better segmentations in terms of Hausdorff distance and Dice score. Surprisingly, using the complement of T1 Weighted (i.e. inverting the color of each pixel) also achieves good results. Our new methods make segmentation software more feasible in practice by allowing the software to utilize all four MRI scans, even if one of the scans is missing

Rabphilin localizes with the cell actin cytoskeleton and stimulates association of granules with F-actin cross-linked by α-actinin

In endocrine cell, granules accumulate within an F-actin-rich region below the plasma membrane. The mechanisms involved in this process are largely unknown. Rabphilin is a cytosolic protein that is expressed in neurons and neuroendocrine cells and binds with high affinity to members of the Rab3 family of GTPases localized to synaptic vesicles and dense core granules. Rabphilin also interacts with alpha-actinin, a protein that cross-links F-actin into bundles and networks and associates with the granule membrane. Here we asked whether rabphilin, in addition to its granule localization, also interacts with the cell actin cytoskeleton. Immunofluorescence and immunoelectron microscopy show that rabphilin localizes to the sub-plasmalemmal actin cytoskeleton both in neuroendocrine and unspecialized cells. By using purified components, it is found that association of rabphilin with F-actin is dependent on added alpha-actinin. In an in vitro assay, granules, unlike endosomes or mitochondria, associate with F-actin cross-linked by alpha-actinin. Rabphilin is shown to stimulate this process. Rabphilin enhances by approximately 8-fold the granule ability to localize within regions of elevated concentration of cross-linked F-actin. These results suggest that rabphilin, by interacting with alpha-actinin, organizes the cell cytoskeleton to facilitate granule localization within F-actin-rich regions

Cross-validation of active and passive microwave snowfall products over the continental United States

Surface snowfall rate estimates from the Global Precipitation Measurement (GPM) mission’sCoreObservatorysensors and theCloudSatradar are compared to those from the Multi-Radar Multi-Sensor (MRMS) radarcomposite product over the continental United States during the period from November 2014 to September 2020. Theanalysis includes the Dual-Frequency Precipitation Radar (DPR) retrieval and its single-frequency counterparts, the GPMCombined Radar Radiometer Algorithm (CORRA), theCloudSatSnow Profile product (2C-SNOW-PROFILE), and twopassive microwave retrievals, i.e., the Goddard Profiling algorithm (GPROF) and the Snow Retrieval Algorithm for GMI(SLALOM). The 2C-SNOW retrieval has the highest Heidke skill score (HSS) for detecting snowfall among the productsanalyzed. SLALOM ranks second; it outperforms GPROF and the other GPM algorithms, all detecting only 30% of thesnow events. Since SLALOM is trained with 2C-SNOW, it suggests that the optimal use of the information content in theGMI observations critically depends on the precipitation training dataset. All the retrievals underestimate snowfall ratesby a factor of 2 compared to MRMS. Large discrepancies (RMSE of 0.7–1.5 mm h21) between spaceborne and ground-based snowfall rate estimates are attributed to the complexity of the ice scattering properties and to the limitations of theremote sensing systems: the DPR instrument has low sensitivity, while the radiometric measurements are affected by theconfounding effects of the background surface emissivity and of the emission of supercooled liquid droplet layers

Diffuse vesicular distribution of Rab3D in the polarized neuroendocrine cell line AtT-20

AbstractThe neuroendocrine cell line AtT-20 has two types of storage vesicles: dense core granules and synaptic vesicles, both sequestered at the tip of the processes. Here we show that Rab3D protein, which is abundant in fat cells, is also expressed in AtT-20 cells. Differently from Rab3A, which is localized in secretory vesicles accumulated at the tips, Rab3D has a diffuse vesicular distribution in the cytoplasm of the cell body, the processes and the tips. In AtT-20 cells, Rab3D may define a regulated secretory pathway which functions independently from cell polarity

Role of mesenchymal stem cells in osteosarcoma and metabolic reprogramming of tumor cells

The tumor microenvironment plays an important role in cancer progression. Here, we focused on the role of reactive mesenchymal stem cells (MSC) in osteosarcoma (OS), and used human adipose MSC and a panel of OS cell lines (Saos-2, HOS, and 143B) to investigate the mutual effect of normal-cancer cell metabolic programming. Our results showed that MSC are driven by oxidative stress induced by OS cells to undergo Warburg metabolism, with increased lactate production. Therefore, we analyzed the expression of lactate monocarboxylate transporters. By real time PCR and immunofluorescence, in MSC we detected the expression of MCT-4, the transporter for lactate efflux, whereas MCT-1, responsible for lactate uptake, was expressed in OS cells. In agreement, silencing of MCT-1 by siRNA significantly affected the ATP production in OS cancer cells. Thus, cancer cells directly increase their mitochondrial biogenesis using this energy-rich metabolite that is abundantly provided by MSC as an effect of the altered microenvironmental conditions induced by OS cells. We also showed that lactate produced by MSC promotes the migratory ability of OS cells. These data provide novel information to be exploited for cancer therapies targeting the mutual metabolic reprogramming of cancer cells and their stroma.The tumor microenvironment plays an important role in cancer progression. Here, we focused on the role of reactive mesenchymal stem cells (MSC) in osteosarcoma (OS), and used human adipose MSC and a panel of OS cell lines (Saos-2, HOS, and 143B) to investigate the mutual effect of normal-cancer cell metabolic programming. Our results showed that MSC are driven by oxidative stress induced by OS cells to undergo Warburg metabolism, with increased lactate production. Therefore, we analyzed the expression of lactate monocarboxylate transporters. By real time PCR and immunofluorescence, in MSC we detected the expression of MCT-4, the transporter for lactate efflux, whereas MCT-1, responsible for lactate uptake, was expressed in OS cells. In agreement, silencing of MCT-1 by siRNA significantly affected the ATP production in OS cancer cells. Thus, cancer cells directly increase their mitochondrial biogenesis using this energy-rich metabolite that is abundantly provided by MSC as an effect of the altered microenvironmental conditions induced by OS cells. We also showed that lactate produced by MSC promotes the migratory ability of OS cells. These data provide novel information to be exploited for cancer therapies targeting the mutual metabolic reprogramming of cancer cells and their stroma

Osteoporosis-related variations of trabecular bone properties of proximal human humeral heads at different scale lengths

Abstract Osteoporosis (OP) is a skeletal disorder responsible for the weakening of the bone structure and, consequently, for an increased fracture risk in the elderly population. In the past, bone mineral density (BMD) variation was considered the best OP indicator, but recently the focus has shifted toward the variation of microstructural bone parameters. This work is based on the characterisation of 8-mm cylindrical biopsies harvested from proximal humeral heads belonging to healthy and osteoporotic patients, in order to assess the OP-related variations of bone properties at different scale lengths. In particular, bone biopsies underwent micro-computed tomography analysis to study the most relevant features of bone architecture and extrapolate the tissue mineral density (TMD) value of bone trabeculae. Compression tests and nanoindentations were performed to investigate the macro- and micromechanical properties of bone biopsies, respectively. In addition, XRD analyses were performed to obtain the mean hydroxyapatite (HA) crystallite size, while Raman spectroscopy investigated the collagen secondary structure. Thermogravimetric analysis was performed to evaluate the ratio between organic and inorganic phases. From the obtained results, OP samples showed a more anisotropic and less interconnected structure responsible for reduced compression strength. From this, it can be supposed that OP caused an alteration of bone structure that led to inferior macroscopic mechanical properties. Furthermore, OP samples possessed higher TMD and bigger HA crystals that are correlated to an increase of the hardness value obtained by means of nanoindentation. This less controlled HA crystal growth is probably due to an alteration of the organic matrix structure, as revealed by the increase of the random coil contribution in the Raman spectra of the OP bone. This higher crystal content led to an increase in trabecular density and hardness. In conclusion, the obtained data showed that OP affects bone properties at different scale lengths causing an alteration of its morphological, structural and mechanical features

MIS-C Treatment: Is IVIG Always Necessary?

Background: MIS-C is a potentially severe inflammatory syndrome associated with SARS-CoV-2 exposure. Intravenous immunoglobulin (IVIG) is considered the first-tier therapy, but it implies infusion of large fluid volumes that may worsen cardiac function. Patients and Methods: Since April 2020, we have developed a treatment protocol that avoids the infusion of IVIG as first-line therapy in the early phase of MIS-C. In this study, we retrospectively analyzed a cohort of consecutive patients treated according to this protocol between 01/04/2020 and 01/04/2021. Results: In the last year, 31 patients have been treated according to the protocol: 25 with high-dose pulse MP (10 mg/kg) and 6 with 2 mg/kg. 67.7% of the patients responded to the initial treatment, while the others needed a step-up, either with Anakinra (25.8%) or with MP dose increase (6.5%). IVIG was administered in four patients. Overall, only one patient (3.2%) needed ICU admission and inotropic support; one patient developed a small coronary artery aneurysm. Conclusions: Timely start of MP therapy and careful fluid management might improve the outcomes of MIS-C patients

Nanocoated fiber label-free biosensing for perfluorooctanoic acid detection by lossy mode resonance

The determination of per- and polyfluoroalkyl substances (PFAS) in environmental samples, such as drinking waters, requires the design of high performing and versatile sensing strategies. Label-free biosensing platforms based on specialty fiber optics are a valid option to face this challenge. Among them, lossy mode resonance (LMR) fiber optic biosensors are showing remarkable performance in terms of detection limit, selectivity, and reproducibility. The detection of small molecules, such as perfluorooctanoic acid (PFOA), can be achieved with the help of well-designed biological recognition layers. In this study, the biosensing potentialities of a label-free LMR-assisted optical platform based on nanocoated fibers are investigated. Delipidated human serum albumin (hSA) was used as biological recognition layer for PFOA in aqueous solution. Different fiber functionalization protocols based on the covalent immobilization of hSA were tested. The conformational changes related to the formation of hSA/PFOA complex were followed via optical monitoring of LMR spectral shift, showing a trend that can be modeled with Langmuir adsorption isotherm. These results confirmed the potentiality of LMR-based fiber biosensors for the detection of small molecules, such as PFOA, in synthetic samples

Altered pH gradient at the plasma membrane of osteosarcoma cells is a key mechanism of drug resistance

Current therapy of osteosarcoma (OS), the most common primary bone malignancy, is based on a combination of surgery and chemotherapy. Multidrug resistance mediated by P-glycoprotein (P-gp) overexpression has been previously associated with treatment failure and progression of OS, although other mechanisms may also play a role. We considered the typical acidic extracellular pH (pHe) of sarcomas, and found that doxorubicin (DXR) cytotoxicity is reduced in P-gp negative OS cells cultured at pHe 6.5 compared to standard 7.4. Short-time (24-48 hours) exposure to low pHe significantly increased the number and acidity of lysosomes, and the combination of DXR with omeprazole, a proton pump inhibitor targeting lysosomal acidity, significantly enhanced DXR cytotoxicity. In OS xenografts, the combination treatment of DXR and omeprazole significantly reduced tumor volume and body weight loss. The impaired toxicity of DXR at low pHe was not associated with increased autophagy or lysosomal acidification, but rather, as shown by SNARF staining, with a reversal of the pH gradient at the plasma membrane (ΔpHcm), eventually leading to a reduced DXR intracellular accumulation. Finally, the reversal of ΔpHcm in OS cells promoted resistance not only to DXR, but also to cisplatin and methotrexate, and, to a lesser extent, to vincristine. Altogether, our findings show that, in OS cells, shortterm acidosis induces resistance to different chemotherapeutic drugs by a reversal of ΔpHcm, suggesting that buffer therapies or regimens including proton pump inhibitors in combination to low concentrations of conventional anticancer agents may offer novel solutions to overcome drug resistance