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摘要： A Correction to this paper has been published: https://***/10.1007/s12026-021-09181-9

关键词： Microfluidic   Angiogenesis   Primary endothelial cell   Pericyte   3D cell culture   NOTCH   VEGF   PATHWAYS   AGENTS  

摘要： Angiogenesis plays a key role in the pathology of diseases such as cancer, diabetic retinopathy, and age-related macular degeneration. Understanding the driving forces of endothelial cell migration and organization, as well as the time frame of these processes, can elucidate mechanisms of action of important pathological pathways. Herein, we have developed an organ-specific microfluidic platform recapitulating the in vivo angiogenic microenvironment by co-culturing mouse primary brain endothelial cells with brain pericytes in a three-dimensional (3D) collagen scaffold. As a proof of concept, we show that this model can be used for studying the angiogenic process and further comparing the angiogenic properties between two different common inbred mouse strains, C57BL/6J and 129S1/SvlmJ. We further show that the newly discovered angiogenesis-regulating genePadi2promotes angiogenesis throughDll4/Notch1signaling by an on-chip mechanistic study. Analysis of the interplay between primary endothelial cells and pericytes in a 3D microfluidic environment assists in the elucidation of the angiogenic response.

关键词： Light irradiation   Photo stimulation   Schwann cells   Dorsal root ganglion neurons   Optogenetics  

摘要： The expansion of optogenetics via the development and application of new opsins has opened a new world of possibilities as a research and therapeutic tool. Nevertheless, it has also raised questions about the innocuity of using light irradiation on tissues and cells such as those from the Peripheral Nervous System (PNS). Thus, to investigate the potential of PNS being affected by optogenetic light irradiation, rat dorsal root ganglion neurons and Schwann cells were isolated and their response to light irradiation examined in vitro. Light irradiation was delivered as millisecond pulses at wavelengths in the visible spectrum between 627 and 470 nm, with doses ranging between 4.5 and 18 J/cm(2) at an irradiance value of 1 mW/mm(2). Results show that compared to cultures kept in dark conditions, light irradiation at 470 nm reduced neurite outgrowth in dissociated dorsal root neurons in a dose dependent manner while higher wavelengths had no effect on neuron morphology. Although neurite outgrowth was limited by light irradiation, no signs of cell death or apoptosis were found. On the other hand, peripheral glia, Schwann cells, were insensitive to light irradiation with metabolism, proliferation, and RNA levels of transcription factors c-Jun and krox-20 remaining unaltered following stimulation. As the fields of photostimulation and optogenetics expand, these results indicate the need for consideration to cell type response and stimulation parameters for applications in vitro and further investigation on specific mechanisms driving response.

摘要： AIM: To test the hypothesis that computed tomography (CT) and magnetic resonance imaging (MRI) could help distinguish between giant cell tumours with prominent aneurysmal bone cysts (GABCs) and primary aneurysmal bone cysts (PABCs) of the extremities. MATERIALS AND METHODS: CT and MRI features of 13 patients with GABCs and 13 patients with PABCs in the extremities were analysed retrospectively. The ages and sex of the patients were also recorded. Independent-samples t-tests were used for continuous variables and Fisher's exact tests were used for categorical variables to compare the differences between the two groups. Diagnostic accuracy, sensitivity, and interobserver agreement were calculated. RESULTS: The average age of patients with GABCs (38.2 +/- 15.8 years) was higher than that of patients with PABCs (19.3 +/- 12.7 years; p =0.003). The transverse/longitudinal diameter ratio was different between GABCs (0.8 +/- 0.3) and PABCs (0.6 +/- 0.2; p=0.007). Subchondral bone involvement (92.3% versus 30.8%, p =0.004) and deep lobulation (38.5% versus 0%, p=0.039) were more likely to be noted in patients with GABCs. Surrounding blood vessels were identified in six cases of PABCs (6/13), but not in GABCs (p=0.015). The following characteristics were suggestive of GABCs, older patient age, higher transverse/longitudinal diameter ratio, subchondral bone involvement, and deep lobulation indicated a sensitivity of 84.6%, 76.9%, 75%, and 100%, and a specificity of 84.6%, 69.2%, 90%, and 61.9%, respectively. Conversely, surrounding blood vessels were suggestive of PABCs, with a sensitivity of 46.2% and specificity of 100%. The concordance between the two readers was moderate to nearly perfect. CONCLUSION: Age, subchondral bone involvement, lobulation, transverse/longitudinal diameter ratio, and surrounding blood vessels can be used to distinguish GABCs from PABCs. (C) 2020 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

关键词： Lymph node topography   Oral cavity   Squamous cell carcinoma   Lymph node yield   Head and neck cancer   ELECTIVE NECK DISSECTION   LYMPH-NODES   TONGUE   HEAD   SURVIVAL   PATTERNS   FLOOR  

摘要： Objectives: Nodal metastasis is an important prognostic factor in oral squamous cell carcinoma (OSCC). Detailed topographic study of metastasis can guide surgical and adjuvant radiation treatment protocols. Methods: Retrospective analysis of distribution of nodal spread was done by auditing pathology records of 1004 patients who underwent primary surgical management at our center. Results: The median nodal yield was 41 (range of 9-166) nodes, per patient. Metastasis was present in 42.9% patients, of which 52.3% demonstrated extranodal extension. Reclassification by AJCC8 criteria resulted in upstaging in 35.6% patients (pN1, pN2a, pN2b, pN2c, pN3a and pN3b in 13.1%, 3.7%, 6.9%, 0.9%, 0%, 18.1% respectively). Ipsilateral levels Ib and IIa were involved in a quarter of patients each, while IIb, IV and V were involved in < 4%, 3% and 1% of patients, respectively. Contralateral nodal metastasis was present in 5.4%. Skip metastases to level IV were 2.2% and 1.2% for tongue and gingivobuccal primaries. Tongue primaries had a lower likelihood of involving level Ib, but higher of level IIa and III, compared to gingivobuccal primaries, and a lower likelihood of extranodal extension. Primary site did not influence nodal metastasis to levels IIb, IV or V, but other factors like lymphovascular invasion, pT stage and margin status had an influence. Conclusion: This large series with high nodal yield, shows low level of metastasis to level IIb, IV and V, which can help modify future guidelines for extent of surgery and avoid targeted adjuvant radiation to specific levels.

关键词： Eulerian-Eulerian model   Fluidized bed flotation cell   Particle size   Particle shape factor   Voidage   NONSPHERICAL PARTICLES   ASSISTED FLUIDIZATION   NUMERICAL-SIMULATION   IRREGULAR PARTICLES   TURBULENCE MODELS   DRAG COEFFICIENT   FROTH FORMATION   CFD SIMULATION   KINETIC-THEORY   BED  

摘要： The separation of coarse particles by flotation can be maximized by the support of fluidized bed hydrodynamics. Here, we investigated the effect of particle size and shape on the liquid-solid fluidization in a HydroFloat cell that was developed for the special separation process using CFD results and experimental data. Specifically, a 3D CFD model was developed to study the liquid and aspherical quartz particle flow behaviors in a fluidized bed in the cell. The Eulerian-Eulerian formulation with the RNG k-epsilon turbulence model was applied for the liquid phase, while the kinetic theory of granular flow was utilized for the particle phase. The Gidaspow with Haider and Levenspiel equations were used for the drag force coupling between the liquid and the aspherical particles. The CFD results agreed with the experimental data for the bed voidage and pressure drop. The CFD model was further applied to investigate the effect of particle size (d(S)) and particle shape factor (psi) on the bed expansion, pressure drop, and voidage of the fluidization for Re (particle Reynolds number) < 11.6. The Richardson-Zaki equation was modified to predict the voidage, within 12% of relative errors. The prediction was further improved by our semi-empirical correlation that reduced the errors to 8%. The particle size and shape were also found to significantly affect the time-averaged radial distribution of the axial velocity and volume fraction of the particles, granular temperature, dissipation rate, and viscosity of turbulence. The outcomes of this paper are useful for optimizing the operation of the HydroFloat cell. (C) 2020 Elsevier B.V. All rights reserved.

关键词： adjuvant radiation   controversy   margin size   excision   local disease   local recurrence   Merkel cell carcinoma   nonmelanoma skin cancer   surgical margins   radiation   radiation therapy  

摘要： Background: Merkel cell carcinoma (MCC) management typically includes surgery with or without adjuvant radiation therapy (aRT). Major challenges include determining surgical margin size and whether aRT is indicated. Objective: To assess the association of aRT, surgical margin size, and MCC local recurrence. Methods: Analysis of 188 MCC cases presenting without clinical nodal involvement. Results: aRT-treated patients tended to have higher-risk tumors (larger diameter, positive microscopic margins, immunosuppression) yet had fewer local recurrences (LRs) than patients treated with surgery only (1% vs 15%; P = .001). For patients who underwent surgery alone, 7 of 35 (20%) treated with narrow margins (defined as <= 1.0 cm) developed LR, whereas 0 of 13 patients treated with surgical margins greater than 1.0 cm developed LR (P = .049). For aRT-treated patients, local control was excellent regardless of surgical margin size; only 1% experienced recurrence in each group (1 of 70 with narrow margins cm and <= 1 of 70 with margins 1 cm; P = .56). Limitations: This was a retrospective study. Conclusions: Among patients treated with aRT, local control was superb even if significant risk factors were present and margins were narrow. We propose an algorithm for managing primary MCC that integrates risk factors and optimizes local control while minimizing morbidity.

关键词： Differentiation   Muscle   Proliferation   Satellite cell   Temperature extremes   MALE BROILER-CHICKENS   HEAT-STRESS   SKELETAL-MUSCLE   BREAST MUSCLE   BODY-TEMPERATURE   DOMESTIC-FOWL   MEAT QUALITY   POSTHATCH   PROTEIN   THERMOTOLERANCE  

摘要： Satellite cell (SCs), the main progenitors for post-hatch poultry muscle growth, has maximal mitotic activity and sensitivity to temperature during the first week after hatch. The objective of the present study was to determine the effect of hot and cold temperatures on the proliferation and differentiation of SCs from pectoralis major (P. major) muscle of fast-growing 1-week-old Nicholas commercial (NC) turkeys compared to Randombred Control Line 2 (RBC2) turkeys representing commercial turkeys from 1966. Three temperature regimens were used: SCs proliferation at 38 degrees C (control) with differentiation at 43 degrees or 33 degrees C; proliferation at 43 degrees or 33 degrees C with differentiation at 38 degrees C; or both proliferation and differentiation at 43 degrees, 38 degrees, or 33 degrees C. Satellite cell proliferation and differentiation increased at 43 degrees C and decreased at 33 degrees C in both lines. When a thermal challenge was administered during proliferation, greater stimulatory or suppressive effects on differentiation were observed compared to if the thermal challenge was applied only during differentiation in both lines. Expression of myoblast determination protein 1 during proliferation showed a higher increase in the NC line compared to the RBC2 line at 43 degrees C. Increased myogenin expression was observed in all hot treatment groups in the NC line but was only observed in the RBC2 line if the hot treatment was administered throughout proliferation and differentiation. Cold treatment suppressed myogenin expression independent of line. These results suggest turkey P. major muscle SCs are more sensitive to environmental temperatures during proliferation, and SCs from growth-selected NC turkeys are more sensitive to thermal stress compared to the RBC2 turkeys.

关键词： Indirect comparison   Type 2 diabetes   Insulin aspart   Glucagon-like peptide 1   Insulin glargine   FIXED-RATIO COMBINATION   GLARGINE   LIXISENATIDE   LIXILAN   PHASE-3  

摘要： Background: Fixed-dose combinations of insulin glargine/lixisenatide (IGlarLixi) or insulin degludec/insulin aspart (IDegAsp) constitute treatment intensification in type 2 diabetes mellitus (T2D). Objectives: Compare efficacy and safety of IGlarLixi and IDegAsp (as intensification from basal insulin), by indirect comparison of phase III trials, in the absence of head-to-head trials. Study eligibility criteria: Studies comparing treatment intensification by once-daily IDegAsp or IGlarLixi to basal insulin. Data were extracted from two trials (BOOST: Intensify-Basal and LixiLan-L) retained for analysis. Synthesis methods: Treatments were compared in terms of estimated treatment difference (ETD) in glycated haemoglobin (HbA1c), fasting and postprandial plasma glucose (FPG and PPG) change from baseline; in addition to hypoglycaemia incidence and weight changes. Results: In a fixed-effect model examining HbA1c control, IGlarLixi was more effective than IDegAsp in reducing HbA1c (ETD 0.53%, P<0.0001]), PPG (ETD 2.65%, P<0.0001), and body weight (ETD 1.73 kg, P<0.0001). Patients on IGlarLixi were more likely to achieve HbA1c < 7% than patients on IDegAsp (odds ratio [OR] = 0.40, P<0.0001), with lower incidence of hypoglycaemia (OR=1.33, P<0.001). Limitations: Limited number of studies; different baseline HbA1c and FPG. Conclusion: Once-daily IGlarLixi is more efficient than once-daily IDegAsp in controlling HbA1c and PPG and associates with greater weight loss and lower hypoglycaemia incidence. (C) 2020 The Author. Published by Elsevier Ltd on behalf of Primary Care Diabetes Europe.