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This study aims to evaluate the effect of a new type of collagen crosslinking (CXL) mediated by microbial transglutaminases (Tgases) on sclera. Porcine eyes were divided into two groups according to the different crosslinking procedures used the double-sided CXL group (D-CXL group) and the single-sided CXL group (S-CXL group). In the D-CXL group, 4.0 × 14.0 mm scleral strips harvested from 40 porcine eyeballs were incubated with 1 U/ml Tgases for 30 min at 37 °C. Parallel scleral strips from the same eyeball were incubated with PBS under the same conditions as the controls. In the S-CXL group, 80 whole globes were directly incubated with 1 U/ml Tgases and PBS as the controls for 30 min at 37 °C. After incubation, 4.0 × 14.0 mm scleral strips were cut from each eyeball. Biomechanical testing and light microscopy were used. In the D-CXL group, the general elastic modulus of the Tgases-treated scleral strips was 14.89 ± 6.05 MPa, and the controls was 6.72 ± 2.58 MPa, indicating an increase of 121% with Tgases treatment. In the S-CXL group, the general elastic modulus of the Tgases-treated scleral strips was 12.88 ± 4.29 MPa, and the controls was 7.00 ± 2.45 MPa, indicating an increase of 84% with Tgases treatment. In both the D-CXL and S-CXL groups, significant increases in scleral rigidity were observed compared to that of the respective controls (P less then 0.05). The histology indicated increased collagen bundle density, decreased interfibrillar spaces and increased interlamellar spaces after CXL. In conclusion, scleral collagen crosslinking mediated by Tgases produced a significant increase in biomechanical strength.The recent release of COVID-19 spike glycoprotein allows detailed analysis of the structural features that are required for stabilizing the infective form of its quaternary assembly. Trying to disassemble the trimeric structure of COVID-19 spike glycoprotein, we analyzed single protomer surfaces searching for concave moieties that are located at the three protomer-protomer interfaces. The presence of some druggable pockets at these interfaces suggested that some of the available drugs in Drug Bank could destabilize the quaternary spike glycoprotein formation by binding to these pockets, therefore interfering with COVID-19 life cycle. The approach we propose here can be an additional strategy to fight against the deadly virus. Ligands of COVID-19 spike glycoprotein that we have predicted in the present computational investigation, might be the basis for new experimental studies in vitro and in vivo.The accurate estimation of the State of Charge (SOC) and an acceptable prediction of the Remaining Useful Life (RUL) of batteries in autonomous vehicles are essential for safe and lifetime optimized operation. The estimation of the expected RUL is quite helpful to reduce maintenance cost, safety hazards, and operational downtime. This paper proposes an innovative health-aware control approach for autonomous racing vehicles to simultaneously control it to the driving limits and to follow the desired path based on maximization of the battery RUL. To deal with the non-linear behavior of the vehicle, a Linear Parameter Varying (LPV) model is developed. Based on this model, a robust controller is designed and synthesized by means of the Linear Matrix Inequality (LMI) approach, where the general objective is to maximize progress on the track subject to win racing and saving energy. The main contribution of the paper consists in preserving the lifetime of battery and optimizing a lap time to achieve the best path of a racing vehicle. The control design is divided into two layers with different time scale, path planner and controller. The first optimization problem is related to the path planner where the objective is to optimize the lap time and to maximize the battery RUL to obtain the best trajectory under the constraints of the circuit. The proposed approach is formulated as an optimal on-line robust LMI based Model Predictive Control (MPC) that steered from Lyapunov stability. The second part is focused on a controller gain synthesis solved by LPV based on Linear Quadratic Regulator (LPV-LQR) problem in LMI formulation with integral action for tracking the trajectory. The proposed approach is evaluated in simulation and results show the effectiveness of the proposed planner for optimizing the lap time and especially for maximizing the battery RUL.Objective We performed a validation study to confirm the prognostic importance of the presence of a ground-glass opacity component based on data of the Japan Clinical Oncology Group study, JCOG0201, which was a prospective observational study to predict the pathological noninvasiveness of clinical stage IA lung cancer in Japan. Methods Among the 811 patients registered in JCOG0201, 671 were confirmed eligible by study monitoring and a central review of computed tomography. Registered c-stage IA lung cancer was less than 30 mm in maximum tumor size, which was classified into a with ground-glass opacity group (pure ground-glass opacity and part-solid tumor) or solid group based on the status of a ground-glass opacity component. T staging was reassigned in accordance with the 8th edition of the TNM staging system. To validate the prognostic impact, overall survival was estimated. Results Of the cases, 432 (64%) were in the with ground-glass opacity group and 239 (36%) were in the solid group with a median follow-up time of 10.1 years. The 5-year overall survival was significantly different between the with ground-glass opacity group and solid group (95.1% vs 81.1%). The 5-year overall survival was excellent regardless of the solid component size in the with ground-glass opacity group (c-T1a or less 97.2%, c-T1b 93.4%, c-T1c 91.7%). In contrast, prognostic impact of the tumor size was definitive in the solid group (c-T1a 87.5%, c-T1b 85.9%, c-T1c 73.7%). Conclusions Favorable prognostic impact of the presence of a ground-glass opacity component was demonstrated in JCOG0201. The presence or absence of a ground-glass opacity should be considered as an important parameter in the next clinical T classification.The brain glycogen reserve is a source of oxidizable substrate fuel. Lactoprivic-sensitive hindbrain A2 noradrenergic neurons provide crucial metabolic-sensory input to downstream hypothalamic glucose-regulatory structures. Current research examined whether hindbrain glycogen fuel supply impacts A2 energy stability and governance of ventromedial hypothalamic nucleus (VMN) metabolic transmitter signaling. Male rats were injected into the caudal fourth ventricle (CV4) with the glycogen phosphorylase inhibitor 1,4-dideoxy-1,4-imino-D-arabinitol (DAB) prior to continuous intra-CV4 infusion of L-lactate or vehicle. Lactate reversed DAB suppression of A2 neuron AMPK protein and up-regulated phosphoAMPK profiles. A2 dopamine-β-hydroxylase expression was refractory to DAB, but elevated by DAB/lactate. Lactate normalized A2 estrogen receptor-alpha and GPER proteins and up-regulated estrogen receptor-beta levels in DAB-treated rats. VMN norepinephrine content was decreased by DAB, but partially restored by lactate. DAB caused lactate-reversible or -irreversible augmentation of VMN glycogen phosphorylase-brain (GPbb) and -muscle type (GPmm) variant profiles, and correspondingly up- or down-regulated VMN protein markers of glucose-stimulatory nitrergic and glucose-inhibitory γ-aminobutyric acid transmission. DAB did not alter plasma glucose, but suppressed or elevated circulating glucagon and corticosterone in that order. Results show that diminished hindbrain glycogen breakdown is communicated to the VMN, in part by NE signaling, to up-regulate VMN glycogen breakdown and trigger neurochemical signaling of energy imbalance in that site. DAB effects on GPmm, VMN glycogen content, and counter-regulatory hormone secretion were unabated by lactate infusion, suggesting that aside from substrate fuel provision rate, additional indicators of glycogen metabolism such as turnover rate may be monitored in the hindbrain.Radiation induced lymphopenia is frequent and can be severe and durable. Although lymphocytes have long been known as highly radiosensitive cells, it is poorly characterized. Radiation-induced lymphopenia seems to affect lymphocyte subpopulations differently and seems to be influenced by radiation modalities. The depth and duration of lymphopenia depend on the location of the irradiation and the volumes of treatment. Importantly, radiation-induced lymphopenia has been associated with poorer prognosis in several tumor types. The knowledge about radiation-induced lymphopenia might lead to a rethinking of the modalities of radiotherapy and new approaches to restore lymphocytes counts.Objective To evaluate the impact of an organisational change in the musculoskeletal referral pathway in our health management area (HMA) by identifying changes in the ability to improve healthcare outcomes by facilitating referral to the most suitable specialty. Design This prospective descriptive study aimed to evaluate referral trends from primary care services (PCS) and hospital care (PHS) to musculoskeletal services from 2012 to 2018. Materials and methods We included all patients who were referred to any of the 3 musculoskeletal services from our HMA catchment area, without specifying sample size. The variables studied were PCS, PHS, service of origin and destination. We used the SPSS programme for the statistical analysis and obtained absolute frequency data. Results The total number of referrals from PCS increased from 25,575 in 2012 to 24,871 in 2018. PHS referrals decreased from 17,207 in 2012 to 9,803 in 2018. With regards to PCS referrals, the service most increasing the number of referrals to the musculoskeletal team was the Rehabilitation Service, from 8.2% in 2012 to 47% in 2018. Regarding PHSs referrals by specialty, the service that most reduced the number of referrals to the musculoskeletal team was the Traumatology Service, from 10,587 in 2012 to 3,911 in 2018. Conclusions The redesign of the musculoskeletal referral pathway improved healthcare outcomes by improving the quality of the referral process. In this organisational change, the Rehabilitation Service took the leadership from the point of view of healthcare and management of the musculoskeletal process, collaborating in the improvement of the healthcare outcomes of these processes.Background Whether early gastric cancer with mixed histologic type should be considered for endoscopic submucosal dissection (ESD) remains controversial. The objective of this study was to evaluate the risk of lymph node metastasis (LNM) and prognostic significance for early gastric cancer with mixed histologic type. Methods We retrospectively reviewed clinicopathologic and survival data of 302 patients who underwent surgical resection for early gastric cancer. Based on the histologic components, all patients were classified as pure differentiated type, pure undifferentiated type and mixed histologic type. The prognostic differences between different types were compared and predictive factors for LNM were evaluated. Results Histopathologically, the proportion of mixed histologic type was 12.3% in early gastric cancer. In terms of LNM, mixed histologic type had a more frequent incidence than pure differentiated type (32.4% vs 11.1%, P 0.05). Everolimus Conclusion Mixed histologic type was an independent risk factor for lymph node metastasis in early gastric cancer patients.
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