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1.
Neurol India ; 69(4): 1002-1004, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34507429

RESUMO

Wall-eyed monocular internuclear ophthalmoplegia (WEMINO) is a rare variant of internuclear ophthalmoplegia (INO), consisting of unilateral INO and ipsilateral exotropia. This distinctive syndrome is probably associated with damage to the medial longitudinal fasciculus. However, WEMINO caused by a midbrain lesion has not been previously reported. We herein report a 50-year-old man presenting with WEMINO and vertical gaze dysfunction resulting from infarction of the midbrain tegmentum.


Assuntos
Exotropia , Transtornos da Motilidade Ocular , Oftalmoplegia , Humanos , Infarto , Masculino , Mesencéfalo/diagnóstico por imagem , Pessoa de Meia-Idade , Transtornos da Motilidade Ocular/etiologia
2.
Int Immunopharmacol ; 100: 108138, 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34509934

RESUMO

OBJECTIVE: Long noncoding RNAs (lncRNAs) regulate the occurrence and development of osteoarthritis (OA), whereas the biological roles and mechanisms of the lncRNA THUMPD3-AS1 (THUMPD3 antisense RNA 1) in OA remain still unclear. This study described the role and molecular mechanism of lncRNA THUMPD3-AS1 in regulating OA biology. METHOD: The knee normal and OA cartilage tissues from ten participants were sequenced to reveal the differentially expressed lncRNAs. The interleukin (IL)-1ß-stimulated C28/I2 cell served as OA cells. Flow cytometry assays, Western blot, enzyme-linked immunosorbent assays were used for our experiments. RESULTS: The results revealed that lncRNA THUMPD3-AS1 was downregulated in OA cartilage tissues and IL-1ß-stimulated chondrocyte cell line. Overexpression of lncRNA THUMPD3-AS1 alleviated cell apoptosis and facilitated inflammatory responses, whereas knockdown had opposite effects. LncRNA THUMPD3-AS1 markedly increased the cyclin E2, cyclin-dependent kinase 4, B-cell lymphoma 2, tumor necrosis factor-α, nitric oxide, and IL-6 levels, and decreased the caspase-3 level. Furthermore, the target proteins of phosphorylation were identified as nuclear factor-κB p65 and mitogen-activated protein kinase p38, which could be indirectly suppressed by lncRNA THUMPD3-AS1 knockdown. CONCLUSION: Our findings highlight the different effects of lncRNA THUMPD3-AS1 on cell apoptosis and inflammatory response, which extend the multiple functions of lncRNA epigenetics in OA biology.

3.
Dalton Trans ; 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34522941

RESUMO

Three mononuclear Co(II) complexes with the compositions of [Co(L1)2] (1), [Co(L2)2(CH3CN)] (2) and [Co(L3)2] (3) (HL1 = 2-((E)-(2-fluorobenzylimino)methyl)-4,6-dibromophenol, HL2 = 2-((E)-(3-fluorobenzylimino)methyl)-4,6-dibromophenol and HL3 = 2-((E)-(4-fluorobenzylimino)methyl)-4,6-dibromophenol) were prepared and structurally determined. The changes in the F-positions in the ligands and solvents led to the formation of these products with various coordination geometries. Both complexes 1 and 3 are four-coordinated and their coordination geometries can be described as tetrahedron and seesaw, whereas complex 2 is five coordinated with a coordination configuration in between trigonal bipyramid and square pyramid. Static magnetic studies reveal that all these complexes exhibit considerable easy-axis magnetic anisotropy. The easy-axis magnetic anisotropy of 1 and 3 mainly derives from the first quartet excited state, whereas that of 2 primarily originates from the first, third and fourth quartet excited states established by theoretical calculations. All the resulting complexes display field-induced slow magnetic relaxation. Complex 3 represents the first Co(II) single ion magnet with a seesaw coordination geometry. Ab initio calculations predict that the magnetic anisotropy will enhance when the seesaw coordination geometry varies from distortion to regulation.

4.
Chemosphere ; 287(Pt 1): 132061, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34523448

RESUMO

The photo-Fenton system exhibits great potential in environmental remediation. However, photo-Fenton process suffers from slow reaction kinetics, which is caused by the low yield of available charge carriers and active radicals. In this work, the 2D/2D FeNi-layered double hydroxide/bimetal-organic frameworks nanosheets (FeNi-LDH/BMNSs) photocatalyst was fabricated via an in-situ semi-sacrificial template strategy. The optimized FeNi-LDH/BMNSs + H2O2+Vis system showed excellent tetracycline hydrochloride (TC-HCl) removal rate of 95.76% in 60 min. Besides, the high TC-HCl degradation rates (above 80%) are obtained in a wide pH range and the total organic carbon (TOC) removal rate of 48.98% was remained after four cycles. Experiments and characterizations identified the fast catalysis process were ascribed to the synergetic effect between 2D/2D heterojunctions and Lewis acid sites with mixed-valence (Fe (III)/Ni (II)) in FeNi-LDH/BMNSs. As a result, the catalysis of H2O2 and the reduction of O2 was accelerated by the continuous generation of Fe (II) and available photogenerated electrons, respectively, producing abundant active radicals including OH and O2-. Finally, this photo-Fenton system exhibited high removal rate to oxycycline, levofloxacin, norfloxacin and doxycycline and showed excellent performance for TC-HCl removal in different composed wastewater. The findings provide a new strategy towards creating 2D/2D active heterogeneous catalysts for photo-Fenton catalytic application.

5.
J Phys Chem B ; 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34519209

RESUMO

Stimulation of cells by nanosecond pulsed electric fields (nsPEFs) has attracted attention as a technology for medical applications such as cancer treatment. nsPEFs have been shown to affect intracellular environments without significant damage to cell membranes; however, the mechanism underlying the effect of nsPEFs on cells remains unclear. In this study, we constructed electrodes for applying nsPEFs and analyzed the change in volume of a single cell due to nsPEFs using fluorescence and Raman microscopy. It was shown that the direction of the change depended on the applied electric field; expansion due to the influx of water was observed at high electric field, and cell shrinkage was observed at low electric field. The change in cell volume was correlated to the change in the intracellular Ca2+ concentration, and nsPEFs-induced shrinking was not observed when the Ca2+-free medium was used. This result suggests that the cell shrinkage is related to the regulatory volume decrease where the cell adjusts the increase in intracellular Ca2+ concentration, inducing the efflux of ions and water from the cell.

6.
J Environ Sci (China) ; 108: 201-216, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34465433

RESUMO

Biochar as an emerging carbonaceous material has exhibited a great potential in environmental application for its perfect adsorption ability. However, there are abundant persistent free radicals (PFRs) in biochar, so the direct and indirect PFRs-mediated removal of organic and inorganic contaminants by biochar was widely reported. In order to comprehend deeply the formation of PFRs in biochar and their interactions with contaminants, this paper reviews the formation mechanisms of PFRs in biochar and the PFRs-mediated environmental applications of biochar in recent years. Finally, future challenges in this field are also proposed. This review provides a more comprehensive understanding on the emerging applications of biochar from the viewpoint of the catalytic role of PFRs.


Assuntos
Carvão Vegetal , Recuperação e Remediação Ambiental , Adsorção , Radicais Livres
7.
ACS Nano ; 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34478265

RESUMO

The renaissance of aqueous Zn ion batteries has drawn intense attention to Zn metal anode issues, including dendrites growth, dead Zn, low efficiency, and other parasitic reactions. However, against the widely used 2D Zn foil, in fact, the Zn powder anode is a more practical choice for Zn-based batteries in industrial applications, but the related solutions are rarely investigated. Herein, we focus on the Zn powder anode and disclose its unknown failure mechanism different from Zn foils. By utilization of 2D flexible conductive Ti3C2Tx MXene flakes with hexagonal close-packed lattice as electrons and ions redistributor, a stable and highly reversible Zn powder anode without dendrite growth and low polarization is constructed. Low lattice mismatch (∼10%) enables a coherent heterogeneous interface between the (0002) plane of deposited Zn and (0002) plane of the Ti3C2Tx MXene. Thus, the Zn2+ ions are induced to undergo rapid uniform nucleation and sustained reversible stripping/plating with low energy barriers via the internally bridged shuttle channels. Paired with cyano group iron hexacyanoferrate (FeHCF) cathode, the FeHCF//MXene@Zn full battery delivers superior cycle durability and rate capability, whose service life with a CE of near 100% touches 850% of bare Zn powder counterparts. The proposed Ti3C2Tx MXene redistributor strategy concerning high-speed electrons/ions channel, low-barrier heterogeneous interface, is expected to be widely applied to other alkali metal anodes.

8.
Neuroscience ; 472: 103-115, 2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-34364954

RESUMO

The global fractional anisotropy (gFA) is a structural marker of white matter myelination and integrity. Previous studies already evidenced that aging-related reduced integrity of specific white matter tracts is associated with decreased functional connectivity in several hubs. However, the correlations between gFA and functional brain connectivity remain unknown. In this cross-sectional study, we analyzed structural and functional MR datasets of 79 healthy participants from the Leipzig Study for Mind-Body-Emotion Interactions. DTI model-based method was used to quantify gFA values. We tested associations between gFA, age, and gender. The fractional amplitude of low-frequency fluctuations (fALFF) and ROI-to-ROI connectivity were analyzed in a regression model for evaluating the effects of gFA on brain activity and networking, respectively. A negative correlation was found between gFA and age (ρ = -0.343; p = 0.002). No statistically significant correlation as found between gFA and gender (p = 0.229). Higher values of gFA were associated with increased brain regional activity, including areas of the default mode network. There was a higher degree of correlation between some regions, particularly those that conform to the limbic system. Our study demonstrates that gFA influences regional neural activity and brain networking on resting, particularly the limbic system.


Assuntos
Encéfalo , Substância Branca , Anisotropia , Encéfalo/diagnóstico por imagem , Estudos Transversais , Voluntários Saudáveis , Humanos , Imageamento por Ressonância Magnética , Substância Branca/diagnóstico por imagem
9.
J Food Biochem ; 45(9): e13898, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34378802

RESUMO

Hypericum patulum has been used as a folk medicine for its varied therapeutic effects including antifungal, wound-healing, spasmolytic, stimulant, hypotensive activities. The water decoction is drank as tea could treat cold, infantile malnutrition. The present study aims to isolate the constituents of the plant and investigate their effects on the glucose consumption in insulin-resistant HepG2 cells, furthermore, lipid metabolism in oleic acid (OA)-treated HepG2 cells was also studied. The phytochemical investigation of the plant led to the isolation of eleven compounds, and their structures were identified by spectroscopic analysis as n-dotriacontanol (1), shikimic acid (2), 1-O-caffeoylquinic acid methyl ester (3), 5-O-caffeoylquinic acid methyl ester (4), 5-O-coumaroylquinic acid methyl ester (5), 5-O-caffeoylquinic acid butyl ester (6), quercetin-3-O-α-L-rhamnoside (7), quercetin (8), quercetin-3-O-(4×´-methoxy)-α-L-rahmnopyranosyl (9), hyperoside (10), and rutin (11). The results revealed that compounds 7, 9, and 10 could enhance glucose consumption significantly in hyperglycemia induced HepG2 cells and insulin-resistant HepG2 cells. In addition, the western blotting analysis result exhibited that compounds 7, 9, and 10 in high concentration (5 µM, H) group could dramatically upregulate the expression of PPARγ protein, and even the effect of them had no significant difference compared with that of rosiglitazone. Furthermore, compounds 9 and 10 in middle concentration (2.5 µM, M) group and H group could dramatically promote triglyceride metabolism and decrease TG content in OA-treated HepG2 cells, and even in H group, reactive oxygen species (ROS) level were significantly decreased compared with model group. PRACTICAL APPLICATIONS: Hypericum patulum is a well-known plant of the genera Hypericum for its varied preventive and therapeutic potential activities. To study the chemical constituents and their effects on glucose and lipid metabolism in vitro, we detected glucose consumption in insulin-resistant HepG2 cells, triglyceride content and reactive oxygen species level in OA-treated HepG2 cells. In addition, PPARγ protein was also detected by western blotting analysis in the study. Compounds 1, 2, 3, 5, 6, 9, 10, and 11 were isolated from the plant for the first time. Quercetin-3-O-(4"-methoxy)-α-L-rahmnopyranosyl (9) and hyperoside (10) had potential therapeutic benefit against glucose and lipid metabolic disease. Therefore, this study might have certain guiding significance for further research and development of H. patulum.

10.
World Neurosurg ; 2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34418611

RESUMO

OBJECTIVE: Occlusion of ventriculoperitoneal shunts placed after intraventricular hemorrhage occurs frequently. The objective of this study was to develop a hemorrhagic hydrocephalus model to assess the ability of an oscillating microactuator within the ventricular catheter (VC) to prevent shunt obstruction. METHODS: An in vitro hydrocephalus model with extreme risk of shunt obstruction was created. Phosphate-buffered saline, blood, and thrombin were driven through ventriculoperitoneal shunts for 8 hours. Five VCs were fitted with a microactuator and compared with 5 control VCs. The microactuator was actuated by an external magnetic field for 30 minutes. Pressure within the imitation lateral ventricle was measured. RESULTS: In the 5 control shunts, 6 obstructions developed (3 VC, 3 valve-distal catheter) compared with 1 obstruction (VC) in the 5 microactuator shunts. In the control and microactuator groups, the median volume exiting the shunts in 8 hours was 30 mL versus 256 mL. Median time to reach an intraventricular pressure of 40 mm Hg (13.8 minutes vs. >8 hours), median total time >40 mm Hg (6.2 hours vs. 0.0 hours), and median maximum pressure (192 mm Hg vs. 36 mm Hg) were significantly improved in the microactuator group (P < 0.01). CONCLUSIONS: In addition to protecting the VC, the microactuator appeared to prevent hematoma obstructing the valve or distal catheter, resulting in a much longer duration of low intraventricular pressures. A microactuator activated by placing the patient's head in an external magnetic field could reduce shunt obstructions in hemorrhagic hydrocephalus.

11.
Molecules ; 26(16)2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34443299

RESUMO

Phycocyanin, derived from marine algae, is known to have noteworthy antineoplastic properties. However, the underlying mechanism involved in phycocyanin-mediated anti-growth function on non-small cell lung cancer (NSCLC) cells is still ambiguous. Here, we investigated the mechanism of action of phycocyanin on H1299, A549, and LTEP-a2 cells. According to the results obtained, insulin receptor substrate 1 (IRS-1) expression was reduced by phycocyanin. Cell phenotype tests showed that siRNA knockdown of IRS-1 expression significantly inhibited the growth, migration, colony formation, but promoted the apoptosis of NSCLC cells. Meanwhile, phycocyanin and IRS-1 siRNA treatment both reduced the PI3K-AKT activities in NSCLC cells. Moreover, overexpression of IRS-1 accelerated the proliferation, colony formation, and migration rate of H1299, A549, and LTEP-a2 cells, which was contradicting to the knockdown results. Overall, this study uncovered a regulatory mechanism by which phycocyanin inhibited the growth of NSCLC cells via IRS-1/AKT pathway, laying the foundation for the potential target treatment of NSCLC.

12.
Artigo em Inglês | MEDLINE | ID: mdl-34410922

RESUMO

Increasing attention has been attracted to the research of ultrasound computed tomography (USCT). This paper reports the design considerations and implementation details of a novel USCT research system named UltraLucid, which aims to provide a user-friendly platform for researchers to develop new algorithms and conduct clinical trials. The modular design strategy is adopted to make the system highly scalable. A prototype has been assembled in our laboratory, which is equipped with a 2048-element ring transducer, 1024 transmit (TX) channels, 1024 receive (RX) channels, two servers, and a control unit. The prototype can acquire raw data from 1024 channels simultaneously using a modular data acquisition and transfer system, consisting of sixteen excitation and data acquisition (EDAQ) boards. Each EDAQ board has 64 independent TX and RX channels and 4 Gigabit Ethernet interfaces for raw data transmission. The raw data can be transferred to two servers at a theoretical rate of 64 Gbps. Both servers are equipped with a 10.9 TB solid-state drive (SSD) array that can store raw data for offline processing. Alternatively, after processing by onboard field-programmable gate arrays (FPGAs), the raw data can be processed online using multi-core central processing units (CPUs) and graphics processing units (GPUs) in each server. Through a control software running on the host computer, the researchers can configure parameters for transmission, reception, and data acquisition. Novel transmit-receive scheme and coded imaging can be implemented. The modular hardware structure and the software-based processing strategy make the system highly scalable and flexible. The system performance is evaluated with phantoms and in vivo experiments.

13.
Zhongguo Gu Shang ; 34(8): 710-6, 2021 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-34423613

RESUMO

OBJECTIVE: To explore the methods and efficacy of unilateral extra-pedicle precision puncture percutaneous vertebroplasty (PVP) or percutaneous kyphoplasty(PKP) by digital subtraction angiography (DSA) for the treatment of osteoporotic vertebral compression fractures (OVCFs). METHODS: The clinical data of 68 patients with osteoporotic vertebral compression fractures treated from August 2015 to December 2018 were retrospectively analyzed. There were 20 males and 48 females, aged 56 to 90(73.5±8.0) years, 40 cases of double segments, 28 cases of three segments, a total of 168 vertebrae. All the patients were performed PVP orPKP through unilateral extra pedicle precision puncture under the guidance of DSA. The vertebrae were distributed in T1-T6(29 vertebrae), T6-T12(89 vertebrae), and L1-L5(50 vertebrae). Whether the puncture needle tip reached the midline of vertebral body was observed during operation, the leakage rate of bone cement was recorded after operation. The height of anterior edge and middle of the fractured vertebral body were measured after operation. Visual analogue scale (VAS) and the Oswestry Disability Index (ODI) were used to assess pain and lumbar function before operation, 3 days after operation and final follow-up time. RESULTS: All the punctures were successful in 68 patients. All the puncture needles reached the midline of vertebral body, and the bone cement was well dispersed in the vertebral body with symmetrical distribution. The operation time was 35 to 60 (41.6±3.2) minutes, and there was no puncture complications. The injection volume of bone cement was 3 to 5 (3.6±0.5) ml in each vertebra. There were 8 cases of bone cement leakage, with a leakage rate of 11.76%. All 68 patients were followed up from 12 to 27 (14.3±3.5) months in the study. VAS score and ODI at 3 days after surgery and at final follow-up time were significantly improved (P<0.05). The height of the anterior edge and the middle of vertebral body at 3 days after operation and at final were significantly recovered (P<0.05). CONCLUSION: PVP or PKP under the guidance of DSA via a unilateral extrapedicular approach with precision puncture can effectively relieve pain, restore vertebral body height and spinal function, which is a safe, fast and effective method in the treatment of osteoporotic vertebral compression fractures.


Assuntos
Fraturas por Compressão , Cifoplastia , Fraturas por Osteoporose , Fraturas da Coluna Vertebral , Vertebroplastia , Angiografia Digital , Feminino , Fraturas por Compressão/diagnóstico por imagem , Fraturas por Compressão/cirurgia , Humanos , Masculino , Fraturas por Osteoporose/diagnóstico por imagem , Fraturas por Osteoporose/cirurgia , Estudos Retrospectivos , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/cirurgia
14.
Neurobiol Aging ; 106: 292-303, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34340010

RESUMO

Increasing evidence has placed inflammation and immune dysfunction at the center of the pathogenesis of Alzheimer's disease (AD). The mitochondrial protein translocator protein (18 kDa) (TSPO) is highly upregulated in microglia and astrocytes in response to inflammatory stimulation. However, the biological action of TSPO in the pathogenesis of AD has not been determined to date. In this study, we showed that TSPO expression was upregulated in brain tissues from AD patients and AD model mice. APP/PS1 mice lacking TSPO generated significantly higher levels of Aß1-40 and Aß1-42 peptides and more Aß plaques, as well as enhanced microglial activation, in the brain. TSPO-deficient microglia cultured in vitro showed a significant decrease in the ability to phagocytose Aß peptides or latex beads and generated more proinflammatory cytokines (TNF-α and IL-1ß) in response to Aß peptides. Our findings suggest that TSPO has protective functions against neuroinflammation and Aß pathogenesis in AD. TSPO may be a potential drug target for the development of drugs that have therapeutic or preventive effects in neuroinflammatory diseases.

15.
Med Sci Monit ; 27: e930588, 2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34388144

RESUMO

BACKGROUND By using functional magnetic resonance imaging (fMRI), we aimed to study the changes in potential brain function network activity in patients with acute eye pain. Also, by using the voxel-wise degree centrality (DC) method, we aimed to explore the relationship between spontaneous brain activity and the clinical features of patients with acute eye pain. MATERIAL AND METHODS A total of 15 patients with acute eye pain (5 women and 10 men; EP group) and 15 healthy controls (5 women and 10 men; HC group), were scanned by fMRI. The DC method was used to evaluate changes in spontaneous brain activity. Receiver operating characteristic (ROC) curves were analyzed, and Pearson correlation analysis was used to study the relationship between DC values and clinical manifestations in different regions of brain. RESULTS The area of the left limbic lobe showed a reduction in DC value in patients in the EP group. DC values were elevated in the left cerebellum posterior lobe, left inferior parietal lobule, left inferior temporal gyrus, left precuneus, and right cerebellum posterior lobe in the EP group. The visual analog scale value of the eyes in the EP group was negatively correlated with the left limbic lobe signal value and positively correlated with the left inferior parietal lobule signal value. Further, the scores of the hospital anxiety and depression scale and DC value of the left limbic lobe were negatively correlated. CONCLUSIONS Compared with the HC group, patients with acute eye pain had abnormal patterns of intrinsic brain activity in different brain regions, which may help reveal the potential neural mechanisms involved in eye pain.

16.
Oral Oncol ; 121: 105472, 2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34333450

RESUMO

OBJECTIVES: Anti-PD-1/PD-L1 therapy has recently been approved for head and neck squamous cell carcinoma (HNSCC). However, given that large numbers of patients with HNSCC do not respond to PD-1/PD-L1 antibodies, combination strategies for elevating the response rate need to be further investigated. The goal of this study was to explore the possibility of dual-targeting CD155/TIGIT and PD-1/PD-L1 signalling in HNSCC. MATERIALS AND METHODS: Multiplex flow cytometry was performed to determine the co-expression of CD155 and PD-L1 in human HNSCC and transgenic HNSCC mouse models. The combined application of TIGIT mAb and PD-L1 mAb in a mouse model was used to explore the therapeutic effect. RESULTS: CD155 and PD-L1 were highly co-expressed on myeloid-derived suppressor cells (MDSCs) derived from patients with HNSCC and were inversely associated with the percentage of tumour CD3+ T and effector memory T cells. CD155+PD-L1+ MDSCs in the mouse model were gradually enriched in the tumour microenvironment in the middle and late stages of tumour progression. Anti-PD-L1 treatment alone upregulated the expression of CD155 on MDSCs and while anti-TIGIT treatment upregulated the expression of PD-L1 on MDSCs in mice. The combined blockade of TIGIT/CD155 and PD-1/PD-L1 signalling in mice significantly inhibited tumour growth, enhanced the percentages of effector T cells and cytokine secretion and elicited immune memory effects. CONCLUSION: Our study indicated that CD155+PD-L1+ MDSCs are enriched in the tumour microenvironment and blocking TIGIT/CD155 can effectively enhance the response rate of HNSCC to PD-L1 mAb therapy, which provides the clinical potential of co-targeting TIGIT/CD155 and PD-1/PD-L1 signalling.

17.
Neuroimage ; 242: 118451, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34358660

RESUMO

When investigating connectivity and microstructure of white matter pathways of the brain using diffusion tractography bundle segmentation, it is important to understand potential confounds and sources of variation in the process. While cross-scanner and cross-protocol effects on diffusion microstructure measures are well described (in particular fractional anisotropy and mean diffusivity), it is unknown how potential sources of variation effect bundle segmentation results, which features of the bundle are most affected, where variability occurs, nor how these sources of variation depend upon the method used to reconstruct and segment bundles. In this study, we investigate six potential sources of variation, or confounds, for bundle segmentation: variation (1) across scan repeats, (2) across scanners, (3) across vendors (4) across acquisition resolution, (5) across diffusion schemes, and (6) across diffusion sensitization. We employ four different bundle segmentation workflows on two benchmark multi-subject cross-scanner and cross-protocol databases, and investigate reproducibility and biases in volume overlap, shape geometry features of fiber pathways, and microstructure features within the pathways. We find that the effects of acquisition protocol, in particular acquisition resolution, result in the lowest reproducibility of tractography and largest variation of features, followed by vendor-effects, scanner-effects, and finally diffusion scheme and b-value effects which had similar reproducibility as scan-rescan variation. However, confounds varied both across pathways and across segmentation workflows, with some bundle segmentation workflows more (or less) robust to sources of variation. Despite variability, bundle dissection is consistently able to recover the same location of pathways in the deep white matter, with variation at the gray matter/ white matter interface. Next, we show that differences due to the choice of bundle segmentation workflows are larger than any other studied confound, with low-to-moderate overlap of the same intended pathway when segmented using different methods. Finally, quantifying microstructure features within a pathway, we show that tractography adds variability over-and-above that which exists due to noise, scanner effects, and acquisition effects. Overall, these confounds need to be considered when harmonizing diffusion datasets, interpreting or combining data across sites, and when attempting to understand the successes and limitations of different methodologies in the design and development of new tractography or bundle segmentation methods.

18.
Oral Oncol ; 121: 105494, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34425533

RESUMO

BACKGROUND: Our previous trial confirmed that induction chemotherapy (IC) improved long-term survival outcomes in patients with locoregionally advanced nasopharyngeal carcinoma (NPC). In this study, we investigated the impact of IC on long-term quality of life (QoL) in this cohort. METHODS: Our trial was a randomised, open-label phase 3 trial comparing IC followed by concurrent chemoradiotherapy (CCRT) versus CCRT alone in patients with stage III-IVB (except T3N0-1) NPC. All participants completed two self-administered questionnaires, the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 (QLQ-C30) and the EORTC QLQ Head and Neck Cancer-Specific Module (H&N35). As per protocol, the questionnaires had to be completed before knowledge of treatment allocation by the patient (baseline). Patients were then approached to enroll at the time of the present study period. RESULTS: Ultimately, QoL data from 228 patients were included in the analysis. Most scales were both statistically and clinically decreased in both groups between baseline and the latest follow-up. The IC followed by CCRT group had significantly better outcome in role functioning, cognitive functioning, social functioning, fatigue, pain, and constipation in QLQ-C30 scales at the last follow-up. Similarly, in H&N35 scales, a significantly better result was observed in pain, sexuality, sticky saliva, pain killers use, nutritional supplements, and weight loss, but a poorer result in senses problems, for those treated by IC followed by CCRT. CONCLUSION: IC followed by CCRT seemed to have better long-term QoL outcomes compared with CCRT alone in patients with locoregionally advanced NPC.

19.
Int J Oncol ; 59(4)2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34414460

RESUMO

Sequestosome 1 (SQSTM1)/p62 is an adapter protein mainly involved in the transportation, degradation and destruction of various proteins that cooperates with components of autophagy and the ubiquitin­proteasome degradation pathway. Numerous studies have shown that SQSTM1/p62 functions at multiple levels, including involvement in genetic stability or modification, post­transcriptional regulation and protein function. As a result, SQSTM1/p62 is a versatile protein that is a critical core regulator of tumor cell genetic stability, autophagy, apoptosis and other forms of cell death, malignant growth, proliferation, migration, invasion, metastasis and chemoradiotherapeutic response, and an indicator of patient prognosis. SQSTM1/p62 regulates these processes via its distinct molecular structure, through which it participates in a variety of activating or inactivating tumor­related and tumor microenvironment­related signaling pathways, particularly positive feedback loops and epithelial­mesenchymal transition­related pathways. Therefore, functioning as a proto­oncogene or tumor suppressor gene in various types of cancer and tumor­associated microenvironments, SQSTM1/p62 is capable of promoting or retarding malignant tumor aggression, giving rise to immeasurable effects on tumor occurrence and development, and on patient treatment and prognosis.

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