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Glycerol, a primary by-product of biodiesel production, can be oxidized into various value-added chemicals, significantly enhancing the techno-economic value of photoelectrochemical (PEC) cells. Several studies have explored various photoelectrode materials and co-catalysts, but the influence of electrolytes on PEC glycerol oxidation has remained relatively unexplored despite its significance. Here, we explore the impact of various acidic (pH = 2) electrolytes, namely NaNO3, NaClO4, Na2SO4, K2SO4, and KPi, on PEC glycerol oxidation using nanoporous thin film BiVO4 as a model photoanode. Our experimental findings reveal that the choice of electrolyte anion and cation significantly affects the PEC performance (i.e., photocurrent, onset potential, stability, and selectivity towards value-added products) of BiVO4 for glycerol oxidation. To explain this interesting phenomenon, we correlate the observed performance trend with the ion specificity in the Hofmeister series as well as the buffering capacity of the electrolytes. Notably, NaNO3 is identified as the optimal electrolyte for PEC glycerol oxidation with BiVO4 when considering various factors such as stability and production rates for glycerol oxidation reaction (GOR) products, surpassing the previously favored Na2SO4. Glycolaldehyde emerges as the most dominant product with â¼50% selectivity in NaNO3. The general applicability of our findings is confirmed by similar observation in electrochemical (EC) GOR with a polycrystalline platinum anode. Overall, these results emphasize the critical role of electrolyte selection in enhancing the efficiency of EC/PEC glycerol oxidation.
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Background: Diagnosing lung diseases accurately is crucial for proper treatment. Convolutional neural networks (CNNs) have advanced medical image processing, but challenges remain in their accurate explainability and reliability. This study combines U-Net with attention and Vision Transformers (ViTs) to enhance lung disease segmentation and classification. We hypothesize that Attention U-Net will enhance segmentation accuracy and that ViTs will improve classification performance. The explainability methodologies will shed light on model decision-making processes, aiding in clinical acceptance. Methodology: A comparative approach was used to evaluate deep learning models for segmenting and classifying lung illnesses using chest X-rays. The Attention U-Net model is used for segmentation, and architectures consisting of four CNNs and four ViTs were investigated for classification. Methods like Gradient-weighted Class Activation Mapping plus plus (Grad-CAM++) and Layer-wise Relevance Propagation (LRP) provide explainability by identifying crucial areas influencing model decisions. Results: The results support the conclusion that ViTs are outstanding in identifying lung disorders. Attention U-Net obtained a Dice Coefficient of 98.54% and a Jaccard Index of 97.12%. ViTs outperformed CNNs in classification tasks by 9.26%, reaching an accuracy of 98.52% with MobileViT. An 8.3% increase in accuracy was seen while moving from raw data classification to segmented image classification. Techniques like Grad-CAM++ and LRP provided insights into the decision-making processes of the models. Conclusions: This study highlights the benefits of integrating Attention U-Net and ViTs for analyzing lung diseases, demonstrating their importance in clinical settings. Emphasizing explainability clarifies deep learning processes, enhancing confidence in AI solutions and perhaps enhancing clinical acceptance for improved healthcare results.
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Crise Blástica , Proteínas de Fusão bcr-abl , Células-Tronco Neoplásicas , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/patologia , Células-Tronco Neoplásicas/metabolismo , Proteínas de Fusão bcr-abl/antagonistas & inibidores , Proteínas de Fusão bcr-abl/genética , Crise Blástica/patologia , Crise Blástica/tratamento farmacológico , Humanos , Animais , Camundongos , Pirazóis/farmacologia , Pirazóis/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas c-abl/metabolismo , Proteínas Proto-Oncogênicas c-abl/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-abl/genética , Niacinamida/análogos & derivadosRESUMO
The myeloproliferative disease polycythemia vera (PV) driven by the JAK2 V617F mutation can transform into myelofibrosis (post-PV-MF). It remains an open question how JAK2 V617F in hematopoietic stem cells induces MF. Megakaryocytes are major players in murine PV models but are difficult to study in the human setting. We generated induced pluripotent stem cells (iPSCs) from JAK2 V617F PV patients and differentiated them into megakaryocytes. In differentiation assays, JAK2 V617F iPSCs recapitulated the pathognomonic skewed megakaryocytic and erythroid differentiation. JAK2 V617F iPSCs had a TPO-independent and increased propensity to differentiate into megakaryocytes. RNA sequencing of JAK2 V617F iPSC-derived megakaryocytes reflected a proinflammatory, profibrotic phenotype and decreased ribosome biogenesis. In three-dimensional (3D) coculture, JAK2 V617F megakaryocytes induced a profibrotic phenotype through direct cell contact, which was reversed by the JAK2 inhibitor ruxolitinib. The 3D coculture system opens the perspective for further disease modeling and drug discovery.
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Células-Tronco Pluripotentes Induzidas , Policitemia Vera , Humanos , Camundongos , Animais , Medula Óssea/patologia , Megacariócitos , Janus Quinase 2/genética , Policitemia Vera/genética , Policitemia Vera/patologia , Fenótipo , Fibrose , MutaçãoRESUMO
PURPOSE: To evaluate the clinical and electrographic characteristics of critically ill pediatric patients with lateralized rhythmic delta activity (LRDA) and compare them with patients with lateralized periodic discharges (LPDs). METHODS: This was a retrospective study examining consecutive critically ill pediatric patients (1 month-18 years) with LRDA or LPDs monitored on continuous electroencephalography. Clinical, radiologic, and electrographic characteristics; disease severity; and acute sequelae were compared between the two groups. RESULTS: Of 668 pediatric patients monitored on continuous electroencephalography during the study period, 12 (1.79%) patients had LRDA and 15 (2.24%) had LPDs. The underlying etiologies were heterogeneous with no difference in the acuity of brain MRI changes between both groups. Lateralized rhythmic delta activity and LPDs were concordant with the side of MRI abnormality in most patients [85.7% (LRDA) and 83.3% (LPD)]. There was no difference in the measures of disease severity between both groups. Seizures were frequent in both groups (42% in the LRDA group and 73% in the LPD group). Patients in the LPD group had a trend toward requiring a greater number of antiseizure medications for seizure control (median of 4 vs. 2 in the LRDA group, p = 0.09), particularly those patients with LPDs qualifying as ictal-interictal continuum compared with those without ictal-interictal continuum (p = 0.02). CONCLUSIONS: Lateralized rhythmic delta activity and LPDs are uncommon EEG findings in the pediatric population. Seizures occur commonly in patients with these patterns. Seizures in patients with LPDs, especially those qualifying as ictal-interictal continuum, showed a trend toward being more refractory. Larger studies are needed in the future to further evaluate these findings.
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BACKGROUND AND AIM: The impact of chronic low-grade inflammation in the development of non-alcoholic fatty liver disease (NAFLD) has been studied widely. Previous studies showed gut pathogens' effects on inflammation development in NAFLD patients; hence, hypothetically, gut microbial therapy by administration of probiotics, synbiotics, and prebiotics may alleviate inflammation in these individuals. Several studies were performed in this regard; however, conflicting results were obtained. In this study, we aimed to comprehensively evaluate the effects of gut microbial therapy on inflammatory markers in NAFLD patients in a meta-umbrella design. METHODS: Two independent researchers investigated international databases, including PubMed, Web of Science, Scopus, and Cochrane Library, from inception until March 2023. Meta-analyses evaluating the impact of probiotics, synbiotics, or prebiotics on inflammatory markers of patients with NAFLD were eligible for our study. AMASTAR 2 checklist was used to evaluate the quality of included studies. Random effect model was performed for the analysis, and Egger's regression test was conducted to determine publication bias. RESULTS: A total number of 12 studies were entered into our analysis. Our findings revealed that gut microbial therapy could significantly reduce serum C-reactive protein (CRP) levels among NAFLD patients (ES: -0.58; 95% CI: -0.73, -0.44, P < 0.001). In subgroup analysis, this reduction was observed with both probiotics (ES: -0.63; 95% CI: -0.81, -0.45, P < 0.001) and synbiotics (ES: -0.49; 95% CI: -0.74, -0.24, P < 0.001). In addition, gut microbial therapy could significantly decrease tumor necrosis factor-a (TNF-a) levels in NAFLD patients (ES: -0.48; 95% CI: -0.67 to -0.30, P < 0.001). In subgroup analysis, this decrease was observed with probiotics (ES: -0.32; 95% CI: -0.53, -0.11, P = 0.002) and synbiotics (ES: -0.96; 95% CI: -1.32, -0.60, P < 0.001). Not enough information was available for assessing prebiotics' impacts. CONCLUSION: The results of this umbrella review suggest that probiotics and synbiotics have promising effects on inflammatory markers, including TNF-a and CRP; however, more research is needed regarding the effects of prebiotics. PROSPERO REGISTRATION CODE: CRD42022346998.
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Hepatopatia Gordurosa não Alcoólica , Probióticos , Simbióticos , Humanos , Hepatopatia Gordurosa não Alcoólica/terapia , Prebióticos , Probióticos/uso terapêutico , Inflamação , Anti-InflamatóriosRESUMO
Rett syndrome is an X-linked neurodevelopmental disorder caused by mutation of Mecp2 gene and primarily affects females. Glial cell dysfunction has been implicated in in Rett syndrome (RTT) both in patients and in mouse models of this disorder and can affect synaptogenesis, glial metabolism and inflammation. Here we assessed whether treatment of adult (5-6 months old) symptomatic Mecp2-heterozygous female mice with N-acetyl cysteine conjugated to dendrimer (D-NAC), which is known to target glia and modulate inflammation and oxidative injury, results in improved behavioral phenotype, sleep and glial inflammatory profile. We show that unbiased global metabolomic analysis of the hippocampus and striatum in adult Mecp2-heterozygous mice demonstrates significant differences in lipid metabolism associated with neuroinflammation, providing the rationale for targeting glial inflammation in this model. Our results demonstrate that treatment with D-NAC (10 mg/kg NAC) once weekly is more efficacious than equivalently dosed free NAC in improving the gross neurobehavioral phenotype in symptomatic Mecp2-heterozygous female mice. We also show that D-NAC therapy is significantly better than saline in ameliorating several aspects of the abnormal phenotype including paw clench, mobility, fear memory, REM sleep and epileptiform activity burden. Systemic D-NAC significantly improves microglial proinflammatory cytokine production and is associated with improvements in several aspects of the phenotype including paw clench, mobility, fear memory, and REM sleep, and epileptiform activity burden in comparison to saline-treated Mecp2-hetereozygous mice. Systemic glial-targeted delivery of D-NAC after symptom onset in an older clinically relevant Rett syndrome model shows promise in improving neurobehavioral impairments along with sleep pattern and epileptiform activity burden. These findings argue for the translational value of this approach for treatment of patients with Rett Syndrome.
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Introduction: Preclinical studies in a mouse model have shown that SYNGAP1 haploinsufficiency results in an epilepsy phenotype with excessive GluA2-AMPA insertion specifically on the soma of fast-spiking parvalbumin-positive interneurons associated with significant dysfunction of cortical gamma homeostasis that was rescued by perampanel (PER), an AMPA receptor blocker. In this single case, we aimed to investigate the presence of dysregulated cortical gamma in a toddler with a pathogenic SYNGAP1 variant and report on the effect of low-dose PER on electroencephalogram (EEG) and clinical profile. Methods: Clinical data from physician's clinic notes; genetic testing reports; developmental scores from occupational therapy, physical therapy, speech and language therapy evaluations; and applied behavioral analysis reports were reviewed. Developmental assessments and EEG analysis were done pre- and post-PER. Results: Clinically, the patient showed improvements in the developmental profile and sleep quality post-PER. EEG spectral power analysis in our patient revealed a loss of gamma power modulation with behavioral-state transitions similar to what was observed in Syngap1+/- mice. Furthermore, the administration of low-dose PER rescued the dysfunctional cortical gamma homeostasis, similar to the preclinical study. However, as in the epileptic mice, PER did not curb epileptiform discharges or clinical seizures. Conclusion: Similar to the Syngap1+/- mice, cortical gamma homeostasis was dysregulated in the patient. This dysfunction was rescued by PER. These encouraging results necessitate further validation of gamma dysregulation as a potential translational EEG biomarker in SYNAP1-DEE. Low-dose PER can be explored as a therapeutic option through clinical trials.
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In this report, we propose a novel technique for identifying and analyzing diverse nanoscale carbon allotropes using scanning electron micrographs. By precisely controlling the quenching rates of undercooled molten carbon through laser irradiation, we achieved the formation of microdiamonds, nanodiamonds, and Q-carbon films. However, standard laser irradiation without proper undercooling control leads to the formation of sparsely located diverse carbon polymorphs, hindering their discovery and classification through manual analyses. To address this challenge, we applied transfer-learning approaches using convolutional neural networks and computer vision techniques to achieve allotrope discovery even with sparse spatial presence. Our method achieved high accuracy rates of 92% for Q-carbon identification and 94% for distinguishing it from nanodiamonds. By leveraging scanning electron micrographs and precise undercooling control, our technique enables the efficient identification and characterization of nanoscale carbon structures. This research significantly contributes to the advancement of the field, providing automated tools for Q-materials and carbon polymorph identification. It opens up new opportunities for the further exploration of these materials in various applications.
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Membrane electrode assemblies enable CO2 electrolysis at industrially relevant rates, yet their operational stability is often limited by formation of solid precipitates in the cathode pores, triggered by cation crossover from the anolyte due to imperfect ion exclusion by anion exchange membranes. Here we show that anolyte concentration affects the degree of cation movement through the membranes, and this substantially influences the behaviors of copper catalysts in catholyte-free CO2 electrolysers. Systematic variation of the anolyte (KOH or KHCO3) ionic strength produced a distinct switch in selectivity between either predominantly CO or C2+ products (mainly C2H4) which closely correlated with the quantity of alkali metal cation (K+) crossover, suggesting cations play a key role in C-C coupling reaction pathways even in cells without discrete liquid catholytes. Operando X-ray absorption and quasi in situ X-ray photoelectron spectroscopy revealed that the Cu surface speciation showed a strong dependence on the anolyte concentration, wherein dilute anolytes resulted in a mixture of Cu+ and Cu0 surface species, while concentrated anolytes led to exclusively Cu0 under similar testing conditions. These results show that even in catholyte-free cells, cation effects (including unintentional ones) significantly influence reaction pathways, important to consider in future development of catalysts and devices.
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Herein, we report a straightforward, scalable synthetic route towards poly(ionic liquid) (PIL) homopolymer nanovesicles (NVs) with a tunable particle size of 50 to 120 nm and a shell thickness of 15 to 60 nm via one-step free radical polymerization induced self-assembly. By increasing monomer concentration for polymerization, their nanoscopic morphology can evolve from hollow NVs to dense spheres, and finally to directional worms, in which a multilamellar packing of PIL chains occurred in all samples. The transformation mechanism of NVs' internal morphology is studied in detail by coarse-grained simulations, revealing a correlation between the PIL chain length and the shell thickness of NVs. To explore their potential applications, PIL NVs with varied shell thickness are in situ functionalized with ultra-small (1 â¼ 3 nm in size) copper nanoparticles (CuNPs) and employed as electrocatalysts for CO2 electroreduction. The composite electrocatalysts exhibit a 2.5-fold enhancement in selectivity towards C1 products (e.g., CH4), compared to the pristine CuNPs. This enhancement is attributed to the strong electronic interactions between the CuNPs and the surface functionalities of PIL NVs. This study casts new aspects on using nanostructured PILs as new electrocatalyst supports in CO2 conversion to C1 products.
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Central granular cell odontogenic tumor (CGCOT) is a rare, benign odontogenic tumor resulting from the jaw bone, especially the mandible or maxilla. It affects women of middle age and usually occurs as a painless swelling of the mandibular premolar-molar area. CGCOT is characterized by the presence of granular cells, which are large, eosinophilic, granular-looking cells found in the tumor tissue. We report an unusual CGCOT in a 38-year-old male patient's mandibular region. We also describe the clinical, radiological, and pathological characteristics along with the immunohistochemical investigation of the tumor.
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Background: Many quantitative MRI parameters and clinical scores have been used patients with lumbar spinal stenosis (LSS). However, the correlation between clinical scores and MRI parameters is not very clear. The objective of the study was to find out the correlation between commonly used clinical scoring systems and quantitative MRI parameters. Methods: Eighty two patients (more than 40 years) with clinical and radiological characteristics of degenerative LSS completed 10 clinical questionnaires which included Oswestry disability index (ODI), Swiss spinal stenosis (SSS) questionnaire, Quebec pain disability scale (QPD), Visual analogue scale (VAS), modified Japanese orthopaedic association scale (mJOA), Pain disability index (PDI), Short form health survey (SF-36), Self-paced walking test (SPWT), Euro quality of life-5D (EQ-5D) and Neurogenic claudication outcome score (NCOS). Lumbosacral MRIs were performed and 8 quantitative parameters namely transverse & AP diameter of dural sac (TDD, APDD), anteroposterior diameter of spinal canal (APDS), ligamentous interfacet distance (LID), mid-sagittal diameter of thecal sac (MSDT), cross-sectional area dural sac (CSAD), lateral recess depth and angle (LRD, LRA) were measured at the maximum stenotic level at the level of the disc. The clinical and radiological parameters were then statistically analysed. Results: There were 51 females and 31 males in the study with a mean age of 53.0253.02 ± 9.18 years. NCOS score had a moderate correlation with CSAD, LID and TDS (p<0.05,0.7>r ≥ 0.3). MSDT showed a moderate negative correlation with SSS, VAS, ODI and QPD (p<0.05,0.7>r ≥ 0.3). LRD had a moderate negative correlation with ODI and VAS score (p<0.05,0.7>r ≥ 0.3). LRA had a moderate correlation with the EQ-5D and ODI (p<0.05,0.7>r ≥ 0.3). The CSAD had a moderate negative correlation with PDI (r = -0.383, p = 0.000). For all other comparisons, there was poor or no correlation. MRI parameters showed poor or no correlation with most of components of SF-36 score. Conclusions: A poor correlation or no correlation was noted for most of the MRI parameters when compared to commonly used clinical scores. Hence, poor MRI's don't necessarily mean poor clinical scores in LSS. The role of MRI parameters should be supplementary and overreliance on them in LSS management should be avoided.
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Background: Pathogenic variants in SCN1B, the gene encoding voltage-gated sodium channel b1/b1B subunits are associated with a spectrum of epileptic disorders. This study describes a child with early myoclonic encephalopathy and a compound heterozygous variant in the SCN1B gene (p.Arg85Cys and c.3G>C/p.Met1), along with the child's clinical response to anti-seizure medications (ASMs) and the ketogenic diet. We reviewed the current clinical literature pertinent to SCN1B-related epilepsy. Methods: We described the evaluation and management of a patient with SCN1B-related developmental and epileptic encephalopathy (DEE). We used the Medline and Pubmed databases to review the various neurological manifestations associated with SCN1B genetic variants, and summarize the functional studies performed on SCN1B variants. Results: We identified 20 families and six individuals (including the index case described herein) reported to have SCN1B-related epilepsy. Individuals with monoallelic pathogenic variants in SCN1B often present with genetic epilepsy with febrile seizures plus (GEFS+), while those with biallelic pathogenic variants may present with developmental and epileptic encephalopathy (DEE). Individuals with DEE present with seizures of various semiologies (commonly myoclonic seizures) and status epilepticus at early infancy and are treated with various antiseizure medications. In our index case, adjunctive fenfluramine was started at 8 months of age at 0.2 mg/kg/day with gradual incremental increases to the final dose of 0.7 mg/kg/day over 5 weeks. Fenfluramine was effective in the treatment of seizures, resulting in a 50% reduction in myoclonic seizures, status epilepticus, and generalized tonic-clonic seizures, as well as a 70−90% reduction in focal seizures, with no significant adverse effects. Following the initiation of fenfluramine at eight months of age, there was also a 50% reduction in the rate of hospitalizations. Conclusions: SCN1B pathogenic variants cause epilepsy and neurodevelopmental impairment with variable expressivity and incomplete penetrance. The severity of disease is associated with the zygosity of the pathogenic variants. Biallelic variants in SCN1B can result in early myoclonic encephalopathy, and adjunctive treatment with fenfluramine may be an effective treatment for SCN1B-related DEE. Further research on the efficacy and safety of using newer ASMs, such as fenfluramine in patients under the age of 2 years is needed.
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Although voxel-based morphometry (VBM) of gray matter (GM), white matter (WM) and cerebrospinal fluid (CSF) changes aid in epileptic seizure lateralization, type of T1 pulse sequence, preprocessing steps and tissue segmentation methods lead to variation in tissue classification. Here, we test the prediction accuracy of individual MRI based tissue types and a novel composite ratio parameter [(GM + WM)/CSF], sensitive to parenchymal changes and independent of tissue classification variations. Pediatric patients with partial seizures (both simple and complex), but normal and lesion-free MRI were considered (33 patients; unilateral EEG; 17 female / 16 male; age mean ± SD = 11.5 ± 5 years). MRI based seizure lateralization was performed for each patient and verified with EEG findings alone or in combination with seizure semiology. T1 weighted MRI from patients and normal control subjects was spatially transformed to the Talairach atlas and automatically segmented into GM, WM and CSF tissue types. 41 age matched normal controls (11 female / 30 male; age mean ± SD = 14.6 ± 3 years) served as the null distribution to test tissue type deviations across each epilepsy patient. When verified with the patient EEG prediction, WM, GM and CSF had a hemispheric match of 76%, 70% and 55% respectively, while the composite ratio [(GM + WM)/CSF)] showed the highest accuracy of 85%. When EEG findings and seizure semiology were combined, MRI predictions using the composite ratio improved further to 88%. To further localize the epileptic focus, regional level (frontal, temporal, parietal and occipital) MRI predictions were obtained. The composite ratio performed at 88-91% accuracy, revealing regional MRI changes, not predictable with EEG. The results show inconsistent changes in GM and WM in majority of the pediatric epilepsy patients and demonstrate the applicability of the composite ratio [(GM + WM)/CSF)] as a superior predictor, independent of tissue classification variations. Clinical EEG findings combined with seizure semiology, can overcome scalp EEG's limitations and lean towards the MRI lateralization in specific cases.
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Epilepsia , Substância Branca , Humanos , Masculino , Feminino , Criança , Imageamento por Ressonância Magnética/métodos , Substância Cinzenta , Epilepsia/diagnóstico por imagem , ConvulsõesRESUMO
Ketogenic diets (KDs) are highly effective in the treatment of epilepsy. However, numerous complications have been reported. During the initiation phase of the diet, common side effects include vomiting, hypoglycemia, metabolic acidosis and refusal of the diet. While on the diet, the side effects involve the following systems: gastrointestinal, hepatic, cardiovascular, renal, dermatological, hematologic and bone. Many of the common side effects can be tackled easily with careful monitoring including blood counts, liver enzymes, renal function tests, urinalysis, vitamin levels, mineral levels, lipid profiles, and serum carnitine levels. Some rare and serious side effects reported in the literature include pancreatitis, protein-losing enteropathy, prolonged QT interval, cardiomyopathy and changes in the basal ganglia. These serious complications may need more advanced work-up and immediate cessation of the diet. With appropriate monitoring and close follow-up to minimize adverse effects, KDs can be effective for patients with intractable epilepsy.
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To employ graphene's rapid conduction in 2D devices, a heterostructure with a broad bandgap dielectric that is free of traps is required. Within this paradigm, h-BN is a good candidate because of its graphene-like structure and ultrawide bandgap. We show how to make such a heterostructure by irradiating alternating layers of a-C and a-BN film with a nanosecond excimer laser, melting and zone-refining constituent layers in the process. With Raman spectroscopy and ToF-SIMS analyses, we demonstrate this localized zone-refining into phase-pure h-BN and rGO films with distinct Raman vibrational modes and SIMS profile flattening after laser irradiation. Furthermore, in comparing laser-irradiated rGO-Si MS and rGO/h-BN/Si MIS diodes, the MIS diodes exhibit an increased turn-on voltage (4.4 V) and low leakage current. The MIS diode I-V characteristics reveal direct tunneling conduction under low bias and Fowler-Nordheim tunneling in the high-voltage regime, turning the MIS diode ON with improved rectification and current flow. This study sheds light on the nonequilibrium approaches to engineering h-BN and graphene heterostructures for ultrathin field effect transistor device development.
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Background: S100 proteins have been implicated in the tumorigenesis of different human cancers and in oral dysplasia, as they are keratinocytes. Materials and Methods: In the present study, we have attempted to compare the expression of S100-A7 within young-onset (age ≤45 years, Group 1) oral squamous cell carcinoma (OSCC), OSCC in older age groups (age >45 years Group 2), oral potentially malignant disorders (OPMDs, Group 3) and inflammatory lesions (Group 4). The tissue sections were scored based on the percentage of immunostained cells and staining intensity. Nuclear, cytoplasmic and membrane immunoreactivity were also scored. Results: The present study comprised 153 histopathologically diagnosed case subjects of OSCC >45 years (n = 41), OSCC <45 years (n = 36), OPMD (n = 40) and inflammatory lesions (n = 36). The present study revealed a statistically significant difference of distribution with regard to S100A7 staining (cytoplasmic and nuclear) between OPMDs and OSCC (P < 0.05). The nuclear, cytoplasmic and membrane staining as well as the staining intensity had significantly different scoring patterns among the OSCC group, OPMD group and the inflammatory lesions with the OSCC group having the highest scoring of the S100A7 staining (irrespective of the age). Conclusions: The present study concludes that S100A7 can be used as a diagnostic biomarker to differentiate between OPMDs and OSCC lesions. However, the marker is unable to distinguish between OSCCs in younger and older patients as the molecular pathogenesis of tumors in either of these age groups is probably similar.
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The existence of point defects, holes, and corrugations (macroscopic defects) induces high catalytic potential in graphene and its derivatives. We report a systematic approach for microscopic and macroscopic defect density optimization in excimer laser-induced reduced graphene oxide by varying the laser energy density and pulse number to achieve a record detection limit of 7.15 nM for peroxide sensing. A quantitative estimation of point defect densities was obtained using Raman spectroscopy and confirmed with electrochemical sensing measurements. Laser annealing (LA) at 0.6 J cm-2 led to the formation of highly reduced graphene oxide (GO) by liquid-phase regrowth of molten carbon with the presence of dangling bonds, making it catalytically active. Hall-effect measurements yielded a mobility of â¼200 cm2 V-1 s-1. An additional increase in the number of pulses at 0.6 J cm-2 resulted in deoxygenation through the solid-state route, leading to the formation of holey graphene structure. The average hole size showed a hierarchical increase, with the number of pulses characterized with multiple microscopy techniques, including scanning electron microscopy, atomic force microscopy, and transmission electron microscopy. The exposure of edge sites due to high hole density after 10 pulses supported the formation of proximal diffusion layers, which led to facile mass transfer and improvement in the detection limit from 25.4 mM to 7.15 nM for peroxide sensing. However, LA at 1 J cm-2 with 1 pulse resulted in a high melt lifetime of molten carbon and the formation of GO characterized by a high resistivity of 3 × 10-2 Ω-cm, which was not ideal for sensing applications. The rapid thermal annealing technique using a batch furnace to generate holey graphene results in structure with uneven hole sizes. However, holey graphene formation using the LA technique is scalable with better control over hole size and density. This study will pave the path for cost-efficient and high-performance holey graphene sensors for advanced sensing applications.