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Objective Methods Results Interpretation Mitochondria are implicated in regulation of the innate immune response. We hypothesized that abnormalities in interferon signaling may contribute to pathophysiology in patients with primary mitochondrial disease (PMD).Expression of interferon stimulated genes (ISGs) was measured by real‐time polymerase chain reaction (PCR) in whole blood samples from a cohort of patients with PMD.Upregulated ISG expression was observed in a high proportion (41/55, 75%) of patients with PMD on at least 1 occasion, most frequently IFI27 upregulation, seen in 50% of the samples. Some patients had extremely high IFI27 levels, similar to those seen in patients with primary interferonopathies. A statistically significant correlation was observed between elevated IFI27 gene expression and PMD, but not between IFI27 and secondary mitochondrial dysfunction, suggesting that ISG upregulation is a biomarker of PMD. In some patients with PMD, ISG abnormalities persisted on repeat measurement over several years, indicative of ongoing chronic inflammation. Subgroup analyses suggested common ISG signatures in patients with similar mitochondrial disease mechanisms and positive correlations with disease severity among patients with identical genetic diagnoses.Dysregulated interferon signaling is frequently seen in patients with PMD suggesting that interferon dysregulation is a contributor to pathophysiology. This may indicate a role for repurposing of immunomodulatory therapies for the treatment of PMDs by targeting interferon signaling. ANN NEUROL 2024 [ABSTRACT FROM AUTHOR]

The problem of finite‐time state recovery for multivariable second‐order systems with a time‐varying coefficient is considered in this study. The key challenge lies in the time‐varying nature of the regressor coefficient, which possibly results in the lack of a well‐defined relative degree, and renders the synthesis of a finite‐time state observer difficult for such systems. In order to overcome this challenge, a novel multivariable sliding‐mode observer is developed that relies on an information‐rich term based on concurrent learning to ensure observer convergence. In particular, the concurrent learning‐based augmentation term leverages information contained in prior data, which is recorded over a sliding time window in the recent past, so that the resulting observer structure need only satisfy a relaxed observability condition for ensuring finite‐time convergence. A Lyapunov‐based stability analysis is undertaken to demonstrate finite‐time convergence of the observer estimates to a small uniform ultimate bound around the ground truth for a sufficiently large choice of observer gains. The observer is then applied to accomplish the task of structure and motion recovery from machine vision that involves tracking of a single stationary object feature by a moving camera across the image sequence. Numerical results are used to validate accurate observer performance in the presence of model uncertainty and measurement noise for weakly persistently exciting systems. Furthermore, a detailed comparison study with leading alternative designs is also included that demonstrates the superior performance of the proposed scheme. As the current approach precludes any reliance on a restrictive persistency of excitation condition that is difficult to satisfy apriori, an important advantage of the proposed scheme is its suitability to practical applications such as visual servo control. [ABSTRACT FROM AUTHOR]

The problem of synthesizing a fixed-time depth observer based on monocular image feedback is considered in this study. The key challenge lies in the fact that the perspective dynamical system used to model visual motion is typically characterized as being weakly persistently exciting, which complicates observer synthesis. Furthermore, the key to achieving the task objective (safe obstacle avoidance, for instance) lies in the synthesis of a depth observer that achieves rapid convergence of the (static) obstacle depth estimate to the ground truth in a known fixed-time. To address these challenges, and in contrast with prior schemes that rely on a motion-restrictive persistency of excitation (PE) condition for ensuring exponential convergence, a novel adaptive observer framework is considered in this study that incorporates a concurrent learning (CL) term for ensuring fixed-time observer convergence. In particular, the use of concurrent learning allows for the synthesis of a relaxed finite-time excitation condition that relies on historical data recorded over a dynamic sliding window in the recent past that the proposed observer relies on to ensure fixed-time convergence. Thus, a continuous-time reduced-order observer formulation is presented that relies on camera motion data to achieve fixed-time convergence to a uniform ultimate bound for a suitably large choice of the observer gains. Experimental results are used to demonstrate the efficacy of the proposed scheme in the presence of significant measurement noise. A performance comparison study is also undertaken to demonstrate superior performance of the proposed scheme compared to leading alternative designs. Finally, the practical applicability of the proposed scheme is verified by incorporating the proposed scheme within a reactive navigation scheme to accomplish obstacle avoidance. By incorporating a suitably informative CL term within the observer framework, the proposed scheme eliminates the need to rely on a difficult-to-verify PE condition, thus rendering it more suitable for practical applications like visual target-tracking and visual servo control. • A novel feature depth observer is proposed that converges in a fixed convergence time. • Concurrent learning-based observability condition is used to ensure observer convergence. • Experimental results are used to demonstrate safe obstacle avoidance in cluttered arenas. [ABSTRACT FROM AUTHOR]

Deoxyguanosine kinase deficiency is one genetic cause of mtDNA depletion syndrome. Its major phenotypes include neonatal/infantile-onset hepatocerebral disease, isolated hepatic disease and myopathic disease. In this retrospective study, we seek to describe the natural history of deoxyguanosine kinase deficiency and identify any genotype-phenotype correlations. Retrospective literature search and collation of data from genetically confirmed cases of deoxyguanosine kinase deficiency. 173 cases of DGUOK deficiency were identified. Neonatal/infantile-onset hepatocerebral disease accounted for 128 (74%) of cases. Isolated liver disease was seen in 36 (21%) and myopathic disease in 9 (5%) of cases. The most frequently involved systems were liver (98%), brain (75%), growth (46%) and gastrointestinal tract (26%). Infantile-onset disease typically presented with cholestatic jaundice and lactic acidosis. Neurological involvement included hypotonia, nystagmus and developmental delay with MRI brain abnormalities in about half of cases. Missense variants accounted for 48% of all pathogenic variants while variants resulting in truncated transcripts accounted for 39%. Prognosis was poor, especially for neonatal/ infantile-onset hepatocerebral disease for which 1 year survival was 11%. Twenty-three patients received liver transplants, of whom 12 died within 2 years of transplant. Patients with two truncating variants had a higher risk of death and were more likely to have the neonatal/infantile-onset hepatocerebral disease phenotype. No blood biomarker predictive of neurological involvement was identified. Earlier onset correlated with increased mortality. There is a narrow window for therapeutic intervention. For the hepatocerebral disease phenotype, median age of onset was 1 month while the median age of death was 6.5 months implying rapid disease progression. [ABSTRACT FROM AUTHOR]

Although cerebrospinal fluid (CSF) biomarker testing is incorporated into some current guidelines for the diagnosis of dementia (such as England's National Institute for Health and Care Excellence (NICE)), it is not widely accessible for most patients for whom biomarkers could potentially change management. Here we share our experience of running a clinical cognitive CSF service and discuss recent developments in laboratory testing including the use of the CSF amyloid-β 42/40 ratio and automated assay platforms. We highlight the importance of collaborative working between clinicians and laboratory staff, of preanalytical sample handling, and discuss the various factors influencing interpretation of the results in appropriate clinical contexts. We advocate for broadening access to CSF biomarkers by sharing clinical expertise, protocols and interpretation with colleagues working in psychiatry and elderly care, especially when access to CSF may be part of a pathway to disease-modifying treatments for Alzheimer's disease and other forms of dementia. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) may affect the nervous system in many ways. We describe an immunocompetent teenage girl with lymph node TB who had first presented with bilateral optic neuritis. Detailed history identified features inconsistent with immune-mediated optic neuritis. Several unusual features prompted further investigation, including transient visual obscurations without raised intracranial pressure, prominent disc swelling and absence of laboratory findings to support an immune- mediated cause. Whole body PET/ MR imaging identified widespread mediastinal and supraclavicular lymphadenopathy. Despite no known TB contacts, a negative interferon gamma release assay and a normal chest X-ray, a targeted lymph node biopsy confirmed TB. [ABSTRACT FROM AUTHOR]

• Bark extract contains highest content of CPT confirmed by HPLC. • Total yield of pure camptothecin after purification was 62 mg from 50 g of bark. • Chitin treated N. nimmoniana suspension cells showed an 11.48-fold increase in CPT levels. • Jasmonic acid treatment of suspension cells shows a 4.65-fold increase in CPT levels. Camptothecin (CPT) and its analogs are gaining prominence for its promising anti-cancer activity and are used throughout the world for the treatment of colorectal, breast, and lung cancers in particular. Nothapodytes nimmoniana (J. Graham) Mabb. (Olacaceae), a plant native to India's Western Ghats, has been harnessed for the production of CPT. The endangered nature of its wild population has urged plant tissue culture and engineering techniques to increase CPT production in multifold levels by adapting elicitation methods using chemical stress-inducing substances called elicitors. The main objective of this study is to increase the CPT production through in vitro cell suspension culture of N. nimmoniana by treating it with 5 different biotic elicitors such as chitin, chitosan, pullulan, glutathione, and jasmonic acid. The preliminary quantification of CPT in methanolic extracts of wild N. nimmoniana revealed that the bark extracts showed higher level of CPT than the leaf extracts. Further, column chromatography technique was employed to obtain CPT with 99.25 % purity. The elemental composition and structure of the purified compound was confirmed through HR-MS and Proton NMR spectroscopy. Shake flask in vitro elicitation of CPT was observed at a maximum level in 10 % chitin treated elicited culture with a yield of 15.06 μg/150 ml culture followed by 5 % jasmonic acid amounting to 6.025 μg/150 ml of culture as compared with other elicitors and control. LC-MS/MS fragmentation analysis was utilized for the structural confirmation of CPT. In conclusion, the biotic elicitor chitin 10 % treated suspension cells of N. nimmoniana showed maximum level (11.48-fold) of CPT elicitation followed by 4.65-fold in 5 % jasmonic acid treatment as compared with other elicitors and control suspension cells. [ABSTRACT FROM AUTHOR]

Carbon nanotubes (CNTs) have been extensively investigated, and several studies have shown that multi-walled CNTs can trigger inflammation and fibrosis in animal models. However, while neutrophils are involved in inflammation, most in vitro studies have addressed macrophages. Here we explored the impact of three MWCNTs with varying morphology (i.e. long and rigid versus short and/or tangled) on primary human macrophages and macrophage-differentiated THP-1 cells versus primary human neutrophils and neutrophil-differentiated HL-60 cells. We found that long and rigid MWCNTs triggered caspase-dependent cell death in macrophages, accompanied by NLRP3 inflammasome activation and gasdermin D (GSDMD)-mediated release of pro-inflammatory IL-1β. The release of IL-1β was suppressed by disulfiram, an FDA-approved drug known to act as an inhibitor of membrane pore formation by GSDMD. Evidence of autophagic cell death was noted in macrophages exposed to higher concentrations of the long and rigid MWCNTs. Furthermore, lysosomal damage with cytosolic release of cathepsin B was observed in macrophages exposed to the latter MWCNTs. On the other hand, there was little evidence of uptake of MWCNTs in neutrophils and the cells failed to undergo MWCNT-triggered cell death. Our studies have demonstrated that long and rigid MWCNTs trigger pyroptosis in human macrophages. [ABSTRACT FROM AUTHOR]

In recent times, polymer composites have played an epochal role in transforming material science. Some of their properties such as toughness, strength, flexibility and rigidity have helped them supplant conventional materials such as iron, steel, and aluminium on several occasions. Apart from this, they are light in weight and more cost-efficient, which make them a viable alternative. They have found their application in several fields such as automobile industry, aerospace industry, construction and pipeline industry. Owing to its excellent impact strength, tensile and hardness, natural fibres serve as an excellent replacement. Natural fibres are an environmental friendly, biodegradable and are readily available. The present investigation uses a new fibre for manufacturing the eco-friendly composite material. Mechanical properties such as tensile strength, shear stress, flexural rigidity, impact strength and hardness of a coconut fibre-reinforced polymer composite material are evaluated as per respective ASTM standards. A surface analysis of the material using a scanning electron microscope is also performed. The results are categorized and tabulated accordingly. The values obtained appear to fall in line with the experimental data and hence can be espoused as an alternative material especially in the automotive sector. [ABSTRACT FROM AUTHOR]

Alzheimer's disease has a preclinical stage when cerebral amyloid-β deposition occurs before symptoms emerge, and when amyloid-β-targeted therapies may have maximum benefits. Existing amyloid-β status measurement techniques, including amyloid PET and CSF testing, are difficult to deploy at scale, so blood biomarkers are increasingly considered for screening. We compared three different blood-based techniques-liquid chromatography-mass spectrometry measures of plasma amyloid-β, and single molecule array (Simoa) measures of plasma amyloid-β and phospho-tau181-to detect cortical 18F-florbetapir amyloid PET positivity (defined as a standardized uptake value ratio of >0.61 between a predefined cortical region of interest and eroded subcortical white matter) in dementia-free members of Insight 46, a substudy of the population-based British 1946 birth cohort. We used logistic regression models with blood biomarkers as predictors of amyloid PET status, with or without age, sex and APOE ε4 carrier status as covariates. We generated receiver operating characteristics curves and quantified areas under the curves to compare the concordance of the different blood tests with amyloid PET. We determined blood test cut-off points using Youden's index, then estimated numbers needed to screen to obtain 100 amyloid PET-positive individuals. Of the 502 individuals assessed, 441 dementia-free individuals with complete data were included; 82 (18.6%) were amyloid PET-positive. The area under the curve for amyloid PET status using a base model comprising age, sex and APOE ε4 carrier status was 0.695 (95% confidence interval: 0.628-0.762). The two best-performing Simoa plasma biomarkers were amyloid-β42/40 (0.620; 0.548-0.691) and phospho-tau181 (0.707; 0.646-0.768), but neither outperformed the base model. Mass spectrometry plasma measures performed significantly better than any other measure (amyloid-β1-42/1-40: 0.817; 0.770-0.864 and amyloid-β composite: 0.820; 0.775-0.866). At a cut-off point of 0.095, mass spectrometry measures of amyloid-β1-42/1-40 detected amyloid PET positivity with 86.6% sensitivity and 71.9% specificity. Without screening, to obtain 100 PET-positive individuals from a population with similar amyloid PET positivity prevalence to Insight 46, 543 PET scans would need to be performed. Screening using age, sex and APOE ε4 status would require 940 individuals, of whom 266 would proceed to scan. Using mass spectrometry amyloid-β1-42/1-40 alone would reduce these numbers to 623 individuals and 243 individuals, respectively. Across a theoretical range of amyloid PET positivity prevalence of 10-50%, mass spectrometry measures of amyloid-β1-42/1-40 would consistently reduce the numbers proceeding to scans, with greater cost savings demonstrated at lower prevalence. [ABSTRACT FROM AUTHOR]

Background and Purpose: Neurosurgical resection is one of the few opportunities researchers have to image the human brain pre- and postfocal damage. A major challenge associated with brains undergoing surgical resection is that they often do not fit brain templates most image-processing methodologies are based on. Manual intervention is required to reconcile the pathology, requiring time investment and introducing reproducibility concerns, and extreme cases must be excluded.Methods: We propose an automatic longitudinal pipeline based on High Angular Resolution Diffusion Imaging acquisitions to facilitate a Pathway Lesion Symptom Mapping analysis relating focal white matter injury to functional deficits. This two-part approach includes (i) automatic segmentation of focal white matter injury from anisotropic power differences, and (ii) modeling disconnection using tractography on the single-subject level, which specifically identifies the disconnections associated with focal white matter damage.Results: The advantages of this approach stem from (1) objective and automatic lesion segmentation and tractogram generation, (2) objective and precise segmentation of affected tissue likely to be associated with damage to long-range white matter pathways (defined by anisotropic power), (3) good performance even in the cases of anatomical distortions by use of nonlinear tensor-based registration, which aligns images using an approach sensitive to white matter microstructure.Conclusions: Mapping a system as variable and complex as the human brain requires sample sizes much larger than the current technology can support. This pipeline can be used to execute large-scale, sufficiently powered analyses by meeting the need for an automatic approach to objectively quantify white matter disconnection. [ABSTRACT FROM AUTHOR]

BACKGROUND: Moringa oleifera (MO) kernel oil is categorized as a high‐oleic oil that resembles olive oil. However, unlike olive trees, MO trees are largely present in most subtropical and tropical countries. In these countries, therefore, the benefits of oleic acid can be obtained at a cheaper price through the consumption of MO kernel oil. This study reports on the effect of different extraction methods on oxidative properties of MO kernel oil during storage for 140 days at 13, 25, and 37 °C. RESULTS: All aqueous enzymatic extraction (AEE)‐based methods generally resulted in oil with better oxidative properties and higher tocopherol retention than the use of solvent. Prior to AEE, boiling pre‐treatment deactivated the hydrolytic enzymes and preserved the oil's quality. In contrast, high‐pressure processing (HPP) pre‐treatment accelerated hydrolytic reaction and resulted in an increase in free fatty acids after 140 days at all temperatures. No significant changes were detected in the oils' iodine values and fatty acid composition. The tocopherol content decreased significantly at both 13 and 25 °C after 60 days in the oil from SE method, and after 120 days in oils from AEE‐based methods. CONCLUSION: These findings are significant in highlighting the extraction methods resulting in crude MO kernel oil with greatest oxidative stability in the storage conditions tested. Subsequently, the suitable storage condition of the oil prior to refining can be determined. Further studies are recommended in determining the suitable refining processes and parameters for the MO kernel oil prior to application in variety food products. © 2019 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

A growing understanding of the neurobiology of psychosis offers hope for an improvement in the standard of care; this includes the development of individualized, precision therapeutics. However, the path to precision psychiatry is long, and progress would be accelerated by greater collaboration with the fields of neurology and neuroscience. [ABSTRACT FROM AUTHOR]

In grid connected Photovoltaic (PV) systems, Multilevel Inverters (MLI) are commonly employed for providing better reliability and getting minimal harmonics. Most of the MLIs function with Phase-Shifted Pulse Width Modulation (PSPWM) techniques for achieving high level performance. However, in the in existing PSPWM techniques, the harmonic voltage profiles are not efficient. This paper aims to improve the harmonic voltage profile of the 4 KW grid-connected PV system using a novel hybrid PSPWM-Modified Synchronous Optimal PWM (PS-MSOPWM) technique for a 27-level inverter. With the combination of these hybrid PSPWM-Modified SOPWM techniques, optimum switching angles are computed to match the switching frequency with the fundamental frequency. From the results, it is identified that the proposed hybrid modulation method effectively reduces the Total Harmonic Distortion (THD) and exhibits improved reliability of the grid-connected solar system. • Reliability improvement of the grid-connected PV system. • Design of 27-level Cascaded H-bridge inverter with only 12 switches. • PV system with a Novel phase shifted-modified synchronous optimal PWM technique. • Optimization of switching frequency with the fundamental frequency. • Low level of THD with the three-phase induction motor. [ABSTRACT FROM AUTHOR]

Transepithelial electrical resistance (TEER) measures electrical resistance across epithelial tissue barriers involving confluent layer(s) of cells. TEER values act as a prerequisite for determining the barrier integrity of cells, which play a key role in evaluating the transport of drugs, materials or chemicals of interest across an epithelial barrier. The measurements can be performed non-invasively by measuring ohmic resistance across a defined area. Thus, the TEER values are reported in Ω·cm2. In vitro epithelial models are typically assembled on semi-permeable inserts providing two-chamber compartments, and the majority of the studies use inserts with polyethylene terephthalate (PET) membranes. Recently, new inserts with different membrane types and properties have been introduced. However, the TEER values presented so far did not allow a direct comparison. This study presents the characterization of selected epithelial tissues, i.e. , lung, retina, and intestine, grown on an ultra-thin ceramic microporous permeable insert (SiMPLI) and PET membranes with different properties, i.e. , thickness, material, and pore numbers. We verified the epithelial cell growth on both inserts via phase-contrast and confocal laser scanning microscope imaging. Barrier characteristics were assessed by TEER measurements and also by evaluating the permeability of fluorescein isothiocyanate through cell layers. The findings indicated that background TEER value calculations and the available surface area for cell growth must be thoroughly assessed when new inserts are introduced, as the values cannot be directly compared without re-calculations. Finally, we proposed electrical circuit models highlighting the contributors to TEER recordings on PET and SiMPLI insert membranes. This study paves the way for making the ohmic-based evaluation of epithelial tissues' permeability independent of the material and geometry of the insert membrane used for cell growth. [Display omitted] [ABSTRACT FROM AUTHOR]

Aim: Early interventions are well understood to improve psychosis outcomes, but their successful implementation remains limited. This article introduces a three‐step roadmap for advancing the implementation of evidence‐based practices to operate as a learning health system, which can be applied to early interventions for psychosis and is intended for an audience that is relatively new to systematic approaches to implementation. Methods: The roadmap is grounded in implementation science, which specializes in methods to promote routine use of evidence‐based innovations. The roadmap draws on learning health system principles that call for commitment of leadership, application of evidence, examination of care experiences, and study of health outcomes. Examples are discussed for each roadmap step, emphasizing both data‐ and stakeholder‐related considerations applicable throughout the roadmap. Conclusions: Early psychosis care is a promising topic through which to discuss the critical need to move evidence into practice. Despite remarkable advances in early psychosis interventions, population‐level impact of those interventions is yet to be realized. By providing an introduction to how implementation science principles can be operationalized in a learning health system and sharing examples from early psychosis care, this article prompts inclusion of a wider audience in essential discourse on the role that implementation science can play for moving evidence into practice for other realms of psychiatric care as well. To this end, the proposed roadmap can serve as a conceptual guiding template and framework through which various psychiatric services can methodically pursue timely implementation of evidence‐based interventions for higher quality care and improved outcomes. [ABSTRACT FROM AUTHOR]

Summary: Post‐harvest maturation of two Malaysian honeys, the Tualang and Kelulut was studied by measuring changes in physicochemical and antioxidant properties, hydroxymethylfurfural (HMF) contents and bacterial profiles at room temperature of 23–26 °C. After maturation at the recommended period of 26 weeks, water activity of both honeys increased between 0.89% and 2.34% while free acidity increased between 2.05% and 2.24%. Results suggested the prominence of fermentation reactions in honey during post‐harvest maturation as fructose concentration reduced by 10.6% and 1.05% for the Tualang and Kelulut honey, respectively, while HMF concentrations were kept at a safe limit of 48.00 and 61.23 mg/kg honey. The total phenolic content of Tualang and Kelulut honey increased significantly by 12.61% and 54.66% respectively. The highlight of this post‐harvest maturation process for Kelulut honey was the improvement found in antioxidant properties of DPPH radical scavenging activity by 10.01%–54.74% and also the probiotic‐like potential in terms significant increase in relative abundance of the Bacillus genera to 2.6% and Lactobacillus to 6.25% at 26 weeks. The prolonged maturation process up to 1 year however revealed continuous accumulation of HMF to values above 80 mg/kg honey, surpassing the limits by the Codex Alimentarius Commission despite improvements of antioxidant properties and bacterial profiles. [ABSTRACT FROM AUTHOR]

Background: A quantitative measurement of serum proteome biomarkers that would associate with disease progression endpoints can provide risk stratification for persons with multiple sclerosis (PwMS) and supplement the clinical decision‐making process. Materials and Methods: In total, 202 PwMS were enrolled in a longitudinal study with measurements at two time points with an average follow‐up time of 5.4 years. Clinical measures included the Expanded Disability Status Scale, Timed 25‐foot Walk, 9‐Hole Peg, and Symbol Digit Modalities Tests. Subjects underwent magnetic resonance imaging to determine the volumetric measures of the whole brain, gray matter, deep gray matter, and lateral ventricles. Serum samples were analyzed using a custom immunoassay panel on the Olink™ platform, and concentrations of 18 protein biomarkers were measured. Linear mixed‐effects models and adjustment for multiple comparisons were performed. Results: Subjects had a significant 55.6% increase in chemokine ligand 20 (9.7 pg/mL vs. 15.1 pg/mL, p < 0.001) and neurofilament light polypeptide (10.5 pg/mL vs. 11.5 pg/mL, p = 0.003) at the follow‐up time point. Additional changes in CUB domain‐containing protein 1, Contactin 2, Glial fibrillary acidic protein, Myelin oligodendrocyte glycoprotein, and Osteopontin were noted but did not survive multiple comparison correction. Worse clinical performance in the 9‐HPT was associated with neurofilament light polypeptide (p = 0.001). Increases in several biomarker candidates were correlated with greater neurodegenerative changes as measured by different brain volumes. Conclusion: Multiple proteins, selected from a disease activity test that represent diverse biological pathways, are associated with physical, cognitive, and radiographic outcomes. Future studies should determine the utility of multiple protein assays in routine clinical care. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has emerged as a major stressor of a global scale, affecting all aspects of our lives, and is likely to contribute to a surge of mental ill health. Ancient Hindu scriptures, notably the Bhagavad Gita, have a wealth of insights that can help approaches to build psychological resilience for individuals at risk, those affected, as well as for caregivers. The path of knowledge (Jnana yoga) promotes accurate awareness of nature of the self, and can help reframe our thinking from an "I" to a "we mode," much needed for collectively mitigating the spread of the coronavirus. The path of action (Karma yoga) teaches the art of selfless action, providing caregivers and frontline health-care providers a framework to continue efforts in the face of uncertain consequences. Finally, the path of meditation (Raja yoga) offers a multipronged approach to healthy lifestyle and mindful meditation, which may improve resilience to the illness and its severe consequences. While more work is needed to empirically examine the potential value of each of these approaches in modern psychotherapy, the principles herein may already help individuals facing and providing care for the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Foxtail millet (Setaria italica L.) is one of the earliest cultivated crops, extensively grown in the arid and semi-arid regions of Asia and Africa, as well as in some other economically developed countries of the world where it is more commonly used as bird feed. This article presents a comprehensive review of the physicochemical and health-functional properties of foxtail millet, and the processing technologies employed to improve these properties and develop more palatable food products. Foxtail millet contains significant levels of protein, fiber, mineral, and phytochemicals. Anti-nutrients such as phytic acid and tannin present in this millet can be reduced to negligible levels by using suitable processing methods. The millet is also reported to possess hypolipidemic, low-glycemic index, and antioxidant characteristics. This review concludes that, like most millet varieties, foxtail millet remains under-utilized as a food source. It is however receiving increased research and commercial attention, especially because its cultivation is not too demanding from point of view of agricultural inputs and it can grow in difficult terrains. It would be reasonable to surmise that foxtail millet has a promising role to play in enhancing nutritional and food security. [ABSTRACT FROM AUTHOR]

Tissue classification plays a crucial role in the investigation of normal neural development, brain-behavior relationships, and the disease mechanisms of many psychiatric and neurological illnesses. Ensuring the accuracy of tissue classification is important for quality research and, in particular, the translation of imaging biomarkers to clinical practice. Assessment with the human eye is vital to correct various errors inherent to all currently available segmentation algorithms. Manual quality assurance becomes methodologically difficult at a large scale - a problem of increasing importance as the number of data sets is on the rise. To make this process more efficient, we have developed Mindcontrol, an open-source web application for the collaborative quality control of neuroimaging processing outputs. The Mindcontrol platform consists of a dashboard to organize data, descriptive visualizations to explore the data, an imaging viewer, and an in-browser annotation and editing toolbox for data curation and quality control. Mindcontrol is flexible and can be configured for the outputs of any software package in any data organization structure. Example configurations for three large, open-source datasets are presented: the 1000 Functional Connectomes Project (FCP), the Consortium for Reliability and Reproducibility (CoRR), and the Autism Brain Imaging Data Exchange (ABIDE) Collection. These demo applications link descriptive quality control metrics, regional brain volumes, and thickness scalars to a 3D imaging viewer and editing module, resulting in an easy-to-implement quality control protocol that can be scaled for any size and complexity of study. [ABSTRACT FROM AUTHOR]

This study proposes a novel complete-order nonlinear structure and motion observer for monocular vision systems subjected to significant measurement noise. In contrast with previous studies that assume noise-free measurements, and require prior knowledge of either the relative motion of the camera or scene geometry, the proposed scheme assumes a single component of linear velocity as known. Under a persistency of excitation condition, the observer then relies on filtered estimates of optical flow to yield exponentially convergent estimates of the unknown motion parameters and feature depth that converge to a uniform, ultimate bound in the presence of measurement noise. The unknown linear and angular velocities are assumed to be generated using an imperfectly known model that incorporates a bounded uncertainty, and optical flow estimation is accomplished using a robust differentiator that is based on the sliding-mode technique. Numerical results are used to validate and demonstrate superior observer performance compared to an alternative leading design in the presence of model uncertainty and measurement noise. [ABSTRACT FROM AUTHOR]

Real-world image sequences are usually characterized by frequent loss and replacement of tracked feature data, and the key to accurate motion recovery from such image sequences lies in the synthesis of a structure-independent dynamic filter that enables the replacement of lost point features with newly acquired points in a seamless manner. In this note, a novel nonlinear observer is proposed that relies on filtered estimates of optical flow to accomplish structure-independent motion recovery from monocular image sequences with a low fill fraction. With a single component of linear velocity assumed known, the proposed scheme relies on the perspective observation of at least five points to yield exponentially convergent estimates of the unknown motion parameters that converge to a uniform, ultimate bound in the presence of model error. The unknown linear and angular velocities are assumed to be generated using an imperfectly known model that incorporates a bounded uncertainty, and optical flow estimation is accomplished using a robust differentiator that is based on the sliding-mode technique. Numerical results are used to validate and demonstrate superior observer performance compared to a leading alternative design on a real-world-like image sequence that is characterized by significant measurement noise and high feature turnover rate. [ABSTRACT FROM AUTHOR]

Why some individuals, when presented with unstructured sensory inputs, develop altered perceptions not based in reality, is not well understood. Machine learning approaches can potentially help us understand how the brain normally interprets sensory inputs. Artificial neural networks (ANN) progressively extract higher and higher-level features of sensory input and identify the nature of an object based on a priori information. However, some ANNs which use algorithms such as the "deep-dreaming" developed by Google, allow the network to over-emphasize some objects it "thinks" it recognizes in those areas, and iteratively enhance such outputs leading to representations that appear farther and farther from "reality". We suggest that such "deep dreaming" ANNs may model aberrant salience, a mechanism suggested for pathogenesis of psychosis. Such models can generate testable predictions for psychosis. [ABSTRACT FROM AUTHOR]

All currently approved drugs for schizophrenia work mainly by dopaminergic antagonism. While they are efficacious for psychotic symptoms, their efficacy is limited for negative symptoms and cognitive deficits which underlie the substantive disability in this illness. Recent insights into the biological basis of schizophrenia, especially in relation to non-dopaminergic mechanisms, have raised the efforts to find novel and effective drug targets, though with relatively little success thus far. Potential impediments to novel drug discovery include the continued use of symptom based disease definitions which leads to etiological and pathophysiological heterogeneity, lack of valid preclinical models for drug testing, and design limitations in clinical trials. These roadblocks can be addressed by (i) characterizing trans-diagnostic, translational pathophysiological dimensions as potential treatment targets, (ii) efficiency, accountability and, transparency in approaches to the clinical trials process, and (iii) leveraging recent advances in genetics and in vitro phenotypes. Accomplishing these goals is urgent given the significant unmet needs in the pharmacological treatment of schizophrenia. As this happens, it is imperative that clinicians employ optimal dosing, measurement-based care, and other best practices in utilizing existing treatments to optimize outcomes for their patients today. [ABSTRACT FROM AUTHOR]

Objective Schizophrenia is characterized by impaired -social and non social cognition both of which lead to functional deficits. These deficits may benefit from cognitive remediation, but the neural underpinnings of such improvements have not been clearly delineated. Methods We conducted a functional magnetic resonance (fMRI) study in early course schizophrenia patients randomly assigned to cognitive enhancement therapy (CET) or enriched supportive therapy (EST) and treated for two years. Imaging data over three time points including fMRI blood oxygen level dependent (BOLD) data were acquired during performance of a cognitive control paradigm, the Preparing to Overcome Prepotency (POP) task, and functional connectivity data, were analyzed. Results During the two years of treatment, CET patients showed a continual increase in BOLD activity in the right dorsolateral prefrontal cortex (DLPFC), whereas EST patients tended to show no change in prefrontal brain function throughout treatment. Increases in right DLPFC activity were modestly associated with improved neurocognition ( β = .14, p = .041), but not social cognition. Functional connectivity analyses showed reduced connectivity between the DLPFC and the anterior cingulate cortex (ACC) in CET compared to EST over the two years of treatment, which was associated with neurocognitive improvement. Conclusions. These findings suggest that CET leads to enhanced neural activity in brain regions mediating cognitive control and increased efficiency in prefrontal circuits; such changes may be related to the observed therapeutic effects of CET on neurocognitive function. [ABSTRACT FROM AUTHOR]

Important issues in optoelectronic devices based on exfoliated graphene are the electronic noise due to the interaction between graphene flakes and the substrate, and the accumulation of electrical charge at the flake edges. These effects, in addition to the distribution of flakes in the composites, being random and locally showing multiple overlaps, cause significant Inhomogeneity in the measured work function of the graphene-based materials. To shed light on the above effects, we investigated both graphene flakes and single-layer graphene by means of scanning Kelvin probe microscopy in ambient conditions. The graphene materials were deposited on rough substrates of silver with a top layer of titanium dioxide. The roughness caused the random disorder of interest for characterization, while the thin dielectric layer of titanium dioxide helped in keeping the electric field localized and provided better contrast in the surface potential images. It is demonstrated that proper engineering of the substrate can minimize the work function inhomogeneity. Additionally, SKPM allows for local mapping of graphene flakes overlaps and thus effective thickness, for possible quality control in produced devices. [ABSTRACT FROM AUTHOR]

Biomarkers in Alzheimer's disease (AD) have the potential to allow early and more accurate diagnosis, predict disease progression, stratify individuals and track response to candidate therapies in drug trials. The first fluid biomarkers reflecting aspects of AD neuropathology were identified in cerebrospinal fluid (CSF) in the 1990s. Three CSF biomarkers (amyloid-β 1-42, total tau and phospho-tau) have consistently been shown to have diagnostic utility and are incorporated into the new diagnostic criteria for AD. These markers have also been shown in longitudinal studies to predict conversion of mild cognitive impairment to AD. However, a key issue with the use of CSF biomarkers as a screening test is the invasiveness of lumbar puncture. Over the last 20 years there has been an active quest for blood biomarkers, which could be easily acquired and tested repeatedly throughout the disease course. One approach to identifying such markers is to attempt to measure candidates that have already been identified in CSF. Until recently, this approach has been limited by assay sensitivity, but newer platforms now allow single molecule-level detection. Another approach is identification of candidates in large multiplex panels that allow for multiple analytes to be quantified in parallel. While both approaches show promise, to date no blood-based biomarker or combination of biomarkers has sufficient predictive value to have utility in clinical practice. In this review, an overview of promising blood protein candidates is provided, and the challenges of validating and converting these into practicable tests are discussed. [ABSTRACT FROM AUTHOR]

Pulmonary fibrosis (PF) is a chronic, irreversible lung disease that is typically fatal and characterized by an abnormal fibrotic response. As a result, vast areas of the lungs are gradually affected, and gas exchange is impaired, making it one of the world's leading causes of death. This can be attributed to a lack of understanding of the onset and progression of the disease, as well as a poor understanding of the mechanism of adverse responses to various factors, such as exposure to allergens, nanomaterials, environmental pollutants, etc. So far, the most frequently used preclinical evaluation paradigm for PF is still animal testing. Nonetheless, there is an urgent need to understand the factors that induce PF and find novel therapeutic targets for PF in humans. In this regard, robust and realistic in vitro fibrosis models are required to understand the mechanism of adverse responses. Over the years, several in vitro and ex vivo models have been developed with the goal of mimicking the biological barriers of the lung as closely as possible. This review summarizes recent progress towards the development of experimental models suitable for predicting fibrotic responses, with an emphasis on cell culture methods, nanomaterials, and a comparison of results from studies using cells from various species. [Display omitted] [ABSTRACT FROM AUTHOR]

The current study aimed at the improvement of raw meatball (Cig Kofte) safety, by using high hydrostatic pressure (HP) treatment. Beef mince, one of the main raw material of meatball, was treated by high HP at 400 MPa for 15 minutes at 22 °C. After the HP treatment, 3- decimal reduction was achieved, by measuring total viable counts. HP treated and non-treated (control) beef mince were used in Cig Kofte preparation for evaluation. Any colour change was observed visually between the HP treated and control group samples. Indigenous microbial load of beef mince was inactivated by high HP that increased safety of traditional Turkish food. Therefore, it is proposed to process meat with high HP to prepare a safe ready-to-eat Cig Kofte. [ABSTRACT FROM AUTHOR]

The current construct of schizophrenia as a unitary disease is far from satisfactory, and is in need of reconceptualization. The first five papers in our "facts" series reviewed what is known about schizophrenia to date, and a limited number of key facts appear to stand out. Schizophrenia is characterized by persistent cognitive deficits, positive and negative symptoms typically beginning in youth, substantive heritability, and brain structural, functional and neurochemical alterations including dopaminergic dysregulation. Several pathophysiological models have been proposed with differing interpretations of the illness, like the fabled six blind Indian men groping different parts of an elephant coming up with different conclusions. However, accumulating knowledge is integrating the several extant models of schizophrenia etiopathogenesis into unifying constructs; we discuss an example, involving a neurodevelopmental imbalance in excitatory/inhibitory neural systems leading to impaired neural plasticity. This imbalance, which may be proximal to clinical manifestations, could result from a variety of genetic, epigenetic and environmental causes, as well as pathophysiological processes such as inflammation and oxidative stress. Such efforts to "connect the dots" (and visualizing the elephant) are still limited by the substantial clinical, pathological, and etiological heterogeneity of schizophrenia and its blurred boundaries with several other psychiatric disorders leading to a "fuzzy cluster" of overlapping syndromes, thereby reducing the content, discriminant and predictive validity of a unitary construct of this illness. The way ahead involves several key directions: a) choosing valid phenotype definitions increasingly derived from translational neuroscience; b) addressing clinical heterogeneity by a cross-diagnostic dimensional and a staging approach to psychopathology; c) addressing pathophysiological heterogeneity by elucidating independent families of "extended" intermediate phenotypes and pathophysiological processes (e.g. altered excitatory/inhibitory, salience or executive circuitries, oxidative stress systems) that traverse structural, functional, neurochemical and molecular domains; d) resolving etiologic heterogeneity by mapping genomic and environmental factors and their interactions to syndromal and specific pathophysiological signatures; e) separating causal factors from consequences and compensatory phenomena; and f) formulating or reformulating hypotheses that can be refuted/tested, perhaps in the mouse or other experimental models. These steps will likely lead to the current entity of schizophrenia being usefully deconstructed and reconfigured into phenotypically overlapping, but etiopathologically unique and empirically testable component entities (similar to mental retardation, epilepsy or cancer syndromes). The mouse may be the way to rescue the trapped elephant! [ABSTRACT FROM AUTHOR]

In vivo proton ((1)H) Magnetic Resonance spectroscopy ((1)H MRS) has shown abnormalities in young first-episode patients with schizophrenia. It is unclear whether these abnormalities reflect trait related vs. state related alterations in schizophrenia. We compared young first-degree relatives of schizophrenia patients and healthy controls using (1)H MRS. We hypothesized alterations in the (1)H MRS metabolites N-acetyl aspartate (NAA) and glutamate in corticostriatal and thalamic brain regions. We obtained multi-voxel, short-TE (1)H MRS measurements at 1.5 Tesla in 40 consenting adolescent offspring at risk for schizophrenia (HR), and 48 age matched healthy controls (HC). Absolute levels of NAA, phosphocreatine plus creatine (PCr+Cr), choline-containing compounds (GPC+PC), myo-inositol and glutamate plus glutamine (Glu+Gln) were obtained from the seven different anatomical brain areas (nominal voxel size of 4.5cm(3) each) and corrected for tissue voxel composition. HR subjects showed NAA (p=.0049), PCr+Cr (p=0.028) and GPC+PC (p=0.0086) reductions in the caudate compared with HC subjects. Male HR subjects had significant Glu+Gln reductions compared to male HC subjects (p=.0022). HR subjects had increased NAA in prefrontal white matter. NAA levels in the prefrontal white matter and Glu+Gln levels in the inferior parietal/occipital region were both increased in HR without psychopathology compared with HC subjects. Lower NAA, PCr+Cr and GPC+PC levels may reflect an overall reduction in cellular processes in the caudate of HC subjects, perhaps related to decreases in cell density, or synaptic overpruning. Further studies are needed to examine the pathophysiologic significance of these observations, and their potential predictive value for schizophrenia related psychopathology that may emerge in these at risk relatives during adolescence and early adulthood. [ABSTRACT FROM AUTHOR]

Investigating the neurobiological basis of schizophrenia is a critical step toward establishing its diagnostic validity, predicting outcome, delineating causative mechanisms and identifying objective targets for treatment research. Over the past two decades, there have been several advances in this field, principally related to developments in neuroimaging, electrophysiological and neuropathological approaches. Several neurobiological alterations in domains of brain structure, physiology and neurochemistry have been documented that may reflect diverse pathophysiological pathways from the "genome to the phenome". While none of the observed abnormalities are likely to qualify as diagnostic markers at this time, many can serve as potential intermediate phenotypes for elucidating etiological factors including susceptibility genes, and as therapeutic targets for novel drug discovery. Despite several challenges including the substantial phenotypic, pathophysiologic and etiological heterogeneity of schizophrenia, technological limitations, and the less than ideal animal models, considerable progress has been made in characterizing the neurobiological substrate of schizophrenia. The accumulating fact-base on the neurobiology of schizophrenia calls for novel integrative model(s) that may generate new, testable predictions. [ABSTRACT FROM AUTHOR]