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Circulating interleukin-8 dynamics parallels disease course and is linked to clinical outcomes in severe COVID-19.
No full textSevere COVID-19 frequently features a systemic deluge of cytokines. Circulating cytokines that can stratify risks are useful for more effective triage and management. Here, we ran a machine-learning algorithm on a dataset of 36 plasma cytokines in a cohort of severe COVID-19 to identify cytokine/s useful for describing the dynamic clinical state in multiple regression analysis. We performed RNA-sequencing of circulating blood cells collected at different time-points. From a Bayesian Information Criterion analysis, a combination of interleukin-8 (IL-8), Eotaxin, and Interferon-γ (IFNγ) was found to be significantly linked to blood oxygenation over seven days. Individually testing the cytokines in receiver operator characteristics analyses identified IL-8 as a strong stratifier for clinical outcomes. Circulating IL-8 dynamics paralleled disease course. We also revealed key transitions in immune transcriptome in patients stratified for circulating IL-8 at three time-points. The study identifies plasma IL-8 as a key pathogenic cytokine linking systemic hyper-inflammation to the clinical outcomes in COVID-19
5 - Host immune responses in COVID-19: implication for preexisting chronic systemic inflammation.
No full textCOVID-19 or the respiratory infection caused by SARS-CoV2 virus has spread all over the world and the pandemic is still on the run. Notably, older age or preexisting comorbidities like cardiovascular diseases, hypertension, cancer, and diabetes increase the risk of more severe disease manifestations and fatalities. The co-morbid conditions in COVID patients also include chronic inflammatory and autoimmune diseases, characterized by preexisting long-term, persistent inflammation due to aberrant activation of immune system, which may be organ specific or systemic in nature. This review explores how the preexisting systemic immune activation might pose a greater risk of developing severe disease phenotype in case of the possible coincidence of COVID-19 and chronic inflammatory disorders
From Feline Classification to Skills Evaluation: A Multitask Learning Framework for Evaluating Micro Suturing Neurosurgical Skills
No full textAutomated skill evaluation of a trainee is key to the utility of the surgical training system. The focus of this paper is to develop an automated tool for the assessment of trainees for micro-suturing task. The real-life training datasets for the micro-suturing task are often small, with long-tailed distribution, making it difficult to develop machine-learning-based tools for automated assessment. Further, micro-suturing is often performed at various magnifications and suture sizes, which makes the automated assessment more challenging compared to macro-suturing. Hence, currently, assessment is done manually by an expert using the final outcome image. In this paper, we propose a multi-task learning-based convolutional-neural-network regression model to score the effectualness of the micro-suturing task from the final outcome image. We propose a novel equivalent of the logit-adjustment (used in classification) applicable to regression formulation which effectively handles the problems associated with the long-tail distribution of the data. Additionally, we contribute the largest open-access dataset for suturing images and the first dataset pertaining to the micro-suturing task. We also demonstrate that the performance of the proposed algorithm surpasses the performance of human experts and also other state-of-the-art (SOTA) algorithms
Permafrost estimation model in Upper Indus Basin
No full textRemotely sensed topo-climatic factors, potential incoming solar radiation (PISR), land surface temperature (LST), topographic wetness index (TWI), Surface emissivity, and elevation, and machine learning techniques are used for mapping the spatial distribution of permafrost in the Tso Kar, a sub-basin of Upper Indus Basin (UIB) in Leh, Ladakh (UT). This schematic model is employed to identify remotely sensed parameters which are crucial in assessing permafrost extent over the study region. It is followed by the application and tuning of several machine learning models to deliver an expected accuracy in terms of permafrost classes demarcated over the study region based on literature. Results show that the PISR, LST and TWI are the most significant remotely sensed parameters affecting the permafrost and associated processes. Above 5000 m a.s.l., the proportion of permafrost in the study catchment is higher. Synergistic use of remote sensing image processing and machine learning techniques together provide mapping of permafrost over the region, which is elusive so fa
Light‐Responsive Nematic Colloids and Colloidal Crystals
No full textRational control over the periodic arrangement of particles by means of external stimuli is a technologically important aspect of colloidal science with important physical underpinnings. Here, robust structural control of particle assemblies in a nematic liquid crystal (NLC) is demonstrated by dissolving trace amounts of light-responsive azo-dendrimer molecules, which spontaneously get adsorbed on the particle surface. The azo-dendrimer molecules in the presence of external UV irradiation undergo conformational change (trans-cis); as a result, they transmit the mechanical torque to surrounding LC molecules and alter the near-field director orientation. The director re-orientation at the surface of the particles causes topological defect transformation, which involves elastic dipoles, quadrupoles, and hexadecapoles. The defect transformation can be emulated in colloidal assemblies toward different purposes such as rotation of chains and restructuring of 2D colloidal crystals. In this study, various topological aspects of light-activated defect transformation and its application in the collective manipulation of colloidal assemblies are presented
Aggregation-induced emission (AIE), life and health
No full textLight has profoundly impacted modern medicine and healthcare, with numerous luminescent agents and imaging techniques currently being used to assess health and treat diseases. As an emerging concept in luminescence, aggregation-induced emission (AIE) has shown great potential in biological applications due to its advantages in terms of brightness, biocompatibility, photostability, and positive correlation with concentration. This review provides a comprehensive summary of AIE luminogens applied in imaging of biological structure and dynamic physiological processes, disease diagnosis and treatment, and detection and monitoring of specific analytes, followed by representative works. Discussions on critical issues and perspectives on future directions are also included. This review aims to stimulate the interest of researchers from different fields, including chemistry, biology, materials science, medicine, etc., thus promoting the development of AIE in the fields of life and health
Nicotinic Acid Catabolism Modulates Bacterial Mycophagy in Burkholderia gladioli Strain NGJ1
No full textBurkholderia gladioli strain NGJ1 exhibits mycophagous activity on a broad range of fungi, including Rhizoctonia solani, a devastating plant pathogen. Here, we demonstrate that the nicotinic acid (NA) catabolic pathway in NGJ1 is required for mycophagy. NGJ1 is auxotrophic to NA and it potentially senses R. solani as a NA source. Mutation in the nicC and nicX genes involved in NA catabolism renders defects in mycophagy and the mutant bacteria are unable to utilize R. solani extract as the sole nutrient source. As supplementation of NA, but not FA (fumaric acid, the end product of NA catabolism) restores the mycophagous ability of ΔnicC/ΔnicX mutants, we anticipate that NA is not required as a carbon source for the bacterium during mycophagy. Notably, nicR, a MarR-type of transcriptional regulator that functions as a negative regulator of the NA catabolic pathway is upregulated in ΔnicC/ΔnicX mutant and upon NA supplementation the nicR expression is reduced to the basal level in both the mutants. The ΔnicR mutant produces excessive biofilm and is completely defective in swimming motility. On the other hand, ΔnicC/ΔnicX mutants are compromised in swimming motility as well as biofilm formation, potentially due to the upregulation of nicR. Our data suggest that a defect in NA catabolism alters the NA pool in the bacterium and upregulates nicR which in turn suppresses bacterial motility as well as biofilm formation, leading to mycophagy defects
An observer-blinded, cluster randomised trial of a typhoid conjugate vaccine in an urban South Indian cohort
No full textBackground
Typhoid fever causes nearly 110,000 deaths among 9.24 million cases globally and disproportionately affects developing countries. As a control measure in such regions, typhoid conjugate vaccines (TCVs) are recommended by the World Health Organization (WHO). We present here the protocol of a cluster randomised vaccine trial to assess the impact of introducing TyphiBEV® vaccine to those between 1 and 30 years of age in a high-burden setting.
Methods
The primary objective is to determine the relative and absolute rate reduction of symptomatic, blood-culture-confirmed S. Typhi infection among participants vaccinated with TyphiBEV® in vaccine clusters compared with the unvaccinated participants in non-vaccine clusters. The study population is residents of 30 wards of Vellore (a South Indian city) with participants between the ages of 1 and 30 years who provide informed consent. The wards will be divided into 60 contiguous clusters and 30 will be randomly selected for its participants to receive TyphiBEV® at the start of the study. No placebo/control is planned for the non-intervention clusters, which will receive the vaccine at the end of the trial. Participants will not be blinded to their intervention. Episodes of typhoid fever among participants will be captured via stimulated, passive fever surveillance in the area for 2 years after vaccination, which will include the most utilised healthcare facilities. Observers blinded to the participants’ intervention statuses will record illness details. Relative and absolute rate reductions will be calculated at the end of this surveillance and used to estimate vaccine effectiveness.
Discussion
The results from our trial will allow countries to make better-informed decisions regarding the TCV that they will roll-out and may improve the global supplies and affordability of the vaccines
A near-complete species-level phylogeny of uropeltid snakes harnessing historical museum collections as a DNA source
No full textUropeltidae is a clade of small fossorial snakes (ca. 64 extant species) endemic to peninsular India and Sri Lanka. Uropeltid taxonomy has been confusing, and the status of some species has not been revised for over a century. Attempts to revise uropeltid systematics and undertake evolutionary studies have been hampered by incompletely sampled and incompletely resolved phylogenies. To address this issue, we take advantage of historical museum collections, including type specimens, and apply genome-wide shotgun (GWS) sequencing, along with recent field sampling (using Sanger sequencing) to establish a near-complete multilocus species-level phylogeny (ca. 87% complete at species level). This results in a phylogeny that supports the monophyly of all genera (if Brachyophidium is considered a junior synonym of Teretrurus), and provides a firm platform for future taxonomic revision. Sri Lankan uropeltids are probably monophyletic, indicating a single colonisation event of this island from Indian ancestors. However, the position of Rhinophis goweri (endemic to Eastern Ghats, southern India) is unclear and warrants further investigation, and evidence that it may nest within the Sri Lankan radiation indicates a possible recolonisation event. DNA sequence data and morphology suggest that currently recognised uropeltid species diversity is substantially underestimated. Our study highlights the benefits of integrating museum collections in molecular genetic analyses and their role in understanding the systematics and evolutionary history of understudied organismal groups
Hiding among colors: background color diversity impedes detection time
No full textAvoiding detection is vital for the survival of many animals. Factors extrinsic to animals, such as the visual complexity of the background, have been shown to impede the detection of animals. Studies using artificial and natural backgrounds have attributed background complexity to various visual features of the background. One feature that has received less attention is the diversity of color (hue) in the background. We used chickens and artificial backgrounds containing perceptually distinct elements in experiments to test whether color and luminance diversity affect detection time. We found that color diversity in the background impeded detection, while color diversity in prey and luminance diversity in the background did not impede detection. We also did not find an effect of luminance contrast on detection time. Our study suggests a prey animal can benefit in terms of increased detection times by predators when resting on backgrounds with enhanced color diversity