Efficient recall of Omicron-reactive B cell memory after a third dose of SARS-CoV-2 mRNA vaccine.

We examined antibody and memory B cell responses longitudinally for ∼9-10 months after primary 2-dose SARS-CoV-2 mRNA vaccination and 3 months after a 3rd dose. Antibody decay stabilized between 6 and 9 months, and antibody quality continued to improve for at least 9 months after 2-dose vaccination. Spike- and RBD-specific memory B cells remained durable over time, and 40%-50% of RBD-specific memory B cells simultaneously bound the Alpha, Beta, Delta, and Omicron variants. Omicron-binding memory B cells were efficiently reactivated by a 3rd dose of wild-type vaccine and correlated with the corresponding increase in neutralizing antibody titers. In contrast, pre-3rd dose antibody titers inversely correlated with the fold-change of antibody boosting, suggesting that high levels of circulating antibodies may limit the added protection afforded by repeat short interval boosting. These data provide insight into the quantity and quality of mRNA-vaccine-induced immunity over time through 3 or more antigen exposures.

Prediction of transcript structure and concentration using RNA-Seq data.

Alternative splicing (AS) is a key post-transcriptional modification that helps in increasing protein diversity. Almost 90% of the protein-coding genes in humans are known to undergo AS and code for different transcripts. Some transcripts are associated with diseases such as breast cancer, lung cancer and glioblastoma. Hence, these transcripts can serve as novel therapeutic and prognostic targets for drug discovery. Herein, we have developed a pipeline, Finding Alternative Splicing Events (FASE), as the R package that includes modules to determine the structure and concentration of transcripts using differential AS. To predict the correct structure of expressed transcripts in given conditions, FASE combines the AS events with the information of exons, introns and junctions using graph theory. The estimated concentration of predicted transcripts is reported as the relative expression in terms of log2CPM. Using FASE, we were able to identify several unique transcripts of EMILIN1 and SLK genes in the TCGA-BRCA data, which were validated using RT-PCR. The experimental study demonstrated consistent results, which signify the high accuracy and precision of the developed methods. In conclusion, the developed pipeline, FASE, can efficiently predict novel transcripts that are missed in general transcript-level differential expression analysis. It can be applied selectively from a single gene to simple or complex genome even in multiple experimental conditions for the identification of differential AS-based biomarkers, prognostic targets and novel therapeutics.

Immunologic predictors of vaccine responsiveness in patients with lymphoma and CLL.

Patients with B-cell lymphomas have altered cellular components of vaccine responses due to malignancy and therapy, and the optimal timing of vaccination relative to therapy remains unknown. SARS-CoV-2 vaccines created an opportunity for new insights in vaccine timing because patients were challenged with a novel antigen across multiple phases of treatment. We studied serologic mRNA vaccine response in retrospective and prospective cohorts with lymphoma and CLL, paired with clinical and research immune parameters. Reduced serologic response was observed more frequently during active therapies, but non-response was also common within observation and post-treatment groups. Total IgA and IgM correlated with successful vaccine response. In individuals treated with CART-19, non-response was associated with reduced B and T follicular helper cells. Predictors of vaccine response varied by disease and therapeutic group, and therefore further studies of immune health during and after cancer therapies are needed to allow individualized vaccine timing.

Do Nanobubbles Exist in Pure Alcohol?

The existence of nanobubbles in pure water has been extensively debated in recent years, and it is speculated that nanobubbles may be ion-stabilized. However, nanobubbles in the alcohol-water mixture and pure alcohols are still controversial due to the lack of ions present in the alcohol system. This work tested the hypothesis that stable nanobubbles exist in pure alcohol. The ultrasound and oscillatory pressure fields are used to generate nanobubbles in pure alcohol. The size distribution, concentration, diameter, and scattering intensity of the nanobubbles were measured by nanoparticle tracking analysis. The light scattering method measures the zeta potential. The Mie scattering theory and electromagnetic wave simulation are utilized to estimate the refractive index (RI) of nanobubbles from the experimentally measured scattering light intensity. The average RI of the nanobubbles in pure alcohols produced by ultrasound and oscillating pressure fields was estimated to be 1.17 ± 0.03. Degassing the nanobubble sample reduces its concentration and increases its size. The average zeta potential of the nanobubbles in pure alcohol was measured to be -5 ± 0.9 mV. The mechanical stability model, which depends on force balance around a single nanobubble, also predicts the presence of nanobubbles in pure alcohol. The nanobubbles in higher-order alcohols were found to be marginally colloidally stable. In summary, both experimental and theoretical results suggest the existence of nanobubbles in pure alcohol.

Electrocatalytic Oxidation of Methanol and Ethanol with 3d-Metal Based Anodic Electrocatalysts in Alkaline Media Using Carbon Based Electrode Assembly.

Homogeneous electrocatalytic systems based on readily available, earth-abundant, inexpensive base metals Ni, Co, and Cr have been formulated for the electro-oxidation of alcohols (methanol and ethanol) that constitute a key half-cell component of direct alcohol fuel cells (DAFCs). Notably, excellent results were obtained for both methanol as well as ethanol electro-oxidation while operating with a half-cell assembly based on all-non-noble working and counter electrode systems consisting of glassy carbon and graphite rod, respectively. Using NaOH as the supporting electrolyte, Ni/Co/Cr metal salts and their bis(iminopyridine) complexes have been used as anodic electrocatalysts for the alcohol half-cell reactions, and among them, catalytic systems based on Co outperformed the corresponding systems based on Ni and Cr. The system comprising CoCl2.·6H2O [10 mM] + NaOH [6 M] at room temperature emerged as the best electrocatalyst for both methanol [5 M] electro-oxidation (ca. 522.5 ± 13.5 mA cm-2 at 1.4 V) and ethanol [5 M] electro-oxidation (ca. 209 ± 25 mA cm-2 at 1.34 V). It was observed that regardless of the starting alcohol, the end product is carbon dioxide, all of which gets trapped as sodium carbonate (up to 97% yield), thereby mitigating any possible hazards of greenhouse gas emission. Inferences obtained from FETEM, FESEM, and EDS analysis of both the electrolyte solution and residues deposited on the electrode surface provide evidence for the mostly homogeneous nature of the reaction mixture with the molecular catalyst being the major contributor toward the electrocatalytic activity apart from the minor role played by trace heterogeneous particles. The current cell assembly operating with non-noble working and counter electrodes utilizing a catalytic system based on an earth-abundant, base metal salt/complex that not only results in good half-cell current densities for high-energy power-source DAFCs but also generates high-value sodium carbonate offers an exciting avenue.

Physiological functions, pharmacological aspects and nutritional importance of green tomato- a future food.

Green tomatoes contain significant levels of steroidal glycoalkoids (SGA) such as α-tomatine and green pigment chlorophyll. Tomatine is an admixture of two glycoalkoids; alpha tomatine and dehydrotomatine reported various health beneficial biological activities. Moreover, a hydrolyzed product of tomatine also contributes to age-related atrophy, and muscle weakness and helps the elderly recover from illness and injuries related to age. However, there is a lack of evidence regarding the absorption of tomatine in the human body concerning proposed biological activity, which should be an area of interest in the future. Once, the absorption study is established compounds concentrated in green tomatoes are potentially involved as protective compounds for several diseases and also used for functional food. To facilitate the use of green tomatoes in food processing, this comprehensive review provides data on the nutritional value of green tomatoes, with emphasis on the evolution of the physiological chemistry, analytical, medicinal, and pharmacological effects of the α-tomatine and chlorophyll in an experimental model. The broad aim of this review is to evaluate the health benefits of green tomatoes in addition to their nutritional value and to study the several features of the role of α-tomatine and chlorophyll in human health.

Nephrotoxicity in the Age of Immune Checkpoint Inhibitors: Mechanisms, Diagnosis, and Management.

Immune checkpoint inhibitors (ICI) revolutionized cancer therapy by augmenting anti-tumor immunity via cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed death-1/programmed death-ligand 1 (PD-1/PD-L1). However, this breakthrough is accompanied by immune-related adverse effects (irAEs), including renal complications. ICI-related nephritis involves complex mechanisms like auto-reactive T cells, auto-antibodies, reactivation of drug-specific T cells, and cytokine-driven inflammation culminating in AKI. ICI-AKI typically manifests weeks to months into treatment, often with other irAEs. Timely detection relies on monitoring creatinine levels and urine characteristics. Biomarkers, like soluble interleukin-2 receptor (sIL-2R) and urine cytokine levels, provide non-invasive insights, while renal biopsy remains the gold standard for confirmation. Management of ICI-AKI requires a balance between discontinuing ICI therapy and prompt immunosuppressive intervention, typically with corticosteroids. Some cases permit ICI therapy resumption, but varying renal recovery rates highlight the importance of vigilant monitoring and effective therapy. Beyond its clinical implications, the potential of irAEs to predict positive treatment responses in certain cancers raises intriguing questions. Data on nephritis-treatment response links are limited, and ongoing research explores this complex interaction. In summary, ICI therapy's transformative impact on cancer treatment is counterbalanced by irAEs, including nephritis. Early recognition and management are vital, with ongoing research refining diagnostic and treatment strategies.

Augmenting the Leidenfrost Temperature of Droplets via Nanobubble Dispersion.

Droplets may rebound/levitate when deposited over a hot substrate (beyond a critical temperature) due to the formation of a stable vapor microcushion between the droplet and the substrate. This is known as the Leidenfrost phenomenon. In this article, we experimentally allow droplets to impact the hot surface with a certain velocity, and the temperature at which droplets show the onset of rebound with minimal spraying is known as the dynamic Leidenfrost temperature (TDL). Here we propose and validate a novel paradigm of augmenting the TDL by employing droplets with stable nanobubbles dispersed in the fluid. In this first-of-its-kind report, we show that the TDL can be delayed significantly by the aid of nanobubble-dispersed droplets. We explore the influence of the impact Weber number (We), the Ohnesorge number (Oh), and the role of nanobubble concentration on the TDL. At a fixed impact velocity, the TDL was noted to increase with the increase in nanobubble concentration and decrease with an increase in impact velocity for a particular nanobubble concentration. Finally, we elucidated the overall boiling behaviors of nanobubble-dispersed fluid droplets with the substrate temperature in the range of 150-400 °C against varied impact We through a detailed phase map. These findings may be useful for further exploration of the use of nanobubble-dispersed fluids in high heat flux and high-temperature-related problems and devices.

An Intelligent Sensor Based Decision Support System for Diagnosing Pulmonary Ailment through Standardized Chest X-ray Scans.

Academics and the health community are paying much attention to developing smart remote patient monitoring, sensors, and healthcare technology. For the analysis of medical scans, various studies integrate sophisticated deep learning strategies. A smart monitoring system is needed as a proactive diagnostic solution that may be employed in an epidemiological scenario such as COVID-19. Consequently, this work offers an intelligent medicare system that is an IoT-empowered, deep learning-based decision support system (DSS) for the automated detection and categorization of infectious diseases (COVID-19 and pneumothorax). The proposed DSS system was evaluated using three independent standard-based chest X-ray scans. The suggested DSS predictor has been used to identify and classify areas on whole X-ray scans with abnormalities thought to be attributable to COVID-19, reaching an identification and classification accuracy rate of 89.58% for normal images and 89.13% for COVID-19 and pneumothorax. With the suggested DSS system, a judgment depending on individual chest X-ray scans may be made in approximately 0.01 s. As a result, the DSS system described in this study can forecast at a pace of 95 frames per second (FPS) for both models, which is near to real-time.

Identification of Candidate mRNA Isoforms for Prostate Cancer-Risk SNPs Utilizing Iso-eQTL and sQTL Methods.

Single nucleotide polymorphisms (SNPs) impacting the alternative splicing (AS) process (sQTLs) or isoform expression (iso-eQTL) are implicated as important cancer regulatory elements. To find the sQTL and iso-eQTL, we retrieved prostate cancer (PrCa) tissue RNA-seq and genotype data originating from 385 PrCa European patients from The Cancer Genome Atlas. We conducted RNA-seq analysis with isoform-based and splice event-based approaches. The MatrixEQTL was used to identify PrCa-associated sQTLs and iso-eQTLs. The overlap between sQTL and iso-eQTL with GWAS loci and those that are differentially expressed between cancer and normal tissue were identified. The cis-acting associations (FDR < 0.05) for PrCa-risk SNPs identified 42, 123, and 90 PrCa-associated cassette exons, intron retention, and mRNA isoforms belonging to 25, 95, and 83 genes, respectively; while assessment of trans-acting association (FDR < 0.05) yielded 59, 65, and 196 PrCa-associated cassette exons, intron retention and mRNA isoforms belonging to 35, 55, and 181 genes, respectively. The results suggest that functional PrCa-associated SNPs can play a role in PrCa genesis by making an important contribution to the dysregulation of AS and, consequently, impacting the expression of the mRNA isoforms.

Bile Acid Tethered Docetaxel-Based Nanomicelles Mitigate Tumor Progression through Epigenetic Changes.

In this study, we describe the engineering of sub-100 nm nanomicelles (DTX-PC NMs) derived from phosphocholine derivative of docetaxel (DTX)-conjugated lithocholic acid (DTX-PC) and poly(ethylene glycol)-tethered lithocholic acid. Administration of DTX-PC NMs decelerate tumor progression and increase the mice survivability compared to Taxotere (DTX-TS), the FDA-approved formulation of DTX. Unlike DTX-TS, DTX-PC NMs do not cause any systemic toxicity and slow the decay rate of plasma DTX concentration in rodents and non-rodent species including non-human primates. We further demonstrate that DTX-PC NMs target demethylation of CpG islands of Sparcl1 (a tumor suppressor gene) by suppressing DNA methyltransferase activity and increase the expression of Sparcl1 that leads to tumor regression. Therefore, this unique system has the potential to improve the quality of life in cancer patients and can be translated as a next-generation chemotherapeutic.

Forensic effectiveness and genetic distribution of 23 autosomal STRs included in Verifiler PlusTM multiplex in a population sample from Madhya Pradesh, India.

We report here the first ever global study on genetic polymorphism using a Verifiler PlusTM autosomal STR multiplex system. The study evaluated genetic characteristics of 23 autosomal STRs in 200 unrelated residents of Guna district of Madhya Pradesh, India. Allele frequencies and forensic parameters are reported. Population comparison analysis was also performed using NJ tree and PCA plot. Penta E marker showed highest power of discrimination (0.938) among all 23 studied markers. The study also presents the first ever global forensic assessment in Indian population on D6S1043 marker (PD 0.937). The results demonstrated that all the 23 markers were highly polymorphic and the Verifiler PlusTM kit is suitable for forensic purposes in Indian population.

Marker-Less 3d Object Recognition and 6d Pose Estimation for Homogeneous Textureless Objects: An RGB-D Approach.

The task of recognising an object and estimating its 6d pose in a scene has received considerable attention in recent years. The accessibility and low-cost of consumer RGB-D cameras, make object recognition and pose estimation feasible even for small industrial businesses. An example is the industrial assembly line, where a robotic arm should pick a small, textureless and mostly homogeneous object and place it in a designated location. Despite all the recent advancements of object recognition and pose estimation techniques in natural scenes, the problem remains challenging for industrial parts. In this paper, we present a framework to simultaneously recognise the object's class and estimate its 6d pose from RGB-D data. The proposed model adapts a global approach, where an object and the Region of Interest (ROI) are first recognised from RGB images. The object's pose is then estimated from the corresponding depth information. We train various classifiers based on extracted Histogram of Oriented Gradient (HOG) features to detect and recognize the objects. We then perform template matching on the point cloud based on surface normal and Fast Point Feature Histograms (FPFH) to estimate the pose of the object. Experimental results show that our system is quite efficient, accurate and robust to illumination and background changes, even for the challenging objects of Tless dataset.

First molecular and serological evidence of Coxiella burnetti infection among sheep and goats of Jammu province of India.

The epidemiology and prevalence of Q fever in India is largely unknown. There are very few serologic and molecular reports of Q fever in India and these are old reports. The objective of this study was to investigate, for the first time, the presence of Coxiella burnetii infection in sheep and goat flocks of Jammu province of Jammu and Kashmir, India. A total of 148 milk (110 sheep and 38 goats) samples, 282 sera (170 sheep and 112 goats), and 152 vaginal swabs (123 sheep and 29 goats) were collected from farms with incidences of repeated abortion. The LSI Q fever ruminant serum/milk ELISA kit was used to identify anti-C. burnetii antibodies and nested PCR was employed to detect DNA in vaginal swabs. Overall, 42 (38.2%; 95% CI: 29.2-47.9) sheep and 9 (23.7%; 95% CI: 12.0-40.6) goat milk samples, and 21 (12.4%; 95% CI: 8.0-18.5) sheep and 11 (9.8%; 95% CI: 5.2-17.3) goat sera were ELISA positive. In addition, nine (7.3%; 95% CI: 3.6-13.8) vaginal swabs from sheep tested positive by nested PCR; however, C. burnetii could not be found in any of the vaginal swabs from goat. These results indicate that sheep seem to be a more important reservoir of C. burnetii than goats posing a risk for human infection in this area.

Development and validation of a Bayesian survival model for inclusion body myositis.

BACKGROUND: Associations between disease characteristics and payer-relevant outcomes can be difficult to establish for rare and progressive chronic diseases with sparse available data. We developed an exploratory bridging model to predict premature mortality from disease characteristics, and using inclusion body myositis (IBM) as a representative case study. METHODS: Candidate variables that may be potentially associated with premature mortality were identified by disease experts and from the IBM literature. Interdependency between candidate variables in IBM patients were assessed using existing patient-level data. A Bayesian survival model for the IBM population was developed with identified variables as predictors for premature mortality in the model. For model selection and external validation, model predictions were compared to published mortality data in IBM patient cohorts. After validation, the final model was used to simulate the increased risk of premature death in IBM patients. Baseline survival was based on age- and gender-specific survival curves for the general population in Western countries as reported by the World Health Organisation. RESULTS: Presence of dysphagia, aspiration pneumonia, falls, being wheelchair-bound and 6-min walking distance (6MWD in meters) were identified as candidate variables to be used as predictors for premature mortality based on inputs received from disease experts and literature. There was limited correlation between these functional performance measures, which were therefore treated as independent variables in the model. Based on the Bayesian survival model, among all candidate variables, presence of dysphagia and decrease in 6MWD [m] were associated with poorer survival with contributing hazard ratios (HR) 1.61 (95% credible interval [CrI]: 0.84-3.50) and 2.48 (95% CrI: 1.27-5.00) respectively. Excess mortality simulated in an IBM cohort vs. an age- and gender matched general-population cohort was 4.03 (95% prediction interval 1.37-10.61). CONCLUSIONS: For IBM patients, results suggest an increased risk of premature death compared with the general population of the same age and gender. In the absence of hard data, bridging modelling generated survival predictions by combining relevant information. The methodological principle would be applicable to the analysis of associations between disease characteristics and payer-relevant outcomes in progressive chronic and rare diseases. Studies with lifetime follow-up would be needed to confirm the modelling results.

Forensic genetic analysis of population of Madhya Pradesh with PowerPlex Fusion 6C™ Multiplex System.

Performance of PowerPlex Fusion 6C kit (PP F6C) was assessed in 374 unrelated individuals belonging to Madhya Pradesh, an Indian state. The study evaluated the forensic parameters for the loci included in PP F6C Multiplex System. The combined discrimination power (CPD) and combined exclusion power (CPE) were 1 and 0.999999995, respectively, for all 23 autosomal STR loci. SE33 showed the greatest power of discrimination (0.990) in the studied population, whereas TPOX showed the lowest (0.843). The availability of three Y-STR loci in the Multiplex System is suitable for assessing male contribution and amelogenin deletion in a single Multiplex PCR simultaneously. The study also presents the first global report on polymorphism in the Indian population on SE 33 autosomal STR loci and PP Fusion 6C Multiplex System. The results revealed that the studied STR Multiplex System is highly polymorphic and suitable for forensic purposes.

Genetic data for PowerPlex 21™ autosomal and PowerPlex 23 Y-STR™ loci from population of the state of Uttar Pradesh, India.

In the present study, the statistical forensic parameters were evaluated for the loci present in PowerPlex 21 autosomal and PowerPlex 23 Y-STR multiplex systems in 168 unrelated individuals living in the state of Uttar Pradesh, India. The combined discrimination power (CPD) and combined exclusion power (CPE) was 1 and 0.999999 respectively for all 20 autosomal STR loci. Penta E showed the greatest (0.980) and CSF1PO showed the lowest (0.855) power of discrimination in the studied population. The haplotype diversity for 23 Y-STR loci was observed to be 0.999. The study also presents the first global report on polymorphism on D1S1656, D6S1043 and D12S391 autosomal STR loci in the Indian population. The resulting data revealed that these STR multiplex systems are highly polymorphic and can be used for forensic purposes.

Enzymatic added extraction and clarification of fruit juices-A review.

Enzymatic treatment for juice extraction is most commonly used now a days. The enzymatic process is claimed to offer a number of advantages over mechanical-thermal comminution of several fruit pulps. Enzymes are an integral component of modern fruit juice manufacturing and are highly suitable for optimizing processes. Their main purposes are: increase extraction of juice from raw material, increase processing efficiency (pressing, solid settling or removal), and generate a final product that is clear and visually attractive. Juice extraction can be done by using various mechanical processes, which may be achieved through diffusion extraction, decanter centrifuge, screw type juice extractor, fruit pulper and by different types of presses. Enzymatic treatment prior to mechanical extraction significantly improves juice recovery compared to any other extraction process. Enzymatic hydrolysis of the cell walls increases the extraction yield, reducing sugars, soluble dry matter content and galacturonic acid content and titrable acidity of the products. Enzymatic degradation of the biomaterial depends upon the type of enzyme, incubation time, incubation temperature, enzyme concentration, agitation, pH and use of different enzyme combinations. We can conclude from the technical literature that use of the enzymes i.e. cellulases, pectinases, amylases and combination of these enzymes can give better juice yield with superior quality of the fruit juice. Pectinase enzyme can give maximum juice yield i.e. 92.4% at 360 minutes incubation time, 37°C incubation temperature and 5 mg/100 g of enzyme concentration. Whereas the combination of two enzymes i.e. pectin methyl esterase (PME) and polygalacturonase (PG) at 120 minutes of incubation time, 50°C of incubation temperature and 0.05 mg/100 gm of enzymatic concentration can give the maximum yield of 96.8% for plum fruits. This paper discusses the use of enzymes in fruit juice production focusing on the juice recovery, clarity and effect of the particular enzyme on the biochemical properties of the fruit juices.

Nanobubbles produced by nanopores to probe gas-liquid mass transfer characteristics.

HYPOTHESIS: This study tested the hypothesis of how the nanopore size of membranes and how the surface charge of nanobubbles responds to its pinch-off from the nanopore. This study also tested the hypothesis that nanobubbles that remain in solution after production may increase the dissolved oxygen content in water. EXPERIMENTS: The effect of membrane pore size, hydrodynamic conditions (gas and liquid flow rates), and physicochemical parameters (pH and temperature) on volumetric mass transfer coefficient (kLa) for oxygen nanobubbles formed by the nanopore diffusion technique was investigated. This study experimentally determined the kLa by carefully removing the dissolved oxygen by nitrogen purging from nanobubble suspension to examine the sole contribution of nanobubble dissolution in water to the reaeration. RESULTS: Scaling estimates indicate that the nanobubble pinch-off radius and nanopore radius have a power-law correlation and that nanobubble size declines with the nanopore size. This is in line with our experimental results. The surface charge of nanobubbles delays its pinch-off at the gas-liquid interface. Nanobubbles offered 3-4 times higher kLa than microbubbles. Standard oxygen transfer efficiency in water was found to be 78%, significantly higher than that in microbubbles. However, dissolving stable nanobubbles in water does not considerably increase dissolved oxygen levels.