Detection of SARS-CoV-2-specific mucosal antibodies in saliva following concomitant COVID-19 and influenza vaccination in the ComFluCOV trial.

The ComFluCOV trial randomized 679 participants to receive an age-appropriate influenza vaccine, or placebo, alongside their second COVID-19 vaccine. Concomitant administration was shown to be safe, and to preserve systemic immune responses to both vaccines. Here we report on a secondary outcome of the trial investigating SARS-CoV-2-specific mucosal antibody responses. Anti-spike IgG and IgA levels in saliva were measured with in-house ELISAs. Concomitant administration of an influenza vaccine did not affect salivary anti-spike IgG positivity rates to Pfizer/BioNTech BNT162b2 (99.1 cf. 95.6%), or AstraZeneca ChAdOx1 (67.8% cf. 64.9%), at 3-weeks post-vaccination relative to placebo. Furthermore, saliva IgG positively correlated with serum titres highlighting the potential utility of saliva for assessing differences in immunogenicity in future vaccine studies. Mucosal IgA was not detected in response to either COVID-19 vaccine, reinforcing the need for novel vaccines capable of inducing sterilising immunity or otherwise reducing transmission. The trial is registered as ISRCTN 14391248.

Water quality monitoring and modeling for an urban storm drainage channel in Thane, India.

The absence of a sewer system and inadequate wastewater treatment plants results in a discharge of untreated wastewater to the urban drainage channels and pollutes receiving waters. Field visits were carried out to observe water quality parameters such as dissolved oxygen (DO), biochemical oxygen demand (BOD), and chemical oxygen demand (COD) in an urban drainage system (Kolshet drain) in Thane City, Mumbai Metropolitan Region, India. Dye-tracing studies using rhodamine WT dye were used for computing the velocity, discharge, and dispersion coefficient of the drain. The data analysis shows that the BOD and COD values in the drain are higher than the permissible limits (30 mg L-1 for BOD and 250 mg L-1 for COD), which is not suitable for disposal to any receiving water body. Also, the DO was less than the permissible limit of a minimum of 3 mg L-1 (for the survival of aquatic life). It is seen that the higher BOD load significantly reduced the DO throughout the drain. The Water Quality Analysis Simulation Program (WASP 8.32, 2019) developed by the US Environmental Protection Agency (USEPA) has been used for the simulation of the DO and BOD in the drainage channel. The model simulates an appropriate estimate of the expected variation of DO and BOD at points of interest. The modeling for the Kolshet drain is expected to enable better estimates of the wastewater parameters and the pollution transport in the drain for planning purposes.

Development of an EN8 Steel Stepped Rotor by a Novel Engraving Milling Technique.

The rotor or impeller is a rotational and key part of a pump and compressor. This article presents the detailed development process of a rotor of small size constructed from an EN8 steel cylindrical blank using a novel technique based on a computer numerical control engraving milling machine (CNC-EMM) equipped with a 4 mm tungsten carbide end mill cutter. We fabricated a total of twenty-eight stepped rotors following the Box-Behnken Design (BBD) DoE technique at fourteen distinct combinations of CNC-EMM variable parameters, namely rotational speed, feed, and plunge feed. Average roughness 'Ra', an important surface quality indicator, has been considered and presented in this article, as a quality measure for the fabricated rotors. Feed and plunge feed have been identified as the most influencing variable parameters as per an analysis of variance (ANOVA) test. The lowest average roughness value obtained by this process for the rotor blade was 0.11 µm. A micrograph obtained from a field-emission scanning electron microscope (FE-SEM) showed a uniform and accurate tooth profile along with burr formation at corner edges. This study claims to establish engraving milling as a viable alternative to other manufacturing processes used for rotor blades. The findings of this study are useful to scholars, engineers, and researchers who are exploring new ways to fabricate mechanical parts and components.

Engineering the ADDobody protein scaffold for generation of high-avidity ADDomer super-binders.

Adenovirus-derived nanoparticles (ADDomer) comprise 60 copies of adenovirus penton base protein (PBP). ADDomer is thermostable, rendering the storage, transport, and deployment of ADDomer-based therapeutics independent of a cold chain. To expand the scope of ADDomers for new applications, we engineered ADDobodies, representing PBP crown domain, genetically separated from PBP multimerization domain. We inserted heterologous sequences into hyper-variable loops, resulting in monomeric, thermostable ADDobodies expressed at high yields in Escherichia coli. The X-ray structure of an ADDobody prototype validated our design. ADDobodies can be used in ribosome display experiments to select a specific binder against a target, with an enrichment factor of ∼104-fold per round. ADDobodies can be re-converted into ADDomers by genetically reconnecting the selected ADDobody with the PBP multimerization domain from a different species, giving rise to a multivalent nanoparticle, called Chimera, confirmed by a 2.2 Å electron cryo-microscopy structure. Chimera comprises 60 binding sites, resulting in ultra-high, picomolar avidity to the target.

Remote photoplethysmography-based human vital sign prediction using cyclical algorithm.

This article aims to predict vital signs like heart rate (HR), respiration rate, and arterial oxygen saturation using ambient light video, eliminating chronic distortions through improved frame quality with BER estimation. The study employs the cascade residual CNN-FPNR technique for preprocessing and SNR enhancement using energy variance maximization. The image cascade network (ICNet) facilitates segmentation, achieving strong segmentation in low-light ambient videos. Remote photoplethysmography (iPPG) enables noncontact vital sign monitoring, predicting HR and respiratory rate (RR). An innovative noninvasive temperature and cyclical algorithm, incorporating principal component analysis and fast Fourier transform, evaluate patient HR and RR. To address challenges related to involuntary movements, a dynamic time-warping-based optimization method is used for precise region selection. The study introduces an intensity variance-based threshold analysis for arterial oxygen saturation level determination. Ultimately, the support vector machine (SVM) classification technique evaluates the ground truth, showcasing the system's promising potential for remote and accurate vital sign assessment.

In vitro generated antibodies guide thermostable ADDomer nanoparticle design for nasal vaccination and passive immunization against SARS-CoV-2.

Background: Due to COVID-19, pandemic preparedness emerges as a key imperative, necessitating new approaches to accelerate development of reagents against infectious pathogens. Methods: Here, we developed an integrated approach combining synthetic, computational and structural methods with in vitro antibody selection and in vivo immunization to design, produce and validate nature-inspired nanoparticle-based reagents against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Results: Our approach resulted in two innovations: (i) a thermostable nasal vaccine called ADDoCoV, displaying multiple copies of a SARS-CoV-2 receptor binding motif derived epitope and (ii) a multivalent nanoparticle superbinder, called Gigabody, against SARS-CoV-2 including immune-evasive variants of concern (VOCs). In vitro generated neutralizing nanobodies and electron cryo-microscopy established authenticity and accessibility of epitopes displayed by ADDoCoV. Gigabody comprising multimerized nanobodies prevented SARS-CoV-2 virion attachment with picomolar EC50. Vaccinating mice resulted in antibodies cross-reacting with VOCs including Delta and Omicron. Conclusion: Our study elucidates Adenovirus-derived dodecamer (ADDomer)-based nanoparticles for use in active and passive immunization and provides a blueprint for crafting reagents to combat respiratory viral infections.

Block sparsity promoting algorithm for efficient construction of cluster expansion models for multicomponent alloys.

Multicomponent alloys are gaining significance as drivers of technological breakthroughs especially in structural and energy storage materials. The vast configuration space of these materials prohibit computational modeling using first-principles based methods alone. The cluster expansion (CE) method is the most widely used tool for modeling configurational disorder in alloys. CE relies on machine learning algorithms to train Hamiltonians and uses first-principles calculated data as training sets. In this paper we present a new compressive sensing-based algorithm for the efficient construction of CE Hamiltonians of multicomponent alloys. Our algorithm constructs highly sparse and physically reasonable models from a carefully selected small training set of alloy structures. Compared to conventional fitting algorithms, the algorithm achieves more than 50% reduction in the training set size. The resultant sparse models can sample the configuration space at least 3 × faster. We demonstrate this algorithm on 4 different alloy systems, namely Ag-Au, Ag-Au-Cu, Ag-Au-Cu-Pd and (Ge,Sn)(S,Se,Te).The sparse CE models for these alloys can rapidly reproduce known ground state orderings and order-disorder transitions. Our method can truly enable high-throughput multicomponent alloy thermodynamics by reducing the cost associated with model construction and configuration sampling.

Ultrasound-guided anterior suprascapular nerve block versus interscalene brachial plexus block for arthroscopic shoulder surgery: A randomised controlled study.

Background and Aims: The interscalene brachial plexus block (ISB) affects the phrenic nerve, resulting in hemi-diaphragmatic paresis (HDP) and, possibly, respiratory distress. Suprascapular nerve block via an anterior approach (SSB-A) is performed more distally at the level of the trunk of the brachial plexus and, thus, may spare the phrenic nerve. This study compares the analgesic efficacy and decline of hemi-diaphragmatic excursion (HDE) following ultrasound (US)-guided SSB-A versus ISB for arthroscopic shoulder surgery. Methods: This study was conducted on 60 adult participants undergoing arthroscopic shoulder surgery under general anaesthesia. Both US-guided SSB-A (n = 30) and ISB (n = 30) were performed with a combination of 10 ml bupivacaine (0.5%) and 4 mg dexamethasone. The primary objective was to compare the duration of analgesia (time to first rescue analgesia), and secondary objectives were to compare 24-h postoperative numerical rating scale (NRS) scores, 24-h morphine consumption and post block change in HDE, and pulmonary function tests (PFTs) between the two groups. For analysing intergroup differences of NRS, HDE and PFT; Pearson's Chi-squared test or Fisher's exact test, unpaired t test, and Mann-Whitney U test were used. For intragroup differences, paired t test was used. A P value <0.05 was considered significant. Results: The duration of analgesia (mean ± Standard Deviation) was similar in two groups (SSB-A = 1,345 ± 182 min, ISB = 1,375 ± 156 min; P = 0.8). The reduction in HDE was significantly greater in the ISB group (44%) than in the SSB-A group (10%). Pulmonary function was better preserved in the SSB-A group. Conclusion: Compared to ISB, SSB-A has a similar analgesic efficacy for arthroscopic shoulder surgeries, but it is superior in preserving diaphragmatic function and pulmonary function.

INSOMNet: Automated insomnia detection using scalogram and deep neural networks with ECG signals.

Sleep is a natural state of rest for the body and mind. It is essential for a human's physical and mental health because it helps the body restore itself. Insomnia is a sleep disorder that causes difficulty falling asleep or staying asleep and can lead to several health problems. Conventional sleep monitoring and insomnia detection systems are expensive, laborious, and time-consuming. This is the first study that integrates an electrocardiogram (ECG) scalogram with a convolutional neural network (CNN) to develop a model for the accurate measurement of the quality of sleep in identifying insomnia. Continuous wavelet transform has been employed to convert 1-D time-domain ECG signals into 2-D scalograms. Obtained scalograms are fed to AlexNet, MobileNetV2, VGG16, and newly developed CNN for automated detection of insomnia. The proposed INSOMNet system is validated on the cyclic alternating pattern (CAP) and sleep disorder research center (SDRC) datasets. Six performance measures, accuracy (ACC), false omission rate (FOR), sensitivity (SEN), false discovery rate (FDR), specificity (SPE), and threat score (TS), have been calculated to evaluate the developed model. Our developed system attained the classifications ACC of 98.91%, 98.68%, FOR of 1.5, 0.66, SEN of 98.94%, 99.31%, FDR of 0.80, 2.00, SPE of 98.87%, 98.08%, and TS 0.98, 0.97 on CAP and SDRC datasets, respectively. The developed model is less complex and more accurate than transfer-learning networks. The prototype is ready to be tested with a huge dataset from diverse centers.

Laser-Based Manufacturing of Ceramics: A Review.

Ceramics are widely used in microelectronics, semiconductor manufacturing, medical devices, aerospace, and aviation, cutting tools, precision optics, MEMS and NEMS devices, insulating components, and ceramic molds. But the fabrication and machining of the ceramic-based materials by conventional processes are always difficult due to their higher hardness and mechanical properties. Therefore, advanced manufacturing techniques are being preferred for these advanced materials, and out of that, laser-based processes are widely used. The benefits of laser fabrication and machining of ceramics include high precision, reduced thermal damage, non-contact processing, and the ability to work with complex geometries. Laser technology continues to advance, enabling even more intricate and diverse applications for ceramics in a wide range of industries. This paper explains various laser based ceramic processing techniques, such as selective laser sintering and melting, and laser machining techniques, such as laser drilling, etc. Identifying and optimizing the process parameters that influence the output quality of laser processed parts is the key technique to improving the quality, which is also focused on in this paper. It aims to facilitate the researchers by providing knowledge on laser-based manufacturing of ceramics and their composites to establish the field further.

Endoscopic Ultrasound Guided Shear Wave Elastography Is Safe With High Feasibility and Reproducibility When Used in the Pancreas: Findings From a Prospective Cohort.

OBJECTIVES: The aim of this study was to assess the safety, feasibility, and reproducibility of endoscopic ultrasound shear wave elastography (EUS-SWE) in the pancreas. METHODS: This is a prospective registry of consecutive patients undergoing clinically indicated EUS. Ten readings of SWE velocities (Vs [distance/time, m/s]) were obtained in the head (HOP), body, and tail of pancreas to quantify tissue stiffness. Each Vs score was accompanied by a reliability measurement VsN (%) with VsN >50% considered reliable. Safety was evaluated by perioperative complications rate. Feasibility was determined by technical success of obtaining measurements. Reproducibility was evaluated using intraclass correlation coefficient analysis. RESULTS: Total of 3320 EUS-SWE measurements were performed on 117 patients without perioperative complications. Measurement success rate was 100% across all locations. Reliable measurements were more common in the HOP (953/1120 [85.1%]) followed by body (853/1130 [75.5%]) and tail of pancreas (687/1070 [64.2%]) (P < 0.001). The analysis showed good reproducibility in all locations (intraclass correlation coefficient range, 0.80-0.89). CONCLUSIONS: Endoscopic ultrasound-SWE is safe, has 100% technical success rate, and is highly reproducible when used in the pancreas. Our study suggests that SWE measurements in the HOP offer the highest reliability, likely because of large study area and less respiratory artifact.

Sustainable Dry Machining of Stainless Steel with Microwave-Treated Tungsten Carbide Cutting Tools.

This paper presents a research investigation conducted on the turning of stainless steel 316 material under a dry environment using microwave-treated cutting tool inserts. Plain tungsten carbide WC tool inserts were exposed to microwave treatment for enhancement of their performance characteristics. It was found that a 20-min microwave treatment resulted in the best tool hardness and metallurgical characteristics. These tool inserts have been used to machine SS 316 material following the Taguchi L9 design of experimental techniques. A total of eighteen experiments have been conducted by varying three main machining parameters, i.e., cutting speed, feed rate, and depth of cut, at three levels per parameter. It has been found that tool flank wear increased with all three parameters and surface roughness decreased. At the longest dept of cut, surface roughness increased. An abrasion wear mechanism was found on the tool flank face at a high machining speed and adhesion at low speed. Chips with a helical shape and low serrations have been investigated. Turning SS 316 at optimum machining parameters of 170 m/min cutting speed, 0.2 mm/rev feed rate, and 1 mm depth of cut, as obtained by the multiperformance optimization technique grey relational analysis, resulted in the best values of all machinability indicators: 242.21 µm tool flank wear, 3.81 µm mean roughness depth, and 34,000 mm3/min material removal rate, at a single parameter setting. In terms of research achievements, the percentage reduction in surface roughness is approximately 30% and represents an almost ten-fold improvement in the material removal rate. The combination of machining parameters of 70 m/min cutting speed, 0.1 mm/rev feed rate, and 0.5 mm depth of cut is optimum for the lowest value of tool flank wear when considered for single parameter optimization.

Experimental Research on Surface Quality of Titanium Rod Turned by Wire Electrical Discharge Turning Process.

This paper reports the surface quality of a miniature cylindrical titanium rod/bar (MCTB) turned by the wire electrical discharge turning (WEDT) process using a zinc-coated wire of 250 µm diameter. The surface quality was mainly evaluated by considering the very important surface roughness parameters, i.e., the mean roughness depth. A Box-Behnken design (BBD) of the response surface methodology (RSM) based on 17 experimental runs was conducted, where the spark duration "Ton" was found as the most influential parameter affecting the mean roughness depth "RZ" of the miniature titanium bar. Further, using the grey relational analysis (GRA) technique of optimization, we obtained the least value of "RZ" 7.42 µm after machining a miniature cylindrical titanium bar with the optimum combination of WEDT's variable parameters: Ton-0.9 µs, SV-30 V, and DOC-0.35 mm. This optimization led to a 37% reduction in the surface roughness Rz of the MCTB. The tribological characteristics of this MCTB were also found favorable after conducting a wear test. After completing a comparative study, we can claim that our results are better than those of the past research conducted in this area. The findings of this study are beneficial for the micro-turning of cylindrical bars made from a variety of difficult-to-machine materials.

Prevalence of arrhythmia in COVID-19 patients with mild/moderate and severe illness: a prospective cohort study.

OBJECTIVES: The type of arrhythmias, and their prevalence in mild/moderate and severe COVID-19 patients admitted to the hospital are unknown from a prospective cohort study. METHODS: We did continuous electrocardiograms along with multiple ECGs in 305 consecutive hospitalized COVID-19 patients. RESULTS: The incidence of arrhythmias was 6.8% (21/305) in the target population. The incidence of arrhythmias was 9.2% (17/185) in patients with severe COVID-19 illness and 3.3% (4/120) in patients with mild/moderate COVID-19 illness with no significant difference (p = 0.063). All the arrhythmias were new-onset arrhythmias in this study. 95% (20/21) of these arrhythmias were atrial arrhythmia with 71.42% (15/21) being atrial fibrillation and one episode of sustained polymorphic ventricular tachycardia. No episode of high-grade atrioventricular block, sustained monomorphic ventricular arrhythmia, or torsades de pointes arrhythmias were observed in this study. The patients with arrhythmias were admitted to the intensive care unit (80.9% vs. 50.7%; p: 0.007), were on a ventilator (47.6% vs. 21.4%; p: 0.006), and had high in-hospital mortality (57.1% vs. 21.1%; p: 0.0001) than patients without arrhythmias. CONCLUSION: Atrial arrhythmias were the most frequent arrhythmias in hospital-admitted COVID-19 patients with atrial fibrillation being the most common arrhythmia. TRIAL REGISTRATION: Clinical Trial Registry India (CTRI) (CTRI/2021/01/030788). (https://www.ctri.nic.in/).

Outcomes, Mortality, and Cost Burden of Acute Kidney Injury and Hepatorenal Syndrome in Patients with Cirrhosis.

BACKGROUND AND AIMS: Cirrhosis is associated with an increased risk of acute kidney injury (AKI) and hepatorenal syndrome (HRS). Healthcare utilization and cost burden of AKI and HRS in cirrhosis is unknown. We aimed to analyze the health care use and cost burden associated with AKI and HRS in patients with cirrhosis in the United States by using real-world claims data. METHODS: We conducted a case-control study using the Truven Health MarketScan Commercial Claims databases from 2007-2017. A total of 34,398 patients with cirrhosis with or without AKI and 4,364 patients with cirrhosis with or without HRS were identified using International Classification of Diseases, Ninth or Tenth Revision, codes and matched 1:1 by sociodemographic characteristics and comorbidities using propensity scores. Total and service-specific were quantified for the 12-months following versus the 12-months before the first date of AKI or HRS diagnosis and over 12-months following a randomly selected date for cirrhosis controls to capture entire disease burdens. RESULTS: The AKI and HRS group had a higher number of comorbidities and were associated with higher rates of readmission and mortality. The AKI and HRS groups had a significantly higher prevalence of ascites, spontaneous bacterial peritonitis (SBP), encephalopathy, gastrointestinal bleeding, septic shock, pulmonary edema, and respiratory failure. Compared to patients with cirrhosis only, AKI was associated with higher number of claims per person (AKI vs. cirrhosis only, 60.30 vs. 47.09; p<0.0001) and total annual median health care costs (AKI vs. cirrhosis only, $46,150 vs. $26,340; p<0.0001). Compared to patients with cirrhosis only, the HRS cohort was associated with a higher number of claims per person (HRS vs. cirrhosis only, 44.96 vs. 43.50; p<0.0009) and total annual median health care costs (HRS vs. cirrhosis only, $34,912 vs. $23,354; p<0.0001). Inpatient costs were higher than the control cohort for AKI (AKI vs. cirrhosis only, $72,720 vs. $29,111; p<0.0001) and HRS (HRS vs. cirrhosis only, $ 98,246 vs. $27,503; p<0.0001). Compared to the control cohort, AKI and HRS had a higher rate of inpatient admission, mean number of inpatient admissions, and mean total length of stay. CONCLUSIONS: AKI and HRS are associated with higher health care utilization and cost burden compared to cirrhosis alone, highlighting the importance for improved screening and treatment modalities.

Evaluation and deployment of isotype-specific salivary antibody assays for detecting previous SARS-CoV-2 infection in children and adults.

BACKGROUND: Saliva is easily obtainable non-invasively and potentially suitable for detecting both current and previous SARS-CoV-2 infection, but there is limited evidence on the utility of salivary antibody testing for community surveillance. METHODS: We established 6 ELISAs detecting IgA and IgG antibodies to whole SARS-CoV-2 spike protein, to its receptor binding domain region and to nucleocapsid protein in saliva. We evaluated diagnostic performance, and using paired saliva and serum samples, correlated mucosal and systemic antibody responses. The best-performing assays were field-tested in 20 household outbreaks. RESULTS: We demonstrate in test accuracy (N = 320), spike IgG (ROC AUC: 95.0%, 92.8-97.3%) and spike IgA (ROC AUC: 89.9%, 86.5-93.2%) assays to discriminate best between pre-pandemic and post COVID-19 saliva samples. Specificity was 100% in younger age groups (0-19 years) for spike IgA and IgG. However, sensitivity was low for the best-performing assay (spike IgG: 50.6%, 39.8-61.4%). Using machine learning, diagnostic performance was improved when a combination of tests was used. As expected, salivary IgA was poorly correlated with serum, indicating an oral mucosal response whereas salivary IgG responses were predictive of those in serum. When deployed to household outbreaks, antibody responses were heterogeneous but remained a reliable indicator of recent infection. Intriguingly, unvaccinated children without confirmed infection showed evidence of exposure almost exclusively through specific IgA responses. CONCLUSIONS: Through robust standardisation, evaluation and field-testing, this work provides a platform for further studies investigating SARS-CoV-2 transmission and mucosal immunity with the potential for expanding salivo-surveillance to other respiratory infections in hard-to-reach settings.

If a person has been previously infected with SARS-CoV-2 they will produce specific proteins, called antibodies. These are present in the saliva and blood. Saliva is easier to obtain than blood, so we developed and evaluated six tests that detect SARS-CoV-2 antibodies in saliva in children and adults. Some tests detected antibodies to a particular protein made by SARS-CoV-2 called the spike protein, and these tests worked best. The most accurate results were obtained by using a combination of tests. Similar tests could also be developed to detect other respiratory infections which will enable easier identification of infected individuals.

Cryo-EM reveals binding of linoleic acid to SARS-CoV-2 spike glycoprotein, suggesting an antiviral treatment strategy.

The COVID-19 pandemic and concomitant lockdowns presented a global health challenge and triggered unprecedented research efforts to elucidate the molecular mechanisms and pathogenicity of SARS-CoV-2. The spike glycoprotein decorating the surface of SARS-CoV-2 virions is a prime target for vaccine development, antibody therapy and serology as it binds the host cell receptor and is central for viral cell entry. The electron cryo-microscopy structure of the spike protein revealed a hydrophobic pocket in the receptor-binding domain that is occupied by an essential fatty acid, linoleic acid (LA). The LA-bound spike protein adopts a non-infectious locked conformation which is more stable than the infectious form and shields important immunogenic epitopes. Here, the impact of LA binding on viral infectivity and replication, and the evolutionary conservation of the pocket in other highly pathogenic coronaviruses, including SARS-CoV-2 variants of concern (VOCs), are reviewed. The importance of LA metabolic products, the eicosanoids, in regulating the human immune response and inflammation is highlighted. Lipid and fatty-acid binding to a hydrophobic pocket in proteins on the virion surface appears to be a broader strategy employed by viruses, including picornaviruses and Zika virus. Ligand binding stabilizes their protein structure and assembly, and downregulates infectivity. In the case of rhinoviruses, this has been exploited to develop small-molecule antiviral drugs that bind to the hydrophobic pocket. The results suggest a COVID-19 antiviral treatment based on the LA-binding pocket.