Search

Abstract Five dimethylamino-based chalcone derivatives (AC) were synthesized and evaluated for their inhibition degree against monoamine oxidase (MAO) enzymes. All AC compounds showed better inhibitory activity against MAO-B than that against MAO-A. AC4 showed the highest inhibitory ability with an IC50 value of 0.020 µM, similar to that of a reference drug safinamide (IC50 = 0.019 µM) against MAO-B, followed by AC1 (IC50 = 0.068 µM) and AC3 (IC50 = 0.083 µM). Substituent -F in ring A (AC4) increased the MAO-B inhibition, followed by -H (AC1), -Br (AC3), and -Cl (AC2). The selectivity index (SI) value of AC4 was high (SI = 82.00) as well as other compounds (44.41 to 98.15). AC4 was found to be a reversible inhibitor as confirmed through analysis using the dialysis method. Interestingly, AC4 was observed to be a noncompetitive MAO-B inhibitor with a rare case and with Ki values of 0.011 ± 0.0036 µM. These experiments confirmed that AC4 is a reversible and potent selective inhibitor of MAO-B. Molecular docking experiments revealed that AC4 showed the highest inhibitory activity with a docking score (-9.510 kcal/mol). A study using molecular dynamics modeling revealed that the protein–ligand complex was more stable. It was observed that AC4 was non-cytotoxic in the study using L929 cell line. In conclusion, compound AC4 shows promise as a MAO-B inhibitor.

Abstract Myeloid derived suppressor cells (MDSCs) are key regulators of immune responses and correlate with poor outcomes in hematologic malignancies. Here, we identify that MDSC mitochondrial fitness controls the efficacy of doxorubicin chemotherapy in a preclinical lymphoma model. Mechanistically, we show that triggering STAT3 signaling via β2-adrenergic receptor (β2-AR) activation leads to improved MDSC function through metabolic reprograming, marked by sustained mitochondrial respiration and higher ATP generation which reduces AMPK signaling, altering energy metabolism. Furthermore, induced STAT3 signaling in MDSCs enhances glutamine consumption via the TCA cycle. Metabolized glutamine generates itaconate which downregulates mitochondrial reactive oxygen species via regulation of Nrf2 and the oxidative stress response, enhancing MDSC survival. Using β2-AR blockade, we target the STAT3 pathway and ATP and itaconate metabolism, disrupting ATP generation by the electron transport chain and decreasing itaconate generation causing diminished MDSC mitochondrial fitness. This disruption increases the response to doxorubicin and could be tested clinically.

Background and Objectives: Spinal anesthesia is the technique of choice for elective cesarean section with a prominent side effect of postspinal anesthesia hypotension (PSH). This needs an early prediction to avoid feto-maternal complication. This study aimed to assess the diagnostic accuracy of perfusion index (PI) and inferior vena cava collapsibility index (IVCCI) in the prediction of PSH. Material and Methods: Thirty parturients of American Society of Anesthesiologists Physical Status (ASA-PS) 1 and two undergoing cesarean delivery participated in the study. IVCCI, PI, baseline systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MBP), and heart rate (HR) were noted in the preoperative period. The fall of MBP by 20% from baseline or below 65 mm Hg was considered PSH. After spinal anesthesia, SBP, DBP, MBP, and HR were noted again for diagnosing PSH. Results: It did not show any statistical difference when comparing the PI between the PSH and non-PSH groups in both the PSH definition groups. IVCCI was significantly higher when PSH was considered MBP

Fingerprints are considered as one of the most important and prominent feature for an individual identification. Due to their consistency and reliability in biometric feature identification, they are most widely used for biometric recognition systems. In these systems, the relevant feature extraction plays important role in achieving required classification accuracy. In recent time, deep learning techniques are being used for fingerprint recognition with more accuracy and efficient results. Major difficulty which has been reported in previous researches, is the limited size of samples. Therefore, we propose two approaches, inversion and multi augmentation to augment the sample size with newly generated images for each feature map. Besides this, multiple networks are used simultaneously for feature extraction from newly generated images in parallel mode. Deep neural network architectures are used with proposed inversion methods and multi augmentation methods to classify the samples of fingerprints for personnel identification and verification. Pre-trained deep convolutional models like VGG16, VGG19, ResNet50 and InceptionV3 are fine-tuned with new processed fingerprint images for feature extraction and classification. The collective samples of fingerprints have been classified into 10 classes. The simulation results have been obtained with different optimizers and it has been observed that VGG 19 model exhibits the accuracies of 88 % and 93 % with inversion and multi augmentation approaches respectively. Whereas, VGG16 model exhibits 93 % with inversion approach and 97 % with multi augmentation approach. Thus, the proposed approach exhibits the accuracy up to 97 % with VGG16 model which is significantly much higher than that of any other model with the same dataset FVC2000_DB4.

Large-scale cell flow characterizes gastrulation in animal development. In amniote gastrulation, particularly in avian gastrula, a bilateral vortex-like counter-rotating cell flow, called ‘polonaise movements’, appears along the midline. Here, through experimental manipulations, we addressed relationships between the polonaise movements and morphogenesis of the primitive streak, the earliest midline structure in amniotes. Suppression of the Wnt/planar cell polarity (PCP) signaling pathway maintains the polonaise movements along a deformed primitive streak. Mitotic arrest leads to diminished extension and development of the primitive streak and maintains the early phase of the polonaise movements. Ectopically induced Vg1, an axis-inducing morphogen, generates the polonaise movements, aligned to the induced midline, but disturbs the stereotypical cell flow pattern at the authentic midline. Despite the altered cell flow, induction and extension of the primitive streak are preserved along both authentic and induced midlines. Finally, we show that ectopic axis-inducing morphogen, Vg1, is capable of initiating the polonaise movements without concomitant PS extension under mitotic arrest conditions. These results are consistent with a model wherein primitive streak morphogenesis is required for the maintenance of the polonaise movements, but the polonaise movements are not necessarily responsible for primitive streak morphogenesis. Our data describe a previously undefined relationship between the large-scale cell flow and midline morphogenesis in gastrulation.

The “Construction 2025” is a United Kingdom (UK) Government Strategy introduced in 2013 to improve the construction industry in the United Kingdom by meeting outlined performance targets by 2025. However, with only a few years left to reach the targets, it is unclear how much industry is advancing to meet them. This paper reviews the progress to achieve the Strategy targets. The data collected from 96 UK construction professionals was utilised to assess the key barriers to achieving the UK “Construction 2025” Strategy targets. Results indicate that industry professionals are uncertain about reaching the reduction in overall cost and time targets by 2025. However, they are more positive about reducing greenhouse gas emissions and the trade gap. In terms of the key barriers, the results revealed a reluctance to adopt change, lack of implementation of new technology, fragmentation in the industry, and failure to adopt modern construction methods as the key barriers to the Strategy targets. The research is the first attempt at a comprehensive assessment of the progress and barriers to the UK “Construction 2025” Strategy. The results reinforce the call for government initiatives to transform the industry.

Abstract Introduction Peripheral T‐cell lymphoma, not otherwise specified (PTCL‐NOS) is a rare, highly heterogeneous group of mature T‐cell neoplasms that historically has been associated with poor outcomes. We sought to investigate the influence of primary disease site on PTCL‐NOS outcomes using a large national cancer registry. Methods Baseline clinical and demographic data including primary organ of involvement and Ann Arbor disease stage were extracted from the SEER database. Patients were grouped into nine organ system groups and compared to nodal disease acting as a control. Cox regression models were utilized for adjusted survival analyses. Results A total of 3095 patients were identified in the SEER database and included in the final analysis. The median age was 61 and a majority of patients were male (60%) and identified as non‐Hispanic white (68%). A plurality of patients had stage IV disease (32%). Lymph nodes and spleen were the most common primary disease sites (67%), while central nervous system was the least common (1%). Patients with early‐stage PTCL‐NOS of the gastrointestinal/genitourinary systems had worse overall survival [HR = 1.97 (1.50–2.59); p

We provide a comprehensive overview of a reconnaissance expedition aimed at identifying new possible meteorite stranding zones in the surrounding of the Belgian Princess Elisabeth Antarctica (PEA) station in the Sør Rondane Mountains during the BELARE 2022-2023 field season. The team was composed of four scientists and one field guide. Several areas of interest were identified and daily searches occurred in two phases, first from a base camp and then from PEA. The first phase was in the Nils Larsenfjellet area, and a camp, accessible from the H.E. Hansenbreen (S72° 13.260' E22° 37.779'; altitude 1640 m), was set up from December 21 to 27, 2022. Systematic searches were performed in moraines and on blue ice areas (BIAs) during day trips, including the Verheyefjellet BIA, several BIAs surrounding an alignment of nunataks south of PEA, centered on S72° 18.403' E23° 13.191', and the Røysane nunatak at the eastern edge of Nils Larsenfjellet. Four meteorites were recovered during the first phase of the expedition, and another one in the second phase, also in the Nils Larsenfjellet area. In addition, nine surface ice samples and 18 kg of micrometeorite-bearing sediments were collected. Preliminary classification, performed on-site using magnetic susceptibility, tentatively indicated H and L chondrites. The recovered meteorites were transported in frozen state to the Royal Belgian Institute of Natural Sciences in Brussels to be thawed in vacuum conditions and classified based on their mineralogy. The Nils Larsenfjellet is identified as a potential new Dense Collection Area.

Blocking the mitogen‐activated protein kinase (MAPK) pathway with the MEK1/2 inhibitor trametinib has produced promising results in patients with head and neck squamous cell carcinoma (HNSCC). In the current study, we showed that trametinib treatment leads to overexpression and activation of the epidermal growth factor receptor (EGFR) in HNSCC cell lines and patient‐derived xenografts. Knockdown of EGFR improved trametinib treatment efficacy both in vitro and in vivo. Mechanistically, we demonstrated that trametinib‐induced EGFR overexpression hyperactivates the phosphatidylinositol 3‐kinase (PI3K)/AKT pathway. In vitro, blocking the PI3K pathway with GDC‐0941 (pictilisib), or BYL719 (alpelisib), prevented AKT pathway hyperactivation and enhanced the efficacy of trametinib in a synergistic manner. In vivo, a combination of trametinib and BYL719 showed superior antitumor efficacy vs. the single agents, leading to tumor growth arrest. We confirmed our findings in a syngeneic murine head and neck cancer cell line in vitro and in vivo. Taken together, our findings show that trametinib treatment induces hyperactivation of EGFR/PI3K/AKT; thus, blocking of the EGFR/PI3K pathway is required to improve trametinib efficacy in HNSCC.

Abstract Agaves are robust, drought tolerant plants that have been cultivated for their high-strength fibers for centuries and they hold promise as a crop in the face of increasing water scarcity associated with a warming planet. Meanwhile, millions of women lack access to sanitary products to safely manage their menstruation particularly in low- and middle-income countries characterized by a dry climate. To address this issue, we show a processing route that transforms the leaves of the succulent Agave sisalana into a highly absorbent and retentive (23 g/g) material. The process involves delignification combined with mechanical fluffing to increase affinity for water and porosity, respectively. This process leads to a material with an absorption capacity exceeding those found in commercially available products such as menstrual pads. Finally, the carbon footprint and water usage associated with this process are comparable to those with common alternatives with the added benefit that it can be carried out at small scales while remaining environmentally sustainable. Our work represents a step towards distributed manufacturing of essential health and hygiene products based on a local bioeconomy.

Pulmonary arterial hypertension (PAH) is a chronic disorder characterized by excessive pulmonary vascular remodeling, leading to elevated pulmonary vascular resistance and right ventricle (RV) overload and failure. MicroRNA-146a (miR-146a) promotes vascular smooth muscle cell proliferation and vascular neointimal hyperplasia, both hallmarks of PAH. This study aimed to investigate the effects of miR-146a through pharmacological or genetic inhibition on experimental PAH and RV pressure overload animal models. Additionally, we examined the overexpression of miR-146a on human pulmonary artery smooth muscle cells (hPASMCs). Here, we showed that miR-146a genic expression was increased in the lungs of patients with PAH and the plasma of monocrotaline (MCT) rats. Interestingly, genetic ablation of miR-146a improved RV hypertrophy and systolic pressures in Sugen 5415/hypoxia (SuHx) and pulmonary arterial banding (PAB) mice. Pharmacological inhibition of miR-146a improved RV remodeling in PAB-wild type mice and MCT rats, and enhanced exercise capacity in MCT rats. However, overexpression of miR-146a did not affect proliferation, migration, and apoptosis in control-hPASMCs. Our findings show that miR-146a may play a significant role in RV function and remodeling, representing a promising therapeutic target for RV hypertrophy and, consequently, PAH.

Microsporidia are eukaryotic, obligate intracellular parasites that infect a wide range of hosts, leading to health and economic burdens worldwide. Microsporidia use an unusual invasion organelle called the polar tube (PT), which is ejected from a dormant spore at ultra-fast speeds, to infect host cells. The mechanics of PT ejection are impressive. Anncaliia algerae microsporidia spores (3–4 μm in size) shoot out a 100-nm-wide PT at a speed of 300 μm/s, creating a shear rate of 3000 s-1. The infectious cargo, which contains two nuclei, is shot through this narrow tube for a distance of ∼60–140 μm (Jaroenlak et al, 2020) and into the host cell. Considering the large hydraulic resistance in an extremely thin tube and the low-Reynolds-number nature of the process, it is not known how microsporidia can achieve this ultrafast event. In this study, we use Serial Block-Face Scanning Electron Microscopy to capture 3-dimensional snapshots of A. algerae spores in different states of the PT ejection process. Grounded in these data, we propose a theoretical framework starting with a systematic exploration of possible topological connectivity amongst organelles, and assess the energy requirements of the resulting models. We perform PT firing experiments in media of varying viscosity, and use the results to rank our proposed hypotheses based on their predicted energy requirement. We also present a possible mechanism for cargo translocation, and quantitatively compare our predictions to experimental observations. Our study provides a comprehensive biophysical analysis of the energy dissipation of microsporidian infection process and demonstrates the extreme limits of cellular hydraulics.

Radiation induced sarcomas (RIS) are the most dreaded long-term complications of head and neck irradiation. RISs are usually high grade and aggressive in nature. Although osteosarcoma is a common RIS in head and neck region, radiation induced osteosarcoma of the clavicle is rarely reported and generalized outcome is poor. Here we report a case of radiation induced osteosarcoma of the clavicle following neck irradiation for a carcinoma of tongue.

Rising temperatures impact different developmental stages of summer crops like mung bean, particularly during the crucial seed-filling stage. This study focused on two mung bean genotypes, categorized as heat-tolerant [HT] or heat-sensitive [HS]. These genotypes were grown in pots in an outdoor natural environment (average day/night temperature 36°C/24.3°C) until the onset of podding (40 days after sowing) and subsequently relocated to controlled-environment walk-in growth chambers for exposure to heat stress (42°C/30°C) or control conditions (35°C/25°C) until maturity. For all measured attributes, heat stress had a more pronounced effect on the HS genotype than on the HT genotype. Heat-stressed plants exhibited severe leaf damage, including membrane damage, reduced chlorophyll content, diminished chlorophyll fluorescence, and decreased leaf water content. Heat stress impeded the seed-filling rate and duration, decreasing starch, protein, fat, and mineral contents, with a notable decline in storage proteins. Heat stress disrupted the activities of several seed enzymes, inhibiting starch and sucrose accumulation and consequently decreasing individual seed weights and seed weight plant−1. This study revealed that heat stress during seed filling severely impaired mung bean seed yield and nutritional quality due to its impact on various stress-related traits in leaves and enzyme activities in seeds. Moreover, this research identified potential mechanisms related to heat tolerance in genotypes with contrasting heat sensitivity.

Surgical resection is frequently the intervention required for post-tuberculous empyema or other sequels. However, pneumonectomy may not be feasible in some situations, and video-assisted thoracoscopic surgery (VATS) plays a role in such a scenario. Whether a patient undergoes open resection of VATS, isolation of infected lung is integral to one-lung ventilation and better access to the surgical field, and a double-lumen tube (DLT) remains the preferred choice. Difficulties in DLT placement after pneumonectomy are reported; however, failure to isolate a lung by appropriately placed DLT is scarce or absent. A 28-year cachectic gentleman with poor preoperative lung function was suffering from endobronchial tuberculosis. He also had one episode of tuberculosis twelve-year back. At presentation, he had a massive pneumothorax and stage-III empyema as a sequel, including a rare finding of plastered mediastinum mimicking vanishing lung syndrome. He underwent uniportal-VATS under general anesthesia using one-lung ventilation. Complete lung destruction from active tuberculosis and its sequel leading to the plastered mediastinum and deformed airway pose a significant lung isolation challenge. U-VATS can be considered for therapeutic purpose where standard thoracotomy and pneumonectomy is contra-indicated. However, lung isolation in such patients is tricky and poses a risk. The present case highlights the challenges faced with lung isolation using a DLT and discusses the probable remedy to these problems.

The restoration of an image with blocking artifacts due to compression at low bit rates is a challenging task and blocking artifact measurement algorithms have an important role to play in the computer vision field. An artifacts removal technique is an important step towards the reliability and security of image processing area that delivers a better understanding in many applications like pattern recognition, object classification, surveillance system and many more. We know that the removal of art objects is a scientific method used to provide better image analysis and for this purpose many methods of removal of art objects were already made by researchers during the processing of images such as line, motion, pattern, and hair. But in availability of group of artifacts in an image, they do not achieve an acceptable result. In this research, we proposed a comparative framework for blocking artifacts removal of digital images using hybrid mechanism. The main contribution of this research is developing a new neuro-fuzzy system-based hybrid artifacts removal mechanism to achieve better blocking artifacts efficiency. To remove artifact from an image the proposed framework has its own impact in quality parameters such as Peak Signal to Noise Ratio (PSNR), Mean Square Error (MSE), and Structural Similarity (SSIM) with the execution time. At last, the performance parameters of proposed framework is compare for all five techniques such as line, motion, pattern, hair and combination of all with each other and we observed that the achieved results justify the proposed hybrid artifact removal method in the field of image processing.

Effective use of noninvasive ventilation in patients with chronic obstructive pulmonary disease is well-known. However, noninvasive ventilation in patients presenting with altered sensorium and severe acidosis (pH

Abstract Background In autoimmune inflammatory rheumatological diseases, routine cardiovascular risk assessment is becoming more important. As an increased cardiovascular disease (CVD) risk is recognized in patients with fibromyalgia (FM), a combination of traditional CVD risk assessment tool with Machine Learning (ML) predictive model could help to identify non-traditional CVD risk factors. Methods This study was a retrospective case–control study conducted at a quaternary care center in India. Female patients diagnosed with FM as per 2016 modified American College of Rheumatology 2010/2011 diagnostic criteria were enrolled; healthy age and gender-matched controls were obtained from Non-communicable disease Initiatives and Research at AMrita (NIRAM) study database. Firstly, FM cases and healthy controls were age-stratified into three categories of 18–39 years, 40–59 years, and ≥ 60 years. A 10 year and lifetime CVD risk was calculated in both cases and controls using the ASCVD calculator. Pearson chi-square test and Fisher's exact were used to compare the ASCVD risk scores of FM patients and controls across the age categories. Secondly, ML predictive models of CVD risk in FM patients were developed. A random forest algorithm was used to develop the predictive models with ASCVD 10 years and lifetime risk as target measures. Model predictive accuracy of the ML models was assessed by accuracy, f1-score, and Area Under 'receiver operating Curve' (AUC). From the final predictive models, we assessed risk factors that had the highest weightage for CVD risk in FM. Results A total of 139 FM cases and 1820 controls were enrolled in the study. FM patients in the age group 40–59 years had increased lifetime CVD risk compared to the control group (OR = 1.56, p = 0.043). However, CVD risk was not associated with FM disease severity and disease duration as per the conventional statistical analysis. ML model for 10-year ASCVD risk had an accuracy of 95% with an f1-score of 0.67 and AUC of 0.825. ML model for the lifetime ASCVD risk had an accuracy of 72% with an f1-score of 0.79 and AUC of 0.713. In addition to the traditional risk factors for CVD, FM disease severity parameters were important contributors in the ML predictive models. Conclusion FM patients of the 40–59 years age group had increased lifetime CVD risk in our study. Although FM disease severity was not associated with high CVD risk as per the conventional statistical analysis of the data, it was among the highest contributor to ML predictive model for CVD risk in FM patients. This also highlights that ML can potentially help to bridge the gap of non-linear risk factor identification.

High-throughput molecular surveillance of mosquitoes carrying dangerous pathogens is currently challenging. Here the authors present Vectorchip, a low-cost microfluidic platform enabling multiplexed detection of mosquito DNA, viral RNA and infectious viral particles at single bite resolution.

Observations on confluent epithelial tissues show the emergence of dynamic contraction patterns that are suspected to be governed mechanically. Here, the authors propose a model for epithelial sheets and show that cells’ Extension-Induced-Contraction response explains experimentally-observed contraction pulses, that along with a cell softening response enhances epithelial resistance to rupture.

In every liter of seawater there are between 10 and 100 billion life forms, mostly invisible, called marine plankton or marine microbiome, which form the largest and most dynamic ecosystem on our planet, at the heart of global ecological and economic processes. While physical and chemical parameters of planktonic ecosystems are fairly well measured and modeled at the planetary scale, biological data are still scarce due to the extreme cost and relative inflexibility of the classical vessels and instruments used to explore marine biodiversity. Here we introduce ‘Plankton Planet’, an initiative whose goal is to engage the curiosity and creativity of researchers, makers, and mariners to (i) co-develop a new generation of cost-effective (frugal) universal scientific instrumentation to measure the genetic and morphological diversity of marine microbiomes in context, (ii) organize their systematic deployment through coastal or open ocean communities of sea-users/farers, to generate uniform plankton data across global and long-term spatio-temporal scales, and (iii) setup tools to flow the data without embargo into public and explorable databases. As proof-of-concept, we show how 20 crews of sailors were able to sample plankton biomass from the world surface ocean in a single year, generating the first seatizen-based, planetary dataset of marine plankton biodiversity based on DNA barcodes. The quality of this dataset is comparable to that generated by Tara Oceans and is not biased by the multiplication of samplers. The data unveil significant genetic novelty and can be used to explore the taxonomic and ecological diversity of plankton at both regional and global scales. This pilot project paves the way for construction of a miniaturized, modular, evolvable, affordable and open-source citizen field-platform that will allow systematic assessment of the eco/morpho/genetic variation of aquatic ecosystems and microbiomes across the dimensions of the Earth system.

The oceans represent 97% of all water on Earth and contain microscopic, drifting life, plankton, which drives global biogeochemical cycles. A major hurdle in assessing marine plankton is the planetary scale of the oceans and the logistical and economic constraints associated with their sampling. This difficulty is reflected in the limited amount of scientifically equipped fleets and affordable equipment. Here we present a modular hardware/software open-source strategy for building a versatile, re-configurable imaging platform - the PlanktoScope - that can be adapted to a number of applications in aquatic biology and ecology. We demonstrate high-throughput quantitative imaging of laboratory and field plankton samples while enabling rapid device reconfiguration to match the evolving needs of the sampler. The presented versions of PlanktoScope are capable of autonomously imaging 1.7 ml per minute with a 2.8 µm/px resolution and can be controlled from any WiFi-enabled device. The PlanktoScope’s small size, ease of use, and low cost - under $1000 in parts - enable its deployment for customizable monitoring of laboratory cultures or natural micro-plankton communities. This also paves the way toward consistent and long-term measurement of plankton diversity by an international fleet of citizen vessels at the planetary scale.

World ocean plankton quantitative biodiversity data are still severely limited due to the high cost and logistical constraints associated to oceanographic vessels and collection/analytic devices. Here, we report the first use of an affordable and open-source plankton collection and imaging kit designed for citizen biological oceanography, composed of a high-speed surface plankton net, the Coryphaena, together with a portable in-flux automated imaging device, the PlanktoScope. We deployed this kit in December 2020 along a latitudinal transect across the Atlantic Ocean on board the schooner Tara, during the first Leg of her ‘Mission Microbiomes’. The citizen-science instruments were benchmarked and compared at sea to state-of-the-art protocols applied in previous Tara expeditions, i.e. on-board water pumping and filtration system and the FlowCam to respectively sample and image total micro-plankton. Results show that the Coryphaena can collect pristine micro-plankton at speed up to 11 knots, generating quantitative imaging data comparable to those obtained from total, on-board filtered water, and that the PlanktoScope and FlowCam provide comparable data. Overall, the new citizen tools provided a complete picture of surface micro-plankton composition, biogeography and biogeochemistry, opening the way toward a global, cooperative, and frugal plankton observatory network at planetary scale.

A multiplexed enzyme-linked immunosorbent assay (ELISA) that simultaneously measures antibody binding to multiple antigens can extend the impact of serosurveillance studies, particularly if the assay approaches the simplicity, robustness, and accuracy of a conventional single-antigen ELISA. Here, we report on the development of multiSero, an open-source multiplex ELISA platform for measuring antibody responses to viral infection. Our assay consists of three parts: (1) an ELISA against an array of proteins in a 96-well format; (2) automated imaging of each well of the ELISA array using an open-source plate reader; and (3) automated measurement of optical densities for each protein within the array using an open-source analysis pipeline. We validated the platform by comparing antibody binding to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) antigens in 217 human sera samples, showing high sensitivity (0.978), specificity (0.977), positive predictive value (0.978), and negative predictive value (0.977) for classifying seropositivity, a high correlation of multiSero determined antibody titers with commercially available SARS-CoV-2 antibody tests, and antigen-specific changes in antibody titer dynamics upon vaccination. The open-source format and accessibility of our multiSero platform can contribute to the adoption of multiplexed ELISA arrays for serosurveillance studies, for SARS-CoV-2 and other pathogens of significance.

There are numerous applications based on edge detection have been used in the area of image analysis. The technique of edge detection is an important step towards the visual system reliability and security that delivers a better understanding in many applications like object recognition classification, photography, and many more others computer vision application such as pedestrian detection for a vehicle on the road, face detection in biometric, and video surveillance. We know that detection of edge detection is a scientific technique that is practiced to provide better image analysis and towards this purpose, lots of edge identification approach was already implemented by the researchers in the image processing era, but they do not achieve acceptable results for all types of the image that can help in the image analysis. In this research, we introduced a comparative evaluation of edge detection algorithms for instance Sobel, Canny, and Fuzzy logic-based edge detector with an Improved Fuzzy Inference (IFI) system is presented to preserve image edge for image analysis. The key contribution of this research is developing a new hybrid edge mechanism by utilizing the gradient and standard deviation based fuzzy logic approach to achieve better edge detection efficiency. To provide a better edge or non-edge region from an image the proposed IFI has its impact on quality parameters, for instance, Peak Signal to Noise Ratio (PSNR), Mean Square Error (MSE), Entropy and Structural Similarity (SSIM) with the execution time. At last, the performance parameters of the proposed IFI system is compared with other edge technique and we observed that the achieved results justify the proposed work in image processing.

Introduction: Doctors are at increased risk of exposure to SARS-CoV-2 virus, and use of N95 respirators has emerged as a key preventive measure. This study aimed to study the real-world experiences, practices and adverse effects of N95 respirator usage amongst doctors of India. Methods: An analytical, cross-sectional online survey was conducted between November 2020 and January 2021. Real-world usage characteristics of N-95 respirators were collected via a pre-validated questionnaire (use, reuse, wearing and disposal practices) and compared amongst different sub-cohorts. Results: 453 responses from physicians were analyzed. The most important adjunct to the N95 respirator perceived by the respondents was the full-face shield (81.9%). Most doctors had to purchase extra mask per month (median = 5) and this was more amongst the medical specialties (p = 0.006). Highest mean VAS scores for adverse events were reported for breathing on exertion (6.62 ± 2.25) and ear pain (6.34 ± 2.69). VAS ear pain was higher in ages < 40 and doctors working in the public sector (p = 0.017 and p = 0.019 respectively). Conclusion: There are many inadequacies with regard to proper mask removal and doffing techniques among doctors in India. The major adverse effects faced by the doctors on prolonged mask usage were ear pain and breathing on exertion. However, it can be noted in spite of these deficiencies; there is generally good adherence to protocols and good practices of mask usage in hospital setting.

The tumor microenvironment plays a key role in the pathogenesis of colorectal tumors and contains various cell types including epithelial, immune, and mesenchymal cells. Characterization of the interactions between these cell types is necessary for revealing the complex nature of tumors. In this study, we used single-cell RNA-seq (scRNA-seq) to compare the tumor microenvironments between a mouse model of sporadic colorectal adenoma (Lrig1CreERT2/+;Apc2lox14/+) and a mouse model of inflammation-driven colorectal cancer induced by azoxymethane and dextran sodium sulfate (AOM/DSS). While both models develop tumors in the distal colon, we found that the two tumor types have distinct microenvironments. AOM/DSS tumors have an increased abundance of two populations of cancer-associated fibroblasts (CAFs) compared with APC tumors, and we revealed their divergent spatial association with tumor cells using multiplex immunofluorescence (MxIF) imaging. We also identified a unique squamous cell population in AOM/DSS tumors, whose origins were distinct from anal squamous epithelial cells. These cells were in higher proportions upon administration of a chemotherapy regimen of 5-Fluorouracil/Irinotecan. We used computational inference algorithms to predict cell-cell communication mediated by ligand-receptor interactions and downstream pathway activation, and identified potential mechanistic connections between CAFs and tumor cells, as well as CAFs and squamous epithelial cells. This study provides important preclinical insight into the microenvironment of two distinct models of colorectal tumors and reveals unique roles for CAFs and squamous epithelial cells in the AOM/DSS model of inflammation-driven cancer.

This report summarizes the Belgian Antarctic Expedition (BELARE) 2019－2020 meteorite search and recovery expedition near the Sør Rondane Mountains of East Antarctica during the 2019－2020 field season. This expedition took place from 15 January to 6 February 2020 within the area defined as ＂C＂ of the Nansen Ice Fields (S72°38'−72°48'S, 24°35'−25°06'E). The expedition team consisted of four scientists and two field guides, who systematically searched the ice field area and collected 66 meteorites. The total weight of the meteorites was determined to be ～8 kg. In addition to meteorites, blue ice samples, volcanic ash layers, and wind-blown terrestrial rock fragments were collected from the area to study in detail the nature of the mechanisms concentrating meteorites on the Nansen Ice Fields. The recovered meteorites were transported in a frozen state to the National Institute of Polar Research, Japan for dry-thawing and subsequent classification.

Fusarium head blight (FHB) is a devastating fungal disease of wheat (Triticum aestivum L.). The lack of genetic resources with stable FHB resistance combined with a reliable and rapid screening method to evaluate FHB resistance is a major limitation to the development of FHB resistant wheat germplasm. The present study utilized an immature wheat spike culture method to screen wheat spike culture derived variants (SCDV) for FHB resistance. Mycotoxin concentrations determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) correlated significantly (P < 0.01) with FHB severity and disease progression during in vitro spike culture. Selected SCDV lines assessed for FHB resistance in a Fusarium field disease nursery in Carman, Manitoba, Canada in 2016 showed significant (P < 0.01) correlation of disease severity to the in vitro spike culture screening method. Selected resistant SCDV lines were also crossed with an elite cv. CDC Hughes and the progeny of F2 and BC1F2 were screened by high resolution melt curve (HRM) analyses for the wheat UDPglucosyl transferase gene (TaUGT-3B) single nucleotide polymorphism to identify resistant (T-allele) and susceptible (G-allele) markers. The progeny from the crosses were also screened for FHB severity using the immature spike culture method and identified resistant progeny grouped according to the HRM genotyping data. The results demonstrate a reliable approach using the immature spike culture to screen for FHB resistance in progeny of crosses in early stage of breeding programs.

Background Although the mitogen-activated protein kinases (MAPK) pathway is hyperactive in head and neck cancer (HNC), inhibition of MEK1/2 in HNC patients has not shown clinically meaningful activity. Therefore, we aimed to characterize the effect of MEK1/2 inhibition on the tumor microenvironment (TME) of MAPK-driven HNC, elucidate tumor-host interaction mechanisms facilitating immune escape on treatment, and apply rationale-based therapy combination immunotherapy and MEK1/2 inhibitor to induce tumor clearance.Methods Mouse syngeneic tumors and xenografts experiments were used to analyze tumor growth in vivo. Single-cell cytometry by time of flight, flow cytometry, and tissue stainings were used to profile the TME in response to trametinib (MEK1/2 inhibitor). Co-culture of myeloid-derived suppressor cells (MDSC) with CD8+ T cells was used to measure immune suppression. Overexpression of colony-stimulating factor-1 (CSF-1) in tumor cells was used to show the effect of tumor-derived CSF-1 on sensitivity to trametinib and anti-programmed death- 1 (αPD-1) in mice. In HNC patients, the ratio between CSF-1 and CD8A was measured to test the association with clinical benefit to αPD-1 and αPD-L1 treatment.Results Using preclinical HNC models, we demonstrated that treatment with trametinib delays HNC initiation and progression by reducing tumor cell proliferation and enhancing the antitumor immunity of CD8+ T cells. Activation of CD8+ T cells by supplementation with αPD-1 antibody eliminated tumors and induced an immune memory in the cured mice. Mechanistically, an early response to trametinib treatment sensitized tumors to αPD-1-supplementation by attenuating the expression of tumor-derived CSF-1, which reduced the abundance of two CSF-1R+CD11c+ MDSC populations in the TME. In contrast, prolonged treatment with trametinib abolished the antitumor activity of αPD-1, because tumor cells undergoing the epithelial to mesenchymal transition in response to trametinib restored CSF-1 expression and recreated an immune-suppressive TME.Conclusion Our findings provide the rationale for testing the trametinib/αPD-1 combination in HNC and highlight the importance of sensitizing tumors to αPD-1 by using MEK1/2 to interfere with the tumor–host interaction. Moreover, we describe the concept that treatment of cancer with a targeted therapy transiently induces an immune-active microenvironment, and supplementation of immunotherapy during this time further activates the antitumor machinery to cause tumor elimination.

Centralized manufacturing and global supply chains have emerged as an efficient strategy for large-scale production of goods throughout the 20th century. However, while this system of production is highly efficient, it is not resilient. The COVID-19 pandemic has seen numerous supply chains fail to adapt to sudden changes in supply and demand, including those for goods critical to the pandemic response such as personal protective equipment. Here, we consider the production of the non-woven polypropylene filtration media used in face filtering respirators (FFRs). The FFR supply chain's reliance on non-woven media sourced from large, centralized manufacturing facilities led to a supply chain failure. In this study, we present an alternative manufacturing strategy that allows us to move towards a more distributed manufacturing practice that is both scalable and robust. Specifically, we demonstrate that a fiber production technique known as centrifugal melt spinning can be implemented with modified, commercially-available cotton candy machines to produce nano- and microscale non-woven fibers. We evaluate several post processing strategies to transform the produced material into viable filtration media and then characterize these materials by measuring filtration efficiency and breathability, comparing them against equivalent materials used in commercially-available FFRs. Additionally, we demonstrate that waste plastic can be processed with this technique, enabling the development of distributed recycling strategies to address the growing plastic waste crisis. Since this method can be employed at small scales, it allows for the development of an adaptable and rapidly deployable distributed manufacturing network for non-woven materials that is financially accessible to more people than is currently possible.

Timed feeding drives adipose browning, although the integrative mechanisms for the same remain unclear. Here, we show that twice-a-night (TAN) feeding generates biphasic oscillations of circulating insulin and leptin, representing their entrainment by timed feeding. Insulin and leptin surges lead to marked cellular, functional, and metabolic remodeling of subcutaneous white adipose tissue (sWAT), resulting in increased energy expenditure. Single-cell RNA-sequencing (scRNA-seq) analyses and flow cytometry demonstrate a role for insulin and leptin surges in innate lymphoid type 2 (ILC2) cell recruitment and sWAT browning, since sWAT depot denervation or loss of leptin or insulin receptor signaling or ILC2 recruitment each dampens TAN feeding-induced sWAT remodeling and energy expenditure. Consistently, recreating insulin and leptin oscillations via once-a-day timed co-injections is sufficient to favorably remodel innervated sWAT. Innervation is necessary for sWAT remodeling, since denervation of sWAT, but not brown adipose tissue (BAT), blocks TAN-induced sWAT remodeling and resolution of inflammation. In sum, reorganization of nutrient-sensitive pathways remodels sWAT and drives the metabolic benefits of timed feeding.