ABSTRACT
Antibacterial photodynamic therapy (APDT) has received increased attention as a treatment for multidrug-resistant bacterial infections caused by antibiotic abuse. However, photosensitizers used in APDT have disadvantages such as water insolubility, self-aggregation, and photobleaching. To address these limitations, metal complexes have been explored. However, the use of such complexes tends to confine their antibacterial effectiveness specific bacterial strains. In this study, we report iron (Fe)- and copper (Cu)-based metallosurfactants as unique moieties for antibacterial photodynamic therapy (PDT) under the illumination of visible light. Briefly, our formulated Fe and Cu metallosurfactants, when combined with a fluorescein photosensitizer, exhibit nearly 100% antibacterial efficacy. This high efficiency is primarily attributed to the enhanced generation of singlet oxygen using FL in the presence of metallosurfactants when targeting bacteria such as Escherichia coli and Staphylococcus aureus under laser light. In vitro experiments further confirmed the superior antimicrobial activity of these metallosurfactants against a diverse range of microbial cultures, encompassing Gram-negative and Gram-positive bacteria as well as fungi. This performance outpaces conventional surfactants like cetyltrimethylammonium chloride and cetylpyridinium chloride. The compelling results from MTT assays and flow cytometry endorsed the substantial enhancement in antimicrobial properties achieved through Fe and Cu doping, all without the need for additional secondary agents. Notably, this synergistic antibacterial approach using metallosurfactants in PDT holds significant promise for the elimination of various bacteria in vivo, with the added advantage of mitigating the emergence of multidrug resistance.
ABSTRACT
BACKGROUND: Chronic kidney disease (CKD) patients are at a high risk of tuberculosis (TB), with a relative risk of developing active TB of 10%-25%. Similarly, glomerular disease increases the risk of TB due to diminished glomerular filtration rate, proteinuria, and immunosuppression use. Further, the first-line anti-TB drugs are associated with acute kidney injury (AKI) even in patients with normal kidney functions. METHODS: We retrospectively identified 10 patients hospitalized with unusual adverse effects of antituberculosis therapy (ATT) from 2013 to 2022. RESULTS: We found three cases of AKI caused by rifampicin: acute interstitial nephritis, crescentic glomerulonephritis, and heme pigment-induced acute tubular necrosis. We observed rifampicin-induced accelerated hypertension and thrombocytopenia in two patients on maintenance hemodialysis. Isoniazid caused pancreatitis and cerebellitis in two CKD patients, respectively. In a CKD patient, we detected acute gout secondary to pyrazinamide-induced reduced uric acid excretion. We also observed cases of drug rash with eosinophilia and systemic symptoms and hypercalcemia due to immune reconstitution inflammatory syndrome in patients with glomerular disease on ATT. Immediate discontinuation of the offending drug, along with specific and supportive management, led to a recovery in all cases. CONCLUSION: The adverse effects of ATT may be unusually severe and varied in kidney patients due to decreased renal elimination. Early recognition of these adverse effects and timely discontinuation of the offending drug is essential to limit morbidity and mortality.
Subject(s)
Acute Kidney Injury , Antitubercular Agents , Renal Insufficiency, Chronic , Humans , Antitubercular Agents/adverse effects , Antitubercular Agents/therapeutic use , Male , Retrospective Studies , Female , Middle Aged , Acute Kidney Injury/chemically induced , Aged , Adult , Renal Insufficiency, Chronic/complications , Rifampin/adverse effects , Rifampin/therapeutic use , Isoniazid/adverse effects , Isoniazid/therapeutic use , Nephritis, Interstitial/chemically induced , Tuberculosis/drug therapy , Tuberculosis/complications , Pyrazinamide/adverse effects , Pyrazinamide/therapeutic use , Glomerulonephritis/chemically induced , Immune Reconstitution Inflammatory SyndromeABSTRACT
Timely detection of Barrett's esophagus, the pre-malignant condition of esophageal adenocarcinoma, can improve patient survival rates. The Cytosponge-TFF3 test, a non-endoscopic minimally invasive procedure, has been used for diagnosing intestinal metaplasia in Barrett's. However, it depends on pathologist's assessment of two slides stained with H&E and the immunohistochemical biomarker TFF3. This resource-intensive clinical workflow limits large-scale screening in the at-risk population. To improve screening capacity, we propose a deep learning approach for detecting Barrett's from routinely stained H&E slides. The approach solely relies on diagnostic labels, eliminating the need for expensive localized expert annotations. We train and independently validate our approach on two clinical trial datasets, totaling 1866 patients. We achieve 91.4% and 87.3% AUROCs on discovery and external test datasets for the H&E model, comparable to the TFF3 model. Our proposed semi-automated clinical workflow can reduce pathologists' workload to 48% without sacrificing diagnostic performance, enabling pathologists to prioritize high risk cases.
Subject(s)
Adenocarcinoma , Barrett Esophagus , Deep Learning , Esophageal Neoplasms , Humans , Barrett Esophagus/diagnosis , Barrett Esophagus/pathology , Esophageal Neoplasms/diagnosis , Esophageal Neoplasms/pathology , Adenocarcinoma/diagnosis , Adenocarcinoma/pathology , MetaplasiaABSTRACT
Agriculturally derived by-products generated during the growth cycles of living organisms as secondary products have attracted increasing interest due to their wide range of biomedical and environmental applications. These by-products are considered promising candidates because of their unique characteristics including chemical stability, profound biocompatibility and offering a green approach by producing the least impact on the environment. Recently, micro/nanoengineering based techniques play a significant role in upgrading their utility, by controlling their structural integrity and promoting their functions at a micro and nano scale. Specifically, they can be used for biomedical applications such as tissue regeneration, drug delivery, disease diagnosis, as well as environmental applications such as filtration, bioenergy production, and the detection of environmental pollutants. This review highlights the diverse role of micro/nano-engineering techniques when applied on agricultural by-products with intriguing properties and upscaling their wide range of applications across the biomedical and environmental fields. Finally, we outline the future prospects and remarkable potential that these agricultural by-products hold in establishing a new era in the realms of biomedical science and environmental research.
Subject(s)
Agriculture , Nanotechnology , Agriculture/methods , HumansABSTRACT
Over the past few decades, hydrogels have attracted considerable attention as promising biomedical materials. However, conventional hydrogels require improved mechanical properties, such as brittleness, which significantly limits their widespread use. Recently, hydrogels with remarkably improved toughness have been developed; however, their low biocompatibility must be addressed. In this study, we developed a tough graphene hybrid hydrogel with nanostructures. The resultant hydrogel exhibited remarkable mechanical properties while representing an aligned nanostructure that resembled the extracellular matrix of soft tissue. Owing to the synergistic effect of the topographical properties, and the enhanced biochemical properties, the graphene hybrid hydrogel had excellent stretchability, resilience, toughness, and biocompatibility. Furthermore, the hydrogel displayed outstanding tissue regeneration capabilities (e.g., skin and tendons). Overall, the proposed graphene hybrid tough hydrogel may provide significant insights into the application of tough hydrogels in tissue regeneration.
Subject(s)
Graphite , Nanostructures , Hydrogels/chemistry , Graphite/chemistry , Biocompatible Materials/chemistry , Nanostructures/therapeutic useABSTRACT
RNA structure folding largely influences RNA regulation by providing flexibility and functional diversity. In silico and in vitro analyses are limited in their ability to capture the intricate relationships between dynamic RNA structure and RNA functional diversity present in the cell. Here, we investigate sequence, structure and functional features of mouse and human SINE-transcribed retrotransposons embedded in SINEUPs long non-coding RNAs, which positively regulate target gene expression post-transcriptionally. In-cell secondary structure probing reveals that functional SINEs-derived RNAs contain conserved short structure motifs essential for SINEUP-induced translation enhancement. We show that SINE RNA structure dynamically changes between the nucleus and cytoplasm and is associated with compartment-specific binding to RBP and related functions. Moreover, RNA-RNA interaction analysis shows that the SINE-derived RNAs interact directly with ribosomal RNAs, suggesting a mechanism of translation regulation. We further predict the architecture of 18 SINE RNAs in three dimensions guided by experimental secondary structure data. Overall, we demonstrate that the conservation of short key features involved in interactions with RBPs and ribosomal RNA drives the convergent function of evolutionarily distant SINE-transcribed RNAs.
Subject(s)
RNA, Long Noncoding , Short Interspersed Nucleotide Elements , Humans , RNA, Messenger/metabolism , Short Interspersed Nucleotide Elements/genetics , Gene Expression Regulation , RNA, Untranslated/genetics , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolismABSTRACT
In recent decades, cultured meat has received considerable interest as a sustainable alternative to traditional meat products, showing promise for addressing the inherent problems associated with conventional meat production. However, current limitations on the scalability of production and extremely high production costs have prevented their widespread adoption. Therefore, it is important to develop novel engineering strategies to overcome the current limitations in large-scale cultured meat production. Such engineering considerations have the potential for advancements in cultured meat production by providing innovative and effective solutions to the prevailing challenges. In this review, we discuss how engineering strategies have been utilized to advance cultured meat technology by categorizing the production processes of cultured meat into three distinct steps: (1) cell preparation; (2) cultured meat fabrication; and (3) cultured meat maturation. For each step, we provide a comprehensive discussion of the recent progress and its implications. In particular, we focused on the engineering considerations involved in each step of cultured meat production, with specific emphasis on large-scale production.
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Cardiovascular diseases are a collection of conditions that affect the blood vessels and the heart. These conditions include cardiac rehabilitation, hypertension, cardiac failure, rheumatic heart disease, peripheral artery disease, and coronary heart disease. Poor nutrition, alcohol, lack of exercise, smoking, etc are the main behavioral risk factors for heart disease. This study delivers a methodical review of yoga's role in the management and inhibition of cardiovascular diseases and their associated risk factors. This review suggests that proper maintenance of fitness and stress employing yoga effectively lowers cardiovascular disease. In this review, various asanas, and pranayama like Marjaryasana, Kapalabhati, Halasana, etc have been discussed. Also, their role in the prevention of coronary heart disease (CHD). In addition to this different metabolic syndrome associated with cardiovascular diseases and the relation of yoga with hypertension has been discussed. The review has documented satisfactory proof and concludes that yogic exercise enhances cardiovascular health and reduces associated risk factors.
Subject(s)
Cardiovascular Diseases , Coronary Disease , Hypertension , Meditation , Yoga , Humans , Cardiovascular Diseases/prevention & controlABSTRACT
Leishmaniasis is a vector-borne parasitic infection caused by the infective bite of female Phlebotomine sandflies. Treatment of leishmaniasis by conventional synthetic compounds is met by challenges pertaining to adverse effects which call for the discovery of newer anti-leishmanial molecules. This study was performed to evaluate the effect and modes of action of a sesquiterpene alcoholic molecule Farnesol on Leishmania major, the causative agent of Zoonotic CL. The cytotoxic effect of Farnesol against L.major promastigotes, amastigotes and macrophages was assessed by MTT test and counting. The IC50 on promastigotes by Farnesol on L.major was also evaluated by flow cytometry. In the findings, promastigotes were reduced at 167µM. The mean numbers of L.major amastigotes in macrophages were significantly decreased on exposure to Farnesol at 172µM. In addition, Farnesol induced significant apoptosis dose-dependent on L.major promastigotes. In silico protein-ligand_binding analyses indicated the effect of Farnesol in perturbation of the ergosterol synthesis pathway of Leishmania with attributes suggesting inhibition of Lanosterol-α-demethylase, the terminal enzyme of ergosterol synthesis machinery. Findings from flow cytometry reveal the role of Farnesol in apoptosis-induced killing in promastigotes. Farnesol was effective at very lower concentrations when compared to Paromomycin. Further studies are crucial to evaluate the therapeutic potential of Farnesol alone or in combination with other conventional drugs in animal models.
Subject(s)
Anti-Infective Agents , Antiprotozoal Agents , Leishmania major , Leishmaniasis , Animals , Female , Antiparasitic Agents/pharmacology , Farnesol/pharmacology , Anti-Infective Agents/pharmacology , Leishmaniasis/drug therapy , Ergosterol/pharmacology , Antiprotozoal Agents/pharmacologyABSTRACT
OBJECTIVES: Studies on nontechnical risk factors for ureterovesical leak after renal transplant are scarce. This study aimed to report the possible pre- and postoperative risk factors and the role of acute rejection and antirejection therapies for urine leak after transplant and its effect on graft and patient survival. MATERIALS AND METHODS: We conducted a retrospective analysis of 13 patients (1.17%) with urine leak (case group) and 52 patients without leak (control group) (case-to-control ratio of 1:4) from 1102 living related (first degree) renal transplant recipients seen between January 2012 and December 2021. We analyzed demographic and clinical details and biochemical and outcome parameters using a nested case-control design. RESULTS: Cases were olderthan controls (P = .018), were more ABO incompatible (P = .009), and had more 6/6 HLA mismatch transplants (P = .047). Donors of cases were older than donors of controls (P = .049). The rate of postoperative hypoalbuminemia was greaterin the case group (P = .050). Rates of acute rejection (P = .012) and plasmapheresis (P = .003) were greaterin the case group than in the control group. On multivariate logistic regression analysis, recipient age, 6/6 HLA mismatch, and plasmapheresis were found to independently associated with urine leak. None ofthe patient required surgical repair, as all responded to conservative therapy. Urine leak did not affect graft outcomes (P = .324), but overall survival was less in cases than in controls. CONCLUSIONS: Nontechnical risk factors that cause posttransplant ureteric leak include older donor and recipient age and ABO incompatible and 6/6 HLA mismatch transplants. Acute rejection and plasmapheresis predispose leak, and an indwelling double J stent can allow adequate healing of the anastomosis. High index of suspicion and prompt management are imperative to preserve graft and patient outcome.
Subject(s)
Kidney Transplantation , Humans , Child , Kidney Transplantation/adverse effects , Retrospective Studies , Kidney , Transplant Recipients , Immunosuppression TherapyABSTRACT
Leishmaniasis is a zoonotic disease transmitted by an obligate intra-macrophage protozoan of the genus Leishmania through the infective bite of a vector sandfly. This study investigated the therapeutic efficacy of farnesol, a sesquiterpene compound, for the treatment of cutaneous leishmaniasis (CL) using in vivo BALB/c mouse model. In this study, farnesol's efficacy was compared with the standard drug, paromomycin. It was observed that farnesol significantly reduced lesion sizes and footpad thickness compared to the control group (paromomycin). Lymph node size was also significantly reduced in farnesol-treated mice, indicating its ability to control infection spread. Combination therapy with farnesol and Paromomycin did not demonstrate synergistic effects. These results highlight the potential of farnesol as an alternative therapeutic agent for CL. Further investigations are required to elucidate its mechanism of action and assess potential off-target effects. Optimization of oral delivery methods should be explored to enhance bioavailability. Overall, our findings support farnesol's efficacy in CL treatment, offering promising prospects for improved disease management.
Subject(s)
Leishmania , Leishmaniasis, Cutaneous , Animals , Mice , Farnesol/pharmacology , Farnesol/therapeutic use , Paromomycin , Leishmaniasis, Cutaneous/drug therapy , Administration, Cutaneous , Mice, Inbred BALB CABSTRACT
Inner ear organoids (IEOs) are 3D structures grown in vitro, which can mimic the complex cellular structure and function of the inner ear. IEOs are potential solutions to problems related to inner ear development, disease modeling, and drug delivery. However, current approaches in generating IEOs using chemical factors have a few limitations, resulting in unpredictable outcomes. In this study, we propose the use of nanomaterial-based approaches, specifically by using graphene oxide (GO). GO's unique properties promote cell-extracellular matrix interactions and cell-cell gap junctions, thereby enhancing hair cell formation, which is an essential part of IEO development. We also investigated the potential applications for drug testing. Our findings suggest that GO is a promising candidate for enhancing the functionality of IEOs and advancing our understanding of the problems underlying inner ear development. The use of nanomaterial-based approaches may provide a more reliable and effective method for building better IEOs in the future.
Subject(s)
Ear, Inner , Graphite , Graphite/pharmacology , Hair Cells, Auditory , OrganoidsABSTRACT
Systemic Lupus Erythematosus (SLE) occurs in the reproductive age group. Renal involvement occurs less frequently in late-onset SLE than in reproductive-age SLE patients. Here, we aimed to study the clinical, serological and histopathological characteristics of late-onset lupus nephritis (LN). Late-onset LN was defined as disease onset after 47 years of age, corresponding to the average menopausal age. Records of biopsy proven late-onset lupus nephritis patients diagnosed between June 2000 and June 2020 were reviewed. Late-onset LN constituted 53 of 4420 patients (1.2%) biopsied during the study period. Females represented 90.65% of the cohort. Mean age of the cohort was 49.5 ± 7.05 years at the time of SLE diagnosis while its renal presentation was delayed by median duration of 10 months (IQR 3-48 months). Renal failure was present in 28 patients (52.8%) with acute kidney injury (AKI) (28.3%, n = 15) as the most common presentation. On histopathological analysis, class IV was observed in 23 patients (43.5%), crescents were observed in one-third cases and lupus vasculopathy in 4 patients (7.5%). All patients received steroids. Majority of patients (43.3%; n = 23) received Euro lupus protocol for induction. On median follow up duration of 82 months, renal flares were noted in 9 patients (17%) and 8 patients (15.1%) became dialysis dependent. Among 11 patients (21%) with infectious complications, 7 patients (13.2%) suffered from tuberculosis. Infections caused three-fourth of the deaths. Late-onset lupus nephritis is rare and presents as renal failure in majority. Renal biopsy affects the clinical decision of judicious use of immunosuppression which is imperative due to high rate of infections in this cohort.
Subject(s)
Lupus Erythematosus, Systemic , Lupus Nephritis , Renal Insufficiency , Female , Humans , Adult , Middle Aged , Lupus Nephritis/epidemiology , Lupus Nephritis/therapy , Lupus Nephritis/complications , Retrospective Studies , Kidney/pathology , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/drug therapy , Lupus Erythematosus, Systemic/epidemiology , BiopsyABSTRACT
Hepatocellular carcinoma (HCC) frequently unfolds under an inflammatory condition, which is a hub for a plethora of cytokines. A better understanding of the cytokine functions and their contributions to disease development is key to design of future therapeutic strategies and reduction of global HCC burden. In this context, one of the major cytokines present in the HCC tumour milieu is the transforming growth factor-ß (TGF-ß). One of its classical functions involve facilitation of epithelial to mesenchymal transition (EMT), in tumour cells, promoting an invasive phenotype. In spite of its clinical relevance, the cellular events associated with TGF-ß-induced EMT and its molecular regulation is poorly elucidated. Therefore, as part of this study, we treated HCC cells with TGF-ß and characterized the cellular processes associated with EMT. Interestingly, EMT triggered by TGF-ß was found to be associated with cytostasis and altered cellular metabolism. TGF-ß resulted in down-regulation of cell cycle-associated transcripts, like Cyclin A2 (CCNA2), and metabolic genes, like Glutamic-oxaloacetic transaminase 1 (GOT1) through epigenetic silencing. An overall increase in total histone repressive mark (H3K27me3) associated with a specific enrichment of H3K27me3 at the upstream promoter region of CCNA2 and GOT1 was observed after TGF-ß exposure, leading to their down-regulation. Importantly, TGF-ß-downstream signalling mediator- SMAD and chromatin repressive complex member-enhancer of zeste homolog 2 (EZH2) were found to co-immunoprecipitate and were required for the above effects. Overall, our findings reflect that HCC cells undergoing EMT, attain cytostasis and modulate metabolic demands to efficiently facilitate the EMT differentiation switch, and these events are regulated at the epigenomic level through TGF-ß-mediated signalling. Our results provide better understanding of cellular invasive features which can lead to development of novel therapeutic strategies.
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Over the years, the landscape of cisplatin-based cancer treatment options has undergone continuous transitions. Currently, there is much debate over the optimum dose of cisplatin to be administered to cancer patients. In clinical practice, it can extend from repeated low sub-toxic doses to a few cycles of acute high drug doses. Herein, the molecular understanding of the overall cellular response to such differential doses of cisplatin becomes crucial before any decision making; and it has been a grey area of research. In this study, colorectal cancer (CRC) cells were treated with either- a low sub-toxic dose (LD; 30 µM) or a ten times higher acute dose (HD; 300 µM) of cisplatin, and thereafter, the cellular response was mapped through RNA sequencing followed by transcriptomic analysis. Interestingly, we observed that the tumor cells' response to varying doses of cisplatin is distinctly different, and they activate unique transcriptional programs. The analysis of differentially regulated or uniquely expressed transcripts and corresponding pathways revealed a preferential enrichment of genes associated with chromatin organization, oxidative stress, senescence-associated signaling, and developmentally-active signaling pathways in HD; whereas, modulation of autophagy, protein homeostasis, or differential expression of ABC transporters was primarily enriched in LD. This study is the first of its kind to highlight cellular transcriptomic adaptations to different doses of cisplatin in CRC cells. Consequently, since, protein homeostasis was found to be deeply affected after cisplatin treatment, we further analyzed one of the primary cellular protein homeostatic mechanisms- autophagy. It was activated upon LD, but not HD, and served as a pro-survival strategy through the regulation of oxidative stress. Inhibition of autophagy improved sensitivity to LD. Overall, our study provides a holistic understanding of the distinct molecular signatures induced in CRC cells in response to differential cisplatin doses. These findings might facilitate the design of tailored therapy or appropriate drug dose for enhanced efficacy against CRCs.
Subject(s)
Cisplatin , Colorectal Neoplasms , Humans , Cisplatin/therapeutic use , Transcriptome , Drug Resistance, Neoplasm , Gene Expression Profiling , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Colorectal Neoplasms/metabolismABSTRACT
BACKGROUND: Non-small cell lung carcinoma (NSCLC) is the most common cause of cancer-associated deaths worldwide. Though recent development in targeted therapy has improved NSCLC prognosis, yet there is an unmet need to identify novel causative factors and appropriate therapeutic regimen against NSCLCs. METHODS AND RESULTS: In this study, we identify key molecular factors de-regulated in NSCLCs. Analyze their expression by real-time PCR and immunoblot; map their localization by immuno-fluorescence microscopy. We further propose an FDA approved drug, chloroquine (CQ) that affects the function of the molecular factors and hence can be repurposed as a therapeutic strategy against NSCLCs. Available NSCLC mutation data reflects a high probabilistic chance of patients harboring a p53 mutation, especially a gain of function (GOF)-R273H mutation. The GOF-P53 mutation enables the P53 protein to potentially interact with non-canonical protein partners facilitating oncogenesis. In this context, analysis of existing transcriptomic data from R273H-P53 expressing cells shows a concomitant up-regulation of Yes-associated protein (YAP) transcriptional targets and its protein partner TEAD1 in NSCLCs, suggesting a possible link between R273H-P53 and YAP. We therefore explored the inter-dependence of R273H-P53 and YAP in NSCLC cells. They were found to co-operatively regulate NSCLC proliferation. Genetic or pharmacological inhibition of YAP and GOF-P53 resulted in sensitization of NSCLC cells. Further analysis of pathways controlled by GOF-P53 and YAP showed that they positively regulate the cellular homeostatic process- autophagy to mediate survival. We hence postulated that a modulation of autophagy might be a potent strategy to curb proliferation. In accordance to above, autophagy inhibition, especially with the FDA-approved drug- chloroquine (CQ) resulted in cytoplasmic accumulation and reduced transcriptional activity of GOF-P53 and YAP, leading to growth arrest of NSCLC cells. CONCLUSION: Our study highlights the importance of GOF-P53 and YAP in NSCLC proliferation and proposes autophagy inhibition as an efficient strategy to attenuate NSCLC tumorigenesis.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism , Chloroquine/pharmacology , Chloroquine/therapeutic use , Cell Line, Tumor , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Carcinogenesis/genetics , Cell Transformation, Neoplastic , Cell ProliferationABSTRACT
Obstetric ultrasound assessment of fetal anatomy in the first trimester of pregnancy is one of the less explored fields in obstetric sonography because of the paucity of guidelines on anatomical screening and availability of data. This paper, for the first time, examines imaging proficiency and practices of first trimester ultrasound scanning through analysis of full-length ultrasound video scans. Findings from this study provide insights to inform the development of more effective user-machine interfaces, of targeted assistive technologies, as well as improvements in workflow protocols for first trimester scanning. Specifically, this paper presents an automated framework to model operator clinical workflow from full-length routine first-trimester fetal ultrasound scan videos. The 2D+t convolutional neural network-based architecture proposed for video annotation incorporates transfer learning and spatio-temporal (2D+t) modelling to automatically partition an ultrasound video into semantically meaningful temporal segments based on the fetal anatomy detected in the video. The model results in a cross-validation A1 accuracy of 96.10% , F1=0.95 , precision =0.94 and recall =0.95 . Automated semantic partitioning of unlabelled video scans (n=250) achieves a high correlation with expert annotations ( ρ = 0.95, p=0.06 ). Clinical workflow patterns, operator skill and its variability can be derived from the resulting representation using the detected anatomy labels, order, and distribution. It is shown that nuchal translucency (NT) is the toughest standard plane to acquire and most operators struggle to localize high-quality frames. Furthermore, it is found that newly qualified operators spend 25.56% more time on key biometry tasks than experienced operators.
Subject(s)
Nuchal Translucency Measurement , Ultrasonography, Prenatal , Pregnancy , Female , Humans , Pregnancy Trimester, First , Workflow , Ultrasonography, Prenatal/methods , Nuchal Translucency Measurement/methods , Machine LearningABSTRACT
In this work, we present a novel gaze-assisted natural language processing (NLP)-based video captioning model to describe routine second-trimester fetal ultrasound scan videos in a vocabulary of spoken sonography. The primary novelty of our multi-modal approach is that the learned video captioning model is built using a combination of ultrasound video, tracked gaze and textual transcriptions from speech recordings. The textual captions that describe the spatio-temporal scan video content are learnt from sonographer speech recordings. The generation of captions is assisted by sonographer gaze-tracking information reflecting their visual attention while performing live-imaging and interpreting a frozen image. To evaluate the effect of adding, or withholding, different forms of gaze on the video model, we compare spatio-temporal deep networks trained using three multi-modal configurations, namely: (1) a gaze-less neural network with only text and video as input, (2) a neural network additionally using real sonographer gaze in the form of attention maps, and (3) a neural network using automatically-predicted gaze in the form of saliency maps instead. We assess algorithm performance through established general text-based metrics (BLEU, ROUGE-L, F1 score), a domain-specific metric (ARS), and metrics that consider the richness and efficiency of the generated captions with respect to the scan video. Results show that the proposed gaze-assisted models can generate richer and more diverse captions for clinical fetal ultrasound scan videos than those without gaze at the expense of the perceived sentence structure. The results also show that the generated captions are similar to sonographer speech in terms of discussing the visual content and the scanning actions performed.
Subject(s)
Algorithms , Neural Networks, Computer , Humans , Pregnancy , Female , Ultrasonography, PrenatalABSTRACT
BACKGROUND: Acute kidney injury (AKI) is associated with morbidity and mortality in COVID-19 patients. The incidence of AKI and its outcomes vary in different parts of the world. We aimed to analyze the AKI incidence, predictors of AKI, mortality, and renal function outcomes on follow-up in hospitalized patients with COVID-19. MATERIALS AND METHODS: The study was designed as a retrospective, observational study of electronically captured data on the hospital information system of laboratory-confirmed COVID-19 patients, with and without AKI, between March 2020 to June 2021. The predictor of AKI and mortality and residual damage in recovered AKI patients were analyzed. RESULTS: Of the 3395 patients, 3010 COVID-19 patients were eligible. AKI occurred in 951 (31.5%); with stages 1, 2, and 3 in 605 (63.7%), 138 (14.5%), and 208 (21.8%) patients, respectively. AKI severity increased with COVID-19 severity. Of 951 AKI patients, 403 died, and 548 were discharged. AKI group had higher mortality (42.3%) than the non-AKI (6.6%). At discharge, complete recovery was noticed in 370(67.5%), while 178 (32.5%) had residual damage. At three months of follow-up, 108 (69.6%) of 155 patients showed complete recovery. Residual damage was observed in 47 (30.3%). In 14 (9%) patients, serum creatinine remained elevated above the baseline. Thirty-three (21.2%) patients showed proteinuria (n = 24) and microscopic hematuria (n = 9). CONCLUSIONS: AKI is common among patients hospitalized with COVID-19 and is associated with high mortality. Residual kidney damage post-COVID-19 in recovered AKI patients may increase the CKD burden.