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Collective intelligent strategy for improved segmentation of COVID-19 from CT
No full textWe propose a novel non-invasive tool, using deep learning and imaging, for delineating COVID-19 infection in lungs. The Ensembling of selective Focus-based Multi-resolution Convolution network (EFMC), employing Leave-One-Patient-Out (LOPO) training, exhibits high sensitivity and precision in outlining infected regions along with assessment of severity. The selective focus mechanism combines contextual with local information, at multiple resolutions, for accurate segmentation. Ensemble learning integrates heterogeneity of decision through different base classifiers. The superiority of EFMC, even with severe class imbalance, is established through comparison with existing state-of-the-art learning models over four publicly-available COVID-19 datasets. The results are suggestive of the relevance of deep learning in providing assistive intelligence to medical practitioners, when they are overburdened with patients as in pandemics
Wound-induced small-peptide-mediated signaling cascade, regulated by OsPSKR, dictates balance between growth and defense in rice
No full textWounding is a general stress in plants that results from various pest and pathogenic infections in addition to environment-induced mechanical damages. Plants have sophisticated molecular mechanisms to recognize and respond to wounding, with those of monocots being distinct from dicots. Here, we show the involvement of two distinct categories of temporally separated, endogenously derived peptides, namely, plant elicitor peptides (PEPs) and phytosulfokine (PSK), mediating wound responses in rice. These peptides trigger a dynamic signal relay in which a receptor kinase involved in PSK perception named OsPSKR plays a major role. Perturbation of OsPSKR expression in rice leads to compromised development and constitutive autoimmune phenotypes. OsPSKR regulates the transitioning of defense to growth signals upon wounding. OsPSKR displays mutual antagonism with the OsPEPR1 receptor involved in PEP perception. Collectively, our work indicates the presence of a stepwise peptide-mediated signal relay that regulates the transition from defense to growth upon wounding in monocots
The B-box protein BBX13/COL15 suppresses photoperiodic flowering by attenuating the action of CONSTANS in Arabidopsis
No full textThe optimal timing of transition from vegetative to floral reproductive phase is critical for plant productivity and agricultural yields. Light plays a decisive role in regulating this transition. The B-box (BBX) family of transcription factors regulates several light-mediated developmental processes in plants, including flowering. Here, we identify a previously uncharacterized group II member of the BBX family, BBX13/COL15, as a negative regulator of flowering under long-day conditions. BBX13 is primarily expressed in the leaf vasculature, buds, and flowers. Its spatial expression pattern is similar to the major flowering time regulators CO and FT. bbx13 mutants flower early, while BBX13 -overexpressors exhibit delayed flowering under long days. Genetic analyses showed that BBX13 acts upstream to CO and FT in the flowering pathway and negatively regulates their expression. We found that BBX13 physically interacts with CO and inhibits the CO-mediated transcriptional activation of FT . In addition, BBX13 directly binds to the CORE2 motif on the FT promoter, a site where CO also binds. Furthermore, our ChIP data indicates that BBX13 reduces the in vivo binding of CO on the FT promoter. Through luciferase assay, we found that BBX13 inhibits the CO-mediated transcriptional activation of FT. All these data together suggest that BBX13/COL15 represses flowering in Arabidopsis by attenuating CO activity
Seahorse assay for the analysis of mitochondrial respiration using Saccharomyces cerevisiae as a model system
No full textEukaryotic cells require energy to perform diverse cellular functions critical for survival. Mitochondria are multifunctional organelles that generate energy in the form of Adenosine triphosphate by oxidative phosphorylation, emphasizing their importance to eukaryotic cell viability. The ability of mitochondria to consume oxygen for respiration is a key parameter in assessing mitochondrial health. Therefore, developing new techniques to monitor mitochondrial respiration are crucial for advancing our understanding of organelle functioning. Recently, Seahorse technology has emerged as a valuable tool to analyze various aspects of mitochondrial bioenergetics. Although the Seahorse assay is well established in adherent cell lines and other model organisms, it remains challenging to employ it efficiently in yeast, a powerful genetic system for studying mitochondrial biology. In this chapter, we provide a comprehensive methodology for assessing oxygen consumption rate in baker's yeast using Seahorse
Concurrent hypoxia and apoptosis imparts immune programming potential in mesenchymal stem cells: Lesson from acute graft-versus-host-disease model
No full textBackground
Mesenchymal stem cells (MSCs) have emerged as promising candidates for immune modulation in various diseases that are associated with dysregulated immune responses like Graft-versus-Host-Disease (GVHD). MSCs are pleiotropic and the fate of MSCs following administration is a major determinant of their therapeutic efficacy.
Methods
Human MSCs were derived from bone marrow (BM) and Wharton’s Jelly (WJ) and preconditioned through exposure to hypoxia and induction of apoptosis, either sequentially or simultaneously. The immune programming potential of preconditioned MSCs was evaluated by assessing their effects on T cell proliferation, induction of Tregs, programming of effector T-cell towards Th2 phenotype, macrophage polarization in the direct co-culture of MSCs and aGVHD patients-derived PBMNCs. Additionally, efferocytosis of MSCs and relative change in the expression of immunomodulatory soluble factors were examined.
Results
Our study demonstrated that hypoxia preconditioned apoptotic MSCs (BM-MSCs, WJ-MSCs) bear more immune programming ability in a cellular model of acute Graft-versus-Host-Disease (aGVHD). Our findings revealed that WJ-MSCsHYP+APO were superior to BM-MSCsHYP+APO for immune regulation. These induced the differentiation of CD4+T-cell into Tregs, enhanced Th2 effector responses, and simultaneously mitigated Th1- and Th17 responses. Additionally, this approach led to the polarization of M1 macrophages toward an M2 phenotype.
Conclusion
Our study highlights the potential of WJ-MSCs conditioned with hypoxia and apoptosis concurrently, as a promising therapeutic strategy for aGVHD. It underscores the importance of considering MSC apoptosis in optimizing MSCs-based cellular therapy protocols for enhanced therapeutic efficacy in aGvHD
Antioxidant polymers with phenolic pendants for the mitigation of cellular oxidative stress.
No full textOverproduction of reactive oxygen species (ROS) in cells is a major health concern as it may lead to various diseases through oxidative damage of biomolecules. Commonly used traditional small molecular antioxidants (polyphenols, carotenoids, vitamins, etc.) have inadequate efficacy in lowering excessive levels of ROS due to their poor aqueous solubility and bioavailability. In response to the widespread occurrence of antioxidant polyphenols in various biorenewable resources, we aimed to develop water-soluble antioxidant polymers with side chain phenolic pendants. Four different types of copolymers (P1–P4) containing phenyl rings with different numbers of hydroxy (−OH) substituents (0: phenylalanine, 1: tyrosyl, 2: catechol, or 3: gallol) were synthesized via reversible addition–fragmentation chain transfer (RAFT) polymerization with a desired molar mass (8500–10000 g/mol) and a narrow dispersity (Đ ≤ 1.3). After successful characterizations of P1–P4, their in vitro antioxidant properties were analyzed by different methods, including 2,2-diphenyl-1-picrylhydrazyl (DPPH•), 2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS•+), 4,4′-diamino-3,3′,5,5′-tetramethylbiphenyl (TMB), and β-carotene (βC) assays. Our results revealed that the gallol pendant polymers can effectively scavenge ROS. Furthermore, electron paramagnetic resonance (EPR) spectroscopy with DPPH• also confirmed the radical quenching ability of the synthesized polymers. The gallol pendant polymers, at a well-tolerated concentration, could effectively penetrate the macrophage cells and restore the H2O2-induced ROS to the basal level. Overall, the present approach demonstrates the efficacy of water-soluble antioxidant polymers with gallol pendants toward the mitigation of cellular oxidative stress
A real-world study on the clinicopathological profile, treatment outcomes and health-related quality of life, anxiety and depression among patients with desmoid tumor at two tertiary care centers in India
No full textBackground: The medical management of DT comprises tyrosine kinase inhibitors (TKIs), hormonal agents, anti-inflammatory drugs with the recently approved gamma secretase inhibitor nirogacestat being the current standard of care. Real-world data on evolving treatment landscapes of DT remains scarce.
Methods: This is a retrospective study of patients with DT registered between 1995 and 2020 at All India Institute of Medical Sciences, New Delhi and Tata Medical Center, Kolkata. Baseline characteristics were analyzed in form of median values and interquartile range. Categorical and continuous variables were compared by chi square and independent samples T- tests respectively. Anxiety, depression and QoL were prospectively measured among 30 patients using Hospital Anxiety and Depression (HADS) and Functional Assessment of Cancer Therapy-General (FACT-G) scales respectively between 2022 to 2023.
Results: 200 patients were included with a male-predominant (n=111, 55.5%) population and median age 26.5 (2.5-75) years. Extremity (n=100, 50%) and abdomen (n=65, 32.5%) were commonest primary sites and median of 2 (1–4) lines of treatment were received. First-line included surgery (n=116, 58%), systemic therapy (n=67, 33.5%), radiotherapy (10, n=5%) and active surveillance (n=7, 3.5%). First-line systemic agents included tamoxifen (n=55, 27.5%), imatinib (n=7, 3.5%), sorafenib (n=1, 0.5%) and chemotherapy (n=4, 2%). 2019 onward, 3% and 63% underwent active surveillance and surgery respectively. Best radiological response obtained with tamoxifen was stable disease (SD) (n=76, 59%) and partial response (PR) (n=31, 24.2%). Best radiological response obtained with sorafenib was PR (n=17, 60.7%) and SD (n=9, 32.1%). Thirty patients underwent HADS and FACT-G scale assessment. Mean HADS-Anxiety subscale score was 3.6 (+/-3.9 SD) and HADS-Depression sub-scale score was 2.6 (+/-3.5 SD) with clinically significant anxiety and depression in 2 (6.7%) patients each. The overall mean FACT-G score was 87.5 (+/-12.6 SD) and lower mean physical well-being (p=0.006) and emotional well-being (0.017) scores were significantly associated with higher HADS-anxiety (>/=8) scores.
Conclusions: Assessment of anxiety, depression and QoL are paramount to gauge the psychological impact of DT. This study gives an overview of clinical and management profile of patients with DT in India, with limitations of selection bias, heterogeneous population and small sample size for QoL assessment
Automated Texture Feature Based Bone Tumor Segmentation and Image Analysis Using Supervised Machine Learning
No full textManual demarcation of tumors in MR images is time-consuming, hard to reproduce, and prone to intra-rater variability. Accurate tumor demarcation is required for diagnosis and prognosis of tumors and in quantitative image analysis techniques like Apparent Diffusion Coefficients (ADC) using diffusion weighted (DW) MRI. In this study, fully automated machine learning algorithms were developed using textural features extracted from multimodal MRI. A total of 20 patients (n=20; Male:Female=16:4; Age=15.5±2.6 years) with biopsy-proven osteosarcoma were analyzed. Multimodal MRI datasets including T1, T2, and proton density weighted MRI and DW-MRI were acquired before treatment using a 1.5 T Philips Achieva MRI scanner. 15 textural features were extracted using Grey-level co-occurrence matrices and Grey-level run length matrices in tumor volume from multimodal MRI. Four fully automated supervised machine learning algorithms — (1) Logistic Regression, (2) Linear Support Vector Machines (L-SVMs), (3) Random Forests, and (4) Gradient Boosted D-Trees (GBDTs) — were implemented and tested using accuracy metrics such as dice coefficient (DC), precision, recall, and accuracy.
The ADC values calculated in manually demarked and segmented tumor volume were compared for clinical reliability. Logistic Regression demonstrated the best performance (DC: 0.70±0.12; precision: 0.72±0.18; recall: 0.74±0.19; accuracy: 0.98±0.02), while Random Forest and GBDTs showed comparable performance (DC: 0.68±0.14, 0.68±0.14; precision: 0.73±0.19, 0.71±0.20; recall: 0.73±0.22, 0.75±0.22; accuracy: 0.98±0.02, 0.98±0.02 respectively); and L-SVM showed comparatively inferior performance (DC: 0.61±0.16; precision: 0.63±0.20; recall: 0.74±0.24; accuracy: 0.97±0.03) than the other methods.
The masks segmented by the four methods have ADC values ((1.17–1.21)×10⁻³ mm²/sec) similar to those of manually demarcated masks (1.27×10⁻³ mm²/sec) and can be used for tumor assessment in clinical settings. Therefore, proposed segmentation methods showed clinically acceptable accuracies and considerable reduction of manual effort involved
Polymeric materials as a promising platform for suppressing protein Aggregation process.
No full textThe idea of designing novel anti-amyloid therapeutic agents has generated a lot of scientific interest and the potential for treating a variety of human pathophysiologies, such as neurodegenerative and non-neuropathic diseases linked to amyloid protein aggregation. To address this, different small molecules, peptides, surfactants, nanomaterials, etc., have been thoroughly investigated to learn more about their anti-amyloidogenic capabilities, offering a great deal of potential for them to show up as future anti-amyloidogenic agents. In contrast to existing small-molecule analogues, polymers have been envisaged as promising anti-amyloid agents for treating these diseases because of their enthralling physicochemical features and simplicity of functionalisation. This review article emphasises the latest developments in the design of synthetic polymers such as amino acid-conjugated polymers, glycopolymers, zwitterionic polymers and so on reported in the last decade in modulating amyloid aggregation process. Additionally, the structural function and mechanism involved in modifying the aggregation process are highlighted in order to inspire the researchers even more and provide insight into this important field of study
LncRNA Malat1 suppresses pyroptosis and T cell-mediated killing of incipient metastatic cells
No full textThe contribution of antitumor immunity to metastatic dormancy is poorly understood. Here we show that the long noncoding RNA Malat1 is required for tumor initiation and metastatic reactivation in mouse models of breast cancer and other tumor types. Malat1 localizes to nuclear speckles to couple transcription, splicing and mRNA maturation. In metastatic cells, Malat1 induces WNT ligands, autocrine loops to promote self-renewal and the expression of Serpin protease inhibitors. Through inhibition of caspase-1 and cathepsin G, SERPINB6B prevents gasdermin D-mediated induction of pyroptosis. In this way, SERPINB6B suppresses immunogenic cell death and confers evasion of T cell-mediated tumor lysis of incipient metastatic cells. On-target inhibition of Malat1 using therapeutic antisense nucleotides suppresses metastasis in a SERPINB6B-dependent manner. These results suggest that Malat1-induced expression of SERPINB6B can titrate pyroptosis and immune recognition at metastatic sites. Thus, Malat1 is at the nexus of tumor initiation, reactivation and immune evasion and represents a tractable and clinically relevant drug target