Autophagy and mitophagy: physiological implications in kidney inflammation and diseases.

Autophagy is a ubiquitous intracellular cytoprotective quality control program that maintains cellular homeostasis by recycling superfluous cytoplasmic components (lipid droplets, protein, or glycogen aggregates) and invading pathogens. Mitophagy is a selective form of autophagy that by recycling damaged mitochondrial material, which can extracellularly act as damage-associated molecular patterns, prevents their release. Autophagy and mitophagy are indispensable for the maintenance of kidney homeostasis and exert crucial functions during both physiological and disease conditions. Impaired autophagy and mitophagy can negatively impact the pathophysiological state and promote its progression. Autophagy helps in maintaining structural integrity of the kidney. Mitophagy-mediated mitochondrial quality control is explicitly critical for regulating cellular homeostasis in the kidney. Both autophagy and mitophagy attenuate inflammatory responses in the kidney. An accumulating body of evidence highlights that persistent kidney injury-induced oxidative stress can contribute to dysregulated autophagic and mitophagic responses and cell death. Autophagy and mitophagy also communicate with programmed cell death pathways (apoptosis and necroptosis) and play important roles in cell survival by preventing nutrient deprivation and regulating oxidative stress. Autophagy and mitophagy are activated in the kidney after acute injury. However, their aberrant hyperactivation can be deleterious and cause tissue damage. The findings on the functions of autophagy and mitophagy in various models of chronic kidney disease are heterogeneous and cell type- and context-specific dependent. In this review, we discuss the roles of autophagy and mitophagy in the kidney in regulating inflammatory responses and during various pathological manifestations.

Conditional deletion of myeloid-specific mitofusin 2 but not mitofusin 1 promotes kidney fibrosis.

Macrophages exert critical functions during kidney injury, inflammation, and tissue repair or fibrosis. Mitochondrial structural and functional aberrations due to an imbalance in mitochondrial fusion/fission processes are implicated in the pathogenesis of chronic kidney disease. Therefore, we investigated macrophage-specific functions of mitochondrial fusion proteins, mitofusin (MFN)1 and MFN2, in modulating macrophage mitochondrial dynamics, biogenesis, oxidative stress, polarization, and fibrotic response. MFN1 and MFN2 were found to be suppressed in mice after adenine diet-induced chronic kidney disease, in transforming growth factor-beta 1-treated bone marrow-derived macrophages, and in THP-1-derived human macrophages (a human leukemic cell line). However, abrogating Mfn2 but not Mfn1 in myeloid-lineage cells resulted in greater macrophage recruitment into the kidney during fibrosis and the macrophage-derived fibrotic response associated with collagen deposition culminating in worsening kidney function. Myeloid-specific Mfn1 /Mfn2 double knockout mice also showed increased adenine-induced fibrosis. Mfn2-deficient bone marrow-derived macrophages displayed enhanced polarization towards the profibrotic/M2 phenotype and impaired mitochondrial biogenesis. Macrophages in the kidney of Mfn2-deficient and double knockout but not Mfn1-deficient mice exhibited greater mitochondrial mass, size, oxidative stress and lower mitophagy under fibrotic conditions than the macrophages in the kidney of wild-type mice. Thus, downregulation of MFN2 but not MFN1 lead to macrophage polarization towards a profibrotic phenotype to promote kidney fibrosis through a mechanism involving suppression of macrophage mitophagy and dysfunctional mitochondrial dynamics.

Effects of pointing movements on visuospatial working memory in a joint-action condition: Evidence from eye movements.

Previous studies showed that (a) performing pointing movements towards to-be-remembered locations enhanced their later recognition, and (b) in a joint-action condition, experimenter-performed pointing movements benefited memory to the same extent as self-performed movements. The present study replicated these findings and additionally recorded participants' fixations towards studied arrays. Each trial involved the presentation of two consecutive spatial arrays, where each item occupied a different spatial location. The item locations of one array were encoded by mere visual observation (the no-move array), whereas the locations of the other array were encoded by observation plus pointing movements (the move array). Critically, in Experiment 1, participants took turns with the experimenter in pointing towards the move arrays (joint-action condition), while in Experiment 2 pointing was performed only by the experimenter (passive condition). The results showed that the locations of move arrays were recognized better than the locations of no-move arrays in Experiment 1, but not in Experiment 2. The pattern of eye-fixations was in line with behavioral findings, indicating that in Experiment 1, fixations to the locations of move arrays were higher in number and longer in duration than fixations to the locations of no-move arrays, irrespective of the agent who performed the movements. In contrast, no differences emerged in Experiment 2. We propose that, in the joint-action condition, self- and other-performed pointing movements are coded at the same representational level and their functional equivalency is reflected in a similar pattern of eye-fixations.

Bringing high spatial resolution to the far-infrared: A giant leap for astrophysics.

The far-infrared (FIR) regime is one of the wavelength ranges where no astronomical data with sub-arcsecond spatial resolution exist. None of the medium-term satellite projects like SPICA, Millimetron, or the Origins Space Telescope will resolve this malady. For many research areas, however, information at high spatial and spectral resolution in the FIR, taken from atomic fine-structure lines, from highly excited carbon monoxide (CO), light hydrides, and especially from water lines would open the door for transformative science. A main theme will be to trace the role of water in proto-planetary discs, to observationally advance our understanding of the planet formation process and, intimately related to that, the pathways to habitable planets and the emergence of life. Furthermore, key observations will zoom into the physics and chemistry of the star-formation process in our own Galaxy, as well as in external galaxies. The FIR provides unique tools to investigate in particular the energetics of heating, cooling, and shocks. The velocity-resolved data in these tracers will reveal the detailed dynamics engrained in these processes in a spatially resolved fashion, and will deliver the perfect synergy with ground-based molecular line data for the colder dense gas.

Carbonyl iron and iron dextran therapies cause adverse effects on bone health in juveniles with chronic kidney disease.

Anemia is a frequent complication of chronic kidney disease (CKD), related in part to the disruption of iron metabolism. Iron therapy is very common in children with CKD and excess iron has been shown to induce bone loss in non-CKD settings, but the impact of iron on bone health in CKD remains poorly understood. Here, we evaluated the effect of oral and parenteral iron therapy on bone transcriptome, bone histology and morphometry in two mouse models of juvenile CKD (adenine-induced and 5/6-nephrectomy). Both modalities of iron therapy effectively improved anemia in the mice with CKD, and lowered bone Fgf23 expression. At the same time, iron therapy suppressed genes implicated in bone formation and resulted in the loss of cortical and trabecular bone in the mice with CKD. Bone resorption was activated in untreated CKD, but iron therapy had no additional effect on this. Furthermore, we assessed the relationship between biomarkers of bone turnover and iron status in a cohort of children with CKD. Children treated with iron had lower levels of circulating biomarkers of bone formation (bone-specific alkaline phosphatase and the amino-terminal propeptide of type 1 procollagen), as well as fewer circulating osteoblast precursors, compared to children not treated with iron. These differences were independent of age, sex, and glomerular filtration rate. Thus, iron therapy adversely affected bone health in juvenile mice with CKD and was associated with low levels of bone formation biomarkers in children with CKD.

Pointing movements and visuo-spatial working memory in a joint setting: the role of motor inhibition.

Previous studies have shown that, under specific conditions, arrays that have been pointed at encoding are recognized better than passively viewed ones. According to one interpretation, the superior recognition of pointed-to arrays can be explained by the motor inhibition of passively viewed arrays. The present study sought to determine whether a similar motor inhibition can be induced also when the participants observed a co-actor perform the pointing movements. Participants were presented with two spatial arrays, one of which was encoded via observation only (the no-move array), while the other was encoded with pointing movements (the move array); movements were performed either by the participant or by the experimenter. Experiment 1 replicated the advantage of self-pointed arrays over passively viewed arrays. Experiment 2 showed that, when participants passively observed the pointing movements performed by the experimenter, move arrays were recognized no better than no-move arrays. Finally, Experiment 3 demonstrated that, in a joint-action condition in which participants alternated with the experimenter in making pointing movements, the advantage of experimenter-pointed arrays over passively viewed arrays was significant and similar in size to the advantage produced by self-performed movements. Importantly, a series of cross-experiment comparisons indicated that the higher recognition of both self- and experimenter-pointed arrays in Experiment 3 could be explained by the motor inhibition of no-move arrays. We propose that, in a joint condition, the pointing movements performed by the experimenter were represented in the same functional way as self-performed movements and that this produced the motor inhibition of passively viewed arrays.

Collaborative remembering reduces suggestibility: A study with the Gudjonsson Suggestibility Scale.

Collaboration during the retrieval phase can have both negative and positive effects (referred to as collaborative inhibition and error pruning, respectively) on emotional and eyewitness memory. To further elucidate these issues, the present experiment used the Gudjonsson Suggestibility Scale to investigate the question of whether collaborative remembering reduced post-event suggestibility. Collaborative and nominal pairs listened to the GSS2, provided immediate and delayed (after 30 min) free recalls, and answered a series of leading questions before or after receiving a negative feedback about their performance. We found no evidence of collaborative inhibition in the immediate and delayed free recall tasks. Importantly, however, collaborative pairs produced less confabulated elements in the free recall tasks, were considerably less prone to give in to leading questions (both before and after receiving the negative feedback), and exhibited lower levels of Total Suggestibility, compared to both nominal and individual dyads. Taken together, these results support the conclusion that collaboration can have a beneficial influence on eyewitnesses' accuracy, by strengthening their resistance to post-event suggestibility.

Rituximab modulates T- and B-lymphocyte subsets and urinary CD80 excretion in patients with steroid-dependent nephrotic syndrome.

BACKGROUND: Rituximab, a monoclonal antibody targeting B lymphocytes, effectively sustains remission in steroid-dependent nephrotic syndrome (SDNS). We studied its effects on lymphocyte subsets and urinary CD80 excretion (uCD80) in patients with SDNS. METHODS: Blood and urine samples were collected from 18 SDNS patients before rituximab, and after 1 month and 1 year or at first relapse. T and B lymphocytes and uCD80 were determined by flow cytometry and ELISA, respectively. RESULTS: Treatment was associated with reduction in counts of Th17, Th2, and memory T cells, and increased T-regulatory (Treg) cells. The Th17/Treg ratio declined from baseline (median 0.6) to 1 month (0.2, P = 0.006) and increased during relapse (0.3, P = 0.016). Ratios of Th1/Th2 cells at baseline, 1 month after rituximab, and during relapse were 7.7, 14.0 (P = 0.0102), and 8.7, respectively. uCD80 decreased 1 month following rituximab (45.5 vs. 23.0 ng/g creatinine; P = 0.0039). B lymphocytes recovered earlier in relapsers (60.0 vs.183.0 days; P < 0.001). Memory B cells were higher during relapse than remission (29.7 vs.18.0 cells/µL; P = 0.029). CONCLUSION: Rituximab-induced sustained remission and B-cell depletion was associated with reduced numbers of Th17 and Th2 lymphocytes, and increased Treg cells; these changes reversed during relapses. Recovery of B cells and memory B cells predicted the occurrence of a relapse.

Efficacy and safety of rituximab in children with difficult-to-treat nephrotic syndrome.

BACKGROUND: Rituximab has emerged as an important medication for patients with steroid-dependent or steroid-resistant nephrotic syndrome. PATIENTS: We report the efficacy and safety of therapy with intravenous rituximab, administered once weekly for 2-4 doses, in 193 patients (mean age 10.9, range 2.2-18.7 years) with difficult-to-treat steroid dependence (n = 101), calcineurin inhibitor (CNI)-dependent steroid resistance (n = 34) and CNI-resistant nephrotic syndrome (n = 58) managed at this center during 2006-13. OUTCOMES: Therapy in patients with steroid dependence and CNI-dependent steroid resistance led to significantly reduced relapse rates (respective mean difference 2.7 relapses/year and 2.2 relapses/year, corresponding to a decrease in relapses by 81.8 and 71.0%; both P < 0.0001). This resulted in a significant reduction in steroid requirement (mean difference 104.5 and 113.6 mg/kg/year, respectively; both P < 0.0001) and a trend to improved standard deviation scores for height (P = 0.069) and body mass index (P = 0.029). Remission was longer in patients with steroid dependence compared with CNI-dependent steroid resistance (median 16 versus 10 months; P < 0.0001). Prior response to cyclophosphamide predicted a lower risk of relapse in the former (hazard ratio, HR 0.56; P = 0.045); patients with initial resistance and CNI-dependent steroid resistance had increased risk of relapse (HR 2.66; P = 0.042). B-cell recovery, noted in 62.5% patients at 6 months, was not related to occurrence of relapse; redosing (n = 42 patients) was safe and effective. Response to therapy was unsatisfactory in patients with steroid- and CNI-resistant nephrotic syndrome, with remission in 29.3%. Focal segmental glomerulosclerosis was associated with higher odds of non-response (odds ratio 11.1; P = 0.028) and lack of response was associated with progressive chronic kidney disease (HR 9.97; P = 0.035). Therapy with rituximab was safe; adverse effects or infections were noted in 19 (9.8%) patients. CONCLUSIONS: Therapy with rituximab is effective and safe in reducing relapse rates and need for immunosuppressive medications in patients with steroid-dependent and CNI-dependent steroid-resistant nephrotic syndrome.

Incomplete penetrance of CD46 mutation causing familial atypical hemolytic uremic syndrome.

BACKGROUND: Hemolytic uremic syndrome (HUS) secondary to homozygous mutations in CD46 is uncommon. While heterozygous individuals may remain asymptomatic, homozygous mutations with severely depleted CD46 surface expression without disease manifestation is rare. METHODS: We report on two siblings with features suggestive of hemolytic uremic syndrome. Estimation of CD46 expression by flow cytometry and gene sequencing were performed in members of this family. RESULTS: Three siblings, two of whom were symptomatic, had markedly decreased (<10%) cell surface expression of CD46 and homozygous splice site mutation (IVS2 + 2 T > G) in the CD46 gene; the other 10-year-old sibling was asymptomatic. The illness was preceded by dengue shock syndrome in the index case. Both parents and two other siblings were heterozygous for this CD46 mutation. CONCLUSIONS: Homozygous IVS2 + 2 T > G mutation in CD46 gene, similar to heterozygous mutation, may be clinically silent at least during childhood. The role of antecedent infections in triggering the disease requires further examination.

Serum-soluble urokinase receptor levels do not distinguish focal segmental glomerulosclerosis from other causes of nephrotic syndrome in children.

In this prospective study, we measured serum levels of the soluble urokinase receptor (suPAR) in pediatric patients with nephrotic syndrome of various etiologies. Mean levels of suPAR were 3316 pg/ml in 99 patients with steroid-resistant focal segmental glomerulosclerosis and 3253 pg/ml in 117 patients with biopsy-proven minimal change disease, which were similar to that of 138 patients with steroid-sensitive nephrotic syndrome (3150 pg/ml) and 83 healthy controls (3021 pg/ml). Similar proportions of patients in each group had suPAR over 3000 pg/ml. Compared with controls, suPAR levels were significantly higher in patients with focal segmental glomerulosclerosis (FSGS) and estimated glomerular filtration rate (eGFR) under 30 ml/min per 1.73 m(2) (6365 pg/ml), congenital nephrotic syndrome (4398 pg/ml), and other proteinuric diseases with or without eGFR under 30 ml/min per 1.73 m(2) (5052 and 3875 pg/ml, respectively; both significant). There were no changes following therapy and during remission. Levels of suPAR significantly correlated in an inverse manner with eGFR (r=-0.36) and directly with C-reactive protein (r=0.20). The urinary suPAR-to-creatinine ratio significantly correlated with proteinuria (r=0.25) in 151 patients and controls. Using generalized estimating equations approach, serum suPAR significantly correlated with eGFR (coefficient=-13.75), age at sampling (2.72), and C-reactive protein (39.85). Thus, serum suPAR levels in nephrotic syndrome are similar to controls, and do not discriminate between FSGS, minimal change disease, or steroid-responsive illness.

Prompt plasma exchanges and immunosuppressive treatment improves the outcomes of anti-factor H autoantibody-associated hemolytic uremic syndrome in children.

Antibodies to complement factor H are an uncommon cause of hemolytic uremic syndrome (HUS). Information on clinical features and outcomes in children is limited. In order to explore this we studied a multicenter cohort of 138 Indian children with anti-complement factor H antibody associated HUS, constituting 56% of patients with HUS. Antibody titers were high (mean 7054 AU/ml) and correlated inversely with levels of complement C3, but not complement factor H. Homozygous deletion of the CFHR1 gene was found in 60 of 68 patients. Therapies included dialysis in 119 children, 105 receiving plasma exchanges and 26 intravenous immunoglobulin. Induction immunosuppression consisted of 87 children receiving prednisolone with or without intravenous cyclophosphamide or rituximab. Antibody titers fell significantly following plasma exchanges and increased during relapses. Adverse outcome (stage 4-5 CKD or death) was seen in 36 at 3 months and 41 by last follow up, with relapse in 14 of 122 available children. Significant independent risk factors for adverse outcome were an antibody titer over 8000 AU/ml, low C3 and delay in plasma exchange. Combined plasma exchanges and induction immunosuppression resulted in significantly improved renal survival: one adverse outcome prevented for every 2.6 patients treated. Maintenance immunosuppressive therapy, of prednisolone with either mycophenolate mofetil or azathioprine, significantly reduced the risk of relapses. Thus, prompt use of immunosuppressive agents and plasma exchanges are useful for improving outcomes in pediatric patients with anti-complement factor H-associated HUS.

A prospective observational study correlating possible novel biomarkers with disease severity and antihistamine response in chronic spontaneous urticaria.

Background: Role of complement fraction 5a (C5a), interleukin (IL)-9, and apolipoprotein (apo) A-IV as biomarkers of disease severity and antihistamine response in chronic spontaneous urticaria (CSU) remains elusive. Objective: To identify the role of C5a, IL-9, and apo A-IV as potential biomarkers in predicting disease severity and antihistamine response in CSU patients. Methods: This was a prospective observational study of 95 patients and 42 controls. Serum analysis of C5a, IL-9, and apo A-IV was done using enyzme linked immunosorbent assay kits. Also, serum IgE and anti-thyroid peroxidase (TPO) levels were assessed in all patients. All patients were started on oral levocetirizine 5 mg at baseline and dose was titrated upwards to maximum of 20 mg based on response. Patients were categorized into antihistamine responders or nonresponders as per their disease response. Serological markers, serum IgE, and anti-TPO were correlated with baseline disease severity and antihistamine response. Results: C5a levels were significantly higher in cases as compared to controls (P = 0.004). Significantly higher IL-9 levels were observed in antihistamine responders than nonresponders (P = 0.008). Baseline urticaria severity demonstrated a statistically significant positive and negative correlations with IL-9 (ρ = 0.277, P = 0.007) and apo A-IV (ρ = -0.271, P = 0.008) levels, respectively. Levels of serum IgE (P = 0.031) and anti-TPO (P = 0.039) were significantly higher in antihistamine nonresponders compared to responders. Conclusions: IL-9 and apo A-IV might be potential novel biomarkers to predict urticaria severity. Higher IL-9 might be a predictor of antihistamine response. Elevated anti-TPO and serum IgE might predict poor antihistamine response.

Neuroscience Engagement and Outreach on Neurodevelopmental Disorders: A Report from India.

The current project was funded by the Global Engagement Seed Grant from the International Brain Research Organisation (IBRO) as part of the IBRO-led Global Engagement Initiative. The project was focused on public awareness about neurodevelopmental disorders (NDDs) as well as neuroscience engagement. Thus, the project had two specific aims: (a) public awareness about epidemiology, diagnosis, risk factors, prevention of NDDs and relevant government guidelines and available policies (b) public engagement in neuroscience. Therefore, the current project report with an emphasis on the requirement of neuroscience engagement and outreach at the societal level, highlights several activities such as population-based workshops and webinars, carried out as part of the project in both rural and urban areas to enhance the public engagement in neuroscience and awareness on several NDDs. Key message: India is an extremely diverse country with significant variations in cultural, educational, financial, socioeconomic status and linguistic aspects. With about 27% of its population living below the poverty line, India accounts for about 23 million children suffering from a disability, most of whom do not seek medical help. These data highlight the gravity of the situation which calls for urgent actions from governments, healthcare professionals, researchers and policymakers to design adequate public awareness programs regarding several prevalent NDDs. Therefore, the current project was an effort to bring public awareness about brain health and the epidemiology, diagnosis and prevention of NDDs and relevant government guidelines and available policies.

Automated Shoulder Implant Manufacturer Detection using Encoder Decoder based Classifier from X-ray Images.

Total shoulder arthroplasty is the process of replacing the damaged ball and socket joint in the shoulder with a prosthesis made with polyethylene and metal components. The prosthesis helps to restore the normal range of motion and reduce pain, enabling the patient to return to their daily activities. These implants may need to be replaced over the years due to damage or wear and tear. It is a tedious and time-consuming process to identify the type of implant if medical records are not properly maintained. Artificial intelligence systems can speed up the treatment process by classifying the manufacturer and model of the prosthesis. We have proposed an encoder-decoder based classifier along with the supervised contrastive loss function that can identify the implant manufacturer effectively with increased accuracy of 92% from X-ray images overcoming the class imbalance problem.

Iron therapy mitigates chronic kidney disease progression by regulating intracellular iron status of kidney macrophages.

Systemic iron metabolism is disrupted in chronic kidney disease (CKD). However, little is known about local kidney iron homeostasis and its role in kidney fibrosis. Kidney-specific effects of iron therapy in CKD also remain elusive. Here, we elucidate the role of macrophage iron status in kidney fibrosis and demonstrate that it is a potential therapeutic target. In CKD, kidney macrophages exhibited depletion of labile iron pool (LIP) and induction of transferrin receptor 1, indicating intracellular iron deficiency. Low LIP in kidney macrophages was associated with their defective antioxidant response and proinflammatory polarization. Repletion of LIP in kidney macrophages through knockout of ferritin heavy chain (Fth1) reduced oxidative stress and mitigated fibrosis. Similar to Fth1 knockout, iron dextran therapy, through replenishing macrophage LIP, reduced oxidative stress, decreased the production of proinflammatory cytokines, and alleviated kidney fibrosis. Interestingly, iron markedly decreased TGF-ß expression and suppressed TGF-ß-driven fibrotic response of macrophages. Iron dextran therapy and FtH suppression had an additive protective effect against fibrosis. Adoptive transfer of iron-loaded macrophages alleviated kidney fibrosis, validating the protective effect of iron-replete macrophages in CKD. Thus, targeting intracellular iron deficiency of kidney macrophages in CKD can serve as a therapeutic opportunity to mitigate disease progression.

Moderate intrinsic phenotypic alterations in C9orf72 ALS/FTD iPSC-microglia despite the presence of C9orf72 pathological features.

While motor and cortical neurons are affected in C9orf72 amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD), it remains largely unknown if and how non-neuronal cells induce or exacerbate neuronal damage. We differentiated C9orf72 ALS/FTD patient-derived induced pluripotent stem cells into microglia (iPSC-MG) and examined their intrinsic phenotypes. Similar to iPSC motor neurons, C9orf72 ALS/FTD iPSC-MG mono-cultures form G4C2 repeat RNA foci, exhibit reduced C9orf72 protein levels, and generate dipeptide repeat proteins. Healthy control and C9orf72 ALS/FTD iPSC-MG equally express microglial specific genes and perform microglial functions, including inflammatory cytokine release and phagocytosis of extracellular cargos, such as synthetic amyloid beta peptides and healthy human brain synaptoneurosomes. RNA sequencing analysis revealed select transcriptional changes of genes associated with neuroinflammation or neurodegeneration in diseased microglia yet no significant differentially expressed microglial-enriched genes. Moderate molecular and functional differences were observed in C9orf72 iPSC-MG mono-cultures despite the presence of C9orf72 pathological features suggesting that a diseased microenvironment may be required to induce phenotypic changes in microglial cells and the associated neuronal dysfunction seen in C9orf72 ALS/FTD neurodegeneration.

Cardiac Anomaly Detection from Cine MRI Images using Physiological Features and Random Forest Classifier.

Computer-aided diagnosis (CAD) with cine MRI is a foremost research topic to enable improved, faster, and more accurate diagnosis of cardiovascular diseases (CVD). However, current approaches that use manual visualization or conventional clinical indices can lack accuracy for borderline cases. Also, manual visualization of 3D/4D MR data is time-consuming and expert-dependent. We try to simplify this process by creating an end-to-end automated CAD system that segments the critical substructures of the heart. The new domain-related physiological features are then calculated from the segmented regions. These features are fed to a random forest classifier that identifies the anomaly. We have obtained a very high accuracy when testing this end-to-end approach on the Automated Cardiac Diagnosis challenge (ACDC) dataset (4 pathologies, 1 normal). To prove the generalizability of the method we have blind-tested this approach on M&Ms-2 dataset which is a multi-center, multi-vendor, and multi-disease dataset with better than 90% accuracy.

3D Cardiac Substructures Segmentation from CMRI using Generative Adversarial Network (GAN).

Cardiac magnetic resonance imaging (CMRI) improves the diagnosis of cardiovascular diseases by providing images at high spatio-temporal resolution helping physicians in providing correct treatment plans. Segmentation and identification of various substructures of the heart at different cardiac phases of end-systole and end-diastole helps in the extraction of ventricular function information such as stroke volume, ejection fraction, myocardium thickness, etc. Manual delineation of the substructures is tedious, time-consuming, and error-prone. We have implemented a 3D GAN that includes 3D contextual information capable of segmenting and identifying the substructures at different cardiac phases with improved accuracy. Our method is evaluated on the ACDC dataset (4 pathologies, 1 healthy group) to show that the proposed out-performs other methods in literature with less amount of data. Also, the proposed provided a better Dice score in segmentation surpassing other methods on a blind-tested M&Ms dataset.

Antimicrobial potential and in vitro cytotoxicity study of polyvinyl pyrollidone-stabilised silver nanoparticles synthesised from Lysinibacillus boronitolerans.

The main emphasis herein is on the eco-friendly synthesis and assessment of the antimicrobial potential of silver nanoparticles (AgNPs) and a cytotoxicity study. Silver nanoparticles were synthesised by an extracellular method using bacterial supernatant. Biosynthesised silver nanoparticles were characterised by UV-vis spectroscopy, transmission electron microscopy (TEM), Fourier transform infrared spectroscopy, dynamic light scattering, and zeta potential analysis. The synthesised silver nanoparticles exhibited a characteristic peak at 420 nm. TEM analysis depicted the spherical shape and approximately 20 nm size of nanoparticles. Silver nanoparticles carry a charge of -33.75 mV, which confirms their stability. Biogenic polyvinyl pyrrolidone-coated AgNPs exhibited significant antimicrobial effects against all opportunistic pathogens (Gram-positive and Gram-negative bacteria, and fungi). Silver nanoparticles equally affect the growth of both Gram-positive and Gram-negative bacteria, with a maximum inhibition zone observed at 22 mm and a minimum at 13 mm against Pseudomonas aeruginosa and Fusarium graminearum, respectively. The minimum inhibitory concentration (MIC) of AgNPs against P. aeruginosa and Staphylococcus aureus was recorded at between 15 and 20 µg/ml. Synthesised nanoparticles exhibited a significant synergistic effect in combination with conventional antibiotics. Cytotoxicity estimates using C2C12 skeletal muscle cell line via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test and lactate dehydrogenase assay were directly related to the concentration of AgNPs and length of exposure. On the basis of the MTT test, the IC50 of AgNPs for the C2C12 cell line was approximately 5.45 µg/ml concentration after 4 h exposure.