Measurements of seeing-induced crosstalk in tip-tilt corrected solar polarimetry.

We present measurements of seeing-induced crosstalk using spectropolarimetric observations of sunspots recorded simultaneously in the H α and Ca ii 8662 Å lines with the Kodaikanal Tower Tunnel (KTT) telescope. The Kodaikanal Tower Tunnel telescope is integrated and installed with an image stabilization system consisting of a tip-tilt and an autoguider system. Additionally, the spectropolarimeter at KTT is upgraded to allow for the simultaneous recording of spectropolarimetric observations in three spectral lines. The tip-tilt system is shown to have a cutoff frequency of 80 Hz, effectively reducing the seeing induced crosstalk in the measured Stokes parameters by at least a factor of 2.

Spectropolarimeter on board the Aditya-L1: polarization modulation and demodulation.

One of the major science goals of the Visible Emission Line Coronagraph (VELC) payload aboard the Aditya-L1 mission is to map the coronal magnetic field topology and quantitative estimation of longitudinal magnetic field on a routine basis. The infrared channel of VELC is equipped with a polarimeter to carry out full Stokes spectropolarimetric observations in the Fe xiii line at 1074.7 nm. The polarimeter is in a dual-beam setup with a continuously rotating wave plate as the polarization modulator. Detection of circular polarization due to the Zeeman effect and depolarization of linear polarization in the presence of a magnetic field due to the saturated Hanle effect in the Fe xiii line require a high signal-to-noise ratio (SNR). Due to the limited number of photons, long integration times are expected to build the required SNR. In other words, signals from a large number of modulation cycles are to be averaged to achieve the required SNR. This poses several difficulties. One is the increase in data volume and the other is the change in the modulation matrix in successive modulation cycles. The latter effect arises due to a mismatch between the retarder's rotation period and the length of the signal detection time in the case of the VELC spectropolarimeter. It is shown in this paper that by appropriately choosing the number of samples per half rotation, the data volume can be optimized. A potential solution is suggested to account for modulation matrix variation from one cycle to another.

Fusion of Graph and Tabular Deep Learning Models for Predicting Chronic Kidney Disease.

Chronic Kidney Disease (CKD) represents a considerable global health challenge, emphasizing the need for precise and prompt prediction of disease progression to enable early intervention and enhance patient outcomes. As per this study, we introduce an innovative fusion deep learning model that combines a Graph Neural Network (GNN) and a tabular data model for predicting CKD progression by capitalizing on the strengths of both graph-structured and tabular data representations. The GNN model processes graph-structured data, uncovering intricate relationships between patients and their medical conditions, while the tabular data model adeptly manages patient-specific features within a conventional data format. An extensive comparison of the fusion model, GNN model, tabular data model, and a baseline model was conducted utilizing various evaluation metrics, encompassing accuracy, precision, recall, and F1-score. The fusion model exhibited outstanding performance across all metrics, underlining its augmented capacity for predicting CKD progression. The GNN model's performance closely trailed the fusion model, accentuating the advantages of integrating graph-structured data into the prediction process. Hyperparameter optimization was performed using grid search, ensuring a fair comparison among the models. The fusion model displayed consistent performance across diverse data splits, demonstrating its adaptability to dataset variations and resilience against noise and outliers. In conclusion, the proposed fusion deep learning model, which amalgamates the capabilities of both the GNN model and the tabular data model, substantially surpasses the individual models and the baseline model in predicting CKD progression. This pioneering approach provides a more precise and dependable method for early detection and management of CKD, highlighting its potential to advance the domain of precision medicine and elevate patient care.

Optimizing Inference Distribution for Efficient Kidney Tumor Segmentation Using a UNet-PWP Deep-Learning Model with XAI on CT Scan Images.

Kidney tumors represent a significant medical challenge, characterized by their often-asymptomatic nature and the need for early detection to facilitate timely and effective intervention. Although neural networks have shown great promise in disease prediction, their computational demands have limited their practicality in clinical settings. This study introduces a novel methodology, the UNet-PWP architecture, tailored explicitly for kidney tumor segmentation, designed to optimize resource utilization and overcome computational complexity constraints. A key novelty in our approach is the application of adaptive partitioning, which deconstructs the intricate UNet architecture into smaller submodels. This partitioning strategy reduces computational requirements and enhances the model's efficiency in processing kidney tumor images. Additionally, we augment the UNet's depth by incorporating pre-trained weights, therefore significantly boosting its capacity to handle intricate and detailed segmentation tasks. Furthermore, we employ weight-pruning techniques to eliminate redundant zero-weighted parameters, further streamlining the UNet-PWP model without compromising its performance. To rigorously assess the effectiveness of our proposed UNet-PWP model, we conducted a comparative evaluation alongside the DeepLab V3+ model, both trained on the "KiTs 19, 21, and 23" kidney tumor dataset. Our results are optimistic, with the UNet-PWP model achieving an exceptional accuracy rate of 97.01% on both the training and test datasets, surpassing the DeepLab V3+ model in performance. Furthermore, to ensure our model's results are easily understandable and explainable. We included a fusion of the attention and Grad-CAM XAI methods. This approach provides valuable insights into the decision-making process of our model and the regions of interest that affect its predictions. In the medical field, this interpretability aspect is crucial for healthcare professionals to trust and comprehend the model's reasoning.

A new cerebral ischemic injury model in rats, preventive effect of gallic acid and in silico approaches.

Current study was designed multiple occlusions and reperfusion of bilateral carotid arteries induced cerebral injury model and evaluated the protective effect of gallic acid on it. In silico study was involved to study gallic acid binding affinity on cerebrotonic proteins compared with standard drugs using Autodoc vina tool. Cerebral ischemia was induced by occlusion of bilateral common carotid arteries for 10 mins followed by 10 reperfusions (1 cycle), cycle was continued to 3 cycles (MO/RCA), then pathological changes were observed by estimation of brain antioxidants as superoxide dismutase, glutathione, catalase, oxidants like malonaldehyde, cerebral infarction area, histopathology, and study gallic acid treatment against cerebral injury. Gallic acid exhibited a strong binding affinity on targeted cerebrotoxic proteins. MO/RCA rat brain antioxidant levels were significantly decreased and increased MDA levels (p < 0.0001), Infarction size compared to sham rats. Gallic acid treatment rat brain MDA levels significantly decreased (p < 0.4476) and increased SOD (p < 0.0001), CAT (p < 0.0001), GSH (p < 0.0001), cerebral infarction area when compared to MO/RCA group. Developed model showed significant cerebral ischemic injury in rats, injury was ameliorated by Gallic acid treatment and in silico approaches also inhibit the cerebrotoxic protein function by targeting on active sites.

Marginal and conditional approaches to multivariate variables subject to limit of detection.

A marginal approach and a variance-component mixed effect model approach (here called a conditional approach) are commonly used to analyze variables that are subject to limit of detection. We examine the theoretical relationship and investigate the numerical performance of these two approaches. We make some recommendations based on our results. The marginal approach is recommended for bivariate normal variables, and the variance-component mixed effect model is preferable for other multivariate analysis in most circumstances. Two approaches are illustrated through one case study from a preclinical experiment.

A cellular automaton model to find the risk of developing autism through gut-mediated effects.

BACKGROUND: One of the risk factors for the development of Autism Spectrum Disorder (ASD) is hypothesized to be an imbalance in the gut microbiome. Alterations in the relative numbers of gut microbiota may contribute to such a disruption in normal bacterial diversity. It is assumed that this process may be adequately mirrored for the purpose of the current paper by modeling the dynamic shifts in the numbers of three bacterial species, namely Clostridium, Desulfovibrio, and Bifidobacterium. Such imbalances in the gut microbiome are thought to promote the development of increased gut permeability (the so-called "leaky gut") which in turn is a potential risk factor for the development of ASD. METHODS: We constructed a mathematical model using 2-D Cellular Automata to simulate the growth rates and interactions of three bacterial species, namely Bifidobacterium, Clostridium and Desulfovibrio, with each other and with available nutrients in the gut, and particularly following the introduction of lysozyme into the gut. RESULTS: It was observed from the modeled simulation that increasing or decreasing the population of Clostridium in the gut produces key shifts in the gut microbiome which could potentially increase or decrease the risk of ASD. CONCLUSION: Simulations using our cellular automaton model suggest that it could be useful in predicting the effects produced by alterations to key components of the gut microbiome. In particular, the model demonstrated that the introduction of lysozyme in the gut results in steep reductions in Clostridium growth rate, which in turn could potentially alter the gut microbiome population in such a way as to significantly reduce the risk of developing ASD.

Radiological analysis of the sella turcica and its correlations with body mass index in a North Indian population.

OBJECTIVES: The sella turcica is an important component situated in the mid-third of the cranial fossa. Knowledge about its normal morphologies and dimensions may play a crucial role in diagnosing underlying pathologies. The present study aimed to analyze the principal morphological shapes of the sella turcica, measure its linear dimensions, and determine whether any correlations exist between its dimensions and body mass index (BMI) in subjects in a North Indian population. METHODS: The study was conducted on 100 subjects (50 men; 50 women) who underwent cone-beam computed tomography scans at our Oral Medicine and Radiology Department. The subjects had an age range of 20-60 years. The morphology of the sella turcica was examined according to age and various measurements were taken to determine its size. Possible correlations between the dimensions of the sella turcica and BMI were evaluated by statistical analysis. RESULTS: In the present study, 69% of the subjects had a normal morphology. No uniform increases in length, width, and depth of the sella turcica were observed with aging. When Pearson correlation coefficients were calculated, no strong correlations were found between the dimensions of the sella turcica and BMI. A mild correlation was seen between the length and width of the sella turcica. CONCLUSION: No significant correlations were found between the dimensions of the sella turcica and BMI in the present study. These findings may have arisen through the small sample size, and thus further studies with larger groups of subjects are warranted.

Granzyme B: evidence for a role in the origin of myasthenia gravis.

PURPOSE OF RESEARCH: Although the pathogenesis of myasthenia gravis (MG) as an antibody mediated disorder of acetylcholine receptors (AChRs) at neuromuscular junctions is well understood, the origin of the autoimmune response is unclear. The thymus is intimately involved in initiation of the autoimmune response; the antigen, AChR, is present in the thymus, but how the autoimmune response is triggered is not known. Granzyme B (GrB), a proteolytic enzyme present in cytolytic T cells and natural killer (NK) cells, selectively cleaves many potential autoantigens (but few non-autoantigens), generating novel fragments that trigger autoreactive responses. This protease has been strongly implicated in the pathogenesis of several autoimmune diseases including lupus, rheumatoid arthritis, dermatomyositis, and others. In the studies described in this manuscript, we examined the ability of GrB to cleave the AChR subunits, and performed biochemical, immunohistochemical and molecular studies on thymus glands from myasthenic patients and controls to assess GrB expression. MAIN RESULTS: GrB efficiently and specifically cleaves subunits of AChR, especially the epsilon subunit. GrB is present in thymus glands from myasthenia patients, but is absent in control thymuses. CONCLUSIONS: Our results provide evidence supporting a potential role for GrB in the process of initiation of MG, and are consistent with the concept of an immunodominant epsilon epitope.

Use of Ponseti's technique in recurrent clubfeet following Kite's method of correction.

We report the results of 18 recurrent clubfeet in 13 children after Kite's method of casting treated successfully by Ponseti's technique. The average age was 8.3 months. The average preoperative Pirani's midfoot contracture score was 1.8, hindfoot contracture score was 2.4, and total score was 4.2. All patients had full correction of deformities with plantigrade feet and the scores were reduced to zero at the end of treatment. Three recurrences were found at 6 months follow-up, amounting to 17% failure rate. Two of them necessitated percutaneous tenotomy of the tendoachilles, and one underwent posteromedial soft tissue release with good result at the end of 1 year. Ponseti's method is an effective treatment option in the management of recurrent clubfeet after Kite's method. Although short-term results are promising, larger series with long-term follow-up is warranted.

Congenital pseudarthrosis of the ulna.

We report a case of congenital pseudarthrosis of the ulna along with generalized neurofibromatosis (type I). The patient had a good clinical outcome after single-bone forearm reconstruction. In the setting of radial head dislocation following long-standing congenital pseudarthrosis of the ulna, single-bone forearm reconstruction is a viable option. It prevents the loss of hand function by the effective shortening of flexor tendons and spares movements of the humeroulnar and radiocarpal joints.

An amphipathic trans-acting phosphorothioate RNA element delivers an uncharged phosphorodiamidate morpholino sequence in mdx mouse myotubes.

An efficient method for the delivery of uncharged polyA-tailed phosphorodiamidate morpholino sequences (PMO) in mammalian cells consists of employing a synthetic 8-mer amphipathic trans-acting poly-2'-O-methyluridylic thiophosphate triester element (2'-OMeUtaPS) as a transfection reagent. Unlike the dTtaPS DNA-based element, this RNA element is potent at delivering polyA-tailed PMO sequences to HeLa pLuc 705 cells or to myotube muscle cells. However, much like dTtaPS, the 2'-OMeUtaPS-mediated internalization of PMO sequences occurs through an energy-dependent mechanism; macropinocytosis appears to be the predominant endocytic pathway used for cellular uptake. The transfected PMO sequences induce alternate splicing of either the pre-mRNA encoding luciferase in HeLa pLuc 705 cells or the excision of exon 23 from the pre-mRNA encoding dystrophin in myotube muscle cells of the mdx mouse model of muscular dystrophy with an efficiency comparable to that of commercial cationic lipid reagents but without detrimental cytotoxicity.

Airway Diseases Education and Expertise (ADEX ) in Pediatrics: Adaptation for Clinical Practice in India.

JUSTIFICATION: Asthma and allergic rhinitis together are part of the concept of one airway, one disease or united airway disease. The management of allergic airway diseases should address this united concept and manage the issue by educating the patients and their parents and health care providers, along with environmental control measures, pharmacotherapy and immunotherapy. Here, we present recommendations from the module of Airway Diseases Education and Expertise (ADEX) that focused on allergic rhinitis, asthma and sleep disorder breathing as a single entity or Allergic Airway Disease. PROCESS: A working committee was formed by the collaboration of Pediatric Allergy Association of India (PAAI) and Indian Academy of Pediatrics (IAP) Allergy and Applied Immunology chapter to develop a training module on united airway disease. OBJECTIVE: To increase awareness, understanding and acceptance of the concept of United Airway disease and to educate the primary health care providers for children and public health officials, in the management of united airway diseases. RECOMMENDATIONS: Recommendations for diagnosis, management and follow-up of Allergic airway disease are presented in this document. A better compliance by linking education of child, parent, grandparents and other health care providers, and scientific progress by collaboration between practitioners, academicians, researchers and pharmaceutical companies is suggested.

Scrub typhus: audit of an outbreak.

OBJECTIVES: To document the epidemiological, clinical and laboratory profile of all children with scrub typhus at a tertiary care centre in Chennai between September 2010 and June 2011. METHODS: The case records of all children admitted and diagnosed with scrub typhus between September 2010 and June 2011 were analysed to look for salient clinical and laboratory parameters. RESULTS: During the study period, 52 children were admitted with scrub typhus in the authors' hospital. The presenting complaints included fever in all cases. Other symptoms included swelling of legs (50 %) and vomiting (45 %). 13 % presented with CNS symptoms. The commonest physical findings included eschar (67 %), hepatomegaly (94 %), splenomegaly (73 %) and third spacing (67 %). Salient lab parameters included packed cell volume (PCV) <30 (48 %), leucocytosis (56 %), positive C-reactive protein (CRP) (92 %), hypoalbuminemia (79 %). Common complications included acute kidney injury (10 %) and peripheral gangrene (4 %). There was no mortality in the present case series. CONCLUSIONS: The clinical profile of children with scrub typhus in a tertiary care centre is reported. Eschar and hepatosplenomegaly with a high CRP value is helpful in diagnosis. All patients responded well to the treatment.

Design, architecture and application of nanorobotics in oncology.

Oncologists all over the globe, relentlessly research on methodologies for detection of cancer and precise localization of cancer therapeutics with minimal adverse effects on healthy tissues. Since the previous decade, the fast growing research in nanotechnology has shown promising possibilities for achieving this dream of every oncologist.Nanorobots (or nanobots) are typical devices ranging in size from 0.1 to 10 µm and constructed of nanoscale or molecular components. Robots will augment the surgeon's motor performance, diagnostic capability and sensations with haptics and augmented reality. The article here aims in briefly describing the architecture of the nanorobots and their role in oncotherapy. Although, research into nanorobots is still in its preliminary stages, the promise of such technology is endless.

Experimental autoimmune uveitis: molecular mimicry and oral tolerance.

Intraocular inflammatory disease or uveitis, which affects the uveal tract and the retina of the eyes in human, is the major cause of visual impairment. Experimental autoimmune uveitis (EAU) is a T-cell-mediated autoimmune disease directed against retinal proteins and has been studied in several mammalian species including subhuman primates as a model for human posterior uveitis. Autoimmune responses provoked by molecular mimicry occur when the nonself and host determinants are similar enough to cross-react yet different enough to break immunological tolerance, and is one of the proposed mechanisms for induction of autoimmune diseases. Therapeutic immunomodulatory strategies have been used to induce antigen-specific peripheral immune tolerance in animal models of T-cell-mediated autoimmune diseases by oral administration of autoantigens. Oral tolerance leads to unique mechanisms of tissue and disease-specific immunosuppression, which would circumvent the immunotherapeutic problem of multiple target tissue autoreactivity. Several groups have investigated the effects of delivering autoantigens across gastric mucosal surfaces. This review briefly discusses molecular mimicry and the mechanism of induction of oral tolerance with respect to immunopathogenesis of T-cell-mediated autoimmune disease in general and EAU in particular.

Adeno-associated virus in normal and myositis human skeletal muscle.

The normal tissue tropism of adeno-associated virus (AAV) is poorly defined, although the majority of humans test seropositive for this virus. Eighty-five muscle biopsy specimens were tested for AAV genomes; AAV DNA was identified in 17% of normal and 10% of Duchenne muscular dystrophy muscle biopsy specimens, but in only 3% of peripheral blood samples. AAV genomes were absent from all 37 muscle biopsy specimens from patients with myositis tested. Muscle is a major target organ for AAV, and infection is associated with autoimmune disease of muscle.

Modulation of disease severity in mice with targeted disruption of the acid alpha-glucosidase gene.

Glycogen storage disease type II (GSDII) is a recessively inherited disorder caused by defects in lysosomal acid alpha-glucosidase. In an attempt to reproduce the range of clinical manifestations of the human illness we have created null alleles at the acid alpha-glucosidase locus (GAA) with several gene targeting strategies. In each knockout strain, enzyme activity was completely abolished and glycogen accumulated at indistinguishable rates. The phenotypes, however, differed strikingly. Acid alpha-glucosidase deficiency on a 129xC57BL/6 background resulted in a severe phenotype with progressive cardiomyopathy and profound muscle wasting similar to that in patients with glycogen storage disease type II. On a 129/C57BL/6xFVB background, homozygous mutants developed a milder phenotype with a later age of onset. Females were more affected than males irrespective of genetic background. As in humans with glycogen storage disease type II, therefore, other genetic loci affect the phenotypic expression of a single gene mutation.

Lack of in vitro lymphoproliferative response to hepatitis B surface antigen in healthy vaccine recipients.

A majority of HBsAg vaccine recipients show good anti-HBs antibody responses but poor antigen specific lymphoproliferative responses. We investigated the basis for this poor in vitro antigen specific proliferative responsiveness in vaccinees who had received the standard three dose schedule (0, 1 and 6 months) of plasma derived HBsAg vaccine. Peripheral blood mononuclear cells (PBMC) from 26 of 29 (89.7%) vaccinees failed to show lymphoproliferative responses to HBsAg in spite of having a very good anti-HBs antibody response (geometric mean titre 3154 IU/1). The mitogen (phytohaemagglutinin, PHA) and antigen (purified protein derivative, PPD) driven lymphoproliferative responses in these individuals were normal. Addition of exogenous recombinant interleukin-2 (rIL-2) along with HBsAg had no effect in the response to HBsAg in six of nine vaccinees, who were tested six months after the third vaccine dose or in four unvaccinated controls. However, in three vaccinees who did not have lymphoproliferative response to HBsAg alone, addition of exogenous rIL-2 resulted in a synergistic response. These data suggest that HBsAg reactive cells are few in the peripheral circulation of a majority of individuals following the standard three dose schedule of vaccination and addition of exogenous rIL-2 induces a response only in a subgroup of individuals. The inability of HBsAg to induce a T cell proliferative response may have implications for the maintenance of protective immunity and immunological memory following vaccination.

Chronic hepatitis B virus carriers have low lymphoproliferative responses to HBsAg and reduced interleukin-2 synthesis.

BACKGROUND: Chronic carriers of hepatitis B virus (HBV) have impairment of lymphoproliferative responses. Recently HBV infection of peripheral blood mononuclear cells (PBMC) has been reported. The defect in the proliferative capacity of carrier PBMC has not been correlated to the presence of HBV in these cells. METHODS: PBMC of fourteen HBV carriers and 14 healthy individuals were stimulated with phytohemagglutinin (PHA), pokeweed mitogen (PWM) or anti-CD3 for 3 days and with HBsAg and purified protein derivative (PPD) for 6 days. The supernatants of unstimulated and PHA-stimulated PBMC cultures were bioassayed for interleukin-2 (IL-2); the supernatants of unstimulated and lipopolysaccharide (LPS)-stimulated cultures were bioassayed for IL-1. DNA extracted from PBMC was hybridized with a 32P-labeled HBV probe to look for HBV DNA. RESULTS: HBV carriers' PBMC showed impaired responses to PHA, PWM and anti-CD3. No carrier demonstrated lymphoproliferative response to hepatitis B surface antigen (HBsAg). Seven of eight carriers with impaired HBsAg-specific proliferative responses who were tested for their response to an unrelated antigen showed a positive response to PPD. PBMC from HBV carriers produced similar amounts of IL-1 as normal PBMC on LPS stimulation; however, they produced significantly lower amounts of IL-2 as compared to normal PBMC under both spontaneous and PHA-stimulated conditions. HBV DNA was demonstrable in the PBMC of all fourteen carriers. CONCLUSIONS: The abnormal immune function found in chronic HBV carriers may be a consequence of replicative viral infection of the mononuclear cells.