Discrimination of pediatric cryptogenic multifocal ulcerous stenosing enteritis from small bowel Crohn's disease and gastrointestinal tuberculosis: A retrospective study (with videos).

INTRODUCTION: Cryptogenic multifocal ulcerous stenosing enteritis (CMUSE) is a rare entity that mimics various inflammatory strictures of the small intestine. Pediatric literature is scarce. We analyzed the clinical, radiological, endoscopic and histopathological features of children with CMUSE that differentiate it from small bowel Crohn's disease (SBCD) and gastrointestinal tuberculosis (GITB). METHODS: CMUSE was diagnosed by the following criteria: (1) unexplained small bowel strictures with superficial ulcers, (2) chronic/relapsing ulcers of small bowel after resection, (3) no signs of systemic inflammation, (4) absence of other known etiologies of small bowel ulcers. SBCD and GITB were diagnosed based on standard criteria. The clinical features, laboratory parameters, radioimaging, endoscopy (including video capsule endoscopy [VCE], intra-operative endoscopy), histopathological features and treatment outcome were noted. RESULTS: Out of 48, CMUSE was diagnosed in 13 (27%) isolated small bowel and ileocecal strictures, while GITB and SBCD accounted for 41% and 21% cases, respectively. Common presentations were sub-acute obstruction (46%), obscure gastrointestinal bleeding (38%) and protein-losing enteropathy (38%). CMUSE patients had significantly longer disease duration compared to SBCD and GITB (p < 0.001). SBCD (90.0%) and GITB (85%) cases had elevated C-reactive protein (CRP), none with CMUSE had elevated CRP (p < 0.001). The disease was localized in jejunum (100%) and proximal ileum (56%) in CMUSE, ileocecal region (85%) in GITB, but evenly distributed in small intestine in SBCD. Endoscopy showed evenly placed, superficial, circumferential ulcers with strictures in CMUSE, deep linear ulcers in SBCD and circumferential ulcers in GITB. Upfront immunosuppression was given in four; three (75%) of them relapsed. Only surgery was done in three with one (25%) having relapse. Upfront surgery followed by immunosuppression was used in six, but all relapsed and two required repeat surgery. CONCLUSION: CMUSE is important but underdiagnosed in children. Lack of constitutional symptoms, normal inflammatory parameters and characteristic ulcers with strictures helped in differentiating CMUSE from GITB and SBCD.

Exploring aptamers for targeted enrichment of X sperm in bovine: unraveling selective potential.

Nucleic acid aptamers have been used in the past for the development of diagnostic methods against a number of targets such as bacteria, pesticides, cancer cells etc. In the present study, six rounds of Cell-SELEX were performed on a ssDNA aptamer library against X-enriched sperm cells from Sahiwal breed cattle. Sequencing was used to examine the aptamer sequences that shown affinity for sperm carrying the X chromosome in order to find any possible X-sperm-specific sequences. Out of 35 identified sequences, 14 were selected based on bioinformatics analysis like G-Score and Mfold structures. Further validation of their specificity was done via fluorescence microscopy. The interaction of biotinylated-aptamer with sperm was also determined by visualizing the binding of streptavidin coated magnetic beads on the head region of the sperm under bright field microscopy. Finally, a real-time experiment was designed for the validation of X-sperm enrichment by synthesized aptamer sequences. Among the studied sequences, aptamer 29a exhibited a higher affinity for X sperm compared to Y sperm in a mixed population of sperm cells. By using aptamer sequence 29a, we obtained an enrichment of 70% for X chromosome bearing sperm cells.

Impact assessment of integrated-pathy on cancer-related fatigue in cancer patients: an observational study.

BACKGROUND: Integrated-pathy aims to integrate modern medicine with traditional systems via applying the holistic approach of Ayurveda, Yoga, and natural medicine. This is important for addressing the challenges surrounding the delivery of long-term palliative care for chronic ailments including cancer. The prime intent of this study was to substantiate the underlying hypothesis behind the differential and integrative approach having a positive impact on Quality of Life of cancer patients. STUDY DESIGN: Cross-sectional Observational study. METHODS: A standardized questionnaire was developed and used, after obtaining written informed consent from patients to assess the impact of Integrated-pathy on patients (n = 103) diagnosed with cancer receiving care at Patanjali Yoggram. The research was carried out over 8 months. All participants received a uniform treatment protocol as prescribed by Patanjali. For the sample size determination and validation, α and 1-ß was calculated and for the significance of the pre- and post-treatment QoL ratings, Shapiro wilk test and other descriptive statistics techniques were explored. RESULTS: A total of 103 patients seeking cancer special-healthcare were interviewed, out of which 39 (37.86%) remained finally based on the inclusion/exclusion criteria with age (25-65 years), types of cancers (Carcinoma and Sarcoma), chemotherapy/radiotherapy received or not, before opting Integrated-pathy. Follow-ups revealed a significant increase in the QoL (17.91%) after receiving the integrated therapy over a course of at least 1 month. Further, a significant reduction in cancer-related pain followed by an increase in QoL index was reported in the patients. Shapiro-wilk test revealed significant pairing (p < 0.001) with validation of the model using test. CONCLUSIONS: To bolster evidence-based backing for Integrated-pathy, there is a need for clearly delineated clinical indicators that are measurable and trackable over time. Clinical investigators are encouraged to incorporate Integrated-pathy into their proposed interventions and conduct analogous studies to yield sustained advantages in the long run.

Physico-Chemical and Rheological Trait-Based Identification of Indian Wheat Varieties Suitable for Different End-Uses.

India has increased its wheat production phenomenally in the last two decades and it now has a buffer stock of 9.7 million tonnes. However, despite the release of several wheat cultivars, the end-use quality traits of Indian wheat varieties have not been explored in-depth to determine the increasing demand of the domestic processing industry as well as export. In this study, 55 wheat genotypes including 47 released varieties, and 8 genetic stocks were grown along with 10 Australian varieties grown during cropping seasons: 2019-2020 and 2020-2021 and diversity in different physiochemical and rheological traits was evaluated. They showed considerable diversity in all the quality traits studied. However, very few genotypes could be found suitable for any one end-use. Five genotypes were found to possess four to five traits for superior bread-making quality. Two varieties and three advanced breeding lines had up to four good chapati quality traits. None of the released varieties investigated had suitable traits for biscuit making; however, two breeding lines possessed requisite quality traits suitable for biscuit making. It is, therefore, concluded that systematic breeding efforts are required to develop genotypes that bring together the most important quality traits in a single genotype to be suitable for domestic industry as well as for export.

Alzheimer's disease: A role of biomarkers in early diagnosis and evidences from African ethnomedicinal knowledge.

Alzheimer's disease (AD) is a neurological ailment that primarily affects the elderly and necessitates an efficient treatment regimen backed up by extensive care. Despite advancement in the in vivo imaging techniques focussing on early diagnosis of reliable biomarkers using novel magnetic resonance imaging (MRI) and positron emission topography (PET) scans, AD remains largely unexplained and effective preventative and treatment strategies are still lacking. Consequently, research groups are constantly attempting to improve its early detection, using both invasive and non-invasive techniques with established core markers like Aß and Tau (t-tau and p-tau) proteins. Unfortunately, African American and other black races are facing an increasing burden of closely associated risk factors, and only a few attempts have been made to find effective complementary and alternative therapies for AD cure and management. A greater epidemiology and natural product research are required to deal with the concurrent rise of dementia among quickly ageing African population, which so far have largely been ignored in addition to a disparity in the AD risk factors. We have tried to bring attention to the issue by reviewing up on this predisposition while generating a perspective on how race may affect AD risk and expression. This article also puts emphasis on finding new research leads from African phytodiversity while presenting several of the important species along with their biological agents found helpful in dementia related symptoms.

Hereditary fructose intolerance: A comprehensive review.

Hereditary fructose intolerance (HFI) is a rare autosomal recessive inherited disorder that occurs due to the mutation of enzyme aldolase B located on chromosome 9q22.3. A fructose load leads to the rapid accumulation of fructose 1-phosphate and manifests with its downstream effects. Most commonly children are affected with gastrointestinal symptoms, feeding issues, aversion to sweets and hypoglycemia. Liver manifestations include an asymptomatic increase of transaminases, steatohepatitis and rarely liver failure. Renal involvement usually occurs in the form of proximal renal tubular acidosis and may lead to chronic renal insufficiency. For confirmation, a genetic test is favored over the measurement of aldolase B activity in the liver biopsy specimen. The crux of HFI management lies in the absolute avoidance of foods containing fructose, sucrose, and sorbitol (FSS). There are many dilemmas regarding tolerance, dietary restriction and occurrence of steatohepatitis. Patients with HFI who adhere strictly to FSS free diet have an excellent prognosis with a normal lifespan. This review attempts to increase awareness and provide a comprehensive review of this rare but treatable disorder.

Skin Cancer Diagnosis Based on Neutrosophic Features with a Deep Neural Network.

Recent years evidenced an increase in the total number of skin cancer cases, and it is projected to grow exponentially. This paper proposes a computer-aided diagnosis system for the classification of a malignant lesion, where the acquired image is primarily pre-processed using novel methods. Digital artifacts such as hair follicles and blood vessels are removed, and thereafter, the image is enhanced using a novel method of histogram equalization. Henceforth, the pre-processed image undergoes the segmentation phase, where the suspected lesion is segmented using the Neutrosophic technique. The segmentation method employs a thresholding-based method along with a pentagonal neutrosophic structure to form a segmentation mask of the suspected skin lesion. The paper proposes a deep neural network base on Inception and residual blocks with softmax block after each residual block which makes the layer wider and easier to learn the key features more quickly. The proposed classifier was trained, tested, and validated over PH2, ISIC 2017, ISIC 2018, and ISIC 2019 datasets. The proposed segmentation model yields an accuracy mark of 99.50%, 99.33%, 98.56% and 98.04% for these datasets, respectively. These datasets are augmented to form a total of 103,554 images for training, which make the classifier produce enhanced classification results. Our experimental results confirm that the proposed classifier yields an accuracy score of 99.50%, 99.33%, 98.56%, and 98.04% for PH2, ISIC 2017, 2018, and 2019, respectively, which is better than most of the pre-existing classifiers.

Generation of Ince-Gaussian Beams Using Azocarbazole Polymer CGH.

Ince-Gaussian beams, defined as a solution to a wave equation in elliptical coordinates, have shown great advantages in applications such as optical communication, optical trapping and optical computation. However, to ingress these applications, a compact and scalable method for generating these beams is required. Here, we present a simple method that satisfies the above requirement, and is capable of generating arbitrary Ince-Gaussian beams and their superposed states through a computer-generated hologram of size 1 mm2, fabricated on an azocarbazole polymer film. Other structural beams that can be derived from the Ince-Gaussian beam were also successfully generated by changing the elliptical parameters of the Ince-Gaussian beam. The orthogonality relations between different Ince-Gaussian modes were investigated in order to verify applicability in an optical communication regime. The complete python source code for computing the Ince-Gaussian beams and their holograms are also provided.

Genome-wide association study identifies loci and candidate genes for grain micronutrients and quality traits in wheat (Triticum aestivum L.).

Malnutrition due to micronutrients and protein deficiency is recognized among the major global health issues. Genetic biofortification of wheat is a cost-effective and sustainable strategy to mitigate the global micronutrient and protein malnutrition. Genomic regions governing grain zinc concentration (GZnC), grain iron concentration (GFeC), grain protein content (GPC), test weight (TW), and thousand kernel weight (TKW) were investigated in a set of 184 diverse bread wheat genotypes through genome-wide association study (GWAS). The GWAS panel was genotyped using Breeders' 35 K Axiom Array and phenotyped in three different environments during 2019-2020. A total of 55 marker-trait associations (MTAs) were identified representing all three sub-genomes of wheat. The highest number of MTAs were identified for GPC (23), followed by TKW (15), TW (11), GFeC (4), and GZnC (2). Further, a stable SNP was identified for TKW, and also pleiotropic regions were identified for GPC and TKW. In silico analysis revealed important putative candidate genes underlying the identified genomic regions such as F-box-like domain superfamily, Zinc finger CCCH-type proteins, Serine-threonine/tyrosine-protein kinase, Histone deacetylase domain superfamily, and SANT/Myb domain superfamily proteins, etc. The identified novel MTAs will be validated to estimate their effects in different genetic backgrounds for subsequent use in marker-assisted selection.

Assessment of Functional Characterization and Comparability of Biotherapeutics: a Review.

The development of monoclonal antibody (mAb) biosimilars is a complex process. The key to their successful development and commercialization is an in-depth understanding of the key product attributes that impact safety and efficacy and the strategies to control them. Functional assessment of mAb is a crucial part of the comparability of biopharmaceutical drugs. The development of a relevant and robust functional assay requires an interdisciplinary approach and sufficient flexibility to balance regulatory concerns as well as dynamics and variability during the manufacturing process. Although many advanced tools are available to study and compare the potency and bioactivity of the protein, most of these techniques suffer from major shortcomings that limit their routine use. These include the complexity of the task, establishment of the relevance of the chosen method with the mechanism of action (MOA) of the biosimilar, cost and extended time of analysis, and often the ambiguity in interpretation of the resulting data. To overcome or to address these challenges, the use of multiple orthogonal state-of-the-art techniques is a necessary prerequisite.

Identification of Novel Genomic Regions for Biofortification Traits Using an SNP Marker-Enriched Linkage Map in Wheat (Triticum aestivum L.).

Micronutrient and protein malnutrition is recognized among the major global health issues. Genetic biofortification is a cost-effective and sustainable strategy to tackle malnutrition. Genomic regions governing grain iron concentration (GFeC), grain zinc concentration (GZnC), grain protein content (GPC), and thousand kernel weight (TKW) were investigated in a set of 163 recombinant inbred lines (RILs) derived from a cross between cultivated wheat variety WH542 and a synthetic derivative (Triticum dicoccon PI94624/Aegilops tauschii [409]//BCN). The RIL population was genotyped using 100 simple-sequence repeat (SSR) and 736 single nucleotide polymorphism (SNP) markers and phenotyped in six environments. The constructed genetic map had a total genetic length of 7,057 cM. A total of 21 novel quantitative trait loci (QTL) were identified in 13 chromosomes representing all three genomes of wheat. The trait-wise highest number of QTL was identified for GPC (10 QTL), followed by GZnC (six QTL), GFeC (three QTL), and TKW (two QTL). Four novel stable QTL (QGFe.iari-7D.1, QGFe.iari-7D.2, QGPC.iari-7D.2, and QTkw.iari-7D) were identified in two or more environments. Two novel pleiotropic genomic regions falling between Xgwm350-AX-94958668 and Xwmc550-Xgwm350 in chromosome 7D harboring co-localized QTL governing two or more traits were also identified. The identified novel QTL, particularly stable and co-localized QTL, will be validated to estimate their effects on different genetic backgrounds for subsequent use in marker-assisted selection (MAS). Best QTL combinations were identified by the estimation of additive effects of the stable QTL for GFeC, GZnC, and GPC. A total of 11 RILs (eight for GZnC and three for GPC) having favorable QTL combinations identified in this study can be used as potential donors to develop bread wheat varieties with enhanced micronutrients and protein.

Peptide profiling in cow urine reveals molecular signature of physiology-driven pathways and in-silico predicted bioactive properties.

Peptidomics allows the identification of peptides that are derived from proteins. Urinary peptidomics has revolutionized the field of diagnostics as the samples represent complete systemic changes happening in the body. Moreover, it can be collected in a non-invasive manner. We profiled the peptides in urine collected from different physiological states (heifer, pregnancy, and lactation) of Sahiwal cows. Endogenous peptides were extracted from 30 individual cows belonging to three groups, each group comprising of ten animals (biological replicates n = 10). Nano Liquid chromatography Mass spectrometry (nLC-MS/MS) experiments revealed 5239, 4774, and 5466 peptides in the heifer, pregnant and lactating animals respectively. Urinary peptides of <10 kDa size were considered for the study. Peptides were extracted by 10 kDa MWCO filter. Sequences were identified by scanning the MS spectra ranging from 200 to 2200 m/z. The peptides exhibited diversity in sequences across different physiological states and in-silico experiments were conducted to classify the bioactive peptides into anti-microbial, anti-inflammatory, anti-hypertensive, and anti-cancerous groups. We have validated the antimicrobial effect of urinary peptides on Staphylococcus aureus and Escherichia coli under an in-vitro experimental set up. The origin of these peptides was traced back to certain proteases viz. MMPs, KLKs, CASPs, ADAMs etc. which were found responsible for the physiology-specific peptide signature of urine. Proteins involved in extracellular matrix structural constituent (GO:0005201) were found significant during pregnancy and lactation in which tissue remodeling is extensive. Collagen trimers were prominent molecules under cellular component category during lactation. Homophilic cell adhesion was found to be an important biological process involved in embryo attachment during pregnancy. The in-silico study also highlighted the enrichment of progenitor proteins on specific chromosomes and their relative expression in context to specific physiology. The urinary peptides, precursor proteins, and proteases identified in the study offers a base line information in healthy cows which can be utilized in biomarker discovery research for several pathophysiological studies.

LC-MS based case-by-case analysis of the impact of acidic and basic charge variants of bevacizumab on stability and biological activity.

The present study investigates the impact of charge variants on bevacizumab's structure, stability, and biological activity. Five basic and one acidic charge variants were separated using semi-preparative cation exchange chromatography using linear pH gradient elution with purity > 85%. Based on the commercial biosimilar product's composition, two basic variants, one acidic and the main bevacizumab product, were chosen for further investigation. Intact mass analysis and tryptic peptide mapping established the basic variants' identity as those originating from an incomplete clipping of either one or both C-terminal lysine residues in the heavy chain of bevacizumab. Based on peptide mapping data, the acidic variant formation was attributed to deamidation of asparagine residue (N84), oxidation of M258, and preservation of C-terminal lysine residue, located on the heavy chain of bevacizumab. None of the observed charge heterogeneities in bevacizumab were due to differences in glycosylation among the variants. The basic (lysine) variants exhibited similar structural, functional, and stability profiles as the bevacizumab main product. But it was also noted that both the variants did not improve bevacizumab's therapeutic utility when pooled in different proportions with the main product. The acidic variant was found to have an equivalent secondary structure with subtle differences in the tertiary structure. The conformational difference also translated into a ~ 62% decrease in biological activity. Based on these data, it can be concluded that different charge variants behave differently with respect to their structure and bioactivity. Hence, biopharmaceutical manufacturers need to incorporate this understanding into their process and product development guidelines to maintain consistency in product quality.

Antimicrobial Peptides in Farm Animals: An Updated Review on Its Diversity, Function, Modes of Action and Therapeutic Prospects.

Antimicrobial peptides (AMPs) are the arsenals of the innate host defense system, exhibiting evolutionarily conserved characteristics that are present in practically all forms of life. Recent years have witnessed the emergence of antibiotic-resistant bacteria compounded with a slow discovery rate for new antibiotics that have necessitated scientific efforts to search for alternatives to antibiotics. Research on the identification of AMPs has generated very encouraging evidence that they curb infectious pathologies and are also useful as novel biologics to function as immunotherapeutic agents. Being innate, they exhibit the least cytotoxicity to the host and exerts a wide spectrum of biological activity including low resistance among microbes and increased wound healing actions. Notably, in veterinary science, the constant practice of massive doses of antibiotics with inappropriate withdrawal programs led to a high risk of livestock-associated antimicrobial resistance. Therefore, the world faces tremendous pressure for designing and devising strategies to mitigate the use of antibiotics in animals and keep it safe for posterity. In this review, we illustrate the diversity of farm animal-specific AMPs, and their biochemical foundations, mode of action, and prospective application in clinics. Subsequently, we present the data for their systematic classification under the major and minor groups, antipathogenic action, and allied bioactivities in the host. Finally, we address the limitations of their clinical implementation and envision areas for further advancement.

Development of integrated neonatal cholestasis card for early recognition and referral of neonatal cholestasis.

INTRODUCTION AND AIM: Delayed referral of neonatal cholestasis (NC) can result in significant morbidity and mortality. In this multi-center study, we aimed to evaluate the reliability of the stool card in the Indian population and develop an integrated NC card with (a) urine color identification and (b) stool color for early referral. METHODS: Consecutive children with NC were enrolled and divided into two groups (biliary atresia [BA] and non-BA). Normal healthy children at 6-8 weeks of age served as controls. Each photograph of stool and urine samples of every child was evaluated by 6 parents, 6 paramedical staff, and 4 trainee doctors using a stool color card as a reference for stool samples. RESULTS: Of 319 children (BA [n = 58], non-BA [n = 62], and controls [n = 199]), parents correctly detected dark yellow urine in all NC. Stool samples of 50 (86%) children with BA were unanimously labeled as pale by all observers. The average inter-item correlation showed good correlation between parents and trainee doctors of 0.77 and 0.64 with paramedical staff. CONCLUSION: The integrated NC card proposes to recognize neonatal cholestasis at an early stage irrespective of etiology. It is a major step towards public health benefit both at the community as well as physicians' levels to enable early detection and timely referral and management.

Understanding Oxidation Propensity in GCSF and Assessment of its Safety and Efficacy.

PURPOSE: To understand the impact of methionine oxidation in GCSF on efficacy (neutrophil production/activation) and safety (biochemical and histopathological changes). METHODS: Nine GCSF biosimilars were analyzed for the levels of residual iron and copper content. Oxidation in GCSF was induced by H2O2 treatment and four samples were prepared: wtGCSF (no oxidation), MetO (1138), MetO (1,138,127) and MetO (1138,127,122). These samples were used to evaluate binding affinity with the GCSF receptor (GCSFR) using biolayer interferometry, thermal stability using circular dichroism and in vitro potency using a relevant cell-based assay. In vivo pharmacodynamics examined changes in neutrophil production upon GCSF methionine oxidation, with the outcome correlated with the differential expression of genes implicated in the GCSF mediated neutrophil activation/ maturation. Pre-clinical safety studies including biochemical and histopathological changes were also performed. RESULTS: Met 122 and Met 127 have the most deleterious effect on the potency. Lower binding affinity with GCSFR was identified as the underlying cause for lower efficacy and potency. Role of Asp 110 in GCSF as the critical residue having adverse impact on efficacy in context of methionine oxidation has been elucidated. Impairment of in vitro binding affinity with GCSF manifests as in vivo pharmacodynamic differences via differential expression of downstream genes required for neutrophil maturation. CONCLUSION: The data from the present study suggests that methionine oxidation in GCSF is a critical quality attribute that needs careful monitoring and control during commercial manufacturing and subsequent supply chain stages.

Modulation of granulocyte colony stimulating factor conformation and receptor binding by methionine oxidation.

Biosimilars offer an avenue for potential cost savings and enhanced patient access to various emerging therapies in a budget neutral way. Biosimilars of the granulocyte colony stimulating factor (GCSF) are an excellent example in this regard with as many as 18 versions of the drug being currently approved across globe for treatment of neutropenia. Here, we identified oxidation of the various methionine residues in GCSF as a key heterogeneity that adversely impact its efficacy. In agreement with earlier studies, it was found that oxidation of Met 122 and Met 127 significantly contributes toward reduction of GCSF efficacy, measured using binding affinity to the GCSF receptor. The combination of molecular dynamics simulation along with structural characterization studies established that oxidation of Met 127 and Met 122 brings about a small local conformational change around the B-C loop in GCSF structure due to slight displacement of Asp113 and Thr117 residues. The simulation studies were validated using fluorescence quenching experiments using acrylamide as quencher and site-directed mutagenesis by replacing Met 122 and Met 127 residues with alanine. The results of this study lead to an enhanced mechanistic understanding of the oxidation in GCSF and should be useful in protein engineering efforts to design stable, safe, and efficacious GCSF product. In addition, the structure-function information can provide targets for protein engineering during early drug development and setting specifications of allowable limits of product variants in biosimilar products.

Melanoma Diagnosis Using Deep Learning and Fuzzy Logic.

Melanoma or malignant melanoma is a type of skin cancer that develops when melanocyte cells, damaged by excessive exposure to harmful UV radiations, start to grow out of control. Though less common than some other kinds of skin cancers, it is more dangerous because it rapidly metastasizes if not diagnosed and treated at an early stage. The distinction between benign and melanocytic lesions could at times be perplexing, but the manifestations of the disease could fairly be distinguished by a skilled study of its histopathological and clinical features. In recent years, deep convolutional neural networks (DCNNs) have succeeded in achieving more encouraging results yet faster and computationally effective systems for detection of the fatal disease are the need of the hour. This paper presents a deep learning-based 'You Only Look Once (YOLO)' algorithm, which is based on the application of DCNNs to detect melanoma from dermoscopic and digital images and offer faster and more precise output as compared to conventional CNNs. In terms with the location of the identified object in the cell, this network predicts the bounding box of the detected object and the class confidence score. The highlight of the paper, however, lies in its infusion of certain resourceful concepts like two phase segmentation done by a combination of the graph theory using minimal spanning tree concept and L-type fuzzy number based approximations and mathematical extraction of the actual affected area of the lesion region during feature extraction process. Experimented on a total of 20250 images from three publicly accessible datasets-PH2, International Symposium on Biomedical Imaging (ISBI) 2017 and The International Skin Imaging Collaboration (ISIC) 2019, encouraging results have been obtained. It achieved a Jac score of 79.84% on ISIC 2019 dataset and 86.99% and 88.64% on ISBI 2017 and PH2 datasets, respectively. Upon comparison of the pre-defined parameters with recent works in this area yielded comparatively superior output in most cases.

Late-Onset Hepatic Failure in Children: Risk Factors that Determine the Outcome.

BACKGROUND: Late-onset hepatic failure (LOHF) is a distinct entity of intractable liver diseases with limited pediatric experience. We aimed to identify the etiology and risk factors that determine the poor outcome (PO) of pediatric LOHF. METHODS: LOHF was defined as liver failure occurring 5-24 weeks after onset of jaundice and without any evidence of underlying chronic liver disease. PO (death or liver transplantation within 160 days) was compared with spontaneous recovery (SR; complete normalization of liver functions in the native liver). Pediatric end-stage liver disease (PELD) score and King's College Criteria (KCC) were applied to investigate their prognostic value. RESULTS: We enrolled 47 children (6 [2-16] years) with LOHF. Hepatitis A was the most common etiology (15, 32%) and 64% complicated with infections. Twelve children (25%) had SR over 6 (1-24) months, while 28 (60%) children had PO. Univariate analysis showed indeterminate etiology, hepatic encephalopathy (HE), infection, acute kidney injury, and high PELD score determined PO. On multivariate regression analysis, only PELD score with a cutoff 32 (area under curve 0.833, sensitivity 68%, specificity 92%) predicted PO. KCC showed a sensitivity of 85.7%, specificity of 41.7% to determine PO in our cohort. CONCLUSION: Indeterminate etiology, presence of HE, occurrence of infection at any site, and acute kidney injury lead to the PO. PELD score ≥32 can be utilized to optimize the listing for liver transplantation. A significant proportion survives with the native liver.

Ascitic fluid infection in children with liver disease: time to change empirical antibiotic policy.

BACKGROUND AND AIMS: Recent years have shown a rise in occurrence of multidrug resistant ascitic fluid infection (AFI) including resistant to third generation cephalosporins. Our aim was to find the prevalence, antibiotics resistance and outcome of AFI in children with liver disease. METHODS: Children (≤ 18 years) with liver disease-related ascites were prospectively enrolled from April 2015 to October 2017. Based on the results of ascitic fluid examination and culture, patients were classified as having AFI [spontaneous bacterial peritonitis (SBP), culture negative neutrocytic ascites (CNNA) and monomicrobial non-neutrocytic bacterascites (MNB)] and no-AFI. AFI diagnosed after 48 h of index hospitalization was considered as nosocomial. RESULTS: We enrolled 194 children with a median age of 85 [2-216] months. Chronic liver disease was the commonest etiology (153, 79%). AFI was present in 60 (31%) children [SBP (n = 13), CNNA (n = 39), MNB (n = 8)] of which 53% were nosocomial and resulted in high in-hospital mortality. Gram-negative bacilli dominated the ascitic fluid culture (12/21, 57%) and 10/12 (83%) of them were extended spectrum beta-lactamases (ESBL) producers. Six (60%) ESBL producers were sensitive to cefoperazone-sulbactam and 70% to carbapenems. Child-Pugh-Turcotte (CPT) score of ≥ 11 independently determined in-hospital mortality in children with AFI. CONCLUSIONS: AFI was found in 31% children with liver disease and almost half of them were nosocomial resulting in high mortality. ESBL producing Gram-negative bacteria were the most frequently isolated organisms. Cefoperazone-sulbactam or carbapenems may be useful empirical antibiotics in nosocomial setting. Children with AFI and CPT score ≥ 11 should be evaluated for liver transplantation.