Smart Contract Authentication assisted GraphMap-Based HL7 FHIR architecture for interoperable e-healthcare system.

The exponential growth in the global population and significant advancements in healthcare broadened the scope of intervention for e-Healthcare through decentralized data access and information exchange, making complex clinical decisions. e-Healthcare can perform several functionalities, including EHR communication, telemedicine, and complex clinical decision systems (CCDS), but large-scale users still find it challenging to maintain interoperability, stability, and scalability. Accommodating an extensive array of stakeholders, which includes patients, doctors, hospitals, and laboratories, demands interoperability to serve scalable services. FHIR frameworks have played a vital role in e-Healthcare designs. Most of the existing HL7-FHIR frameworks have used REST-API using HTTP-query for CRUD tasks that impose numerous rules and constraints, making the process more complex and time-consuming, violating the quality-of-service (QoS) standards on different levels. This paper develops a novel, robust Smart-Contract Authentication Assisted HL7-FHIR framework toward an interoperable e-Healthcare solution. Unlike classical REST API-based FHIR, our proposed method applies a Graph-mapping concept that transforms each resource variable into an equivalent Graph-Mapped Data Structure (GMS), which is subsequently stored in the NoSQL MongoDB database, reducing computational costs and time to meet QoS demands. The proposed model employs three key components, GMS-driven HL7 FHIR Gateway Model, Smart Contract Authentication and Client Model. The Smart Contract function helped verify and authenticate users to ensure privacy and secure EHR exchange. The assessment of the performance of the proposed model reveals a significant reduction in computational time with optimal resource utilization making it a significant and viable option to better the real-world e-Healthcare mechanisms.

Dynamic Data Infrastructure Security for Interoperable e-Healthcare Systems: A Semantic Feature-Driven NoSQL Intrusion Attack Detection Model.

The exponential rise in advanced software computing and low-cost hardware has broadened the horizon for the Internet of Medical Things (IoMT), interoperable e-Healthcare systems serving varied purposes including electronic healthcare records (EHRs) and telemedicine. However, being heterogeneous and dynamic in nature, their database security remains a challenge forever. Numerous intrusion attacks including bot-attack and malware have confined major classical databases towards e-Healthcare. Despite the robustness of NoSQL over the structured query language databases, the dynamic data nature over a heterogeneous environment makes it vulnerable to intrusion attacks, especially over interoperable e-Healthcare systems. Considering these challenges, this work proposed a first of its kind semantic feature-driven NoSQL intrusion attack (NoSQL-IA) detection model for interoperable e-Healthcare systems. This work assessed the efficacy of the different semantic feature-extraction methods like Word2Vec, Continuous Bag of Words, N-Skip Gram (SKG), Count Vectorizer, TF-IDF, and GLOVE towards NoSQL-IA prediction. Subsequently, to minimize computational exhaustion, different feature selection methods including Wilcoxon Rank Sum Test (WRST), significant predictor test, principal component analysis, Select K-Best, and variance threshold feature selection algorithms were employed. To alleviate the data imbalance problem, it applied different resampling methods including upsampling, downsampling, and synthetic minority oversampling technique (SMOTE) over the selected features. Later, Min-Max normalization was performed over the input feature vectors to alleviate any possibility of overfitting. Towards NoSQL-IA prediction, different machine learning methods like Multinomial Naïve Bayes, decision tree, logistic regression, support vector machine, k-NN, AdaBoost, Extra Tree Classifier, random forest ensemble, and XG-Boost were applied, which classified each input query as the regular query or the NoSQL-IA attack query. The depth performance assessment revealed that the use of Word2Vec features SKG in sync with VTFS feature selection and SMOTE resampling processed with the bootstrapped random forest classifier can provide the best performance in terms of high accuracy (98.86%), F-Measure (0.974), and area under the curve (AUC) (0.981), thus enabling it suitable for interoperable e-Healthcare database security.

Techno economic analysis of malic acid production using crude glycerol derived from waste cooking oil.

In the present work, Aspergillus niger was employed to produce commercially valuable malic acid from crude glycerol derived from waste cooking oil. Crude glycerol dosage, yeast extract dosage and initial pH were the influencing factors playing a significant role in the malic acid synthesis. The optimal condition for malic acid biosynthesis was studied by using response surface methodology. Further the feasibility analysis for biosynthesis of malic acid from crude glycerol was studied using the laboratory scale optimized data, with this experimentally optimized data, plant was simulated using SuperPro Designer (v10). The cost involved for malic acid synthesis per unit volume was likely expected to be $0.43/kg of malic acid using reactive extraction method. Thus, process optimization combined with techno-economical analysis of malic acid production could be beneficial.

Comparative analysis of two discretizations of Ricci curvature for complex networks.

We have performed an empirical comparison of two distinct notions of discrete Ricci curvature for graphs or networks, namely, the Forman-Ricci curvature and Ollivier-Ricci curvature. Importantly, these two discretizations of the Ricci curvature were developed based on different properties of the classical smooth notion, and thus, the two notions shed light on different aspects of network structure and behavior. Nevertheless, our extensive computational analysis in a wide range of both model and real-world networks shows that the two discretizations of Ricci curvature are highly correlated in many networks. Moreover, we show that if one considers the augmented Forman-Ricci curvature which also accounts for the two-dimensional simplicial complexes arising in graphs, the observed correlation between the two discretizations is even higher, especially, in real networks. Besides the potential theoretical implications of these observations, the close relationship between the two discretizations has practical implications whereby Forman-Ricci curvature can be employed in place of Ollivier-Ricci curvature for faster computation in larger real-world networks whenever coarse analysis suffices.

Kyasanur Forest Disease - First Reported Case in Kerala.

Kyasanur Forest disease is a tick-borne arboviral fever with biphasic course of illness with prominent hemorrhagic features in the first phase and encephalitic picture in the second phase. So far it has been described in the southern Karnataka only. Here we report a case of Kyasanur Forest Disease for the first time from Kerala in an 18 year old male from Noolpuzha - Alathoor colony of Wayanad district.

Cowden syndrome with Lhermitte- Duclos disease presenting as ataxia.

Cowden syndrome or multiple hamartoma syndrome is a rare genodermatosis of autosomal dominant inheritance characterized by multiple hamartomatous lesions of ectodermal, mesodermal and endodermal origin. A 45-year-old man presented to us with a history of dural arteriovenous fistula and intracerebral bleed in the past with gradually progressive difficulty in walking. Magnetic resonance imaging (MRI) of the brain showed a heterogeneous lesion in the cerebellum which was diagnosed as adult Lhermitte-Duclos disease which is considered a component of Cowden syndrome. On examination we found florid skin and mucosal manifestations of Cowden syndrome. A family history of thyroid malignancy was also present. Using the Cleveland Clinic web calculator, the patient had an 82% chance of having a phosphatase and tensin homologue (PTEN) mutation.

Vimentin is a component of a complex that binds to the 5'-UTR of human heme-regulated eIF2α kinase mRNA and regulates its translation.

The human heme-regulated eIF2α kinase, also called the human heme-regulated inhibitor (hHRI) is significantly up-regulated particularly at the level of translation during stress. In this report we show that during lead-stress, the regulation of hHRI mRNA translation is mediated through its 5'-untranslated region (UTR) that interacts with specific trans-acting factors. Further, vimentin has been identified as one of the trans-acting factors that contribute to this regulation.

Interfacial interactions involved in the biological assembly of Chandipura virus nucleocapsid protein.

The biological assembly of Chandipura virus nucleocapsid (N) protein has been modeled and the amino acid residues involved in specific intermolecular interactions among N monomers during oligomerisation have been predicted.

Deciphering the host-pathogen protein interface in chikungunya virus-mediated sickness.

Successful infection with chikungunya virus (CHIKV) depends largely on the ability of this virus to manipulate cellular processes in its favour through specific interactions with several host factors. The knowledge of virus-host interactions is of particular value for understanding the interface through which therapeutic strategies could be applied. In the current study, the authors have employed a computational method to study the protein interactions between CHIKV and both its human host and its mosquito vector. In this structure-based study, 2028 human and 86 mosquito proteins were predicted to interact with those of CHIKV through 3918 and 112 unique interactions, respectively. This approach could predict 40 % of the experimentally confirmed CHIKV-host interactions along with several novel interactions, suggesting the involvement of CHIKV in intracellular cell signaling, programmed cell death, and transcriptional and translational regulation. The data corresponded to those obtained in earlier studies for HIV and dengue viruses using the same methodology. This study provides a conservative set of potential interactions that can be employed for future experimental studies with a view to understanding CHIKV biology.

Mapping interactions of Chikungunya virus nonstructural proteins.

The four nonstructural proteins (nsPs1-4) of Chikungunya virus (CHIKV) play important roles involving enzymatic activities and specific interactions with both viral and host components, during different stages of viral pathogenesis. Elucidation of the presence and/or absence of interactions among nsPs in a systematic manner is thus of scientific interest. In the current study, each pair-wise combination among the four nonstructural proteins of CHIKV was systematically analyzed for possible interactions. Six novel protein interactions were identified for CHIKV, using systems such as yeast two-hybrid, GST pull down and ELISA, three of which have not been previously reported for the genus Alphavirus. These interactions form a network of organized associations that suggest the spatial arrangement of nonstructural proteins in the late replicase complex. The study identified novel interactions as well as concurred with previously described associations in related alphaviruses.

Intraviral protein interactions of Chandipura virus.

Chandipura virus (CHPV) is an emerging rhabdovirus responsible for several outbreaks of fatal encephalitis among children in India. The characteristic structure of the virus is a result of extensive and specific interplay among its five encoded proteins. The revelation of interactions among CHPV proteins can help in gaining insight into viral architecture and pathogenesis. In the current study, we carried out comprehensive yeast two-hybrid (Y2H) analysis to elucidate intraviral protein-protein interactions. All of the interactions identified by Y2H were assessed for reliability by GST pull-down and ELISA. A total of eight interactions were identified among four viral proteins. Five of these interactions are being reported for the first time for CHPV. Among these, the glycoprotein (G)-nucleocapsid (N) interaction could be considered novel, as this has not been reported for any members of the family Rhabdoviridae. This study provides a framework within which the roles of the identified protein interactions can be explored further for understanding the biology of this virus at the molecular level.

Conformational transitions of the catalytic domain of heme-regulated eukaryotic initiation factor 2α kinase, a key translational regulatory molecule.

In mammalian cells, the heme-regulated inhibitor (HRI) plays a critical role in the regulation of protein synthesis at the initiation step through phosphorylation of α-subunit of the eukaryotic initiation factor 2 (eIF2). In this study we have cloned and performed biophysical characterization of the kinase catalytic domain (KD) of rabbit HRI. The KD described here comprises kinase 1, the kinase insertion domain (KI) and kinase 2. We report here the existence of an active and stable monomer of HRI (KD). The HRI (KD) containing three tryptophan residues was examined for its conformational transitions occurring under various denaturing conditions using steady-state and time-resolved tryptophan fluorescence, circular dichroism (CD) and hydrophobic dye binding. The parameter A and phase diagram analysis revealed multi-state unfolding and existence of three stable intermediates during guanidine hydrochloride (Gdn-HCl) induced unfolding of HRI (KD). The protein treated with 6 M Gdn-HCl showed collisional and static mechanism of acrylamide quenching and the constants (K(sv) = 3.08 M(-1) and K(s)= 5.62 M(-1)) were resolved using time resolved fluorescence titration. Based on pH, guanidine hydrochloride and temperature mediated transitions, HRI (KD) appears to exemplify a rigid molten globule-like intermediate with compact secondary structure, altered tertiary structure and exposed hydrophobic patches at pH 3.0. The results indicate the inherent structural stability of HRI (KD), a member of the class of stress response proteins.

Reviewing host proteins of Rhabdoviridae: possible leads for lesser studied viruses.

Rhabdoviridae, characterized by bullet-shaped viruses, is known for its diverse host range, which includes plants, arthropods, fishes and humans. Understanding the viral-host interactions of this family can prove beneficial in developing effective therapeutic strategies. The host proteins interacting with animal rhabdoviruses have been reviewed in this report. Several important host proteins commonly interacting with animal rhabdoviruses are being reported, some of which, interestingly, have molecular features, which can serve as potential antiviral targets. This review not only provides the generalized importance of the functions of animal rhabdovirus-associated host proteins for the first time but also compares them among the two most studied viruses, i.e. Rabies virus (RV) and Vesicular Stomatitis virus (VSV). The comparative data can be used for studying emerging viruses such as Chandipura virus (CHPV) and the lesser studied viruses such as Piry virus (PIRYV) and Isfahan virus (ISFV) of the Rhabdoviridae family.

Primary haemophagocytic syndrome in a young girl.

Haemophagocytic syndrome is a life-threatening systemic illness characterized by an uncontrolled inflammatory response. Patients present with fever, hepatosplenomegaly, jaundice and liver dysfunction, neurological manifestations and often pancytopenla. Bone marrow, lymph node, hepatic or splenic biopsy shows macrophages with Ingested blood cells or their precursors. Laboratory markers include elevated triglycerides and ferritin, low fibrinogen with normal or low erythrocyte sedimentation rate (ESR). Familial haemophagocytic lymphohistiocytosis (HLH) is an autosomal recessive disorder. Secondary haemophagocytic syndrome results from infections, malignancy and collagen vascular disorders. We describe a young girl with primary haemophagocytic syndrome.

Oestrus ovis ophthalmomyiasis with keratitis.

A 35-year-old male patient presented with complaints of redness, swelling around the eyelids, watering, and irritation in the right eye. At presentation his best-corrected visual acuity was 20/20 partial in the right eye. The tarsal conjunctiva of the upper eyelid showed injection with pseudomembrane. Underneath the pseudomembrane we noticed four motile larvae. The cornea showed an irregular cobweb-like mucous plaque adherent to the epithelium, with a clear stroma. The pseudomembrane was easily peeled-off under topical anaesthesia. The organisms were removed and identified as Oestrus ovis. Three days later the patient was comfortable and his visual acuity was 20/20 in the right eye.

Distance between RBS and AUG plays an important role in overexpression of recombinant proteins.

The spacing between ribosome binding site (RBS) and AUG is crucial for efficient overexpression of genes when cloned in prokaryotic expression vectors. We undertook a brief study on the overexpression of genes cloned in Escherichia coli expression vectors, wherein the spacing between the RBS and the start codon was varied. SDS-PAGE and Western blot analysis indicated a high level of protein expression only in constructs where the spacing between RBS and AUG was approximately 40 nucleotides or more, despite the synthesis of the transcripts in the representative cases investigated.

Conformational characterization of human eukaryotic initiation factor 2alpha: a single tryptophan protein.

The alpha-subunit of the human eukaryotic initiation factor 2 (heIF2alpha), a GTP binding protein, plays a major role in the initiation of protein synthesis. During various cytoplasmic stresses, eIF2alpha gets phosphorylated by eIF2alpha-specific kinases resulting in inhibition of protein synthesis. The cloned and over expressed heIF2alpha, a protein with a single tryptophan (trp) residue was examined for its conformational characteristics using steady-state and time-resolved tryptophan fluorescence, circular dichroism (CD) and hydrophobic dye binding. The steady-state fluorescence spectrum, fluorescence lifetimes (tau(1)=1.13ns and tau(2)=4.74ns) and solute quenching studies revealed the presence of trp conformers in hydrophobic and differential polar environment at any given time. Estimation of the alpha-helix and beta-sheet content showed: (i) more compact structure at pH 2.0, (ii) distorted alpha-helix and rearranged beta-sheet in presence of 4M guanidine hydrochloride and (iii) retention of more than 50% ordered structure at 95 degrees C. Hydrophobic dye binding to the protein with loosened tertiary structure was observed at pH 2.0 indicating the existence of a molten globule-like structure. These observations indicate the inherent structural stability of the protein under various denaturing conditions.