In silico screening of potential plant peptides against the Non-structural proteins of Dengue virus.

BACKGROUND OBJECTIVES: Peptides isolated from different sources of plants have the advantages of specificity, lower toxicity, and increased therapeutic effects; hence, it is necessary to search for newer antivirals from plant sources for the treatment of dengue viral infections. METHODS: In silico screening of selected plant peptides against the non-structural protein 1, NS3 protease domain (NS2B-NS3Pro) with the cofactor and ATPase/Helicase domain (NS3 helicase domain/NS3hel) of Dengue virus was performed. The physicochemical characteristics of the peptides were calculated using Protparam tools, and the allergenicity and toxicity profiles were assessed using allergenFP and ToxinPred, respectively. RESULTS: Among the tested compounds, Ginkbilobin demonstrated higher binding energy against three tested non-structural protein targets. Kalata ß-8 demonstrated maximum binding energy against NSP-1 and NSP-2, whereas Circulin A acted against the NSP3 protein of the dengue virus. INTERPRETATION CONCLUSION: Hence, the three compounds identified by in silico screening can be tested further for in vitro studies, which could act as potential leads as they are involved in hampering the replication of the dengue virus by interacting with the three prime non-structural proteins.

In silico screening of potential plant peptides against the non-structural proteins of dengue virus.

BACKGROUND OBJECTIVES: Peptides isolated from different sources of plants have the advantages of specificity, lower toxicity, and increased therapeutic effects; hence, it is necessary to search for newer antivirals from plant sources for the treatment of dengue viral infections. METHODS: In silico screening of selected plant peptides against the non-structural protein 1, NS3 protease domain (NS2B-NS3Pro) with the cofactor and ATPase/helicase domain (NS3 helicase domain/NS3hel) of dengue virus was performed. The physicochemical characteristics of the peptides were calculated using Protparam tools, and the allergenicity and toxicity profiles were assessed using allergenFP and ToxinPred, respectively. RESULTS: Among the tested compounds, Ginkbilobin demonstrated higher binding energy against three tested nonstructural protein targets. Kalata B8 demonstrated maximum binding energy against NSP-1 and NSP-2, whereas Circulin A acted against the NSP3 protein of dengue virus. INTERPRETATION CONCLUSION: The three compounds identified by in silico screening can be tested in vitro, which could act as potential leads as they are involved in hampering the replication of the dengue virus by interacting with the three prime non-structural proteins.

Pediatric cancer-associated thrombosis: Analysis from a tertiary care cancer center in India.

BACKGROUND AND AIMS: Thrombotic events (TEs) have been extensively studied in adult cancer patients, but data in children are limited. We prospectively analyzed pediatric cancer-associated thrombosis (PCAT) in children with malignancies. METHODS: Children below 15 years of age with confirmed malignancies, treated at a large tertiary cancer center in India from July 2015 to March 2020 developing any TE were eligible. A standardized approach for detection and management was followed. Data were collected after informed consent. RESULTS: Of 6132 eligible children, 150 (2.44%) had 152 TEs, with median age 8.5 years and male:female of 1.83:1. Most TEs occurred on chemotherapy: 111 (74.0%). The most common site was central nervous system (CNS) 59 (39.3%), followed by upper-limb venous system 37 (24.7%). Hemato-lymphoid (HL) malignancies were more prone to PCAT than solid tumors (ST) (incidence 3.23% vs. 1.58%; odds ratio [OR] = 2.06, 95% confidence interval [CI] [1.36-2.88]; p < .001). Malignancies associated with PCAT were acute lymphoblastic leukemia (ALL) 2.94%, acute myeloid leukemia (AML) 6.66%, and non-Hodgkin lymphomas 5.35%. Response imaging done in 106 (70.7%) children showed complete to partial resolution in almost 90% children. Death was attributable to TE in seven (4.66%) children. Age above 10 years (OR 2.33, 95% CI [1.59-3.41]; p < .001), AML (OR 4.62, 95% CI [1.98-10.74]; p = .0062), and non-Hodgkin lymphoma (OR 4.01, 95% CI [1.15-14.04]; p = .029) were significantly associated with TEs. In ALL, age more than 10 years (OR 1.86, 95% CI [1.06-3.24]; p < .03), T-ALL (OR 3.32, 95% CI [1.69-6.54]; p = .001), and intermediate-risk group (OR 4.97, 95% CI [1.12-22.02]; p = .035) were significantly associated with thrombosis. The 2-year event-free survival (EFS) for HL malignancies with PCAT was 55.3% versus 72.1% in those without PCAT (p = .05), overall survival (OS) being 84.6% versus 80.0% (p = .32). CONCLUSION: Incidence of PCAT was 2.4%, and occurred predominantly in older children with hematolymphoid malignancies early in treatment. Most resolved completely with low molecular weight heparin (LMWH) and mortality was low. In hematolymphoid malignancies, PCAT reduce EFS, highlighting the need for prevention.

Neuropsychiatric manifestations are associated with increased mortality in Indian patients with lupus: A single centre retrospective observational study.

OBJECTIVE: To study the prevalence of different NPSLE manifestations in our cohort and to compare clinical and immunological features and outcomes including mortality of patients with NPSLE and SLE controls without NP involvement. METHODS: This was a retrospective study in a tertiary care referral centre. All patients of SLE seen in the last 10 years and fulfilling the SLICC criteria with neuropsychiatric manifestations as per the ACR definitions were included. Patients of SLE without NP involvement were sequentially assigned as controls in a ratio of 1:2. RESULTS: Of the 769 patients diagnosed with SLE from Jan 2011 to December 2020, 128 (16.6%) had NPSLE manifestations as per the ACR definitions. The commonest NPSLE manifestation was seizures (6.5%) followed by cerebrovascular accident (3.9%). NPSLE manifestation occurred at the first presentation of SLE in 99/128 (77.3%) patients and 58 (45.3%) patients had more than one NPSLE manifestation. Lupus anticoagulant and anticardiolipin antibody were tested in 120 patients and were positive in 16 (13.3%) and 12 (10%), respectively. No difference was found in anti-ribosomal p, lupus anticoagulant and anticardiolipin antibodies between the cases and controls. Twenty-one (16.4%) deaths occurred in patients with NPSLE (median follow-up of 40 months) as compared to 13 (5%) in controls (median follow-up of 32 months) (p = <0.001). The cumulative survival of patients with NPSLE was lower as compared to controls (p < 0.001). Relapse of NPSLE was seen in 11(8.6%) patients and was associated with mortality (p = 0.017). CONCLUSIONS: Seizures and cerebrovascular accidents are the commonest NPSLE syndromes in our patients. The presence of NPSLE was associated with high mortality in Indian patients with lupus.

Adopting a vein assessment tool improves procedural outcomes in double dose platelet collections - A prospective study.

BACKGROUND: This study aims to determine the phlebotomy and procedural outcomes using a vein assessment tool (VAT) in Double Dose Platelet (DDP) collections by apheresis. METHODS: VAT was based on assessing vein visibility, palpation and size with maximum score of 12 and the least being 0 and the scores were graded as adequate and inadequate. A vein-viewer was used for studying cubital vein patterns (type 1-5). Phlebotomy outcome was defined based on need for re-puncture. Procedural outcomes in terms of target yield attained and RBC reinfusion completed. Chi square test and Mann- Whitney U test were used to assess the vein score and pattern against phlebotomy and procedural outcome. RESULTS: Out of 200 DDP collections, the phlebotomy was successful in 88 % with good procedural outcome in 94 % donations. The cut off in VAT scores for successful phlebotomy was ≥8 (AUC: 70 %). Median vein scores of the arm selected for phlebotomy was 9 and graded adequate in 154 (77 %) donations.Odds for successful phlebotomy was 3.7 times higher when donors had an adequate VAT grades(p = 0.003). Procedural outcomes was favourable when at least one arm had adequate VAT grade when compared to both arms being inadequate (98 % vs 82 %; p < 0.001). Phlebotomy failure was more with first time apheresis donors than repeat apheresis donors (p = 0.014). CONCLUSION: This study indicated that a VAT score with a cut off of ≥8 had better phlebotomy and procedural outcomes in DDP collections and that donor with at least one arm having the VAT score of ≥8 are preferred for DDP collections.

Recurrent hyperhemolytic transfusion reaction in myelodysplastic syndrome- A case based approach.

We present here a case report of a 27 year old female, with myelodysplatic syndrome suspected to have recurrent hyperhemolytic transfusion reactions (HHTR). Patient was transfusion dependent for ten years and was transfused with leukodepleted and irradiated Packed Red Blood Cells (PRBC). She presented with signs and symptoms of acute intravascular hemolysis, deranged coagulation profile with post transfusion Hb lower than baseline. Post transfusion workup was uneventful. She was managed conservatively with fluid support and methylprednisolone initially. After few uneventful transfusions, patient developed second episode of HHTR with compatible unit.Immunophenotype favored an inflammatory response possibly induced by monocytic lineage. As transfusion dependent, the patient required methylprednisolone as premedication and all subsequent transfusions were uneventful.

Expression of p16INK4a in oropharyngeal squamous cell carcinoma from a tertiary cancer centre of South India: A preliminary study.

Background & objectives: Human papillomavirus (HPV) and oropharyngeal squamous cell carcinoma (OPSCC) are found to be strongly associated with each other with an increase in incidence has been noted globally over the years. A literature search for data depicting the role of HPV in oropharyngeal carcinoma in South India, however, has resulted in little information, thus, the present study was aimed to assess a possible association between the two among OPSCC patients from a tertiary care cancer centre in South India. Methods: One hundred and fourty three OPSCC cases were included in the study and analyzed for age, gender, marital status, habits, clinical TNM staging, site, laterality, symptoms, histological type (keratinizing and non-keratinizing), primary treatment and follow up period. All the cases were subjected to p16INK4a immunostaining. Statistical analysis was done using SPSS software. Results: Of the 143 cases 12 were found to be p16 positive with no significant difference between the study variables among p16 positive and negative cases. Base of the tongue was the most commonly involved site for the p16 positive cases. The p16 positive cases presented at an elderly age, early stage and were mainly the keratinizing type. Interpretation & conclusions: The p16 positive OPSCC cases constituted a small proportion in the present study and behaved similar to p16 negative cases. Usage of tobacco and alcohol appear to be the susceptible factors even in p16 positive cases. More studies from other States would be helpful to determine if HPV-related SCC in the Indian subcontinent behave differently or similarly to cases from Western countries.

Molecular docking and antiviral activities of plant derived compounds against zika virus.

Zika virus (ZIKV), a recently emerged pathogen of the genus flavivirus causes Guillain-Barré syndrome and microcephaly in fetus and newborns . Until date, there are no licensed vaccine or approved drug to treat ZIKV infection. Thus, in this study, 5550 phytochemicals retrieved from various databases were subjected for molecular docking in Discovery studio V.4.0 against the ZIKV helicase protein and envelope protein domain III. In addition, in silico ADMET and Density function theory studies were performed to retain the final hit compounds. Further, four of the identified compounds (eleutheroside B, neoandrographolide, apigenin, and madecassic acid) were tested for in vitro cytotoxicity and antiviral activities against ZIKV. Except madecassic acid, the other three compounds reduced ZIKV infection at non-cytotoxic concentrations. Hence, this study encourages the screening of more phytochemicals against druggable targets of ZIKV to identify new promising drug candidates.

Functional variations between Mesenchymal Stem Cells of different tissue origins: A comparative gene expression profiling.

BACKGROUND: Mesenchymal Stem Cells (MSCs), regardless of the tissue sources, are considered as excellent candidates for cellular therapy as they are immune-privileged cells containing a multitude of therapeutic functions that aid in tissue regeneration and repair. For the effective application of these cells in cell therapy, it is important to understand and characterize their biological functions. OBJECTIVES: The present study attempts to characterize the variations in multipotent function such as cell surface antigen levels, proliferation, differentiation and stemness (pluripotency) potential of MSCs isolated from foetal [wharton's jelly (WJ), foetal and maternal side of placenta (PF and PM)] and adult tissue sources [bone marrow (BM) and adipose tissue (AT)] using gene expression by real time PCR (qRT-PCR). RESULTS: Amongst the different tissue sources, PM, PF and AT-MSCs exhibited significant increase (p < 0.001, p < 0.001 and p < 0.01 respectively) in CD 73 expression and therefore could have a role in immunomodulation. WJ-MSCs exhibited superior proliferation potential based on growth curve, PCNA and Wnt gene expression. BM-MSCs were superior in exhibiting trilineage differentiation. Enhanced stemness potential (Oct 4 and Nanog) was observed for both BM and WJ-MSCs. In addition, BM and WJ-MSCs expressed high levels of CD 90 making them suitable in bone repair and regeneration. CONCLUSION: Thus to conclude, out of the five different sources tested, BM an adult source and WJ-MSCs a foetal source were superior in exhibiting most of the biological functions indicating that these sources may be suitable candidates for cell repair and regeneration studies.

Dexamethasone promotes hypertrophy of H9C2 cardiomyocytes through calcineurin B pathway, independent of NFAT activation.

Metabolic syndrome-induced cardiac hypertrophy is a global concern leading to an increase in the morbidity and mortality of patients, with the signalling mechanism associated with them still unclear. The present study attempts to understand the metabolic syndrome-associated cardiac hypertrophy through an in vitro model using external stimuli well known for inducing metabolic disorders, i.e. dexamethasone (DEX), a synthetic glucocorticoid. DEX (0.1 and 1 µM) promoted cardiac hypertrophy in H9C2 cells at 4 days of treatment as evidenced through increased cell size and protein content. A significant induction in foetal gene reprogramming was observed, confirming the establishment of hypertrophy. Moreover, the hypertrophic response at 4 days was perceived to be physiological at 0.1 µM and pathological at 1 µM based on α-MHC and IGF1R expression, but complete inhibition in the PKB/AKT expression confirmed it to be pathological hypertrophy at both the concentrations (0.1 and 1 µM). The present study reports for the first time the mechanistic insights into DEX-mediated hypertrophy. It is hypothesized to be orchestrated through the activation of AT1R that is involved in the alteration of the cardiac isoform of SERCA2 expression perturbing the calcium homeostasis. This leads to the activation of calcineurin B, independent of NFAT involvement, which in coordination with ROS induces the activation of JNK of the MAPK signalling.

p53 mediates impaired insulin signaling in 3T3-L1 adipocytes during hyperinsulinemia.

Hyperinsulinemia is being implicated in the development of insulin resistance but remains poorly understood. The present study focuses on p53-mediated impaired insulin signaling by hyperinsulinemia in 3T3-L1 adipocytes. Hyperinsulinemia impairs insulin-stimulated glucose uptake and its cellular signaling in a dose- and time-dependent manner. An increased level of reactive oxygen species (ROS) and stress response signals were observed, and quenching of the ROS by an antioxidant N-acetylcysteine (NAC) did not revert impaired insulin sensitivity. The tumor suppressor p53 has emerged as a crucial factor in the metabolic adaptation of cancer cells under nutritional starvation and is being studied in the development of insulin resistance in adipocytes at physiological level. Interestingly, we observed hyperinsulinemia-enhanced p53 level in a time-dependent manner without exhibiting cytotoxicity. Transient knockdown of p53 partially improved insulin sensitivity revealing a novel link between p53 and insulin signaling in adipocytes. The findings suggest that hyperinsulinemia-induced p53 impairs insulin sensitivity in 3T3-L1 adipocytes.

Evaluation of cytocompatibility and cell proliferation of electrospun chitosan/polyvinyl alcohol/montmorillonite clay scaffold with l929 cell lines in skin regeneration activity and in silico molecular docking studies.

The present investigation describes the development of a novel Chitosan/Polyvinyl Alcohol/Montmorillonite Clay (CS/PVA/MMT) scaffold by adopting an electrospinning method, and their biocompatibility was evaluated in vitro with L929 fibroblast cell line to ascertain its use in wound healing applications. The fabricated scaffold was characterized using analytical techniques. FT-IR measurement exhibited the existence of relevant functional groups and XRD implies scaffolds' amorphous nature. The scaffold's morphology and pore diameter were assessed using TEM and SEM. The pore diameter of the as-prepared scaffold was approximately 125 nm. The antimicrobial assay of the scaffold was evaluated against selected pathogens which demonstrated higher antimicrobial efficacy. The scavenging activity tested using the DPPH assay showed remarkable scavenging capability. The wound healing properties were tested through the Cytotoxicity assay conducted on the L929 assay which proved the scaffold to be a suitable material for cell proliferation. Also, a Molecular docking investigation was carried out for CS/PVA/MMT ligand using human neutrophil elastase (HNE) 1H1B protein as a receptor in the CB-Dock server. Studies conducted in silico revealed strong interaction and high binding energy ratings of CS/PVA/MMT ligand with key residues of human neutrophil elastase (HNE) 1H1B proteins that help in tissue regeneration activity.

Whole genome based identification of BAHD acyltransferase gene involved in piperine biosynthetic pathway in black pepper.

Black pepper (Piper nigrum L.), a crop of the genus Piper, is an important spice that has both economic and ecological significance. It is widely regarded as the "King of Spices" because of its pungency, attributed to the presence of piperine. BAHD acyl transferase, the crucial enzyme involved in the final step in piperine biosynthesis was the focus of our study and the aim was to identify the candidate isoform involved in biosynthesis of piperine. Reference genome-based analysis of black pepper identified six BAHD-AT isoforms and mapping of these sequences revealed that the isoforms were situated on six distinct chromosomes. By using specific primers for each of these transcripts, qPCR analysis was done in different tissues as well as berry stages to obtain detectable amplification products. Expression profiles of isoforms from chromosome 6 correlated well with piperine content compared to other five isoforms, across tissues and was therefore assumed to be involved in biosynthesis of piperine. In addition to this, we could also identify the binding sites of MYB transcription factor in the cis-regulatory regions of the isoforms. We also used in-silico docking and molecular dynamics simulation to calculate the binding free energy of the ligand and confirmed that among all the isoforms, BAHD-AT from chromosome 6 had the lowest free binding energy and highest affinity towards the ligand. Our findings are expected to aid the identification of new genes connecting enzymes involved in the biosynthetic pathway of piperine, which will have major implications for future research in metabolic engineering.Communicated by Ramaswamy H. Sarma.

Origin and survival outcomes of Pseudomyxoma peritonei-A retrospective study.

BACKGROUND: Pseudomyxoma peritonei (PMP) is an unusual clinical condition typically presenting with widespread mucinous neoplastic lesions within the peritoneum resulting in gelatin material-rich ascites. It was first described by Werth in 1884. Ever since, its clinical presentation, definition, site of origin, and prognosis have been a subject of debate. However, many histopathologic, immunohistochemical, and genetic studies have attempted to locate the primary lesion in the appendix in both genders. OBJECTIVES: To analyze the histological origin and survival outcomes of pseudomyxoma peritonei in patients treated at a regional cancer center. MATERIALS AND METHODS: Fifteen cases of PMP were diagnosed during the five-year study period. The demographic and clinicopathological details were retrieved; the slides were reviewed and histological parameters reassessed. Descriptive statistics were used to express proportions. Continuous variables were recorded as mean (SD) or median (IQR). Kaplan-Meier (KM) curve was used to estimate overall survival. RESULTS: Mean age for PMP was found to be 47.5 years for low grade Mucinous Carcinoma Peritonei (MCP), 54.2 years for high grade MCP, and 58 years for high grade MCP with signet ring cells. Most common overall presentation was abdominal distension in 53.3% (8/15) of cases, followed by acute appendicitis in 20% (3/15) cases. PMP was detected synchronous with the primary tumor in 9/15 cases (60%). Primary lesion in the appendix was grossly identified in 7/15 cases, while it was not explored in the remaining eight cases. Yet, by combined clinical, radiological, histopathological, and immunohistochemical analysis, we identified that most of the cases (14/15) had an appendiceal origin (93.3%). The overall survival for 12 months was 50% and for 18 months was 37%. CONCLUSION: The surgeon and radiologist may well bear in mind the most common possibility of an appendiceal origin for PMP and resect the appendix, irrespective of the presence of a grossly or radiologically detectable lesions. We emphasize that immunohistochemistry helped to detect the site of origin even when the primary was occult.

In silico screening of plant peptides against the envelope protein of dengue virus.

Peptide therapeutics are found to be an emerging and attractive class of treatment due to their highly specific and safe nature. Hence twenty plant peptides were subjected to screening by molecular docking against the envelope protein of the dengue virus using Clus Pro, Patch Dock, and HADDOCK servers. Physicochemical parameters, allergenicity, and toxicity profile of the plant peptides were estimated by Protparam analysis, AllergenFP, and ToxinPred web servers. Six potential compounds namely Ginkbilobin, Cycloviolin-D, Circulin-B, Circulin-A, Cycloviolacin-013, and Circulin-C showed the highest binding energy with both nonallergenic and nontoxic properties. They also exhibited desirable half-lives extending to 30 hrs except for Ginkbilobin, which showed the least half-life of 4.4 hours and non-polar activity. The residues of Ala-4 of Ginkbilobin; Arg-30 of Cycloviolin D; Arg-29 of Circulin A and C interacted with the Try 101 of the domain II of Envelope protein, implying the possible inhibition of the insertion process of the trimeric E protein during fusion with the host cells. Thus, the identified plant peptides could serve as potential leads upon further subjection to in vitro studies.

Predicting donor-related factors for high platelet yield donations by classification and regression tree analysis.

INTRODUCTION: Collecting high-dose (HD) or double-dose (DD) apheresis platelets units from a single collection offers significant benefit by improving inventory logistics and minimizing the cost per unit produced. Platelet collection yield by apheresis is primarily influenced by donor factors, but the cell separator used also affects the collection yield. OBJECTIVES: To predict the cutoff in donor factors resulting in HD and DD platelet collections between Trima/Spectra Optia and MCS+ apheresis equipment using Classification and Regression Trees (CART) analysis. METHODS: High platelet yield collections (target ≥ 4.5 × 1011 platelets) using MCS+, Trima Accel and Spectra Optia were included. Endpoints were ≥ 6 × 1011 platelets for DD and ≥ 4.5 to < 6 × 1011 for HD collections. The CART, a tree building technique, was used to predict the donor factors resulting in high-yield platelet collections in Trima/Spectra Optia and MCS+ equipment by R programming. RESULTS: Out of 1,102 donations, the DDs represented 60% and the HDs, 31%. The Trima/Spectra Optia predicted higher success rates when the donor platelet count was set at ≥ 205 × 103/µl and ≥ 237 × 103/µl for HD and DD collections. The MCS+ predicted better success when the donor platelet count was ≥ 286 × 103/µl for HD and ≥ 384 × 103/µl for DD collections. Increased donor weight helped counter the effects of lower donor platelet counts only for HD collections in both the equipment. CONCLUSIONS: The donor platelet count and weight formed the strongest criteria for predicting high platelet yield donations. Success rates for collecting DD and HD products were higher in the Trima/Spectra Optia, as they require lower donor platelet count and body weight than the MCS+.

Ghost Cell Odontogenic Carcinoma with Sarcomatous Transformation : Report of a Rare Case with Review of Literature.

Ghost Cell Odontogenic Carcinoma is a rare malignant odontogenic tumor that can appear as "de novo " or arises from malignant transformation of preexisting benign calcifying odontogenic cysts or dentinogenic ghost cell tumors after multiple recurrences. Ghost cell odontogenic carcinoma is histopathologically characterized by ameloblast-like islands of epithelial cells with aberrant keratinization, simulating a ghost cell, with varying amounts of dysplastic dentine. This article reports an extremely rare case of ghost cell odontogenic carcinoma with foci of sarcomatous change, involving maxilla andnasal cavity which arose from a previously existing recurrent calcifying odontogenic cysts in a 54-year-old man and reviews the features of this unusual and rare tumor. To the best of our knowledge, this is the first case of ghost cell odontogenic carcinoma with sarcomatous transformation to be reported till date. Owing to its rarity and unpredictability of clinical course, long -term follow up of patients with ghost cell odontogenic carcinoma, is mandatory for observation of recurrence and distant metastasis. Keywords: Ghost cell odontogenic carcinoma, maxilla, sarcoma, calcifying odontogenic cysts, ghost cells, odontogenic tumour.

Intracellular Toll-Like Receptors Modulate Adaptive Immune Responses in Head and Neck Cancer.

The percentage of head and neck cancer (HNC) positive for human papillomavirus (HPV) is unknown in most parts of India. How toll-like receptors (TLRs) affect the adaptive immune response in HNC is also mainly unknown. We here assessed the expressions of HPV DNA, p16, inflammation, and TLRs in oral squamous cell carcinoma (OC) and oropharyngeal squamous cell carcinoma (OPC). Patients with OC (n = 31) and OPC (n = 41), diagnosed during 2017-2018 at the Malabar Cancer Centre (tertiary cancer center), Kerala, India, were included in the study. Immunohistochemistry was performed on tumor specimens against p16, TLR3, TLR7, TLR8, TLR9, CD4, and CD8. Quantitate polymerase chain reaction for 14 high-risk HPVs (HPV16/18/31/33/35/39/45/51/52/56/58/59/66/68) was performed. Seven out of 31 OC (22.6%) were p16+ but only 3.2% (1/31) of OC were positive for HPV DNA. While 24.4% (10/41) of OPC were p16+, HPV DNA was found in only one P16+ OPC and in no P16- OPC. TLR3, TLR7, TLR8, and TLR9 were expressed both in OC and in OPC. The expression of TLR7 was significantly higher in OPC compared with OC. TLR8 expression was correlated with and TLR7 tended to be correlated with the inflammatory score in OPC (r = 0.56, p < 0.05 and r = 0.52, p = 0.08, respectively). In conclusion, the role of HPV in OC and OPC is minor, and p16 constitutes a poor biomarker for HPV positivity in Kerala, India. Intracellular TLRs are correlated with the degree of inflammation in OPC but not in OC and may potentially constitute a medical target in the therapy of HNC in the future.

Frequency of EGFR mutations in lung adenocarcinoma patients - A study from tertiary cancer center of South India.

BACKGROUND AND OBJECTIVES: Epidermal growth factor receptor (EGFR) mutation analysis has become an important part of the initial workup of non-squamous non-small cell lung cancer (NS-NSCLC) patients. This study is attempted as South Indians population is comprised of ethnic groups with diverse genetic makeup and only very limited data on EGFR mutation is available from south India. A detailed understanding of EGFR mutation profile will help in better planning of treatment strategies and resource allocation. METHODS: A retrospective analysis of EGFR mutation frequency in 350 patients diagnosed with adenocarcinoma of lung and its association with pathological characteristics was done. RESULTS: Out of 350 cases of pulmonary adenocarcinoma, within an age group ranging from 30 to 86 years. EGFR mutations were identified in 34.8% (n = 122) cases, out of which 35.24% (n = 43) were in non-smoker females (P = 0.001). Of the 14 cases with resistant type of EGFR mutations, nine were in smoker males and the remaining five in non-smoker females. INTERPRETATION AND CONCLUSION: Overall EGFR mutation frequency observed in our study was similar to other Indian studies. However, in our study, we observed that mutation in exon 21 was less frequent compared to other studies. A similar slightly increased frequency of rare mutations and double mutations were observed in our study. A detailed study of the molecular epidemiology of lung cancer and its association with different geographical zones of India is needed. This understanding will help in better planning of treatment strategies and resource allocation.

Hybrid Optimized GRU-ECNN Models for Gait Recognition with Wearable IOT Devices.

With the advent of the Internet of Things (IoT), human-assistive technologies in healthcare services have reached the peak of their application in terms of diagnosis and treatment process. These devices must be aware of human movements to provide better aid in clinical applications as well as the user's daily activities. In this context, real-time gait analysis remains to be key catalyst for developing intelligent assistive devices. In addition to machine and deep learning algorithms, gait recognition systems have significantly improved in terms of high accuracy recognition. However, most of the existing models are focused on improving gait recognition while ignoring the computational overhead that affects the accuracy of detection and even remains unsuitable for real-time implementation. In this research paper, we proposed a hybrid gated recurrent unit (GRU) based on BAT-inspired extreme convolutional networks (BAT-ECN) for the effective recognition of human activities using gait data. The gait data are collected by implanting the wearable Internet of Things (WIoT) devices invasively. Then, a novel GRU and ECN networks are employed to extract the spatio-temporal features which are then used for classification to realize gait recognition. Extensive and comprehensive experimentations have been carried out to evaluate the proposed model using real-time datasets and also other benchmarks such as whuGait and OU-ISIR datasets. To prove the excellence of the proposed learning model, we have compared the model's performance with the other existing hybrid models. Results demonstrate that the proposed model has outperformed the other learning models in terms of high gait classification and less computational overhead.