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Background: Protein sequence and structure analyses have been essential components of bioinformatics and structural biology. They provide a deeper insight into the physicochemical properties, structure, and subsequent functions of a protein. Advanced computational approaches and bioinformatics utilities help solve several issues related to protein analysis. Still, beginners and non-professional may struggle when encountering a wide variety of computational tools and the sheer number of input parameter variables required by each tool. Methods: We introduce a free-to-access graphical user interface (GUI) named PyPAn 'Python-based Protein Analysis' for varieties of protein sequence/structure analyses. PyPAn serves as a universal platform to analyze protein sequences, structure, and their properties. PyPAn facilitates onboard analysis of each task in just a single click. It can be used to calculate the physicochemical properties, including instability index and molar extinction coefficient, for a protein. PyPAn is one of the few computational tools that allow users to generate a Ramachandran plot and calculate solvent accessibility and the radius of gyration (Rg) of proteins at once. In addition, it can refine the protein model along with computation and minimization of its energy. Results: PyPAn can generate a recommendation for an appropriate structure modelling method to employ for a query protein sequence. PyPAn is one of the few, if not the only, Python-based computational GUI tools with an array of options for the user to employ as they see fit. Conclusion: PyPAn aims to unify many successful academically significant proteomic applications and is freely available for academic and industrial research uses at https://hassanlab.org/pypan.

A continual rise in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection causing coronavirus disease (COVID-19) has become a global threat. The main problem comes when SARS-CoV-2 gets mutated with the rising infection and becomes more lethal for humankind than ever. Mutations in the structural proteins of SARS-CoV-2, i.e., the spike surface glycoprotein (S), envelope (E), membrane (M) and nucleocapsid (N), and replication machinery enzymes, i.e., main protease (Mpro) and RNA-dependent RNA polymerase (RdRp) creating more complexities towards pathogenesis and the available COVID-19 therapeutic strategies. This study analyzes how a minimal variation in these enzymes, especially in S protein at the genomic/proteomic level, affects pathogenesis. The structural variations are discussed in light of the failure of small molecule development in COVID-19 therapeutic strategies. We have performed in-depth sequence- and structure-based analyses of these proteins to get deeper insights into the mechanism of pathogenesis, structure-function relationships, and development of modern therapeutic approaches. Structural and functional consequences of the selected mutations on these proteins and their association with SARS-CoV-2 virulency and human health are discussed in detail in the light of our comparative genomics analysis.

Background: Various studies have associated inflammation with carcinogenesis. But still, the role of inflammatory markers in oral cancer has not been evaluated extensively. Most of the existing studies have been done on patients of varied sites, and their sample size is also scarce. In this study, we have evaluated the impact of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) on various clinicopathological factors and survival. Methodology: This was a retrospective analysis of prospectively collected data of 400 patients with oral squamous cell cancer. The pretreatment neutrophil and lymphocyte and platelet counts were recorded, and NLR and PLR were calculated for all patients. The NLR and PLR tertiles were correlated with the incidence of various clinicopathological factors and overall survival. Results: The median follow-up of the cohort was 36 months. The mean survival of the cohort was 41.7 months. PLR was associated with higher incidence of adverse clinicopathological factors. There was a trend of decreased overall survival with increasing NLR tertile. It was found to be significant only for the group which received adjuvant chemoradiotherapy (P 0.01). Patients with higher PLR values have been found to have a lower overall survival (P 0.006). Conclusion: NLR and PLR can be used to predict survival and outcomes in patients oral cavity cancer. PLR is a good predictor for adverse clinicopathological factors and survival. NLR can predict survival only in the subset of patients who have received chemotherapy.

This study was undertaken to assess the effects of neo-adjuvant chemotherapy (NACT) on patients with head and neck squamous cell carcinoma (HNSCC) having advanced unresectable cervical nodal metastasis. A retrospective cohort study was conducted to assess the response of unresectable nodes to NACT in a pragmatic manner. Patients were grouped according to the response noted and the treatment offered after chemotherapy. The median survival amongst the patients in these groups was compared. The study included 51 patients. Oral cavity was the commonest site (67.2%). Favourable nodal response was seen in 64.7% of the patients. Up to 87.9% of the nodal responders were amenable to curative intent therapy. The overall survival of patients undergoing surgery, definitive chemoradiotherapy, palliative chemotherapy and palliative radiotherapy was 24, 13, 10 and 9 months, respectively. NACT may be utilized in HNSCC with advanced inoperable nodal disease to make them amenable to definitive therapy.

As for situation responsiveness, audio and video signals are very important. Audio is significant because it can enlighten us concerning situations, character, time, and place. The study describes a distress audio (scream or shout) event classification system which precisely classifies an audio event as ambient noise, screams, and shouts. Scream is a high-pitch vocalized sound in the absence of phonological structure. This study, researched the classification system using a three-phase SVM-based classifier model for segregating human distress sound from noise and then scream from a shout. The training of SVM-based classifier is done with audio MFCC as feature vectors, appropriately chosen from a set of 400 audio sets, which are selected according to a two-phase process. A classifier is trained and tested with each feature subset. SVM-based classifier analyses and predicts the sound which works with linear kernel and radial basis function (rbf) kernel. The obtained classification performance then again passes through the Multilayer Perceptron Model. When the model gets any sound then it tries to identify patterns in it using perceptron weights and biases if it can’t get success it slightly changes its weights for getting the correct result if it successfully detects a scream in sound then it calls the emergency function. Our results demonstrate that the system can generate a 90% accuracy.

Exploring protein–ligand interactions is a subject of immense interest, as it provides deeper insights into molecular recognition, mechanism of interaction and subsequent functions. Predicting an accurate model for a protein–ligand interaction is a challenging task. Molecular docking is a computational method used for predicting the preferred orientation, binding conformations and the binding affinity of a ligand to a macromolecular target, especially protein. It has been applied in ‘virtual high-throughput screening’ of chemical libraries containing millions of compounds to find potential leads in drug design and discovery. Here, we have developed InstaDock, a free and open access Graphical User Interface (GUI) program that performs molecular docking and high-throughput virtual screening efficiently. InstaDock is a single-click GUI that uses QuickVina-W, a modified version of AutoDock Vina for docking calculations, made especially for the convenience of non-bioinformaticians and for people who are not experts in using computers. InstaDock facilitates onboard analysis of docking and visual results in just a single click. To sum up, InstaDock is the easiest and more interactive interface than ever existing GUIs for molecular docking and high-throughput virtual screening. InstaDock is freely available for academic and industrial research purposes via https://hassanlab.org/instadock.

Low-dimensional embeddings for knowledge graph entities and relations help preserve their latent semantics while enabling computation efficiency. These embeddings are often used to perform tasks such as knowledge graph completion, question answering and inference. Knowledge graph embedding methods aid in the representation of entities and relationships of a knowledge graph in continuous vector spaces. However, most existing techniques ignore the inherent hierarchical structure of entities present in the knowledge graph, defined by ontological relationships between entity types. This paper introduces a novel score function called GrCluster that helps fill that gap. GrCluster is a simple, intuitive and efficient scoring function that incorporates the entity hierarchical correlation into existing knowledge graph embeddings. The effectiveness of GrCluster is demonstrated by integrating it into several well known embedding models. The experimental results show consistent improvements across metrics and embedding models for the tasks of entity prediction and triplet classification.

Poorly differentiated thyroid cancer (PDTC) is biologically more aggressive. Surgery remains the mainstay of treatment. The utility of radioactive iodine (RAI) after surgery is unclear. In this retrospective study, patients treated between Jan 2012 and Dec 2017 were included. The demographic, clinical and treatment-related details, including RAI ablation, were recorded and their survival analyzed. Thirty-five patients fulfilled the eligibility criteria. Majority was treatment naive at presentation. All patients underwent surgery followed by RAI ablation, with a cumulative median dose of 220 mCi (range 40–1140). Sixteen patients received more than one radioiodine treatment for distant metastases. Incomplete resection, age > 45 years and the presence of distant metastasis influenced survival the most. The 3-year PFS of patients with PDTC was 69%. All patients in our series showed uptake and responded to treatment. Further use of molecular markers and functional molecular imaging would better our understanding of this entity.

Objective Presence of extracapsular spread (ECS) significantly decreases survival in oral cancer patients. Considering its prognostic impact, we have studied the incidence and factors predicting ECS in clinically node negative early oral cancers. Materials and Methods We performed a retrospective chart review of 354 treatment naive clinically node negative early oral cancer patients operated between 2012 and 2014. Chi-square test and logistic regression were used for identifying predictors of ECS, while cox-regression test was used for survival analysis. Results The incidence of occult nodal metastasis was 28.5% (101/354). Among them, ECS was seen in 15.3%(54/354) patients. The incidence of ECS in T1 and T2 lesion was 13.4% (21/157) and 16.8% (33/197), respectively. The overall incidence of ECS was 48% and 29% in lymph nodes smaller than 10 mm and 5 mm respectively. We found that tumor depth of invasion (>5 mm; p-0.027) and node (metastatic) size >15 mm (p-0.018) were significant predictors of ECS. p N2b disease was seen in 41/354 (11.6%) of which 31/354 (8.7%) had ECS, i.e. 75.6% of pN2b patients been ECS positive (p-0.000). The 3-year OS of patients without nodal metastasis, nodal metastasis without ECS and nodal metastasis with ECS was 88.4%, 66.9% and 59.2% (p-0.000) respectively. Conclusion A significant number of patients with metastatic nodal size less than 1 cm have ECS which suggests aggressive behavior of the primary tumor. Thus, elective neck dissection is the only way of detecting ECS in these patients which may warrant treatment intensification.

Background: Bronchial asthma (BA) and allergic rhinitis (AR) are among the most common allergic disorders. Identification of specific causative allergens is of paramount importance for further management. Aims: This study aims (1) to find out the prevalence of various allergens leading to AR and/or BA through skin prick test (SPT), (2) to identify the trigger factors in these patients, (3) to study correlations of allergens and seasonal variations in patients suffering from AR and/or BA. Materials and Methods: A total of 134 patients were collected from outpatient department and inpatient department of Respiratory Medicine Department of Geetanjali Medical College and Hospital, Udaipur, from January 2016 to December 2017. The diagnosis of BA and AR was made according to the GINA and ARIA guidelines, respectively. SPT was done with 78 different types of aeroallergens, which included 23 types of pollens, 6 types of fungi, 10 types of insects, 6 types of dusts, 6 types of dander, 3 fabrics, 2 feathers, and 22 food allergens. Patients who had taken short-acting oral antihistaminics, beta-blockers, steroids, tricyclic antidepressants or any other drug that could affect the test within one week prior to testing were excluded. Also, patients on long-acting oral antihistaminics within four weeks of testing and pregnant women were excluded. Results: A total of 134 patients consisting of 73 (54.48%) males and 61 (45.52%) females, in the age group of 5–65 years, were included in the study. The maximum numbers of patients (50; 37.31%) were between the age group of 20 and 35 years. The maximum number of patients (94; 70.15%) had a duration of suffering from >1 years. AR was found in 60 (44.78%), BA associated with AR was found in 39 (29.1%), while BA alone was found in 35 (26.12%). In 54% of patients, triggers were found for exacerbation of their symptoms, the most common being air pollution (48%) followed by cold exposure (20%), physical activity (12%), irritants (9%), smoke (7%), and fumes and odors (4%). A total of 10,452 SPTs were done, out of which 265 (%) showed positive reactions. The positivity for pollens was seen in 116 (43.77%) patients followed by insects [79 (29.81%)], fungi [22 (8.3%)], house dust mite [15 (5.66%)], dusts [11 (4.15%)], fabrics [10 (3.77%)], danders [9 (3.4%)], and feathers [3 (1.13%)], respectively. Food allergens showed no significant reactions to SPT. Conclusions: Our study showed that insects were the most common allergen in BA patients, while pollens were the most common allergen in patients of AR with or without BA. Intermittent symptoms were common with pollen allergy.

Background: Silicosis is an occupational lung disease caused by inhalation of dust containing crystalline silica particles of size 0.5-5 microns in diameter. It commonly occurs in workers involved in quarrying, mining, sandblasting, tunneling, foundry work and ceramics. Pneumothorax is one of the complications of silicosis. The occurrence of pneumothorax in a patient with silicosis is a rare event, but it may be fatal. The incidence of secondary spontaneous pneumothorax (SSP) in silicosis as such is not known. This study aims to report the cases of secondary spontaneous pneumothorax in patients of silicosis in Southern part of Rajasthan. Methods: 50 patients of silicosis established by historical, clinical evaluation and radiological evidence with increased dyspnoea were included in the study. In all patients Chest X ray was done immediately. Results: Among 50 patients of silicosis with increased dyspnoea, Chest X ray showed pneumothorax in 20 patients of which 4 had bilateral pneumothorax, 7 had right pneumothorax and 9 had left pneumothorax. The mean duration of exposure to silica particles was 10 years (5 to 15 years). All the patients had various degrees of dyspnoea and chest pain. Tube thoracostomy was performed in 15 patients while 5 patients were managed conservatively with oxygen and bronchodilators. Conclusions: Our study showed an increased incidence of secondary pneumothorax in silicosis patients. The occurrence of pneumothorax, though rare in silicosis is a potentially life-threatening complication and may cause serious morbidity and mortality. The patients of silicosis who develop sudden onset of dyspnoea should be promptly investigated for this complication.