From Data to Cure: A Comprehensive Exploration of Multi-omics Data Analysis for Targeted Therapies.

In the dynamic landscape of targeted therapeutics, drug discovery has pivoted towards understanding underlying disease mechanisms, placing a strong emphasis on molecular perturbations and target identification. This paradigm shift, crucial for drug discovery, is underpinned by big data, a transformative force in the current era. Omics data, characterized by its heterogeneity and enormity, has ushered biological and biomedical research into the big data domain. Acknowledging the significance of integrating diverse omics data strata, known as multi-omics studies, researchers delve into the intricate interrelationships among various omics layers. This review navigates the expansive omics landscape, showcasing tailored assays for each molecular layer through genomes to metabolomes. The sheer volume of data generated necessitates sophisticated informatics techniques, with machine-learning (ML) algorithms emerging as robust tools. These datasets not only refine disease classification but also enhance diagnostics and foster the development of targeted therapeutic strategies. Through the integration of high-throughput data, the review focuses on targeting and modeling multiple disease-regulated networks, validating interactions with multiple targets, and enhancing therapeutic potential using network pharmacology approaches. Ultimately, this exploration aims to illuminate the transformative impact of multi-omics in the big data era, shaping the future of biological research.

CORRELATION OF SPINOPELVIC PARAMETERS WITH DISABILITY STATUS IN PATIENTS WITH DEGENERATIVE LUMBAR DISEASES.

Lumbar degenerative disease usually manifests in spine clinics. This study examines the spino-pelvic characteristics of lumbar degenerative disease patients as well as the clinical ramifications in the Indian population which help in early identification of sagittal spine anomalies. Purpose - to study the spinopelvic parameters and correlate them with disability status in patients with degenerative lumbar diseases. This cross-sectional observational study focused on patients aged 40 to 60, diagnosed with degenerative lumbar spine diseases, seen at the Orthopedics Outpatient Department. Thorough history, clinical examination, and disability assessment were conducted using the modified Oswestery Disability Questionnaire (ODI). Radiological evaluation included measuring spinopelvic parameters-Pelvic Incidence (PI), Pelvic Tilt (PT), Sacral Slope (SS), and Lumbar Lordosis (LL)-correlated with disability. Disability status was determined through the Oswestry Low Back Pain Disability (ODI) Questionnaire. Among the study population, the difference in mean of Pelvic Tilt, Sacral slope, Lumbar lordosis, Pelvic incidence across disability status was not statistically significant. BMI and sacral slope showed positive correlation to sacral slope and negative correlation to Pelvic Tilt, Lumbar Lordosis, ODI. This study concluded there was no association between spinopelvic characteristics and level of disability in degenerative lumbar disease. Early detection of spinopelvic changes can aid in early intervention, slow down disease progression, and lessen impairment brought on by degenerative disc diseases.

FUNCTIONAL AND RADIOLOGICAL OUTCOME FOLLOWING EXTENDED POSTERIOR CIRCUMFERENTIAL DECOMPRESSION IN THE TUBERCULOSIS OF DORSAL SPINE.

Spinal Tuberculosis ranks as one of the most common extrapulmonary varieties of tuberculosis. The study outlines the Extended Posterior Circumferential Decompression (EPCD) procedure for managing tuberculous spondylitis, a prevalent extrapulmonary form of tuberculosis. EPCD involves 360-degree dural decompression, anterior column debridement, and reconstruction following posterior instrumentation. This technique addresses both the infection and associated complications, particularly beneficial in cases with or without paraplegia. EPCD aims to improve outcomes by effectively tackling the pathology and restoring spinal stability. Purpose - to evaluate the functional and radiological outcome following Extended Posterior Circumferential Decompression in the tuberculosis of dorsal spine. A total of 10 patients were included after fulfilling inclusion criteria between July 2019 to December 2021, all patient underwent Extended Posterior Circumferential Decompression. All patients assessed using Visual analog scale (VAS), Medical Research council (MRC) grading, Frankel grading, Kyphus angle, Erythrocyte sedimentation rate (ESR), X-rays preoperative, immediate postoperative period and 9 month follow up. All patients were available for follow up, in this study mean age was 55.7±17.91. Out of 10 patients 60% were female, 40% was male. VAS, MRC grading, Frankel, ESR values, Kyphus angle showed better results in terms of functional and radiological outcome at 9 month follow up compared to preoperative values. The Employed Posterior Costotransversectomy Decortication (EPCD) technique grants ample ingress to both the lateral and anterior domains of the spinal cord, ensuring an equally efficacious decompression. This approach, characterized by its diminished morbidity, steers clear of the entanglements linked with thoracotomy and laparotomy. Moreover, it fosters prompt mobilization, thereby forestalling the adversities entailed by protracted immobility. With its capability for favorable kyphosis correction, adept surgical decompression, and enhanced functional outcomes, it stands as a beacon of surgical finesse.

Comparative evaluation of volumetric changes following rotary and hand files' canal preparation of primary maxillary canine: an in vitro nano-CT analysis.

PURPOSE: To evaluate the volumetric changes of two recently introduced paediatric rotary file systems in comparison with conventional hand file systems in primary maxillary canines using an ultra-high-resolution nano-computed tomography. METHODS: This in vitro study was performed in extracted primary maxillary canines based on certain inclusion and exclusion criteria. Samples were prepared, and working length was determined after the pre-operative scan using a high-resolution nano-CT device (SkyScan 2214, Bruker, Kontich, Belgium). A single well-experienced paediatric dentist prepared the canals using three file systems: Kedo-S plus, Kedo-SG blue and hand K-files. All samples were subjected to post-operative scans performed similar to pre-operative scans. Image reconstruction was performed with NRecon software for 3D volumetric visualisation and analysis of the root canals. RESULTS: Kedo-SG blue file systems had the highest mean difference in the canal volume (4.05%). Hand K-files had the least difference at (3.71%) of canal volume. Kedo-S plus file system had a moderate mean canal volume difference (3.82%) which is closer to hand K-files. Intergroup comparison between the three groups showed that the mean difference in canal volume was statistically significant between all three file systems (p = 0.000). CONCLUSION: Within the limitations of the current study, rotary file systems produced a significant enlargement of canals as compared to hand files. Kedo-SG blue created a uniform preparation of the canal cervico-apically. Kedo-S plus files were prepared more coronally with minimal preparation apically as close to the preparation of hand files. TRIAL REGISTRATION: Trial registration number: IHEC/SDC/PEDO-2103/22/651, Date of registration: 2022.

Immunoinformatic exploration of a multi-epitope-based peptide vaccine candidate targeting emerging variants of SARS-CoV-2.

Many countries around the world are facing severe challenges due to the recently emerging variants of SARS-CoV-2. Over the last few months, scientists have been developing treatments, drugs, and vaccines to subdue the virus and prevent its transmission. In this context, a peptide-based vaccine construct containing pathogenic proteins of the virus known to elicit an immune response was constructed. An analysis of the spike protein-based epitopes allowed us to design an "epitope-based subunit vaccine" against coronavirus using the approaches of "reverse vaccinology" and "immunoinformatics." Computational experimentation and a systematic, comprehensive protocol were followed with an aim to develop and design a multi-epitope-based peptide (MEBP) vaccine candidate. Our study attempted to predict an MEBP vaccine by introducing mutations of SARS-CoV-2 (Delta, Lambda, Iota, Omicron, and Kappa) in Spike glycoprotein and predicting dual-purpose epitopes (B-cell and T-cell). This was followed by screening the selected epitopes based on antigenicity, allergenicity, and population coverage and constructing them into a vaccine by using linkers and adjuvants. The vaccine construct was analyzed for its physicochemical properties and secondary structure prediction, and a 3D structure was built, refined, and validated. Furthermore, the peptide-protein interaction of the vaccine construct with Toll-like receptor (TLR) molecules was performed. Immune profiling was performed to check the immune response. Codon optimization of the vaccine construct was performed to obtain the GC content before cloning it into the E. coli genome, facilitating its progression it into a vector. Finally, an in-silico simulation of the vaccine-protein complex was performed to comprehend its stability and conformational behavior.

Median mandibular cleft in SAMS syndrome - A rare case report.

Rationale: SAMS syndrome is a rare genetic disorder characterized by midline facial clefting, skeletal anomalies, and other defects. Salient Features: Among the craniofacial manifestations of SAMS syndrome is the presence of a median mandibular cleft (MMC). MMC is a rare occurrence and in this syndrome, it poses a complex challenge for both functional and aesthetic reasons. Patient. Findings: This rare case report describes the successful correction of an MMC in an 18-month-old child diagnosed with SAMS syndrome. Treatment: This report describes the presentation, diagnosis and treatment. The surgical intervention involved a meticulous, single stage, osseous reconstruction. The mechanism of MMC in SAMS syndrome is discussed. Outcomes: Early intervention for MMC in SAMS syndrome patients can offer promising outcomes.

A Novel Approach in the Management of Tibial Plateau Fractures with Compartment Syndrome.

Background: Compartment syndrome in tibial plateau fractures presents a formidable challenge for treating orthopedic surgeons. The most common strategy is early fasciotomy and external fixation, followed by a second stage definitive fixation. We conducted a prospective study of tibial plateau fractures of Schatzker Type V and VI with impending compartment syndrome treated by single-stage double incision fasciotomy and dual internal fixation and Vacuum-Assisted Closure (VAC). Materials and Methods: The study was between May 2014 and February 2019. 21 patients with impending compartment syndrome who underwent single-stage double incision fasciotomy and Open Reduction and Internal Fixation (ORIF) with dual plate were included in the study. The functional and radiological outcome was measured using the modified Rasmussen functional and radiological scoring and The Western Ontario and McMaster Universities Arthritis Index (WOMAC). Results: The mean age of patients was 38.7 years (Standard deviation of ± 9.48). The mean follow-up period was 27 months (Standard deviation of ± 6.51). The mean functional and radiological modified Rasmussen score was 27.28 (range 21 to 29) & 8 (range 7 to 10), respectively. 4 patients had excellent outcomes, and 17 patients had good results. The mean WOMAC score was 8.04 (Standard deviation of ± 5.35). Five patients had a score of 0, 14 patients had a score of 1-10 and 2 had a score of 11-20. Conclusions: The early double incision fasciotomy and definitive internal fixation with dual plate and VAC as single-stage surgery in patients with impending compartment syndrome help to obtain excellent to good functional outcomes with reduced complications.

Arrhythmia During Anaphylaxis-An Intrinsic or Extrinsic Cause?

A patient in their 50s presented to the emergency department (ER) within 30 minutes of ingestion of prawns at a restaurant with complaints of an itchy skin rash, and generalized weakness; his pulse rate was 79 bpm, his blood pressure was 50/30 mm Hg, and his respiratory rate was 20 per minute. What is your diagnosis?

Cellular allostatic load is linked to increased energy expenditure and accelerated biological aging.

Stress triggers anticipatory physiological responses that promote survival, a phenomenon termed allostasis. However, the chronic activation of energy-dependent allostatic responses results in allostatic load, a dysregulated state that predicts functional decline, accelerates aging, and increases mortality in humans. The energetic cost and cellular basis for the damaging effects of allostatic load have not been defined. Here, by longitudinally profiling three unrelated primary human fibroblast lines across their lifespan, we find that chronic glucocorticoid exposure increases cellular energy expenditure by ∼60%, along with a metabolic shift from glycolysis to mitochondrial oxidative phosphorylation (OxPhos). This state of stress-induced hypermetabolism is linked to mtDNA instability, non-linearly affects age-related cytokines secretion, and accelerates cellular aging based on DNA methylation clocks, telomere shortening rate, and reduced lifespan. Pharmacologically normalizing OxPhos activity while further increasing energy expenditure exacerbates the accelerated aging phenotype, pointing to total energy expenditure as a potential driver of aging dynamics. Together, our findings define bioenergetic and multi-omic recalibrations of stress adaptation, underscoring increased energy expenditure and accelerated cellular aging as interrelated features of cellular allostatic load.

Comparative analysis of experimental and numerical investigation on multiple projectile impact of AA5083 friction stir welded targets.

This research aims to investigate the ballistic resistance of base material (BM)and "Friction Stir Welded (FSW)", AA5083 aluminum alloy. The primary objective was to build a finite element model to predict kinetic energy absorption and target deformation under single and multiple projectile impact conditions. This study employed 7.62mm Hard Steel Core (HSC) projectiles produced from Steel 4340. The target was analyzed using commercially available Abaqus Explicit software for Finite Element Analysis. It was noticed that the generation of kinetic energy and surface residual velocity increases as the number of projectile strikes increases. In addition, the experimental ballistic test was conducted to validate the numerical results. Using the analytical Recht-Ipson model, each target's experimental residual velocity was determined. It was determined that weldments perform less well (30%) as compared to BM targets. Occurrence of plastic deformation during welding causes reduction in ballistic performance of weldments. For both the computational and experimental approaches, a correlation between residual velocities was found. The plastic deformations with ductile hole formation were observed in all the cases.

'Frozen eye' - Post blowout fracture surgical correction - A case report.

The Rationale: "Frozen Eye" is a very uncommon sequel after treatment of orbital blowout fractures requiring implant placement. Patient Concerns: The implant may faultily impinge on the ocular and extra-ocular muscle(s), causing the abnormality in the movement of the eye. Diagnosis: We present a 56-year-old male whose ocular implant impinged on muscle, causing "frozen eye" and had an infected implant. Treatment Outcomes: The same was removed and surgically corrected. The manuscript describes the details and discusses the possible mechanism that led to the "Frozen Eye".

An early prediction and classification of lung nodule diagnosis on CT images based on hybrid deep learning techniques.

Detection of malignant lung nodules at an early stage may allow for clinical interventions that increase the survival rate of lung cancer patients. Using hybrid deep learning techniques to detect nodules will improve the sensitivity of lung cancer screening and the interpretation speed of lung scans. Accurate detection of lung nodes is an important step in computed tomography (CT) imaging to detect lung cancer. However, it is very difficult to identify strong nodes due to the diversity of lung nodes and the complexity of the surrounding environment. Here, we proposed lung nodule detection and classification with CT images based on hybrid deep learning (LNDC-HDL) techniques. First, we introduce a chaotic bird swarm optimization (CBSO) algorithm for lung nodule segmentation using statistical information. Second, we illustrate an improved Fish Bee (IFB) algorithm for feature extraction and selection. Third, we develop a hybrid classifier i.e. hybrid differential evolution-based neural network (HDE-NN) for tumor prediction and classification. Experimental results have shown that the use of computed tomography, which demonstrates the efficiency and importance of the HDE-NN specific structure for detecting lung nodes on CT scans, increases sensitivity and reduces the number of false positives. The proposed method shows that the benefits of HDE-NN node detection can be reaped by combining clinical practice.

Deep Learning-Based Modeling of Drug-Target Interaction Prediction Incorporating Binding Site Information of Proteins.

Chemogenomics, also known as proteochemometrics, covers various computational methods for predicting interactions between related drugs and targets on large-scale data. Chemogenomics is used in the early stages of drug discovery to predict the off-target effects of proteins against therapeutic candidates. This study aims to predict unknown ligand-target interactions using one-dimensional SMILES as inputs for ligands and binding site residues for proteins in a computationally efficient manner. We first formulate a Deep learning CNN model using one-dimensional SMILES for drugs and motif-rich binding pocket subsequences of proteins as inputs. We evaluate and compare the proposed deep learning model trained on expert-based features against shallow feature-based machine learning methods. The proposed method achieved better or similar performance on the MSE and AUPR metrics than the shallow methods. Additionally, We show that our deep learning model, DeepPS is computationally more efficient than the deep learning model trained on full-length raw sequences of proteins. We conclude that a beneficial research approach would be to integrate structural information of proteins for modeling drug-target interaction prediction of large datasets for more interpretability, high throughput, and broad applicability.

Favourable Interfacial Characteristics of A2 Milk Protein Monolayer.

Shielding of the specific body organ using the biocompatible material helps preventing direct exposure of that part to the foreign entities responsible for infections. Here we show the potential of the A2 milk protein recovered from the milk of cow from Indian origin for possible prevention of the direct exposure to other foreign molecules. We measured the surface pressure of the monolayers of different types of protein samples using Langmuir isotherm experiments. The surface pressure measurements for the monolayer of four types of protein macromolecules have been carried out using the Wilhelmy plate micro pressure sensor. We studied the self-organization of different protein macromolecules and their monolayer compression characteristics. The electrochemical behaviour is studied using electrochemical impedance spectroscopy. We found the highest surface pressure for the monolayer of A2 protein. Further, it is also found that A2 protein exhibited the highest surface activity amongst the other proteins. This property can be effectively used for making the envelope of the A2 protein surrounding the targeted entity.

Modified Placement of C-flap in Unilateral Cleft Lip Repair to Avoid Alar Base Scar - A Retrospective Study.

Introduction: In spite of several techniques, Millard's approach for the correction of cleft lip still is widely used. Although versatile, it has certain drawbacks including scar contraction, short lip and notching. A modification of the 'C' arm helps to address this drawback. The purpose of this study was to describe the qualitative and quantitative outcomes of the author's modification of Millard's C flap. Materials and Methods: Archival photographic records of cleft lip repairs and post-operative photos of cases treated by author were screened. Anthropometric measurements of the height and width of the lip, the height of the vermilion and the width of the alar base were considered. The outcome was quantified by comparing the ratio of each feature between the cleft and normal sides. The quality of cleft lip repair was assessed using the Steffensen criteria. Appropriate statistical tests were performed. Results: In all, 233 cases with a mean age of 4.46 ± 0.91 years and 106 (45.5%) males formed the study group. The mean lip height ratio was 0.936 ± 0.04, the mean lip width ratio was 0.938 ± 0.037, the mean vermillion height ratio was 0.9433 ± 0.35 while the mean alar base width ratio was 0.932 ± 0.35. The physical parameter ratios' mean difference between the normal side and the cleft side was below 0.06 mm. Discussion: The mechanism behind the drawback of the classical Millard's technique is discussed and compared with present modification. The authors' modification shows that modified Millard's technique produces better aesthetic outcomes.