COVID-19 vaccine hesitancy among adults in India: A primary study based on health behavior theories and 5C psychological antecedents model.

Despite the significant success of India's COVID-19 vaccination program, a sizeable proportion of the adult population remains unvaccinated or has received a single dose of the vaccine. Despite the recommendations of the Government of India for the two doses of the COVID-19 vaccine and the precautionary booster dose, many people were still hesitant towards the COVID-19 full vaccination. Hence, this study aimed to identify the primary behavioral and psychological factors contributing to vaccine hesitancy. Cross-sectional data was collected via a multi-stage sampling design by using a scheduled sample survey in the Gorakhpur district of Uttar Pradesh, India, between 15 July 2022 to 30 September 2022. This study has utilized three health behavior models-the Health Belief Model (HBM), the Theory of Planned Behavior (TPB), and the 5C Psychological Antecedents of vaccination, and employed bivariate and multivariable binary logistic regression model to assess the level of vaccine hesitancy and predictive health behavior of the respondents. Results indicate that among the constructs of the HBM and 5C Antecedents models, "perceived benefits", "confidence" and "collective responsibility" showed a lesser likelihood of COVID-19 vaccine hesitancy. However, in the TPB model constructs, a 'negative attitude towards the vaccine' showed a four times higher likelihood of COVID-19 vaccine hesitancy. From the future policy perspective, this study suggested that addressing the issue of 'negative attitudes towards the vaccine' and increasing the trust or confidence for the vaccine through increasing awareness about the benefits of the vaccination in India may reduce vaccine hesitancy.

Effect of Whole-Body Vibration Exercise on Pain, Disability, Balance, Proprioception, Functional Performance and Quality of Life in People with Non-Specific Chronic Low Back Pain: A Systematic Review and Meta-Analysis.

Background: Non-specific chronic low back pain (NSCLBP) presents significant treatment challenges due to its multifactorial nature. Whole-body vibration exercise (WBVE) has emerged as a potential therapeutic modality, offering benefits across various domains, including pain reduction, improved balance, and enhanced quality of life (QoL). The aim of this present systematic review and meta-analysis is to evaluate the effects of WBVE on pain, disability, balance, proprioception, functional performance, and QoL in individuals with NSCLBP. Methods: We comprehensively searched PubMed, Web of Science, Scopus, and CENTRAL databases from October 2023 to January 2024, including RCTs with a PEDro score of ≥5 for high-quality evidence. Outcome measures included pain intensity, Oswestry Disability Index (ODI) score, Roland-Morris Disability Questionnaire (RMDQ) score, balance, proprioception, functional performance (through a progressive iso-inertial lifting evaluation), and QoL (SF-36) in NSCLBP patients. The risk of bias was assessed using ROB-2, and the certainty of evidence for each outcome indicator was analyzed using GRADE. A meta-analysis was conducted using standardized mean differences (SMD) and mean differences (MD) for continuous outcomes. Results: Ten randomized controlled trials fulfilled the inclusion criteria for the systematic review, and nine were suitable for the meta-analysis. The qualitative synthesis revealed WBVE is effective in improving pain, disability, balance, proprioception, and functional performance and QoL. Further, the results of the quantitative review demonstrated WBVE significantly reduced pain [visual analogue scale: SMD = -0.81, 95% CI (-1.11, -0.50), I2 = 0%, p < 0.01], disability [ODI: MD = -3.78, 95% CI (-5.27, -2.29), I2 = 24%, p < 0.01]; RMDQ: MD = -1.43, 95% CI (-2.04, -0.82), I2 = 51%, p < 0.01], balance [SMD = -0.28, 95% CI (-0.52, -0.05), I2 = 0%, p = 0.02], and proprioception [SMD = -4.20, 95% CI (-7.50, -0.89), I2 = 99%, p = 0.01]. Conclusions: This review and meta-analysis indicate that WBVE significantly improves pain, disability, balance and proprioception in individuals with non-specific chronic low back pain. These findings suggest potential benefits of incorporating WBVE into the management strategies for NSCLBP.

Correction: Integrated biosensors for monitoring microphysiological systems.

Correction for 'Integrated biosensors for monitoring microphysiological systems' by Lei Mou et al., Lab Chip, 2022, 22, 3801-3816, https://doi.org/10.1039/D2LC00262K.

Effects of physical interventions on pain and disability in chronic low back pain with pronated feet: a systematic review and meta-analysis.

BACKGROUND: A link between pronated feet (PF) and chronic low back pain (CLBP) has been reported in the literature. However, physical interventions (PI) like physiotherapy and orthotics mainly target the lower back, neglecting the broader biomechanical impacts of PF that affect the feet, ankles, and overall posture. Currently, there is a lack of comprehensive meta-analyses or systematic reviews on this subject. OBJECTIVES: This systematic review with a meta-analysis aimed to evaluate the effects of PI on pain and disability in patients having CLBP with PF. METHODS: From inception until October 15, 2023, Medline/PubMed, Web of Science, and Scopus databases were searched using the desired keywords for randomized control trials (RCTs). The quality of the RCTs was evaluated using the PEDro scale and risk of bias tool. RESULTS: Four studies involving 268 patients were identified, two compared custom-made foot orthoses to non-biomechanical foot insoles, while the other two used exercises. The meta-analysis included four studies for pain and three for disability. The results showed a significant change in pain [-2.43 (95% CI -2.73 to -2.13, p < .001)] and disability of -6.69 (95% CI -8.04 to -5.33, p < .001)]. CONCLUSIONS: This systematic review and meta-analysis of four RCTs elucidates that PI, specifically targeting PF, significantly alleviate pain and reduce disability in patients having CLBP with PF. These findings advocate for integrating foot-based PI within the treatment protocols for patients suffering from CLBP accompanied by PF.

Pan-Indian Clinical Registry of Invasive Fungal Infections Among Patients in the Intensive Care Unit: Protocol for a Multicentric Prospective Study.

BACKGROUND: Fungal infections are now a great public health threat, especially in those with underlying risk factors such as neutropenia, diabetes, high-dose steroid treatment, cancer chemotherapy, prolonged intensive care unit stay, and so on, which can lead to mycoses with higher mortality rates. The rates of these infections have been steadily increasing over the past 2 decades due to the increasing population of patients who are immunocompromised. However, the data regarding the exact burden of such infection are still not available from India. Therefore, this registry was initiated to collate systematic data on invasive fungal infections (IFIs) across the country. OBJECTIVE: The primary aim of this study is to create a multicenter digital clinical registry and monitor trends of IFIs and emerging fungal diseases, as well as early signals of any potential fungal outbreak in any region. The registry will also capture information on the antifungal resistance patterns and the contribution of fungal infections on overall morbidity and inpatient mortality across various conditions. METHODS: This multicenter, prospective, noninterventional observational study will be conducted by the Indian Council of Medical Research through a web-based data collection method from 8 Advanced Mycology Diagnostic and Research Centers across the country. Data on age, gender, clinical signs and symptoms, date of admission, date of discharge or death, diagnostic tests performed, identified pathogen details, antifungal susceptibility testing, outcome, and so on will be obtained from hospital records. Descriptive and multivariate statistical methods will be applied to investigate clinical manifestations, risk variables, and treatment outcomes. RESULTS: These Advanced Mycology Diagnostic and Research Centers are expected to find the hidden cases of fungal infections in the intensive care unit setting. The study will facilitate the enhancement of the precision of fungal infection diagnosis and prompt treatment modalities in response to antifungal drug sensitivity tests. This registry will improve our understanding of IFIs, support evidence-based clinical decision-making ability, and encourage public health policies and actions. CONCLUSIONS: Fungal diseases are a neglected public health problem. Fewer diagnostic facilities, scanty published data, and increased vulnerable patient groups make the situation worse. This is the first systematic clinical registry of IFIs in India. Data generated from this registry will increase our understanding related to the diagnosis, treatment, and prevention of fungal diseases in India by addressing pertinent gaps in mycology. This initiative will ensure a visible impact on public health in the country. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/54672.

The Development of a Clinical Registry Digital Database on Invasive Fungal Infections in India: Advancing Epidemiological Understanding and Patient Care.

A well-structured digital database is essential for any national priority project as it can provide real-time data analysis and facilitate quick decision making. In recent times, particularly after the COVID-19 pandemic, invasive fungal infections (IFIs) have emerged as a significant public health challenge in India, affecting vulnerable population, including immunocompromised individuals. The lack of comprehensive and well-structured data on IFIs has hindered efforts to understand their true burden and optimize patient care. To address this critical knowledge gap, the ICMR has undertaken a Pan-India pioneer initiative to develop a network of Advanced Mycology Diagnostic research centres in different geographical zones of the country (ICMR-MycoNet). Under the aegis of this project, a clinical registry on IFIs in the ICUs is initiated. This process paper presents a detailed account of the steps involved in the establishment of a web-based data entering and monitoring platform to capture data electronically, ensuring robust and secure data collection and management. This system not only allows participating ICMR-MycoNet centres to enter patient information directly into the database using standardized Case Report Form (CRF) but also includes data validation checks to ensure the accuracy and completeness of entered data. It is complemented by a real-time, web-based, and adaptable data visualization platform. This registry aims to provide crucial epidemiological insights, promote evidence-based hospital infection control programs, and ultimately improve patient outcomes in the face of this formidable healthcare challenge.

Structure-based identification of potential natural compound inhibitors targeting bacterial cytoskeleton protein FtsZ from Acinetobacter baumannii by computational studies.

Acinetobacter baumannii is one of the multi-drug-resistant pathogens responsible for hospital-acquired infections reported worldwide. Clinically it is challenging to treat these pathogens as they have developed resistance against the existing class of antibiotics. Hence, there is an urgent need to develop a new class of antibiotics against these pathogens to prevent the spread of infections and mortality. In Acinetobacter baumannii, the filamentous temperature-sensitive mutant Z protein polymerizes at the imminent division site to form a Z-ring at the mid-point of the cell and act as a scaffold to recruit other cell division proteins involved in orchestrating septum synthesis in bacteria. Perturbation in the assembly of FtsZ affects bacterial cell dynamics and survival. Hence, FtsZ has emerged as a new drug target in antibiotic discovery to identify compounds that inhibit bacterial cell division. In this study, we have performed a virtual screening of 30,000 compounds from the ZINC Biogenic natural compound library targeting the nucleotide-binding site of FtsZ from Acinetobacter baumannii. We have identified 8 new natural compounds with binding energy in the range of -8.66 to -6.953 kcal/mol and analyzed them by 200 ns molecular dynamics simulations. Out of these eight compounds, ZINC14708526 showed the best binding with relatively optimal drug-likeness and medicinal chemistry as a potent inhibitor of abFtsZ. Thus, the identified FtsZ inhibitor ZINC14708526 is a promising lead compound to develop potent antimicrobial agents against Acinetobacter baumannii infections.Communicated by Ramaswamy H. Sarma.

Effect of wire diameter and extent of wire composite splint on the mobility of luxated and anchor primary teeth: A typodont study.

BACKGROUND/AIMS: The recommendations for splinting are well established for the injuries of permanent dentition; however, ambiguity still exists for the injuries in primary dentition. Hence, this study aimed to determine the most appropriate dimensions of stainless steel wire and its extent, for achieving the physiologic mobility in primary dentition. MATERIAL AND METHODS: This study was designed as an in vitro experiment by using a typodont model of primary dentition. The baseline mobility of primary maxillary incisors was calibrated to the physiologic mobility of natural primary incisors by using a Teflon tape wrapped around the roots of resin teeth. Splinting was done using a stainless steel wire of 0.2 mm (Group I), 0.3 mm (Group II), and 0.4 mm (Group III). These groups were subdivided (a, b, and c) on the basis of the extent of the splint, and pre splint mobility (Pre-PV) and post-splint mobility (Post-PV) were tested by Periotest M. The splint effect was calculated by subtracting Post-PVs and Pre-PVs. RESULTS: The normal values of mobility in healthy human volunteers ranged from 10.5 to 13. The overall splint effect was higher in Group III irrespective of the extent of the splint, whereas it was found to be the lowest in Group I (b and c). The splint effect increased with the extent of the splint in all the groups. Among all the groups, the splint effect on the anchor teeth was observed to increase with the extent of the splint and the diameter of the wire. CONCLUSION: The mobility of the injured and anchor teeth splinted with 0.2-mm stainless steel wire was similar to the pre-splint and physiologic mobility. The most favorable extension was one tooth adjacent to the injured tooth on each side for both 0.2- and 0.3-mm wires.

Quality analysis of the clinical practice guidelines for management of impacted maxillary central incisors: a systematic review.

PURPOSE: To assess the quality of clinical practice guidelines (CPG) for management of impacted central incisors. METHODS: Search was performed in PubMed, LILACS, Web of Science, EMBASE, Scopus, and Cochrane databases, and guideline-focused databases/repositories on 15-09-2022 without any limitations and was updated on 15-07-2023. Grey literature search was also performed. Two independent reviewers were involved in the study selection and data extraction. Quality assessment of the included CPG was performed by four independent appraisers using the AGREE-II instrument. The degree of agreement among the appraisers was calculated using the intraclass correlation coefficient (ICC). RESULTS: Five CPG were included in the review. The Ministry of Health, Malaysia (MHM) guideline obtained the highest scores in all six domains of AGREE-II and an overall score of 73% demonstrating the "highest" quality. The remaining four guidelines obtained overall "low-quality" scores ranging from 34.57-37.52%. The ICC scores ranged from 0.530 to 0.990 for various domains of AGREE-II. CONCLUSION: MHM guidelines demonstrated high-quality scores in domains of 'scope and purpose', 'clarity of presentation', 'applicability domain', and 'editorial independence', while others were found to have moderate or low quality. This review identified areas that can be addressed by future guideline developers to avoid these discrepancies.

Effects of facilitatory and inhibitory Kinesio taping on lateral gastrocnemius muscle activity, motor neuron excitability, and countermovement jump height in university athletes from multiple sports: A randomized controlled trial.

Objectives: This study aims to investigate the temporal effects of two Kinesio Taping (KT) techniques on lateral gastrocnemius muscle activity, motor neuron excitability, and countermovement jump height in university athletes from hockey, football, basketball, and volleyball. Additionally, it investigates whether the athletes' playing positions-either attacker or defender-influence these outcomes following the KT application. Methods: Forty-eight subjects were randomly assigned to one of three groups: Group A (n = 16), Group B (n = 16), and Group C (n = 16). All groups were further subdivided into attackers and defenders. Adhesive Kinesio tape was applied to the lateral gastrocnemius using the Y-shaped technique for three days. Facilitatory KT was applied from the origin to the insertion of the lateral gastrocnemius, while inhibitory KT was applied from the insertion to the origin. Motor neuron excitability, electromyographic activity, and countermovement jump height were tested at baseline, as well as after KT application, to evaluate if the dependent variables had changed. One-way ANOVA was used for baseline comparison, and mixed ANOVA was applied to assess post-interventional effects on the outcome measures. Results: Significant group effects for lateral gastrocnemius activation were found, measured using percentage of maximum voluntary isometric contraction (% MVIC) average root mean square (RMS). In motor neuron excitability, maximal M-wave (Mmax) was significantly improved in group comparison. Further, there was also a significant increase in countermovement jump height. There was no significant difference in outcome measures based on playing position (attacker and defender). Conclusion: Both KT techniques effectively influenced the lateral gastrocnemius muscle's activity, motor neuron excitability, and jump height when compared with the control group. Additionally, there is no effect of playing position, specifically attacker or defender, on the examined variables following KT application.

Evaluation of methods for assigning causes of death from verbal autopsies in India.

Background: Physician-coded verbal autopsy (PCVA) is the most widely used method to determine causes of death (COD) in countries where medical certification of death is low. Computer-coded verbal autopsy (CCVA), an alternative method to PCVA for assigning the COD is considered to be efficient and cost-effective. However, the performance of CCVA as compared to PCVA is yet to be established in the Indian context. Methods: We evaluated the performance of PCVA and three CCVA methods i.e., InterVA 5, InSilico, and Tariff 2.0 on verbal autopsies done using the WHO 2016 VA tool on 2,120 reference standard cases developed from five tertiary care hospitals of Delhi. PCVA methodology involved dual independent review with adjudication, where required. Metrics to assess performance were Cause Specific Mortality Fraction (CSMF), sensitivity, positive predictive value (PPV), CSMF Accuracy, and Kappa statistic. Results: In terms of the measures of the overall performance of COD assignment methods, for CSMF Accuracy, the PCVA method achieved the highest score of 0.79, followed by 0.67 for Tariff_2.0, 0.66 for Inter-VA and 0.62 for InSilicoVA. The PCVA method also achieved the highest agreement (57%) and Kappa scores (0.54). The PCVA method showed the highest sensitivity for 15 out of 20 causes of death. Conclusion: Our study found that the PCVA method had the best performance out of all the four COD assignment methods that were tested in our study sample. In order to improve the performance of CCVA methods, multicentric studies with larger sample sizes need to be conducted using the WHO VA tool.

Ligand-mediated Targeted Drug Delivery Approaches against Hepatocellular Carcinoma.

One of the most important health problems in the world today is cancer. The World Health Organization (WHO) reported that it results in 8.9 million deaths annually. Malignant tumours and unregulated cell proliferation are features of malignant neoplasms, which can also invade nearby body regions. Hepatocellular carcinoma is the third most prevalent cause of cancer-related death worldwide and the fifth most common kind of cancer, according to a recent analysis. Patients with liver disease as well as chronic hepatitis B and C are more likely to develop hepatocellular carcinoma (HCC). Physical barriers, including RES absorption, opsonization, and first-pass drug metabolism, make drug therapy more challenging. Conventional cancer therapy procedures have a low response rate or may continue to be unsuccessful due to multi-drug resistance (MDR), high clearance rates, and other side effects because of suboptimal drug distribution and insufficient drug concentration reaching cancer cells. Innovative target drug molecules that are tailored to the injured liver cells must be developed in order to improve medication administration and drug targeting. The use of targeting ligands that have been joined to drug molecules or nanocarriers forms the basis of innovative targeting techniques. After being conjugated with the treatment method, ligands for targeting hepatocellular carcinoma cells included asialoglycoprotein, galactoside, lactobionic acid, mannose-6-phosphate, PDGF, antibodies, and aptamers.

Structural-Based Virtual Screening of FDA-Approved Drugs Repository for NSP16 Inhibitors, Essential for SARS-COV-2 Invasion Into Host Cells: Elucidation From MM/PBSA Calculation.

NSP16 is one of the structural proteins of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) necessary for its entrance to the host cells. It exhibits 2'O-methyl-transferase (2'O-MTase) activity of NSP16 using methyl group from S-adenosyl methionine (SAM) by methylating the 5-end of virally encoded mRNAs and shields viral RNA, and also controls its replication as well as infection. In the present study, we used in silico approaches of drug repurposing to target and inhibit the SAM binding site in NSP16 using Food and Drug Administration (FDA)-approved small molecules set from Drug Bank database. Among the 2 456 FDA-approved molecules, framycetin, paromomycin, and amikacin were found to be significant binders against the SAM binding cryptic pocket of NSP16 with docking score of -13.708, -14.997 and -15.841 kcal/mol, respectively. Classical molecular dynamics (MD) simulation and molecular mechanics Poisson-Boltzmann surface area (MM/PBSA)-based binding free energy calculation depicted that all these three framycetin, paromomycin, and amikacin might be promising therapeutic leads towards SARS-CoV-2 infections via host immune escape inhibition pathway.

Sodium-Glucose Cotransporter-2 Inhibitors and Primary Prevention of Atherosclerotic Cardiovascular Disease: A Meta-Analysis of Randomized Trials and Systematic Review.

Background Sodium-glucose cotransporter-2 (SGLT2) inhibitors reduce atherosclerotic cardiovascular disease (ASCVD) events in patients with prior ASCVD and type 2 diabetes; however, this benefit is uncertain in patients without established ASCVD. Methods and Results Large-scale cardiovascular outcome randomized controlled trials or their prespecified subgroup analyses were selected, evaluating SGLT2 inhibitors versus placebo for primary prevention of ASCVD (inception, March 2023). The primary outcome was atherosclerotic major adverse cardiovascular events (MACEs), which was a composite of cardiovascular mortality, myocardial infarction, and stroke. The secondary outcomes were individual components of MACEs and all-cause mortality. The outcomes were reported as random-effect relative risk (RR) with a 95% CI. This analysis, comprising 23 987 patients enrolled in 5 randomized controlled trials with a mean follow-up duration of ≈135 weeks, found no significant reduction in atherosclerotic MACEs with SGLT2 inhibitors in comparison to placebo (RR, 0.85 [95% CI, 0.71-1.01]; P=0.07; I2=44). There were no significant differences in cardiovascular mortality (RR, 0.93 [95% CI, 0.77-1.14]; P=0.50; I2=0), myocardial infarction (RR, 0.88 [95% CI, 0.69-1.11]; P=0.28; I2=23), and stroke (RR, 0.84 [95% CI, 0.62-1.16]; P=0.29; I2=46). SGLT2 inhibitors significantly improved all-cause mortality (RR, 0.85 [95% CI, 0.72-1.0]; P=0.04; I2=23). On subgroup analyses, the use of SGLT2 inhibitors led to significant reductions in MACEs (RR, 0.74 [95% CI, 0.61-0.89]; P=0.001), myocardial infarction (RR, 0.67 [95% CI, 0.47-0.97]; P=0.03), and stroke (RR, 0.61 [95% CI, 0.41-0.91]; P=0.01) primarily in patients with chronic kidney disease along with type 2 diabetes, whereas these benefits were not observed in patients with type 2 diabetes without chronic kidney disease. Conclusions SGLT2 inhibitors significantly reduced atherosclerotic MACEs in subjects having both chronic kidney disease and type 2 diabetes without established ASCVD.

Short- and long-term safety and efficacy of corneal collagen cross-linking in progressive keratoconus: A systematic review and meta-analysis of randomized controlled trials.

PURPOSE: The purpose of the study is to evaluate the safety and outcomes of corneal collagen cross-linking (CXL) and different CXL protocols in progressive keratoconus (PK) population at short and long-term. MATERIALS AND METHODS: A systematic review and meta-analysis was conducted. A total of eight literature databases were searched (up to February 15, 2022). Randomized controlled trials (RCTs) comparing CXL versus placebo/control or comparing different CXL protocols in the PK population were included. The primary objective was assessment of outcomes of CXL versus placebo and comparison of different CXL protocols in terms of maximum keratometry (Kmax) or Kmax change from baseline (Δ), spherical equivalent, best corrected visual acuity (BCVA), and central corneal thickness (CCT) in both at short term (6 months) and long term (1st, 2nd, and 3rd year or more). The secondary objective was comparative evaluation of safety. For the meta-analysis, the RevMan5.3 software was used. RESULTS: A total of 48 RCTs were included. Compared to control, CXL was associated with improvement in Δ Kmax at 1 year (4 RCTs, mean difference [MD], -1.78 [-2.71, -0.86], P = 0.0002) and 2 and 3 years (1 RCT); ΔBCVA at 1 year (7 RCTs, -0.10 [-0.14, -0.06], P < 0.00001); and Δ CCT at 1 year (2 RCTs) and 3 years (1 RCT). Compared to conventional CXL (C-CXL), deterioration in Δ Kmax, ΔBCVA and endothelial cell density was seen at long term in the transepithelial CXL (TE-CXL, chemical enhancer). Up to 2 years, there was no difference between TE-CXL using iontophoresis (T-ionto) and C-CXL. At 2 and 4 years, C-CXL performed better compared to accelerated CXL (A-CXL) in terms of improving Kmax. Although CCT was higher in the A-CXL arm at 2 years, there was no difference at 4 years. While exploring heterogeneity among studies, selection of control eye (fellow eye of the same patient vs. eye of different patient) and baseline difference in Kmax were important sources of heterogeneity. CONCLUSION: CXL outperforms placebo/control in terms of enhancing Kmax and CCT, as well as slowing disease progression over time (till 3 years). T-ionto protocol, on the other hand, performed similarly to C-CXL protocol up to 2 years.

Radiation response of Y3Al5O12 and Nd3+-Y3Al5O12 to Swift heavy ions: insight into structural damage and defect dynamics.

Understanding the behavior of a material under irradiation is paramount to its application in the nuclear industry. The present work explores the radiation response of garnet Y3Al5O12 (YAG) and Nd3+-substituted Y3Al5O12 (Nd-YAG) under a 100 MeV Iodine beam at varying fluences to mimic the effect of fission fragments. This is relevant to the potential application of garnet as a host for minor actinide (MA) transmutation (Nd3+: surrogate for long-lived MA (Am3+, Np3+, Cm3+)). The un-irradiated and irradiated YAG and Nd-YAG samples were investigated by X-ray diffraction and Raman spectroscopy. Positron annihilation spectroscopy, thermal spike modelling and theoretical studies have been employed to understand the role of substitution and defect energetics in influencing this radiation response. Although both materials were not completely amorphized under the present irradiation conditions, a tremendous loss in crystallinity could be observed with increase in fluence, the damage being much more in Nd-YAG. Ion track radii of 2.17 nm and 2.91 nm were estimated for YAG and Nd-YAG respectively. Thermal-spike calculations show an increase in radiation-induced transient temperatures upon Nd-substitution that causes greater radiation damage in Nd-YAG. The enhancement in radiation-induced damage with increasing ion-fluence manifests in broadening and weakening of the Raman modes and XRD peaks. An increase in the average positron annihilation lifetime indicated the creation of oxygen vacancies. The defect formation energies of Y3Al5O12 have been theoretically estimated via density functional theory (DFT) and unfavorable energies required for creating cation pair anti-sites have been proposed as one of the possible reasons for the relatively poorer radiation response of YAG. The irradiation behavior of Y3Al5O12 has been compared with disordered fluorite (YSZ) and zirconate pyrochlores, which are well-researched ceramics for MA transmutation.

Investigating the novel-binding site of RPA2 on Menin and predicting the effect of point mutation of Menin through protein-protein interactions.

Protein-protein interactions (PPIs) play a critical role in all biological processes. Menin is tumor suppressor protein, mutated in multiple endocrine neoplasia type 1 syndrome and has been shown to interact with multiple transcription factors including (RPA2) subunit of replication protein A (RPA). RPA2, heterotrimeric protein required for DNA repair, recombination and replication. However, it's still remains unclear the specific amino acid residues that have been involved in Menin-RPA2 interaction. Thus, accurately predicting the specific amino acid involved in interaction and effects of MEN1 mutations on biological systems is of great interests. The experimental approaches for identifying amino acids in menin-RPA2 interactions are expensive, time-consuming, and challenging. This study leverages computational tools, free energy decomposition and configurational entropy scheme to annotate the menin-RPA2 interaction and effect on menin point mutation, thereby proposing a viable model of menin-RPA2 interaction. The menin-RPA2 interaction pattern was calculated on the basis of different 3D structures of menin and RPA2 complexes, constructed using homology modeling and docking strategy, generating three best-fit models: Model 8 (- 74.89 kJ/mol), Model 28 (- 92.04 kJ/mol) and Model 9 (- 100.4 kJ/mol). The molecular dynamic (MD) was performed for 200 ns and binding free energies and energy decomposition analysis were calculated using Molecular Mechanics Poisson-Boltzmann Surface Area (MM/PBSA) in GROMACS. From binding free energy change, model 8 of Menin-RPA2 exhibited most negative binding energy of - 205.624 kJ/mol, followed by model 28 of Menin-RPA2 with - 177.382 kJ/mol. After S606F point mutation in Menin, increase of BFE (ΔGbind) by - 34.09 kJ/mol in Model 8 of mutant Menin-RPA2 occurs. Interestingly, we found a significant reduction of BFE (ΔGbind) and configurational entropy by - 97.54 kJ/mol and - 2618 kJ/mol in mutant model 28 as compared the o wild type. Collectively, this is the first study to highlight the configurational entropy of protein-protein interactions thereby strengthening the prediction of two significant important interaction sites in menin for the binding of RPA2. These predicted sites could be vulnerable for structural alternation in terms of binding free energy and configurational entropy after missense mutation in menin.