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False smut caused by Ustilaginoidea virens is an emerging disease of rice in India. The disease is causing economic loss to farmers through the reduction of yield and quality of rice. To devise a suitable approach to manage the disease effectively, an understanding of the genetic diversity and population structure of the pathogen is essential. Hence, a total of 34 isolates of U. virens obtained from different locations in India were characterized using 25 genomes-specific SSR markers showing higher polymorphic information content (PIC) that produced 203 alleles with a mean of 8.12 per marker. The genetic diversity varied from 0.00 to 0.885 with an average of 0.673. Based on the phylogenetic tree, the 34 isolates of U. virens were grouped into two major clusters (Cluster I and Cluster II). Cluster I included isolates from Andhra Pradesh, Bihar, Kerala, Manipur, Mizoram, Punjab, and West Bengal, while Cluster II included isolates from Assam, Manipur, Meghalaya, and Odisha. The isolates from the same/nearby locations were partially assembled into the same cluster. The analysis of molecular variance (AMOVA) showed the highest variation of 86% found among the individuals while the least variation of 14% was observed between the populations. The population structures of 34 isolates of U. virens evaluated using STRUCTURE and Principal coordinates analysis (PCoA) separated the 34 isolates into two distinct subpopulations. The high genetic variation in the isolates indicated their substantial potential to evolve and mutate, potentially causing damage to rice crops in future., Competing Interests: Declarations. Conflict of interest: The authors declare no conflict of interest. Ethics Approval: This study did not involve experiments on humans or animals, and no ethical approval was required. Consent to Participate: Not applicable as this study did not involve human participants. Consent for Publication: All authors have reviewed the manuscript and consent to its publication., (© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: This randomized-controlled trial assessed the safety and effectiveness of intra-articular hyaluronic acid (IAHA) when administered at various time points following arthroscopic anterior cruciate ligament reconstruction (ACLR) surgery., Methods: Ninety ACL tear patients undergoing arthroscopic ACLR were divided into three groups: Early HA group received HA on day 2 and saline at 2 months; Late HA group received saline on day 2 and HA at 2 months; Placebo group received saline at both times. Clinical (range of motion-ROM, knee circumference, Lysholm score, IKDC, VAS, EQ5D5L, Tegner scores) and blood parameters (blood ESR, and CRP) were assessed at baseline, monthly up to 6 months, and at 12 months. The synovial TNF-alpha level was measured at baseline, day 2, and 3 months., Results: Early HA group showed significantly better ROM than Placebo (P=0.041) and Late HA groups (P=0.029) at one and two months' post-surgery. Pain was significantly lower in Early HA group at one month compared to Placebo (P=0.033). Early HA group achieved a faster median recovery to a Lysholm score of 83 (P=0.01) and had superior Lysholm scores at two months. EQ5D5L and IKDC scores were also significantly better at one and two months in Early HA group. There were no differences in blood ESR and CRP levels between the groups at any follow up. However, both HA groups had a significant decrease in TNF-alpha from baseline (P<0.05). No adverse events were reported. The Minimal Clinically Important Difference (MCID) for the VAS at one month was achieved by 93.3%, 60.7% and 65.5% participants respectively (p-value<0.01). However, no significant differences were observed between the groups in the percentages of patients achieving MCID for VAS at one year or for IKDC and Lysholm scores at one month, two months, and one year., Conclusion: Early IAHA injection following ACLR effectively reduces pain and improves ROM during the early postoperative period, leading to enhanced functional outcomes and quality of life. However, these benefits were not sustained beyond 2 months and no clinical benefits were noted at 6- and 12-month follow-ups. The treatment was found to be safe and well-tolerated for postoperative use. Notably, there was no significant difference in the number of patients achieving MCID for functional scores, except for pain at one month., (Copyright © 2025. Published by Elsevier Inc.)

The topological properties of the A15-type compound Ti 3 Pd reveal a complex landscape of multi-fold fermionic and bosonic states, as uncovered through ab initio calculations within the framework of density functional theory (DFT). The electronic band structure shows multi-fold degenerate crossings at the high-symmetry point R near the Fermi level, which evolves into 4-fold and 8-fold degenerate fermionic states upon the introduction of spin-orbit coupling (SOC). Likewise, the phononic band structure features multi-fold degenerate bosonic crossings at the same R point. Topological analysis, including the calculation of  2 invariant and surface states, confirms the non-trivial nature of Ti 3 Pd. Moreover, both fermionic and bosonic quasiparticles exhibit nodal line features, whose topological non-triviality is further substantiated by Berry phase calculation. This research illuminates the intricate topological framework of Ti 3 Pd, opening avenues for experimental exploration in the field of topological quantum materials.

Background: Equine herpesvirus type 1 (EHV1) is a ubiquitous viral pathogen infecting the equine population worldwide. EHV1 infection causes respiratory illness, abortion, neonatal foal mortality, and myeloencephalopathy. The currently available modified live EHV1 vaccines have safety and efficacy limitations. The two mutant EHV1 viruses (vToH-DMV (∆IR6/gE) and vToH-QMV (∆IR6/UL43/gE/UL56)), generated by the deletion of genes responsible for virulence (gE and IR6) and immunosuppression (uL43 and uL56), have been previously characterized by our group and found to generate good immune responses. The present study aimed to determine the safety and protective efficacy of the above mutants against a virulent EHV1 challenge in a murine model., Methods: BALB/c mice were intranasally immunized with a live vToH-QMV or vToH-DMV vaccine. Intranasal booster immunization was given at 14 days post-vaccination (dpv). Both mutants induced an optimal level of EHV1-specific humoral and cell-mediated immune responses, as determined by virus neutralization assay, ELISA, and immunophenotyping. At 35 dpv, the mice were intranasally challenged with wild-type EHV1 (vRaj strain)., Results: Amongst the two mutants, vToH-QMV induced a better immune response than the vToH-DMV vaccine. Furthermore, vToH-QMV provided good protection in mice against the virulent challenge. It specifically exhibited less severe clinical disease in terms of clinical signs, body weight reduction, and gross and histopathological lung lesions accompanied by early virus clearance., Conclusions: These studies are suggestive of vToH-QMV EHV1 being a potential vaccine candidate against EHV1 infection, which needs to be finally tested in the main host, i.e., horses.

Antibiotics are extensively used to manage human, animal and plant ailments caused by microbial infections. However, rampant use of antibiotics has led to the development of antibiotic resistance, which is a public health concern. The development of antibiotic resistance is significantly influenced by agro-ecosystems. Rice agroecosystem receives high levels of antibiotics from direct applications, and sources like manure and irrigation water. Consequently, uptake of antibiotic residues by rice (Oryza sativa L.) is resulting in accumulation of antibiotics in plant parts. Accumulation of these antibiotics can be toxic to plant, and can be partitioned to rice grain and straw, and reach the human and animal food chain leading to the development of antibiotic resistance. Moreover, the antibiotics can alter soil microbes, which would result in loss of production. This study compiles information from existing literature on global antibiotic usage and explores how antibiotics enter the rice ecosystem through contaminated wastewater, manure, sewage sludge, and through direct application. A detailed discussion on the persistence and movement of antibiotics in different environment compartments is provided. The review also highlights the impacts of antibiotics on plants and natural microbiota, as well as issues pertaining to antimicrobial resistance in public health sectors. For sustainable mitigation of the issues of antibiotic residues in rice ecosystem, we suggest application of decontaminated manure, microbial bioremediation, optimization of the use of plant-based alternatives, enhancing regulations, and fostering global collaboration. We advocate integrated disease management approaches which can significantly reduce the antibiotic use in rice agroecosystem., Competing Interests: Declarations. Ethics approval: The study did not involve any human or animal testing and thus ethics approval is not required. Consent to participate: Not applicable Conflict of interest: The authors declare that they have no conflict of interest., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Despite early promising results with denosumab treatment in giant cell tumor of bone (GCTB), recent studies have raised concerns about a high local recurrence rate following preoperative denosumab administration and joint preservation surgery. This retrospective study evaluated data from 25 high-risk GCT patients (Campanacci grade II or III with features like soft tissue extension, pathological fracture, minimal periarticular or subarticular bone) treated with five doses of neoadjuvant denosumab injection followed by either curettage and cementing ( n  = 13) or joint reconstruction with fibular graft/endoprosthesis ( n  = 12) between 2014 and 2019. With an average follow-up of 40 months, the study found only one patient of local recurrence. All patients were independently ambulant, with a mean MSTS score of 26.32. Subgroup analysis revealed an MSTS score of 27.76 in the joint preservation group, and 24.75 in the excision with reconstruction/prosthetic replacement group (unpaired t -test, p -value < 0.001). Five patients experienced postoperative complications, including two infections, one recurrence, one mediolateral instability in the prosthetic component, and one restriction of wrist movement. A short course of neoadjuvant denosumab, followed by curettage and cementing or wide excision with joint reconstruction/prosthetic replacement, appears to be an effective strategy for high-risk GCTB patients. This approach not only minimizes surgical morbidity but also does not increase the local recurrence rate. The short course regimen may present a cost-effective and practical option in clinical practice., Competing Interests: Conflict of InterestThe authors declare no competing interests., (© The Author(s), under exclusive licence to Indian Association of Surgical Oncology 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

A microcosm experiment was performed to quantify the residues of antibiotics [tetracycline (TC), streptomycin (STR), and streptocycline (STC; a mixture of TC and STR)] in rice soil and to assess their impact on microbial community structure and function using Illumina-MiSeq metagenomic analysis. Antibiotics were applied at half the recommended dose (0.5RD), recommended dose (RD), and double the recommended dose (2RD). At RD, TC was degraded in soil within 9 days of its application, whereas it took 21 days for STR and STC to degrade below limit of quantification (LOQ) level. The residue data were fitted in decay models, and half-lives (DT 50 ) were 46.5-53.3 h and 177.6-198 h for TC and STR, respectively. Soil enzyme activities (dehydrogenase, β-glucosidase, fluorescein diacetate hydrolase, acid phosphatase, alkaline phosphatase) were negatively affected in the antibiotic-treated soil. Targeted metagenomic analysis showed that the major bacterial phyla such as Chloroflexi, Actinobacteria, Planctomycetes, Crenarchaeota, and Gemmatimonadetes were suppressed by antibiotic treatments as compared to control. Shannon, Simpson, ACE, and Chao1 diversity indices showed that bacterial diversity decreased with the application of antibiotics, and decrease in bacterial diversity was more prominent in case of STC as compared to TC and STR. Overall, the combination of antibiotics negatively affected the soil microbial community structure and function in comparison to their individual application., Competing Interests: Declarations. Ethics approval: The study did not involve any human or animal testing, and thus ethics approval is not required. Consent to participate: Not applicable Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Aneurysmal bone cyst (ABC) is a rare, benign, cystic, hemorrhagic expansile osteolytic lesion of unknown etiology resembling multiple intraosseous blood-filled spaces mostly seen in the first two decades of life. It accounts for <1% of all bone tumors and the usual sites are the metaphyses of the proximal and distal femur, proximal tibia, and posterior elements of the spine. Affection of other sites is unusual., Case Report: A 55-year-old female with a 5-month history of pain and swelling of distal ulna. She was operated on with curettage, bone grafting, and plating. At 1-year follow-up, she regained complete movements without any recurrence., Conclusion: In this article, we present a case of a primary ABC of distal ulna in an unusual age group of 55 years in a female. The clinical presentation, diagnosis, surgical management, and clinical outcome at 1 year are described., Competing Interests: Conflict of Interest: Nil, (Copyright: © Indian Orthopaedic Research Group.)

Background: Intraarticular anteroinferior iliac spine (AIIS) avulsion fractures combined with hip dislocation are infrequently reported in medical literature. This study aims to present the outcomes of surgical treatment for this rare type of injury., Methods: We retrospectively analyzed six cases of AIIS avulsion fracture with hip dislocation treated surgically. All patients underwent emergency hip reduction under sedation followed by open reduction and internal fixation using 4 mm cannulated screws through the iliofemoral approach., Results: After an average follow-up period of 50 months, all fractures healed. Clinically, four patients were rated as having an excellent outcome and two as good, according to the Harris Hip Score. Radiological assessment using Matta's grading system showed excellent results in five patients and good in one. All patients were able to resume their pre-injury activity levels within six months post-surgery., Conclusion: Surgical fixation of AIIS avulsion fractures with associated hip instability demonstrates favourable outcomes, ranging from good to excellent, in both clinical and radiological assessments at medium-term follow-up. This suggests that surgical intervention is a viable option for managing such injuries., Competing Interests: We declare that there is no conflict of interest to disclose for the article submitted titled, “"Intraarticular Anterior Inferior Iliac Spine Avulsion with Hip Instability: A Case Series of Six Patients"., (© 2024 Delhi Orthopedic Association. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Background: The foremost concern and challenge in managing drug-resistant tuberculosis is ensuring a high health-related quality of life (HRQoL). The effectiveness of pre-extensively drug-resistant (Pre-XDR) tuberculosis management hinges on patients adhering to therapy, a crucial factor in averting the development of drug-resistant strains, ultimately enhancing HRQoL., Methodology: This analytical longitudinal study spanned two years at a teaching hospital and involved collaboration between the Departments of Pharmacology and Pulmonary Medicine. A case record form was utilized to gather baseline data, encompassing patient demographics, medication details, WHO BREF HRQoL scores, and treatment adherence. Patients were classified as either adherent or nonadherent using three distinct criteria: the guidelines of the Revised National Tuberculosis Programme (RNTCP), the Morisky-Green-Levine Scale (MGLS), and the Batalla test. The sample size was determined based on 30% nonadherence rates from preliminary analysis of prior data, resulting in 86 patients included in the study. The association between the improvement of HRQoL score from the baseline with the predictor variables was assessed with a linear regression model. Comparison of nonadherence with the different predictors of the study population was assessed with binary logistic regression model., Results: Analysis of demographic data revealed no notable differences in age and BMI between the Bedaquiline and Delamanid groups. However, there was a gender-related difference in treatment distribution, with more men in the Bedaquiline group. Other factors, such as marital status, socioeconomic status, employment status, stigma/discrimination, comorbidity, and addiction, showed no significant differences between the groups. Comparing HRQoL scores at baseline and after six months showed substantial improvements in all domains, indicating a positive impact of the treatment. Linear regression analysis revealed a strong association between QoL improvement and adherence. Adherence patterns did not significantly differ between the two treatment groups, as assessed by various criteria. The patients with high stigma, newly diagnosed Pre-XDR cases, and the presence of adverse events had higher odds of nonadherence., Conclusion: This study highlights the substantial impact of Bedaquiline and Delamanid treatment on the HRQoL of Pre-XDR TB patients in Eastern India. Adherence to treatment plays a crucial role in improving QoL, and factors like stigma, newly diagnosed Pre-XDR patients, and adverse drug reactions influence adherence adversely. The findings emphasize the importance of patient support and education to enhance treatment outcomes., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Family Medicine and Primary Care.)

Objective: The objective of this study is to evaluate the prognostic value of nutritional scores comprising the Controlling Nutritional Status (CONUT) score and the Prognostic Nutritional Index (PNI), in prediction of multilevel vertebral involvement (> 2 vertebra) in Spinal Tuberculosis (STB)., Methods: Retrospective analysis of 39 STB patients was conducted to assess nutritional indices (CONUT and PNI) and the numbers of vertebral affection. Spearman's correlation was used to examine the association between these variables. Receiver Operating Characteristic (ROC) curves were utilized to determine optimal cutoff values, with Area Under the Curve (AUROC) evaluation. Additionally, multiple logistic regression was performed as a predictive model., Results: There were 24 males and 15 females, with a mean BMI of 18.88 kg/m² (± 1.37). Spearman's correlation analysis revealed negative correlations between BMI, PNI (rho - 0.68, p < 0.001) and multilevel vertebra involvement, while ESR (rho 0.83, p < 0.001), CRP (rho 0.81, p < 0.001), and CONUT score (rho 0.83, p < 0.001) positively correlated with multilevel vertebral affection (> 2 vertebra). Age and comorbidities showed no correlation with the level of vertebral affection. ROC analysis revealed a CONUT Score ≥ 3 cutoff (sensitivity-95.7%, specificity-87.5%) and PNI ≤ 38.605 (sensitivity-78.3%, specificity-93.8%) for predicting multilevel STB (> 2). PNI exhibited superior specificity and positive predictive value where as CONUT score was a better parameter for sensitivity, negative predictive value and diagnostic accuracy. Both CONUT score and PNI were significant predictors of vertebral involvement in univariate analysis, with multivariate analysis identifying CONUT score as the sole predictor of multilevel vertebral affection., Conclusion: Nutritional scores, including CONUT score and PNI, emerged as significant predictors of multilevel STB. CONUT score displayed superior sensitivity, negative predictive value, and overall diagnostic accuracy, while PNI served as a nutritional marker with high specificity and positive predictive value in predicting multilevel involvement in spinal tuberculosis., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Context: Access to safe and nutritious food is key to promoting good health. An estimated 600 million fall ill after eating contaminated food, for which food handlers may constitute a common source of contamination. In addition to unhealthy food handlers, disease carriers handling the food play an equally important role in transmitting these diseases and pose a significant threat to public health. This study, therefore, aimed to know the morbidity profile among the food handlers employed in various food establishments in Panaji city., Methods and Material: Using stratified sampling techniques, we conducted a cross-sectional study among 227 participants selected from 12 food establishments. We did three visits to each food establishment. We excluded food handlers who were unavailable despite three visits at fortnightly intervals and those who did not consent to the study. We administered a pre-designed and pre-structured questionnaire to each participant. A general examination and laboratory investigations, including stool and urine routine, were performed on all participants. We performed descriptive and analytical statistics by using SPSS version 14., Results: Out of the 227 study participants, 79 (34.8%) had at least one morbidity at the time of examination. None of the food handlers had received a single dose of typhoid, hepatitis A, or cholera vaccines. Most (74.4%) study participants did not administer deworming tablets., Conclusions: We found that the health status of the study participants was substandard. Food safety may be in peril among food handlers with lower education backgrounds with morbidities as they may have little understanding of the risk of microbial contamination of food. Therefore, it is essential to create awareness among them., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Family Medicine and Primary Care.)

In the present study, we report the evolution of stabilizing Pickering emulsions using brush-modified Janus particles (JPs), utilizing the dissipative particle dynamics (DPD) simulation technique. Our results are subsequently corroborated with experimental findings. Each JP has one-half of the hydrophobic surface, with the other half embedded with hydrophilic polymer brushes grown via atom transfer radical polymerization (ATRP). Our generic simulation model analyzes the chemical kinetics of polymer brush growth on one-half of the initiator-embedded microparticle (MP) surface, resulting in the formation of JP. This involves evaluating monomer conversion and reaction rates. Our results exhibit a substantial influence of the number of JPs, grafted brush density, and brush length on oil-in-water emulsion stability. We studied the evolution kinetics and stability of emulsion formation by analyzing the growth of average domain size and corresponding scaling functions up to a late time limit. This study aims to clarify the connection between the size, quantity, and functionality of JPs and the stability of Pickering emulsions.

Background: The interaction between the recipient area and the graft is one of the key factors in the success of periodontal plastic surgery. This randomized controlled, split-mouth, double-blinded clinical trial aimed to compare the clinical and aesthetic outcomes of epithelialized palatal graft (EPG) and gingival unit graft (GUG) in achieving root coverage in localized (Recession Type 1) RT1 recession defects., Methods: Twenty participants with forty bilateral recession defects randomly received EPG or GUG surgical treatment modalities for each of the recession defects. Clinical measurements recorded at baseline and after six months included recession depth (RD), recession width (RW), probing depth (PD), clinical attachment level (CAL), keratinized tissue width (KTW), and the average width of mesial and distal interdental papilla (aWIDP)., Results: There was a statistically significant greater mean root coverage (MRC) percentage at GUG sites (80.68 ± 16.12%) in comparison to EPG sites (71.05 ± 17.23%) ( p  = 0.01). The treatment satisfaction ( p  = 0.009) and aesthetic satisfaction ( p  < 0.001) experienced were significantly better for GUG as compared to EPG. The regression model ( R 2  = 0.56) significantly predicted MRC percentage in GUG sites with baseline RD ( β  = -12.49; p  = 0.02) and aWIDP ( β  = -9.31; p  = 0.02)., Conclusion: GUG showed a better MRC, aesthetics and increased KTW. Root coverage procedures often need to suffice the dual objective of coverage and aesthetics at the same time. GUG is a simple modification of the conventional EPG that can provide better clinical and aesthetic outcomes., (© 2024 Director General, Armed Forces Medical Services. Published by Elsevier, a division of RELX India Pvt. Ltd.)

Novel structurally intriguing heterocycles embedded with spiropyrrolidine, quinoxaline and chromanone units were synthesized in good yields using a [Bmim]Br accelerated multicomponent reaction strategy. The key step of the reaction is 1,3-dipolar cycloaddition involving highly functionalized dipolarophile, viz. 3-benzylidenechroman-4-one, to afford spiroquinoxalinopyrrolidine embedded chromanone hybrid heterocycles. The formation of spiro products occurs via two C-C, two N-C and one C-N bonds possessing four adjoining stereogenic centers, two of which are spiro carbons. The newly synthesized spiro compounds showed potent acetylcholinesterase and butyrylcholinesterase inhibitory activities. Moreover, compounds with fluorine displayed the highest AChE (3.20 ± 0.16 μM) and BChE (18.14 ± 0.06 μM) inhibitory activities. Further, docking studies, followed by all-atom molecular dynamics, showed results that are consistent with in vitro experimental findings. Although docking scores for the synthesized derivatives were higher than those of the standard drug, MD MMPBSA results showed better binding of synthesized derivatives (-93.5 ± 11.9 kcal mol -1 ) compared to the standard drug galantamine (-66.2 ± 12.3 kcal mol -1 ) for AChE but exhibited similar values (-98.1 ± 11.2 and -97.9 ± 11.5 kcal mol -1 ) for BChE. These differences observed in drug binding with AChE/BChE are consistent with RMSD, RMSF, LIG plots, and FEL structural analysis. Taken together, these derivatives could be potential candidates as inhibitors of AChE and BChE., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

A man in his 30s came to our clinic with a year-long history of progressive pain and swelling in his knee. Diagnostic imaging revealed a displaced patellar fracture with an osteolytic, septated lesion and thinned expanded cortex in both fracture fragments. A core needle biopsy confirmed the diagnosis of giant cell tumour. Treatment involved wide excision of the tumour and the use of polypropylene mesh and a peroneal longus tendon autograft to reconstruct the extensor mechanism of the knee joint. One year postoperatively, the patient experienced no pain, demonstrated full range of motion and showed no signs of functional impairment or local tumour recurrence. This case highlights that reconstruction of the extensor mechanism of the knee after tumour excision with synthetic mesh is an affordable, user-friendly and widely accessible method. It can address large defects effectively while minimising the risks of disease transmission and graft lengthening, resulting in satisfactory outcomes., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

The escalating research in the field of topology necessitates an understanding of the underlying rich physics behind the materials possessing unique features of non-trivial topology in both electronic and phononic states. Due to the interaction between electronic quasiparticles and spin degrees of freedom, the realization of magnetic topological materials has opened up a new frontier with unusual topological phases, however, these are rarely reported alongside phononic quasiparticle excitations. In this work, by first-principles calculations and symmetry analysis, the intermetallic ferromagnetic compounds MnGaGe and MnZnSb with the coexistence of exceptional topological features in the electronic and phononic states are proposed. These compounds host nodal surface onky=πplane in bulk Brillouin zone in the electronic and phononic spectra protected by the combination of time-reversal symmetry and nonsymmorphic two-fold screw-rotation symmetry. In the former case, a spin-polarized nodal surface is present in the majority and minority spin channels and found to be robust to ground-state magnetic polarization. The presence of nodal line features is analyzed in both the quasiparticle spectra, whose non-trivial nature is confirmed by the Berry phase calculation. The incorporation of spin-orbit coupling in the electron spectra introduces distinctive characteristics in the transport properties, facilitating the emergence of anomalous Hall conductivity through Berry curvature in both bulk and monolayer. Furthermore, the monolayer has been proposed as a two-terminal device model to investigate the quantum transport properties using the non-equilibrium Green's function approach. This superlative combination of observations and modeling sets the path for a greater level of insight into the behavior and aspects of topological materials at the atomic scale., (© 2024 IOP Publishing Ltd.)

Huntington's disease is associated with increased CAG repeat resulting in an expanded polyglutamine tract in the protein Huntingtin (HTT) leading to its aggregation resulting in neurodegeneration. Previous studies have shown that N-terminal HTT with 46Q aggregated in the stationary phase but not the logarithmic phase in the yeast model of HD. We carried out a metabolomic analysis of logarithmic and stationary phase yeast model of HD expressing different polyQ lengths attached to N-terminal HTT tagged with enhanced green fluorescent protein (EGFP). The results show significant changes in the metabolic profile and deregulated pathways in stationary phase cells compared to logarithmic phase cells. Comparison of metabolic pathways obtained from logarithmic phase 46Q versus 25Q with those obtained for presymptomatic HD patients from our previous study and drosophila model of HD showed considerable overlap. The arginine biosynthesis pathway emerged as one of the key pathways that is common in stationary phase yeast compared to logarithmic phase and HD patients. Treatment of yeast with arginine led to a significant decrease, while transfer to arginine drop-out media led to a significant increase in the size of protein aggregates in both logarithmic and stationary phase yeast model of HD. Knockout of arginine transporters in the endoplasmic reticulum and vacuole led to a significant decrease in mutant HTT aggregation. Overall our results highlight arginine as a critical metabolite that modulates the aggregation of mutant HTT and disease progression in HD.Communicated by Ramaswamy H. Sarma.

Transcriptomics is a complex process that involves raw data extraction, normalization, differential gene expression, and analysis. The Gene Expression Omnibus (GEO) database at the National Center for Biotechnology Information (NCBI) is a repository of experimental datasets. Amyotrophic lateral sclerosis (ALS) datasets are deposited by various scientists and research investigators to expand the horizon of scientific knowledge. R-statistical tools are the most common ways for conducting these kinds of studies. The first step is the identification of appropriate datasets. Since the raw data is available in a variety of formats, a large array of software is used for extraction and analysis. Normalization is conducted for the datasets using NetworkAnalyst. Differential analysis is further conducted on the normalized data to identify significantly enriched genes. The significant genes are then grouped into pathways. The results were validated using yeast model of ALS in which the yeast is transformed with ALS plasmids encoding genes associated with ALS. The resulting GFP-tagged protein aggregates are imaged using fluorescence microscopy and subsequently validated using filter retardation assay and quantified using ImageJ software. Functional role of different genes is studied using metabolite treatment and knockout studies., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Avascular necrosis of femoral head (AVNFH) is a debilitating disease of the young, affecting the quality of life significantly and eventually leading to total hip replacement surgery. The disease is diagnosed clinico-radiologically and MRI is the investigation of choice to diagnose the early stages of the disease. There is neither an early biomarker for detection nor is there a permanent cure for the disease and most of the patients are managed with various combinations of surgical and medical management protocols. In this review, we comprehensively address the etiopathogenesis, clinical characteristics, therapeutic procedures, bone characteristics, histopathology, multi-omic studies, finite element modeling, and systems analysis that has been performed in AVNFH. The etiology includes various factors that compromise the blood supply to the femoral head which also includes contributions by environmental and genetic factors. Multi-omic analysis has shown an association of deregulated pathways with the disease. The cell types involved include mesenchymal stem cells, osteoblasts, osteoclasts, endothelial and immune cells. Biochemical, hematological, histopathology, IHC, and other bone remodeling and degradation marker studies have been performed. A systems analysis using multi-omic data sets from published literature was carried out, the relevance of which is discussed to delineate potential mechanisms in etiopathogenesis, diagnosis, and effective management of this debilitating disease., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

The article deals with the integrated and comprehensive study of the coal-bearing horizons from the South Karanpura Basin to delineate the biostratigraphy, palaeovegetation, palaeodepositional settings, and palaeoclimate in and around the investigated area during the deposition of Permian sediments. Highly diversified megafloral assemblages consist 13 genera and 72 species of order Glossopteridales, Cordaitales and Equisetales are documented among which 37 taxa are newly reported from Barakar and Raniganj formations of the area. Palynoassemblages-I and -II are recovered, which demonstrate the biostratigraphic age as Kungurian and Wordian-Capitanian, respectively. Overall the vegetation represents a luxuriant forest subjugated by arborescent deciduous trees bearing Glossopteris foliage with some conifers, cordaites, filicales, and peltaspermales. The biomarker study of the basin illustrates the unimodal distribution of n-alkanes in the sample set ranges from C 14 to C 29 which suggests major input from a single source of organic matter. The involvement of microbial activity and algal input is suggested for the basin. A relatively moderate-to-high water level condition can be inferred from elevated n-C 25 . The high CIA, PIA values and A-CN-K plot suggest intense weathering conditions in the source area. The source rocks are characterized by mature clayey type with abundant clay mineral, i.e., kaolinite. The current study portrays that the Permian climate was cooler in initial phase, which later on became warm temperate with high humidity. The palaeofloral entities and geochemical parameters suggest absolute diversification of Permian flora, the existence of continental freshwater setting in the vicinity and oxic to anoxic environment with fluctuating ground water conditions during the deposition of sediments., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Rheumatoid Arthritis (RA) is a chronic systemic autoimmune disease leading to inflammation, cartilage cell death, synoviocyte proliferation, and increased and impaired differentiation of osteoclasts and osteoblasts leading to joint erosions and deformities. Transcriptomics, proteomics, and metabolomics datasets were analyzed to identify the critical pathways that drive the RA pathophysiology. Single nucleotide polymorphisms (SNPs) associated with RA were analyzed for the functional implications, clinical outcomes, and blood parameters later validated by literature. SNPs associated with RA were grouped into pathways that drive the immune response and cytokine production. Further gene set enrichment analysis (GSEA) was performed on gene expression omnibus (GEO) data sets of peripheral blood mononuclear cells (PBMCs), synovial macrophages, and synovial biopsies from RA patients showed enrichment of Th1, Th2, Th17 differentiation, viral and bacterial infections, metabolic signalling and immunological pathways with potential implications for RA. The proteomics data analysis presented pathways with genes involved in immunological signaling and metabolic pathways, including vitamin B12 and folate metabolism. Metabolomics datasets analysis showed significant pathways like amino-acyl tRNA biosynthesis, metabolism of amino acids (arginine, alanine aspartate, glutamate, glutamine, phenylalanine, and tryptophan), and nucleotide metabolism. Furthermore, our commonality analysis of multi-omics datasets identified common pathways with potential implications for joint remodeling in RA. Disease-modifying anti-rheumatic drugs (DMARDs) and biologics treatments were found to modulate many of the pathways that were deregulated in RA. Overall, our analysis identified molecular signatures associated with the observed symptoms, joint erosions, potential biomarkers, and therapeutic targets in RA.Communicated by Ramaswamy H. Sarma.

Purpose: Dengue is a mosquito vector-borne disease caused by the dengue virus, which affects 125 million people globally. The disease causes considerable morbidity. The disease, based on symptoms, is classified into three characteristic phases, which can further lead to complications in the second phase. Molecular signatures that are associated with the three phases have not been well characterized. We performed an integrated clinical and metabolomic analysis of our patient cohort and compared it with omics data from the literature to identify signatures unique to the different phases., Methods: The dengue patients are recruited by clinicians after standard-of-care diagnostic tests and evaluation of symptoms. Blood from the patients was collected. NS1 antigen, IgM, IgG antibodies, and cytokines in serum were analyzed using ELISA. Targeted metabolomics was performed using LC-MS triple quad. The results were compared with analyzed transcriptomic data from the GEO database and metabolomic data sets from the literature., Results: The dengue patients displayed characteristic features of the disease, including elevated NS1 levels. TNF-α was found to be elevated in all three phases compared to healthy controls. The metabolic pathways were found to be deregulated compared to healthy controls only in phases I and II of dengue patients. The pathways represent viral replication and host response mediated pathways. The major pathways include nucleotide metabolism of various amino acids and fatty acids, biotin, etc. CONCLUSION: The results show elevated TNF-α and metabolites that are characteristic of viral infection and host response. IL10 and IFN-γ were not significant, consistent with the absence of any complications., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

To date, the synthesis of efficient and safe gene carriers with low toxicity and appreciable gene transfection efficiency has been the major hurdle associated with non-viral gene carriers. Herein, we synthesized three amino acid-based diblock copolymers comprising glycine-leucine, leucine-phenyl alanine and glycine-phenyl alanine group containing blocks. The synthesis of all the diblock copolymers was confirmed by FTIR, 1 H NMR, DLS and GPC techniques. All the polymers showed a high positive zeta potential value that varies from 45 ± 1 mV to 56 ± 1 mV, and the hydrodynamic size of the polymers varies from 250 ± 8 to 303 ± 14 nm. The three polymers showed negligible cytotoxicity compared with PEI (25 kDa) for MDA-MB-231 and NKE cells. Among all other polymers, P(HGN) n - b -P(HPN) m exhibited the highest biocompatibility with ∼70% cell viability at a concentration of 200 μg mL -1 . Hemolysis data revealed that among all three polymers, P(HGN) n - b -P(HPN) m exhibited the highest blood compatibility, while up to a high concentration of 200 μg mL -1 , it showed a very negligible amount (∼18%) of hemolysis. Most importantly, excellent gene complexation capability and good protection of pDNA against enzymatic degradation were observed with all three diblock copolymers. Interestingly, P(HGN) n - b -P(HPN) m /pDNA complex showed the smallest particle size (∼15 nm) and highest positive zeta potential as observed from TEM micrographs and DLS analysis, which probably results significantly higher level of cellular uptake and hence the highest transfection efficiency (∼85%) against MDA-MB-231 cells. Therefore, the diblock copolymer P(HGN) n - b -P(HPN) m with superior gene transfection efficiency in triple negative breast cancer may be an efficient non-viral vector for successful TNBC therapy in the future.

Amyotrophic lateral sclerosis (ALS) is a multi-systemic, incurable, amyloid disease affecting the motor neurons, resulting in the death of patients. The disease is either sporadic or familial with SOD1, C9orf72, FUS, and TDP-43 constituting the majority of familial ALS. Multi-omics studies on patients and model systems like mice and yeast have helped in understanding the association of various signaling and metabolic pathways with the disease. The yeast model system has played a pivotal role in elucidating the gene amyloid interactions. We carried out an integrated transcriptomic and metabolomic analysis of the TDP-43 expressing yeast model to elucidate deregulated pathways associated with the disease. The analysis shows the deregulation of the TCA cycle, single carbon metabolism, glutathione metabolism, and fatty acid metabolism. Transcriptomic analysis of GEO datasets of TDP-43 expressing motor neurons from mice models of ALS and ALS patients shows considerable overlap with experimental results. Furthermore, a yeast model was used to validate the obtained results using metabolite addition and gene knock-out experiments. Taken together, our result shows a potential role for the TCA cycle, cellular redox pathway, NAD metabolism, and fatty acid metabolism in disease. Supplementation of reduced glutathione, nicotinate, and the keto diet might help to manage the disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by the formation of amyloid plaques implicated in neuronal death. Genetics, age, and sex are the risk factors attributed to AD. Though omics studies have helped to identify pathways associated with AD, an integrated systems analysis with the available data could help to understand mechanisms, potential biomarkers, and therapeutic targets. Analysis of transcriptomic data sets from the GEO database, and proteomic and metabolomic data sets from literature was performed to identify deregulated pathways and commonality analysis identified overlapping pathways among the data sets. The deregulated pathways included those of neurotransmitter synapses, oxidative stress, inflammation, vitamins, complement, and coagulation pathways. Cell type analysis of GEO data sets showed microglia, endothelial, myeloid, and lymphoid cells are affected. Microglia are associated with inflammation and pruning of synapses with implications for memory and cognition. Analysis of the protein-cofactor network of B 2 , B 6, and pantothenate shows metabolic pathways modulated by these vitamins which overlap with the deregulated pathways from the multi-omics analysis. Overall, the integrated analysis identified the molecular signature associated with AD. Treatment with anti-oxidants, B 2 , B 6 , and pantothenate in genetically susceptible individuals in the pre-symptomatic stage might help in better management of the disease., (© 2023. The Author(s).)

Huntington's disease (HD) is an incurable and progressive neurodegenerative disease affecting the basal ganglia of the brain. HD is caused due to expansion of the polyglutamine tract in the protein Huntingtin resulting in aggregates. The increased PolyQ length results in aggregation of protein Huntingtin leading to neuronal cell death. Vitamin B 6 , B 12 and folate are deficient in many neurodegenerative diseases. We performed an integrated analysis of transcriptomic, metabolomic and cofactor-protein network of vitamin B 6 , B 12 and folate was performed. Our results show considerable overlap of pathways modulated by Vitamin B 6 , B 12 and folate with those obtained from transcriptomic and metabolomic data of HD patients and model systems. Further, in yeast model of HD we showed treatment of B 6 , B 12 or folate either alone or in combination showed impaired aggregate formation. Transcriptomic analysis of yeast model treated with B 6 , B 12 and folate showed upregulation of pathways like ubiquitin mediated proteolysis, autophagy, peroxisome, fatty acid, lipid and nitrogen metabolism. Metabolomic analysis of yeast model shows deregulation of pathways like aminoacyl-tRNA biosynthesis, metabolism of various amino acids, nitrogen metabolism and glutathione metabolism. Integrated transcriptomic and metabolomic analysis of yeast model showed concordance in the pathways obtained. Knockout of Peroxisomal (PXP1 and PEX7) and Autophagy (ATG5) genes in yeast increased aggregates which is mitigated by vitamin B 6 , B 12 and folate treatment. Taken together our results show a role for Vitamin B 6 , B 12 and folate mediated modulation of pathways important for preventing protein aggregation with potential implications for HD., Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03525-y., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest in the publication., (© King Abdulaziz City for Science and Technology 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Equid alphaherpesvirus 1 (EHV-1) infection causes significant health problems in equines. The EHV-1 infection leads to abortion storm in mares, respiratory disease and myeloencephalopathy. Despite the wide use of vaccines, the outbreaks of EHV-1 infections keep occurring globally, suggesting the need for the development of improved vaccines. Gene deletion attenuated mutant viruses could be a good candidate for the development of modified live vaccines. Here, we report the generation of mutant EHV-1 by deleting virulence (glycoprotein E & internal repeat 6; IR6) and immune evasive (pUL43 & pUL56) associated genes either individually or in combinations; and comprehensive evaluation of mutants through in vitro characterization followed by in vivo study in murine model to adjudge the attenuation of the virus and immune responses generated by mutants vis-à-vis wild type (wt) virus. The EHV-1 mutants with deletion of IR6 and gE genes (vToH-DMV) and four genes (i.e., gE, IR6, pUL43 and pUL56) (vToH-QMV) revealed a significant reduction in plaque size with minimal loss in replication efficiency in comparison to the wt virus. Further, in vivo studies showed virus attenuation adjudged through significant reduction in clinical signs, weight loss, gross and histopathological lesions in comparison to wt virus also revealed improved immune responses estimated through serum neutralization and flow cytometric analysis of CD4 + and CD8 + cell populations. Thus it can be concluded that EHV-1 mutants viz. vToH-DMV and vToH-QMV (novel combination) are promising vaccine candidates and qualify to be studied for adjudging the protective efficacy with wt virus challenge., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Amyotrophic lateral Sclerosis is an incurable, progressive neurodegenerative motor neuron disease. The disease is characterized by protein aggregates. The symptoms include weakness, denervation of muscles, atrophy and progressive paralysis of bulbar and respiratory muscles and dysphagia. Various secondary metabolites are evaluated for their ability to improve symptoms in ALS. Ginseng has been traditionally used for treating several neurodegenerative diseases. Several studies using model systems have shown a potential role of Ginseng catechins and Ginsenosides in clearing protein aggregation associated with ALS. We focus on Network pharmacology approach to understand the effect of Ginseng catechins or ginsenosides on protein aggregation associated with ALS. A catechin/ginsenoside-protein interaction network was generated and the pathways obtained were compared with those obtained from transcriptomic datasets of ALS from GEO database. Knock out of MAPK14, AKT and GSK from Catechin and BACE 1 from ginsenoside modulated pathways inhibited protein aggregation. Catechins and ginsenosides have potential as therapeutic agents in the management of ALS., Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-022-03401-1., Competing Interests: Conflict of interestAll authors declare no conflict of interest., (© King Abdulaziz City for Science and Technology 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Tacrolimus (TAC) is a very effective medication in routine use after solid organ transplantation. The potential, but infrequently reported neurological adverse effect of TAC is peripheral neuropathy (PN). This has rarely been reported in heart transplant patients. To the best of our knowledge, the data regarding mononeuropathy of common peroneal nerve presented with foot drop due to low whole blood trough TAC level are very limited in the early days postheart transplantation. An idiosyncratic reaction might be suspected in the early postoperative period, when the whole blood trough levels of TAC fall below or within the desired therapeutic range associated with any adverse events after ruling out other causes. We report a 21-year-old patient, who underwent heart transplantation after a suitable donor was identified, and presented with a new-onset right side foot drop on the 10 th postoperative day. According to the WHO-Uppsala Monitoring Center causality assessment scale, the likely culprit agent is TAC. Rapid and progressive improvement of foot drop occurred after stopping it and changed over to cyclosporine., Competing Interests: None

Huntington disease (HD) is a neurodegenerative disease associated with polyglutamine expansion in the protein huntingtin (HTT). Although the length of the polyglutamine repeat correlates with age at disease onset and severity, psychological, cognitive and behavioral complications point to the existence of disease modifiers. Mitochondrial dysfunction and metabolic deregulation are both associated with the HD but, despite multi-omics characterization of patients and model systems, their mechanisms have remained elusive. Systems analysis of multi-omics data and its validation by using a yeast model could help to elucidate pathways that modulate protein aggregation. Metabolomics analysis of HD patients and of a yeast model of HD was, therefore, carried out. Our analysis showed a considerable overlap of deregulated metabolic pathways. Further, the multi-omics analysis showed deregulated pathways common in human, mice and yeast model systems, and those that are unique to them. The deregulated pathways include metabolic pathways of various amino acids, glutathione metabolism, longevity, autophagy and mitophagy. The addition of certain metabolites as well as gene knockouts targeting the deregulated metabolic and autophagy pathways in the yeast model system showed that these pathways do modulate protein aggregation. Taken together, our results showed that the modulation of deregulated pathways influences protein aggregation in HD, and has implications for progression and prognosis. This article has an associated First Person interview with the first author of the paper., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2022. Published by The Company of Biologists Ltd.)

Context: The changes in the volume and dimensions of the alveolar bone after tooth extraction often lead to challenges in prosthetic rehabilitation of the same necessitating ridge preservation procedures (RPP)., Aim: The aim of this randomized clinical trial was to evaluate and compare the dimensional and histomorphometric changes of the sites preserved using the collagen membrane with and without demineralized bone matrix (DMBM)., Settings and Design: Interventional, parallel-design, double blinded, randomized controlled trail., Materials and Methods: A randomized controlled trial was designed with 45 participants having at least 2 teeth indicated for were enrolled in this study. The sites were randomly assigned to the control group (RPP using collagen membrane) and the test group (RPP using collagen membrane with DMBM). The clinical parameters assessed were alveolar bone width and alveolar bone height. Histomorphometric analysis was carried out on tissue trephined from the preserved sites to evaluate the percentage of bone and connective tissue (CT %) formed 8 months postRPP., Statistical Analysis Used: Shapiro - Wilk test and paired and unpaired t -test., Results: Horizontal resorption was significantly less in the test group (7.375 ± 1.64). Histomorphometry of these sites revealed a complete absence of residual graft particles, presence of trabecular bone, and a more mineralized matrix (63.256%) as compared to the control sites (46.833%)., Conclusions: The use of DMBM along with the collagen membrane for RPP yielded better results both clinically and histomorphometically., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Contemporary Clinical Dentistry.)

Background: Collagen membrane and platelet-rich fibrin (PRF) have emerged as vital biomaterials in the field of periodontal regeneration. Minimally invasive techniques are being preferred by most periodontists, as it is patient compliant with fewer post-surgical complications as compared to conventional surgical techniques. Thus, in this study we have evaluated the effect of injectable PRF (i-PRF) with collagen membrane compared with collagen membrane alone using vestibular incision subperiosteal tunnel access (VISTA) technique for gingival recession coverage., Aim: To compare the efficacy of VISTA using collagen membrane with collagen membrane soaked in injectable PRF for gingival recession coverage., Methods: A split mouth randomized controlled clinical trial was designed;13 subjects having at least 2 teeth indicated for recession coverage were enrolled in this study. The sites were randomly assigned to control group (VISTA using collagen membrane alone) and the test group (VISTA using collagen membrane with i-PRF). The clinical parameters assessed were pocket depth, recession depth (RD), recession width (RW), relative attachment level, keratinised tissue width (KTW), keratinised tissue thickness (KTT), and percentage root coverage., Results: RD showed a statistically significant difference between the test group at 3 mo (0.5 ± 0.513) and 6 mo (0.9 ± 0.641) and the control group at 3 mo (0.95 ± 0.51) and 6 mo (1.5 ± 0.571), with P values of 0.008 and 0.04, respectively. RW also showed a statistically significant difference between the test group at 3 mo (1 ± 1.026) and 6 mo (1.65 ± 1.04) and the control group at 3 mo (1.85 ± 0.875) and 6 mo (2.25 ± 0.759), with P values of 0.008 and 0.001, respectively. Results for KTW showed statistically significant results between the test group at 1 mo (2.85 ± 0.489), 3 mo (3.5 ± 0.513), and 6 mo (3.4 ± 0.598) and the control group at 1 mo (2.45 ± 0.605), 3 mo (2.9 ± 0.447), and 6 mo (2.75 ± 0.444), with P values of 0.04, 0.004, and 0.003, respectively. Results for KTT also showed statistically significant results between test group at 1 mo (2.69 ± 0.233), 3 mo (2.53 ± 0.212), and 6 mo (2.46 ± 0.252) and the control group at 1 mo (2.12 ± 0.193), 3 mo (2.02 ± 0.18), and 6 mo (1.91 ± 0.166), with P values of 0.001, 0.001, and 0.001, respectively. The test group showed 91.6%, 81.6%, and 67% root coverage at 1 mo, 3 mo, and 6 mo, while the control group showed 82.3%, 66.4%, and 53.95% of root coverage at 1 mo, 3 mo, and 6 mo, respectively., Conclusion: The use of minimally invasive VISTA technique along with collagen membrane and injectable form of platelet-rich fibrin can be successfully used as a treatment method for multiple or isolated gingival recessions of Miller's class-I and class-II defects., Competing Interests: Conflict-of-interest statement: No conflict of interest., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Transcriptomic profiling of several drugs in cancer cell lines has been utilised to obtain drug-specific signatures and guided combination therapy to combat drug resistance and toxicity. Global metabolomics reflects changes due to altered activity of enzymes, environmental factors, etc. Integrating transcriptomics and metabolomics can provide genotype-phenotype correlation, providing meaningful insights into alterations in gene expression and its outcome to understand differential metabolism and guide therapy. This study uses a multi-omics approach to understand the global gene expression and metabolite changes induced by Disarib, a novel Bcl2-specific inhibitor in the Ehrlich adenocarcinoma (EAC) breast cancer mouse model. RNAseq analysis was performed on EAC mouse tumours treated with Disarib and compared to the controls. The expression of 6 oncogenes and 101 tumour suppressor genes interacting with Bcl2 and Bak were modulated upon Disarib treatment. Cancer hallmark pathways like DNA repair, Cell cycle, angiogenesis, and mitochondrial metabolism were downregulated, and programmed cell death platelet-related pathways were upregulated. Global metabolomic profiling using LC-MS revealed that Oncometabolites like carnitine, oleic acid, glycine, and arginine were elevated in tumour mice compared to normal and were downregulated upon Disarib treatment. Integrated transcriptomic and metabolomic profiles identified arginine metabolism, histidine, and purine metabolism to be altered upon Disarib treatment. Pro-angiogenic metabolites, arginine, palmitic acid, oleic acid, and myristoleic acid were downregulated in Disarib-treated mice. We further validated the effect of Disarib on angiogenesis by qRT-PCR analysis of genes in the VEGF pathway. Disarib treatment led to the downregulation of pro-angiogenic markers. Furthermore, the chorioallantoic membrane assay displayed a reduction in the formation of the number of secondary blood vessels upon Disarib treatment. Disarib reduces tumours by reducing oncometabolite and activating apoptosis and downregulating angiogenesis.

Background: Gingival recession leads to root surface exposure devoid of periodontal attachment. Recession defects with interdental attachment loss (RT2, RT3), further increase the avascular area which is critical for survival of soft-tissue grafts. Nonsubmerged grafts such as free gingival grafts and gingival unit grafts (GUGs) rely primarily on plasmatic circulation from the recipient area during the initial stages of healing for its survival., Methods: Nineteen isolated RT2 recession defects, in the mandibular anterior region, were treated using GUG. The clinical parameters of recession depth (RD), recession width (RW), interdental clinical attachment levels (iCAL) were measured at baseline. Percentage of mean root coverage (MRC) was calculated at 3 months and 6 months., Results: The percentage of mean root coverage (MRC) achieved at the end of 6 months was 81.79% ± 6.16%. Further, Simple linear regression analysis to predict MRC at 6 months using baseline RW revealed, for every 1 mm decrease in RW, the percentage of root coverage significantly increased by 5.25% ( P = 0.04)., Conclusion: GUG can be used as an alternative treatment modality to achieve successful root coverage in RT2 recession defects. Baseline RW can be used to predict the outcome of root coverage at the end of 6 months., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Indian Society of Periodontology.)

Background: Limb length alteration following total knee arthroplasty (TKA) has been under-reported. Few studies have shown a significant association between limb length discrepancy (LLD) and poor functional outcome. This prospective study evaluated the impact of radiographic and perceived LLD on functional outcome in TKA. The variables affecting LLD were also evaluated., Methods: The preoperative and postoperative limb lengths of TKA patients (112 knees, 81 patients, KL grade ≥ 3) were measured in full-length digital radiographs. The Hip-Knee-Ankle (HKA) angles were also measured. The functional outcome (Western Ontario and McMaster Universities Arthritis Index) and perception about LLD were evaluated after six months., Results: The mean preoperative radiographic LLD in the unilateral and bilateral TKA groups was 0.75 cm ± 0.60 cm and 0.58 cm ± 0.52 cm (P = 0.197), respectively. Similarly, postoperative LLD was 0.76 cm ± 0.85 cm in the unilateral group and was 0.59 cm ± 0.92 cm (P = 0.402) in the bilateral group. Only 19.7% of patients had postoperative radiographic LLD of ≥ 10 mm, and 80.2% of patients had LLD of < 10 mm. The functional outcome was significantly affected when LLD exceeded 10 mm (correlation coefficient 0.54, P < 0.001). Linear regression analysis revealed no significant effects of age, sex, height, weight, BMI, preoperative LLD and difference in deformity between the limbs on postoperative LLD. 34.5% of patients perceived LLD in the preoperative period, which decreased to 3.7% in the postoperative period. Perceived LLD did not correlate to radiographic LLD and functional outcome., Conclusions: There is no significant difference in radiographic LLD between unilateral and bilateral TKA. The functional outcome is adversely affected by radiographic LLD of ≥ 10 mm. Age, sex, BMI, preoperative LLD and difference in deformity angle do not affect the LLD. About one-third of patients perceive LLD in the preoperative period, which improves significantly after TKA., Levels of Evidence: II., (© 2022. The Author(s).)

Triflumezopyrim (TMP), a mesoionic insecticide, is commonly used for controlling planthoppers in rice. However, the relationship between the TMP residue and toxicity against brown planthoppers (BPHs) has not been studied in detail. We are reporting the dissipation of TMP from rice plant and soil under field conditions. The median lethal dose and median lethal concentration were 0.036 ng per insect and 0.525 mg L -1 , respectively. TMP at recommended dose (25 g a.i. ha -1 ) recorded 1.25 live BPH per hill as against 25.5 per hill in control at 14 days after treatment. TMP was considered to be harmless to the natural enemies, namely, Cyrtorhinus lividipennis and Lycosa pseudoannulata in the rice ecosystem. The residue of TMP from rice plant and soil was estimated using the QuEChERS method using three different doses (12.5, 25, and 50 g a.i. ha -1 ). The limit of quantitation (LOQ) of TMP in plant and soil was 5 µg kg -1 and 1 µg kg -1 , respectively. The maximum content of TMP in soil was less than 1% that of plant content on day 1. The dissipation pattern of TMP both from plant and soil was better explained by the first-order double-exponential decay model (FODED) as compared to the first-order kinetic model. Overall, the half-lives of TMP were ranged from 2.21 to 3.02 days in plant tissues and 3.78 to 4.79 days in soil as per the FODED model. Based on the persistence and toxicity of TMP, we could conclude that TMP will be effective against BPH up to 7-10 days after application. Triflumezopyrim with reasonable persistence and high efficacy could be recommended as an alternate pesticide in BPH management in rice., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Current advancements in the creation of anisotropy in particles and their surface modification with polymer brushes have established a new class of hybrid materials termed polymer brush modified anisotropic particles (PBMAP). PBMAPs display unique property combinations, e.g., multi-functionality in multiple directions along with smart behavior, which is not easily achievable in traditional hybrid materials. Typically, anisotropic particles can be categorized based on three different factors, such as shape anisotropy (geometry driven), compositional anisotropy (functionality driven), and surface anisotropy (spatio-selective surface modification driven). In this review, we have particularly focused on the synthetic strategies to construct the various type of PBMAPs based on inorganic or organic core which may or may not be isotropic in nature, and their applications in various fields ranging from drug delivery to catalysis. In addition, superior performances and fascinating properties of PBMAPs over their isotropic analogues are also highlighted. A brief overview of their future developments and associated challenges have been discussed at the end., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Aim: The study aimed to longitudinally evaluate the efficacy of gingival unit grafts (GUGs), a modification of free gingival grafts, in the management of Miller's class I and class II recession defects in mandibular anterior region, over a period of 18 months., Materials and Methods: 17 subjects with 21 recession defects in mandibular anterior region were treated using GUG. Clinical parameters of recession depth (RD), clinical attachment levels (CALs), and keratinized tissue width (KTW) were recorded at baseline, 1, 6, and 18 months. Patient-centered outcomes were measured using a visual analog scale (VAS) for pain and discomfort on 14th postoperative day and for treatment satisfaction at the end of 18 months., Results: There was a statistically significant improvement in RD, CAL, and KTW at 18 months when compared to baseline levels. A mean root coverage (MRC) percentage of 84.76 ± 11.79% was achieved at the end of 18 months. Patient-related outcomes for VAS for pain and discomfort as well as treatment satisfaction showed favorable results., Conclusion: GUG can be used as a predictable treatment modality for Miller's class I and class II recession defects in mandibular anterior region. The results obtained can be well maintained over 18-month period with optimal maintenance care., Clinical Significance: The advantage of involving marginal gingiva in GUG results in a well-contoured graft, which increases the ease of adaptation and suturing. The biological characteristic of intact marginal vasculature results in early integration of graft into the recipient area and greater success in graft survival over denuded root surface, causing better long-term RC outcomes.

Acute-on-Chronic Liver Failure (ACLF) is associated with innate immune dysfunction and high short-term mortality. Neutrophils have been identified to influence prognosis in ACLF. Neutrophil biology is under-evaluated in ACLF. Therefore, we investigated neutrophil-specific genes and their association with ACLF outcomes. This is an observational study. Enriched granulocytes, containing neutrophils, isolated from study participants in three groups- ACLF(n = 10), chronic liver disease (CLD, n = 4) and healthy controls (HC, n = 4), were analysed by microarray. Differentially expressed genes were identified and validated by qRT-PCR in an independent cohort of ACLF, CLD and HC (n = 30, 15 and 15 respectively). The association of confirmed overexpressed genes with ACLF 28-day non-survivors was investigated. The protein expression of selected neutrophil genes was confirmed using flow cytometry and IHC. Differential gene expression analysis showed 1140 downregulated and 928 upregulated genes for ACLF versus CLD and 2086 downregulated and 1091 upregulated genes for ACLF versus HC. Significant upregulation of neutrophilic inflammatory signatures were found in ACLF compared to CLD and HC. Neutrophil enriched genes ELANE, MPO and CD177 were highly upregulated in ACLF and their expression was higher in ACLF 28-day non-survivors. Elevated expression of CD177 protein on neutrophil surface in ACLF was confirmed by flow cytometry. IHC analysis in archival post mortem liver biopsies showed the presence of CD177 + neutrophils in the liver tissue of ACLF patients. Granulocyte genes ELANE, MPO and CD177 are highly overexpressed in ACLF neutrophils as compared to CLD or HC. Further, this three-gene signature is highly overexpressed in ACLF 28-day non-survivors., (© 2021. The Author(s).)

Background: Huntington's disease (HD) is a progressive neurodegenerative disorder characterized by motor, cognitive, and psychiatric abnormalities. Currently, matched analyses of structural and functional differences in the brain from the same study cohort and, specifically, in HD patients from an ethnically diverse Indian population are lacking. Such findings aid in identifying noninvasive and sensitive imaging biomarkers., Objective: The aim of the study was to understand the structural and functional differences between HD and control brain, and presymptomatic and symptomatic HD brain in the Indian population., Materials and Methods: Seventeen HD (11 symptomatic HD [S-HD] and six presymptomatic HD [P-HD], with comparable CAG repeats), and 12 healthy controls were examined. Macrostructural (volume), microstructural (diffusivity), and functional (neurochemical levels and glucose metabolism) imaging of the brain was done along with the determination of visual latencies., Results: HD brain showed increased intercaudate distance; significant subcortical volumetric loss; reduced fractional anisotropy; increased mean, axial, and radial diffusivity; lower levels of total N-acetyl aspartate; elevated total choline levels; and reduced glucose metabolism compared with control brain. Interestingly, compared with P-HD, S-HD patients demonstrated a strong inverse correlation between age at onset and CAG repeat length, and prolonged P100 latency. In addition, caudate and putamen in S-HD brain showed significant volumetric loss and increased diffusivity compared with P-HD brain., Conclusions: HD brain showed distinct macrostructural, microstructural, and functional differences compared with control brain in the Indian population. Interestingly, patients with S-HD had a significant volumetric loss, increased diffusivity, altered neurochemical profile, and delayed P100 latency compared with P-HD patients. Examining these alterations clinically could aid in monitoring the progression of HD., Competing Interests: None

Background: Limb length discrepancy (LLD) after total knee arthroplasty (TKA) has been considered as one of the reasons for the unsatisfactory outcome. However, there is no consensus about the extent of LLD that can be considered as clinically relevant., Aim: To evaluate the incidence of radiographic LLD and its impact on functional outcome following TKA., Methods: All randomized-controlled trial and observational studies on LLD in TKA, published till 22 nd June 2020, were systematically searched and reviewed. The primary outcome was "limb lengthening or LLD after TKA". The secondary outcomes included "assessment of LLD in varus/valgus deformity" and "impact of LLD on the functional outcome"., Results: Of 45 retrieved studies, qualitative and quantitative assessment of data was performed from eight studies and six studies, respectively. Five studies ( n = 1551) reported the average limb lengthening of 5.98 mm. The LLD after TKA was ranging from 0.4 ± 10 mm to 15.3 ± 2.88 mm. The incidence of postoperative radiographic LLD was reported in 44% to 83.3% of patients. There was no difference in the preoperative and postoperative LLD (MD -1.23; 95%CI: -3.72, 1.27; P = 0.34). Pooled data of two studies ( n = 219) revealed significant limb lengthening in valgus deformity than varus (MD -2.69; 95%CI: -5.11, 0.27; P = 0.03). The pooled data of three studies ( n = 611) showed significantly worse functional outcome in patients with LLD of ≥ 10 mm compared to < 10 mm (standard MD 0.58; 95%CI: 0.06, 1.10; P = 0.03)., Conclusion: Limb lengthening after TKA is common, and it is significantly more in valgus than varus deformity. Significant LLD (≥ 10 mm) is associated with suboptimal functional outcome., Competing Interests: Conflict-of-interest statement: On behalf of all authors, the corresponding author states that there is no conflict of interest., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Our aim is to report the periodontal findings of a 10-year-old boy who visited the outpatient department of periodontology, with the chief complaint of swelling in the right cheek region for the last 2 months, increasing mobility of the teeth, and frequent bleeding from the gums. Since the age of 4 years, he suffered from recurrent febrile episodes, with boils and furuncles on the face. After several hematological and immunological investigations, he was diagnosed with chronic idiopathic neutropenia. He was prescribed a 150 μg subcutaneous injection of recombinant granulocyte colony-stimulating factor, once daily for 8 days. For reducing oral inflammation, he was advised an oral rinse of 15 ml of chlorhexidine gluconate (0.12%) twice daily and advised for a routine periodontal checkup, every 3-4 weeks for evaluation, maintenance, and avoiding any acute inflammatory flare-ups., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Journal of Indian Society of Periodontology.)

Inflammation is a ubiquitous factor accompanying normal aging and neurodegeneration, and recent studies indicate a major contribution of inducible cyclooxygenase (COX-2) and its downstream prostaglandin signaling pathways in modulating neuroinflammatory responses and neuronal function. We have previously shown that the prostaglandin PGE 2 receptor EP4 suppresses innate immune responses in models of systemic inflammation. Here we investigated the role of the EP4 receptor in models of Parkinson's disease (PD). Systemic co-administration of the EP4 agonist ONO-AE1-329 with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) prevented loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc) without significant changes in glial activation, suggesting a potent neuroprotective effect of EP4 signaling in this acute model of DA neuronal loss. Cell-specific conditional ablation of EP4 in Cd11bCre;EP4 lox/lox mice exacerbated MPTP-associated glial activation and T-cell infiltration in SNpc, consistent with anti-inflammatory functions of microglial EP4 signaling. In vitro, in primary microglia stimulated with oligomeric α-synuclein, EP4 receptor activation suppressed generation of pro-inflammatory and oxidative stress factors. Taken together, these findings suggest a dual neuroprotective and anti-inflammatory mechanism of action by the EP4 receptor in models of PD.

Background: High blood pressure (BP) is a leading contributor to cardiovascular mortality globally. There is scarcity of information on effective health systems interventions to lower BP and reduce cardiovascular risk in Southeast Asian countries. We conducted a pilot exploratory trial on 100 adults aged 40 years or older with uncontrolled hypertension to optimize the design for a structured multi-component intervention in primary care clinics for management of hypertension., Methods: Two clinics were involved, each enrolling 50 participants, with one as the intervention clinic and the other as the control (usual care). The intervention comprised the following four components: 1) an algorithm-driven intervention using a fixed-dose combination (FDC) antihypertensive treatment and lipid lowering medication for high risk individuals, 2) subsidized FDC antihypertensive medication; 3) motivational conversation (MC) for high risk individuals; and 4) telephone follow-ups of all individuals. The process outcomes were intervention fidelity measures. The outcomes of change in parameters of interest were healthy lifestyle index (composite score of body mass index, physical activity, dietary habit, dietary quality and smoking), adherence to antihypertensive medications, and systolic and diastolic BP from baseline to follow-up at 3 months., Results: Greater than 90 % fidelity was achieved for 3 of the 4 intervention components. Although not designed for conclusive results, the healthy lifestyle score increased by 0.16 (±0.68) with the intervention and decreased by 0.18 (±0.75) with usual care (p = 0.02). Adherence to anti-hypertensive medications at follow-up was 95.3 % in the intervention group compared to 83.8 % for usual care (p = 0.01). Systolic and diastolic BP decreased in both intervention and control groups, although statistical significance between groups was not achieved. Hypertensive individuals rated all intervention components 'highly favorable' on a Likert scale., Conclusions: Our findings indicate that the proposed, structured multi-component approach for management of hypertension is feasible for implementation in primary care clinics in Singapore, with some changes to the protocol. The observed improvement in the healthy lifestyle index and adherence to anti-hypertensive medications is promising. A large scale, adequately powered trial would be informative to assess intervention effectiveness on BP and cardiovascular risk reduction., Trial Registration: This trial has been registered at ClinicalTrials.gov. ClinicalTrials.gov number NCT02330224 . Registered on 28 December 2014.