Contralateral Nodal Relapse in Well-lateralised Oral Cavity Cancers Treated Uniformly with Ipsilateral Surgery and Adjuvant Radiotherapy With or Without Concurrent Chemotherapy: a Retrospective Study.

AIMS: To evaluate the incidence and pattern of contralateral nodal relapse (CLNR), contralateral nodal relapse-free survival (CLNRFS) and risk factors predicting CLNR in well-lateralised oral cavity cancers (OCC) treated with unilateral surgery and adjuvant ipsilateral radiotherapy with or without concurrent chemotherapy. MATERIALS AND METHODS: Consecutive patients of well-lateralised OCC treated between 2012 and 2017 were included. The primary endpoint was incidence of CLNR and CLNRFS. Univariable and multivariable analyses were carried out to identify potential factors predicting CLNR. RESULTS: Of the 208 eligible patients, 21 (10%) developed isolated CLNR at a median follow-up of 45 months. The incidence of CLNR was 21.3% in node-positive patients. CLNR was most common at level IB (61.9%) followed by level II. The 5-year CLNRFS and overall survival were 82.5% and 57.7%, respectively. Any positive ipsilateral lymph node (P = 0.001), two or more positive lymph nodes (P < 0.001), involvement of ipsilateral level IB (P = 0.002) or level II lymph node (P < 0.001), presence of extranodal extension (P < 0.001), lymphatic invasion (P = 0.015) and perineural invasion (P = 0.021) were significant factors for CLNR on univariable analysis. The presence of two or more positive lymph nodes (P < 0.001) was an independent prognostic factor for CLNR on multivariable analysis. CLNR increased significantly with each increasing lymph node number beyond two compared with node-negative patients. CONCLUSION: The overall incidence of isolated CLNR is low in well-lateralised OCC. Patients with two or more positive lymph nodes have a higher risk of CLNR and may be considered for elective treatment of contralateral neck.

Synthesis, characterization, mechanical and magnetic characteristics of Gd3+ /PO4 3 - substituted zircon for application in hard tissue replacements.

The study reports on the use of sol-gel technique to yield zircon type [Zr(1-0.1-x) GdxTi0.1 ] [(SiO4 )1-x (PO4 )x ] solid solution. Titanium has been used as a mineralizer to trigger zircon formation while equimolar concentrations of Gd3+ and PO4 3- were added to determine their accommodation limits in the zircon structure. The crystallization of t-ZrO2 as a dominant phase alongside the crystallization of m-ZrO2 and zircon were detected at 1200°C while their further annealing revealed the formation of zircon as a major phase at 1300°C. Heat treatment at 1400°C revealed the formation of zircon-type solid solution [Zr(1-0.1-x) Gdx Ti0.1 ][(SiO4 )1-x (PO4 )x ] comprising the accommodation of 10 mol.% of Gd3+ /PO4 3- at the zircon lattice. Beyond 10 mol.% of Gd3+ /PO4 3- , the crystallization of GdPO4 as a secondary phase is noticed. Structural analysis revealed the expansion of zircon lattice due to the simultaneous occupancy of Gd3+ /PO4 3- for the corresponding Zr4+ /SiO4 4- sites. The mechanical strength of single-phase zircon solid solution was higher in comparison to that of multiphase materials, namely in the presence of GdPO4 formed as a secondary phase in samples with added equimolar Gd3+ /PO4 3- contents beyond 10 mol.%. Nevertheless, the paramagnetic behavior of the samples demonstrated a steady surge as a function of enhanced Gd3+ content.

Enhancing the zircon yield through the addition of calcium phosphates into ZrO2-SiO2 binary systems: synthesis and structural, morphological, mechanical and in vitro analysis.

The crystallization of ZrSiO4 is generally accomplished by the addition of mineralizers into ZrO2-SiO2 binary oxides. The current investigation aimed to investigate the effect of adding calcium phosphates into ZrO2-SiO2 binary oxides on the yield of ZrSiO4. The concentration of calcium phosphate additions were varied to obtain ZrSiO4 that fetches improved mechanical and biological properties for application in hard tissue replacements. The findings highlight the significant role of Ca2+ and P5+ in triggering the ZrSiO4 formation via their accommodation at the Zr4+ and Si4+ sites. Especially, calcium phosphate additions trigger the t- → m-ZrO2 transition beyond 1000 °C, which consequently reacts with SiO2 to promote ZrSiO4 formation. Calcium phosphates are accommodated at the lattice sites of ZrSiO4 with a maximum limit of 20 mol%, beyond which the crystallization of ß-Ca3(PO4)2 is noticed. The optimum amount of 20 mol% of calcium phosphates displayed a better strength than that of all the investigated specimens. More than 80% of cell viability in MG-63 cells was invariably determined in all the calcium phosphate-added ZrSiO4 systems.

Development, Physiochemical characterization, Mechanical and Finite element analysis of 3D printed Polylactide-ß-TCP/α-Al2O3 composite.

Herein, material extrusion (MEX) technique is utilized to develop 3D printed models based on reinforcing ß-Ca3(PO4)2/α-Al2O3 composite in polylactide (PLA) matrix. ß-Ca3(PO4)2/α-Al2O3 composite has been synthesized through co-precipitation method and the phase content of ß-Ca3(PO4)2 and α-Al2O3 components are respectively determined as 64 and 36 wt%. The resultant ß-Ca3(PO4)2/α-Al2O3 composite mixed with PLA at various weight ratios were extruded as filaments and subsequently 3D printed into definite shapes for the physiochemical, morphological and mechanical evaluation. 3D printed bodies that comprise 5 wt % ß-Ca3(PO4)2/α-Al2O3 composite yielded an increasing tensile, compressive and flexural strength in the corresponding order of ∼15, ∼15 and 22% than 3D printed pure PLA. Further, the Representative volume element (RVE) unit cells developed based on the various investigated compositions of PLA-ß-Ca3(PO4)2/α-Al2O3 were subjected to mechanical evaluation through Finite element analysis (FEA) under both static and dynamic loading conditions on ASTM standard specimens. The results from experimental and FEA analysis demonstrated good uniformity that confirmed the reinforcement of 5 wt % ß-Ca3(PO4)2/α-Al2O3 in PLA matrix as an optimum combination to yield better mechanical strength.

Identification of salivary metabolic biomarker signatures for oral tongue squamous cell carcinoma.

OBJECTIVE: To identify the salivary metabolites associated with squamous cell carcinoma of the tongue to develop easy and non-invasive potential biomarkers for disease diagnosis. DESIGN: Initially, the study utilized untargeted metabolomics to analyze 20 samples of tongue squamous cell carcinoma and 10 control samples. The objective was to determine the salivary metabolites that exhibited differential expression in tongue squamous cell carcinoma. Then the selected metabolites were validated using targeted metabolomics in saliva samples of 100 patients diagnosed with squamous cell carcinoma of the tongue, as well as 30 healthy control individuals. RESULTS: From the analysis of untargeted metabolomics, 10 metabolites were selected as potential biomarkers. In the subsequent targeted metabolomics study on these selected metabolites, it was observed that N-Acetyl-D-glucosamine, L-Pipecolic acid, L-Carnitine, Phosphorylcholine, and Deoxyguanosine exhibited significant differences. The receiver operating characteristic curve analysis indicates a combination of three important metabolites such as N-Acetyl-D-glucosamine, L-Pipecolic acid and L-Carnitine provided the best prediction with an area under the curve of 0.901. CONCLUSIONS: The present result reveals that the N-Acetyl-D-glucosamine, L-Pipecolic acid and L-Carnitine are the signature diagnostic biomarkers for oral tongue squamous cell carcinoma. These findings can be used to develop a rapid and non-invasive method for disease monitoring and prognosis in oral tongue cancer.

Design and fabrication of dysprosium impregnated polyvinyl alcohol hydrogels. Physiochemical, mechanical, bioimaging and in vitro evaluation.

Tissue engineering has gained prominence during the past decade since it offers a key solution to defects associated with the tissue regeneration. The limited healing potential of the cartilage tissue damage has significant clinical implications. Herein, dysprosium (Dy3+) impregnated polyvinyl alcohol (PVA) hydrogels have been developed to enhance the therapeutic efficacy, enabling simultaneous diagnostic imaging and antibacterial drug delivery for potential applications in articular cartilage. Based on the favorable imaging features, Dy3+ impregnated PVA hydrogels with enhanced stability were formed through successive steps of repeated cycles of freezing at - 30 °C for 21 h, thawing at 25 °C for 4 h and lyophilization. The tensile and compression tests of the hydrogels respectively determined a maximum of 3.88 and 1.58 MPa, which reflected better compatibility towards cartilage. The hydrogels fetched a sustained drug release for a period of 12 h with an associated swelling ratio of 80%. The potential of the resultant hydrogels in image diagnosis has been deliberated through their blue and yellow emissions in the visible region. Further, the computed tomography (CT) and magnetic resonance imaging characteristics of the hydrogels respectively accomplished a maximum of 343 Hounsfiled units (HU) and relaxivity of 7.25 mM-1s-1. The cytocompatibility of the hydrogels is also determined through in vitro tests performed in Murine pro B cell line (BA/F3) and human Megakaryocyte cell line (Mo7e) cell lines.

Retraction: Fabrication of divalent ion substituted hydroxyapatite/gelatin nanocomposite coating on electron beam treated titanium: mechanical, anticorrosive, antibacterial and bioactive evaluations.

[This retracts the article DOI: 10.1039/C5RA05624A.].

Retraction: Smart rose flower like bioceramic/metal oxide dual layer coating with enhanced anti-bacterial, anti-cancer, anti-corrosive and biocompatible properties for improved orthopedic applications.

[This retracts the article DOI: 10.1039/C5RA17747B.].

Monkeypox: epidemiology, mode of transmission, clinical features, genetic clades and molecular properties.

OBJECTIVE: Recently monkeypox cases have been reported from many non-endemic countries. The objective of this article is to bring out the epidemiology, mode of transmission, clinical features, genetic clades, and molecular properties of monkeypox virus. MATERIALS AND METHODS: A detailed literature review was conducted on monkeypox, using databases PubMed/Medline, EMBASE, PMC and Cochrane Library, for the period between 1985 to 2022. RESULTS: Genetically monkeypox virus can be classified into Central African clade and Western African clades. The sequence similarity between the two strains was found to be 99.5%. However, some significant differences were found in the virulent and nonvirulent genes of the strains, such as BR-203, BR-209, COP-C3L b and COP-H5R, COP-A9L, COP-A50R, and COP-A36R, respectively. Human to human transmission occurs after exposure to respiratory droplets, oral secretions, contact with lesions, fomites, and direct/sexual contact. Monkeypox can also be transmitted from the infected mother to the fetus through the placenta leading to congenital infection. In May 2022 several cases have been reported from Europe, North America, and Australia, particularly from homosexual men. CONCLUSIONS: Monkeypox is a zoonotic disease which was prevalent in Central and Western African countries. Recently, human to human spread was noticed in developed countries of Europe, North America and Australia. Despite with a close genetic similarity between the two clades, the Central African strain is comparatively very virulent with high mortality. Monkeypox should be considered a re-emerging, neglected disease and proper measures like hand hygiene, wearing masks and vaccination to the high-risk groups are advised.

Maintenance therapy with a poly(ADP-ribose) polymerase inhibitor in patients with newly diagnosed advanced epithelial ovarian cancer: individual patient data and trial-level meta-analysis.

BACKGROUND: We synthesize the efficacy and toxicity of poly(ADP-ribose) polymerase inhibitors (PARPis) in patients with newly diagnosed advanced ovarian cancer. PATIENTS AND METHODS: We manually extracted individual patient data (IPD) for progression-free survival (PFS) from published survival curves of randomized controlled trials (RCTs) that compared PARPi versus placebo as maintenance therapy in first-line treatment, for whole study populations and subgroups, based on BRCA1/BRCA2 mutation (germline and/or somatic) and homologous recombination deficiency (HRD) status, using WebPlotDigitizer software. The respective PFS curves for each study and combined population were reconstructed from extracted IPD. The primary outcome was PFS in combined whole population and subgroups. RESULTS: In IPD analysis of combined population from three RCTs, with 2296 patients and 1287 events, PFS was significantly longer in PARPi versus placebo [median 20.4 (95% confidence interval (CI) 18.6-21.9) versus 14.9 (95% CI 13.9-16.5) months, respectively; hazard ratio (HR) 0.67, 95% CI 0.60-0.75; P < 0.001]. In IPD subgroup analyses from four eligible RCTs (2687 patients and 1485 events), median PFS was significantly longer in PARPi versus placebo arm, in the BRCA-mutated (45.7 versus 17.7 months, respectively; HR 0.38, 95% CI 0.32-0.46; P < 0.001), HRD-positive including BRCA-mutated (34.7 versus 17.9 months, respectively; HR 0.45, 95% CI 0.38-0.54; P < 0.001), and HRD positive excluding BRCA-mutated (22.3 versus 13.1 months, respectively; HR 0.47, 95% CI 0.34-0.65; P < 0.001) subgroups, but not in the HRD-negative (15.0 versus 11.3 months, respectively; HR 0.90, 95% CI 0.76-1.05; P = 0.75) subgroup. Results of trial-level meta-analysis were concordant with IPD analysis in whole population and subgroups. CONCLUSIONS: Among newly diagnosed ovarian cancer patients, PARPi maintenance therapy significantly improves PFS in those with germline and/or somatic BRCA mutation and/or HRD-positive tumor but not in those with HRD-negative tumor.

Effective Evaluation of Medical Images Using Artificial Intelligence Techniques.

This work is implemented for the management of patients with epilepsy, and methods based on electroencephalography (EEG) analysis have been proposed for the timely prediction of its occurrence. The proposed system is used for crisis detection and prediction system; it is useful for both patients and medical staff to know their status easily and more accurately. In the treatment of Parkinson's disease, the affected patients with Parkinson's disease can assess the prognostic risk factors, and the symptoms are evaluated to predict rapid progression in the early stages after diagnosis. The presented seizure prediction system introduces deep learning algorithms into EEG score analysis. This proposed work long short-term memory (LSTM) network model is mainly implemented for the identification and classification of qualitative patterns in the EEG of patients. While compared with other techniques like deep learning models such as convolutional neural networks (CNNs) and traditional machine learning algorithms, the proposed LSTM model plays a significant role in predicting impending crises over 4 different qualifying intervals from 10 minutes to 1.5 hours with very few wrong predictions.

Perceptions on COVID-19 Vaccination among People Aged more than 50 years in Urban Field Practice Area of Department of Community Medicine in a Tertiary Care Teaching Hospital, Hyderabad: A Reflection from Focus Group Discussions.

Background: Despite several efforts to limit the viral transmission, the COVID-19 vaccine has been the only "the ray of hope" to end the pandemic. However, vaccine hesitancy could reduce coverage and hinder herd immunity. People's intention to get vaccinated can be shaped by several factors, including risk perception which, in turn, is influenced by effect. The need to acquaint oneself to the beliefs, concerns, and circumstances of one's own population in the community becomes important for successful implementation of the program. Therefore, the present study was conducted to gain insights into perceptions of vaccination. Objectives: The objective is to understand the felicitating factors and hindering factors for acceptance of vaccines by the population among people aged 50 years in urban field practice area of the Department of Community Medicine in a Tertiary care teaching hospital, Hyderabad. Subjects and Methods: Data were extracted from audio recording of five focus group discussions that were conducted in the urban field practice care of a tertiary care teaching hospital in Hyderabad through open-ended questions. Categories, subcategories, and themes were created by deductive approach. Results: The motivating factors for vaccine acceptance were found to be fear of getting disease, wanting to return normalcy, and trust in treating doctors, whereas, barriers were fear of death due to vaccine, opacity in vaccine details, anxiety, and misinterpretation of adverse events. Conclusion: Having a clear understanding about the belief system of the target population could help in designing the guidelines for vaccination program to escalate the immunization and increase the acceptance.

Quantum chemical calculations, spectroscopic studies and molecular docking investigations of the anti-cancer drug quercitrin with B-RAF inhibitor.

Quercitrin is an anti-lung cancer agent. It is a naturally occurring flavonoid and its derivatives are mainly present in nuts and beverages. It is mainly available as a glycoside, and the quercitrin glycosides are found to prevent the metastasis of cancer. Quercitrin is optimized with 6-311++G(d,p) basis set using the B3LYP method to attain its minimum energy structure. The vibrational studies of the Quercitrin compound were elucidated with reference to Potential Energy Distribution (PED). The geometrical parameters were obtained and correlated with experimental values. To examine the nature of the charge transfer mechanism of Quercitrin, the HOMO-LUMO energy gap is computed. The anti-cancer activity of Quercitrin has been explored using molecular docking study that are used to estimate how the ligand interacts with protein, specifically to identify the best-fit orientation of the ligand, its binding mode, and intermolecular interactions of amino acid residues in the binding region of B-RAF kinase protein. The binding affinity of the compound Quercitrin (-7.14 kcal/mol) was found using AutoDock and validated with a Glide XP score in Schrodinger tool (-8.01 kcal/mol). MD simulations of protein-ligand complexes were monitored for 100 ns, from which the RMSD, RMSF, Rg, H-bonds, and interaction energy calculations were executed. From these investigations, it is identified that the compound quercitrin has maintained good structural stability, compactness, higher Hydrogen bonds, and interaction energies than the Imidazopyridinyl benzamide inhibitor.

A LONG-TERM 10G-HYPERGRAVITY EXPOSURE PROMOTES CELL-CELL CONTACTS AND REDUCES ADHESIVENESS TO A SUBSTRATE, MIGRATION, AND INVASIVENESS OF MCF-7HUMAN BREAST CANCER CELLS.

BACKGROUND: G-force is a fundamental force controlling human cells. Cancer is one of the 4 major health challenges in the Space missions. Cancer in Space project evaluates the reaction of human cancer cells to the conditions of the space flights, including an exposure to high g-forces. AIM: Explore an impact of 10 g force on the oncogenic properties of human breast adenocarcinoma cells MCF-7. MATERIALS AND METHODS: Cells were exposed to 10 g force for 10 days, as part of a 6-week simulation of conditions of a space flight. Then the cells were cultured for one week under normal culture conditions, before performing tests. Cell proliferation, cell viability, cell-cell contact inhibition, migration, and invasiveness were measured. Immunoblotting was used to evaluate expression of proteins. RESULTS: Proliferation, cell-cell interaction and formation of 3D structures, migration, and invasiveness of cells exposed to 10 g were compared to parental cells cultured at 1 g condition. 10 g exposed cells showed a higher propensity for cell-cell contact inhibitions and lower for 3-dimensional growth in dense culture. This correlated with the decrease of proliferation in a dense culture as compared to the parental cells. The decrease of migration, adherence to a surface, and invasiveness was observed for cells subjected to the hypergravity, as compared to the parental MCF-7 cells. Enhanced expression of E-cadherin and phosphorylated pY576-FAK were observed in 10 g exposed cells but no impact on the expression of Erk, pErk, FAK and p53 was detected. CONCLUSION: The prolonged exposure of MCF-7 cells to 10 g force targets cell-cell and cell-substrate interactions.

Oral metronomic chemotherapy after definitive chemoradiation in esophageal squamous cell carcinoma: a randomized clinical trial.

BACKGROUND: Improving outcomes in locally advanced esophageal/GEJ squamous cell cancer (SCC) is an unmet need. We investigated the addition of oral metronomic chemotherapy (OMC) following definitive chemoradiotherapy (CRT). MATERIALS AND METHODS: This was a randomized open-label integrated phase II/III study in patients with SCC of esophagus/GEJ following definitive CRT who had no radiologic evidence of progression, and no endoscopically detected disease. Randomization was 1:1 to OMC (celecoxib 200 mg twice daily and methotrexate 15 mg/m2 weekly) for 12 months or observation. The primary endpoint for the phase II portion was progression-free survival (PFS); secondary endpoints were overall survival (OS) and toxicity. P ≤ 0.2 for PFS was required to proceed to phase III. RESULTS: Between Jan 2016 and Dec 2019, we enrolled 151 patients for the phase II portion, 75 to OMC and 76 to observation. The tumor originated in the upper thoracic esophagus in 79% patients. Concurrent CRT consisted of median 63 Gy in a median of 35 fractions; concurrent chemotherapy was weekly paclitaxel + carboplatin in 91%. OMC was started at a median of 2.6 months (IQR 2.3-2.8) from CRT completion. Grade 3 or higher toxicities occurred in 18 patients (24%) in the OMC arm and 9 (12%) in the observation arm; P = 0.071. Median PFS was 25 months (95% CI, 17-58) in the OMC arm and was not attained [NA] (95% CI, 25-NA) in the observation arm; HR, 1.51, 95% CI, 1-2; P = 0.073. Median OS was 36 months (95% CI, 23-NA) in the OMC arm, and not attained (95% CI, NA-NA) in the observation arm; HR, 1.77; 95% CI, 1-2.9; P = 0.023. CONCLUSION: Oral metronomic methotrexate and celecoxib in patients who have not progressed radiologically and have no endoscopic evidence of disease following radical CRT for locally advanced esophageal/GEJ SCC does not improve outcomes and may lower survival. [Funded by the TMC-Research Administration Council (TRAC); CHROME study (CHemoRadiotherapy followed by Oral Metronomic therapy in Esophageal cancer); ctri.nic.in number: CTRI/2015/09/006204]. TRIAL REGISTRATION NUMBER: CTRI/2015/09/006204.

Concurrent Cetuximab-based bioradiotherapy versus Cisplatin-based Chemoradiotherapy in the Definitive Management of Favourable Biology Human Papillomavirus-associated Oropharyngeal Squamous Cell Carcinoma: Systematic Review and Meta-analysis.

Replacing cisplatin with cetuximab concurrently during radiotherapy has been one of the strategies of treatment de-escalation in human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC). However, until recently, there were limited data on the efficacy and safety of such an approach. A systematic search of the literature was carried out to identify prospective randomised controlled trials comparing definitive cisplatin-based chemoradiotherapy (CT-RT) versus cetuximab-based bioradiotherapy (BRT) in HPV-positive OPSCC. Overall survival and locoregional control were primary outcomes of interest; rates of acute and late toxicities (≥grade 3) were secondary end points. Outcome data were aggregated using a random-effects model as per Cochrane methodology including risk of bias assessment and expressed as hazard ratio or risk ratio as appropriate with respective 95% confidence intervals. Data from five randomised controlled trials involving 1560 patients with HPV-positive OPSCC were aggregated in the meta-analysis. Cetuximab-based BRT was associated with a significantly increased risk of death (hazard ratio = 2.83, 95% confidence interval 1.22-6.57; P = 0.02) and locoregional relapse (hazard ratio = 2.78, 95% confidence interval 1.77-4.39; P < 0.0001) compared with cisplatin-based CT-RT. Cisplatin was associated with higher rates of acute ≥grade 3 toxicity in terms of acute kidney injury, dry mouth, febrile neutropenia, hearing impairment, nausea and vomiting, whereas dermatitis and acneiform rash were more common with cetuximab. There were no significant differences in overall rates of late ≥grade 3 toxicity (risk ratio = 0.63, 95% confidence interval = 0.36-1.10; P = 0.10). In conclusion, there is moderate-certainty evidence that cetuximab-based BRT leads to inferior efficacy outcomes compared with cisplatin-based CT-RT in the definitive curative-intent management of HPV-associated OPSCC.

Short report - Lethal and aggressive pancreatic cancer: molecular pathogenesis, cellular heterogeneity, and biomarkers of pancreatic ductal adenocarcinoma.

This short report describes the carcinogenesis of the pancreas leading to pancreatic ductal adenocarcinoma (PDAC) determined by molecular, cellular, and functional heterogeneity. Among the diverse types of pancreatic cancers, PDAC is the most lethal, aggressive, and one of the leading cancers associated with the highest mortality. Pancreatic cellular components like pancreatic stellate cells (PSC), mesenchymal stem cells (MSC), and pancreatic fibroblast cells (PFC) exhibit these properties in PDAC. After the appearance of point mutations in KRAS, the mutations in tumor suppressor genes appear sequentially in the order of CDKN2A, TP53, and SMAD4 that eventually resulting in PDAC development. As of today, there are no effective therapeutic options or treatments available for PDAC. The main difficulty in managing PDAC cases is its defiance to chemotherapy and radiotherapy. There were several attempts to identify a suitable biomarker for the early diagnosis and prognosis of PDAC. Anyway, these recently discovered biomarkers vary in their sensitivity and specificities. Some of the other important and reliable biomarkers for PDAC are carbohydrate antigen 19-9 (CA 19-9), carcinoembryonic antigen (CEA), cell migration-inducing hyaluronan binding protein (CEMIP), serum fatty acid metabolite PC-594, and micro-RNAs (miRNAs).