A New Validated Liquid Chromatographic Method for the Determination of Loratadine and its Impurities

An improved gradient, reversed-phase liquid chromatographic (RP-LC) method was developed and subsequently validated for the determination of Loratadine and its impurities/degradation products in pharmaceutical drug substance. Separation was achieved with Inertsil ODS-3V, 250 × 4.6 mm, 5μ column with gradient elution at a flow rate of 1.0 mL min−1. UV detection was performed at 220 nm. The described method is linear over a range of LOQ (0.044, 0.088, 0.084, and 0.072 μg mL−1 for impurity-B, impurity-C, impurity-D, and impurity-E respectively) to 1.2 μg mL−1 (0.6 μg mL−1 of the specification limit) for all the impurities and degradation products. The recovery of impurities were found to be in the range of 85–115 %. The method is simple, selective, and accurate for the quantification of impurities and degradation products of Loratadine in its bulk drug samples

Synthesis and Characterisation of Diaryl Furoxans

The paper discusses the synthesis, characterisation, and performance evaluation of diarylfuroxans namely, bis-phenyl-3,4-furoxan (5) and bis-(4’-nitrophenyl)-3,4-furoxan (6). Themolecules have been synthesised on the lines of reported method by cyclodimerisation of thenitrile oxides generated from benzaldoxime and p-nitro benzaldoxime, respectively. The synthesisedfuroxans (5 ) and (6) were characterised by the elemental analysis, UV, IR, and 1H NMRspectroscopy. The hazard characteristics (impact and friction sensitivity) confirm that thecompounds are safe to handle. The oxygen balance, velocity of detonation and detonationpressure have been computed. The detonation velocity and pressure along with oxygen balanceincreased with the substitution of nitro group in the benzene ring, as expected. Thethermogravimetric studies on promising compound (6) brings out that maximum weight lossoccurs at decomposition temperature of 259–260 °C

Artificial intelligence applications in implant dentistry: A systematic review

Statement of problem. Artificial intelligence (AI) applications are growing in dental implant procedures. The current expansion and performance of AI models in implant dentistry applications have not yet been systematically documented and analyzed. Purpose. The purposeof this systematic review was to assess the performance of Ai models in implant dentistry for implant type recognition, implant success prediction by using patient risk factors and ontology criteria, and implant design optimization combining finite element analysis (FEA) calculations and AI models. Material and methods. An electronic systematic review was completed in 5 databases: MEDLINE/ PubMed, EMBASE, World of Science, Cochrane, and Scopus. A manual search was also conducted. Peerreviewed studies that developed AI models for implant type recognition, implant success prediction, and implant design optimization were included. The search strategy included articles published until February 21, 2021. Two investigators independently evaluated the quality of the studies by applying the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Quasi-Experimental Studies (nonrandomized experimental studies). A third investigator was consulted to resolve lack of consensus. Results. Seventeen articles were included: 7 investigations analyzed AI models for implant type recognition, 7 studies included AI prediction models for implant success forecast, and 3 studies evaluated AI models for optimization of implant designs. The AI models developed to recognize implant type by using periapical and panoramic images obtained an overall accuracy outcome ranging from 93.8% to 98%. The models to predict osteointegration success or implant success by using different input data varied among the studies, ranging from 62.4% to 80.5%. Finally, the studies that developed AI models to optimize implant designs seem to agree on the applicability of AI models to improve the design of dental implants. This improvement includes minimizing the stress at the implant-bone interface by 36.6% compared with the finite element model; optimizing the implant design porosity, length, and diameter to improve the finite element calculations; or accurately determining the elastic modulus of the implant-bone interface. Conclusions. AI models for implant type recognition, implant success prediction, and implant design optimization have demonstrated great potential but are still in development. Additional studies are indispensable to the further development and assessment of the clinical performance of AI models for those implant dentistry applications reviewed

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field

Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing

Chromothripsis is a mutational phenomenon characterized by massive, clustered genomic rearrangements that occurs in cancer and other diseases. Recent studies in selected cancer types have suggested that chromothripsis may be more common than initially inferred from low-resolution copy-number data. Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), we analyze patterns of chromothripsis across 2,658 tumors from 38 cancer types using whole-genome sequencing data. We find that chromothripsis events are pervasive across cancers, with a frequency of more than 50% in several cancer types. Whereas canonical chromothripsis profiles display oscillations between two copy-number states, a considerable fraction of events involve multiple chromosomes and additional structural alterations. In addition to non-homologous end joining, we detect signatures of replication-associated processes and templated insertions. Chromothripsis contributes to oncogene amplification and to inactivation of genes such as mismatch-repair-related genes. These findings show that chromothripsis is a major process that drives genome evolution in human cancer

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Synthesis and nuclear magnetic resonance spectroscopy of geometrical isomers of 1,3,5-Trimethyl-2,4,6-tris(p-methylphenoxy)-2,4,6-trioxocyclotri-phosphazane: X-Ray crystal structure of the trans isomer

Both cis and trans isomers of tri(N-methyl)tris(p-methylphenoxy)trioxocyclotriphosphazane,$N_3Me_3P_3O_3(OC_6H_4Me-p)_3$, have been prepared by the thermal rearrangement of the respective trimethoxycyclophosphazenes, $N_3P_3(OC_6H_4Me-p)_3(0Me)_3$. The crystal and molecular structure of the trans isomer has been determined; it crystallises in the P1 space group with a = 8.444(1), b = 11.753(1),c = 14.196(1)\AA,\alpha = 97.408(8), \beta = 92.487(10),\gamma = $102.325(10)^0$,andZ = 2.The structure has been solved by direct methods and refined to a R value of 0.060. The six-membered $N_3P_3$ phosphazane ring adopts a twist-boat confirmation. The structural data have been used to explain the n.m.r. spectroscopic features. A chair conformation is proposed for cis- $N_3Me_3P_3O_3-(OC_6H_4Me-p)_3$ on the basis of n.m.r. data