Emerging nosocomial strains of Acinetobacter baumannii are of recent concern as they are expressing extensive drug resistance (XDR). Using whole‐genome sequencing and molecular characterisation ...analysis, the current study reveals the presence of carbapenemase genes in 92.86% of studied Indian isolates. These included blaOXA‐51, blaOXA‐23, blaOXA‐58, and blaNDM genes, with over a third expressing dual carbapenemase genes. As per the MLST scheme, IC2Oxf/CC2Pas was the predominant clone, with 57.14% isolates belonging to this lineage. The presence of these carbapenemase genes resulted in sulbactam (SUL) resistance (MIC: 16–256 µg/ml) in all of the studied isolates. The efficacy of durlobactam (DUR), a novel β‐lactamase inhibitor that also inhibits PBP2 was assessed through in silico intermolecular interaction analysis. Several nonsynonymous single nucleotide polymorphisms were identified in PBP2 (G264S, I108V, S259T) and PBP3 (A515V, T526S) sequences. Minimal variations were recorded in the protein backbone dynamics in active‐site motifs of wild‐type and mutants, which correlated with negligible binding energy fluctuations for the PBP3‐SUL (−5.85 ± 0.04 kcal/mol) and PBP2‐DUR (−5.16 ± 0.66 kcal/mol) complexes. Furthermore, higher binding affinities and low inhibition constants were noted in OXA23‐DUR (−7.36 kcal/mol; 4.01 µM), OXA58‐DUR (−6.44 kcal/mol; 19.07 µM), and NDM‐DUR (−6.82 kcal/mol; 10.01 µM) complexes when compared with the conventional drugs avibactam and aztreonam. Stable interaction profiles of DUR with carbapenemases can possibly restore SUL activity against both PBP3WT and PBP3MTs. The study establishes the efficacy of the novel SUL–DUR combination as a successful treatment strategy in combating emerging XDR strains of A. baumannii.
International cancer registries make real-world genomic and clinical data available, but their joint analysis remains a challenge. AACR Project GENIE, an international cancer registry collecting data ...from 19 cancer centers, makes data from >130,000 patients publicly available through the cBioPortal for Cancer Genomics (https://genie.cbioportal.org). For 25,000 patients, additional real-world longitudinal clinical data, including treatment and outcome data, are being collected by the AACR Project GENIE Biopharma Collaborative using the PRISSMM data curation model. Several thousand of these cases are now also available in cBioPortal. We have significantly enhanced the functionalities of cBioPortal to support the visualization and analysis of this rich clinico-genomic linked dataset, as well as datasets generated by other centers and consortia. Examples of these enhancements include (i) visualization of the longitudinal clinical and genomic data at the patient level, including timelines for diagnoses, treatments, and outcomes; (ii) the ability to select samples based on treatment status, facilitating a comparison of molecular and clinical attributes between samples before and after a specific treatment; and (iii) survival analysis estimates based on individual treatment regimens received. Together, these features provide cBioPortal users with a toolkit to interactively investigate complex clinico-genomic data to generate hypotheses and make discoveries about the impact of specific genomic variants on prognosis and therapeutic sensitivities in cancer.
Enhanced cBioPortal features allow clinicians and researchers to effectively investigate longitudinal clinico-genomic data from patients with cancer, which will improve exploration of data from the AACR Project GENIE Biopharma Collaborative and similar datasets.
Abandoned, lost, or otherwise discarded fishing gear contributes considerably to global marine debris. These lost gears, mostly made of non-biodegradable synthetic materials, persist in the marine ...environment for longer periods of time and pose a great threat to marine life by entangling and killing target fishes and other non-target species such as turtles, birds, and mammals, a phenomenon known as ghost fishing. Other environmental impacts include physical impacts on aquatic habitats, transfer of microplastics into food web, and interference with fishing. Information regarding the catching efficiency and catch rates of lost nets in Indian waters is lacking. Ghost fishing capacity of simulated lost gillnets is being reported for the first time in India. This study investigates the ghost fishing capacity of lost gillnets through an experimental approach at Aroor, Vembanad lake, Kerala, India. Simulation studies using purposefully abandoned shrimp gillnets (32 mm mesh size) were conducted to understand the fishing capacity of lost gillnets during two seasons (monsoon and post-monsoon) as separate experiments. The gillnets maintained their catching efficiency until the 15th day during the first experiment and up to the 50th day in the second experiment. Catches showed an exponential reduction over time in both experiments. A total of 251 specimens comprising of 27 species were caught from both sets of experimental nets, and the state of catch in the nets showed different decaying stages from the second day itself along with fresh stages. As the days progressed, particulate matter and detritus began to accumulate on the experimental nets, increasing net visibility and reducing their catching efficiency. The results of the study on ghost fishing capability will contribute to the development of strategies for reducing the effects of lost nets on the aquatic ecosystem and for suggesting improved management strategies.
Cosmetic treatments aim at improving skin appearance through vehicles of good sensory properties. Those vehicles are mainly emulsions and gels designed to deliver safe and effective compounds to ...skin. Creams and serums are widely used to achieve these goals, but recently a new type of formulation known as organogels triggered scientific attention, particularly in the design of both topical and cosmetic formulations. It has been established that the lipophilic nature of organogels makes it an excellent candidate for the delivery of cosmetic molecules through skin. In this review, we discuss the properties and characteristics of organogels and present the advantages of the application of these systems in cosmetics.
Résumé
Les traitements cosmétiques visent à améliorer l'apparence de la peau grâce à des véhicules dotés de bonnes propriétés sensorielles. Ces véhicules sont principalement des émulsions et gels conçus pour livrer des composants sûrs et efficaces à la peau. Crèmes et sérums sont largement utilisés pour atteindre ces objectifs mais un nouveau type de formulation appelé organogels a récemment attiré l'attention des scientifiques, en particulier en ce qui concerne la conception de formulations à la fois topiques et cosmétiques. Il a été établi que la nature lipophile des organogels en fait d'excellents candidats pour la livraison de molécules cosmétiques à la peau. Dans cette analyse, nous discutons des propriétés et des caractéristiques des organogels, et présentons les avantages de l'utilisation de ces systèmes dans la cosmétique.
This review discusses the properties and characteristics of organogels and presents the advantages of the application of these systems in cosmetics.
Evidence for perceptual bias toward the Scheduled Caste/Scheduled Tribes (SC/ST)—a community historically oppressed and treated as untouchables in India—was found through a series of studies. We ...hypothesized that the SC/ST are perceived as less human in comparison to the dominant castes (General Category), leading to adverse consequences to the dehumanized group. Studies were designed to measure the effect of Caste on social perception by including participants belonging to General and SC/ST categories. Study 1 used an implicit association test and found that SC/ST are subjected to subtle dehumanization. Study 2 extended the findings using a moderately explicit measure of dehumanization and the results indicated biased perception of humanness in the SC/ST targets, albeit a valence effect. Study 3 demonstrated blatant dehumanization of SC/ST using an explicit measure. Overall the results indicate the dehumanization of the marginalized community that can have implications on attitudes and behaviors toward them.
Gallbladder carcinoma (GBC) is an uncommon and aggressive disease, which remains poorly defined at a molecular level. Here, we aimed to characterize the molecular landscape of GBC and identify ...markers with potential prognostic and therapeutic implications.
GBC samples were analyzed using the MSK-IMPACT (Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets) platform (targeted NGS assay that analyzes 505 cancer-associated genes). Variants with therapeutic implications were identified using OncoKB database. The associations between recurrent genetic alterations and clinicopathologic characteristics (Fisher exact tests) or overall survival (univariate Cox regression) were evaluated. P values were adjusted for multiple testing.
Overall, 244 samples (57% primary tumors and 43% metastases) from 233 patients were studied (85% adenocarcinomas, 10% carcinomas with squamous differentiation, and 5% neuroendocrine carcinomas). The most common oncogenic molecular alterations appeared in the cell cycle (TP53 63% and CDKN2A 21%) and RTK_RAS pathways (ERBB2 15% and KRAS 11%). No recurrent structural variants were identified. There were no differences in the molecular landscape of primary and metastasis samples. Variants in SMAD4 and STK11 independently associated with reduced survival in patients with metastatic disease. Alterations considered clinically actionable in GBC or other solid tumor types (e.g., NTRK1 fusions or oncogenic variants in ERBB2, PIK3CA, or BRCA1/2) were identified in 35% of patients; 18% of patients with metastatic disease were treated off-label or enrolled in a clinical trial based on molecular findings.
GBC is a genetically diverse malignancy. This large-scale genomic analysis revealed alterations with potential prognostic and therapeutic implications and provides guidance for the development of targeted therapies.
The Andaman Sea adjoining the Indian Territory is biologically rich in terms of marine diversity. However, inadequate surveys during the post-independence era have resulted in large lacunae in data ...on the species composition in these waters. In this paper, we report the first observation of two species of dendrobranchiate prawns, Metapenaeopsis difficilis Crosnier, 1991 and Haliporus taprobanensis Alcock and Anderson, 1899, in the Indian seas, supplemented with notes on their morphological diagnoses, comparison with closely related species and zoogeographical distribution. Crustacean specimens were collected using trawl nets and a naturalists' dredge on board the Fisheries Oceanography Research Vessel Sagar Sampada in the deeper offshore region between 124 and 850 m depth in the Andaman Sea during the period 2015-2017. Metapenaeopsis difficilis is distinguished by an oval-shaped thelycal plate and a low, unarmed bead-like plate on the thoracic sternum between the third pereiopods. Metapenaeopsis difficilis is previously reported from the Philippines, Indonesia, Coral Sea, New Caledonia, Marquesas Islands, and Wallis and Futuna Islands at depths between 21 and 440 m, thereby indicating its westward range extension. Haliporus taprobanensis is distinguished by a tough integument, presence of a postero-dorsal spine on the fourth pleonal somite, and smooth dorsum of the first four pleonal somites. Haliporus taprobanensis is previously reported from South Africa, Madagascar, off Sri Lanka, Indonesia, Philippines and northern Australia at depths between 300 and 1650 m.
Cancer classification is foundational for patient care and oncology research. Systems such as International Classification of Diseases for Oncology (ICD-O), Systematized Nomenclature of Medicine ...Clinical Terms (SNOMED-CT), and National Cancer Institute Thesaurus (NCIt) provide large sets of cancer classification terminologies but they lack a dynamic modernized cancer classification platform that addresses the fast-evolving needs in clinical reporting of genomic sequencing results and associated oncology research.
To meet these needs, we have developed OncoTree, an open-source cancer classification system. It is maintained by a cross-institutional committee of oncologists, pathologists, scientists, and engineers, accessible via an open-source Web user interface and an application programming interface.
OncoTree currently includes 868 tumor types across 32 organ sites. OncoTree has been adopted as the tumor classification system for American Association for Cancer Research (AACR) Project Genomics Evidence Neoplasia Information Exchange (GENIE), a large genomic and clinical data-sharing consortium, and for clinical molecular testing efforts at Memorial Sloan Kettering Cancer Center and Dana-Farber Cancer Institute. It is also used by precision oncology tools such as OncoKB and cBioPortal for Cancer Genomics.
OncoTree is a dynamic and flexible community-driven cancer classification platform encompassing rare and common cancers that provides clinically relevant and appropriately granular cancer classification for clinical decision support systems and oncology research.
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