Harnessing imaging tools to guide immunotherapy trials: summary from the National Cancer Institute Cancer Imaging Steering Committee workshop.

As the immuno-oncology field continues the rapid growth witnessed over the past decade, optimising patient outcomes requires an evolution in the current response-assessment guidelines for phase 2 and 3 immunotherapy clinical trials and clinical care. Additionally, investigational tools-including image analysis of standard-of-care scans (such as CT, magnetic resonance, and PET) with analytics, such as radiomics, functional magnetic resonance agents, and novel molecular-imaging PET agents-offer promising advancements for assessment of immunotherapy. To document current challenges and opportunities and identify next steps in immunotherapy diagnostic imaging, the National Cancer Institute Clinical Imaging Steering Committee convened a meeting with diverse representation among imaging experts and oncologists to generate a comprehensive review of the state of the field.

Formulation, biopharmaceutical evaluation and in-vitro screening of polyherbal phytosomes for breast cancer therapy.

Saudi Arabia has a rich culture of folk medicines and three such common herbs used by Saudi people for therapy of breast cancer are Turmeric (Kurkum) Curcuma longa, Chamomile (Babunaj) Matricaria chamomilla, and Aswaghantha (Aswaghadh) Withania somnifera. Hence, the present study aims to develop a polyherbal phytosome formulation by thin film hydration technique with a synergistic anti-cancer effect for the treatment of breast cancer. The phytosomes were standardized for their phytoconstituents by HPTLC and showed the best optimal properties with a mean vesicle diameter of less than 200 nm, zeta potential in the range of -24.43 to -35.70 mV, and relatively integrated structure with fairly uniform size on TEM. The in vitro MTT assay on MCF-7 breast cancer cell lines and MDA MB 231 breast adenocarcinoma cell lines was carried out. MTT assay on MCF-7 breast cancer cell lines indicated that plant extract-loaded phytosomes exhibited enhanced cytotoxic effects at IC50 values. of 55, 50, 45, 52, 42, 44, and 20 µg/mL compared to the extracts of C. longa, M. chamomilla, W. somnifera, and their combined extracts (80, 82, 74, 60, 70, 60, and 35 µg/mL respectively). Moreover, intracellular reactive oxygen species production was found to be higher for phytosomes treated cells at respective IC50 concentrations when compared to extracts. Overall, the developed polyherbal phytosomes were found to be effective and afford synergistic effects for breast cancer therapy.

Characterization of V. cholerae O1 biotype El Tor serotype Ogawa possessing the ctxB gene of the classical biotype isolated from well water associated with the cholera outbreak in Kerala, South India.

We investigated 22 water samples (17 well water and five pipe water - both chlorinated) and six soil samples from the surroundings of wells of the households of suspected patients from Palakkad district, Kerala (India), from where a cholera outbreak was reported during June-July 2016. A total of 25 Vibrio cholerae isolates were collected from three well water samples during a recent cholera outbreak. Biochemical and serological studies revealed that all of the isolates belonged to serogroup O1, biotype El Tor, serotype Ogawa. PCR assays confirmed the occurrence of ctxB, ctxA, hlyA, tcpA El Tor,VPI, ace, zot, ompW, rfbO1 and toxR genes in all isolates. The presence of the ctxB gene of the classical biotype in all of the El Tor isolates suggests that it is a new variant of El Tor biotype. Antibiogram profile of all V. cholerae O1 isolates revealed resistance towards five classes of antibiotics island and indicates that they were multidrug resistant. ERIC-PCR and PFGE finger prints showed the clonal relationship among the V. cholerae O1 isolates. The results of this study revealed the emergence of a new variant of El Tor biotype in the water samples from Palakkad district, from where a cholera outbreak was reported.

Quorum quenching Bacillus spp.: an alternative biocontrol agent for Vibrio harveyi infection in aquaculture.

Quorum sensing (QS) is a type of cell to cell communication in bacteria that can also regulate the virulence potential in pathogenic strains. Hence, QS disruption, i.e. the quorum quenching (QQ) mechanism, is presently being explored as a novel bio-control strategy to counter bacterial infections. In the present study, we characterized the QQ ability of Bacillus spp. strains to reduce the expression of some virulence factors of a shrimp pathogen, Vibrio harveyi. We screened a total of 118 spore-forming bacterial isolates from aquaculture ponds and mangrove soil for their ability to degrade the synthetic N-acyl-homoserine lactones (AHLs) C4-HSL, C6-HSL, C8-HSL, and C10-HSL. We then selected the top 17 isolates with high AHL-degradation ability for further study. Among them, B. subtilis MFB10, B. lentus MFB2, and B. firmus MFB7 had the highest ability for degradation. These 3 isolates suppressed the expression of virulence genes encoding protease, lipase, phospholipase, caseinase, chitinase, and gelatinase, and potentially inhibited the biofilm formation of V. harveyi MFB32. The reduction in expression of virulence genes like those coding for metalloprotease, serine protease, and haemolysin were confirmed by real-time PCR analysis. Moreover, in an in vivo challenge experiment, these Bacillus spp. protected Penaeus monodon post-larvae against V. harveyi MFB3 infection. Our results demonstrate the potential application of AHL-degrading Bacillus spp. as an alternative to antibiotics in shrimp hatcheries to control luminescent vibriosis. This novel bio-therapeutic method is a promising approach towards disease control in shrimp aquaculture.

Vibrio harveyi virulence gene expression in vitro and in vivo during infection in black tiger shrimp Penaeus monodon.

Luminescent Vibrio harveyi is common in sea and estuarine waters. It produces several virulence factors and negatively affects larval penaeid shrimp in hatcheries, resulting in severe economic losses to shrimp aquaculture. Although V. harveyi is an important pathogen of shrimp, its pathogenicity mechanisms have yet to be completely elucidated. In the present study, isolates of V. harveyi were isolated and characterized from diseased Penaeus monodon postlarvae from hatcheries in Kerala, India, from September to December 2016. All 23 tested isolates were positive for lipase, phospholipase, caseinase, gelatinase and chitinase activity, and 3 of the isolates (MFB32, MFB71 and MFB68) showed potential for significant biofilm formation. Based on the presence of virulence genes, the isolates of V. harveyi were grouped into 6 genotypes, predominated by vhpA+ flaB+ ser+ vhh1- luxR+ vopD- vcrD+ vscN-. One isolate from each genotype was randomly selected for in vivo virulence experiments, and the LD50 ranged from 1.7 ± 0.5 × 103 to 4.1 ± 0.1 × 105 CFU ml-1. The expression of genes during the infection in postlarvae was high in 2 of the isolates (MFB12 and MFB32), consistent with the result of the challenge test. However, in MFB19, even though all genes tested were present, their expression level was very low and likely contributed to its lack of virulence. Because of the significant variation in gene expression, the presence of virulence genes alone cannot be used as a marker for pathogenicity of V. harveyi.

Prevalence, molecular characterization, genetic heterogeneity and antimicrobial resistance of Listeria monocytogenes associated with fish and fishery environment in Kerala, India.

The prevalence of Listeria monocytogenes in the retail fish markets of the Kerala, India was investigated by screening 227 samples comprising of marine finfish (n = 97) shellfish (n = 19), ready-to-cook fish products (n = 47), ready-to-eat fish products (n = 10), dried fish (n = 11) and retail ice (n = 43). The prevalence of L. monocytogenes and L. innocua was 2·7% and 17·2% respectively. Sample category wise, prevalence of L. monocytogenes was higher in marine finfish (1·8%) and retail ice (0·9%). All the L. monocytogenes isolates carried virulent genes namely inlA, inlC, inlJ, hlyA, iap, plcA, prfA genes and majority (82%) belonged to 1/2a, 3a serogroups. L. monocytogenes isolates were multidrug-resistant and showed resistance to ampicillin, penicillin, erythromycin, tetracycline and clindamycin. Enterobacterial repetitive intergenic consensus-polymerase chain reaction (ERIC-PCR) delineated 58% genetic heterogeneity among the L. monocytogenes strains. The study reports that genetic similarities of the isolates were interlinked to their serogroup and sample origin. SIGNIFICANCE AND IMPACT OF THE STUDY: Prevalence of Listeria monocytogenes, in the retail fish markets of Kerala, India was low but their relatively higher presence in marine finfish and retail ice and virulent nature of the isolates signifies food safety concerns. Moreover, multidrug-resistant nature of these isolates may potentially lead to spread of antimicrobial resistance. This study identified retail ice as a vehicle for entry of L. monocytogenes in retail fish and hence, there is a need to ensure quality of retail ice used for maintaining the cold-chain.

Strain variability and pathogenic potential of tdhcarrying Vibrio parahaemolyticus isolated from diseased Penaeus monodon.

A disease outbreak in 42-d-old black tiger shrimp Penaeus monodon juveniles from a commercial aquaculture farm in Kerala, India, was investigated. The cause of the disease outbreak was confirmed as Vibrio parahaemolyticus by biochemical tests, PCR targeting the toxR gene and pathogenicity testing of the isolates. All of the isolates tested negative by PCR specific for V. parahaemolyticus associated with acute hepatopancreatic necrosis disease (AHPND), implicating vibriosis unrelated to AHPND as the cause of mortality. Among the 19 isolates obtained, 2 possessed the tdh gene (coding for thermo-stable hemolysin), whereas none of the isolates possessed trh. The LD50 value of 8 isolates of V. parahaemolyticus from diseased and apparently healthy shrimp ranged from 2.7 × 104 to 4.9 × 105 CFU ml-1 by immersion challenge of P. monodon postlarvae. BOX-PCR and dendrogram analysis of the bacterial isolates revealed that the isolates from moribund and apparently healthy shrimp formed separate clusters, indicating that these isolates originate from separate clones. The isolates from moribund shrimp including tdh-positive V. parahaemolyticus clustered together. The present study represents the first report of tdh-positive V. parahaemolyticus causing disease in a shrimp farm.

Design, synthesis and in vitro study of densely functionalized oxindoles as potent α-glucosidase inhibitors.

Diabetes a non-communicable disease occurs either due to the lack of insulin or the inability of the human body to recognize it. The recent data indicated an increase in the trend of people diagnosed with type 2 diabetes mainly due to unhealthy life style. Here in we report a new class of oxindole derivatives 6a-kvia scaffold hopping of known α-glucosidase inhibitors 1-4. When molecular docking was performed against a homology model of α-glucosidase the resulting compound 6d revealed binding interactions comparable to 1-4. The compounds were accessed through a unique condensation-ring opening protocol of pyridofuranone building blocks. Overall the compounds exhibited decent binding to the yeast α-glucosidase, where the most potent compound 6h, inhibited the enzyme with IC50 of 0.6 µM. This was nearly threefold improvement from the original known compounds 1-4, selected to design the newer analogs. The reaction kinetics of 6h indicated competitive inhibition.

iRECIST: guidelines for response criteria for use in trials testing immunotherapeutics.

Tumours respond differently to immunotherapies compared with chemotherapeutic drugs, raising questions about the assessment of changes in tumour burden-a mainstay of evaluation of cancer therapeutics that provides key information about objective response and disease progression. A consensus guideline-iRECIST-was developed by the RECIST working group for the use of modified Response Evaluation Criteria in Solid Tumours (RECIST version 1.1) in cancer immunotherapy trials, to ensure consistent design and data collection, facilitate the ongoing collection of trial data, and ultimate validation of the guideline. This guideline describes a standard approach to solid tumour measurements and definitions for objective change in tumour size for use in trials in which an immunotherapy is used. Additionally, it defines the minimum datapoints required from future trials and those currently in development to facilitate the compilation of a data warehouse to use to later validate iRECIST. An unprecedented number of trials have been done, initiated, or are planned to test new immune modulators for cancer therapy using a variety of modified response criteria. This guideline will allow consistent conduct, interpretation, and analysis of trials of immunotherapies.

Critical Role of Monoclinic Polarization Rotation in High-Performance Perovskite Piezoelectric Materials.

High-performance piezoelectric materials constantly attract interest for both technological applications and fundamental research. The understanding of the origin of the high-performance piezoelectric property remains a challenge mainly due to the lack of direct experimental evidence. We perform in situ high-energy x-ray diffraction combined with 2D geometry scattering technology to reveal the underlying mechanism for the perovskite-type lead-based high-performance piezoelectric materials. The direct structural evidence reveals that the electric-field-driven continuous polarization rotation within the monoclinic plane plays a critical role to achieve the giant piezoelectric response. An intrinsic relationship between the crystal structure and piezoelectric performance in perovskite ferroelectrics has been established: A strong tendency of electric-field-driven polarization rotation generates peak piezoelectric performance and vice versa. Furthermore, the monoclinic M_{A} structure is the key feature to superior piezoelectric properties as compared to other structures such as monoclinic M_{B}, rhombohedral, and tetragonal. A high piezoelectric response originates from intrinsic lattice strain, but little from extrinsic domain switching. The present results will facilitate designing high-performance perovskite piezoelectric materials by enhancing the intrinsic lattice contribution with easy and continuous polarization rotation.

Investigation of transferrin interaction with medicinally important noble metal ions using affinity capillary electrophoresis.

Transferrins (TFs) consist of a large group of glycoproteins, whose function is to transport iron across the cell membrane. Apart from iron, serum transferrin can also bind several other metal ions and hence can offer a potential route for the delivery of these metal ions into the cellular fluids. In the present study the interaction behavior of nine noble metal ions, Ag+, Au+, Au3+, Os3+, Pd2+, Pt4+, Rh3+, Ru3+ and Ir3+ with transferrin was investigated by affinity capillary electrophoresis (ACE) using the dynamic mobility shift mode. A proper rinsing procedure was applied to regenerate the capillary tube. The influence of these metal ions on transferrin was studied through comparison of the mobility ratios of free protein and protein-metal ion complex. The interaction results were expressed by the normalized difference of the mobility ratios (ΔR/Rf) and its confidence intervals. Most of the tested metal ions showed significant interaction with transferrin with small confidence intervals, except Ag+, Au+ and Rh3+ that exhibited very weak interactions. Maximum interaction was observed between transferrin and Ir3+, followed by Pd2+ that also showed strong affinity towards the test protein. The screening results were compared with Bovine Serum Albumin (BSA)- and Human Serum Albumin (HSA)-noble metal ions interactions. An excellent precision (% RSD of mobility ratios were less than 1%, except for transferrin-Pd2+ interaction ≈ 4%) was recorded for repeated runs of transferrin-metal ions interactions. This study contributes to the understanding of the affinity of transferrin to the tested metal ions and will provide preliminary information for the investigation of other protein-ligands interactions.

Effect of chitosan on shelf life of restructured fish products from pangasius (pangasianodon hypophthalmus) surimi during chilled storage.

In the present study, restructured products were prepared from pangasius surimi and their qualities were analysed under chilled storage. Pangasius surimi had 75.82 % moisture, 16.91 % protein, 2.76 % fat and 0.95 % ash. Restructured products were prepared in three different formulations by incorporating corn starch (10 %) and chitosan (0.75 %). Formulation containing only corn starch (10 %) was served as control. In all the formulations, mono unsaturated fatty acids were higher (45.14 %). The total volatile base nitrogen (TVB-N) showed an increasing trend and it was found to be higher in control (4.8 mg/100 g) on 10(th) day than the chitosan incorporated sample (3.5-4.2 mg/100 g) on 17(th) day during chill storage. Similarly, peroxide value (PV) was found to higher (8.85 milliequivalent of O2/kg) in control than the chitosan incorporated sample (4.5-6.8 milliequivalent of O2/kg) on 10(th) day. All the three formulations had an acceptable level of thiobarbituric acid (TBA) value that ranged between 0.023-0.098 mg of malanoldehyde/kg during chilled storage. Based on the sensory and microbiological analysis, products prepared without chitosan had a shelf life of 10 day whereas, products incorporated with chitosan had an extended shelf life of 17 day.

A risk management approach for imaging biomarker-driven clinical trials in oncology.

Imaging has steadily evolved in clinical cancer research as a result of improved conventional imaging methods and the innovation of new functional and molecular imaging techniques. Despite this evolution, the design and data quality derived from imaging within clinical trials are not ideal and gaps exist with paucity of optimised methods, constraints of trial operational support, and scarce resources. Difficulties associated with integrating imaging biomarkers into trials have been neglected compared with inclusion of tissue and blood biomarkers, largely because of inherent challenges in the complexity of imaging technologies, safety issues related to new imaging contrast media, standardisation of image acquisition across multivendor platforms, and various postprocessing options available with advanced software. Ignorance of these pitfalls directly affects the quality of the imaging read-out, leading to trial failure, particularly when imaging is a primary endpoint. Therefore, we propose a practical risk-based framework and recommendations for trials driven by imaging biomarkers, which allow identification of risks at trial initiation to better allocate resources and prioritise key tasks.

Biochemical, textural, microbiological and sensory attributes of gutted and ungutted sutchi catfish (Pangasianodon hypophthalmus) stored in ice.

Pangasianodon hypophthalmus (sutchi catfish) is a fresh water catfish extensively being cultured in the South East Asian countries in the recent years. The present study provides the first report on the effects of gutting on the quality characteristics of aquacultured sutchi catfish stored in ice. pH of whole ungutted and gutted catfish didn't show significant difference (p > 0.05) during ice storage period. Total Volatile Base Nitrogen (TVB-N), Alpha Amino Nitrogen (AAN), Free Fatty Acids (FFA) and Thio Barbituric Acid Reactive Substance (TBARS) were lower in gutted fish compared to whole ungutted fish at any particular day during ice storage. However, gutted fish expressed higher rate of primary lipid oxidation than ungutted fish. Textural degradation of the fish muscle as indicated by hardness, cohesiveness, springiness and chewiness was lower in gutted fish. Results of sensory evaluation revealed that gutting has significantly improved the sensory quality of the fish. However, microbiological analysis revealed higher Total Plate Count (TPC) and Enterobactereaceae count in gutted fish. The shelf life of gutted and whole ungutted sutchi cat fish as determined by microbiological analysis was 16-18 days and 18-20 days respectively while storage in ice.

Resource requirements to accelerate clinical applications of next-generation sequencing and radiomics: workshop commentary and review.

The National Institutes of Health-US Food and Drug Administration Joint Leadership Council Next-Generation Sequencing and Radiomics Working Group was formed by the National Institutes of Health-Food and Drug Administration Joint Leadership Council to promote the development and validation of innovative next-generation sequencing tests, radiomic tools, and associated data analysis and interpretation enhanced by artificial intelligence and machine learning technologies. A 2-day workshop was held on September 29-30, 2021, to convene members of the scientific community to discuss how to overcome the "ground truth" gap that has frequently been acknowledged as 1 of the limiting factors impeding high-quality research, development, validation, and regulatory science in these fields. This report provides a summary of the resource gaps identified by the working group and attendees, highlights existing resources and the ways they can potentially be employed to accelerate growth in these fields, and presents opportunities to support next-generation sequencing and radiomic tool development and validation using technologies such as artificial intelligence and machine learning.

A Neuroradiologist's Guide to Operationalizing the Response Assessment in Neuro-Oncology (RANO) Criteria Version 2.0 for Gliomas in Adults.

Radiographic assessment plays a crucial role in the management of patients with central nervous system (CNS) tumors, aiding in treatment planning and evaluation of therapeutic efficacy by quantifying response. Recently, an updated version of the Response Assessment in Neuro-Oncology (RANO) criteria (RANO 2.0) was developed to improve upon prior criteria and provide an updated, standardized framework for assessing treatment response in clinical trials for gliomas in adults. This article provides an overview of significant updates to the criteria including (1) the use of a unified set of criteria for high and low grade gliomas in adults; (2) the use of the post-radiotherapy MRI scan as the baseline for evaluation in newly diagnosed high-grade gliomas; (3) the option for the trial to mandate a confirmation scan to more reliably distinguish pseudoprogression from tumor progression; (4) the option of using volumetric tumor measurements; and (5) the removal of subjective non-enhancing tumor evaluations in predominantly enhancing gliomas (except for specific therapeutic modalities). Step-by-step pragmatic guidance is hereby provided for the neuroradiologist and imaging core lab involved in operationalization and technical execution of RANO 2.0 in clinical trials, including the display of representative cases and in-depth discussion of challenging scenarios.

Nurses' perception about a DVD module on 'mental status examination demonstration'.

Computer-based multimedia can improve learning and retention of learnt material A video recorded DVD module on role play of mental status examination was visualised by 226 nursing students and 133 nursing teachers. Their opinion of the DVD on various parameters such as audibility, visibility, clarity, methodical, organisation of content, following the principles of psychiatric interview, symptom elicitation, therapist behaviour, therapist communication skill and ease in understanding revealed that the DVD module was of high quality and could be used as a teaching tool

Meta-Analysis of the Test-Retest Repeatability of [18F]-Fluorodeoxyglucose Standardized Uptake Values: Implications for Assessment of Tumor Response.

PURPOSE: Currently, guidelines for PET with 18F-fluorodeoxyglucose (FDG-PET) interpretation for assessment of therapy response in oncology primarily involve visual evaluation of FDG-PET/CT scans. However, quantitative measurements of the metabolic activity in tumors may be even more useful in evaluating response to treatment. Guidelines based on such measurements, including the European Organization for Research and Treatment of Cancer Criteria and PET Response Criteria in Solid Tumors, have been proposed. However, more rigorous analysis of response criteria based on FDG-PET measurements is needed to adopt regular use in practice. EXPERIMENTAL DESIGN: Well-defined boundaries of repeatability and reproducibility of quantitative measurements to discriminate noise from true signal changes are a needed initial step. An extension of the meta-analysis from de Langen and colleagues (2012) of the test-retest repeatability of quantitative FDG-PET measurements, including mean, maximum, and peak standardized uptake values (SUVmax, SUVmean, and SUVpeak, respectively), was performed. Data from 11 studies in the literature were used to estimate the relationship between the variance in test-retest measurements with uptake level and various study-level, patient-level, and lesion-level characteristics. RESULTS: Test-retest repeatability of percentage fluctuations for all three types of SUV measurement (max, mean, and peak) improved with higher FDG uptake levels. Repeatability in all three SUV measurements varied for different lesion locations. Worse repeatability in SUVmean was also associated with higher tumor volumes. CONCLUSIONS: On the basis of these results, recommendations regarding SUV measurements for assessing minimal detectable changes based on repeatability and reproducibility are proposed. These should be applied to differentiate between response categories for a future set of FDG-PET-based criteria that assess clinically significant changes in tumor response.