Whole genome sequencing reveals the mutational landscape from disease diagnosis to relapse in patients with childhood acute myeloid leukaemia.

INTRODUCTION: Leukaemia is the most common cancer in children, however, there is still a big gap in knowledge about the genomic alterations in childhood acute myeloid leukaemia (AML) compared to adult AML. Relapsed AML remains as a leading cause of cancer deaths among children. This study aims to understand the molecular mechanisms of relapsed AML by elucidating the mutational landscape before and during relapse. MATERIALS AND METHODS: Whole genome sequencing was performed on matched samples collected at diagnosis, remission and relapse from three patients of de novo childhood AML. Sanger sequencing was performed for validation in 47 patients' samples, followed by functional analysis. RESULTS: Overall, we identified 312 somatic mutations including synonymous single nucleotide variants (SNVs), missense SNVs, deletions and insertion frameshifts, stopgains and splice sites. After prioritisation, only 46 variants were present at diagnosis (13-17 mutations per patient) and 49 variants at relapse (12-20 mutations per patient). Out of 81 variants, there were 35 new variants detected at relapse but not present at diagnosis. Six potential driver mutations (KIT, CDC73, HNF1A, RBM10, ZMYM4 and ETV6) were identified in predicting relapse for the 3 patients, with recurrent mutations of the ETV6 gene in 2 patients. Functional analysis of the ETV6 mutation showed that ETV6 lost its tumour suppressive function when both mutant ETV6 p.P25fs and ETV6 p.N75fs were tested in vitro. CONCLUSION: This study has uncovered the mutational landscape in three local childhood AML patients and contributes to a better understanding of the molecular mechanisms of relapsed AML.

Cutting Through the Noise: Auditory Scenes and Their Effects on Visual Object Processing.

Despite the intuitive feeling that our visual experience is coherent and comprehensive, the world is full of ambiguous and indeterminate information. Here we explore how the visual system might take advantage of ambient sounds to resolve this ambiguity. Young adults (ns = 20-30) were tasked with identifying an object slowly fading in through visual noise while a task-irrelevant sound played. We found that participants demanded more visual information when the auditory object was incongruent with the visual object compared to when it was not. Auditory scenes, which are only probabilistically related to specific objects, produced similar facilitation even for unheard objects (e.g., a bench). Notably, these effects traverse categorical and specific auditory and visual-processing domains as participants performed across-category and within-category visual tasks, underscoring cross-modal integration across multiple levels of perceptual processing. To summarize, our study reveals the importance of audiovisual interactions to support meaningful perceptual experiences in naturalistic settings.

Antagonistic and enzymatic activities of Bacillus species isolated from the fish gastrointestinal tract as potential probiotics use in Artemia culture.

Probiotics have been used successfully in aquaculture to enhance disease resistance, nutrition, and/or growth of cultured organisms. Six strains of Bacillus were isolated from the intestinal tracts of fish and recognised by conventional biochemical traits. The six isolated strains were Bacillus cereus and Bacillus subtilis using MALDI-TOF-MS technique. The probiotic properties of these Bacillus strains were studied. The tested bacillus strains exhibit antibacterial activity against the different pathogens. The strain S5 gave the important inhibition zones against most pathogens (20.5, 20.33, 23, and 21 mm against Vibrio alginolyticus, Vibrio parahaemolyticus, Staphylococcus aureus, and Salmonella typhimurium, respectively). According to our results, all Bacillus strains have extracellular components that can stop pathogenic bacteria from growing. The enzymatic characterization showed that the tested strains can produce several biotechnological enzymes such as α-glucosidase, naphtol-AS-BI-Phosphohydrolase, esterase lipase, acid phosphatase, alkaline phosphatase, amylase, lipase, caseinase, and lecithinase. All Bacillus strains were adhesive to polystyrene. The adding Bacillus strains to the Artemia culture exerted significantly greater effects on the survival of Artemia. The challenge test on Artemia culture showed that the protection against pathogenic Vibrio was improved. These findings allow us to recommend the examined strains as prospective probiotic options for the Artemia culture, which will be used as food additives to improve the culture conditions of crustacean larvae and marine fish.

Improving the anti-diabetic and anti-hyperlipidemic activities of extra virgin olive oil by the incorporation of diallyl sulfide.

Development of novel functional foods is trending as one of the hot topics in food science and food/beverage industries. In the present study, the anti-diabetic, anti-hyperlipidemic and histo-protective effects of the extra virgin olive oil (EVOO) enriched with the organosulfur diallyl sulfide (DAS) (DAS-rich EVOO) were evaluated in alloxan-induced diabetic mice. The ingestion of EVOO (500µL daily for two weeks) attenuated alloxan-induced elevated glucose, alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase, lactate dehydrogenase (LDH), urea and creatinine. It also normalized the levels of triglycerides (TG), total cholesterols (TC), low-density lipoprotein-cholesterol (LDL-c) and their consequent atherogenic index of plasma (AIP) in diabetic animals. Additionally, EVOO prevented lipid peroxidation (MDA) and reduced the level of hydrogen peroxide (H2O2) in diabetic animals. Concomitantly, it enhanced the activity of the antioxidant enzymes catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD), reducing thereby tissue oxidative stress injury. The overall histologic (pancreas, liver, and kidney) alterations were also improved after EVOO ingestion. The manifest anti-diabetic, lipid-lowering and histo-protective properties of EVOO were markedly potentiated with DAS-rich EVOO suggesting possible synergistic interactions between DAS and EVOO lipophilic bioactive ingredients. Overall, EVOO and DAS-rich EVOO show promise as functional foods and/or adjuvants for the treatment of diabetes and its complications.

Green synthesis and characterization of silver nanoparticles from Ducrosia flabellifolia Boiss. aqueous extract: Anti-quorum sensing screening and antimicrobial activities against ESKAPE pathogens.

Biosynthesis of silver nanoparticles using natural compounds derived from plant kingdom is currently used as safe and low-cost technique for nanoparticles synthesis with important abilities to inhibit multidrug resistant microorganisms (MDR). ESKAPE pathogens, especially MDR ones, are widely spread in hospital and intensive care units. In the present study, AgNPs using Ducrosia flabellifolia aqueous extract were synthesized using a reduction method. The green synthesized D. flabellifolia-AgNPs were characterized by UV-Vis spectrophotometer, Scanning electron microscopy (SEM), and X-ray diffraction assays. The tested D. flabellifolia aqueous extract was tested for its chemical composition using Liquid Chromatography-Electrospray Ionization-Mass Spectrometry (LC-ESI-MS). Anti-quorum sensing and anti-ESKAPE potential of D. flabellifolia-AgNPs was also performed.  Results from LC-ESI-MS technique revealed the identification of chlorogenic acid, protocatechuic acid, ferulic acid, caffeic acid, 2,5-dihydroxybenzoic acid, and gallic acid as main phytoconstituents. Indeed, the characterization of newly synthetized D. flabellifolia-AgNPs revealed spherical shape with mean particle size about 16.961±2.914 nm. Bio-reduction of silver was confirmed by the maximum surface plasmon resonance of D. flabellifolia-AgNPs at 430 nm. Newly synthetized D. flabellifolia-AgNPs were found to possess important anti-ESKAPE activity with low minimal inhibitory concentrations (MICs) ranging from 0.078 to 0.312 mg/mL, and low minimal bactericidal concentrations (MBCs) varying from 0.312 to 0.625 mg/mL. Moreover, D. flabellifolia-AgNPs were active against Candida utilis ATCC 9255, C. tropicalis ATCC 1362, and C. albicans ATCC 20402 with high mean diameter of growth inhibition at 5 mg/mL, low MICs, and minimal fungicidal concentrations values (MFCs). The newly synthetized D. flabellifolia-AgNPs were able to inhibit violacein production in Chromobacterium violaceum, pyocyanin in Pseudomonas aeruginosa starter strains.  Hence, the newly synthesized silver nanoparticles using D. flabellifolia aqueous extract can be used as an effective alternative to combat ESKAPE microorganisms. These silver nanoparticles can attenuate virulence of Gram-negative bacteria by interfering with the quorum sensing system and inhibiting cell-to-cell communication.

The Cross Talk Between Psoriasis, Obesity, and Dyslipidemia: A Meta-Analysis.

Although psoriasis is a multi-organ disease, it is usually managed as a skin disease, ignoring its associated serious comorbidities. This meta-analysis aimed to investigate the relationship between psoriasis, dyslipidemia, and obesity. Two authors independently searched three databases (PubMed, Medical Literature Analysis and Retrieval System Online (MEDLINE), The Cochrane Library, and Google Scholar). The search was set for articles published in the English language during the period from January 2013 to August 2023. The keywords "psoriasis", "hypercholesterolemia", "dyslipidemia", "low-density lipoproteins", "high body mass index", and "obesity", were used. Out of the 145 full texts reviewed, only seven studies fulfilled the inclusion and exclusion criteria (773,761 participants and 196,593 events). Psoriasis was associated with dyslipidemia and obesity (odds ratio (OR)=1.63, 95% CI: 1.42-1.88 and OR=1.70, 95% CI: 1.43-2.02), respectively, with significant heterogeneity (98% and 97%, respectively). Dyslipidemia and obesity were significant psoriasis comorbidities; a broader approach, viewing psoriasis as a multi-organ disease, is recommended for optimal treatment and outcomes.

Chemical control and herbicide resistance of hairy fleabane (Erigeron bonariensis L.) in Jordan.

The effect of paraquat, oxadiazon and oxyfluorfen herbicides was tested on two populations of hairy fleabane (Erigeron bonariensis L.), collected from a date palm orchard at Tal al-Ramil (Central Jordan Valley) and al-Twal (Northern Jordan Valley) sites using the recommended rates (0.5, 1.25 and 0.792kg a.i ha-1 for each herbicide, respectively) and 10-fold (5, 12.50 and 7.92 kg a.i. ha-1, respectively) under glasshouse conditions. Results showed that the date palm weed population was resistant to the three herbicides at both application rates and al-Twal site population was highly susceptible. Two field experiments were conducted to evaluate the effectiveness of 12 herbicides in controlling the weed in the date palm orchard during the spring of 2017, revealed that E. bonariensis resists paraquat (0.5, 1.0 and 1.5 kg a.i. ha-1), oxadiazon (1.25 kg a.i. ha-1) and oxyfluorfen (0.792 kg a.i. ha-1) herbicides. None of the three herbicides was effective against the weed and treated plants continued to grow normally similar to those of untreated control. Ten-fold higher rates of these herbicides failed to control the weed. The effect of other tested herbicides was variable with bromoxynil plus MCPA (buctril®M), 2,4-D- iso-octyl ester, glyphosate, glyphosate trimesium and triclopyr being the most effective and completely controlling the weed at recommended rates of application. It is concluded that the tested populations of E. bonariensis developed resistance to paraquat, oxadiazon and oxyfluorfen but control of the weed was possible using other herbicides with different mechanisms of action. Herbicide rotation or other nonchemical weed control methods have been suggested to prevent or reduce the buildup and spread of resistant populations of this weed. These results represent the first report of herbicide resistance of E. bonariensis in Jordan.

There Is no Theory-Free Measure of "Swaps" in Visual Working Memory Experiments.

Visual working memory is highly limited, and its capacity is tied to many indices of cognitive function. For this reason, there is much interest in understanding its architecture and the sources of its limited capacity. As part of this research effort, researchers often attempt to decompose visual working memory errors into different kinds of errors, with different origins. One of the most common kinds of memory error is referred to as a "swap," where people report a value that closely resembles an item that was not probed (e.g., an incorrect, non-target item). This is typically assumed to reflect confusions, like location binding errors, which result in the wrong item being reported. Capturing swap rates reliably and validly is of great importance because it permits researchers to accurately decompose different sources of memory errors and elucidate the processes that give rise to them. Here, we ask whether different visual working memory models yield robust and consistent estimates of swap rates. This is a major gap in the literature because in both empirical and modeling work, researchers measure swaps without motivating their choice of swap model. Therefore, we use extensive parameter recovery simulations with three mainstream swap models to demonstrate how the choice of measurement model can result in very large differences in estimated swap rates. We find that these choices can have major implications for how swap rates are estimated to change across conditions. In particular, each of the three models we consider can lead to differential quantitative and qualitative interpretations of the data. Our work serves as a cautionary note to researchers as well as a guide for model-based measurement of visual working memory processes.

Effect of natural and synthetic androgen hormone on sex reversal of Nile Tilapia (Oreochromis niloticus).

The present study aimed to produce a monosex population of all male Nile tilapia (Oreochromis spp.) using 17α-methyl testosterone and common carp testes (as a source of natural androgen). Trial was conducted into two consecutive phases, the first was fry (4-5 days old)administration with negative control (without hormone) and positive control (with hormone) feed viz., MT1:60mg/kg, MT2:70mg/kg (17α-MT), carp testis CT1:70% and CT2:80% for 30 days to reverse the sex of male fish and the second phase was nursing the fingerlings for two months on control diet (32% Crude protein).Results revealed a significant growth rate (P<0.05) in the control group where final weight (4.8±0.34ab) and weight gained was recorded as 0.66±0.03ac. In proximate chemical composition of body meat, CT2 treatment showed maximum retention of crude protein, crude fat, and ash whereas dry matter showed maximum retention in MT2 and CT1 treatments. Morphological and histological examination revealed significant difference (p<0.05) in phenotypic males of Nile tilapia fed with the highest percent in MT-treated diet (MT2) of 95±0.58a while MT1, CT2 and CT1 had males of 85±6.0b, 70±5.0b and 65±6.5b, respectively. It was concluded that synthetic androgen (17αMT) was more effective for masculinization but natural androgen scan be an alternative method to produce male tilapia population in an environment-friendly manner as they are inexpensive, eco-friendly, and radially available. These results suggested that synthetic and natural androgen supplementation in the diet plays a significant role in improving growth performance and body composition.

Measuring memory is harder than you think: How to avoid problematic measurement practices in memory research.

We argue that critical areas of memory research rely on problematic measurement practices and provide concrete suggestions to improve the situation. In particular, we highlight the prevalence of memory studies that use tasks (like the "old/new" task: "have you seen this item before? yes/no") where quantifying performance is deeply dependent on counterfactual reasoning that depends on the (unknowable) distribution of underlying memory signals. As a result of this difficulty, different literatures in memory research (e.g., visual working memory, eyewitness identification, picture memory, etc.) have settled on a variety of fundamentally different metrics to get performance measures from such tasks (e.g., A', corrected hit rate, percent correct, d', diagnosticity ratios, K values, etc.), even though these metrics make different, contradictory assumptions about the distribution of latent memory signals, and even though all of their assumptions are frequently incorrect. We suggest that in order for the psychology and neuroscience of memory to become a more cumulative, theory-driven science, more attention must be given to measurement issues. We make a concrete suggestion: The default memory task for those simply interested in performance should change from old/new ("did you see this item'?") to two-alternative forced-choice ("which of these two items did you see?"). In situations where old/new variants are preferred (e.g., eyewitness identification; theoretical investigations of the nature of memory signals), receiver operating characteristic (ROC) analysis should be performed rather than a binary old/new task.

You cannot "count" how many items people remember in visual working memory: The importance of signal detection-based measures for understanding change detection performance.

Change detection tasks are commonly used to measure and understand the nature of visual working memory capacity. Across three experiments, we examine whether the nature of the memory signals used to perform change detection are continuous or all-or-none and consider the implications for proper measurement of performance. In Experiment 1, we find evidence from confidence reports that visual working memory is continuous in strength, with strong support for an equal variance signal detection model with no guesses or lapses. Experiments 2 and 3 test an implication of this, which is that K should confound response criteria and memory. We found K values increased by roughly 30% when criteria are shifted despite no change in the underlying memory signals. Overall, our data call into question a large body of work using threshold measures, like K, to analyze change detection data. This metric confounds response bias with memory performance and is inconsistent with the vast majority of visual working memory models, which propose variations in precision or strength are present in working memory. Instead, our data indicate an equal variance signal detection model (and thus, d')-without need for lapses or guesses-is sufficient to explain change detection performance. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

What You See Is What You Hear: Sounds Alter the Contents of Visual Perception.

Visual object recognition is not performed in isolation but depends on prior knowledge and context. Here, we found that auditory context plays a critical role in visual object perception. Using a psychophysical task in which naturalistic sounds were paired with noisy visual inputs, we demonstrated across two experiments (young adults; ns = 18-40 in Experiments 1 and 2, respectively) that the representations of ambiguous visual objects were shifted toward the visual features of an object that were related to the incidental sound. In a series of control experiments, we found that these effects were not driven by decision or response biases (ns = 40-85) nor were they due to top-down expectations (n = 40). Instead, these effects were driven by the continuous integration of audiovisual inputs during perception itself. Together, our results demonstrate that the perceptual experience of visual objects is directly shaped by naturalistic auditory context, which provides independent and diagnostic information about the visual world.

Guidance of attention by working memory is a matter of representational fidelity.

Items that are held in visual working memory can guide attention toward matching features in the environment. Predominant theories propose that to guide attention, a memory item must be internally prioritized and given a special template status, which builds on the assumption that there are qualitatively distinct states in working memory. Here, we propose that no distinct states in working memory are necessary to explain why some items guide attention and others do not. Instead, we propose variations in attentional guidance arise because individual memories naturally vary in their representational fidelity, and only highly accurate memories automatically guide attention. Across a series of experiments and a simulation we show that (a) items in working memory vary naturally in representational fidelity; (b) attention is guided by all well-represented items, though frequently only one item is represented well enough to guide; and (c) no special working memory state for prioritized items is necessary to explain guidance. These findings challenge current models of attentional guidance and working memory and instead support a simpler account for how working memory and attention interact: Only the representational fidelity of memories, which varies naturally between items, determines whether and how strongly a memory representation guides attention. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Associated genetic polymorphisms and clinical manifestations in systemic lupus erythematosus in Asian populations - A systematic literature review.

INTRODUCTION: Systemic lupus erythematosus (SLE) is a chronic and life-threatening autoimmune disease. Its prevalence and clinical manifestations are known to be particularly severe in the Asian populations. Although genetics is known to play an important role in SLE susceptibility and clinical manifestations, the specific polymorphisms associated with these phenotypes in Asia are unclear. Therefore, we aim to review the association of SLE genetic polymorphisms with lupus manifestations across Asian populations and their role in the pathogenesis of SLE. METHODS: A systematic search was conducted on PubMed, EBSCOHost, and Web of Science. We identified 22 casecontrol studies that matched our inclusion and exclusion criteria. Information such as study characteristics, genetic polymorphisms associated with SLE, and organ manifestations was extracted and reported in this review. RESULTS: In total, 30 polymorphisms in 16 genes were found to be associated with SLE among Asians. All included polymorphisms also reported associations with various SLE clinical features. The association of rs1234315 in TNFSF4 linking to SLE susceptibility (P=4.17x10-17 OR=1.45 95% CI=1.34-1.59) and musculoskeletal manifestation (P=3.35x10-9, OR=1.37, 95%CI= 1.23-1.51) might be the most potential biomarkers to differentiate SLE between Asian and other populations. In fact, these associated genetic variants were found in loci that were implicated in immune systems, signal transduction, gene expression that play important roles in SLE pathogenesis. DISCUSSIONS AND CONCLUSIONS: This review summarized the potential correlation between 30 genetic polymorphisms associated with SLE and its clinical manifestations among Asians. More efforts in dissecting the functional implications and linkage disequilibrium of associated variants may be required to validate these findings.

Burden of Ileal Perforations Among Surgical Patients Admitted in Tertiary Care Hospitals of Three Asian countries: Surveillance of Enteric Fever in Asia Project (SEAP), September 2016-September 2019.

BACKGROUND: Typhoid fever is caused by Salmonella enterica subspecies enterica serovar Typhi (S. Typhi) and can lead to systemic illness and complications. We aimed to characterize typhoid-related ileal perforation in the context of the population-based Surveillance of Enteric Fever in Asia Project (SEAP) in Bangladesh, Nepal and Pakistan. METHODS: Between September 2016 and September 2019, all cases of nontraumatic ileal perforation with a clinical diagnosis of typhoid were enrolled from 4 tertiary care hospitals in Karachi, 2 pediatric hospitals in Bangladesh, and 2 hospitals in Nepal. Sociodemographic data were collected from patients or their caregivers, and clinical and outcome data were retrieved from medical records. Tissue samples were collected for histopathology and blood cultures where available. RESULTS: Of the 249 enrolled cases, 2 from Bangladesh, 5 from Nepal and 242 from Pakistan. In Pakistan, most of the cases were in the 0-15 (117/242; 48%) and 16-30 (89/242; 37%) age groups. In all countries, males were most affected: Pakistan 74.9% (180/242), Nepal 80% (4/5), and Bangladesh 100% (2/2). Blood culture was done on 76 cases; 8 (11%) were positive for S. Typhi, and all were extensively drug resistant (XDR) S. Typhi. Tissue cultures was done on 86 patients; 3 (3%) were positive for S. Typhi, and all were XDR S. Typhi, out of 86 samples tested for histopathology 4 (5%) revealed ileal perforation with necrosis. Culture or histopathology confirmed total 15 (11%) enteric fever cases with ileal perforation are similar to the clinically diagnosed cases. There were 16/242 (7%) deaths from Pakistan. Cases of ileal perforation who survived were more likely to have sought care before visiting the sentinel hospital (P = .009), visited any hospital for treatment (P = .013) compared to those who survived. CONCLUSIONS: Although surveillance differed substantially by country, one reason for the higher number of ileal perforation cases in Pakistan could be the circulation of XDR strain of S. Typhi in Karachi.

Gene-environment interaction in chronic kidney disease among people with type 2 diabetes from The Malaysian Cohort project: a case-control study.

AIM: To examine the possible gene-environment interactions between 32 single nucleotide polymorphisms and environmental factors that could modify the probability of chronic kidney disease. METHODS: A case-control study was conducted involving 600 people with type 2 diabetes (300 chronic kidney disease cases, 300 controls) who participated in The Malaysian Cohort project. Retrospective subanalysis was performed on the chronic kidney disease cases to assess chronic kidney disease progression from the recruitment phase. We genotyped 32 single nucleotide polymorphisms using mass spectrometry. The probability of chronic kidney disease and predicted rate of newly detected chronic kidney disease progression were estimated from the significant gene-environment interaction analyses. RESULTS: Four single nucleotide polymorphisms (eNOS rs2070744, PPARGC1A rs8192678, KCNQ1 rs2237895 and KCNQ1 rs2283228) and five environmental factors (age, sex, smoking, waist circumference and HDL) were significantly associated with chronic kidney disease. Gene-environment interaction analyses revealed significant probabilities of chronic kidney disease for sex (PPARGC1A rs8192678), smoking (eNOS rs2070744, PPARGC1A rs8192678 and KCNQ1 rs2237895), waist circumference (eNOS rs2070744, PPARGC1A rs8192678, KCNQ1 rs2237895 and KCNQ1 rs2283228) and HDL (eNOS rs2070744 and PPARGC1A rs8192678). Subanalysis indicated that the rate of newly detected chronic kidney disease progression was 133 cases per 1000 person-years (95% CI: 115, 153), with a mean follow-up period of 4.78 (SD 0.73) years. There was a significant predicted rate of newly detected chronic kidney disease progression in gene-environment interactions between KCNQ1 rs2283228 and two environmental factors (sex and BMI). CONCLUSIONS: Our findings suggest that the gene-environment interactions of eNOS rs2070744, PPARGC1A rs8192678, KCNQ1 rs2237895 and KCNQ1 rs2283228 with specific environmental factors could modify the probability for chronic kidney disease.

In vitro cytotoxicity analysis of Zizyphus spina-christi stem bark extract on human cancer cell lines.

Zizyphus spina-christi (Rhamnaceae family) is an edible plant used in folk medicine. Therefore, it is of interest to report the cytotoxic effects of Z. spina-christi bark crude extract on human cell lines. Crude ethanol extract of Z. spina-christi bark was fractionated with increasing polarity (diethyl ether, chloroform, ethyl acetate and butanol fractions). The fractions were examined for their cytotoxicity against human colon cancer (HCT-116 and CACO-2), cervical cancer (HeLa and HEp-2), lung carcinoma (A-549), hepatocellular carcinoma (HepG-2), breast cancer (MCF-7) and prostate cancer (PC-3) cell lines using viability assay. Diethyl ether fraction of Z. spina-christi showed the highest cytotoxic effects among the four extracts of Z. spina-christi. The IC50 of diethyl ether fraction was 7.14, 11.2, 11.6, 15.4, 39.8, 42.2, 84.2 and 153.8 µg/ml on HepG-2, A-549, CACO-2, HCT-116, MCF-7, PC-3, HeLa, and HEp-2 cell lines, respectively. Data shows that the diethyl ether fraction of Z. spina-christi showed effective cytotoxic effects in colon, lung and hepatocellular cancer cell lines.

Utility of a chemotherapy toxicity prediction tool for older patients in a community setting.

Background: Expert groups have recommended incorporation of a geriatric assessment into clinical practice for older patients starting oncologic therapy. However, that practice is not standard primarily because of resource limitations. In the present study, we evaluated the effect on treatment decisions by oncologists in the community oncology setting of a brief geriatric assessment tool that estimates risk of toxicity. Methods: This prospective longitudinal study in 5 community oncology practices in British Columbia involved patients 70 years of age and older starting a new cytotoxic chemotherapy regimen. Clinical personnel completed a brief validated geriatric assessment tool-the Cancer and Aging Research Group chemotherapy toxicity tool (carg-tt)-that estimates the risk of grade 3 or greater toxicity in older patients. Physicians were asked if the carg-tt changed their treatment plan or prompted extra supports. Patients were followed to assess the incidence of toxicity during treatment. Results: The study enrolled 199 patients between July 2016 and February 2018. Mean age was 77 years. Treatment was palliative in 61.4% of the group. Compared with physician judgment, the carg-tt predicted higher rates of toxicity. In 5 patients, treatment was changed based on the carg-tt. In 38.5% of the patients, data from the tool prompted extra supports. Within the first 3 cycles of treatment, 21.3% of patients had experienced grade 3 or greater toxicity. Conclusions: This study demonstrates that use of a brief geriatric assessment tool is possible in a broad community oncology practice. The tool modified the oncologist's supportive care plan for a significant number of older patients undertaking cytotoxic chemotherapy.

Phase Ib study of atezolizumab combined with cobimetinib in patients with solid tumors.

BACKGROUND: Preclinical evidence suggests that MEK inhibition promotes accumulation and survival of intratumoral tumor-specific T cells and can synergize with immune checkpoint inhibition. We investigated the safety and clinical activity of combining a MEK inhibitor, cobimetinib, and a programmed cell death 1 ligand 1 (PD-L1) inhibitor, atezolizumab, in patients with solid tumors. PATIENTS AND METHODS: This phase I/Ib study treated PD-L1/PD-1-naive patients with solid tumors in a dose-escalation stage and then in multiple, indication-specific dose-expansion cohorts. In most patients, cobimetinib was dosed once daily orally for 21 days on, 7 days off. Atezolizumab was dosed at 800 mg intravenously every 2 weeks. The primary objectives were safety and tolerability. Secondary end points included objective response rate, progression-free survival, and overall survival. RESULTS: Between 27 December 2013 and 9 May 2016, 152 patients were enrolled. As of 4 September 2017, 150 patients received ≥1 dose of atezolizumab, including 14 in the dose-escalation cohorts and 136 in the dose-expansion cohorts. Patients had metastatic colorectal cancer (mCRC; n = 84), melanoma (n = 22), non-small-cell lung cancer (NSCLC; n = 28), and other solid tumors (n = 16). The most common all-grade treatment-related adverse events (AEs) were diarrhea (67%), rash (48%), and fatigue (40%), similar to those with single-agent cobimetinib and atezolizumab. One (<1%) treatment-related grade 5 AE occurred (sepsis). Forty-five (30%) and 23 patients (15%) had AEs that led to discontinuation of cobimetinib and atezolizumab, respectively. Confirmed responses were observed in 7 of 84 patients (8%) with mCRC (6 responders were microsatellite low/stable, 1 was microsatellite instable), 9 of 22 patients (41%) with melanoma, and 5 of 28 patients (18%) with NSCLC. Clinical activity was independent of KRAS/BRAF status across diseases. CONCLUSIONS: Atezolizumab plus cobimetinib had manageable safety and clinical activity irrespective of KRAS/BRAF status. Although potential synergistic activity was seen in mCRC, this was not confirmed in a subsequent phase III study. CLINICALTRIALS.GOV IDENTIFIER: NCT01988896 (the investigators in the NCT01988896 study are listed in the supplementary Appendix, available at Annals of Oncology online).

LOC285629 regulates cell proliferation and motility in colorectal cancer cells

Purpose: Colorectal cancer (CRC) is one of the most widely diagnosed cancers in men and women worldwide. With the advancement of next-generation sequencing technologies, many studies have highlighted the involvement of long non-coding RNAs (lncRNAs) in cancer development. Growing evidence demonstrates that lncRNAs play crucial roles in regulating gene and protein expression and are involved in various cancers, including CRC. The field of lncRNAs is still relatively new and a lot of novel lncRNAs have been discovered, but their functional roles are yet to be elucidated. This study aims to characterize the expression and functional roles of a novel lncRNA in CRC. Method: Several methods were employed to assess the function of LOC285629 such as gene silencing, qPCR, proliferation assay, BrdU assay, transwell migration assay, ELISA and protein profiler. Results: Via in silico analyses, we identified significant downregulation of LOC285629, a novel lncRNA, across CRC stages. LOC285629 expression was significantly downregulated in advanced stages (Stage III and IV) compared to Stage I (Kruskal-Wallis Test; p = 0.0093). Further in-house validation showed that the expression of LOC285629 was upregulated in colorectal cancer tissues and cell lines compared to the normal counterparts, but was downregulated in advanced stages. By targeting LOC285629, the viability, proliferative abilities, invasiveness and resistance of colorectal cancer cells towards 5-fluorouracil were reduced. It was also discovered that LOC285629 may regulate cancer progression by targeting several different proteins, namely survivin, BCL-xL, progranulin, PDGF-AA, enolase 2 and p70S6 K. Conclusion: Our findings suggest that LOC285629 may be further developed as a potential therapeutic target for CRC treatment

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