A cross-sectional study evaluating the exercise discussion with oncologist during cancer consultation: the CONNECT study.

BACKGROUND: Evidence demonstrates that physical exercise confers several psycho-physical benefits on patients with cancer. This study aims to investigate the role of oncologists in exercise promotion. PATIENTS AND METHODS: A multicenter, cross-sectional study was conducted by distributing an anonymous, self-administered questionnaire to patients with cancer. The questionnaire enclosed demographic, health, and exercise variables. The exercise-related questions included in the study used the Godin-Shephard Leisure-Time Physical Activity Questionnaire to measure the amount of physical exercise. In addition, the survey gathered information on whether exercise was discussed with patients, and whether oncologists followed the assess, advise, reinforce, and refer (AARR) process regarding exercise. The survey also asked if patients preferred that exercise be discussed during their consultations. Descriptive statistics and logistic regression were applied. RESULTS: With a response rate of 75%, a total of 549 patients completed the survey. Regarding the exercise discussion, 38% of patients stated that their oncologist initiated an exercise discussion, 14% started the discussion themselves, and 48% said that the issue was not considered. Overall, 35% of patients reported that the oncologist assessed their exercise level, 22% and 42% received advice or reinforcement to increase their exercise, respectively, and 10% were referred to a dedicated service. Regarding preferences, 72% of patients thought that the oncologists should initiate an exercise discussion, 2% that only patients should start the discussion, and 26% thought that the issue should not be discussed. Similarly, 74% of patients are willing to receive the exercise assessment, 59% and 75% the advice and reinforcement to increase their exercise, and 46% to be referred to an exercise service. CONCLUSIONS: Although exercise promotion rates are low, patients are willing to receive exercise information. Dedicated strategies should be developed to support oncologists in promoting exercise to their patients.

Inactivation of Ymr1, Sjl2/3 phosphatases promotes stress resistance and longevity in wild type and Ras2G19V yeast.

In Saccharomyces cerevisiae, RAt Sarcoma (Ras) activity plays a central role in mediating the effect of glucose in decreasing stress resistance and longevity, with constitutive Ras activation mutations promoting cell growth and oncogenesis. Here, we used transposon mutagenesis in yeast to identify suppressors of the constitutively active Ras2G19V, orthologue of the KRASG12C mammalian oncogene. We identified mutations in Yeast Myotubularin Related (YMR1), SynaptoJanin-Like (SJL2) and SJL3 phosphatases, which target phosphatidylinositol phosphates, as the most potent suppressors of constitutive active Ras, able to reverse its effect on stress sensitization and sufficient to extend longevity. In sjl2 mutants, the staining of Ras-GTP switched from membrane-associated to a diffuse cytoplasmic staining, suggesting that it may block Ras activity by preventing its localization. Whereas expression of the Sjl2 PI 3,4,5 phosphatase mediated stress sensitization in both the Ras2G19V and wild type backgrounds, overexpression of the phosphatidylinositol 3 kinase VPS34 (Vacuolar Protein Sorting), promoted heat shock sensitization only in the Ras2G19V background, suggesting a complex relationship between different phosphatidylinositol and stress resistance. These results provide potential targets to inhibit the growth of cancer cells with constitutive Ras activity and link the glucose-dependent yeast pro-aging Ras signaling pathway to the well-established pro-aging PhosphoInositide 3-Kinase(PI3K) pathway in worms and other species raising the possibility that the conserved longevity effect of mutations in the PI3K-AKT (AK strain Transforming) pathway may involve inhibition of Ras signaling.

Fasting mimicking diet in mice delays cancer growth and reduces immunotherapy-associated cardiovascular and systemic side effects.

Immune checkpoint inhibitors cause side effects ranging from autoimmune endocrine disorders to severe cardiotoxicity. Periodic Fasting mimicking diet (FMD) cycles are emerging as promising enhancers of a wide range of cancer therapies including immunotherapy. Here, either FMD cycles alone or in combination with anti-OX40/anti-PD-L1 are much more effective than immune checkpoint inhibitors alone in delaying melanoma growth in mice. FMD cycles in combination with anti-OX40/anti-PD-L1 also show a trend for increased effects against a lung cancer model. As importantly, the cardiac fibrosis, necrosis and hypertrophy caused by immune checkpoint inhibitors are prevented/reversed by FMD treatment in both cancer models whereas immune infiltration of CD3+ and CD8+ cells in myocardial tissues and systemic and myocardial markers of oxidative stress and inflammation are reduced. These results indicate that FMD cycles in combination with immunotherapy can delay cancer growth while reducing side effects including cardiotoxicity.

The impact of a fasting mimicking diet on the metabolic health of a prospective cohort of patients with prostate cancer: a pilot implementation study.

BACKGROUND: This pilot prospective study investigated the effect of a periodic fasting mimicking diet (FMD) on metabolic health factors in patients with Prostate Cancer (PC). There is a well-documented association between PC and metabolic health. Impaired metabolic health is a significant risk factor for the development of PC, and a metabolic syndrome can be induced by hormonal therapies commonly required for its management. (ClinicalTrials.gov Identifier: NCT04292041). METHODS: We introduced a periodic 4-day FMD -low in calories, sugars, and proteins but high in unsaturated fats -to a cohort of PC patients and features of metabolic syndrome. 29/35 patients completed 3-monthly cycles of the 4-consecutive day packaged FMD. We compared the subjects' baseline weight, abdominal circumference (AC), blood pressure (BP) and selected laboratory results to the same measurements 3-months after completing the FMD cycles. RESULTS: Several important metabolic factors showed improvements post-intervention. On average patients' weights dropped by 3.79 kg (95% CI: -5.61, -1.97, p = 0.0002). AC was reduced on average by 4.57 cm, (95% CI: -2.27, -6.87, p = 0.0003). There was also a decrease in systolic and diastolic BP by 9.52 mmHg (95% CI: -16.16, -2.88, p = 0.0066) and 4.48 mmHg (95% CI: -8.85, -0.43, p = 0.0316) respectively. A sub-analysis indicates that FMD had more relevant effects in 'at-risk' patients than those with normal values of risk factors for metabolic syndrome. For example, subjects with baseline levels of systolic BP > 130 mmHg experienced a greater reduction in BP(-16.04 mmHg, p = 0.0001) than those with baseline systolic BP < 130 mmHg (-0.78 mmHg, p = 0.89). CONCLUSIONS: The FMD cycles were safely introduced to this small cohort of PC patients with little or no observed toxicity, and a high overall compliance of 83%. Analysis of the metabolic variables showed an overall decrease in weight, AC, and BP. Larger clinical trials focused on metabolic risk factors, PC quality of life and progression free survival are needed to assess the effect of the FMD on prostate cancer patients.

Presence, enzymatic activity, and subcellular localization of paraoxonases 1, 2, and 3 in human lung tissues.

AIMS: The human paraoxonases family (PONs) includes three calcium-dependent esterases: PON1, PON2, and PON3. The presence of PONs mRNA in human lungs is known, however, their enzymatic activity and subcellular localization have not been sufficiently explored. MAIN METHODS: In this work, the presence of PONs in human lung tissues, at both mRNA and protein levels, was confirmed by Real-Time RT-PCR and Western blot analysis. Moreover, the activities of PONs were determined in cytosol and microsomes of 30 subjects and in mitochondria of 8 representative lung tissues using selective and non-selective substrates. Besides, to exclude the possible contribution of other esterases on PON1 organophosphate activity, the effect of bis-p-nitrophenyl phosphate (BNPP) and phenylmethylsulfonyl fluoride (PMSF), esterase inhibitors, and ethylenediaminetetraacetic acid (EDTA), a general paraoxonase inhibitor, was tested. Finally, the presence and activities of PONs in the A549 pulmonary cell line were also evaluated in order to be used as a model for studies on paraoxonases' metabolism. KEY FINDINGS: Our results demonstrated high interindividual variability in both PONs mRNA/protein levels and enzymatic activities and pointed out the presence of all PONs in human lungs and their subcellular distribution in the cytosol, microsomes, and mitochondria. SIGNIFICANCE: These findings add further information to our knowledge of pulmonary metabolism and, given that PON1 can metabolize some drugs used for respiratory diseases, the presence of PON1 activity in the lung tissue should no longer be ignored in the development of treatment plans and the design of new drugs.

Project for interventional Oncology LArge-database in liveR Hepatocellular carcinoma - Preliminary CT-based radiomic analysis (POLAR Liver 1.1).

OBJECTIVE: The objective of this study is to find a contrast-enhanced CT-radiomic signature to predict clinical incomplete response in patients affected by hepatocellular carcinoma who underwent locoregional treatments. PATIENTS AND METHODS: 190 patients affected by hepatocellular carcinoma treated using focal therapies (radiofrequency or microwave ablation) from September 2018 to October 2020 were retrospectively enrolled. Treatment response was evaluated on a per-target-nodule basis on the 6-months follow-up contrast-enhanced CT or MR imaging using the mRECIST criteria. Radiomics analysis was performed using an in-house developed open-source R library. Wilcoxon-Mann-Whitney test was applied for univariate analysis; features with a p-value lower than 0.05 were selected. Pearson correlation was applied to discard highly correlated features (cut-off=0.9). The remaining features were included in a logistic regression model and receiver operating characteristic curves; sensitivity, specificity, positive and negative predictive value were also computed. The model was validated performing 2000 bootstrap resampling. RESULTS: 56 treated lesions from 42 patients were selected. Treatment responses were: complete response for 26 lesions (46.4%), 18 partial responses (32.1%), 10 stable diseases (17.9%), 2 progression diseases (3.6%). Area-Under-Curve value was 0.667 (95% CI: 0.527-0.806); accuracy, sensitivity, specificity, positive and negative predictive values were respectively 0.66, 0.85, 0.50, 0.59 and 0.79. CONCLUSIONS: This contrast-enhanced CT-based model can be helpful to early identify poor responder's hepatocellular carcinoma patients and personalize treatments.

Changes in growth hormone secretion and leptin receptor mRNA expression under the influence of leptin and adrenocorticotropin in pituitary cells of early weaned ewe lambs.

Early weaning of ewe lambs strongly stimulates the hypothalamic-pituitary-adrenal axis and is associated with suppressed growth rate despite the increased food intake. At the same time, plasma leptin concentration increases only slightly or undetectably. To better understand this atypical interdependence among somatic stress, leptin, and lamb growth rate, we analyzed impact of leptin and/or adrenocorticotropic hormone (ACTH) on growth hormone (GH) secretion as well as the effect of ACTH on mRNA expression of two splice variants of leptin receptor (LEPRa, LEPRb) in pituitary cells isolated from early weaned ewe lambs. The GH secretion under the influence of leptin and/or ACTH depended on the timing of exposure and hormone concentration. After 6 - 30 h, GH secretion increased under 10-11 - 10-8 M leptin (P ≤ 0.05). However, after 24 - 30 h, GH secretion significantly increased only in cells exposed to both leptin and ACTH compared to culture with leptin only. Simultaneously, there was a significant (P ≤ 0.05) decrease in leptin receptor mRNA expression under the influence of ACTH at 10-8 - 10-6 M after 12 - 30 and 24 - 30 h for LEPRa and LEPRb, respectively. ACTH-related downregulation of LEPR mRNA was associated with a significant (P ≤ 0.05) reduction in leptin-stimulated GH secretion, also after 24 - 30 hours. Thus, the timing of ACTH exposure, followed by decreased leptin receptor mRNA, converged with the timing of decreased GH secretion under the influence of leptin with ACTH. The ACTH-induced downregulation of LEPR mRNA therefore may underlie the decrease in GH. These results show a direct role for leptin, ACTH, and leptin receptor expression in modulation of pituitary GH secretion in early weaned ewe lambs. During the early weaning-induced stress response, the ACTH-mediated decrease in sensitivity of pituitary cells to leptin may abolish a stimulatory effect of leptin on GH secretion and explain in part, the reduction in lamb growth rate.

In vitro profiling of endothelial volatile organic compounds under resting and pro-inflammatory conditions.

INTRODUCTION: The evaluation of volatile organic compounds(VOCs) emitted by human body offers a unique tool to set up new non-invasive devices for early diagnosis and long-lasting monitoring of most human diseases. However, their cellular origin and metabolic fate have not been completely elucidated yet, thus limiting their clinical application. Endothelium acts as an interface between blood and surrounding tissues. As such, it adapts its physiology in response to different environmental modifications thus playing a role in the pathogenesis of many metabolic and inflammatory diseases. OBJECTIVES: Since endothelium specifically reshapes its physiologic functions upon environmental changes the objective of this study was to evaluate if and how pro-inflammatory stimuli affect VOC metabolism in endothelial cell in culture. METHODS: Gas chromatography with mass spectrometric detection was applied to profile VOCs in the headspace of cultured endothelial cells (EC) in the absence or presence of the pro-inflammatory stimulus lipopolysaccharide (LPS). RESULTS: We observed that, under resting conditions, EC affected the amount of 58 VOCs belonging to aldehyde, alkane and ketone families. Among these, LPS significantly altered the amount of 15 VOCs. ROC curves show a perfect performance (AUC = 1) for 10 metabolites including 1-butanol, 3-methyl-1-butanol and 2-ethyl-1-hexanol. DISCUSSION: The emission and uptake of the aforementioned VOCs disclose potential unexplored metabolic pathways for EC that deserve to be investigated. Overall, we identified new candidate VOC potentially exploitable, upon experimental confirm in in vivo model of disease, as potential biomarkers of sepsis and pro-inflammatory clinical settings.

Biological therapy downregulates the heterodimer S100A8/A9 (calprotectin) expression in psoriatic patients.

The pathophysiology of psoriasis is very complex and involves an interplay between immune cells and keratinocytes. The keratinocyte production of calprotectin (S100A8/A9), induced by the inflammatory psoriatic milieu, may be involved in initiating immune cell invasion, as well as in propagating inflammation. However, the exact role of calprotectin in psoriasis remains unclear. Therapeutic approaches utilizing adalimumab, etanercept and ustekinumab are widely used in psoriatic treatment, but their anti-inflammatory mechanisms are not fully understood. The aim of this study was to investigate, by immunohistochemical analysis, the expression of the heterocomplex S100A8/A9 in lesional skin from psoriatic patients undergoing biological therapy with adalimumab, etanercept or ustekinumab. Our results showed that S100A8/A9, absent or present at very low level in skin biopsies from healthy subjects, is dramatically upregulated in each epidermal layer from psoriatic patients. Interestingly, calprotectin was mainly localized in keratinocyte nuclei from psoriatic patients, suggesting a role of S100A8/A9 in keratinocyte nuclear function. Furthermore, we have shown that the biological treatment induced a drastic reduction of S100A8/A9 expression in skin biopsies from treated patients, correlating with PASI reduction. Our results suggest that calprotectin may play a crucial role as a significant marker of inflammation in psoriasis, and that its reduction of expression may be considered a favourable prognostic marker in psoriasis.

Metabolic Alterations at the Crossroad of Aging and Oncogenesis.

Aging represents the major risk factor for cancer. Cancer and aging are characterized by a similar dysregulated metabolism consisting in upregulation of glycolysis and downmodulation of oxidative phosphorylation. In this respect, metabolic interventions can be viewed as promising strategies to promote longevity and to prevent or delay age-related disorders including cancer. In this review, we discuss the most promising metabolic approaches including chronic calorie restriction, periodic fasting/fasting-mimicking diets, and pharmacological interventions mimicking calorie restriction. Metabolic interventions can also be viewed as adjuvant anticancer strategies to be combined to standard cancer therapy (chemotherapeutic agents, ionizing radiation, and drugs with specific molecular target), whose major limiting factors are represented by toxicity against healthy cells but also limited efficacy easily circumvented by tumor cells. In fact, conventional cancer therapy is unable to distinguish normal and cancerous cells and thus causes toxic side effects including secondary malignancies, cardiovascular and respiratory complications, endocrinopathies, and other chronic conditions, that resemble and, in some cases, accelerate the age-related disorders and profoundly affect the quality of life. In this scenario, geroscience contributes to the understanding of the mechanisms of protection of normal cells against a cytotoxic agent and finding strategies focused on the preserving healthy cells while enhancing the efficacy of the treatment against malignant cells.

Fasting-induced differential stress sensitization in cancer treatment.

Most tumors are generated and evolve under high-nutrient conditions, yet therapy does not include dietary changes generating a hostile environment for cancer cells. Because fasting promotes the most drastic change in the levels of plasma macro- and micro-nutrients, and consequently in glucose and growth factors, it has the potential to maximize cancer cell sensitization.

Soluble endothelial protein C receptor (sEPCR) as an inflammatory biomarker in naive HIV-infected patients during ART.

BACKGROUND: After the advent of ART, non-AIDS-related comorbidities are the main causes of death in HIV patients. Multiple biomarkers have been studied as markers of disease. We wanted to test soluble endothelial protein C receptor (sEPCR) in an HIV setting. OBJECTIVES: The primary objective was to determine whether sEPCR decreases after 48 weeks of ART in naive HIV patients. Secondary objectives were to compare sEPCR levels between patients with chronic HIV infection (CHI) and primary HIV infection (PHI) and to analyse if there is a correlation between sEPCR and both immunovirological parameters and different markers of inflammation. PATIENTS AND METHODS: We analysed sEPCR in 33 patients with CHI and 19 patients with PHI naive to ART. sEPCR was compared together with immunovirological parameters (HIV RNA and CD4 cell count) and IL-6 or D-dimer (DD). RESULTS AND CONCLUSIONS: After 48 weeks of ART, in CHI, the sEPCR decrease was significant (P = 0.0006) and sEPCR at baseline was correlated with both CD4 cell increase (r = +0.463, P = 0.007) and HIV RNA decrease (r = -0.363, P = 0.038). In PHI, sEPCR was stable (P = 0.35); there was a correlation between 48 week DD change and IL-6 change (r = +0.696, P = 0.0009) and also between 48 week DD change and sEPCR change (r = +0.553, P = 0.014). Despite the small sample size, we hypothesize that sEPCR levels reflect coagulant pathway activation caused by the endothelial damage during chronic infection more than a marker of the cytokine storm that occurs during PHI. Alternatively, in PHI, the link found between sEPCR and DD secondary to IL-6 suggests sEPCR is an indirect marker of inflammation.

Microwave-assisted hydrothermal synthesis of Ag2(W(1-x)Mox)O4 heterostructures: Nucleation of Ag, morphology, and photoluminescence properties.

Ag2W(1-x)MoxO4 (x=0.0 and 0.50) powders were synthesized by the co-precipitation (drop-by-drop) method and processed using a microwave-assisted hydrothermal method. We report the real-time in situ formation and growth of Ag filaments on the Ag2W(1-x)MoxO4 crystals using an accelerated electron beam under high vacuum. Various techniques were used to evaluate the influence of the network-former substitution on the structural and optical properties, including photoluminescence (PL) emission, of these materials. X-ray diffraction results confirmed the phases obtained by the synthesis methods. Raman spectroscopy revealed significant changes in local order-disorder as a function of the network-former substitution. Field-emission scanning electron microscopy was used to determine the shape as well as dimensions of the Ag2W(1-x)MoxO4 heterostructures. The PL spectra showed that the PL-emission intensities of Ag2W(1-x)MoxO4 were greater than those of pure Ag2WO4, probably because of the increase of intermediary energy levels within the band gap of the Ag2W(1-x)MoxO4 heterostructures, as evidenced by the decrease in the band-gap values measured by ultraviolet-visible spectroscopy.

Prevention of vascular damage with Lisosan G wheat extract: the in vitro basis for a clinical investigation.

Vascular damage and impairment play a crucial role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Nutraceutical supplements might have a role in reducing vascular damage, provided that their efficacy is proven by controlled studies and is supported by a mechanistic rationale. Therefore, the use of nutraceutical supplements can have some effects also in the prevention of NFLD. Epidemiological evidence correlates the intake of whole grain and whole-grain products with a reduced occurrence of vascular disease. Lisosan G is a powder obtained from Triticum Sativum (wheat), which is registered with the Italian Ministry of Health as a nutritional supplement. In vivo, Lisosan G has been shown to protect against cisplatin induced toxicity, and the use of this compound in the prevention of cirrhosis and steatosis has been recently been proposed thanks to its marked anti-oxidant activity. We discuss here the rationale for further investigation on this compound in the prevention of NAFLD.

Lack of genotypephenotype correlation in congenital adrenal hyperplasia due to a CYP21A2-like gene.

CONTEXT: Congenital Adrenal Hyperplasia (CAH) due to 21-hydroxylase deficiency, encoded by CYP21A2 gene, is an autosomal recessive disorder. The CYP21A2 gene, localized in a genetic unit defined RCCX module, is considered one of the most polymorphic of human genes. OBJECTIVES: We considered new evidences about the presence of a RCCX trimodular haplotype with a CYP21A2-like gene to explain the lack of a genotype-phenotype correlation in individuals of two different families. DESIGN AND METHODS: To verify gene duplication we used Multiplex Ligation Probe-Dependent Amplifications (MLPA) and to confirm the presence of a CYP21A2-like gene downstream TNXA gene we used previously described amplification and restriction strategy followed by the sequencing of the CYP21A2 gene downstream TNXB gene. RESULTS: The amplification strategy and restriction analysis of CYP21A1P/CYP21A2-TNXA PCR product in association with MLPA assay and sequencing of CYP21A2 gene downstream TNXB were able to identify the presence of the CYP21A2-like gene in healthy subjects of the two families, wherein the direct sequencing of CYP21A2 gene showed genotypes correlated to pathological phenotypes. CONCLUSIONS: The strategy suggested is useful to facilitate molecular testing in CAH patients, considering the new evidence about possible different haplotypes.

Drug metabolism enzymes in a steatotic model of rat treated with a high fat diet and a low dose of streptozotocin.

Herein we have characterized CYPs and antioxidant enzymes in a new steatotic rat model induced with a high fat diet (HFD) combined with a low dose of streptozotocin (STZ). This model was recently put forward in order to better replicate the NAFLD human pathology. HFD/STZ rats developed hyperglycemia, hypercholesterolemia and overt steatosis. The treatment also caused liver damage, but not lipid peroxidation, suggesting this damage was due to hepatic fat deposition and excess formation of toxic free fatty acids, rather than to oxidative stress. In the HFD/STZ group, a significant rise in total CYP content was found, in conjunction with increased activity and protein levels of CYP2E1 and CYP4A, the latter also up-regulated at the transcriptional level. A significant decrease of CYP2C11 was observed at the transcriptional and protein level, whereas CYP3A2 did not change in response to HFD/STZ treatment. In our experimental conditions, the activity of the HO-1 and NQO1 enzymes, whose genes are regulated by Nrf2, were not affected, and nor were the antioxidant enzymes SOD and CAT, confirming the lack of oxidative stress. Our HFD/STZ treatment, which established overt steatosis and changes in CYPs expression, but not oxidative stress, likely reflects an early stage of NAFLD.

Cloning, expression in E. coli and immunological characterization of Par j 3.0201, a Parietaria pollen profilin variant.

Parietaria judaica pollen is one of the main sources of allergens in the Mediterranean area. Its allergenic composition has been studied in detail showing the presence of two major allergens (Par j 1 and Par j 2) and two minor allergens belonging to the profilin and calcium binding protein families of allergens (Par j 3 and Par j 4, respectively). Clinical reports support the hypothesis of a limited cross-reactivity between profilin from Parietaria and unrelated sources. We screened a P. judaica cDNA library to identify novel forms of profilins with allergenic activity. This strategy allowed us to isolate a 767 bp cDNA containing the information for a 131 amino acids protein with homology to profilins from unrelated sources greater than that observed with the already published Parietaria profilins. This profilin was expressed in Escherichia coli as a recombinant protein and its immunological prevalence was studied in a population of Parietaria allergic patients from Southern Europe. Immunoblotting analysis showed that the Parietaria profilin was recognized by IgE from 6.5% of the allergic population. Finally, a selected population of profilin allergic patients was enrolled to demonstrate the cross-reactivity of this novel variant with other profilins from grass and date palm. In conclusion, molecular cloning and immunological studies have allowed the isolation, expression and immunological characterization of a novel cross-reactive profilin allergen from P. judaica pollen named Par j 3.0201.

Direct in situ observation of the electron-driven synthesis of Ag filaments on α-Ag2WO4 crystals.

In this letter, we report, for the first time, the real-time in situ nucleation and growth of Ag filaments on α-Ag2WO4 crystals driven by an accelerated electron beam from an electronic microscope under high vacuum. We employed several techniques to characterise the material in depth. By using these techniques combined with first-principles modelling based on density functional theory, a mechanism for the Ag filament formation followed by a subsequent growth process from the nano- to micro-scale was proposed. In general, we have shown that an accelerated electron beam from an electronic microscope under high vacuum enables in situ visualisation of Ag filaments with subnanometer resolution and offers great potential for addressing many fundamental issues in materials science, chemistry, physics and other fields of science.