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1
Rodrigues, Stephen F., Shantel A. Vital, and D. Neil Granger. "Mild Hypercholesterolemia Blunts the Proinflammatory and Prothrombotic Effects of Hypertension on the Cerebral Microcirculation." Journal of Cerebral Blood Flow & Metabolism 33, no. 4 (January 2, 2013): 483–89. http://dx.doi.org/10.1038/jcbfm.2012.194.
Повний текст джерелаАнотація:
Although an increased leukocyte and platelet adhesion is observed in cerebral venules of mice with either hypertension (HTN) or hypercholesterolemia (HCh), it remains unclear whether the combination of HTN and HCh exerts a comparable effect on leukocyte and platelet recruitment in the cerebral microvasculature. Thus, we examined whether HCh alters platelet and leukocyte adhesion, and blood–brain barrier (BBB) permeability, in cerebral venules in two models of murine HTN: DOCA salt-induced and angiotensin II (Ang II) induced. In both models, the mice were placed on either a normal or cholesterol-enriched diet. An enhanced recruitment of adherent leukocytes and platelets in cerebral venules was noted in both HTN models in the absence of HCh, but not in its presence. The Ang II-induced increase in BBB permeability was attenuated by HCh as well. Both total and high-density lipoprotein (HDL) cholesterol levels were elevated in the HCh mice. The HTN-induced increase in leukocyte and platelet adhesion was attenuated in apolipoprotein A-I transgenic mice (ApoA1-Tg) and blunted in wild-type mice treated with the ApoA1 mimetic peptide, 4F. Our findings indicate that mild HCh significantly blunts the cerebral microvascular responses to HTN and that HDL may have a role in mediating this beneficial effect of HCh.
2
Brown, Russell F., and Mark T. Holtzapple. "A comparison of the Michaelis-Menten and HCH-1 models." Biotechnology and Bioengineering 36, no. 11 (December 20, 1990): 1151–54. http://dx.doi.org/10.1002/bit.260361110.
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Rubini, Elisabetta, Giuliano Paglia, David Cannella, Alberto Macone, Antonella Di Sotto, Marco Gullì, Fabio Altieri та Margherita Eufemi. "β-Hexachlorocyclohexane: A Small Molecule with a Big Impact on Human Cellular Biochemistry". Biomedicines 8, № 11 (16 листопада 2020): 505. http://dx.doi.org/10.3390/biomedicines8110505.
Повний текст джерелаАнотація:
Organochlorine pesticides (OCPs) belong to a heterogeneous class of organic compounds blacklisted by the Stockholm Convention in 2009 due to their harmful impact on human health. Among OCPs, β-hexachlorocyclohexane (β-HCH) is one of the most widespread and, at the same time, poorly studied environmental contaminant. Due to its physicochemical properties, β-HCH is the most hazardous of all HCH isomers; therefore, clarifying the mechanisms underlying its molecular action could provide further elements to draw the biochemical profile of this OCP. For this purpose, LNCaP and HepG2 cell lines were used as models and were subjected to immunoblot, immunofluorescence, and RT-qPCR analysis to follow the expression and mRNA levels, together with the distribution, of key biomolecules involved in the intracellular responses to β-HCH. In parallel, variations in redox homeostasis and cellular bioenergetic profile were monitored to have a complete overview of β-HCH effects. Obtained results strongly support the hypothesis that β-HCH could be an endocrine disrupting chemical as well as an activator of AhR signaling, promoting the establishment of an oxidative stress condition and a cellular metabolic shift toward aerobic glycolysis. In this altered context, β-HCH can also induce DNA damage through H2AX phosphorylation, demonstrating its multifaceted mechanisms of action.
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Cumming, Jacqueline, Phoebe Dunn, Lesley Middleton, and Claire O’Loughlin. "The health care home in New Zealand: rolling out a new model of primary health care." Journal of Integrated Care 26, no. 3 (July 2, 2018): 242–52. http://dx.doi.org/10.1108/jica-04-2018-0031.
Повний текст джерелаАнотація:
Purpose The purpose of this paper is to report on the origins, development and early impacts of a Health Care Home (HCH) model of care being rolled out around New Zealand (NZ). Design/methodology/approach This paper draws on a literature review on HCHs and related developments in primary health care, background discussions with key players, and a review of significant HCH implementation documents. Findings The HCH model of care is emerging from the sector itself and is being tailored to local needs and to meet the needs of local practices. A key focus in NZ seems to be on business efficiency and ensuring sustainability of general practice – with the assumption that freeing up general practitioner time for complex patients will mean better care for those populations. HCH models of care differ around the world and NZ needs its own evidence to show the model’s effectiveness in achieving its goals. Research limitations/implications It is still early days for the HCH model of care in NZ and the findings in this paper are based on limited evidence. Further evidence is needed to identify the model’s full impact over the next few years. Originality/value This paper is one of the first to explore the HCH model of care in NZ.
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Zazo, Santiago, José-Luis Molina, Verónica Ruiz-Ortiz, Mercedes Vélez-Nicolás, and Santiago García-López. "Modeling River Runoff Temporal Behavior through a Hybrid Causal–Hydrological (HCH) Method." Water 12, no. 11 (November 9, 2020): 3137. http://dx.doi.org/10.3390/w12113137.
Повний текст джерелаАнотація:
The uncertainty in traditional hydrological modeling is a challenge that has not yet been overcome. This research aimed to provide a new method called the hybrid causal–hydrological (HCH) method, which consists of the combination of traditional rainfall–runoff models with novel hydrological approaches based on artificial intelligence, called Bayesian causal modeling (BCM). This was implemented by building nine causal models for three sub-basins of the Barbate River Basin (SW Spain). The models were populated by gauging (observing) short runoff series and from long and short hydrological runoff series obtained from the Témez rainfall–runoff model (T-RRM). To enrich the data, all series were synthetically replicated using an ARMA model. Regarding the results, on the one hand differences in the dependence intensities between the long and short series were displayed in the dependence mitigation graphs (DMGs), which were attributable to the insufficient amount of data available from the hydrological records and to climate change processes. The similarities in the temporal dependence propagation (basin memory) and in the symmetry of DMGs validate the reliability of the hybrid methodology, as well as the results generated in this study. Consequently, water planning and management can be substantially improved with this approach.
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O'Driscoll, K., B. Mayer, J. Su, and M. Mathis. "The effects of climate change on persistent organic pollutants (POPs) in the North Sea." Ocean Science Discussions 10, no. 5 (September 10, 2013): 1525–57. http://dx.doi.org/10.5194/osd-10-1525-2013.
Повний текст джерелаАнотація:
Abstract. The fate and cycling of two selected legacy persistent organic pollutants (POPs), PCB 153 and γ-HCH, in the North Sea in the 21st century have been modelled with combined hydrodynamic and fate and transport ocean models. To investigate the impact of climate variability on POPs in the North Sea in the 21st century, future scenario model runs for three 10 yr periods to the year 2100 using plausible levels of both in situ concentrations and atmospheric, river and open boundary inputs are performed. Since estimates of future concentration levels of POPs in the atmosphere, oceans and rivers are not available, our approach was to reutilise 2005 values in the atmosphere, rivers and at the open ocean boundaries for every year of the simulations. In this way, we attribute differences between the three 10 yr simulations to climate change only. For the HAMSOM and atmospheric forcing, results of the IPCC A1B (SRES) 21st century scenario are utilised, where surface forcing is provided by the REMO downscaling of the ECHAM5 global atmospheric model, and open boundary conditions are provided by the MPIOM global ocean model. Dry gas deposition and volatilisation of γ-HCH increase in the future relative to the present. In the water column, total mass of γ-HCH and PCB 153 remain fairly steady in all three runs. In sediment, γ-HCH increases in the future runs, relative to the present, while PCB 153 in sediment decreases exponentially in all three runs, but even faster in the future, both of which are the result of climate change. Annual net sinks exceed sources at the ends of all periods.
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Veal, Britney, Jessica Yauk, and Hongdao Meng. "ARE CAREGIVERS HEALTHIER?: ASSESSING CAREGIVERS' EPISODIC MEMORY IN A MATCHED AND UNMATCHED SAMPLE." Innovation in Aging 6, Supplement_1 (November 1, 2022): 548. http://dx.doi.org/10.1093/geroni/igac059.2077.
Повний текст джерелаАнотація:
Abstract Recent findings using an advanced methodological technique of propensity matching have found that caregivers may have better cognitive health compared to non-caregivers. However, there are limited studies assessing how personality and other psychosocial variables may affect the relationship between caregiver status and cognition. Utilizing the healthy caregiver hypothesis (HCH), the current study examined the association between caregiving and episodic memory in a matched (N= 1,246) and unmatched (N=3,112) sample of caregivers from the 2016 wave of the Health and Retirement Study. The interaction between caregiving status and personality was also examined. Unadjusted models showed no difference between caregiver status and episodic memory in the samples; however, depression was significantly (p=<.0001) related to cognition in the unmatched sample. In adjusted models for the unmatched sample, conscientiousness (p=0.043), pessimism (p=0.006), and feeling constrained (p=0.028) were found to be significantly associated with episodic memory. In the matched adjusted models, conscientiousness was no longer a significant predictor, but number of chronic conditions was significantly related to episodic memory (p=0.001). The interaction between caregiving and extraversion also approached significance (p=0.076). Findings suggest extraverted caregivers may have better episodic memory performance. These findings highlight the importance of implementing propensity matching in caregiving research. Future research is needed to examine the relationship between coping style and personality specific domains in relation to the HCH.
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Criswell, Rachel, Virissa Lenters, Siddhartha Mandal, Hein Stigum, Nina Iszatt, and Merete Eggesbø. "Persistent Environmental Toxicants in Breast Milk and Rapid Infant Growth." Annals of Nutrition and Metabolism 70, no. 3 (2017): 210–16. http://dx.doi.org/10.1159/000463394.
Повний текст джерелаАнотація:
Background/Aims: Many environmental toxicants are passed to infants in utero and through breast milk. Exposure to toxicants during the perinatal period can alter growth patterns, impairing growth or increasing obesity risk. Previous studies have focused on only a few toxicants at a time, which may confound results. We investigated levels of 26 toxicants in breast milk and their associations with rapid infant growth, a risk factor for later obesity. Methods: We used data from the Norwegian HUMIS study, a multi-center cohort of 2,606 mothers and newborns enrolled between 2002 and 2008. Milk samples collected 1 month after delivery from a subset of 789 women oversampled by overweight were analyzed for toxicants including polychlorinated biphenyls (PCBs), heavy metals, and pesticides. Growth was defined as change in weight-for-age z-score between 0 and 6 months among the HUMIS population, and rapid growth was defined as change in z-score above 0.67. We used a Bayesian variable selection method to determine the exposures that most explained variation in the outcome. Identified toxicants were included in logistic and linear regression models to estimate associations with growth, adjusting for maternal age, smoking, education, pre-pregnancy body mass index (BMI), gestational weight gain, parity, child sex, cumulative breastfeeding, birth weight, gestational age, and preterm status. Results: Of 789 infants, 19.2% displayed rapid growth. The median maternal age was 29.6 years, and the median pre-pregnancy BMI was 24.0 kg/m2, with 45.3% of mothers overweight or obese. Rapid growers were more likely to be firstborn. Hexachlorobenzene, β-hexachlorocyclohexane (β-HCH), and PCB-74 were identified in the variable selection method. An interquartile range (IQR) increase in β-HCH exposure was associated with a lower odds of rapid growth (OR 0.63, 95% CI 0.42-0.94). Newborns exposed to high levels of β-HCH showed reduced infant growth (β = -0.03, 95% CI -0.05 to -0.01 for IQR increase in breast milk concentration). No other significant associations were found. Conclusions: Our results suggest that early life β-HCH exposure may be linked to slowed growth. Further research is warranted on the potential mechanism behind this association and the longer-term metabolic effects of perinatal β-HCH exposure.
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O'Driscoll, K., B. Mayer, J. Su, and M. Mathis. "The effects of global climate change on the cycling and processes of persistent organic pollutants (POPs) in the North Sea." Ocean Science 10, no. 3 (May 27, 2014): 397–409. http://dx.doi.org/10.5194/os-10-397-2014.
Повний текст джерелаАнотація:
Abstract. The fate and cycling of two selected legacy persistent organic pollutants (POPs), PCB 153 and γ-HCH, in the North Sea in the 21st century have been modelled with combined hydrodynamic and fate and transport ocean models (HAMSOM and FANTOM, respectively). To investigate the impact of climate variability on POPs in the North Sea in the 21st century, future scenario model runs for three 10-year periods to the year 2100 using plausible levels of both in situ concentrations and atmospheric, river and open boundary inputs are performed. This slice mode under a moderate scenario (A1B) is sufficient to provide a basis for further analysis. For the HAMSOM and atmospheric forcing, results of the IPCC A1B (SRES) 21st century scenario are utilized, where surface forcing is provided by the REMO downscaling of the ECHAM5 global atmospheric model, and open boundary conditions are provided by the MPIOM global ocean model. Dry gas deposition and volatilization of γ-HCH increase in the future relative to the present by up to 20% (in the spring and summer months for deposition and in summer for volatilization). In the water column, total mass of γ-HCH and PCB 153 remain fairly steady in all three runs. In sediment, γ-HCH increases in the future runs, relative to the present, while PCB 153 in sediment decreases exponentially in all three runs, but even faster in the future, due to the increased number of storms, increased duration of gale wind conditions and increased water and air temperatures, all of which are the result of climate change. Annual net sinks exceed sources at the ends of all periods. Overall, the model results indicate that the climate change scenarios considered here generally have a negligible influence on the simulated fate and transport of the two POPs in the North Sea, although the increased number and magnitude of storms in the 21st century will result in POP resuspension and ensuing revolatilization events. Trends in emissions from primary and secondary sources will remain the key driver of levels of these contaminants over time.
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Li, Lun, Andrew Wister, and Barbara Mitchell. "EXAMINATION OF THE HEALTHY CAREGIVER EFFECT AMONG OLDER ADULTS FINDING FROM THE CANADIAN LONGITUDINAL STUDY ON AGING." Innovation in Aging 6, Supplement_1 (November 1, 2022): 636–37. http://dx.doi.org/10.1093/geroni/igac059.2359.
Повний текст джерелаАнотація:
Abstract Objective. The Healthy Caregiver Hypothesis (HCH) suggests that caregiving is associated with beneficial health impacts for family caregivers. However, mixed results have been reported, particularly when different levels of caregiving intensity were examined. This study analyzes the relationship between caregiving intensity and three health indicators (functional health, chronic illness, and self-rated general health) among Canadian older adults over three years. Method. We drew upon a sub-sample of 11,344 participants aged 65 and older from the Baseline and Follow-up 1 data of the Canadian Longitudinal Study on Aging and used linear mixed models to test the hypothesis based on different levels of caregiving intensity. Results. Older adults who provided low-intensity care recently or continuously reported better functional health and self-rated health than non-caregivers. In contrast, older adults with low-intensity caregiving responsibility developed more chronic conditions over time compared to non-caregivers, but this association was not found for high-intensity caregivers. Discussion. This study elucidates the HCH by incorporating caregiving intensity to understand patterns of better functional health and perceived health, but more chronic conditions. The findings yielded from different health indicators suggest the impact of caregiving on health may be domain specific.
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Cornelison, A. S., L. A. Karriker, N. H. Williams, B. J. Haberl, K. J. Stalder, L. L. Schulz, and J. F. Patience. "Impact of health challenges on pig growth performance, carcass characteristics, and net returns under commercial conditions." Translational Animal Science 2, no. 1 (February 2018): 50–61. http://dx.doi.org/10.1093/tas/txx005.
Повний текст джерелаАнотація:
Abstract Understanding how disease affects commercial production is imperative for pig producers to quantify its full impact on pig performance, carcass quality, and net returns. The objective of this experiment was to assess the productivity and economic importance of naturally occurring health challenges (HC) under commercial conditions. Three 1,000 pig grow-finish facilities received 936 pigs each. The experimental period started approximately 34 d post placement at an average start BW of 13.1 ± 0.2 kg. Barns were characterized based on the relative HC, determined by diagnostic assessments as the main characterization tool, along with other health indicators. Barns were characterized as low challenge health (LCh), moderate challenge health (MCh), and high challenge health (HCh). All barns tested positive for porcine reproductive and respiratory syndrome virus infection prior to the start of the experiment. Additionally, the MCh and HCh barns experienced influenza type A virus of swine. Similar to commercial production conditions, the disease challenge was not imposed but rather occurred naturally. Reduced ADG, ADFI, and G:F were observed with an increased HC (P < 0.001). Similarly, mortality was increased when the HC increased (P < 0.001). Decreased ADG increased days to achieve harvest BW, by 10 and 15 d in the MCh and HCh treatments compared with LCh, respectively (P < 0.001). No differences were observed for percent lean, loin depth, or fat depth (P > 0.10). The economic impact of the HC was assessed by applying these growth performance data to two economic models encompassing the two main marketing methods used by U.S. pig producers: fixed-weight and fixed-time. Financial losses attributed to the variation in disease severity that occurred in the present study ranged from $8.49 and $26.10 U.S. dollars (USD)/pig marketed using a fixed-market weight model, or between $11.02 and $29.82 USD/pig using a fixed-time model, depending on feed costs and market hog prices. In conclusion, increasing severity of HC under commercial conditions reduced ADG by 8% and 14% and resulted in mortality as high as 19.9%. Losses of $8.49 to $29.82/pig marketed underscore the potential magnitude of the economic impact of mixed etiology concurrent diseases in pork production.
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Zhang, L., J. Ma, C. Tian, Y. Li, and H. Hung. "Atmospheric transport of persistent semi-volatile organic chemicals to the Arctic and cold condensation in the mid-troposphere – Part 2: 3-D modeling of episodic atmospheric transport." Atmospheric Chemistry and Physics 10, no. 15 (August 9, 2010): 7315–24. http://dx.doi.org/10.5194/acp-10-7315-2010.
Повний текст джерелаАнотація:
Abstract. Two 3-dimensional global atmospheric transport models for persistent organic pollutants (POPs) have been employed to investigate the association between the large-scale atmospheric motions and poleward transports of persistent semi-volatile organic chemicals (SVOCs). We examine the modeled daily air concentration of α- and γ-hexachlorocyclohexane (HCH) over a period from 1997 through 1999 during which a number of episodic atmospheric transport events were detected in this modeling study. These events provide modeling evidence for improving the interpretation on the cold condensation effect and poleward atmospheric transport of SVOCs in the mid-troposphere. Two episodic transport events of γ-HCH (lindane) to the high Arctic (80–90° N), one from Asian and another from Eurasian sources, are reported in this paper. Both events suggest that the episodic atmospheric transports occurring in the mid-troposphere (e.g. from 3000 m to 5500 m height) are driven by atmospheric horizontal and vertical motions. The association of the transport events with atmospheric circulation is briefly discussed. Strong southerly winds, forced by the evolution of two semi-permanent high pressure systems over mid-high latitudes in the Northern Hemisphere, play an important role in the long-range transport (LRT) of HCHs to the high latitudes from its sources. Being consistent with the cold condensation effect and poleward atmospheric transport in a mean meridional atmospheric circulation simulated by a 2-D atmospheric transport model, as reported by the first part of this study, this modeling study indicates that cold condensation is likely occurring more intensively in the mid-troposphere where rapid declining air temperature results in condensed phase of the chemical over and near its source regions and where stronger winds convey the chemical more rapidly to the polar region during the episodic poleward atmospheric transport events.
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Semeena, V. S., J. Feichter та G. Lammel. "Impact of the regional climate and substance properties on the fate and atmospheric long-range transport of persistent organic pollutants – examples of DDT and γ-HCH". Atmospheric Chemistry and Physics Discussions 5, № 6 (6 грудня 2005): 12569–615. http://dx.doi.org/10.5194/acpd-5-12569-2005.
Повний текст джерелаАнотація:
Abstract. A global multicompartment model which is based on a 3-D atmospheric general circulation model (ECHAM5) coupled to 2-D soil, vegetation and sea surface mixed layer reservoirs, is used to simulate the atmospheric transports and total environmental fate of dichlorodiphenyltrichloroethane (DDT) and γ-hexachlorocyclohexane (γ-HCH, lindane). Emissions into the model world reflect the substance's agricultural usage in 1980 and 1990 and same amounts in sequential years are applied. Four scenarios of DDT usage and atmospheric decay and one scenario of γ-HCH are studied over a decade. The global environment is predicted to be contaminated by the substances within ca. 2 a (years). DDT reaches quasi-steady state within 3–4 a in the atmosphere and vegetation compartments, ca. 6 a in the sea surface mixed layer and near to or slightly more than 10 a in soil. Lindane reaches quasi-steady state in the atmosphere and vegetation within 2 a, in soils within 8 years and near to or slightly more than 10 a and in the sea surface mixed layer. The substances' differences in environmental behaviour translate into differences in the compartmental distribution and total environmental residence time, τoverall. τoverall≈0.8 a for γ-HCH's and ≈1.0–1.3 a for the various DDT scenarios. Both substances' distributions are predicted to migrate in northerly direction, 5–12° for DDT and 6.7° for lindane between the first and the tenth year in the environment. Cycling in various receptor regions is a complex superposition of influences of regional climate, advection, and the substance's physico-chemical properties. As a result of these processes the model simulations show that remote boreal regions are not necessarily less contaminated than tropical receptor regions. Although the atmosphere accounts for only 1% of the total contaminant burden, transport and transformation in the atmosphere is key for the distribution in other compartments. Hence, besides the physico-chemical properties of pollutants the location of application (entry) affects persistence and accumulation emphasizing the need for georeferenced exposure models.
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Semeena, V. S., J. Feichter та G. Lammel. "Impact of the regional climate and substance properties on the fate and atmospheric long-range transport of persistent organic pollutants - examples of DDT and γ-HCH". Atmospheric Chemistry and Physics 6, № 5 (21 квітня 2006): 1231–48. http://dx.doi.org/10.5194/acp-6-1231-2006.
Повний текст джерелаАнотація:
Abstract. A global multicompartment model which is based on a 3-D atmospheric general circulation model (ECHAM5) coupled to 2-D soil, vegetation and sea surface mixed layer reservoirs, is used to simulate the atmospheric transports and total environmental fate of dichlorodiphenyltrichloroethane (DDT) and γ-hexachlorocyclohexane (γ-HCH, lindane). Emissions into the model world reflect the substance's agricultural usage in 1980 and 1990 and same amounts in sequential years are applied. Four scenarios of DDT usage and atmospheric decay and one scenario of γ-HCH are studied over a decade. The global environment is predicted to be contaminated by the substances within ca. 2a (years). DDT reaches quasi-steady state within 3-4a in the atmosphere and vegetation compartments, ca. 6a in the sea surface mixed layer and near to or slightly more than 10a in soil. Lindane reaches quasi-steady state in the atmosphere and vegetation within 2a, in soils within 8 years and near to or slightly more than 10a and in the sea surface mixed layer. The substances' differences in environmental behaviour translate into differences in the compartmental distribution and total environmental residence time, τoverall. τoverall≈0.8a for γ-HCH's and ≈1.0-1.3 a for the various DDT scenarios. Both substances' distributions are predicted to migrate in northerly direction, 5-12° for DDT and 6.7° for lindane between the first and the tenth year in the environment. Cycling in various receptor regions is a complex superposition of influences of regional climate, advection, and the substance's physico-chemical properties. As a result of these processes the model simulations show that remote boreal regions are not necessarily less contaminated than tropical receptor regions. Although the atmosphere accounts for only 1% of the total contaminant burden, transport and transformation in the atmosphere is key for the distribution in other compartments. Hence, besides the physico-chemical properties of pollutants the location of application (entry) affects persistence and accumulation emphasizing the need for georeferenced exposure models.
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Korenkov, Igor P., V. F. Demin, and V. Yu Soloviev. "PROBLEMS OF THE ESTABLISHMENT OF DOSE - EFFECT RELATIONSHIP FOR RISK ASSESSMENT UNDER EXPOSURE TO IONIZING RADIATION AND HARMFUL CHEMICAL SUBSTANCES." Hygiene and sanitation 98, no. 7 (October 28, 2019): 697–700. http://dx.doi.org/10.18821/0016-9900-2019-98-7-697-700.
Повний текст джерелаАнотація:
The aim of the study. An analysis of the problems of the development of the dose-effect relationship (DER) in the assessment of the risk under exposure to ionizing radiation (IR) and harmful chemicals (HC) on human health and proposals for improving them. Material and methods. Problems of the development and application of the methodology for assessing the risk of exposure to IR and HC are in the area of delivering DER based on the results of biological experiments and epidemiological studies (ES). These problems are associated with such properties of the effects of exposure to IR and HCh as nonspecificity and latency, low statistical power, fragmentation of the actual information available on the studied effects, possible dependence on the level of the associated spontaneous morbidity or mortality rate. A number of DER models have been developed by national and international organizations. However, between these models, there are significant differences in the choice both of model parameters and the ratio between the multiplicative and additive dependencies on spontaneous effects. The relevance of improving DER models suitable for reliable predictive risk assessments of exposure to IR and HC remains. Results. In modern DER models, the ratio between the multiplicative and additive dependencies on spontaneous effects was chosen by an expert way on the basis of the available results of biological experiments and ESs without sufficient rigorous justification. This was reflected in the different choice of this ratio by different developers. For a more reasonable choice of the ratio, it is proposed to consider two possibilities: 1) implementing additional targeted biological research on the molecular-cellular and organismic levels; 2) a joint analysis of the results of two independent ESs on different cohorts affected by exposure to IR or HC. For IR there is a real opportunity to solve the problem according to the second option. A specific possible method of action in the second direction and an algorithm for its implementation are proposed. Conclusion. Current models of DER for IR and HC require further development, in particular, in terms of the relationship between multiplicative and additive dependencies in DER. A method of justifying the choice of this ratio is proposed and an algorithm for its implementation for IR is described.
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Curtin, Karen, Yi Zhao, Donglei Hu, Guido J. Tricot, Elad Ziv, Djordje Atanackovic, and Nicola J. Camp. "A Genome-Wide Association Study of Myeloma Survival in Utah Uncovers Germline Variants That May Influence Survival of Multiple Myeloma Patients." Blood 126, no. 23 (December 3, 2015): 2993. http://dx.doi.org/10.1182/blood.v126.23.2993.2993.
Повний текст джерелаАнотація:
Abstract Background. Recently, the first genome-wide association study (GWAS) for multiple myeloma (MM) survival was performed. It identified 16p13 as a candidate region for germline risk variants influencing survival1. The Utah study contributed to a successful replication of this region. Here, we perform a GWAS of MM survival in 318 MM cases residing or being treated in Utah to identify additional SNPs associated with MM prognosis. Methods. Utah cases were treated in the Huntsman Cancer Hospital (HCH) and/or Intermountain Healthcare systems, and were ascertained either though the HCH or the Utah Cancer Registry. Cases were genotyped on the Illumina 610Q high-density SNP array containing over 600,000 variants across the genome, imputed to the 1000 Genomes sequence data. Only imputed genotypes with information content >0.7 and certainty >0.9 were considered. For all variants (genotyped or imputed) with minor allele frequency of ≥2%, we estimated genome-wide hazard ratios using Cox models to compare survival between MM carriers of major or minor SNP alleles. Models were adjusted for sex, age at diagnosis, and principal components to adjust for possible population stratification as covariates. Disease stage and treatment were considered in sensitivity analyses to ensure that the hazard ratios were robust to these important factors. All Cox analyses were performed in R and Kaplan-Meier estimates of the survival function were graphed. Suggestive regions (p <1×10-6) were taken forward to replication in the UCSF study (352 patients). Combined analyses using METAL were calculated, including Cochran's Q test of heterogeneity. Results. Of 16 regions with p <1×10-6, we identified four regions on chromosomes 9, 10, 11 and 16 that were replicated in the UCSF data (p =0.007 to 0.06): (1) 9q22 rs12346172, p =5.7×10-7, HR=7.7; (2) 10p12.2 rs67205241, p =8.0×10-7, HR=3.1; (3) 11q22 rs142677811, p =1.3×10-9, HR=8.6 (see Figure 1); and, (4) 16q24 rs87814765, p =8.5×10-7, HR=2.1. These regions maintain genome-wide significance (rs142677811, p =2.1×10-8) or near-significance in a Utah-UCSF Meta analysis. Estimates were not sensitive to differences in staging or treatment. Conclusions. We observed that germline variants near genes PTCH1 (9q22.3; tumor suppressor in the patched gene family), EBLN1 (10p12.31), BIRC2 and BIRC3 (inhibitors of apoptosis; 11q22), YAP1 (oncogene in the Hippo signaling pathway; 11q13) and SLC7A5 (16 q24.3; an L-type amino-acid transporter recently associated with poor prognosis in MM2) were associated with decreased survival among MM patients. Somatic mutation and copy number loss for BIRC2/3, proteins in the inhibitor of apoptosis family, are frequently detected in lymphoid malignancies3. Nuclear ABL1 triggers cell death through its interaction with the Hippo pathway coactivator YAP1 in normal cells; it has been shown that low YAP1 levels prevent nuclear ABL1-induced apoptosis in hematological malignancies4. References: 1. Ziv E, Dean E, Hu D, et al. Genome-wide association study identifies variants at 16p13 associated with survival in multiple myeloma patients. Nat Commun. 2015 Jul 22;6:7539. 2. Isoda A, Kaira K, Iwashina M, et al. Expression of L-type amino acid transporter 1 (LAT1) as a prognostic and therapeutic indicator in multiple myeloma. Cancer Sci. 2014 Nov;105(11):1496-502. 3. Yamato A, Soda M, Ueno T, et al. Oncogenic activity of BIRC2 and BIRC3 mutants independent of nuclear factor-κB-activating potential. Cancer Sci. 2015 Jun 19. 4. Cottini F, Hideshima T, Xu C, et al. Rescue of Hippo coactivator YAP1 triggers DNA damage-induced apoptosis in hematological cancers. Nat Med. 2014 Jun;20(6):599-606. Figure 1. Plot of negative log p significance values for association statistics at the chromosome 11q22 region, bp 101282470-103282470 (h.g. build 19) in the Utah study, using locuszoom software (http://csg.sph.umich.edu/locuszoom/). The top associated SNP (rs142677811) is colored in purple and the remaining SNPs are colored according to linkage disequilibrium values (r2) with the top SNP. Figure 1. Plot of negative log p significance values for association statistics at the chromosome 11q22 region, bp 101282470-103282470 (h.g. build 19) in the Utah study, using locuszoom software (http://csg.sph.umich.edu/locuszoom/). The top associated SNP (rs142677811) is colored in purple and the remaining SNPs are colored according to linkage disequilibrium values (r2) with the top SNP. Disclosures No relevant conflicts of interest to declare.
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Yang, Shangguang, Danyang Wang, Wenhui Li, Chunlan Wang, Xi Yang, and Kevin Lo. "Decoupling of Elderly Healthcare Demand and Expenditure in China." Healthcare 9, no. 10 (October 10, 2021): 1346. http://dx.doi.org/10.3390/healthcare9101346.
Повний текст джерелаАнотація:
This study examined the changing trajectory and factors that influenced the health and medical expenditure of the Chinese elderly population over the past two decades. Based on the Chinese Longitudinal Healthy Longevity Survey (CLHLS) from 1998 to 2018, inferential and multiple linear regression models were constructed. The key finding is that China has experienced a decoupling of healthcare demand (HCD) and healthcare expenditure (HCE) since around 2014, when HCE began to decline despite the fact that HCD continued to rise. This is a promising sign, suggesting that the government’s health insurance policy is working. Furthermore, participating in health insurance schemes can significantly reduce the elderly’s HCD and HCE, demonstrating that health insurance can effectively affect the elderly’s decision to seek medical treatment and improve their health condition. We also found that age, region, basic old-age insurance, and care by the government and institutions were significant factors that influenced the healthcare demand and expenditure of the elderly population.
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Herold, Jonas, Kerstin Brügemann, and Sven König. "Herd clustering strategies and corresponding genetic evaluations based on social–ecological characteristics for a local endangered cattle breed." Archives Animal Breeding 64, no. 1 (May 26, 2021): 187–98. http://dx.doi.org/10.5194/aab-64-187-2021.
Повний текст джерелаАнотація:
Abstract. The accuracy of breeding values strongly depends on the population and herd structure, i.e., the number of animals considered in genetic evaluations and the size of contemporary groups (CGs). Local breeds are usually kept in small-sized family farms under alternative husbandry conditions. For such herd structure, consideration of classical herd or herd-test-day effects in CG modeling approaches implies only a few records per effect level. In consequence, the present study aimed on methodological evaluations of different herd clustering strategies, considering social–ecological and herd characteristics. In this regard, we considered 19 herds keeping cows from the small local population of German Black Pied cattle (Deutsches Schwarzbuntes Niederungsrind; DSN), 10 herds keeping Holstein Friesian (HF) cows and one mixed herd with HF and DSN cows. Herds were characterized for 106 variables, reflecting farm conditions, husbandry practices, feeding regime, herd management, herd fertility status, herd health status and breeding strategies as well as social–ecological descriptors. The variables were input data for different clustering approaches including agglomerative hierarchical clustering (AHC), partition around medoids (PAM), fuzzy clustering (FZC) and a clustering of variables combined with agglomerative hierarchical clustering (CoVAHC). The evaluation criterion was the average silhouette width (ASW), suggesting a CoVAHC application and consideration of four herd clusters (HCs) for herd allocation (ASW of 0.510). HC1 comprised the larger, half organic and half conventional DSN family farms, which generate their main income from milk production. HC2 consisted of small organic DSN family farms where cows are kept in tie stables. HC3 included the DSN sub-population from former East Germany, reflecting the large-scale farm types. The specialized HF herds were well separated and allocated to HC4. Generalized linear mixed models with appropriate link functions were applied to compare test-day and female fertility traits of 5538 cows (2341 DSN and 3197 HF) from the first three lactations among the four HCs. Least squares means for milk, fat and protein yield (Mkg, Fkg and Pkg) significantly differed between HC. The significant differences among the four HCs clearly indicate the influence of varying herd conditions on cow traits. The similarities of herds within HC suggested the application of HCs in statistical models for genetic evaluations for DSN. In this regard, we found an increase of accuracies of estimated breeding values of cows and sires and of heritabilities for milk yield when applying models with herd-cluster-test-day or herd-cluster-test-month effects compared to classical herd-test-day models. The identified increase for the number of cows and cow records in CG due to HC effects may be the major explanation for the identified superiority.
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Shankaraiah, Ram C., Laura Gramantieri, Francesca Fornari, Silvia Sabbioni, Elisa Callegari, and Massimo Negrini. "Animal Models of Hepatocellular Carcinoma Prevention." Cancers 11, no. 11 (November 14, 2019): 1792. http://dx.doi.org/10.3390/cancers11111792.
Повний текст джерелаАнотація:
Hepatocellular carcinoma (HCC) is a deadly disease and therapeutic efficacy in advanced HCC is limited. Since progression of chronic liver disease to HCC involves a long latency period of a few decades, a significant window of therapeutic opportunities exists for prevention of HCC and improve patient prognosis. Nonetheless, there has been no clinical advancement in instituting HCC chemopreventive strategies. Some of the major challenges are heterogenous genetic aberrations of HCC, significant modulation of tumor microenvironment and incomplete understanding of HCC tumorigenesis. To this end, animal models of HCC are valuable tools to evaluate biology of tumor initiation and progression with specific insight into molecular and genetic mechanisms involved. In this review, we describe various animal models of HCC that facilitate effective ways to study therapeutic prevention strategies that have translational potential to be evaluated in a clinical context.
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Fornari, Francesca, Laura Gramantieri, Elisa Callegari, Ram C. Shankaraiah, Fabio Piscaglia, Massimo Negrini, and Catia Giovannini. "MicroRNAs in Animal Models of HCC." Cancers 11, no. 12 (December 1, 2019): 1906. http://dx.doi.org/10.3390/cancers11121906.
Повний текст джерелаАнотація:
Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related mortality. Molecular heterogeneity and absence of biomarkers for patient allocation to the best therapeutic option contribute to poor prognosis of advanced stages. Aberrant microRNA (miRNA) expression is associated with HCC development and progression and influences drug resistance. Therefore, miRNAs have been assayed as putative biomarkers and therapeutic targets. miRNA-based therapeutic approaches demonstrated safety profiles and antitumor efficacy in HCC animal models; nevertheless, caution should be used when transferring preclinical findings to the clinics, due to possible molecular inconsistency between animal models and the heterogeneous pattern of the human disease. In this context, models with defined genetic and molecular backgrounds might help to identify novel therapeutic options for specific HCC subgroups. In this review, we describe rodent models of HCC, emphasizing their representativeness with the human pathology and their usefulness as preclinical tools for assessing miRNA-based therapeutic strategies.
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Yim, Sun Young, and Ju-Seog Lee. "Genomic Perspective on Mouse Liver Cancer Models." Cancers 11, no. 11 (October 25, 2019): 1648. http://dx.doi.org/10.3390/cancers11111648.
Повний текст джерелаАнотація:
Selecting the most appropriate mouse model that best recapitulates human hepatocellular carcinoma (HCC) allows translation of preclinical mouse studies into clinical studies. In the era of cancer genomics, comprehensive and integrative analysis of the human HCC genome has allowed categorization of HCC according to molecular subtypes. Despite the variety of mouse models that are available for preclinical research, there is a lack of evidence for mouse models that closely resemble human HCC. Therefore, it is necessary to identify the accurate mouse models that represent human HCC based on molecular subtype as well as histologic aggressiveness. In this review, we summarize the mouse models integrated with human HCC genomic data to provide information regarding the models that recapitulates the distinct aspect of HCC biology and prognosis based on molecular subtypes.
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de Azevedo, Ricardo Alexandre, Hsieh Cheng-En, Priyamvada Jayaprakash, Krithikaa Rajkumar Bhanu, Anupallavi Srinivasamani, Brittany Morrow, Michelle Winkler, Shweta Mahendra Hedge, Arthur Liu, and Michael A. Curran. "Abstract 4213: Targeting the cMet inhibitors combined with anti-PD-1 therapy: Preclinical approach to turn the resistance into opportunities for overcoming tumor evasion." Cancer Research 82, no. 12_Supplement (June 15, 2022): 4213. http://dx.doi.org/10.1158/1538-7445.am2022-4213.
Повний текст джерелаАнотація:
Abstract Liver cancer is the fourth most common cause of cancer-related mortality world-wide, and Hepatocellular carcinoma (HCC) is the most common form of liver cancer accounting for 90% of cases. Therapeutic strategies include surgical resection, radiotherapy, liver transplantation and pharmacological treatment with small-molecules multikinase inhibitors and/or immune-checkpoint blockade (ICB); however, outcomes remain poor and improvements to systemic therapy are desperately needed. Recently, Cabozantinib a kinase inhibitor with activity against VEGFR2, AXL and cMET, has been approved for second line use in advanced HCC; however, monotherapy achieves less than a 4-month extension of overall survival. Previously, our collaborators demonstrated that the efficacy of cMet inhibition is self-limited by induction of high PD-L1 expression. Given this data, the goal of our study was to investigate the efficacy of combining cMet inhibition with either capmatinib or cabozantinib with antibody blockade of the PD-1 immune checkpoint receptor for therapy of HCC. Using multiple syngeneic, immunocompetent models of HCC (Hepa1-6, HCA) in two different strains of mice (C57BL6, C3H), we investigated the combination potential of each of these cMet inhibitors with anti-PD-1 antibodies. Further, we profiled the changes to the tumor infiltrating myeloid and T cell repertoires which correlated to mono- as well as combination therapy responses in these animals using high content flow cytometry on a BD X-30. We found Hepa1-6 to be exquisitely anti-PD-1 sensitive with 100% of animals being cured by the combination. In the less immunotherapy-sensitive HCA-1 model, we also found that the cMet inhibitors cooperate with PD-1 blockade to promote rejection of HCA-1 HCC model. Again, we found that combination therapy could cure nearly all animals of pre-implanted HCA-1 tumors. Mechanistically, we found that concomitant cMet inhibition enhances the efficacy of PD-1 therapy increasing the number of tumor-infiltrating CD4 Teff cells while decreasing the CD4 Treg population. We also found that combined therapy improves CD8+ T cell infiltration, memory CD8 T cell fraction and NK cytotoxic potential within the tumor microenvironment. Within the HCA-1 myeloid compartment, we discovered a significant decrease in the tumor-associated neutrophil (N2-TAN) population (PMN-MDSC). Further, we found that combination therapy promotes pro-inflammatory M1 conversion of stromal macrophages. Collectively, these data provide a rationale for combining anti-PD-1 therapy with cMet inhibitors as a potential strategy to overcome resistance to immune checkpoint blockade therapy in HCC. Citation Format: Ricardo Alexandre de Azevedo, Hsieh Cheng-En, Priyamvada Jayaprakash, Krithikaa Rajkumar Bhanu, Anupallavi Srinivasamani, Brittany Morrow, Michelle Winkler, Shweta Mahendra Hedge, Arthur Liu, Michael A. Curran. Targeting the cMet inhibitors combined with anti-PD-1 therapy: Preclinical approach to turn the resistance into opportunities for overcoming tumor evasion [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 4213.
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Cho, Kyungjoo, Simon Weonsang Ro, Sang Hyun Seo, Youjin Jeon, Hyuk Moon, Do Young Kim, and Seung Up Kim. "Genetically Engineered Mouse Models for Liver Cancer." Cancers 12, no. 1 (December 19, 2019): 14. http://dx.doi.org/10.3390/cancers12010014.
Повний текст джерелаАнотація:
Liver cancer is the fourth leading cause of cancer-related death globally, accounting for approximately 800,000 deaths annually. Hepatocellular carcinoma (HCC) is the most common type of liver cancer, comprising approximately 80% of cases. Murine models of HCC, such as chemically-induced models, xenograft models, and genetically engineered mouse (GEM) models, are valuable tools to reproduce human HCC biopathology and biochemistry. These models can be used to identify potential biomarkers, evaluate potential novel therapeutic drugs in pre-clinical trials, and develop molecular target therapies. Considering molecular target therapies, a novel approach has been developed to create genetically engineered murine models for HCC, employing hydrodynamics-based transfection (HT). The HT method, coupled with the Sleeping Beauty transposon system or the CRISPR/Cas9 genome editing tool, has been used to rapidly and cost-effectively produce a variety of HCC models containing diverse oncogenes or inactivated tumor suppressor genes. The versatility of these models is expected to broaden our knowledge of the genetic mechanisms underlying human hepatocarcinogenesis, allowing the study of premalignant and malignant liver lesions and the evaluation of new therapeutic strategies. Here, we review recent advances in GEM models of HCC with an emphasis on new technologies.
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Pascale, Rosa M., Maria M. Simile, Graziella Peitta, Maria A. Seddaiu, Francesco Feo, and Diego F. Calvisi. "Experimental Models to Define the Genetic Predisposition to Liver Cancer." Cancers 11, no. 10 (September 27, 2019): 1450. http://dx.doi.org/10.3390/cancers11101450.
Повний текст джерелаАнотація:
Hepatocellular carcinoma (HCC) is a frequent human cancer and the most frequent liver tumor. The study of genetic mechanisms of the inherited predisposition to HCC, implicating gene–gene and gene–environment interaction, led to the discovery of multiple gene loci regulating the growth and multiplicity of liver preneoplastic and neoplastic lesions, thus uncovering the action of multiple genes and epistatic interactions in the regulation of the individual susceptibility to HCC. The comparative evaluation of the molecular pathways involved in HCC development in mouse and rat strains differently predisposed to HCC indicates that the genes responsible for HCC susceptibility control the amplification and/or overexpression of c-Myc, the expression of cell cycle regulatory genes, and the activity of Ras/Erk, AKT/mTOR, and of the pro-apoptotic Rassf1A/Nore1A and Dab2IP/Ask1 pathways, the methionine cycle, and DNA repair pathways in mice and rats. Comparative functional genetic studies, in rats and mice differently susceptible to HCC, showed that preneoplastic and neoplastic lesions of resistant mouse and rat strains cluster with human HCC with better prognosis, while the lesions of susceptible mouse and rats cluster with HCC with poorer prognosis, confirming the validity of the studies on the influence of the genetic predisposition to hepatocarinogenesis on HCC prognosis in mouse and rat models. Recently, the hydrodynamic gene transfection in mice provided new opportunities for the recognition of genes implicated in the molecular mechanisms involved in HCC pathogenesis and prognosis. This method appears to be highly promising to further study the genetic background of the predisposition to this cancer.
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Li, Enya, Li Lin, Chia-Wei Chen, and Da-Liang Ou. "Mouse Models for Immunotherapy in Hepatocellular Carcinoma." Cancers 11, no. 11 (November 15, 2019): 1800. http://dx.doi.org/10.3390/cancers11111800.
Повний текст джерелаАнотація:
Liver cancer is one of the dominant causes of cancer-related mortality, and the survival rate of liver cancer is among the lowest for all cancers. Immunotherapy for hepatocellular carcinoma (HCC) has yielded some encouraging results, but the percentage of patients responding to single-agent therapies remains low. Therefore, potential directions for improved immunotherapies include identifying new immune targets and checkpoints and customizing treatment procedures for individual patients. The development of combination therapies for HCC is also crucial and urgent and, thus, further studies are required. Mice have been utilized in immunotherapy research due to several advantages, for example, being low in cost, having high success rates for inducing tumor growth, and so on. Moreover, immune-competent mice are used in immunotherapy research to clarify the role that the immune system plays in cancer growth. In this review paper, the advantages and disadvantages of mouse models for immunotherapy, the equipment that are used for monitoring HCC, and the cell strains used for inducing HCC are reviewed.
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Eisenthal, Joshua. "Models and Multiplicities." Journal of the History of Philosophy 60, no. 2 (April 2022): 277–302. http://dx.doi.org/10.1353/hph.2022.0021.
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Yilma, Mignote, Varun Saxena, and Neil Mehta. "Models to Predict Development or Recurence of Hepatocellular Carcinoma (HCC) in Patients with Advanced Hepatic Fibrosis." Current Gastroenterology Reports 24, no. 1 (January 2022): 1–9. http://dx.doi.org/10.1007/s11894-022-00835-8.
Повний текст джерелаАнотація:
Abstract Purpose of Review Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death in the United States (U.S.).1 The purpose of this review is to highlight published models that predict development of HCC and estimate risk of HCC recurrence after treatments. Recent Findings There have been several models created for both de novo HCC and HCC recurrence, with the more recent models using a combination of age, sex, decompensation, and laboratory values (platelet count, albumin, bilirubin), and liver disease etiology to predict both 5 and 10-year HCC incidence. For chronic hepatitis C, sustained virologic response has been a useful component of understanding HCC risk reduction. BMI and diabetes have been utilized in non-alcoholic fatty liver disease (NAFLD) models to predict HCC risk. For HCC recurrence after treatment (for both surgical resection and liver transplant), tumor size and number, vascular invasion, alpha-fetoprotein (AFP) and neutrophil to lymphocyte ratio (NLR) are all components of HCC recurrence risk models. Summary Although numerous HCC risk prediction models have been established over the last several years, challenges remain including how to best incorporate these models into clinical practice, improve surveillance for NAFLD-HCC development, and determine timing and duration of post-resection recurrence surveillance.
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Yan, Jun, Jorge Matias Caviglia, and Robert F. Schwabe. "Animal models of HCC – When injury meets mutation." Journal of Hepatology 68, no. 1 (January 2018): 193–94. http://dx.doi.org/10.1016/j.jhep.2017.07.023.
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Beachkofski, Brian K. "Probabilistic Rotor Life Assessment Using Reduced Order Models." Shock and Vibration 16, no. 6 (2009): 581–91. http://dx.doi.org/10.1155/2009/717059.
Повний текст джерелаАнотація:
Probabilistic failure assessments for integrally bladed disks are system reliability problems where a failure in at least one blade constitutes a rotor system failure. Turbine engine fan and compressor blade life is dominated by High Cycle Fatigue (HCF) initiated either by pure HCF or Foreign Object Damage (FOD). To date performing an HCF life assessment for the entire rotor system has been too costly in analysis time to be practical. Although the substantial run-time has previously precluded a full-rotor probabilistic analysis, reduced order models make this process tractable as demonstrated in this work. The system model includes frequency prediction, modal stress variation, mistuning amplification, FOD effect, and random material capability. The model has many random variables which are most easily handled through simple random sampling.
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Thevathasan, Tharusan, Teresa Colbatzky, Moritz Schmelzle, Johann Pratschke, and Felix Krenzien. "Risk factors for malignant transformation of hepatocellular adenoma to hepatocellular carcinoma: protocol for systematic review and meta-analysis." BMJ Open 11, no. 8 (August 2021): e045733. http://dx.doi.org/10.1136/bmjopen-2020-045733.
Повний текст джерелаАнотація:
IntroductionHepatocellular adenomas (HCAs) are solid liver tumours that are usually found incidentally during routine medical check-ups. Multiple modifiable and non-modifiable factors constitute a risk for the malignant transformation of HCAs to hepatocellular carcinoma (HCC), which has emerged to be one of the fastest growing causes of cancer-related mortality globally. This study protocol for a planned systematic review and meta-analysis documents the methodological approach to identify risk factors and their risk estimates for the transformation from HCA to HCC.Methods and analysisTwo independent reviewers will systematically search and extract data from studies in patients of all ages published between January 1970 and June 2021 on PubMed, MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature, Scopus Web of Science, Ovid, The Cochrane Hepatobiliary Group Controlled Trials Register and The Cochrane Central Register of Controlled Trials by using an a priori defined search strategy. Study quality will be rated with the National Institute of Health quality assessment tools. Disagreements will be resolved by consensus with a third independent reviewer. The primary outcome will be the odds ratio (OR) of developing HCC in patients with prediagnosed HCA depending on the exposure to risk factors. HCC diagnosis must be inferred based on imaging techniques or pathology. We will use R V.4.0.2 to conduct meta-analyses and generate pooled ORs based on random effects models. Results will be presented as forest plots. Cochran’s Q and I2 test will be performed to assess heterogeneity between included studies. Funnel plots and Egger’s weighted regression will be used to evaluate publication bias.Ethics and disseminationNo ethical approval is required as we will use and analyse data from previously published studies in which informed consent was obtained. The results will be disseminated in a peer-reviewed journal on completion.PROSPERO registration numberCRD42020206578.
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Mancarella, Serena, Silke Krol, Alberto Crovace, Stefano Leporatti, Francesco Dituri, Martina Frusciante та Gianluigi Giannelli. "Validation of Hepatocellular Carcinoma Experimental Models for TGF-β Promoting Tumor Progression". Cancers 11, № 10 (9 жовтня 2019): 1510. http://dx.doi.org/10.3390/cancers11101510.
Повний текст джерелаАнотація:
Transforming growth factor beta (TGF-β) is a pleiotropic cytokine with dual role in hepatocellular carcinoma (HCC). It acts as tumor-suppressor and tumor-promoter in the early and late stage respectively. TGF-β influences the tumor-stroma cross-talk affecting the tumoral microenvironment. Therefore, inhibiting the TGF- β mediated pathway alone and/or in combination with chemotherapeutics represents an important therapeutic option. Experimental models to dissect the role of TGF-β in HCC tumor progression as well as the effectiveness of specific inhibitors are tricky. HCC cell lines respond to TGF-β according to their epithelial phenotype. However, the mesenchymal and more aggressive HCC cell lines in vitro, do not develop tumors when transplanted in vivo, thus hampering the understanding of molecular pathways that dictate outcome. In addition, in this model the native immune system is abolished, therefore the contribution of inflammation in hepatocarcinogenesis is unreliable. Different strategies have been set up to engineer HCC animal models, including genetically modified mice, chemically induced HCC, or hydrodynamic techniques. Patient-derived xenograft is currently probably the most fascinating model, keeping in mind that models cannot mirror all the reality. In this context, we discuss the different available HCC mouse models including our experimental model treated with inhibitor of TGF-β receptor Type I kinase (Galunisertib) and a potential role of exosomes in TGF-β moderated tumor progression of HCC. Unfortunately, no positive results were obtained in our treated orthotopic model because it does not reproduce the critical tumor-stroma interactions of the HCC.
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Li, Yung-Tsung, Hui-Lin Wu, and Chun-Jen Liu. "Molecular Mechanisms and Animal Models of HBV-Related Hepatocellular Carcinoma: With Emphasis on Metastatic Tumor Antigen 1." International Journal of Molecular Sciences 22, no. 17 (August 29, 2021): 9380. http://dx.doi.org/10.3390/ijms22179380.
Повний текст джерелаАнотація:
Hepatocellular carcinoma (HCC) is an important cause of cancer death worldwide, and hepatitis B virus (HBV) infection is a major etiology, particularly in the Asia-Pacific region. Lack of sensitive biomarkers for early diagnosis of HCC and lack of effective therapeutics for patients with advanced HCC are the main reasons for high HCC mortality; these clinical needs are linked to the molecular heterogeneity of hepatocarcinogenesis. Animal models are the basis of preclinical and translational research in HBV-related HCC (HBV-HCC). Recent advances in methodology have allowed the development of several animal models to address various aspects of chronic liver disease, including HCC, which HBV causes in humans. Currently, multiple HBV-HCC animal models, including conventional, hydrodynamics-transfection-based, viral vector-mediated transgenic, and xenograft mice models, as well as the hepadnavirus-infected tree shrew and woodchuck models, are available. This review provides an overview of molecular mechanisms and animal models of HBV-HCC. Additionally, the metastatic tumor antigen 1 (MTA1), a cancer-promoting molecule, was introduced as an example to address the importance of a suitable animal model for studying HBV-related hepatocarcinogenesis.
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Obeid, Michele, Ramzy C. Khabbaz, Kelly D. Garcia, Kyle M. Schachtschneider, and Ron C. Gaba. "Translational Animal Models for Liver Cancer." American Journal of Interventional Radiology 2 (February 24, 2018): 2. http://dx.doi.org/10.25259/ajir-11-2017.
Повний текст джерелаАнотація:
Animal models have become increasingly important in the study of hepatocellular carcinoma (HCC), as they serve as a critical bridge between laboratory-based discoveries and human clinical trials. Developing an ideal animal model for translational use is challenging, as the perfect model must be able to reproduce human disease genetically, anatomically, physiologically, and pathologically. This brief review provides an overview of the animal models currently available for translational liver cancer research, including rodent, rabbit, non-human primate, and pig models, with a focus on their respective benefits and shortcomings. While small animal models offer a solid starting point for investigation, large animal HCC models are becoming increasingly important for translation of preclinical results to clinical practice.
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Serra, Marina, Amedeo Columbano, Andrea Perra, and Marta Anna Kowalik. "Animal Models: A Useful Tool to Unveil Metabolic Changes in Hepatocellular Carcinoma." Cancers 12, no. 11 (November 10, 2020): 3318. http://dx.doi.org/10.3390/cancers12113318.
Повний текст джерелаАнотація:
Hepatocellular carcinoma (HCC) is one the most frequent and lethal human cancers. At present, no effective treatment for advanced HCC exist; therefore, the overall prognosis for HCC patients remains dismal. In recent years, a better knowledge of the signaling pathways involved in the regulation of HCC development and progression, has led to the identification of novel potential targets for therapeutic strategies. However, the obtained benefits from current therapeutic options are disappointing. Altered cancer metabolism has become a topic of renewed interest in the last decades, and it has been included among the core hallmarks of cancer. In the light of growing evidence for metabolic reprogramming in cancer, a wide number of experimental animal models have been exploited to study metabolic changes characterizing HCC development and progression and to further expand our knowledge of this tumor. In the present review, we discuss several rodent models of hepatocarcinogenesis, that contributed to elucidate the metabolic profile of HCC and the implications of these changes in modulating the aggressiveness of neoplastic cells. We also highlight the apparently contrasting results stemming from different animal models. Finally, we analyze whether these observations could be exploited to improve current therapeutic strategies for HCC.
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Tonon, Federica, Rossella Farra, Cristina Zennaro, Gabriele Pozzato, Nhung Truong, Salvatore Parisi, Flavio Rizzolio, et al. "Xenograft Zebrafish Models for the Development of Novel Anti-Hepatocellular Carcinoma Molecules." Pharmaceuticals 14, no. 8 (August 16, 2021): 803. http://dx.doi.org/10.3390/ph14080803.
Повний текст джерелаАнотація:
Hepatocellular carcinoma (HCC) is the sixth most common type of tumor and the second leading cause of tumor-related death worldwide. Liver cirrhosis is the most important predisposing factor for HCC. Available therapeutic approaches are not very effective, especially for advanced HCC, which is the most common form of the disease at diagnosis. New therapeutic strategies are therefore urgently needed. The use of animal models represents a relevant tool for preclinical screening of new molecules/strategies against HCC. However, several issues, including animal husbandry, limit the use of current models (rodent/pig). One animal model that has attracted the attention of the scientific community in the last 15 years is the zebrafish. This freshwater fish has several attractive features, such as short reproductive time, limited space and cost requirements for husbandry, body transparency and the fact that embryos do not show immune response to transplanted cells. To date, two different types of zebrafish models for HCC have been developed: the transgenic zebrafish and the zebrafish xenograft models. Since transgenic zebrafish models for HCC have been described elsewhere, in this review, we focus on the description of zebrafish xenograft models that have been used in the last five years to test new molecules/strategies against HCC.
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Zheng, Jinghui, Youming Tang, Encun Hou, Guangde Bai, Zuping Lian, Peisheng Xie, and Weizhi Tang. "Identification of Susceptibility Genes in Hepatic Cancer Using Whole Exome Sequencing and Risk Prediction Model Construction." Revista Romana de Medicina de Laborator 28, no. 1 (January 1, 2020): 67–74. http://dx.doi.org/10.2478/rrlm-2020-0008.
Повний текст джерелаАнотація:
AbstractObjective: To identify the susceptible single nucleotide polymorphisms (SNPs) loci in HCC patients in Guangxi Region, screen biomarkers from differential SNPs loci by using predictors, and establish risk prediction models for HCC, to provide a basis of screening high-risk individuals of HCC.Methods: Blood sample and clinical data of 50 normal participants and 50 hepatic cancer (HCC) patients in Rui Kang Hospital affiliated to Guangxi University of Traditional Chinese Medicine were collected. Normal participants and HCC patients were assigned to training set and testing set, respectively. Whole Exome Sequencing (WES) technique was employed to compare the exon sequence of the normal participants and HCC patients. Five predictors were used to screen the biomarkers and construct HCC prediction models. The prediction models were validated with both training and testing set.Results: Two-hundred seventy SNPs were identified to be significantly different from HCC, among which 100 SNPs were selected as biomarkers for prediction models. Five prediction models constructed with the 100 SNPs showed good sensitivity and specificity for HCC prediction among the training set and testing set.Conclusion: A series of SNPs were identified as susceptible genes for HCC. Some of these SNPs including CNN2, CD177, KMT2C, and HLADQB1 were consistent with the previously identified polymorphisms by targeted genes examination. The prediction models constructed with part of those SNPs could accurately predict HCC development.
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Macek Jilkova, Zuzana, Keerthi Kurma, and Thomas Decaens. "Animal Models of Hepatocellular Carcinoma: The Role of Immune System and Tumor Microenvironment." Cancers 11, no. 10 (October 2, 2019): 1487. http://dx.doi.org/10.3390/cancers11101487.
Повний текст джерелаАнотація:
Hepatocellular carcinoma (HCC) is the most common type of liver cancer in adults and has one of the highest mortality rates of solid cancers. Ninety percent of HCCs are associated with liver fibrosis or cirrhosis developed from chronic liver injuries. The immune system of the liver contributes to the severity of the necrotic-inflammatory tissue damage, the establishment of fibrosis and cirrhosis, and the disease progression towards HCC. Immunotherapies have emerged as an exciting strategy for HCC treatment, but their effect is limited, and an extensive translation research is urgently needed to enhance anti-tumor efficacy and clinical success. Establishing HCC animal models that are analogous to human disease settings, i.e., mimicking the tumor microenvironment of HCC, is extremely challenging. Hence, this review discusses different animal models of HCC by summarizing their advantages and their limits with a specific focus on the role of the immune system and tumor microenvironment.
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Newson, Jordan, Nickolas Kinachtchouk, Kyle Schachtschneider, Regina Schwind, and Lawrence Schook. "Characteristics and Unmet Clinical Needs Related to Hepatocellular Carcinoma." Digestive Disease Interventions 01, no. 02 (June 2017): 074–82. http://dx.doi.org/10.1055/s-0037-1603812.
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AbstractAdvances in biomedical research require animal models that accurately recapitulate human disease. Without such models, progress against human diseases such as cancer is significantly hindered. Here, we present the current landscape on available and emerging hepatocellular carcinoma (HCC) animal models. HCC is the second leading cause of cancer death worldwide, with an annual death toll exceeding 745,000. Stunningly, only 15% of HCC patients are candidates for curative therapy, leading 85% of patients to seek palliative therapeutic options. The VX2 rabbit model is considered the most relevant and widely used HCC model; however, more reliable HCC models are critically needed. In general, animal models for biomedical research should (1) mimic the human disease on a molecular basis, (2) derive from a relevant cell line that lends itself to in vitro study, (3) be reliable and predictable, (4) manifest survival differences, (5) allow for accurate treatment assessment, (6) be readily imaged, and (7) occur in similar background settings as the human disease. Over the past decades, numerous small animal models have been utilized for HCC studies; however, the development of new large animal models as qualified alternatives to murine models represents a key technology to advance research into human clinical trials.
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Giasson, Laurel. "The Best of Both Models." Health Care Manager 38, no. 3 (2019): 247–52. http://dx.doi.org/10.1097/hcm.0000000000000272.
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Hage, C., S. Hoves, M. Ashoff, L. Strauss, M. Perro, F. Herting, F. Kiessling, and T. Pöschinger. "Orthotopic HCC mouse models to predict response to immunotherapy." European Journal of Cancer 92 (March 2018): S5. http://dx.doi.org/10.1016/j.ejca.2018.01.014.
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Sadek, Salar, and Mårten Olsson. "The probability of HCF – Surface and sub-surface models." International Journal of Fatigue 92 (November 2016): 147–58. http://dx.doi.org/10.1016/j.ijfatigue.2016.06.021.
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Li, Yao, Wei Wang, Weisheng Zeng, Jianjun Wang, and Jinghui Meng. "Development of Crown Ratio and Height to Crown Base Models for Masson Pine in Southern China." Forests 11, no. 11 (November 19, 2020): 1216. http://dx.doi.org/10.3390/f11111216.
Повний текст джерелаАнотація:
Crown ratio (CR) and height to crown base (HCB) are important crown characteristics influencing the behavior of forest canopy fires. However, the labor-intensive and costly measurement of CR and HCB have hindered their wide application to forest fire management. Here, we use 301 sample trees collected in 11 provinces in China to produce predictive models of CR and HCB for Masson pine forests (Pinus massoniana Lamb.), which are vulnerable to forest canopy fires. We first identified the best basic model that used only diameter at breast height (DBH) and height (H) as independent variables to predict CR and HCB, respectively, from 11 of the most used potential candidate models. Second, we introduced other covariates into the best basic model of CR and HCB and developed the final CR and HCB predictive models after evaluating the model performance of different combinations of covariates. The results showed that the Richards form of the candidate models performed best in predicting CR and HCB. The final CR model included DBH, H, DBH0.5 and height-to-diameter ratio (HDR), while the final HCB model was the best basic model (i.e., it did not contain any other covariates). We hope that our CR and HCB predictive models contribute to the forest crown fire management of Masson pine forests.
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Simón Serrano, Sonia, Michele Tavecchio, Alvar Grönberg, Wondossen Sime, Mohamed Jemaà, Steven Moss, Matthew Alan Gregory, et al. "Novel Cyclophilin Inhibitor Decreases Cell Proliferation and Tumor Growth in Models of Hepatocellular Carcinoma." Cancers 13, no. 12 (June 18, 2021): 3041. http://dx.doi.org/10.3390/cancers13123041.
Повний текст джерелаАнотація:
Hepatocellular carcinoma (HCC), the most common primary liver cancer, is usually diagnosed in its late state. Tyrosine kinase inhibitors such as sorafenib and regorafenib are one of the few treatment options approved for advanced HCC and only prolong the patient’s life expectancy by a few months. Therefore, there is a need for novel effective treatments. Cyclophilins are intracellular proteins that catalyze the cis/trans isomerization of peptide bonds at proline residues. Cyclophilins are known to be overexpressed in HCC, affecting therapy resistance and cell proliferation. In the present study, we explored the potential of cyclophilin inhibitors as new therapeutic options for HCC in vitro and in vivo. Our results showed that the novel cyclophilin inhibitor, NV651, was able to significantly decrease proliferation in a diverse set of HCC cell lines. The exposure of HCC cells to NV651 caused an accumulation of cells during mitosis and consequent accumulation in the G2/M phase of the cell cycle. NV651 reduced tumor growth in vivo using an HCC xenograft model without affecting the body weights of the animals. The safety aspects of NV651 were also confirmed in primary human hepatocytes without any cytotoxic effects. Based on the results obtained in this study, we propose NV651 as a potential treatment strategy for HCC.
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Lee, Jae Seung, Tae Seop Lim, Hye Won Lee, Seung Up Kim, Jun Yong Park, Do Young Kim, Sang Hoon Ahn, et al. "Suboptimal Performance of Hepatocellular Carcinoma Prediction Models in Patients with Hepatitis B Virus-Related Cirrhosis." Diagnostics 13, no. 1 (December 20, 2022): 3. http://dx.doi.org/10.3390/diagnostics13010003.
Повний текст джерелаАнотація:
This study aimed to evaluate the predictive performance of pre-existing well-validated hepatocellular carcinoma (HCC) prediction models, established in patients with HBV-related cirrhosis who started potent antiviral therapy (AVT). We retrospectively reviewed the cases of 1339 treatment-naïve patients with HBV-related cirrhosis who started AVT (median period, 56.8 months). The scores of the pre-existing HCC risk prediction models were calculated at the time of AVT initiation. HCC developed in 211 patients (15.1%), and the cumulative probability of HCC development at 5 years was 14.6%. Multivariate Cox regression analysis revealed that older age (adjusted hazard ratio [aHR], 1.023), lower platelet count (aHR, 0.997), lower serum albumin level (aHR, 0.578), and greater LS value (aHR, 1.012) were associated with HCC development. Harrell’s c-indices of the PAGE-B, modified PAGE-B, modified REACH-B, CAMD, aMAP, HCC-RESCUE, AASL-HCC, Toronto HCC Risk Index, PLAN-B, APA-B, CAGE-B, and SAGE-B models were suboptimal in patients with HBV-related cirrhosis, ranging from 0.565 to 0.667. Nevertheless, almost all patients were well stratified into low-, intermediate-, or high-risk groups according to each model (all log-rank p < 0.05), except for HCC-RESCUE (p = 0.080). Since all low-risk patients had cirrhosis at baseline, they had unneglectable cumulative incidence of HCC development (5-year incidence, 4.9–7.5%). Pre-existing risk prediction models for patients with chronic hepatitis B showed suboptimal predictive performances for the assessment of HCC development in patients with HBV-related cirrhosis.
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Galicia-Moreno, Marina, Jorge A. Silva-Gomez, Silvia Lucano-Landeros, Arturo Santos, Hugo C. Monroy-Ramirez, and Juan Armendariz-Borunda. "Liver Cancer: Therapeutic Challenges and the Importance of Experimental Models." Canadian Journal of Gastroenterology and Hepatology 2021 (February 28, 2021): 1–10. http://dx.doi.org/10.1155/2021/8837811.
Повний текст джерелаАнотація:
Liver cancer is one of the main causes of death related to cancer worldwide; its etiology is related with infections by C or B hepatitis virus, alcohol consumption, smoking, obesity, nonalcoholic fatty liver disease, diabetes, and iron overload, among other causes. Several kinds of primary liver cancer occur, but we will focus on hepatocellular carcinoma (HCC). Numerous cellular signaling pathways are implicated in hepatocarcinogenesis, including YAP-HIPPO, Wnt-β-catenin, and nuclear factor-κB (NF-κB); these in turn are considered novel therapeutic targets. In this review, the role of lipid metabolism regulated by peroxisome proliferator-activated receptor gamma (PPARγ) in the development of HCC will also be discussed. Moreover, recent evidence has been obtained regarding the participation of epigenetic changes such as acetylation and methylation of histones and DNA methylation in the development of HCC. In this review, we provide detailed and current information about these topics. Experimental models represent useful tools for studying the different stages of liver cancer and help to develop new pharmacologic treatments. Each model in vivo and in vitro has several characteristics and advantages to offer for the study of this disease. Finally, the main therapies approved for the treatment of HCC patients, first- and second-line therapies, are described in this review. We also describe a novel option, pirfenidone, which due to its pharmacological properties could be considered in the future as a therapeutic option for HCC treatment.
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Romualdo, Guilherme Ribeiro, Kaat Leroy, Cícero Júlio Silva Costa, Gabriel Bacil Prata, Bart Vanderborght, Tereza Cristina da Silva, Luís Fernando Barbisan, et al. "In Vivo and In Vitro Models of Hepatocellular Carcinoma: Current Strategies for Translational Modeling." Cancers 13, no. 21 (November 8, 2021): 5583. http://dx.doi.org/10.3390/cancers13215583.
Повний текст джерелаАнотація:
Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and the third leading cause of cancer-related death globally. HCC is a complex multistep disease and usually emerges in the setting of chronic liver diseases. The molecular pathogenesis of HCC varies according to the etiology, mainly caused by chronic hepatitis B and C virus infections, chronic alcohol consumption, aflatoxin-contaminated food, and non-alcoholic fatty liver disease associated with metabolic syndrome or diabetes mellitus. The establishment of HCC models has become essential for both basic and translational research to improve our understanding of the pathophysiology and unravel new molecular drivers of this disease. The ideal model should recapitulate key events observed during hepatocarcinogenesis and HCC progression in view of establishing effective diagnostic and therapeutic strategies to be translated into clinical practice. Despite considerable efforts currently devoted to liver cancer research, only a few anti-HCC drugs are available, and patient prognosis and survival are still poor. The present paper provides a state-of-the-art overview of in vivo and in vitro models used for translational modeling of HCC with a specific focus on their key molecular hallmarks.
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Bissoondial, Tyler L., Yiguang Han, Stephanie Mullan, Amrit K. Pabla, Kiera Spahn, Steven Shi, Lana Zheng, et al. "Liver Biopsy Hydroxyproline Content Is a Diagnostic for Hepatocellular Carcinoma in Murine Models of Nonalcoholic Steatohepatitis." Diagnostics 10, no. 10 (October 4, 2020): 784. http://dx.doi.org/10.3390/diagnostics10100784.
Повний текст джерелаАнотація:
There is increasing evidence that nonalcoholic steatohepatitis (NASH) is a risk factor for hepatocellular carcinoma (HCC) in the absence of cirrhosis, a phenomenon termed noncirrhotic HCC. Early diagnosis of HCC is critical to a favorable prognosis. We tested the hypothesis that hydroxyproline content of liver biopsy samples is diagnostic for HCC in murine models of NASH induced by diet or by diet and chemicals. The training set comprised mice fed a standard diet or a fast-food diet with or without administration of thioacetamide. At harvest, livers from the modified diet cohort exhibited NASH with a subset of NASH livers exhibiting HCC. Hydroxyproline content was measured in liver biopsy samples with tissue in the NASH+HCC cohort sampled from the remote, nontumor parenchyma. Plotting the receiver operating characteristics (ROC) with hydroxyproline as the continuous variable against the absence or presence of HCC yielded an area under ROC of 0.87, a threshold of >0.18 μg hydroxyproline/mg liver and sensitivity of 91% with a specificity of 83.3%. The use of liver hydroxyproline content as a diagnostic for HCC in a test set comprising healthy, NASH and NASH+HCC livers proved 87% accurate.
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Yang, Zhaohui, Qingwang Liu, Peng Luo, Qiaolin Ye, Guangshuang Duan, Ram P. Sharma, Huiru Zhang, Guangxing Wang, and Liyong Fu. "Prediction of Individual Tree Diameter and Height to Crown Base Using Nonlinear Simultaneous Regression and Airborne LiDAR Data." Remote Sensing 12, no. 14 (July 13, 2020): 2238. http://dx.doi.org/10.3390/rs12142238.
Повний текст джерелаАнотація:
The forest growth and yield models, which are used as important decision-support tools in forest management, are commonly based on the individual tree characteristics, such as diameter at breast height (DBH), crown ratio, and height to crown base (HCB). Taking direct measurements for DBH and HCB through the ground-based methods is cumbersome and costly. The indirect method of getting such information is possible from remote sensing databases, which can be used to build DBH and HCB prediction models. The DBH and HCB of the same trees are significantly correlated, and so their inherent correlations need to be appropriately accounted for in the DBH and HCB models. However, all the existing DBH and HCB models, including models based on light detection and ranging (LiDAR) have ignored such correlations and thus failed to account for the compatibility of DBH and HCB estimates, in addition to disregarding measurement errors. To address these problems, we developed a compatible simultaneous equation system of DBH and HCB error-in-variable (EIV) models using LiDAR-derived data and ground-measurements for 510 Picea crassifolia Kom trees in northwest China. Four versatile algorithms, such as nonlinear seemingly unrelated regression (NSUR), two-stage least square (2SLS) regression, three-stage least square (3SLS) regression, and full information maximum likelihood (FIML) were evaluated for their estimating efficiencies and precisions for a simultaneous equation system of DBH and HCB EIV models. In addition, two other model structures, namely, nonlinear least squares with HCB estimation not based on the DBH (NLS and NBD) and nonlinear least squares with HCB estimation based on the DBH (NLS and BD) were also developed, and their fitting precisions with a simultaneous equation system compared. The leave-one-out cross-validation method was applied to evaluate all estimating algorithms and their resulting models. We found that only the simultaneous equation system could illustrate the effect of errors associated with the regressors on the response variables (DBH and HCB) and guaranteed the compatibility between the DBH and HCB models at an individual level. In addition, such an established system also effectively accounted for the inherent correlations between DBH with HCB. However, both the NLS and BD model and the NLS and NBD model did not show these properties. The precision of a simultaneous equation system developed using NSUR appeared the best among all the evaluated algorithms. Our equation system does not require the stand-level information as input, but it does require the information of tree height, crown width, and crown projection area, all of which can be readily derived from LiDAR imagery using the delineation algorithms and ground-based DBH measurements. Our results indicate that NSUR is a more reliable and quicker algorithm for developing DBH and HCB models using large scale LiDAR-based datasets. The novelty of this study is that the compatibility problem of the DBH model and the HCB EIV model was properly addressed, and the potential algorithms were compared to choose the most suitable one (NSUR). The presented method and algorithm will be useful for establishing similar compatible equation systems of tree DBH and HCB EIV models for other tree species.
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Blidisel, Alexandru, Iasmina Marcovici, Dorina Coricovac, Florin Hut, Cristina Adriana Dehelean, and Octavian Marius Cretu. "Experimental Models of Hepatocellular Carcinoma—A Preclinical Perspective." Cancers 13, no. 15 (July 21, 2021): 3651. http://dx.doi.org/10.3390/cancers13153651.
Повний текст джерелаАнотація:
Hepatocellular carcinoma (HCC), the most frequent form of primary liver carcinoma, is a heterogenous and complex tumor type with increased incidence, poor prognosis, and high mortality. The actual therapeutic arsenal is narrow and poorly effective, rendering this disease a global health concern. Although considerable progress has been made in terms of understanding the pathogenesis, molecular mechanisms, genetics, and therapeutical approaches, several facets of human HCC remain undiscovered. A valuable and prompt approach to acquire further knowledge about the unrevealed aspects of HCC and novel therapeutic candidates is represented by the application of experimental models. Experimental models (in vivo and in vitro 2D and 3D models) are considered reliable tools to gather data for clinical usability. This review offers an overview of the currently available preclinical models frequently applied for the study of hepatocellular carcinoma in terms of initiation, development, and progression, as well as for the discovery of efficient treatments, highlighting the advantages and the limitations of each model. Furthermore, we also focus on the role played by computational studies (in silico models and artificial intelligence-based prediction models) as promising novel tools in liver cancer research.
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Sherman, Morris. "HCC Risk Scores: Useful or Not?" Seminars in Liver Disease 37, no. 04 (November 2017): 287–95. http://dx.doi.org/10.1055/s-0037-1607452.
Повний текст джерелаАнотація:
AbstractThe advent and efficacy of surveillance for hepatocellular carcinoma (HCC) has necessitated the refinement of assessing who is at risk for this cancer. Initially, risk was assessed for all individuals with hepatitis B and all those with cirrhosis. However, the majority of these individuals do not develop HCC so that providing surveillance for all is a waste of resources. There are now many different scores that have been developed that allow better identification of who is at risk and who is not. Specific models have been developed for hepatitis B before and on treatment, for hepatitis C before and after treatment, and for cirrhosis in general. There are also models for assessing risk in the general population. Some models can only be applied to patients coming from the population in which the score was developed (e.g., hepatitis B). Others are more generalizable. Many lack external validation. With some exceptions, the models do not attempt to assess the score at which surveillance should start. Overall, the models provide some useful guidance as to who does not need to undergo surveillance, but the long-term performance and how changes in risk score correlate with changes in HCC risk has not been completely assessed.