rss_2.0Contributions to Tobacco & Nicotine Research FeedSciendo RSS Feed for Contributions to Tobacco & Nicotine Research to Tobacco & Nicotine Research 's Cover Investigation of the Histology and Anatomy of Tobacco. 2nd Report / Mikroaufnahmen zur Histologie und Anatomie des Tabaks: II. Mitteilung Apparatus for the Measurement of the Pressure Drop of Cigarettes and Filter Rods / Automatisches Gerät zum Messen des Luftwiderstandes von Cigaretten und Filterstäben<abstract> <title style='display:none'>Abstract</title> <p> The prototype of an apparatus to measure the pressure drop of cigarettes is described. The apparatus works automatically at a speed of 400 cigarettes per hour. Results are indicated as number of cigarettes per draw resistance class of 5 mm WG</p> </abstract>ARTICLE2014-06-13T00:00:00.000+00:00The Distribution of the Air Flow through a Cigarette / Die Verteilung des Ventilationsstromes auf einer Cigarette<abstract> <p>The distribution of the air flow through the porous wrapping of a cigarette is</p> <p><disp-formula><inline-graphic xmlns:xlink="" xlink:href="graphic/Fig.1.png"/></disp-formula></p> <p>ν (λ, l) being the density of the air flow (cm<sup>3</sup> sec<sup>-1</sup> cm<sup>-1</sup>) on the paper wrapping at the position l if l is the length of the porous paper wrapping between the non-porous tip and the burning cone and l is the distance of the position in question from the non-porous tip. ν (λ, l) is given in air flow per cm rather than in air flow per cm<sup>2</sup> because of the cylindrical shape of the cigarette. I denotes the total stream at the mouth piece, a is the specific conductivity to air flow of the paper wrapping, b is the specific resistance to air flow of the tobacco rod, R<sub>G</sub> is the resistance to air flow of the burning cone [compare (1)]. The formula is derived and discussed. The dependence of the distribution of the ventilation stream on the length l and on the resistance RG is demonstrated for the case of a formerly investigated cigarette rod (1). The gradient of ν (λ, l) is</p> <p><disp-formula><inline-graphic xmlns:xlink="" xlink:href="graphic/Fig.2.png"/></disp-formula></p> <p>so that the density of the ventilation stream through the paper wrapping decreases almost linearly from its maximum at the tip to its minimum at the burning cone if the degree of ventilation is low, i.e. if the air flow I (λ, l) in the cigarette is not much higher at λ = 0 than at λ = l</p> </abstract>ARTICLE2014-06-13T00:00:00.000+00:00An Apparatus for the Determination of the Compactness of Cigarettes / Der Betriebs-Kompazitätsmesser<abstract> <title style='display:none'>Abstact</title> <p> An apparatus for the rapid determination of the compactness of cigarettes is presented. We may recall to mind that the compactness of a cigarette is the subjective measure of its filling regarded as average value of the whole of the cigarette. It does not take into account irregularities along the paper wrapping. The compactness thus applying to the total of cigarette filling has direct relation to the degree of exploitation of cut tobacco. In view of an optimum control of manufacture it is desirable to determine cigarette compactness by representative samples. The apparatus meets these requirements. It permits to measure the average compactness of a sample of 15 cigarettes in a short time and holds a device for the determination of tobacco humidity by which compactness values can be referred to a given standard of moisture. The apparatus is suitable for direct utilization in the factory</p> </abstract>ARTICLE2014-06-13T00:00:00.000+00:00Nicotine Degradation by Microorganisms in Model Experiments / Über Nikotinabbau durch Mikroorganismen in Modellversuchen<abstract xml:lang="de"> <title style='display:none'>Abstract</title> <p> Zur Verminderung des Nikotingehaltes stehen heute technologische Maßnahmen im Vordergrund. Eingangs wurde ein Überblick über die aus diesem Sektor vorliegenden Arbeiten über den mikrobiellen und biochemischen Nikotinabbau gegeben. An Hand von eingehenden Untersuchungen konnte gezeigt werden, daß spezielle Bakterien nach Zugabe von Vitamin- und Wuchsstoffen und bei guter Belüftung bis zu 70% der vorgelegten Nikotinmengen abzubauen imstande sind. Schimmelpilze zeigten sich ebenfalls zum Nikotinabbau befähigt. Die innerhalb der eigenen Versuche erhaltenen Abbaustufen wurden chromatographisch dargestellt. Diese bedürfen der weiteren chemischen und physiologischen Bestimmung. Die aus den eigenen mikrobiologischen Ergebnissen gezogenen Folgerungen wurden diskutiert und, soweit dies heute möglich ist, auf die Belange der praktischen Tabakfermentation, Tabakanalytik und Tabakzüchtung ausgerichtet</p> </abstract>ARTICLE2014-06-13T00:00:00.000+00:00Advancements and Challenges of Cigar Science, Testing and Regulation: A Review<abstract> <title style='display:none'>Summary</title> <p>On May 10, 2016, the U.S. Food and Drug Administration (FDA) published a Final Rule that extended its regulatory authority to all tobacco products, including e-cigarettes, cigars, hookah and pipe tobacco (Deemed Products). Effective August 8, 2016, this decision greatly expanded the scope of tobacco products being regulated by FDA and introduced significant testing challenges that need to be addressed. The major challenge for cigars in particular is testing as well as generation of accurate and reliable data, in the absence of certified reference products and standardized methodology for a product category with significant complexity and high inherent variability. In this article, we provide an overview of recent studies as well as active opportunities and on-going challenges associated with regulating and testing cigars. To the best of our knowledge, this is the first comprehensive review of non-clinical research for this product category (cigars). We are therefore convinced that, tobacco scientists and farmers, analytical chemists, cigar consumers, tobacco legal counsels, state and federal regulatory authorities will find this review beneficial and insightful.</p> </abstract>ARTICLE2022-08-15T00:00:00.000+00:00Editors’ Note Waterpipe is not a Cigarette, it is not Even a Conventional Pipe Susceptibility of Adult (Loew) (Diptera: Phoridae)<abstract> <title style='display:none'>Summary</title> <p><italic>Megaselia scalaris</italic> (Loew) (Diptera: Phoridae) is a synanthropic fly that lives in a wide range of warmer regions globally. Although it is listed as a quarantine pest in the Eurasian Economic Union, phytosanitary protocols have not been established. The larva feeds on moist food material and cannot grow on dry matter, including cured tobacco. However, adults of this species have been detected in containers containing tobacco in Russian ports. In this study, difference in susceptibility to phosphine between developmental stages and the lethal effect of phosphine on adults was evaluated. Fortunately, the adult which is the potential contaminable stage in tobacco was demonstrated to be the least tolerant. The phosphine concentrations to achieve probit 9 mortality (≈LC<sub>99.9968</sub>) for adult flies were calculated to be 636.2 ppm at 15 °C, 565.9 ppm at 20 °C, and 280.1 ppm at 25 °C with 6 h of exposure. The concentration × time products (<italic>Ct</italic>, ppm·d), the cumulative exposure to the fumigant, at respective temperatures were calculated as 159.1 ppm·d at 15 °C, 141.5 ppm·d at 20 °C, and 70.0 ppm·d at 25 °C, which are much lower than those recommended for the control of insect pests of cured tobacco leaves by CORESTA (Cooperation Centre for Scientific Research Relative to Tobacco). These are 1800 ppm·d (300 ppm × 6 d) at 16–20 °C and 800 ppm·d (200 ppm × 4 d) at temperatures higher than 20 °C. The results suggest that the standard fumigation protocol for stored tobacco will be adequate to control adult <italic>M. scalaris</italic>. The probit 9 values obtained in this study can be further utilized for the development of phosphine-based quarantine and preshipment treatments for this species.</p> </abstract>ARTICLE2022-08-15T00:00:00.000+00:00HPHC Testing of Tobacco and Smoke to Examine Cigarette Temporal Variability<abstract> <title style='display:none'>Summary</title> <p>Commercial cigarettes were analyzed for harmful and potentially harmful constituents (HPHCs) in tobacco and smoke to investigate temporal product variability independent of analytical variability over one week, one year, and three years. Cigarettes from the worldwide market with various design features were collected over a 3-year period, stored, and tested concurrently for HPHCs to minimize analytical variability; repeat testing of reference cigarette 3R4F was included as an analytical control for the study design. Physical parameters were found to be relatively consistent. No trends in variability were noted based on blend type, smoke analyte matrix, or magnitude of an HPHC's yield. Combustion-related HPHCs generally showed low variation. Long-term batch-to-batch variability was found to be higher than short-term variability for tobacco-related compounds that have the potential to vary over time due to weather and agronomic practices. “Tar”, nicotine, and carbon monoxide were tested in multiple labs and showed greater lab-to-lab variability than batch-to-batch variability across all phases. Based on the results of this study, commercial cigarette products appear to have relatively low product variability. The low analyte variability noted in this study with products tested under unconventionally controlled analytical conditions serves to indicate that analytical variability may be a significant contributor to overall variability for general product testing over time and in interlaboratory studies. Laboratory controls and using a matched reference product across studies and between laboratories are important to assess testing differences and variability.</p> </abstract>ARTICLE2022-08-15T00:00:00.000+00:00Investigation on the Lignin Removal From Tobacco Stem by a Solvothermal Method Using Ethylene Glycol as a Solvent<abstract> <title style='display:none'>Summary</title> <p>High lignin content of tobacco stem has been addressed as a drawback for its utilization on manufacture of reconstituted tobacco sheet. Therefore, the solvothermal method using ethylene glycol was investigated for the removal of lignin from tobacco stem. It was found that the removal efficiency of ethylene glycol on tobacco stem is much lower than that achieved on wheat straw and corncob, i.e., 13.9% <italic>vs</italic>. 39.3% and 44.1%, respectively. This can be rationalized in terms of the presence of solanesol in tobacco stem, which retards the strong hydrogen bond interaction between ethylene glycol and the free hydroxyl groups present in lignin. When solanesol was eliminated by applying an <italic>n</italic>-hexane extraction procedure, 40.5% of lignin was successfully dissolved from tobacco stem. The successful removal of lignin was further confirmed by the characterizing results of SEM, FT-IR and N<sub>2</sub>-sorption. The developed method provides a promising way to attenuate the negative effects of lignin on utilization of the otherwise wasted tobacco stem for production of reconstituted tobacco sheet.</p> </abstract>ARTICLE2022-08-15T00:00:00.000+00:00Integrated Pest Management Strategies for Cigarette Beetle Control in the Tobacco Industry – A Mini Review<abstract> <title style='display:none'>Summary</title> <p>The cigarette beetle (CB), <italic>Lasioderma serricorne</italic> (Cole-optera: Ptinidae), is a major insect pest to the tobacco industry worldwide. This insect is also a major pest of raw grains such as rough rice, and postharvest foods like certain high-value grain products like pet food, animal feed, breakfast cereals and various dried herbs and spices. Pest control methods and systematic integrated pest management (IPM) strategies are required for the CB in the tobacco industry to prevent economic damage to cured tobacco leaves in storages as well as finished products in retail and distribution chains. This paper presents an overview of the problem of CB infestation in the tobacco industry and describes and discusses strategies and IPM practices for managing the pest.</p> </abstract>ARTICLE2022-08-15T00:00:00.000+00:00Editors’ Note Public Health Gains From German Smokers Switching to Reduced-Risk Alternatives: Results From Population Health Impact Modelling<abstract> <title style='display:none'>Summary</title> <sec><title style='display:none'>Background</title> <p>Smoking is associated with cancer and cardio-respiratory mortality. Reducing smoking prevalence will lead to fewer deaths and more life-years. Here, we estimate the impact of hypothetical introduction of reduced-risk products (heat-not-burn products and e-cigarettes) in Germany from 1995 to 2015 on mortality from lung cancer, chronic obstructive pulmonary disease, ischaemic heart disease, and stroke in men and women aged 30–79 years.</p> </sec> <sec><title style='display:none'>Methods</title> <p>We used a previously described population health impact model, with individuals with a defined baseline cigarette smoking distribution followed under a “Null Scenario”, with reduced-risk products never introduced, and various “Alternative Scenarios” where they are. Transition probabilities allow product use to change annually, with the individual product histories allowing estimation of risks, relative to never users, which are then used to estimate reductions in deaths and life-years lost for each Alternative Scenario.</p> </sec> <sec><title style='display:none'>Results</title> <p>In the Null Scenario, we estimated 852,000 deaths from cigarette smoking (42,600 per year), with 8.61 million life-years lost. Had everyone ceased smoking in 1995, and with no use of reduced-risk products, these numbers would reduce by 217,000 and 2.88 million. Compared to the Null Scenario, the estimated reductions would be 159,000 and 2.06 million with an immediate complete switch to heat-not-burn products and 179,000 and 2.34 million with 50% of smokers immediately switching to heat-not-burn products and 50% to e-cigarettes. In four Scenarios with a more gradual switch, the estimated decreases were 39,800–81,000 deaths and 0.50–1.05 million life-years, representing 17.5%–37.5% of the effect of immediate cessation in 1995. These estimates assume that switching to heat-not-burn products and e-cigarettes involves risk decreases of 80% and 95% of those from quitting, respectively. The reductions in mortality would be greater with more diseases and a wider age range considered or with a longer follow-up period, as the decreases increased markedly with time. Various limitations are discussed, none affecting the conclusion that introducing these new products into Germany in 1995 could have substantially reduced deaths and life-years lost.</p> </sec> <sec><title style='display:none'>Conclusions</title> <p>Deaths from cigarette smoking could be substantially reduced not only by cessation but additionally by switching to reduced-risk products. Respective public health campaigns might increase such switching.</p> </sec> </abstract>ARTICLE2022-05-05T00:00:00.000+00:00Estimated Public Health Gains From Smokers in Germany Switching to Reduced-Risk Alternatives: Results From Population Health Impact Modelling by Socioeconomic Group<abstract> <title style='display:none'>Summary</title> <sec><title style='display:none'>Background</title> <p>We previously estimated the impact of introducing heat-not-burn products and e-cigarettes in Germany on smoking-related disease mortality in men and women aged 30–79 years between 1995 and 2015. Here, we estimate the impact by socioeconomic group.</p> </sec> <sec><title style='display:none'>Methods</title> <p>Individuals with a defined baseline cigarette smoking distribution were followed under a “Null Scenario” (no reduced-risk products) and “Alternative Scenarios” (reduced-risk products introduced). Transition probabilities allowed estimation of annual product use changes, with individual product histories used to estimate reductions in deaths and life-years lost. Here, however, individuals were classified into two socioeconomic groups defined by income and education, with allowance for variation by group in initial smoking prevalence and the probability of changing product use, or of changing socioeconomic group.</p> </sec> <sec><title style='display:none'>Results</title> <p>With no allowance for socioeconomic group, deaths would have reduced by 217,000 (from 852,000 for continued smoking) had everyone immediately ceased smoking in 1995 and by 40,000 to 179,000 had one or two types of reduced-risk products – the heat-not-burn product and the e-cigarette – been adopted by smokers to varying extents. With such allowance, we estimate substantial drops in each socioeconomic group. Where all cigarette smokers switched immediately, half of them to heat-not-burn products, half to e-cigarettes, the estimated drops in deaths were 60,000 in group A (higher socioeconomic group) and 122,000 in group B (lower), about 82% of the drops associated with immediate cessation (73,000 in A and 148,000 in B). With more gradual conversion, the drops were 26,648 in A and 53,000 in B, about 35% of those from cessation. The drops in deaths and life-years saved were about 2 and 1.5 times higher in group B, respectively, associated with its greater numbers, older age, and higher smoking prevalence. The estimated reductions would increase upon considering more diseases, a wider age range, or longer follow-up. Methodological limitations would not affect the conclusion that introducing these products in 1995 in Germany could have substantially reduced deaths and life-years lost in both groups, more so in B.</p> </sec> <sec><title style='display:none'>Conclusions</title> <p>Although cessation is optimal for reducing mortality, switching to reduced-risk products also provides substantial health gains. A public health approach encouraging lower socioeconomic group smokers to switch to reduced-risk products could diminish smoking-related health inequalities relative to continued smoking.</p> </sec> </abstract>ARTICLE2022-05-05T00:00:00.000+00:00A Simultaneous Analytical Method to Profile Non-Volatile Components with Low Polarity Elucidating Differences Between Tobacco Leaves Using Atmospheric Pressure Chemical Ionization Mass Spectrometry Detection<abstract> <title style='display:none'>Summary</title> <p>A comprehensive analytical method using liquid chromatography atmospheric pressure chemical ionization mass spectrometry detector (LC/APCI-MSD) was developed to determine key non-volatile components with low polarity elucidating holistic difference among tobacco leaves. Nonaqueous reversed-phase chromatography (NARPC) using organic solvent ensured simultaneous separation of various components with low polarity in tobacco resin. Application of full-scan mode to APCI-MSD hyphenated with NARPC enabled simultaneous detection of numerous intense product ions given by APCI interface. Parameters for data processing to filter, feature and align peaks were adjusted in order to strike a balance between comprehensiveness and reproducibility in analysis. 63 types of components such as solanesols, chlorophylls, phytosterols, triacylglycerols, solanachromene and others were determined on total ion chromatograms according to authentic components, wavelength spectrum and mass spectrum. The whole area of identified entities among the ones detected on total ion chromatogram reached to over 60% and major entities among those identified showed favorable linearity of determination coefficient of over 0.99. The developed method and data processing procedure were therefore considered feasible for subsequent multivariate analysis. Data matrix consisting of a number of entities was then subjected to principal component analysis (PCA) and hierarchical clustering analysis. Cultivars of tobacco leaves were distributed far from each cultivar on PCA score plot and each cluster seemed to be characterized by identified non-volatile components with low polarity. While fluecured Virginia (FCV) was loaded by solanachromene, phytosterol esters and triacylglycerols, free phytosterols and chlorophylls loaded Burley (BLY) and Oriental (ORI) respectively. Consequently the whole methodology consisting of comprehensive method and data processing procedure proved useful to determine key-components among cultivars of tobacco leaves, and was expected to additionally expand coverage that metabolomics study has ensured. [Beitr. Tabakforsch. Int. 27 (2016) 60-73]</p> </abstract>ARTICLE2016-05-18T00:00:00.000+00:00Influence of Type and Amount of Carbon in Cigarette Filters on Smokers’ Mouth Level Exposure to “Tar”, Nicotine, 1,3-Butadiene, Benzene, Toluene, Isoprene, and Acrylonitrile<abstract> <title style='display:none'>Summary</title> <p>Activated carbons are effective adsorbents for many volatile organic compounds and are used in cigarette filters to remove selected smoke toxicants. Polymer-derived carbon is more effective in removing many vapour phase toxicants found in cigarette smoke than coconut-shell-derived carbon. We compared mouth-level exposure to “tar”, nicotine and five vapour phase constituents (1,3- butadiene, benzene, toluene, isoprene, acrylonitrile) in two groups of Romanian smokers of 4-mg or 8-mg International Organization for Standardization (ISO) “tar” bands. Test cigarettes with 4 and 8 mg ISO “tar” were manufactured for the study with two target levels of polymer-derived carbon (30 mg and 56 mg), along with control cigarettes containing a target level of 56 mg of coconut-shell-derived carbon in both “tar” bands. No significant differences were found between mouth-level exposure to “tar” or nicotine yields obtained from control and test products (p &gt; 0.05) in either ISO “tar” band. Mouth-level exposure to each of the five vapour phase constituents was significantly lower from the test products with polymer-derived carbon (p &lt; 0.0001) than from control cigarettes with coconut-shell-derived carbon, by an average of 25% with 30 mg polymer-derived carbon and around 50% with 56 mg. [Beitr. Tabakforsch. Int. 27 (2016) 40-53]</p> </abstract>ARTICLE2016-05-18T00:00:00.000+00:00Nicotine Analysis in Several Non-Tobacco Plant Materials<abstract> <title style='display:none'>Summary</title> <p>Present study describes the determination of nicotine in various plant samples with a low content of this compound. Nicotine is found naturally in plants from the Solanaceae family. The plants from Nicotiana genus contain large levels of nicotine. However, only low levels are present in plants from Solanum genus including potato, tomato, eggplant, and from Capsicum genus, which are used as food. Because the levels of nicotine in these materials are in the range of parts per billion, the measurements are difficult and the results are very different from study to study. The present study evaluated the level of nicotine in a number of plants (fruits, roots, leaves, tubers) from Solanaceae family (not including Nicotiana genus) and from several other vegetables commonly used as food. The analysis consisted of the treatment of plant material with an aqueous solution 5% NaOH at 70°C for 30 min, followed by extraction with TBME containing d<sub>3</sub>-nicotine as an internal standard. The TBME organic layer was analyzed on a 7890B/7000C GC-MS/MS system with a 30 m × 0.25 mm, 0.25 μm film CAM column. The MS/MS system worked in MRM positive ionization mode monitoring the transition 162 - 84 for nicotine and 165 - 87 for d<sub>3</sub>-nicotine. Particular attention was given to the preservation of the intact levels of nicotine in the plant material. The plant material was analyzed as is, without drying and with minimal exposure to contaminations. Separately, the moisture of the plant material was measured in order to report the nicotine level on a dry-basis. Levels of nicotine around 180 ng/g dry material were obtained for tomatoes and eggplant (fruit) and lower levels were obtained for green pepper and potato. Similar levels to that in the tomato fruit were detected in tomato leaves. Materials from other plant families also showed traces of nicotine. [Beitr. Tabakforsch. Int. 27 (2016) 54-59]</p> </abstract>ARTICLE2016-05-18T00:00:00.000+00:00Cross-Sectional Relations Between Slim Cigarettes and Smoking Prevalence<abstract> <title style='display:none'>Summary</title> <p>Slim cigarettes were defined in the 2012 draft European Union-Tobacco Product Directive (EU-TPD) as cigarettes with a diameter of less than 7.5mm. Allegations that slim cigarettes may negatively impact tobacco control efforts led the European Commission to propose a ban on them in 2012, which was ultimately rejected. This study investigated whether there is any association between slim cigarettes and smoking prevalence rates, in order to see if these allegations are justified. Data was compiled on the market share of slim cigarettes and smoking prevalence rates from the years 2012, 2006 and 1996. The core 2012 sample (once data limitations were accounted for) consisted of 95 countries. Raw correlations between market shares of slim cigarettes and smoking prevalence rates were first examined, followed by multivariate cross-country regressions where various factors were controlled for. This was done for overall smoking prevalence, as well as for male and female prevalence separately. </p> <p>Although raw correlations between the slim cigarette market share and smoking prevalence were sometimes positive and statistically significant, this result disappeared in all cases except for one when potential confounding factors were fully controlled for. The correlation between slim cigarette market share and smoking prevalence remained significant only for males in 2012 at levels of statistical significance of 10% or above when cultural and socio-economic factors were fully controlled for. Importantly, for females no positive statistically significant correlations between the slim cigarette market share and smoking prevalence were found for any year. The cross-country variation in smoking prevalence was substantially explained by a number of regional and cultural dummies, as well as socio-economic factors. </p> <p>This study has found no indication that a higher market share of slim cigarettes was associated with greater smoking prevalence among females, and has failed to find a strong indication among males, once confounding factors were controlled for. [Beitr. Tabakforsch. Int. 27 (2016) 75-99]</p> </abstract>ARTICLE2016-05-18T00:00:00.000+00:00An Experimental Analytical and Approach to Bridge Between Different Heated Tobacco Product Variants<abstract> <title style='display:none'>Summary</title> <p>Tobacco heating products (THPs) have reduced toxicant emissions relative to cigarettes. THPs are continually evolving, but safety and efficacy studies on each new variant involve considerable resources. As employed by the pharmaceutical industry, a “bridging” process could be used to demonstrate product equivalence.</p> <p>Therefore, we investigated the feasibility of a bridging approach by evaluating aerosol emissions and <italic>in vitro</italic> cytotoxicity of five variant THPs in relation to a base product. All products were compared to a reference cigarette and a commercial benchmark. Relative to smoke, chemical reductions in THP aerosols were comparable among the THPs at 94–97%. The aerosols showed similar cytotoxicity in human lung tissues exposed at the air-liquid interface (p = 0.8378) but were significantly less toxic than smoke (p = 0.04). Relative to the THP benchmark, variant THPs showed lower cytotoxicity (p = 0.0141). Emissions and cytotoxicity data demonstrated that the variant THPs were comparable to the base THP, irrespective of consumable format or flavour. This dataset demonstrates the feasibility of a bridging approach and can inform an evidence-based strategy in developing sufficient data to predict similarity against an already established dataset. Therefore, avoiding repetition of vast data generation could ease authorisation requirements of newer products. Finally, we propose that more work is required to understand chemical, biological (<italic>in vitro</italic>), human consumption, and clinical data before the equivalence of these products (and others) can be definitively demonstrated. Future studies maybe needed to assess additional chemical and biological outputs and all data will need to be contextualised against human consumption data in terms of a bridging framework.</p> </abstract>ARTICLE2022-04-16T00:00:00.000+00:00en-us-1