Particulate matter induces arrhythmia-like cardiotoxicity in zebrafish embryos by altering the expression levels of cardiac development- and ion channel-related genes.

Air pollution is a risk factor that increases cardiovascular morbidity and mortality. In this study, we investigated the cardiotoxicity of particulate matter (PM) exposure using a zebrafish embryo model. We found that PM exposure induced cardiotoxicity, such as arrhythmia, during cardiac development. PM exposure caused cardiotoxicity by altering the expression levels of cardiac development (T-box transcription factor 20, natriuretic peptide A, and GATA-binding protein 4)- and ion-channel (scn5lab, kcnq1, kcnh2a/b, and kcnh6a/b)-related genes. In conclusion, this study showed that PM induces the aberrant expression of cardiac development- and ion channel-related genes, leading to arrhythmia-like cardiotoxicity in zebrafish embryos. Our study provides a foundation for further research on the molecular and genetic mechanisms of cardiotoxicity induced by PM exposure.

Cavity-dumped mode-locked Alexandrite laser oscillator with 100 mJ pulses stabilized by using a double trigger system.

We report a mode-locked Alexandrite single pulse laser with cavity dumping. Mode locking was achieved by using an AOM and an EOM was used for Q-switching and cavity dumping. The instability of the single pulse laser energy output was reduced down to a tenth of that of the conventional single trigger system by introducing a novel double trigger system. The single pulse laser energy and pulse width were 100 mJ and 475 ps in multiple mode and 12.5 mJ and 275 ps in single mode, obtained without a laser amplifier.

Pulmonary fibrosis model using micro-CT analyzable human PSC-derived alveolar organoids containing alveolar macrophage-like cells.

Human lung organoids (hLOs) are useful for disease modelling and drug screening. However, a lack of immune cells in hLOs limits the recapitulation of in vivo cellular physiology. Here, we generated hLOs containing alveolar macrophage (AMφ)-like cells derived from pluripotent stem cells (PSC). To bridge hLOs with advanced human lung high-resolution X-ray computed tomography (CT), we acquired quantitative micro-CT images. Three hLO types were observed during differentiation. Among them, alveolar hLOs highly expressed not only lung epithelial cell markers but also AMφ-specific markers. Furthermore, CD68+ AMφ-like cells were spatially organized on the luminal epithelial surface of alveolar hLOs. Bleomycin-treated alveolar hLOs showed upregulated expression of fibrosis-related markers and extracellular matrix deposits in the alveolar sacs. Alveolar hLOs also showed structural alterations such as excessive tissue fraction under bleomycin treatment. Therefore, we suggest that micro-CT analyzable PSC-derived alveolar hLOs are a promising in vitro model to predict lung toxicity manifestations, including fibrosis.

Presence of a survival benefit of HLA-incompatible living donor kidney transplantation compared to waiting or HLA-compatible deceased donor kidney transplantation with a long waiting time.

HLA-incompatible living donor kidney transplantation (LDKT) is one of efforts to increase kidney transplantation opportunity for sensitized patients with kidney failure. However, there are conflicting reports for outcomes of HLA-incompatible kidney transplantation compared to patients who wait for HLA-compatible deceased donor kidney transplantation (DDKT) in the United States and United Kingdom. Waiting for an HLA-compatible DDKT is relatively disadvantageous in Korea, because the average waiting time is more than five years. To study this further, we compared outcomes of HLA-incompatible LDKT with those who wait for HLA-compatible DDKT in Korea. One hundred eighty nine patients underwent HLA-incompatible LDKT after desensitization between 2006 and 2018 in two Korean hospitals (42 with a positive complement-dependent cytotoxicity cross-match, 89 with a positive flow cytometric cross-match, and 58 with a positive donor-specific antibody with negative cross-match). The distribution of matched variables was comparable between the HLA-incompatible LDKT group and the matched control groups (waiting-list-only group; and the waiting-list-or-HLA-compatible-DDKT groups; 930 patients each). The HLA-incompatible LDKT group showed a significantly better patient survival rate compared to the waiting-list-only group and the waiting-list-or-HLA-compatible-DDKT groups. Furthermore, the HLA-incompatible LDKT group showed a significant survival benefit as compared with the matched groups at all strength of donor-specific antibodies. Thus, HLA-incompatible LDKT could have a survival benefit as compared with patients who were waitlisted for HLA-compatible DDKT or received HLA-compatible DDKT in Korea. This suggests that HLA-incompatible LDKT as a good option for sensitized patients with kidney failure in countries with prolonged waiting times for DDKT.

Investigation into the impact of the recovery time of a saturable absorber for stable dissipative soliton generation in Yb-doped fiber lasers.

In this study, we conduct a numerical evaluation of the impact of the recovery time of a saturable absorber (SA) on the output performance of an Yb-doped fiber laser operating in the dissipative soliton regime. Particularly, we evaluate the output pulse characteristics, such as the pulse width, spectral bandwidth, pulse peak power, and pulse energy depending on the change in recovery time. Applying a too-slow SA recovery time above a certain critical value is shown to make the output pulse unstable and broken. Furthermore, we demonstrate that there is an optimum recovery time range for stable dissipative soliton pulse generation, depending on the cavity dispersion and modulation depth of the SA. Further, we perform an additional numerical simulation of the pulse compression to demonstrate the relationship between the output dechirped pulse width and SA recovery time. The optimum approach for the generation of the shortest dechirped pulses in the dissipative soliton regime will be to construct a fiber laser cavity with a small normal cavity group velocity dispersion and use an SA with an appropriate recovery time.

Radiogenomic Analysis of Breast Cancer by Using B-Mode and Vascular US and RNA Sequencing.

Background Radiogenomic investigations for breast cancer provide an understanding of tumor heterogeneity and discover image phenotypes of genetic variation. However, there is little research on the correlations between US features of breast cancer and whole-transcriptome profiling. Purpose To explore US phenotypes reflecting genetic alteration relevant to breast cancer treatment and prognosis by comparing US images of tumor with their RNA sequencing results. Materials and Methods From January to October 2016, B-mode and vascular US images in 31 women (mean age, 49 years ± 9 [standard deviation]) with breast cancer were prospectively analyzed. B-mode features included size, shape, echo pattern, orientation, margin, and calcifications. Vascular features were evaluated by using microvascular US and contrast agent-enhanced US: vascular index, vessel morphologic features, distribution, penetrating vessels, enhancement degree, order, margin, internal homogeneity, and perfusion defect. RNA sequencing was conducted with total RNA obtained from a surgical specimen by using next-generation sequencing. US features were compared with gene expression profiles, and ingenuity pathway analysis was used to analyze gene networks, enriched functions, and canonical pathways associated with breast cancer. The P value for differential expression was extracted by using a parametric F test comparing nested linear models. Results Thirteen US features were associated with various patterns of 340 genes (P < .05). Nonparallel orientation at B-mode US was associated with upregulation of TFF1 (log twofold change [log2FC] = 4.0; P < .001), TFF3 (log2FC = 2.5; P < .001), AREG (log2FC = 2.6; P = .005), and AGR3 (log2FC = 2.6; P = .003). Complex vessel morphologic structure was associated with upregulation of FZD8 (log2FC = 2.0; P = .01) and downregulation of IGF1R (log2FC = -2.0; P = .006) and CRIPAK (log2FC = -2.4; P = .01). The top networks with regard to orientation or vessel morphologic structure were associated with cell cycle, death, and proliferation. Conclusion Compared with RNA sequencing, B-mode and vascular US features reflected genomic alterations associated with hormone receptor status, angiogenesis, or prognosis in breast cancer. © RSNA, 2020 Online supplemental material is available for this article.

532-nm second harmonic generation with enhanced efficiency using subharmonic cavity modulation-based quasi-Q-switched-mode-locked pulses.

We report the results of our investigation of the second harmonic generation (SHG) green pulse generation with an active, quasi-Q-switched-mode-locked (QML) fiber laser based on subharmonic cavity modulation. First, we investigate the working principle of the quasi-QML pulse generation technique, based on subharmonic cavity modulation through analytical calculation. We show that the stable QML-like pulse generation by subharmonic cavity modulation is induced by phase-locked interference of a large number of subharmonic modulation-induced frequency components within a cavity. Next, we experimentally realize a 1064 nm quasi-QML fiber laser with an ytterbium (Yb)-doped fiber ring cavity incorporating an acousto-optic modulator. Finally, using the implemented quasi-QML laser, we experimentally show that the use of 1064 nm quasi-QML pulses could result in the increase of the SHG conversion efficiency in a MgO:PPLN, compared to the use of continuous mode-locked (ML) pulses. For our particular experimental configuration, we could readily achieve a noticeable SHG efficiency increase of 8% by using quasi-QML pulses with a subharmonic order of 80, compared to continuous ML pulses.

Femtosecond harmonic mode-locking of a fiber laser at 3.27 GHz using a bulk-like, MoSe2-based saturable absorber.

We experimentally demonstrate the use of a bulk-like, MoSe2-based saturable absorber (SA) as a passive harmonic mode-locker for the production of femtosecond pulses from a fiber laser at a repetition rate of 3.27 GHz. By incorporating a bulk-like, MoSe2/PVA-composite-deposited side-polished fiber as an SA within an erbium-doped-fiber-ring cavity, mode-locked pulses with a temporal width of 737 fs to 798 fs can be readily obtained at various harmonic frequencies. The fundamental resonance frequency and the maximum harmonic-resonance frequency are 15.38 MHz and 3.27 GHz (212th harmonic), respectively. The temporal and spectral characteristics of the output pulses are systematically investigated as a function of the pump power. The output pulses exhibited Gaussian-temporal shapes irrespective of the harmonic order, and even when their spectra possessed hyperbolic-secant shapes. The saturable absorption and harmonic-mode-locking performance of our prepared SA are compared with those of previously demonstrated SAs that are based on other transition metal dichalcogenides (TMDs). To the best of the authors' knowledge, the repetition rate of 3.27 GHz is the highest frequency that has ever been demonstrated regarding the production of femtosecond pulses from a fiber laser that is based on SA-induced passive harmonic mode-locking.

Graphite saturable absorber based on the pencil-sketching method for Q-switching of an erbium fiber laser.

We experimentally demonstrate a practical and simple method for the preparation of a graphite-based, fiberized saturable absorber (SA). Our SA is prepared by using a low-cost graphite-core pencil that is commercially available from stationary stores to uniformly shade the flat end of a fiber ferrule. The saturable-absorption performance of the prepared SA was experimentally tested, and the feasibility of using the SA as a passive Q-switch was investigated through its incorporation into an erbium-doped-fiber ring cavity. The modulation depth of the SA is ∼1%, and the Q-switched pulses of a 1.98 µs temporal width were readily obtained at a repetition rate of 46.08 kHz.

Femtosecond harmonic mode-locking of a fiber laser based on a bulk-structured Bi(2)Te(3) topological insulator.

We experimentally demonstrate femtosecond harmonic mode-locking of a fiber laser using a bulk-structured Bi(2)Te(3) topological insulator (TI)-deposited on a side-polished fiber as a mode-locker. A bulk-structured Bi(2)Te(3) TI film was prepared at a thickness of ~20 µm using a mechanical exfoliation method. Using the mode-locker in an erbium-doped fiber ring cavity, it was experimentally shown that harmonically mode-locked pulses with temporal widths of 630 ~700 fs could readily be generated upto the 55th harmonics. The pulse repetition rate was shown to be tunable from the fundamental resonance frequency of 14.07 MHz to the harmonic frequency of 773.85 MHz with increasing pump power. The pumping efficiency was measured at ~3.36 MHz/mW. The side mode suppression ratio (SMSR) was observed to be more than 27.3 dB over all harmonic orders, while the corresponding signal-to-noise ratio (SNR) ranged from 46.3 to 63 dB.

Mode-locked, 1.94-µm, all-fiberized laser using WS2 based evanescent field interaction.

We demonstrate the use of an all-fiberized, mode-locked 1.94 µm laser with a saturable absorption device based on a tungsten disulfide (WS2)-deposited side-polished fiber. The WS2 particles were prepared via liquid phase exfoliation (LPE) without centrifugation. A series of measurements including Raman spectroscopy, scanning electron microscopy (SEM), and atomic force microscopy (AFM) revealed that the prepared particles had thick nanostructures of more than 5 layers. The prepared saturable absorption device used the evanescent field interaction mechanism between the oscillating beam and WS2 particles and its modulation depth was measured to be ~10.9% at a wavelength of 1925 nm. Incorporating the WS2-based saturable absorption device into a thulium-holmium co-doped fiber ring cavity, stable mode-locked pulses with a temporal width of ~1.3 ps at a repetition rate of 34.8 MHz were readily obtained at a wavelength of 1941 nm. The results of this experiment confirm that WS2 can be used as an effective broadband saturable absorption material that is suitable to passively generate pulses at 2 µm wavelengths.

A femtosecond pulse erbium fiber laser incorporating a saturable absorber based on bulk-structured Bi2Te3 topological insulator.

We experimentally demonstrate the use of a bulk-structured Bi(2)Te(3) topological insulator (TI) as an ultrafast mode-locker to generate femtosecond pulses from an all-fiberized cavity. Using a saturable absorber based on a mechanically exfoliated layer about 15 µm thick deposited onto a side-polished fiber, we show that stable soliton pulses with a temporal width of ~600 fs can readily be produced at 1547 nm from an erbium fiber ring cavity. Unlike previous TI-based mode-locked laser demonstrations, in which high-quality nanosheet-based TIs were used for saturable absorption, we chose to use a bulk-structured Bi(2)Te(3) layer because it is easy to fabricate. We found that the bulk-structured Bi(2)Te(3) layer can readily provide sufficient nonlinear saturable absorption for femtosecond mode-locking even if its modulation depth of ~15.7% is much lower than previously demonstrated nanosheet-structured TI-based saturable absorbers. This experimental demonstration indicates that high-crystalline-quality atomic-layered films of TI, which demand complicated and expensive material processing facilities, are not essential for ultrafast laser mode-locking applications.

A femtosecond pulse fiber laser at 1935 nm using a bulk-structured Bi2Te3 topological insulator.

We experimentally demonstrate a femtosecond mode-locked, all-fiberized laser that operates in the 2 µm region and that incorporates a saturable absorber based on a bulk-structured bismuth telluride (Bi(2)Te(3)) topological insulator (TI). Our fiberized saturable absorber was prepared by depositing a mechanically exfoliated, ~30 µm-thick Bi(2)Te(3) TI layer on a side-polished optical fiber platform. The bulk crystalline structure of the prepared Bi(2)Te(3) layer was confirmed by Raman and X-ray photoelectron spectroscopy measurements. The modulation depth of the prepared saturable absorber was measured to be ~20.6%. Using the saturable absorber, it is shown that stable, ultrafast pulses with a temporal width of ~795 fs could readily be generated at a wavelength of 1935 nm from a thulium/holmium co-doped fiber ring cavity. This experimental demonstration confirms that bulk structured, TI-based saturable absorbers can readily be used as an ultra-fast mode-locker for 2 µm lasers.

Expression of ß-tubulin isotypes in urothelial carcinoma of the bladder.

PURPOSE: Our study aims to investigate the expressions of ß-tubulin isotypes and their significances in urothelial carcinoma of the bladder (UCB) as altered expression of a specific ß-tubulin isotype is associated with chemoresistance and poor prognosis in other malignancies. MATERIALS AND METHODS: Expression of ß-tubulin isotypes was retrospectively examined in 342 UCB samples obtained from 1995 to 2010 by immunohistochemistry. RESULTS: TUBB1 (307/342, 89.8 %) was most frequently overexpressed in the cytoplasm of UCB cases, followed by TUBB4 (101/342, 29.5 %), TUBB2 (85/342, 24.9 %), and TUBB3 (60/342, 17.5 %). TUBB1 overexpression was associated with older age (p = 0.032), high WHO grade (p = 0.001), and advanced TNM stage (p = 0.006). High levels of TUBB2 expression were associated with high WHO grade (p < 0.001), advanced TNM stage (p < 0.001), and non-papillary growth pattern (p = 0.007). TUBB3 overexpression was related to high WHO grade (p = 0.029). In univariate and multivariate survival analyses, TUBB1 overexpression was associated with poor recurrence-free survival (RFS) rates of all cases (hazard ratio 1.98, p = 0.031) and of the patients with transurethral and/or partial resection (hazard ratio 2.12, p = 0.031). TUBB2 overexpression was correlated with a short RFS of the patients with T2-T4 stages (hazard ratio 3.48, p = 0.007). TUBB3 overexpression was related to a poor RFS of the patients undergoing radical cystectomy (hazard ratio 5.90, p = 0.002). CONCLUSIONS: High TUBB1, TUBB2, and TUBB3 expressions are associated with unfavorable clinicopathologic factors and are independent prognostic factors for recurrence-free survival of UCB.

MAD2 and CDC20 are upregulated in high-grade squamous intraepithelial lesions and squamous cell carcinomas of the uterine cervix.

Abnormal expression of the spindle assembly checkpoint proteins causes tumor cell aneuploidy, which has been reported in various malignancies. The expression of mitotic arrest deficient 2 (MAD2) and cell-division cycle 20 homolog (CDC20), the key spindle assembly checkpoint proteins, has not been studied in cervical carcinogenesis. In this study, we compared the expression of MAD2 and CDC20 in 332 cases, including normal cervical tissues, low-grade squamous intraepithelial lesions, high-grade squamous intraepithelial lesions (HSILs), and invasive squamous cell carcinomas (SCCs). Both MAD2 and CDC20 were overexpressed in the nuclei or cytoplasm of dysplastic and malignant tumor cells. The frequency of MAD2 overexpression was markedly increased from undetectable (0/100) in normal cervical tissues and 2% (1/50) in low-grade squamous intraepithelial lesions to 67.1% (53/79) in HSILs and 52.4% (54/103) in SCCs. Similarly, CDC20 was overexpressed in 49.4% (39/79) of HSILs and 22.3% (23/103) of SCCs, whereas CDC20 was not detectable (0/100) in normal cervical tissues and overexpressed only in 8.0% (4/50) of low-grade squamous intraepithelial lesions. In SCC cases, MAD2 overexpression correlated with a patient age of less than 60 yr (P=0.043), nonkeratinizing histologic type (P=0.018), and a lesser degree of stromal invasion (P=0.026). In conclusion, MAD2 and CDC20 overexpression was increased in HSILs and SCCs, suggesting their involvement in the initiation of cervical cancers. Controlling CDC20 and MAD2 expression may be a therapeutic strategy for cervical cancer.

Mode-locked thulium-bismuth codoped fiber laser using graphene saturable absorber in ring cavity: comment.

We comment on a recent paper [Appl. Opt.52, 1226 (2013)]. We believe that this paper reports significant errors regarding the autocorrelation measurement of output pulses and the associated analysis of their temporal and spectral characteristics.

Xenotransplantation of human mesenchymal stem cells for repair of osteochondral defects in rabbits using osteochondral biphasic composite constructs.

PURPOSE: The aim of this work is to investigate the feasibility of non-autologous transplantation of human mesenchymal stem cells (hMSCs) with or without differentiation for the regeneration of osteochondral defects in rabbits using a biphasic composite construct composed of platelet-rich fibrin glue (PR-FG) and hydroxyapatite. METHODS: After isolation and culture, hMSCs were seeded on biphasic composite constructs (hydroxyapatite + PR-FG) and transplanted into osteochondral defects of adult New Zealand white rabbits. Treatment of individual defects was applied by random assignment to one of five groups: (1) control, defects untreated; (2) hydroxyapatite, defects filled with hydroxyapatite only; (3) hydroxyapatite + PR-FG, defects filled with a composite of hydroxyapatite and PR-FG; (4) hydroxyapatite + PR-FG + undifferentiated hMSCs; and (5) hydroxyapatite + PR-FG + differentiated hMSCs. Rabbits were killed at 4 or 8 weeks post-surgery, at which time osteochondral repair was macroscopically and histologically evaluated and scored using the modified International Cartilage Repair Society scoring system. RESULTS: The group in which defects were seeded with differentiated hMSCs (group 5) showed superior healing of osteochondral defects based on macroscopic and histological observations compared to other groups. Specifically, 8 weeks after implantation, defects were filled with more hyaline-like cartilage and were better integrated with the surrounding native cartilage. The histological scores were significantly better than those of other groups (16.3 at 8 weeks, p < 0.01). CONCLUSION: Xenogeneic transplantation of differentiated hMSCs using a biphasic composite construct effectively repaired osteochondral defect in a rabbit model. Differentiated hMSCs showed superior healing of chondral lesion to undifferentiated hMSCs.

Maternal exposure to airborne particulate matter during pregnancy and lactation induces kidney injury in rat dams and their male offspring: the role of vitamin D in pregnancy and beyond.

BACKGROUND: Little is known about the transgenerational effects of maternal exposure to fine particulate matter (PM2.5) on offspring kidney health. This study investigated the effect of maternal administration of PM2.5 or PM2.5 with vitamin D during pregnancy and lactation on renal injury in rat dams and their offspring. METHODS: Nine pregnant Sprague-Dawley rats received oral administration of normal saline, airborne PM2.5, or PM2.5 with vitamin D from gestational day 11 to postpartum day 21. Kidneys of rat dams (n = 3 for each group) and their male offspring (n = 5 for each group) were taken for analysis on postpartum or postnatal day 21. RESULTS: Maternal PM2.5 exposure increased glomerular damage, tubulointerstitial injury, and cortical macrophage infiltration in both dams and pups; all increases were attenuated by vitamin D administration. In dam kidneys, PM2.5 increased the protein expression of vitamin D receptor (VDR), klotho, and tumor necrosis factor-α; vitamin D lessened these changes. The expressions of renin, nuclear factor erythroid 2-related factor 2 (Nrf2), and nuclear factor-kappa B (NF-κB) p50 decreased in rat dams exposed to PM2.5. In offspring kidneys, exposure to maternal PM2.5 reduced the expression of VDR, renin, angiotensin-converting enzyme (ACE), Nrf2, and NF-κB p50, but increased cytochrome P450 24A1 expression. Maternal vitamin D administration with PM2.5 enhanced VDR, ACE, and NF-κB p50 activities in pup kidneys. CONCLUSION: PM2.5 exposure during nephrogenesis may exert transgenerational renal impairment, and maternal vitamin D intake could attenuate PM2.5-induced kidney damage in mothers and their offspring.

Subchronic particulate matter exposure underlying polyhexamethylene guanidine phosphate-induced lung injury: Quantitative and qualitative evaluation with chest computed tomography.

Our study was to explore the effects of subchronic particulate matter (PM) exposure on lung injury induced by polyhexamethylene guanidine phosphate (PHMG-p) in a rat model. Specifically, we investigated pulmonary inflammation, fibrosis, and tumor formation using chest computed tomography (CT), and histopathologic examination. PHMG-p was administered intratracheally to 20 male rats. After an initial week of PHMG-p treatment, the experimental group (PM group) received intratracheal administration of PM suspension, while the control group received normal saline. This regimen was continued for 10 weeks to induce subchronic PM exposure. Chest CT scans were conducted on all rats, followed by the extraction of both lungs for histopathological analysis. All CT images underwent comprehensive quantitative and qualitative analyses. Pulmonary inflammation was markedly intensified in rats subjected to subchronic PM exposure in the PM group compared to those in the control. Similarly, lung fibrosis was more severe in the PM group as observed on both chest CT and histopathologic examination. Quantitative chest CT analysis revealed that the mean lesion volume was significantly greater in the PM group than in the control group. Although the incidence of bronchiolo-alveolar hyperplasia was higher in the PM group compared to the control group, this difference was not statistically significant. In summary, subchronic PM exposure exacerbated pulmonary inflammation and fibrosis underlying lung injury induced by PHMG-p.

Longitudinal long term follow up investigation on the carcinogenic impact of polyhexamethylene guanidine phosphate in rat models.

Polyhexamethylene guanidine phosphate (PHMG-p) is a major component in humidifier disinfectants, which cause life-threatening lung injuries. However, to our knowledge, no published studies have investigated associations between PHMG-p dose and lung damage severity with long-term follow-up. Therefore, we evaluated longitudinal dose-dependent changes in lung injuries using repeated chest computed tomography (CT). Rats were exposed to low (0.2 mg/kg, n = 10), intermediate (1.0 mg/kg, n = 10), and high (5.0 mg/kg, n = 10) doses of PHMG-p. All rats underwent repeated CT scans after 10 and 40 weeks following the first exposure. All CT images were quantitatively analyzed using commercial software. Inflammation/fibrosis and tumor counts underwent histopathological evaluation. In both radiological and histopathologic results, the lung damage severity increased as the PHMG-p dose increased. Moreover, the number, size, and malignancy of the lung tumors increased as the dose increased. Bronchiolar-alveolar hyperplasia developed in all groups. During follow-up, there was intergroup variation in bronchiolar-alveolar hyperplasia progression, although bronchiolar-alveolar adenomas or carcinomas usually increase in size over time. Thirty-three carcinomas were detected in the high-dose group in two rats. Overall, lung damage from PHMG-p and the number and malignancy of lung tumors were shown to be dose-dependent in a rat model using repeated chest CT scans during a long-term follow-up.