Purpose
Predicting human skin permeability of chemical compounds accurately and efficiently is useful for developing dermatological medicines and cosmetics. However, previous work have two problems; ...1) quality of databases used, and 2) methods for prediction models. In this paper, we attempt to solve these two problems.
Methods
We first compile, by carefully screening from the literature, a novel dataset of chemical compounds with permeability coefficients, measured under consistent experimental conditions. We then apply machine learning techniques such as support vector regression (SVR) and random forest (RF) to our database to develop prediction models. Molecular descriptors are fully computationally obtained, and greedy stepwise selection is employed for descriptor selection. Prediction models are internally and externally validated.
Results
We generated an original, new database on human skin permeability of 211 different compounds from aqueous donors. Nonlinear SVR achieved the best performance among linear SVR, nonlinear SVR, and RF. The determination coefficient, root mean square error, and mean absolute error of nonlinear SVR in external validation were 0.910, 0.342, and 0.282, respectively.
Conclusions
We provided one of the largest datasets with purely experimental log
k
p
and developed reliable and accurate prediction models for screening active ingredients and seeking unsynthesized compounds of dermatological medicines and cosmetics.
To evaluate the accuracy of commercially available hybrid deformable image registration (DIR) algorithms when using planning CT (pCT) and daily cone‐beam computed tomography (CBCT) in radiation ...therapy for prostate cancer. The hybrid DIR algorithms in RayStation and MIM Maestro were evaluated. Contours of the prostate, bladder, rectum, and seminal vesicles (SVs) were used as region‐of‐interest (ROIs) to guide image deformation in the hybrid DIR and to compare the DIR accuracy. To evaluate robustness of the hybrid DIR for prostate cancer patients with organs with volume that vary on a daily basis, such as the bladder and rectum, the DIR algorithms were performed on ten pairs of CT volumes from ten patients who underwent prostate intensity‐modulated radiation therapy or volumetric modulated arc therapy. In a visual evaluation, MIM caused unrealistic image deformation in soft tissues, organs, and pelvic bones. The mean dice similarity coefficient (DSC) ranged from 0.46 to 0.90 for the prostate, bladder, rectum, and SVs; the SVs had the lowest DSC. Target registration error (TRE) at the centroid of the ROIs was about 2 mm for the prostate and bladder, and about 6 mm for the rectum and SVs. RayStation did not cause unrealistic image deformation, and could maintain the shape of pelvic bones in most cases. The mean DSC and TRE at the centroid of the ROIs were about 0.9 and within 5 mm generally. In both software programs, the use of ROIs to guide image deformation had the possibility to reduce any unrealistic image deformation and might be effective to keep the DIR physically reasonable. The pCT/CBCT DIR for the prostate cancer did not reduce the DIR accuracy because of the use of ROIs to guide the image deformation.
Purpose
The solvent effect on skin permeability is important for assessing the effectiveness and toxicological risk of new dermatological formulations in pharmaceuticals and cosmetics development. ...The solvent effect occurs by diverse mechanisms, which could be elucidated by efficient and reliable prediction models. However, such prediction models have been hampered by the small variety of permeants and mixture components archived in databases and by low predictive performance. Here, we propose a solution to both problems.
Methods
We first compiled a novel large database of 412 samples from 261 structurally diverse permeants and 31 solvents reported in the literature. The data were carefully screened to ensure their collection under consistent experimental conditions. To construct a high-performance predictive model, we then applied support vector regression (SVR) and random forest (RF) with greedy stepwise descriptor selection to our database. The models were internally and externally validated.
Results
The SVR achieved higher performance statistics than RF. The (externally validated) determination coefficient, root mean square error, and mean absolute error of SVR were 0.899, 0.351, and 0.268, respectively. Moreover, because all descriptors are fully computational, our method can predict as-yet unsynthesized compounds.
Conclusion
Our high-performance prediction model offers an attractive alternative to permeability experiments for pharmaceutical and cosmetic candidate screening and optimizing skin-permeable topical formulations.
Accidental ingestion of a long dental crown Takaoka, Kensuke; Minemura, Chikashi; Baba, Hiromi ...
Clinical case reports,
September 2021, Letnik:
9, Številka:
9
Journal Article
Recenzirano
Odprti dostop
It is recommended that a sharp‐pointed object, such as a dental crown, in the proximal duodenum be retrieved endoscopically if this can be accomplished safely.
It is recommended that a sharp‐pointed ...object, such as a dental crown, in the proximal duodenum be retrieved endoscopically if this can be accomplished safely.
•Primary female genital tuberculosis might develop after sexual intercourse with a male partner who has tuberculosis of the penis or epididymis. The possibility of sexual transmission has also been ...suggested by an animal model.•Nevertheless, the effectiveness of active screening for an asymptomatic female sexual partner soon after the diagnosis of male genital tuberculosis has not been reported to date.•This appears to be the first report on the sexual transmission of genital tuberculosis from a man to an asymptomatic woman detected by active screening for genital tuberculosis and whole genome sequencing.
Tuberculosis screening was performed for a healthy asymptomatic woman to determine whether she had been infected with active genital tuberculosis via sexual intercourse with her husband who had epididymal tuberculosis. Vaginal swab culture yielded Mycobacterium tuberculosis. Furthermore, whole genome sequencing revealed that the two causative isolates were genetically identical. This appears to be the first report on the sexual transmission of genital tuberculosis from a man to an asymptomatic woman, detected by active screening for genital tuberculosis and molecular analysis, including whole genome sequencing. Active screening for genital tuberculosis in the female partner should be considered soon after diagnosis of male genital tuberculosis, even when the female partner is asymptomatic.
This study aimed to examine late radiological changes after proton beam therapy (PBT) for early-stage non-small cell lung cancer (NSCLC) and to clarify correlations between mass-like radiological ...changes and patient characteristics. CT scans of patients who underwent passive scattering PBT for T1-2N0M0 NSCLC were analyzed retrospectively. Patients were considered eligible if follow-up CT was performed for at least 2 years, with no definite evidence of local recurrence. The following five periods were defined: (i) 6-12 months, (ii) 12-24 months, (iii) 24-36 months, (iv) 36-48 months and (v) 48-60 months after PBT. Late (≥6 months) radiological changes were scored by consensus of three radiation oncologists according to classifications set forth by Koenig (Radiation injury of the lung after three-dimensional conformal radiation therapy. AJR Am J Roentgenol 2002;178:1383-8.). CT scans of 113 patients (median follow-up, 36 months; range, 24-137 months) were evaluated. Late radiological changes during Periods (i), (ii), (iii), (iv) and (v) included modified conventional pattern (80%, 79%, 72%, 58% and 56%, respectively), mass-like changes (8%, 9%, 14%, 22% and 18%, respectively), scar-like changes (4%, 9%, 11%, 17% and 24%, respectively) and no increased density (8%, 3%, 3%, 2% and 2%, respectively). Mass-like changes were observed in 23 patients (20%). Among patients who developed mass-like changes, the median interval between the initiation of PBT and the onset of mass-like changes was 19 months (range, 6-62 months). In multivariate analysis, a peripheral location was found to be a significant factor (P = 0.035; odds ratio: 4.44; 95% confidence interval: 1.12-21.28). In conclusion, mass-like changes were observed in 20% of patients who underwent PBT. Patients with peripheral tumors showed a higher incidence of mass-like changes.
Introduction: To investigate enhancement by 5-fluorouracil (5-FU) of the sensitivity of cancer cells to proton beam irradiation and clarify the differences in the responses of the 5-FU-treated cells ...to proton beam irradiation according to the position of the cells on the spread-out Bragg peak (SOBP).
Methods: OE21 human esophageal squamous cells were irradiated with a 235-MeV proton beam at four different positions on the SOBP. The effects of the irradiation plus 5-FU treatment on the cell survival were assessed by clonogenic assays and determination of the sensitizer enhancement ratio (SER). In addition, DNA double-strand breaks were estimated by measuring phospho-histone H2AX (γH2AX) foci formation in the cells at 0.5 and 24 h after irradiation.
Results: The relative biological effectiveness (RBE) of proton beam irradiation against vehicle-contro
l
cells tended to increase with an increase in the depth of the cells on the SOBP. On the other hand, the degree of enhancement of the cellular sensitivity to proton beam irradiation by 5-FU was similar across all the positions on the SOBP. Furthermore, a marked increase in the number of residual γH2AX foci at 24 h post-irradiation was observed in the cells at the distal end of the SOBP.
Conclusions: Our data indicated that the degree of enhancement by 5-FU of the sensitivity of OE21 cells to 235-MeV proton beam irradiation did not differ significantly depending on the position of the cells on the SOBP. Furthermore, the degree of increase in the number of γH2AX foci at 24 h after proton beam irradiation with or without 5-FU exposure did not differ significantly according to the position on the SOBP. The effect of 5-FU in enhancing the effect of proton beam irradiation on cancer cells may be constant for all positions on the SOBP.
Background:
Radiobiological model-based studies of photon-modulated radiotherapy for pancreatic cancer have reported reduced gastrointestinal (GI) toxicity, although the risk is still high. The ...purpose of this study was to investigate the potential of 3D-passive scattering proton beam therapy (3D-PSPBT) in limiting GI organ at risk (OAR) toxicity in localized pancreatic cancer based on dosimetric data and the normal tissue complication probability (NTCP) model.
Methods:
The data of 24 pancreatic cancer patients were retrospectively analyzed, and these patients were planned with intensity-modulated radiotherapy (IMRT), volume-modulated arc therapy (VMAT), and 3D-PSPBT. The tumor was targeted without elective nodal coverage. All generated plans consisted of a 50.4-GyE (Gray equivalent) dose in 28 fractions with equivalent OAR constraints, and they were normalized to cover 50% of the planning treatment volume (PTV) with 100% of the prescription dose. Physical dose distributions were evaluated. GI-OAR toxicity risk for different endpoints was estimated by using published NTCP Lyman–Kutcher–Burman (LKB) models. Analysis of variance (ANOVA) was performed to compare the dosimetric data, and ΔNTCP
IMRT−PSPBT
and ΔNTCP
VMAT−PSPBT
were also computed.
Results:
Similar homogeneity and conformity for the clinical target volume (CTV) and PTV were exhibited by all three planning techniques (
P
> 0.05). 3D-PSPBT resulted in a significant dose reduction for GI-OARs in both the low-intermediate dose range (below 30 GyE) and the highest dose region (
D
max
and
V
50 GyE
) in comparison with IMRT and VMAT (
P
< 0.05). Based on the NTCP evaluation, the NTCP reduction for GI-OARs by 3D-PSPBT was minimal in comparison with IMRT and VMAT.
Conclusion:
3D-PSPBT results in minimal NTCP reduction and has less potential to substantially reduce the toxicity risk of upper GI bleeding, ulceration, obstruction, and perforation endpoints compared to IMRT and VMAT. 3D-PSPBT may have the potential to reduce acute dose-limiting toxicity in the form of nausea, vomiting, and diarrhea by reducing the GI-OAR treated volume in the low-to-intermediate dose range. However, this result needs to be further evaluated in future clinical studies.
Introduction
To clarify the efficacy and safety of hypofractionated proton beam therapy (PBT) for centrally located lung cancer.
Methods
We retrospectively reviewed 39 patients who received ...hypofractionated ≧3 Gy (relative biological effectiveness: RBE)/fraction PBT for centrally located cT1‐2N0M0 (8th edition) lung cancer between 1999 and 2015. A tumour within 2 cm of the proximal bronchial tree was defined as a centrally located tumour.
Results
Twenty‐four patients (62%) were treated with 80 Gy (RBE) in 20 fractions (112 Gy10), whereas eight (21%) were treated with 66 Gy (RBE) in 10 fractions (109.56 Gy10). The median follow‐up period for censored patients was 48 months (range: 4–140). The 2‐year progression‐free survival (PFS) and overall survival (OS) rates were 86 and 100% for T1 disease and 56 and 94% for T2 disease, respectively. Patients who received 110 Gy10 or higher showed significantly better PFS than those who received less than 110 Gy10, while no significant difference was noted in OS between the two groups. The sites of the first progression were local in six patients (27%), regional in seven (32%), distant in seven (32%), and local and distant in two (9%). Among the 13 patients with loco‐regional recurrence, only two (15%) received treatments with curative intent. Dyspnoea of grade 3 was noted in one patient (3%), and pneumonitis of grade 2 was noted in four patients (10%).
Conclusion
Hypofractionated PBT may be a very safe and effective treatment option for centrally located early lung cancer.
The purpose of this study was to determine the potential of escalated dose radiation (EDR) robust intensity-modulated proton radiotherapy (ro-IMPT) in reducing GI toxicity risk in locally advanced ...unresectable pancreatic cancer (LAUPC) of the head in term of normal tissue complication probability (NTCP) predictive model.
For 9 patients, intensity-modulated radiotherapy (IMRT) was compared with ro-IMPT. For all plans, the prescription dose was 59.4GyE (Gray equivalent) in 33 fractions with an equivalent organ at risk (OAR) constraints. Physical dose distribution was evaluated. GI toxicity risk for different endpoints was estimated using published NTCP Lyman Kutcher Burman (LKB) models for stomach, duodenum, small bowel, and combine stomach and duodenum (Stoduo). A Wilcoxon signed-rank test was used for dosimetry parameters and NTCP values comparison.
The dosimetric results have shown that, with similar target coverage, ro-IMPT achieves a significant dose-volume reduction in the stomach, small bowel, and stoduo in low to high dose range in comparison to IMRT. NTCP evaluation for the endpoint gastric bleeding of stomach (10.55% vs. 13.97%, P = 0.007), duodenum (1.87% vs. 5.02%, P = 0.004), and stoduo (5.67% vs. 7.81%, P = 0.008) suggest reduced toxicity by ro-IMPT compared to IMRT. ∆NTCP
(using parameter from Pan et al. for gastric bleed) of ≥5 to < 10% was seen in 3 patients (33%) for stomach and 2 patients (22%) for stoduo. An overall GI toxicity relative risk (NTCP
/NTCP
) reduction was noted (0.16-0.81) for all GI-OARs except for duodenum (> 1) with endpoint grade ≥ 3 GI toxicity (using parameters from Holyoake et al.).
With similar target coverage and better conformity, ro-IMPT has the potential to substantially reduce the risk of GI toxicity compared to IMRT in EDR of LAUPC of the head. This result needs to be further evaluated in future clinical studies.
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