Use of Receiver Operating Curve Analysis and Machine Learning With an Independent Dose Calculation System Reduces the Number of Physical Dose Measurements Required for Patient-Specific Quality Assurance.

PURPOSE: Our purpose was to assess the use of machine learning methods and Mobius 3D (M3D) dose calculation software to reduce the number of physical ion chamber (IC) dose measurements required for patient-specific quality assurance during corona virus disease 2019. METHODS AND MATERIALS: In this study, 1464 inversely planned treatments using Pinnacle or Raystation treatment planning software (TPS) were delivered using Elekta Versa HD and Varian Truebeam and Truebeam STx linear accelerators between June 2018 and November 2019. For each plan, an independent dose calculation was performed using M3D, and an absolute dose measurement was taken using a Pinpoint IC inside the Mobius phantom. The point dose differences between the TPS and M3D calculation and between TPS and IC measurements were calculated. Agreement between the TPS and IC was used to define the ground truth plan failure. To reduce the on-site personnel during the pandemic, 2 methods of receiver operating characteristic analysis (n = 1464) and machine learning (n = 603) were used to identify patient plans that would require physical dose measurements. RESULTS: In the receiver operating characteristic analysis, a predelivery M3D difference threshold of 3% identified plans that failed an IC measurement at a 4% threshold with 100% sensitivity and 76.3% specificity. This indicates that fewer than 25% of plans required a physical dose measurement. A threshold of 1% on a machine learning model was able to identify plans that failed an IC measurement at a 3% threshold with 100% sensitivity and 54.3% specificity, leading to fewer than 50% of plans that required a physical dose measurement. CONCLUSIONS: It is possible to identify plans that are more likely to fail IC patient-specific quality assurance measurements before delivery. This possibly allows for a reduction of physical measurements taken, freeing up significant clinical resources and reducing the required amount of on-site personnel while maintaining patient safety.

Topical treatment with basic fibroblast growth factor promotes wound healing and barrier recovery induced by skin abrasion.

It has been reported that basic fibroblast growth factor (bFGF) promotes the healing of skin ulceration by inducing fibroblast proliferation, yet the role of bFGF on epidermal barrier function, especially from the perspective of scratch-induced skin abrasion, remains unknown. To this end, we initially developed an epidermal abrasion mouse model induced by scratching with a stainless-steel wire brush, and examined the effects of bFGF on the wound healing induced by skin abrasion. This procedure induced a significant elevation of transepidermal water loss (TEWL) in a scratch-count-dependent manner. This elevated TEWL was significantly decreased following topical application of bFGF to the skin. In addition, bFGF increased the expression of Ki67 in keratinocytes following mechanical scratching. These results suggest that bFGF enhances keratinocyte proliferation, which, in turn, repairs the skin barrier disruption and wounds caused by scratching in mice. Consistently, bFGF stimulated proliferation of normal human epidermal keratinocytes (NHEK). Intriguingly, the effect of bFGF and other growth factors on NHEK proliferation was additive. However, high cell density diminished the effect of bFGF on NHEK proliferation. This particular result can be explained by our observation that FGF receptor mRNA expression in NHEK was low under conditions of high cell density. Our findings suggest that bFGF stimulates keratinocyte proliferation, especially in a lower cell density environment, to repair skin wound in accord with skin barrier recovery.

Five Japanese cases of antidesmoglein 1 antibody-positive and antidesmoglein 3 antibody-negative pemphigus with oral lesions.

BACKGROUND: Oral mucosal lesions develop in pemphigus vulgaris, but not in pemphigus foliaceus. This clinical phenomenon is explained by the 'desmoglein (Dsg) compensation theory'. Dsg3 and Dsg1 are major autoantigens for pemphigus vulgaris and pemphigus foliaceus, respectively. Dsg3 is overexpressed and Dsg1 is weakly expressed on the oral mucosa. Thus, on the oral mucosa, suppression of Dsg3 function by anti-Dsg3 autoantibodies is not compensated by weakly expressed Dsg1 in pemphigus vulgaris, while suppression of Dsg1 function by anti-Dsg1 autoantibodies is perfectly compensated by richly expressed Dsg3 in pemphigus foliaceus. OBJECTIVES: We present five Japanese patients with pemphigus who deviate from this theory, i.e. all patients showed oral lesions (three also had cutaneous lesions) and reacted only with Dsg1, but not with Dsg3, by enzyme-linked immunosorbent assay. METHODS: To confirm whether the unique clinical phenotypes in our patients were due to a different immunological profile from that in classical pemphigus, we examined the reactivity of the patient sera by immunoprecipitation-immunoblotting analysis using five Dsg1/Dsg2 domain-swapped molecules. RESULTS: The sera of two patients who had only oral lesions tended to react with the extracellular (EC) 5 domain of Dsg1, the domain that is considered nonpathogenic in classical pemphigus foliaceus. Sera of three patients with mucocutaneous lesions reacted with EC1 domain or with both EC1 and EC2 domains of Dsg1, like classical pemphigus foliaceus. CONCLUSIONS: These results indicate that antigenic diversity of anti-Dsg1 antibodies in these patients may cause the unique oral mucosal and cutaneous lesions, although further studies are required to elucidate the pathomechanisms.

Spatial inhibition and the visual cortex: a magnetic resonance spectroscopy imaging study.

INTRODUCTION: Deficits in processing spatial information have been observed in clinical populations who have abnormalities within the dopamine (DA) system. As psychostimulants such as methamphetamine (MA) are particularly neurotoxic to the dopaminergic system it was of interest to examine the performance of MA-dependent individuals on a task of spatial attention. METHOD: 51 MA-dependent subjects and 22 age-matched non-substance abusing control subjects were tested on a Spatial Stroop attention test. MR Spectroscopy (MRS) imaging data were analyzed from 32 MA abusers and 13 controls. RESULTS: No group differences in response time or accuracy emerged on the behavioral task with both groups exhibiting equivalent slowing when the word meaning and the spatial location of the word were in conflict. MRS imaging data from the MA abusers revealed a strong inverse correlation between NAA/Cr ratios in the Primary Visual Cortex (PVC) and spatial interference (p=0.0001). Moderate inverse correlations were also seen in the Anterior Cingulate Cortex (ACC) (p=0.02). No significant correlations were observed in the controls, perhaps due to the small sample of imaging data available (n=13). DISCUSSION: The strong correlation between spatial conflict suppression and NAA/Cr levels within the PVC in the MA-dependent individuals suggests that preserved neuronal integrity within the PVC of stimulant abusers may modulate cognitive mechanisms that process implicit spatial information.

An adult case of bleeding Meckel's diverticulum diagnosed by preoperative angiography.

A 19-year-old woman in her 6th month of pregnancy was admitted to our hospital after passing a massive bloody stool. Romanoscopy and upper gastrointestinal panendoscopy revealed no abnormality, but a superior mesenteric arteriography demonstrated an embryonic artery with the extravasation of contrast medium in the distal end of the ileal artery. After the diagnosis of a bleeding Meckel's diverticulum had been established, an emergency operation was successfully performed. At laparotomy, a Meckel's diverticulum was found, about 70 cm toward the oral side from the ileocecal valve, and part of the ileum, including the diverticulum, was resected. Histological examination indicated that the diverticulum had a normal ileal layer with ectopic gastric mucosa and pancreatic tissue. Furthermore, multiple ulcers were observed in the adjacent ileum. Blood coagulation was observed at the site of one of these ulcers, and this was presumed to be the source of the hemorrhage.

[Experimental induction of teratoma in rats].

To induce an experimental teratoma, fetuses of Wistar strain rats were removed from the uterus, and the visceral yolk sac was left hanging through the fetectomy incision. After several weeks of this treatment, a tumor developed in these animals with or without both side oophorectomy. Despite the fact that the visceral yolk sac is composed of endoderm and mesoderm, the tissues in the resulting tumor obtained from the ectopically implanted yolk sac showed derivatives from all three germ layers, including skin, bone, gut and nervous tissues. Changes in hormonal environment induced by oophorectomy did not affect the process of experimental tumor induction. When 7,12-dimethylbenz-(a)-anthracene (DMBA) was directly applied to the yolk sac at the fetectomy, a neoplasm mainly consisted of yolk sac elements was investigated after two to four months of the treatment. From the results of this experiment, it was seemed that an embryonic and extraembryonic teratomatous tumor might have been derived from the visceral yolk sac.

[Induced rat ovarian carcinoma showing mainly squamous components--an experimental approach to common epithelial tumors].

Female Wistar strain rats were treated with a chemical carcinogen DMBA (7,12-Dimethylbenz (a) anthracene) implanted directly into their ovary. In this method of tumor induction, adenocarcinoma commonly developed in the ovary by the direct carcinogenic effect of DMBA during a 30 weeks observation period. However, two cases of primary ovarian carcinoma showing mainly squamous components have been found in a recent experiments. The histological characteristics of these indicated that they were adenoacanthoma and adenosquamous cell carcinoma and both were derived ultimately from the ovarian surface epithelium with interposition of endometrioid type tumor. These two cases of experimental rat ovarian cancer consist of mainly squamous element are studied morphologically and their histogenesis is discussed.

Chemotherapy of malignant ovarian tumors; therapeutic results of ifosfamide.

Here are reported the therapeutic results of ifosfamide on primary ovarian malignancies in 30 cases which were treated at Kurume University Hospital from September 1978 to December 1980. These cases were advanced or recurrent ones, and histologically, they consisted of serous cystadenocarcinoma in 22 cases, mucinous cystadenocarcinoma in 2, unclassified adenocarcinoma in 1, and malignant teratoma in 5. In the ifosfamide therapy, 2 grams or 40 mg/kg per day were given intravenously for 5 consecutive days, and as observing the blood state and the general condition, it was repeated every 3 weeks. The drug was given from 1 to 7 courses, and the average was 3.3 courses. The effect was evaluated by Koyama-Saito's criteria and Karnofsky's criteria; the response rate was 48% in the adenocarcinoma group and 20% in the malignant teratoma by the former criteria, while the rate was 64% and 20%, respectively, by the latter one. As main side effects, there were seen hemorrhagic cystitis, nausea and vomiting, and the myelotoxicity was low.

Malignant degeneration of benign cystic teratomas of the ovary.

In 10 years from January 1971 to January 1981, 145 cases with cystic teratoma were treated at Kurume University Hospital, and malignant degeneration was seen in 7 of them (4.8%). Their age distribution was from 43 to 78 years, and the mean age was 59 years; the distribution shifted to the older side. The malignant degeneration was squamous cell carcinoma in all of the cases, and in 1 case carcinoma in situ leads to invasive carcinoma was observed continuously to a normal epithelium; it was interesting histogenetically. In their prognoses 3 out of 7 cases died (1 case dying from decrepitude) but the rest 4 have been surviving for 4 to 10 years.