Human movement decisions during Coronavirus Disease 2019

To predict epidemics' future course in changing situations, understanding human mobility patterns is important, notwithstanding decision-making process uncertainties owing to difficulties in quantifying people's mobility change decision timings, which make the mobility-epidemic causal relationship unclear. We used the 'mobility avoidance index' to investigate time-series changes during Japan's Coronavirus Disease 2019 (eight waves until February 2023) as a previous study, which measured this index using accommodation reservation data-booking/cancellation timings-was able to quantify the timing of decision-making for mobility changes. Our analyses revealed two general patterns: 1) the index increased/decreased proportional to logarithms of reported cases during the first wave, conforming with Weber-Fechner's psychophysics law; 2) its slope against the change in the number of reported cases had similar values among the waves, but its intercepts changed as the waves passed, suggesting that people neglected reported cases lower than a certain threshold for behavioural decision-making. We shifted the threshold level as the waves passed, and named this pattern 'shift of negligible epidemic' rule. It is the first pattern quantitatively observed, that possesses decision making tendencies for future mobility avoidance. Our findings contribute to constructing a mathematical model, which simultaneously considers epidemics and human mobility dynamics

Role of prostaglandin E receptor subtypes EP2 and EP4 in autocrine and paracrine functions of vascular endothelial growth factor in the inner ear

<p>Abstract</p> <p>Background</p> <p>The physiological effects of prostaglandin E1 (PGE1) and prostaglandin E2 (PGE2) are mediated by the prostaglandin E receptor subtypes EP1, EP2, EP3, and EP4, and the respective agonists have been purified. PGE1 and PGE2 can increase the production of vascular endothelial growth factor (VEGF), particularly through EP2 and EP4. The biological effects of VEGF are mediated by the phosphotyrosine kinase receptors fms-related tyrosine kinase-1 (Flt-1) and fetal liver kinase-1 (Flk-1). Here we examined the effects of EP2 and EP4 agonists on the production of VEGF proteins and <it>VEGF </it>messenger RNAs (mRNAs) in the inner ear, using an enzyme-linked immunosorbent assay and the real-time quantitative reverse transcription-polymerase chain reaction, respectively. We also examined the localization of EP2, VEGF, Flt-1, and Flk-1 in the cochlea by immunohistochemistry.</p> <p>Results</p> <p>The expression of EP2 occurred in the cochlea, and the local application of an EP2 or EP4 agonist increased VEGF protein and <it>VEGF </it>mRNA levels in the inner ear. Furthermore, the intensity of the VEGF immunoreactivity in the spiral ganglion appeared to be increased by the local EP2 or EP4 agonist treatment. Immunoreactivity for Flt-1, and Flk-1 was found in the cochlear sensory epithelium, spiral ganglion, spiral ligament, and stria vascularis.</p> <p>Conclusions</p> <p>These findings demonstrate that EP2 and EP4 agonists stimulate VEGF production in the inner ear, particularly in the spiral ganglions. Moreover, the Flt-1 and Flk-1 expression observed in the present study suggests that VEGF has autocrine and paracrine actions in the cochlea. Thus, EP2 and EP4 might be involved in the mechanisms underlying the therapeutic effects of PGE1 on acute sensorineural hearing loss via VEGF production.</p

Groove Pancreatitis with Several Cystic Lesions around the Pancreatic Head Treated Conservatively: Report of a Case

A 61-year-old man was admitted to our hospital with epigastric pain and vomiting. Enhanced abdominal computed tomography revealed inflammatory change of the pancreatic groove and focal wall thickening of the second portion of the duodenum with several cystic lesions around the head of the pancreas. We diagnosed atypical type of groove pancreatitis. The patient made a satisfactory recovery by conservative medication treatment for acute on chronic pancreatitis and cystic lesions disappeared in parallel with pancreatitis. Groove pancreatitis is a rare form of chronic pancreatitis, and to the best of our knowledge, our patient is the first case in the English literature of groove pancreatitis with cystic lesions around the head of the pancreas, which disappeared after conservative treatment for pancreatitis

Lifetime attributable risk of radiation-induced secondary cancer from proton beam therapy compared with that of intensity-modulated X-ray therapy in randomly sampled pediatric cancer patients

To investigate the amount that radiation-induced secondary cancer would be reduced by using proton beam therapy (PBT) in place of intensity-modulated X-ray therapy (IMXT) in pediatric patients, we analyzed lifetime attributable risk (LAR) as an in silico surrogate marker of the secondary cancer after these treatments. From 242 pediatric patients with cancers who were treated with PBT, 26 patients were selected by random sampling after stratification into four categories: (i) brain, head and neck, (ii) thoracic, (iii) abdominal, and (iv) whole craniospinal (WCNS) irradiation. IMXT was replanned using the same computed tomography and region of interest. Using the dose-volume histograms (DVHs) of PBT and IMXT, the LARs of Schneider et al. were calculated for the same patient. All the published dose-response models were tested for the organs at risk. Calculation of the LARs of PBT and IMXT based on the DVHs was feasible for all patients. The means +/- standard deviations of the cumulative LAR difference between PBT and IMXT for the four categories were (i) 1.02 +/- 0.52% (n = 7, P = 0.0021), (ii) 23.3 +/- 17.2% (n = 8, P = 0.0065), (iii) 16.6 +/- 19.9% (n = 8, P = 0.0497) and (iv) 50.0 +/- 21.1% (n = 3, P = 0.0274), respectively (one tailed t-test). The numbers needed to treat (NNT) were (i) 98.0, (ii) 4.3, (iii) 6.0 and (iv) 2.0 for WCNS, respectively. In pediatric patients who had undergone PBT, the LAR of PBT was significantly lower than the LAR of IMXT estimated by in silico modeling. Although a validation study is required, it is suggested that the LAR would be useful as an in silico surrogate marker of secondary cancer induced by different radiotherapy techniques

Relationship between lymph node metastasis and E-cadherin expression in submucosal invasive gastric carcinomas with gastric-phenotype

Background : Recent advances in immunohistochemical staining have led to the proposition of a classification of gastric carcinomas based on cellular phenotypes, and the degree of biological malignancy of gastric-phenotype carcinomas has attracted particular attention. Subjects and Methods : One hundred and seven submucosal (SM) invasive carcinomas encountered in our center were examined for their histological type, cellular phenotype, and E-cadherin expression status to clarify their relationships with lymph node metastasis. Results : Eleven (10.3%) of 107 SM gastric carcinomas were lymph node metastasis-positive. Gastric-phenotype carcinomas accounted for 20.6%, with a lymph node metastasis rate of 27.3% (6/22), which was significantly higher (p<0.05) than those of intestinal-phenotype carcinomas (5.9%) and mixed-phenotype carcinomas (2.9%). In terms of E-cadherin expression, only carcinomas with reduced E-cadherin expression showed lymph node metastasis at a rate significantly higher than that of carcinomas with normal E-cadherin expression (p<0.05). The lymph node metastasis rate (46.2%) of gastric-phenotype carcinomas with reduced E-cadherin expression was significantly higher than those of carcinomas of other phenotypes (p<0.05). Conclusion : Since gastric-phenotype differentiated carcinomas with reduced E-cadherin expression have the potential for becoming undifferentiated, the risk of lymph node metastasis should be considered

Disorganization of Semantic Brain Networks in Schizophrenia Revealed by fMRI

OBJECTIVES: Schizophrenia is a mental illness that presents with thought disorders including delusions and disorganized speech. Thought disorders have been regarded as a consequence of the loosening of associations between semantic concepts since the term "schizophrenia" was first coined by Bleuler. However, a mechanistic account of this cardinal disturbance in terms of functional dysconnection has been lacking. To evaluate how aberrant semantic connections are expressed through brain activity, we characterized large-scale network structures of concept representations using functional magnetic resonance imaging (fMRI). STUDY DESIGN: We quantified various concept representations in patients' brains from fMRI activity evoked by movie scenes using encoding modeling. We then constructed semantic brain networks by evaluating the similarity of these semantic representations and conducted graph theory-based network analyses. STUDY RESULTS: Neurotypical networks had small-world properties similar to those of natural languages, suggesting small-worldness as a universal property in semantic knowledge networks. Conversely, small-worldness was significantly reduced in networks of schizophrenia patients and was correlated with psychological measures of delusions. Patients' semantic networks were partitioned into more distinct categories and had more random within-category structures than those of controls. CONCLUSIONS: The differences in conceptual representations manifest altered semantic clustering and associative intrusions that underlie thought disorders. This is the first study to provide pathophysiological evidence for the loosening of associations as reflected in randomization of semantic networks in schizophrenia. Our method provides a promising approach for understanding the neural basis of altered or creative inner experiences of individuals with mental illness or exceptional abilities, respectively

Clinicopathological evaluation of biological behavior of submucosal invasive gastric carcinomas : relationship among lymph node metastasis, mucin phenotype and proliferative activity

Background : Gastric carcinomas have been classified into the differentiated and undifferentiated type, on the basis of its tendency to gland formation. As a result of recent advances in mucin histochemistry, mucin phenotypes of gastric carcinomas have been investigated. However, no consensus on the evaluation of the grade of malignancy of early gastric carcinomas regarding mucin phenotype expression has developed. To address this issue, we evaluated the lymph node metastasis rate and proliferative activity of a submucosal invasive (sm) gastric carcinoma according to mucin phenotype expression. Methods : In resected surgical specimens from 108 patients with a single sm gastric carcinoma, the association between clinicopathological factors and lymph node metastasis was evaluated. In all cases, immunohistochemical staining with human gastric mucin, Muc-2, and CD10 and mucin histochemical staining by paradoxical concanavalin A staining were performed. The mucin phenotypes were classified into gastric-type (G-type), intestinal-type (I-type), mixed gastric and intestinal type (M-type), or a lack of mucin (LOM), using these as markers. To evaluate the cell proliferative activity of the gastric carcinoma, proliferating cell nuclear antigen (PCNA) staining was also performed. Results : The rate of lymph node metastasis was higher for G-type sm carcinomas. A multivariate analysis showed that the G-type and lymphatic invasion were independent factors of lymph node metastasis. However, the PCNA-labeling index (PCNA-LI) was low for G-type carcinomas irrespective of the presence or absence of lymph node metastasis. In I-type carcinomas, PCNA-LI was significantly higher in cases that were positive for lymph node metastasis than in negative cases. Conclusion : G-type and lymphatic invasion are independent risk factors for lymph node metastasis of an sm gastric carcinoma, and proliferative activity may be a significant parameter for lymph node metastasis in cases with I-type carcinomas

Lifetime attributable risk of radiation-induced secondary cancer from proton beam therapy compared with that of intensity-modulated X-ray therapy in randomly sampled pediatric cancer patients

To investigate the amount that radiation-induced secondary cancer would be reduced by using proton beam therapy (PBT) in place of intensity-modulated X-ray therapy (IMXT) in pediatric patients, we analyzed lifetime attributable risk (LAR) as an in silico surrogate marker of the secondary cancer after these treatments. From 242 pediatric patients with cancers who were treated with PBT, 26 patients were selected by random sampling after stratification into four categories: (i) brain, head and neck, (ii) thoracic, (iii) abdominal, and (iv) whole craniospinal (WCNS) irradiation. IMXT was replanned using the same computed tomography and region of interest. Using the dose–volume histograms (DVHs) of PBT and IMXT, the LARs of Schneider et al. were calculated for the same patient. All the published dose–response models were tested for the organs at risk. Calculation of the LARs of PBT and IMXT based on the DVHs was feasible for all patients. The means ± standard deviations of the cumulative LAR difference between PBT and IMXT for the four categories were (i) 1.02 ± 0.52% (n = 7, P = 0.0021), (ii) 23.3 ± 17.2% (n = 8, P = 0.0065), (iii) 16.6 ± 19.9% (n = 8, P = 0.0497) and (iv) 50.0 ± 21.1% (n = 3, P = 0.0274), respectively (one tailed t-test). The numbers needed to treat (NNT) were (i) 98.0, (ii) 4.3, (iii) 6.0 and (iv) 2.0 for WCNS, respectively. In pediatric patients who had undergone PBT, the LAR of PBT was significantly lower than the LAR of IMXT estimated by in silico modeling. Although a validation study is required, it is suggested that the LAR would be useful as an in silico surrogate marker of secondary cancer induced by different radiotherapy techniques