Prediction of nodal metastasis based on intraoral sonographic findings of the primary lesion in early-stage tongue cancer.

The aim of this study was to clarify the correlation between imaging findings obtained using intraoral ultrasonography (US) and pathological findings of tongue cancers, and to examine the predictive value of intraoral US findings with respect to occult nodal metastasis. This was a retrospective study based on the medical records of 123 patients with T1-2N0 tongue cancer. The depth of invasion (DOI) on intraoral US was positively correlated with the pathological invasion depth (PID) (ρ = 0.7080, P < 0.0001). Receiver operating characteristic analyses revealed an optimal DOI cut-off value of 4.1 mm and optimal PID cut-off value of 3.9 mm to detect nodal metastasis. Regarding the margin shape of the primary tumour on intraoral US, the incidence of nodal metastasis was significantly higher for the permeated type than for the pressure type (P < 0.001) and wedge-shaped type (P = 0.002). Furthermore, tumours with peritumoural vascularity assessed by power Doppler US had a significantly higher incidence of nodal metastasis than tumours without (P = 0.003). The sensitivity, specificity, and accuracy of the permeated type to predict nodal metastasis was 53.6%, 95.8%, and 86.2%, respectively. These results suggest that intraoral US findings closely reflect pathological findings and could be useful to predict occult nodal metastasis in patients with early-stage tongue cancer.

Monobody adapter for functional antibody display on nanoparticles for adaptable targeted delivery applications.

Vascular endothelial cells (ECs) play a central role in the pathophysiology of many diseases. The use of targeted nanoparticles (NPs) to deliver therapeutics to ECs could dramatically improve efficacy by providing elevated and sustained intracellular drug levels. However, achieving sufficient levels of NP targeting in human settings remains elusive. Here, we overcome this barrier by engineering a monobody adapter that presents antibodies on the NP surface in a manner that fully preserves their antigen-binding function. This system improves targeting efficacy in cultured ECs under flow by >1000-fold over conventional antibody immobilization using amine coupling and enables robust delivery of NPs to the ECs of human kidneys undergoing ex vivo perfusion, a clinical setting used for organ transplant. Our monobody adapter also enables a simple plug-and-play capacity that facilitates the evaluation of a diverse array of targeted NPs. This technology has the potential to simplify and possibly accelerate both the development and clinical translation of EC-targeted nanomedicines.

Synthesis of an azadioxa-planar triphenylborane and investigation of its structural and photophysical properties.

We report here the first successful synthesis of planar triphenylborane 1 with the phenyl groups bridged by oxygen and nitrogen atoms via double nucleophilic aromatic substitution reaction. The hetero atom-bridged 1 has excellent planarity. Its structural and photophysical properties are tunable by altering the bridging atoms.

Elevated expression of protease-activated receptor 1 via ΔNp63 down-regulation contributes to nodal metastasis in oral squamous cell carcinoma.

Protease-activated receptor 1 (PAR1) is known as a thrombin receptor. Recent studies have reported PAR1 expression in various malignancies; however, its role in oral squamous cell carcinoma (OSCC) requires clarification. A previous study showed that down-regulation of ΔNp63, a homolog of p53, augments PAR1 expression in OSCC. In the present study, the association of PAR1 expression with clinicopathological findings in OSCC was examined retrospectively. Expression of PAR1, thrombin, and ΔNp63 was examined immunohistochemically in OSCC specimens. Patients were divided into three groups based on the expression pattern of PAR1 at the invasive front: group A, PAR1-negative in both cancer and stromal cells; group B, positive in stromal cells but negative in cancer cells; group C, positive in both cancer and stromal cells. Histologically high-grade tumours were significantly more common in group C. Patients in group C had the highest incidence rate of nodal metastasis (P<0.001) and a lower survival rate (P=0.085) than those in the other groups. At the invasive front, in group C, thrombin was expressed but ΔNp63 expression was weak. These results indicate that increased PAR1 expression in both cancer and stromal cells could be a useful predictive marker of nodal metastasis and that ΔNp63 is involved in regulating PAR1 expression.

Trend of strengthening clearance regulation in Japan and concerns about its worldwide effects on regulations for natural and artificial radionuclides.

The Nuclear Regulation Authority (NRA) of Japan invited comments from the public on a revised guide on measurement and evaluation for clearance in 2019, which included a strict decision on how to treat uncertainties in the measurement and the nuclide vector. To resolve the issue on the uncertainty in clearance, a probabilistic approach had been established previously in the Atomic Energy Society of Japan Standard and incorporated into International Atomic Energy Agency (IAEA) Safety Report No. 67. NRA's new decision on the uncertainty in clearance was up to 10 times stricter than the probabilistic approach. This issue has been discussed at an international level in the framework of the ongoing revision of IAEA Safety Guide RS-G-1.7. This discussion on the uncertainty in clearance has raised serious concerns about its effects on other radiological protection regulations worldwide. This is because if we need strict treatment for the uncertainty in clearance, the same or even stricter treatment for conformity assessment may have to be applied to other radiological protection criteria for doses exceeding 10 µSv year-1. Radiological protection experts including regulators, professionals, and operators should be aware of the essential meaning of the radiological protection criteria by considering the background scientific basis on which they were established.

Progressive supranuclear palsy often develops idiopathic normal pressure hydrocephalus-like magnetic resonance imaging features.

BACKGROUND AND PURPOSE: Idiopathic normal pressure hydrocephalus (iNPH) is a clinical entity without established pathological hallmarks. Previous autopsy studies reported that patients with an antemortem diagnosis of iNPH had a different postmortem diagnosis, commonly progressive supranuclear palsy (PSP). Disproportionately enlarged subarachnoid space hydrocephalus (DESH) has been reported as a characteristic feature of iNPH on magnetic resonance imaging (MRI). In addition, periventricular white matter hyperintensities (PVHs) are noted in most patients with iNPH; these PVHs are supposed to reflect transependymal movement of ventricular cerebrospinal fluid. It is hypothesized that PSP develops more iNPH-like MRI features than other neurodegenerative disorders. METHODS: Thirty-eight patients with a clinical diagnosis of PSP, 42 with Parkinson's disease (PD) without dementia, 30 with PD with dementia (PDD) and 29 with Alzheimer's disease (AD) were enrolled. The DESH score and PVH grade were measured using the conventional MRI sequence and were compared amongst the patient groups. RESULTS: Disproportionately enlarged subarachnoid space hydrocephalus score was significantly higher in patients with PSP than PD without dementia, and there was a trend that the DESH score was higher in patients with PSP than PDD or Alzheimer's disease. PVH grade was significantly larger in patients with PSP than PD without dementia. In the components of the DESH score, callosal angle was significantly smaller in patients with PSP than in PD without dementia or PDD. CONCLUSIONS: This study demonstrated that some PSP patients develop iNPH-like MRI features, suggesting the presence of iNPH-like features in the clinical spectrum of PSP. A clinical phenotype of PSP with hydrocephalus is proposed, which should be further investigated in future studies.

Phylogenetic placement of Paratrichaptum and reconsideration of Gloeophyllales.

Paratrichaptum accuratum is a large conspicuous polypore fungus growing on dead or living angiosperm trees in subtropical-boreal areas of China, Indonesia, Japan, and Taiwan. The present study places P. accuratum in the family Gloeophyllaceae that belongs to the order Gloeophyllales within Agaricomycetes (Basidiomycota), based on evidence derived from morphological and ecological characteristics, and phylogenetic analyses of sequences of nuclear rDNA regions (5.8S, nuc 18S, nuc 28S) and protein-coding genes (rpb1, rpb2, and tef1). The analyses presented in this study also give strong support for including Jaapia in Gloeophyllaceae and Gloeophyllales. Thus, the names Jaapiaceae and Jaapiales are considered here as synonyms of Gloeophyllaceae and Gloeophyllales. Since Paratrichaptum represents the earliest diverging lineage in Gloeophyllales, pileate basidiocarps and brown rot appear to be ancestral states of Gloeophyllales. Paratrichaptum accuratum may represent a relic species, according to its phylogenetic position, peculiar distribution pattern and rare occurrence.

Pressure-induced stacking disorder in boehmite.

The structure of an aluminum layered hydroxide, boehmite (γ-AlOOH), as a function of pressure was studied by using in situ synchrotron X-ray and neutron diffraction. Peak broadening, which is only found for hkl (h ≠ 0) peaks in the X-ray diffraction patterns, is explained by stacking disorder accompanying a continuously increasing displacement of the AlO6 octahedral layer along the a-axis. This finding could be the first experimental result for pressure-induced stacking disorder driven by continuous layer displacement. The magnitude of the layer displacement was estimated from the X-ray scattering profile calculation based on the stacking disordered structure model. Hydrogen bond geometries of boehmite, obtained by structure refinements of the observed neutron diffraction patterns for the deuterated sample up to 10 GPa, show linearly approaching O-D covalent and DO hydrogen bond distances and they merge below 26 GPa. Pressure-induced stacking disorder makes the electrostatic potential of hydrogen bonds asymmetric, yielding less chance for proton-tunnelling.

Evidence for Spin Singlet Pairing with Strong Uniaxial Anisotropy in URu_{2}Si_{2} Using Nuclear Magnetic Resonance.

In order to identify the spin contribution to superconducting pairing compatible with the so-called "hidden order", ^{29}Si nuclear magnetic resonance measurements have been performed using a high-quality single crystal of URu_{2}Si_{2}. A clear reduction of the ^{29}Si Knight shift in the superconducting state has been observed under a magnetic field applied along the crystalline c axis, corresponding to the magnetic easy axis. These results provide direct evidence for the formation of spin-singlet Cooper pairs. Consequently, results indicating a very tiny change of the in-plane Knight shift reported previously demonstrate extreme uniaxial anisotropy for the spin susceptibility in the hidden order state.

Influence of food on the gastric motor effect of the Kampo medicine rikkunshito in rat.

BACKGROUND: Rikkunshito, one of the Kampo medicines, is widely prescribed as a remedy for various upper gastrointestinal syndromes. The effect of rikkunshito is related to endogenous ghrelin and its active ingredient atractylodin enhances ghrelin receptor signaling. Kampo medicines are traditionally administered before or between meals; however, no definitive benefit of the timing of administration has been proven yet. To clarify the influence of food on the pharmacological action of rikkunshito, we investigated the gastric motor activity and pharmacokinetic profiles of atractylodin after the administration of rikkunshito in fasted and fed rats. METHODS: Phase III-like contractions in the gastric antrum after an injection of ghrelin were measured using a strain gauge force transducer. Rikkunshito was administered to rats during fasting or after a nutrient test meal. Ghrelin was injected 30 minutes later and gastric motility was evaluated. Furthermore, after rikkunshito administration, the pharmacokinetic profiles of atractylodin in the plasma and brain of fasted and free-fed rats were assessed. KEY RESULTS: Rikkunshito administration potentiated ghrelin-induced phase III-like contractions under fasting conditions. This effect was attenuated in animals fed a test meal. Atractylodin was detected pharmacokinetically in the plasma and brain after rikkunshito administration in rats, and free-fed rats exhibited a decreased maximum concentration of plasma atractylodin and a delayed time to reach the maximum concentration. CONCLUSIONS & INFERENCES: We show that the pharmacological action of rikkunshito is influenced by food in rats. The efficacy of rikkunshito may be associated with decreased absorption of its active ingredient atractylodin when food is in the stomach.

The relationship between three signs of fetal magnetic resonance imaging and severity of congenital diaphragmatic hernia.

OBJECTIVE: To seek a simple approach for prenatally classifying congenital diaphragmatic hernia (CDH) severity using fetal magnetic resonance imaging (MRI) markers. STUDY DESIGN: A retrospective, multicenter study using questionnaires to investigate fetal MRI findings. We included fetuses prenatally diagnosed with isolated left-sided CDH and delivered after 36 weeks of gestation. We focused on three fetal MRI morphological signs: incomplete pulmonary baseline (IPB), liver up (LU) and retrocardiac stomach (RCS). We also evaluated the fetal MRI score defined as the total number of positive signs; the primary outcome was survival at discharge. RESULTS: In 256 patients (from 56 institutions), IPB, LU and RCS findings correlated with lower survival: odds ratio (95% confidence interval), 0.16 (0.08 to 0.33); 0.24 (0.12 to 0.51); and 0.14 (0.07 to 0.28); respectively. Patients with higher fetal MRI scores had a higher mortality rate. CONCLUSION: IPB, LU and RCS on fetal MRI are related to CDH severity.

Effect of temperature, relative humidity and rainfall on dengue fever and leptospirosis infections in Manila, the Philippines.

Dengue fever (DF) and leptospirosis are serious public problems in tropical regions, especially in Manila, the Philippines. In attempting to understand the causes of DF and leptospirosis seasonality, meteorological factors have been suspected, but quantitative correlation between seasonality and meteorological factors has not been fully investigated. In this study, we investigated correlation of temporal patterns of reported numbers of laboratory-confirmed cases of both DF and leptospirosis with meteorological conditions (temperature, relative humidity, rainfall) in Manila. We used time-series analysis combined with spectral analysis and the least squares method. A 1-year cycle explained underlying variations of DF, leptospirosis and meteorological data. There was a peak of the 1-year cycle in temperature during May, followed by maxima in rainfall, relative humidity and number of laboratory-confirmed DF and leptospirosis cases. This result suggests that DF and leptospirosis epidemics are correlated not only with rainfall but also relative humidity and temperature in the Philippines. Quantifying the correlation of DF and leptospirosis infections with meteorological conditions may prove useful in predicting DF and leptospirosis epidemics, and health services should plan accordingly.

Novel Mycobacterium avium Complex Species Isolated From Black Wildebeest (Connochaetes gnou) in South Africa.

A study was undertaken to isolate and characterize Mycobacterium species from black wildebeest suspected of being infected with tuberculosis in South Africa. This led to the discovery of a new Mycobacterium avium complex species, provisionally referred to as the Gnou isolate from black wildebeest (Connochaetes gnou). Sixteen samples from nine black wildebeest were processed for Mycobacterium isolation. Following decontamination, samples were incubated in an ordinary incubator at 37°C on Löwenstein-Jensen slants and in liquid medium tubes using the BACTEC™ MGIT™ 960 system, respectively. Identification of the isolate was carried out by standard biochemical tests and using the line probe assay from the GenoType® CM/AS kit (Hain Lifescience GmbH, Nehren, Germany). The DNA extract was also analysed using gene sequencing. Partial gene sequencing and analysis of 16S rRNA gene, and 16S-23S rRNA (ITS), rpoB and hsp65 and phylogenetic analyses by searching GenBank using the BLAST algorithm were conducted. Phylogenetic trees were constructed using four methods, namely Bayesian inference, maximum likelihood, maximum parsimony and neighbour-joining methods. The isolate was identified as Mycobacterium intracellulare using the GenoType® CM/AS kit and as Mycobacterium avium complex (MAC) by gene sequencing. The gene sequence targeting all the genes, ITS, 16S rRNA, rpoB and hsp65 and phylogenetic analyses indicated that this isolate presented a nucleotide sequence different from all currently published sequences, and its position was far enough from other MAC species to suggest that it might be a new species.

Quantitative assessment of provability of radiation-related cancers considering unavoidable existence of unadjusted risk factors.

The attribution of stochastic effects to exposure to ionizing radiation has been qualitatively discussed by introducing two distinct concepts of provability and probability. This study aims to develop a method of quantitatively assessing the provability of radiation-related cancers. To this end, the 'minimum provable dose' (MPD) was developed and applied to actual cancer mortality in Japan. The background lifetime risk of cancer mortality was calculated for the esophagus, stomach, colon, liver, lungs, skin, breasts, ovaries, bladder, and bone marrow as well as the age-specific risk coefficients reproducing those given in the 2007 Recommendations of the International Commission on Radiological Protection (ICRP). Comparing the relative ratio of MPDs, which was defined herein as the 'provability index' (PI), we quantitatively ranked radiation-related cancers for different tissues and organs predicated on provability for ages of 10, 30, 50, and 0-85+ years at exposure. We discuss the radiological protection of male emergency workers focusing on cancers highly prioritized according to the ranking (i.e. colon, bone marrow, and bladder). The present study proposed the system to quantitatively evaluate the level of radiological protection taking into account the variations of the background cancer risk on the provability of radiation-related cancers.

Ice VII from aqueous salt solutions: From a glass to a crystal with broken H-bonds.

It has been known for decades that certain aqueous salt solutions of LiCl and LiBr readily form glasses when cooled to below ≈160 K. This fact has recently been exploited to produce a « salty ¼ high-pressure ice form: When the glass is compressed at low temperatures to pressures higher than 4 GPa and subsequently warmed, it crystallizes into ice VII with the ionic species trapped inside the ice lattice. Here we report the extreme limit of salt incorporation into ice VII, using high pressure neutron diffraction and molecular dynamics simulations. We show that high-pressure crystallisation of aqueous solutions of LiCl∙RH2O and LiBr∙RH2O with R = 5.6 leads to solids with strongly expanded volume, a destruction of the hydrogen-bond network with an isotropic distribution of water-dipole moments, as well as a crystal-to-amorphous transition on decompression. This highly unusual behaviour constitutes an interesting pathway from a glass to a crystal where translational periodicity is restored but the rotational degrees of freedom remaining completely random.

Adsorbed states of chlorophenol on Cu(110) and controlled switching of single-molecule junctions.

A molecular junction of substituted benzene (chlorophenol) is fabricated and controlled by using a scanning tunneling microscope (STM). Prior to the junction formation, the bonding geometry of the molecule on the surface is characterized by STM and electron energy loss spectroscopy (EELS). EELS shows that the OH group of chlorophenol is dissociated on Cu(110) and that the molecule is bonded nearly flat to the surface via an O atom, with the Cl group intact. We demonstrate controlled contact of an STM tip to the "available" Cl group and lift-up of the molecule while it is anchored to the surface via an O atom. The asymmetric bonding motifs of the molecule to the electrodes allow for reversible control of the junction.

Partially ordered state of ice XV.

Most ice polymorphs have order-disorder "pairs" in terms of hydrogen positions, which contributes to the rich variety of ice polymorphs; in fact, three recently discovered polymorphs- ices XIII, XIV, and XV-are ordered counter forms to already identified disordered phases. Despite the considerable effort to understand order-disorder transition in ice crystals, there is an inconsistency among the various experiments and calculations for ice XV, the ordered counter form of ice VI, i.e., neutron diffraction observations suggest antiferroelectrically ordered structures, which disagree with dielectric measurement and theoretical studies, implying ferroelectrically ordered structures. Here we investigate in-situ neutron diffraction measurements and density functional theory calculations to revisit the structure and stability of ice XV. We find that none of the completely ordered configurations are particular favored; instead, partially ordered states are established as a mixture of ordered domains in disordered ice VI. This scenario in which several kinds of ordered configuration coexist dispels the contradictions in previous studies. It means that the order-disorder pairs in ice polymorphs are not one-to-one correspondent pairs but rather have one-to-n correspondence, where there are n possible configurations at finite temperature.