The Efficacy of Immunotherapy and Clinical Utility of Comprehensive Genomic Profiling in Adenoid Cystic Carcinoma of Head and Neck.

Background and Objectives: Adenoid cystic carcinoma (ACC) of the head and neck is generally slow-growing but has a high potential for local recurrence and metastasis to distant organs. There is currently no standard pharmacological treatment for recurrent/metastatic (R/M) ACC, and there are cases in which immune checkpoint inhibitors (ICIs) are administered for ACC according to head and neck squamous cell carcinoma (HNSCC). However, the efficacy of ICIs for ACC remains unclear, and the predictive biomarkers need to be elucidated. Materials and Methods: The Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database enabled the retrospective but nationwide analysis of 263 cases of ACC of the head and neck. Then, we examined and reported four cases of ACC that received ICIs and comprehensive genomic profiling (CGP) in our institution. Results: The C-CAT database revealed that 59 cases out of 263 received ICIs, and the best response was 8% of objective response rate (ORR) and 53% of disease control rate (DCR) (complete response, CR 3%, partial response, PR 5%, stable disease, SD 44%, progressive disease, PD 19%, not evaluated, NE 29%). The tumor mutational burden (TMB) in ACC was lower overall compared to HNSCC and could not be useful in predicting the efficacy of ICIs. Some cases with MYB structural variants showed the response to ICIs in the C-CAT database. A patient with MYB fusion/rearrangement variants in our institution showed long-term stable disease. Conclusions: ICI therapy is a potential treatment option, and the MYB structural variant might be a candidate for predictive biomarkers for immunotherapy in patients with R/M ACC.

Catalytic Behavior of K-doped Fe/MgO Catalysts for Ammonia Synthesis Under Mild Reaction Conditions.

An important part of realizing a carbon-neutral society using ammonia will be the development of an inexpensive yet efficient catalyst for ammonia synthesis under mild reaction conditions (<400 °C, <10 MPa). Here, we report Fe/K(3)/MgO, fabricated via an impregnation method, as a highly active catalyst for ammonia synthesis under mild reaction conditions (350 °C, 1.0 MPa). At the mentioned conditions, the activity of Fe/K(3)/MgO (17.5 mmol h-1 gcat -1 ) was greater than that of a commercial fused iron catalyst (8.6 mmol h-1 gcat -1 ) currently used in the Haber-Bosch process. K doping was found to increase the ratio of Fe0 on the surface and turnover frequency of Fe in our Fe/K(3)/MgO catalyst. In addition, increasing the pressure to 3.0 MPa at the same temperature led to a significant improvement of the ammonia synthesis rate to 29.6 mmol h-1 gcat -1 , which was higher than that of two more expensive, benchmark Ru-based catalysts, which are also potential alternative catalysts. A kinetics analysis revealed that the addition of K enhanced the ammonia synthesis activity at ≥300 °C by changing the main adsorbed species from NH to N which can accelerate dissociative adsorption of nitrogen as the rate limiting step in ammonia synthesis.

High Current Density Oxygen Evolution in Carbonate Buffered Solution Achieved by Active Site Densification and Electrolyte Engineering.

High current density reaching 1 A cm-2 for efficient oxygen evolution reaction (OER) was demonstrated by interactively optimizing electrolyte and electrode at non-extreme pH levels. Careful electrolyte assessment revealed that the state-of-the-art nickel-iron oxide electrocatalyst in alkaline solution maintained its high OER performance with a small Tafel slope in K-carbonate solution at pH 10.5 at 353 K. The OER performance was improved when Cu or Au was introduced into the FeOx -modified nanostructured Ni electrode as the third element during the preparation of electrode by electrodeposition. The resultant OER achieved 1 A cm-2 at 1.53 V vs. reversible hydrogen electrode (RHE) stably for 90 h, comparable to those in extreme alkaline conditions. Constant Tafel slopes, apparent activation energy, and the same signatures from operando X-ray absorption spectroscopy among these samples suggested that this improvement seems solely correlated with enhanced electrochemical surface area caused by adding the third element.

Gas Crossover Regulation by Porosity-Controlled Glass Sheet Achieves Pure Hydrogen Production by Buffered Water Electrolysis at Neutral pH.

Near-neutral pH water electrolysis driven by renewable electricity can reduce the costs of clean hydrogen generation, but its low efficiency and gas crossover in industrially relevant conditions remain a challenge. Here, it was shown that electrolyte engineering could suppress the crossover of dissolved gases such as O2 by regulating their diffusion flux. In addition, a hydrophilized mechanically stable glass sheet was found to block the permeation of gas bubbles, further enhancing the purity of evolved gas from water electrolysis. This sheet had a lower resistance than conventional diaphragms such as Zirfon due to its high porosity and small thickness. A saturated K-phosphate solution at pH 7.2 was used as an electrolyte together with the hydrophilized glass sheet as a gas-separator. This led to a near-neutral pH water electrolysis with 100 mA cm-2 at a total cell voltage of 1.56 V with 99.9 % purity of produced H2 .

Delivering the Full Potential of Oxygen Evolving Electrocatalyst by Conditioning Electrolytes at Near-Neutral pH.

This study reports on the impact of identity and compositions of buffer ions on oxygen evolution reaction (OER) performance at a wide range of pH levels using a model IrOx electrocatalyst. Rigorous microkinetic analysis employing kinetic isotope effects, Tafel analysis, and temperature dependence measurement was conducted to establish rate expression isolated from the diffusion contribution of buffer ions and solution resistance. It was found that the OER kinetics was facile with OH- oxidation compared to H2 O, the results of which were highlighted by mitigating over 200 mV overpotential in the presence of buffer to reach 10 mA cm-2 . This improvement was ascribed to the involvement of the kinetics of the local OH- supply by the buffering action. Further digesting the kinetic data at various buffer pKa and the solution bulk pH disclosed a trade-off between the exchange current density and the Tafel slope, indicating that the optimal electrolyte condition can be chosen at a different range of current density. This study provides a quantitative guideline for electrolyte engineering to maximize the intrinsic OER performance that electrocatalyst possesses especially at near-neutral pH.

Water Electrolysis in Saturated Phosphate Buffer at Neutral pH.

Hydrogen production from renewable energy and ubiquitous water has a potential to achieve sustainability, although current water electrolyzers cannot compete economically with the fossil fuel-based technology. Here, we evaluate water electrolysis at pH 7 that is milder than acidic and alkaline pH counterparts and may overcome this issue. The physicochemical properties of concentrated buffer electrolytes were assessed at various temperatures and molalities for quantitative determination of losses associated with mass-transport during the water electrolysis. Subsequently, in saturated K-phosphate solutions at 80 °C and 100 °C that were found to be optimal to minimize the losses originating from mass-transport at the neutral pH, the water electrolysis performance over model electrodes of IrOx and Pt as an anode and a cathode, respectively, was reasonably comparable with those of the extreme pH. Remarkably, this concentrated buffer solution also achieved enhanced stability, adding another merit of this electrolyte for water electrolysis.

Effectiveness of an interprofessional education program using team-based learning for medical students: A randomized controlled trial.

BACKGROUND: To respond to increasingly complicated healthcare needs in primary care settings, all health and medical welfare professionals are required to collaborate with multiprofessionals, namely via "interprofessional work" (IPW). Interprofessional education (IPE) is essential for effective IPW, especially for medical students. This study aimed to determine whether participation in IPE can increase medical students' readiness for interprofessional learning. METHOD: We examined the difference in readiness of medical students for interprofessional learning before and after an IPE program that used team-based learning (TBL). Each student was assigned to either a uniprofessional or multiprofessional group. They were evaluated using the Japanese version of the Readiness for Interprofessional Learning Scale (RIPLS). Program participants were 126 second-year medical students and 18 students of healthcare professions other than medical doctor who participated in a combined IPE program conducted by two universities. Medical students were allocated to 12 uniprofessional and nine multiprofessional groups at random. RESULTS: One hundred and twelve medical students who replied to the questionnaire both before and after the program (valid response rate, 88.9%) were eligible for analysis. Of these, 42 were assigned to uniprofessional groups and 70 to multiprofessional groups. After the program, the RIPLS total score increased to a greater extent in the multiprofessional groups than in the uniprofessional groups (difference 3.17, 95% confidence interval 0.47-5.88, P = .022). Multiple regression analysis showed the same result. CONCLUSIONS: Learning in multiprofessional groups increased medical students' readiness for interprofessional learning in an IPE program using TBL.

Smoking confers a MTHFR 677C>T genotype-dependent risk for systemic atherosclerosis: results from a large number of elderly autopsy cases that died in a community-based general geriatric hospital.

AIM: We attempted to explore interactions between smoking and the genetic polymorphism of 24 atherosclerosis-related candidate genes in systemic atherosclerosis. METHODS: The study comprised 1,503 consecutive autopsy cases. The male-to-female ratio was 1.16 and the average age at death was 80.3 years. Seventy percent of men and 22% of women were current or past smokers. The degree of atherosclerosis in 10 arteries was semi-quantitatively assessed. Melting curve analysis analyzed 34 single nucleotide polymorphisms (SNPs) of 24 genes. RESULTS: Twenty-four SNPs did not interact with smoking on atherosclerosis, while 7 SNPs interacted in one artery and 2 SNPs in two arteries. The genotypes of MTHFR 677C>T and smoking significantly interacted in four arteries, including the common carotid artery, common and external iliac arteries, and femoral artery. The odds ratios of smoking on atherosclerosis were high (3.034.63) in TT homozygotes, intermediate (1.755.24) in heterozygotes, and low (1.752.63) in CC homozygotes in systemic arteries except for cerebral and coronary arteries. CONCLUSION: MTHFR 677 TT homozygotes are more likely to develop atherosclerosis than heterozygotes or CC homozygotes, if they smoke. Thus, smoking cessation is more important in the prevention of atherosclerosis in MTHFR 677 TT homozygotes.

[Physical and psychological predictors for the onset of certification of long-term care insurance among older adults living independently in a community a 40-month follow-up study].

OBJECTIVE: To ascertain predictors for the onset of different levels of certification of long-term care insurance among older adults living independently in a community. METHODS: Out of all residents aged 65 years and over living in Yoita town, Niigata prefecture, Japan (n = 1,673), 1,544 persons participated in the baseline interview survey in 2000 (response rate, 92.3%). Among these participants, 1,229 persons (79.6% of responders) were ranked as level 1, based on the hierarchical mobility level classification. They were followed up for the subsequent 3 years and 4 months to see whether they continued without certification of long-term care insurance or suffered onset of a "mild level", certified as levels "needing support" and 1 for long-term care insurance, or a "severe level" as 2-5. The Cox proportional hazards model with a stepwise method was used to identify the most parsimonious combination of predictors for each type of long-term care insurance certification. RESULTS: Of those who were followed up, 1,151 persons showed no disability in basic activities of daily living (ADL) at baseline nor died before application for long-term care during the follow-up and thus served for analysis. 1,055 persons (91.7%) remained as "no event", but 49 (4.3%) and 47 persons (4.1%) had onset of the "mild level" and the "severe level" during the follow-up, respectively. The final model for prediction of the "mild level" in both genders included advanced age and poor walking ability (hazard ratio (HR) for either unable or with difficulty: 7.22[95% CI, 1.56-33.52] in males and both unable and with difficulty: 3.28[95% CI, 1.28-8.42] in females). The final model for prediction of the "severe level" in both genders included advanced age and poor instrumental ADL (HR for < or = 4 marks: 3.74[95% CI, 1.59-8.76] in males and 3.90[95% CI, 1.32-11.54] in females). Severe cognitive decline was a predictor only for the "severe level" in males. A history of hospitalization during past 1 year and poor chewing ability were predictive only for the "mild level" in females. CONCLUSIONS: Among older adults living independently in a community, most predictors for subsequent onset of mild level-certification of long-term care insurance, except for advanced age, may be controlled by preventive strategies. Evaluating effectiveness of programs for this purpose warrants further study.