USP35 dimer prevents its degradation by E3 ligase CHIP through auto-deubiquitinating activity.

Recently, a number of reports on the importance of USP35 in cancer have been published. However, very little is known about the exact mechanism by which USP35 activity is regulated. Here, we show the possible regulation of USP35 activity and the structural specificity affecting its function by analyzing various fragments of USP35. Interestingly, the catalytic domain of USP35 alone does not exhibit deubiquitinating activity; in contrast, the C-terminal domain and insertion region in the catalytic domain is required for full USP35 activity. Additionally, through its C-terminal domain, USP35 forms a homodimer that prevents USP35 degradation. CHIP bound to HSP90 interacts with and ubiquitinates USP35. However, when fully functional USP35 undergoes auto-deubiquitination, which attenuates CHIP-mediated ubiquitination. Finally, USP35 dimer is required for deubiquitination of the substrate Aurora B and regulation of faithful mitotic progression. The properties of USP35 identified in this study are a unique homodimer structure, regulation of deubiquitinating activity through this, and utilization of a novel E3 ligase involved in USP35 auto-deubiquitination, which adds another complexity to the regulation of deubiquitinating enzymes.

Continual learning framework for a multicenter study with an application to electrocardiogram.

Deep learning has been increasingly utilized in the medical field and achieved many goals. Since the size of data dominates the performance of deep learning, several medical institutions are conducting joint research to obtain as much data as possible. However, sharing data is usually prohibited owing to the risk of privacy invasion. Federated learning is a reasonable idea to train distributed multicenter data without direct access; however, a central server to merge and distribute models is needed, which is expensive and hardly approved due to various legal regulations. This paper proposes a continual learning framework for a multicenter study, which does not require a central server and can prevent catastrophic forgetting of previously trained knowledge. The proposed framework contains the continual learning method selection process, assuming that a single method is not omnipotent for all involved datasets in a real-world setting and that there could be a proper method to be selected for specific data. We utilized the fake data based on a generative adversarial network to evaluate methods prospectively, not ex post facto. We used four independent electrocardiogram datasets for a multicenter study and trained the arrhythmia detection model. Our proposed framework was evaluated against supervised and federated learning methods, as well as finetuning approaches that do not include any regulation to preserve previous knowledge. Even without a central server and access to the past data, our framework achieved stable performance (AUROC 0.897) across all involved datasets, achieving comparable performance to federated learning (AUROC 0.901).

Fully reconfigurable MEMS-based second-order coupled-resonator optical waveguide (CROW) with ultra-low tuning energy.

Integrated microring resonators are well suited for wavelength-filtering applications in optical signal processing, and cascaded microring resonators allow flexible filter design in coupled-resonator optical waveguide (CROW) configurations. However, the implementation of high-order cascaded microring resonators with high extinction ratios (ERs) remains challenging owing to stringent fabrication requirements and the need for precise resonator tunability. We present a fully integrated on-chip second-order CROW filter using silicon photonic microelectromechanical systems (MEMS) to adjust tunable directional couplers and a phase shifter using nanoscale mechanical out-of-plane waveguide displacement. The filter can be fully reconfigured with regard to both the ER and center wavelength. We experimentally demonstrated an ER exceeding 25 dB and continuous wavelength tuning across the full free spectral range of 0.123 nm for single microring resonator, and showed reconfigurability in second-order CROW by tuning the ER and resonant wavelength. The tuning energy for an individual silicon photonic MEMS phase shifter or tunable coupler is less than 22 pJ with sub-microwatt static power consumption, which is far better than conventional integrated phase shifters based on other physical modulation mechanisms.

Programmable MZI based on a silicon photonic MEMS-tunable delay line.

We report on a scalable and programmable integrated Mach-Zehnder interferometer (MZI) with a tunable free spectral range (FSR) and extinction ratio (ER). For the tunable path of the MZI, we designed and utilized a tunable delay line having high flexibility based on silicon photonic microelectromechanical systems (MEMS). By utilizing MEMS, the length of the delay line can be geometrically modified. In this way, there is no optical loss penalty other than the waveguide propagation loss as the number of tunable steps increases. Therefore, our device is more scalable in terms of optical loss than the previous approaches based on cascaded MZIs. In addition, the tuning energy required to reconfigure the length is only 8.46 pJ.

Cancer Risk According to Alcohol Consumption Trajectories: A Population-based Cohort Study of 2.8 Million Korean Men.

BACKGROUND: Alcohol drinking behaviors change temporally and can lead to changes in related cancer risks; previous studies have been unable to identify the association between the two using a single-measurement approach. Thus, this study aimed to investigate the association of drinking trajectories with the cancer risk in Korean men. METHODS: A trajectory analysis using group-based trajectory modeling was performed on 2,839,332 men using data on alcohol drinking levels collected thrice during the Korean National Health Insurance Service's general health screening program conducted between 2002 and 2007. Cox proportional hazards regression was performed to evaluate the associations between drinking trajectories and cancer incidence, after adjustments for age, income, body mass index, smoking status, physical activity, family history of cancer, and comorbidities. RESULTS: During 10.5 years of follow-up, 189,617 cancer cases were recorded. Six trajectories were determined: non-drinking, light, moderate, decreasing-heavy, increasing-heavy, and steady-heavy. Light-to-heavy alcohol consumption increased the risk for all cancers combined in a dose-dependent manner (adjusted hazard ratio [aHR] 1.03; 95% confidence interval [CI], 1.02-1.05 for light drinking, aHR 1.06; 95% CI 1.05-1.08 for moderate drinking, aHR 1.19; 95% CI, 1.16-1.22 for decreasing-heavy drinking, aHR 1.23; 95% CI, 1.20-1.26 for increasing-heavy drinking, and aHR 1.33; 95% CI, 1.29-1.38 for steady-heavy drinking [P-trend <0.001]). Light-to-heavy alcohol consumption was linked to lip, oral cavity, pharyngeal, esophageal, colorectal, laryngeal, stomach, and gallbladder and biliary tract cancer risks, while heavy alcohol consumption was associated with hepatic, pancreatic, and lung cancer risks. An inverse association was observed for thyroid cancer. The cancer risks were lower for decreasing-heavy drinkers, compared to steady-heavy drinkers. CONCLUSION: No safe drinking limits were identified for cancer risks; reduction in heavy intake had protective effects.

Vision for tobacco endgame in Korea: suggestions for countries with endgame aspirations.

Tobacco endgame is a focal point of discussion at both national and international levels. We aimed to describe efforts related to achieving the tobacco endgame in the Republic of Korea, an exemplar of a country with endgame aspirations, and compare them with the efforts of other nations. We reviewed the tobacco endgame efforts of three nations considered tobacco control leaders: New Zealand (NZ), Australia and Finland. The efforts/attempts of each country were described using an endgame strategy category. The tobacco control leaders had explicit goals to achieve a smoking prevalence of <5% before a target date and had legislation and research centres for tobacco control and/or endgame. NZ is implementing a mixture of conventional and innovative endgame interventions; the others use incremental conventional approaches. In Korea, there has been an attempt to ban the sale and manufacture of combustible cigarettes. The attempt led to the filing of a petition, and a survey of adults showed 70% supported the legislation banning tobacco. The Korean government mentioned a tobacco endgame in a 2019 plan, yet a target and an end date were absent. The 2019 plan in Korea included incremental FCTC strategies. Practices in the leading countries show that legislation and research are key to ending the tobacco epidemic. The MPOWER measures must be strengthened, endgame objectives must be set and bold strategies must be adopted. Key endgame policies include those with evidence of effectiveness, such as retailer reductions.

Modified Impedance Sensing System Determination of Virulence Characteristics of Pathogenic Bacteria Klebsiella Species.

An impedance sensing system is a family of biosensors that measure changes in electrical impedance to perform their functions. Physical and chemical changes in the impedance of the sensing element, such as changes in the concentration of a target analyte or changes in the physical properties of the sensing element, can result in changes in the impedance of the sensing element. Many impedance biosensors have been developed for the detection of pathogens in the past few decades. Several types of biosensors have been developed for the detection of infections, including transduction elements, biorecognition components, and electrochemical approaches. In this review, we discuss the characteristics and pathogenic factors associated with 2,3-butanediol-producing Klebsiella pneumoniae collected using impedance sensors. An impedance sensing system was introduced as a great method for monitoring the virulence factors of Klebsiella spp. in situ. Klebsiella pneumoniae produces virulence factors, including capsules, lipopolysaccharides, fimbriae, and siderophores, as part of its pathogenesis. It is possible to examine virulence factors' pathogenic characteristics in vitro and in vivo using real tissues or mouse models in order to conduct experiments. For the monitoring of virulence factors in situ, a novel alternative method has been developed to mimic the environment of real tissues. For the purpose of developing tissue-mimicking models, mucin and mannose were used to modify the surface of gold electrodes. These components are known to contribute to the adhesion of pathogens to epithelial cells in mammals.

Optimum Urine Cotinine and NNAL Levels to Distinguish Smokers from Non-Smokers by the Changes in Tobacco Control Policy in Korea from 2008 to 2018.

INTRODUCTION: We examined the age- and sex-specific distributions of biomarkers of tobacco smoke exposure to determine the optimal cutoffs to distinguish smokers from non-smokers over the last 10 years in Korea, during which smoking prevalence and secondhand smoke (SHS) exposure declined due to changes in tobacco control policy. METHODS: We analyzed data from the Korea National Health and Nutrition Examination Survey on creatinine-adjusted urinary cotinine (2008-2018; 33 429 adults: 15 653 males and 17 776 females) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL; 2016-2018; 6337 adults: 3091 males and 3246 females). We determined the optimal cutoffs and confidence intervals (CIs) to distinguish smokers from non-smokers using receiver operator characteristic curve analysis and bootstrapping (1000 resamples). RESULTS: The optimal cutoff values of creatinine-adjusted urine cotinine and NNAL concentration were 20.9 ng/mg (95% CI: 20.8-21.0, sensitivity: 96.6%, specificity: 93.8%) and 8.9 pg/mg (95% CI: 8.8-8.9, sensitivity: 94.0%, specificity: 94.7%), respectively, in 2016-2018. The optimal cutoffs of both biomarkers increased with age and were higher in females than in males for NNAL concentration. In both sexes, the optimal cutoff of urine cotinine continuously declined over the study period. CONCLUSIONS: The optimal cotinine cutoff declined along with smoking prevalence and levels of SHS exposure due to enforcement of tobacco control policies, including smoke-free ordinances and tax increases. Monitoring of biomarkers of tobacco exposure appears necessary for verification of smoking status and regulatory use. IMPLICATIONS: Our results based on nationally representative data suggest that a large decrease in the optimal cutoff value of urine cotinine to distinguish smokers from non-smokers was caused by decreases in smoking prevalence and SHS exposure following enforcement of tobacco control policies over the last 10 years. We determined the optimal cutoff values of urine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), which were not previously reported in representative population in Asia, to enable more accurate estimation of exposure to tobacco smoke and proper assessment of disease risks. Gender- and age-specific differences in the optimal cutoffs require further study. Monitoring of biomarkers of tobacco smoke exposure seems necessary for verification of smoking status and regulatory use.

Perceptions of Heated Tobacco Products (HTPs) and Intention to Quit Among Adult Tobacco Users in Korea.

BACKGROUND: The popularity of heated tobacco products (HTPs) has been growing globally but, limited information exists on tobacco use behaviors and its impact on tobacco control. This study investigates awareness and perception of HTPs among tobacco users and whether perceptions of HTPs are associated with HTP use and intention to quit. METHODS: We invited 2,000 tobacco users aged 19-65 years with countrywide representation to an online survey in November 2018. Information on general characteristics, tobacco use behaviors, awareness and perception of HTPs, and intention to quit were gathered. Multinomial logistic regression analysis and ANCOVA were used for estimation of association and comparison. RESULTS: Among all tobacco users, 36.8% were classified as ever users, whereas 28.3% had used HTPs in the past 30 days, which was higher than expected. Users of liquid-based e-cigarettes (odds ratio [OR] 1.578; 95% confidence interval [CI], 1.210-2.056) and poly-product users (OR 2.029; 95% CI, 1.121-3.671) showed higher intention to quit within 1 month when compared to users of conventional cigarettes (CCs), whereas HTP users and dual product users did not. HTP users rated HTPs more favorably than CCs in terms of smoke, smell, harm, aid in quitting, design, and price than users of other products did (P-value < 0.001). CONCLUSION: We find that positive perception of HTPs following strategic marketing from tobacco companies could have contributed to a greater increase in HTP use than expected in Korea. However, HTPs might not be considered substitutes for CCs for quitting tobacco use because a significant proportion of dual product users reported a lower intention to quit.

Association between perceived harm of tobacco and intention to quit: a cross-sectional analysis of the Vietnam Global Adult Tobacco Survey.

BACKGROUND: Perception of harm plays an important role in predicting intention to quit-an integral part of the cessation process. Perception on harm from bamboo waterpipe tobacco was unknown, even the predominant of this type of tobacco use. This study investigated the effects of perceived harm from cigarette and bamboo waterpipe tobacco on intention to quit among adult male Vietnamese tobacco users. METHODS: From the nationally-representative 2015 Global Adult Tobacco Survey, we included 1,351 adult males (≥ 18 years old) who used cigarettes, bamboo waterpipes, or both. Demographic characteristics, tobacco use behaviors, perceived harm from tobacco use, and regulation/policy exposure were measured. Effects of perceived harm from cigarette and bamboo waterpipe tobacco on intention to quit were assessed by logistic regression. RESULTS: Intention to quit prevalence was 59.0%, 55.0%, and 58.4% for cigarette, waterpipe, and dual users, respectively. Tobacco users who perceived that "using cigarettes and/or waterpipe could cause severe illness" and "waterpipe use is less harmful than cigarette smoking", had tobacco use bans at home, or were exposed to anti-smoking campaigns or encouragement to quit information were more likely to intend to quit. When analyzed by tobacco users, intention to quit was more likely for those users who perceived their tobacco product as more harmful than the other product type, although statistical significance was only observed for cigarette users. CONCLUSIONS: Misperceptions regarding harm from tobacco use could negatively affect intention to quit. Dissemination of accurate information on the risks from all forms of tobacco use and enforcement of tobacco control policies are important for encouraging intention to quit.

A development of a graph-based ensemble machine learning model for skin sensitization hazard and potency assessment.

Many defined approaches (DAs) for skin sensitization assessment based on the adverse outcome pathway (AOP) have been developed to replace animal testing because the European Union has banned animal testing for cosmetic ingredients. Several DAs have demonstrated that machine learning models are beneficial. In this study, we have developed an ensemble prediction model utilizing the graph convolutional network (GCN) and machine learning approach to assess skin sensitization. The model integrates in silico parameters and data from alternatives to animal testing of well-defined AOP to improve DA predictivity. Multiple ensemble models were created using the probability produced by the GCN with six physicochemical properties, direct peptide reactivity assay, KeratinoSens™, and human cell line activation test (h-CLAT), using a multilayer perceptron approach. Models were evaluated by predicting the testing set's human hazard class and three potency classes (strong, weak, and non-sensitizer). When the GCN feature was used, 11 models out of 16 candidates showed the same or improved accuracy in the testing set. The ensemble model with the feature set of GCN, KeratinoSens™, and h-CLAT produced the best results with an accuracy of 88% for assessing human hazards. The best three-class potency model was created with the feature set of GCN and all three assays, resulting in 64% accuracy. These results from the ensemble approach indicate that the addition of the GCN feature could provide an improved predictivity of skin sensitization hazard and potency assessment.

Synthesis of a New Glycoconjugate with Di-á´ -Psicose Anhydride Structure.

Demand for healthy diets has led researchers to explore new saccharide as sucrose alternatives. ᴅ-Psicose, the C-3 epimer of ᴅ-fructose, has a similar sweetness intensity to sucrose but contributes fewer calories. This study proposes a disaccharide with a stable structure derived from ᴅ-psicose. The compound with a spiro-tricyclic core was generated at 32% conversion via caramelization of ᴅ-psicose under acidic anhydrous conditions. The compound was identified by high-resolution mass spectrometry and multi-dimensional nuclear magnetic resonance (NMR). The molecular formula was established as C12H20O10 from the molecular weight of m/z 324.1055. Twelve signals were observed by the 13C NMR spectrum. This compound, denoted di-ᴅ-psicose anhydride (DPA), exhibited a lower water solubility (40 g/L) and higher thermal stability (peak temperature = 194.7 °C) than that of ᴅ-psicose (peak temperature = 126.5 °C). The quantitatively evaluated metal ion scavenging ability of DPA was the best in magnesium (average 98.6 ± 1.1%). This synthesis methodology can provide disaccharides with high stability-reducing heavy metals.

Rolling Circle Amplification-based Copper Nanoparticle Synthesis on Cyclic Olefin Copolymer Substrate and Its Application in Aptasensor.

This study aimed to develop a label-free fluorescent aptasensor for the detection of diazinon (DZN) on a cyclic olefin copolymer (COC) substrate. The aptasensor design was based on rolling circle amplification (RCA) technology and the use of self-assembled copper nanoparticles (CuNPs). A dual-function (DF) probe, capable of binding to circular DNA and an aptamer, was designed and immobilized on a COC-bottom 96-well plate. An aptamer was used for selective recognition of DZN, and the specific site of the aptamer that strongly reacted with DZN was successfully identified using circular dichroism (CD) analysis. In presence of DZN, the aptamer and DZN formed a strong complex, thus providing an opportunity for hybridization of the DF probe and circular DNA, thereby initiating an RCA reaction. Repetitive poly thymine (T) sequence with a length of 30-mer, generated in the RCA reaction, served as a template for the synthesis of fluorescent copper nanoparticles, emitting an orange fluorescence signal (at approximately 620 nm) proportional to the amount of RCA product, within 10 min under UV irradiation. The CuNP fluorescence was imaged and quantified using an image analysis software. A linear correlation of the fluorescence signal was confirmed in the DZN concentration range of 0.1-3 ppm, with a detection limit of 0.15 ppm. Adoption of a label-free detection method, utilizing RCA and fluorescent CuNPs on COC substrates, reduced the need for complex equipment and requirements for DZN analysis, thereby representing a simple and rapid sensing method circumventing the limitations of current complex and labor-intensive methods. Electronic Supplementary Material ESM: The online version of this article (doi:10.1007/s12257-021-0220-0) contains supplementary material, which is available to authorized users.

The Scientific Method as a Scaffold to Enhance Communication Skills in Chemistry.

Scientific success in the field of chemistry depends upon the mastery of a wide range of soft skills, most notably scientific writing and speaking. However, training for scientific communication is typically limited at the undergraduate level, where students struggle to express themselves in a clear and logical manner. The underlying issue is deeper than basic technical skills; rather, it is a problem of students' unawareness of a fundamental and strategic framework for writing and speaking with a purpose. The methodology has been implemented for individual mentorship and in our regional summer research program to deliver a blueprint of thought and reasoning that endows students with the confidence and skills to become more effective communicators. Our didactic process intertwines undergraduate research with the scientific method and is partitioned into six steps, referred to as "phases", to allow for focused and deep thinking on the essential components of the scientific method. The phases are designed to challenge the student in their zone of proximal development so they learn to extract and ultimately comprehend the elements of the scientific method through focused written and oral assignments. Students then compile their newly acquired knowledge to create a compelling and logical story, using their persuasive written and oral presentations to complete a research proposal, final report, and formal 20 min presentation. We find that such an approach delivers the necessary guidance to promote the logical framework that improves writing and speaking skills. Over the past decade, we have witnessed both qualitative and quantitative gains in the students' confidence in their abilities and skills (developed by this process), preparing them for future careers as young scientists.

Trends in the Socioeconomic Inequalities Related to Second-Hand Smoke Exposure as Verified by Urine Cotinine Levels Among Nonsmoking Adults: Korea National Health and Nutrition Examination Survey 2008-2018.

INTRODUCTION: The expansion of smoke-free policies has reduced the prevalence of second-hand smoke (SHS) exposure; however, declines differ according to socioeconomic positions. We evaluated the trends in socioeconomic inequalities related to SHS exposure in nonsmoking Korean adults from 2008 to 2018. METHODS: We analyzed 30,027 nonsmoking adults from the Korea National Health and Nutrition Examination Survey 2008 to 2018. We evaluated trends in urine cotinine levels, self-reported prevalence of SHS exposure at workplaces and homes, and people exhibiting nonmeasurable urine cotinine levels between 2008 and 2018. To evaluate the yearly decline differences of urine cotinine levels according to socioeconomic positions, we calculated the interaction effects of year and education, household incomes, and occupation from linear regression analysis. RESULTS: In the last 11 years, the geometric means of urine cotinine levels decreased from 3.53 (95% CI 2.96-4.19) ng/mL to 0.60 (0.57-0.64) ng/mL in males, and from 2.36 (2.03-2.73) ng/mL to 0.53 (0.51-0.56) ng/mL in females. The prevalence of SHS exposure at workplaces and homes also declined. In the multivariate model, the interaction effects between education and years were significant; therefore, indicating a substantial yearly decline of urine cotinine levels in higher educated individuals. The interaction effects between household incomes and years were only significant among males; the interaction effects between occupations and years were not significant. CONCLUSIONS: SHS exposure in nonsmoking Korean adults has consistently decreased; however, socioeconomic inequalities related to SHS exposure by education level have widened. Policies targeting socioeconomically disadvantaged populations should be implemented to decrease the disparities of SHS exposure. IMPLICATIONS: Along with tobacco control policies, the prevalence of self-reported and urinary cotinine verified SHS exposure has decreased in the last 11 years. In contrast, the socioeconomic inequalities related to SHS exposure by education level have increased over time. This study emphasizes the need for implementing tobacco control policies to reduce disparities of SHS exposure.

The effect of 5-min mindfulness of love on suffering and spiritual quality of life of palliative care patients: A randomized controlled study.

OBJECTIVE: Suffering is a common experience in palliative care. In our study, we aimed to determine the effect of 5-min mindfulness of love on suffering and the spiritual quality of life of palliative care patients. METHODS: We conducted a parallel-group, blinded, randomized controlled study at the University of Malaya Medical Centre (UMMC), Malaysia from February 2019 to April 2019. Sixty adult palliative care patients with an overall suffering score of 4/10 or above based on the Suffering Pictogram were recruited and randomly assigned to either the 5-min mindfulness of love group (N = 30) or the 5-min supportive listening group (N = 30). RESULTS: There were statistically significant improvements in the overall suffering score (mean difference = -2.9, CI = -3.7 to -2.1, t = -7.268, p = 0.000) and the total FACIT-Sp-12 score (mean difference = 2.9, CI = 1.5 to 4.3, t = 4.124, p = 0.000) in the intervention group compared to the control group. CONCLUSION: The results provided evidence that 5-min mindfulness of love could affect the actual state of suffering and the spiritual quality of life of palliative care patients.

Autoinducer-2 Could Affect Biofilm Formation by Food-Derived Bacillus cereus.

Bacillus cereus is a foodborne pathogen and cause a frequent problem due to the biofilms forming in equipment of food production plants. Autoinducer-2 (AI-2) involved in interspecies communication, plays a role in the biofilm formation of B. cereus. In this study, biofilm formation by thirty-nine B. cereus strains isolated from foods produced in Korea was determined. To investigate the effect of AI-2 on biofilm formation by B. cereus SBC27, which had the highest biofilm-forming ability, biofilm densities formed after addition of the AI-2 from Staphylococcus aureus and Escherichia coli were analysed. As a result, it was found that the quorum sensing molecule AI-2 could induce biofilm formation by B. cereus within 24 h, but it may also inhibit biofilm formation when more AI-2 is added after 24 h. Thus, these results improve our understanding of biofilm formation by food-derived B. cereus and provide clues that could help to reduce the impact of biofilms, the biggest problem in food processing environments, which has an impact on public health as well as the economy.

Development of a Novel Prognostic Model to Predict 6-Month Swallowing Recovery After Ischemic Stroke.

Background and Purpose- The aim of this study was to explore clinical and radiological prognostic factors for long-term swallowing recovery in patients with poststroke dysphagia and to develop and validate a prognostic model using a machine learning algorithm. Methods- Consecutive patients (N=137) with acute ischemic stroke referred for swallowing examinations were retrospectively reviewed. Dysphagia was monitored in the 6 months poststroke period and then analyzed using the Kaplan-Meier method and Cox regression model for clinical and radiological factors. Bayesian network models were developed using potential prognostic factors to classify patients into those with good (no need for tube feeding or diet modification for 6 months) and poor (tube feeding or diet modification for 6 months) recovery of swallowing function. Results- Twenty-four (17.5%) patients showed persistent dysphagia for the first 6 months with a mean duration of 65.6 days. The time duration of poststroke dysphagia significantly differed by tube feeding status, clinical dysphagia scale, sex, severe white matter hyperintensities, and bilateral lesions at the corona radiata, basal ganglia, or internal capsule (CR/BG/IC). Among these factors, tube feeding status (P<0.001), bilateral lesions at CR/BG/IC (P=0.001), and clinical dysphagia scale (P=0.042) were significant prognostic factors in a multivariate analysis using Cox regression models. The tree-augmented network classifier, based on 10 factors (sex, lesions at CR, BG/IC, and insula, laterality, anterolateral territory of the brain stem, bilateral lesions at CR/BG/IC, severe white matter hyperintensities, clinical dysphagia scale, and tube feeding status), performed better than other benchmarking classifiers developed in this study. Conclusions- Initial dysphagia severity and bilateral lesions at CR/BG/IC are revealed to be significant prognostic factors for 6-month swallowing recovery. The prediction of 6-month swallowing recovery was feasible based on clinical and radiological factors using the Bayesian network model. We emphasize the importance of bilateral subcortical lesions as prognostic factors that can be utilized to develop prediction models for long-term swallowing recovery.

The p38-activated ER stress-ATF6α axis mediates cellular senescence.

The importance of proteostasis in preventing cellular senescence has been well recognized. However, the exact mechanism by which the loss of proteostasis or endoplasmic reticulum (ER) stress induces cellular senescence remains unclear. We report that ER stress mediates cellular senescence through the activating transcription factor (ATF)6α branch of the unfolded protein response (UPR). Cellular senescence was induced by the abrogation of neighbor of breast cancer (BRCA)1 gene (NBR1). NBR1 abrogation-induced senescence was p53 dependent and observed in both transformed and nontransformed human cell lines: MCF-7, Caki-1, and MRC-5. NBR1 bound to p38 MAPK, preferentially to an active form, and upon NBR1 abrogation, the activity of p38 increased. NADPH oxidase was activated in turn by p38, and the resulting oxidative stress triggered ER stress. It was found that ER stress mediated cellular senescence through the UPR sensor ATF6α. Knockdown of ATF6α prevented senescence, whereas ATF6α overexpression triggered it. The transcriptional activity of ATF6α was important. The ER stress-ATF6α axis also mediated cellular senescence induced by H-RasV12 overexpression and UV irradiation, suggesting a common role of this axis in senescence induction. In summary, we presented an evidence for the novel role of the ER stress-ATF6α axis in cellular senescence.-Kim, H. S., Kim, Y., Lim, M. J., Park, Y.-G., Park, S. I., Sohn, J. The p38-activated ER stress-ATF6α axis mediates cellular senescence.

Validation of the Brief Ageing Perceptions Questionnaire (B-APQ) in Malaysia.

Objectives: The Brief Ageing Perceptions Questionnaire (B-APQ) has five domains that explore views about own ageing. The aim of this study was to validate the B-APQ for use among older adults in Malaysia and to explore socio-demographic variations in ageing self-perceptions.Method: Older adults aged 50 years and above were randomly selected to complete a set of questionnaires. Cronbach's α was used to measure internal consistency, while corrected item-total correlations and correlation with DASS-21 and the CASP-19 scores were employed to assess convergent and discriminant validity. Confirmatory Factor Analysis (CFA) was conducted to confirm the factorial structure of the B-APQ. Difference in self-perceptions of ageing across socio-demographic variables was assessed.Results: Internal consistency for each of the domains was good. Item-total correlations within each domain were strong (>0.6) or very strong (>0.8). Convergent and discriminant validity were supported by significant correlations with DASS-21 depression and CASP-19 scores. CFA results indicated good model fit with the original B-APQ model. Presence of chronic illness also has a significant impact on B-APQ domain scores.Conclusion: The B-APQ is a valid and reliable instrument which can be used to assess self-perceptions of ageing among older Malaysian adults.