Influence of MAFLD and NAFLD on arterial stiffness: A longitudinal cohort study.

BACKGROUND AND AIMS: This cohort study investigated associations of nonalcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated fatty liver disease (MAFLD) with risk of increase in arterial stiffness (AS), measured as brachial-ankle pulse wave velocity (baPWV). METHODS AND RESULTS: Participants who had health examinations between 2006 and 2019 were analyzed for fatty liver and increased baPWV using liver ultrasonography and automatic volume plethysmography device. Participants were classified based on presence of MAFLD or NAFLD and further divided into subgroups: no fatty liver disease (reference), NAFLD-only, MAFLD-only, and both NAFLD and MAFLD. Subgroups were additionally stratified by sex. Cox proportional hazard model was utilized to analyze the risk of developing baPWV ≥1400 cm/s in participants without baseline elevation of the baPWV. The NAFLD and MAFLD groups exhibited higher risks of increased baPWV (NAFLD: adjusted hazard ratio (aHR), 1.35 [95% CI, 1.29-1.42]; MAFLD: aHR, 1.37 [95% CI, 1.31-1.43]) compared to group without the conditions. Incidence of NAFLD or MAFLD were higher in men than in women but aHR of developing the increase in AS was higher in women. In subgroup analysis, the MAFLD-only group presented the strongest associations with increase in AS (aHR, 1.53 [95% CI, 1.43-1.64]), with the trend more pronounced in women than in men (Women, aHR, 1.63 [95% CI, 1.08-2.46]; Men, aHR 1.45 [95% CI, 1.35-1.56]). CONCLUSIONS: Both NAFLD and MAFLD are significantly associated with elevated AS. These associations tended to be stronger in MAFLD than in NAFLD, in women than in men.

Cardiorespiratory Dynamics During Prone Positioning for Severe Ards: A Retrospective Cohort Study.

Objectives: To elucidate the changes in cardiorespiratory dynamics during neuromuscular blockade and prone positioning and determine the associations between changes in cardiorespiratory dynamics following prone positioning and mortality. Design: Single center retrospective cohort study of patients admitted to the medical ICU between June 1, 2020 and September 1, 2022 who received prone positioning while mechanically ventilated. Results: Our final cohort consisted of 136 patients. Prone position was associated with an improvement in A-a gradient of 113 mmHg (95% CrI 78 - 149) between the pre-proning values and 10 hours post proning. Norepinephrine dose did not significantly change before and after prone positioning (Estimated difference: 0.04 mcg/min 95% CrI -1.00 - 1.07). For the outcome of 7-d mortality, there was a high probability that the baseline factors of increasing age, male sex, and higher baseline A-a gradient were associated with increased risk of death. Increased total vasopressor requirement and increased in PCO2 were associated with worse prognosis while a decrease in instantaneous heart rate and a decrease in heart rate variability were associated with improved prognosis. Conclusion: The immediate changes in prone positioning primarily impact respiratory physiology, with limited influence on circulatory parameters. Predictors of short-term mortality after prone positioning include both respiratory and cardiovascular parameters suggesting that extrapulmonary effects, such as improvement in right ventricular heart function, might also contribute to the benefit of prone positioning.

Low gamma-butyrobetaine dioxygenase (BBOX1) expression as a prognostic biomarker in patients with clear cell renal cell carcinoma: a machine learning approach.

Gamma-butyrobetaine dioxygenase (BBOX1) is a catalyst for the conversion of gamma-butyrobetaine to l-carnitine, which is detected in normal renal tubules. The purpose of this study was to analyze the prognosis, immune response, and genetic alterations associated with low BBOX1 expression in patients with clear cell renal cell carcinoma (RCC). We analyzed the relative influence of BBOX1 on survival using machine learning and investigated drugs that can inhibit renal cancer cells with low BBOX1 expression. We analyzed clinicopathologic factors, survival rates, immune profiles, and gene sets according to BBOX1 expression in a total of 857 patients with kidney cancer from the Hanyang University Hospital cohort (247 cases) and The Cancer Genome Atlas (610 cases). We employed immunohistochemical staining, gene set enrichment analysis, in silico cytometry, pathway network analyses, in vitro drug screening, and gradient boosting machines. BBOX1 expression in RCC was decreased compared with that in normal tissues. Low BBOX1 expression was associated with poor prognosis, decreased CD8+ T cells, and increased neutrophils. In gene set enrichment analyses, low BBOX1 expression was related to gene sets with oncogenic activity and a weak immune response. In pathway network analysis, BBOX1 was linked to regulation of various T cells and programmed death-ligand 1. In vitro drug screening showed that midostaurin, BAY-61-3606, GSK690693, and linifanib inhibited the growth of RCC cells with low BBOX1 expression. Low BBOX1 expression in patients with RCC is related to short survival time and reduced CD8+ T cells; midostaurin, among other drugs, may have enhanced therapeutic effects in this context.

Immediate versus staged complete revascularization in patients with ST-segment elevation myocardial infarction and multivessel coronary artery disease: results from a prematurely discontinued randomized multicenter trial.

BACKGROUND: We aimed to compare clinical outcomes between immediate and staged complete revascularization in primary percutaneous coronary intervention (PCI) for treating ST-segment elevation myocardial infarction (STEMI) and multivessel disease (MVD). METHODS: A total of 248 patients were enrolled in a prospective, randomized, and multicenter registry. Immediate revascularization was defined as one-time PCI of culprit and non-culprit lesions at the initial procedure. Staged revascularization was defined as PCI of non-culprit lesions at a later date (mean, 4.4 days; interquartile range, 1-11.4), following initial culprit revascularization. The end points were major adverse cardiovascular events (MACE; composite of total death, recurrent myocardial infarction, and revascularization), any individual components of MACE, cardiac death, stent thrombosis, and stroke at 12 months. RESULTS: During a follow-up of 1 year, MACE occurred in 12 patients (11.6%) in the immediate revascularization group and in 8 patients (7.5%) in staged revascularization group (hazard ratio [HR] 1.60, 95% confidence interval [CI] 0.65-3.91). The incidence of total death was numerically higher in the immediate group than in the staged group (9.7% vs 2.8%, HR 3.53, 95% CI 0.97-12.84); There were no significant differences between the 2 groups in risks of any individual component of MACE, cardiac death, stroke, and in-hospital complications, such as need for transfusion, bleeding, acute renal failure, and acute heart failure. This study was prematurely terminated due to halt of production of everolimus-eluting stents (manufactured as PROMUS Element by Boston Scientific, Natick, Massachusetts). CONCLUSIONS: Due to its limited power, no definite conclusion can be drawn regarding complete revascularization strategy from the present study. Further large randomized clinical trials would be warranted to confirm optimal timing of complete revascularization for patients with STEMI and MVD.

Anti-adhesion agent to prevent of post-operative adhesion and fibrosis after vasectomy: a study using a rat model.

Background: Post-vasectomy pain syndrome (PVPS) is difficult to treat. Direct damage to the vas deferens, inflammation, compression of nerves through fibrotic adhesions, and congestion of the epididymis are known to cause PVPS. The purpose of this study was to evaluate whether the application of anti-adhesion agents after vasectomy can reduce the degree of adhesion and fibrosis in a rat model. Methods: In the study, 11 Sprague-Dawley rats (22 vas deferens) from each group were evaluated. In the experimental group, surgery was terminated after applying the anti-adhesion agent; this was not applied in the control group. After 14 days of vasectomy, the scrotum was dissected to evaluate the degree of gross adhesion at the vasectomy site. Histological examination of the surrounding tissues, including the vas deferens and the spermatic cord, was also performed. Results: Adhesions were not observed in 72.73% (16/22) rats from the experimental group, in which the anti-adhesion agent was applied; in contrast, the incidence of adhesions in the control group was 100%. There was a statistically significant relationship between the distribution of grades for adhesion and anti-adhesion agent (chi-square, P<0.001). On classification of fibrosis and inflammation, application of the anti-adhesion agent was significantly associated with lower grade inflammation and fibrosis compared to that of the control group (chi-square, P=0.001). The rate of intact muscle structure was 90.91% (20/22) in the experimental group, and 36.36% (8/22) in the control group, and the application of the anti-adhesion agent demonstrated significant association with preservation of intact muscle structure (chi-square, P<0.001). Conclusions: The application of an anti-adhesion agent after vasectomy prevented the development of adhesion, fibrosis, and inflammation reaction and further reduced structural destruction.

Multi-center validation of machine learning model for preoperative prediction of postoperative mortality.

Accurate prediction of postoperative mortality is important for not only successful postoperative patient care but also for information-based shared decision-making with patients and efficient allocation of medical resources. This study aimed to create a machine-learning prediction model for 30-day mortality after a non-cardiac surgery that adapts to the manageable amount of clinical information as input features and is validated against multi-centered rather than single-centered data. Data were collected from 454,404 patients over 18 years of age who underwent non-cardiac surgeries from four independent institutions. We performed a retrospective analysis of the retrieved data. Only 12-18 clinical variables were used for model training. Logistic regression, random forest classifier, extreme gradient boosting (XGBoost), and deep neural network methods were applied to compare the prediction performances. To reduce overfitting and create a robust model, bootstrapping and grid search with tenfold cross-validation were performed. The XGBoost method in Seoul National University Hospital (SNUH) data delivers the best performance in terms of the area under receiver operating characteristic curve (AUROC) (0.9376) and the area under the precision-recall curve (0.1593). The predictive performance was the best when the SNUH model was validated with Ewha Womans University Medical Center data (AUROC, 0.941). Preoperative albumin, prothrombin time, and age were the most important features in the model for each hospital. It is possible to create a robust artificial intelligence prediction model applicable to multiple institutions through a light predictive model using only minimal preoperative information that can be automatically extracted from each hospital.

Phase retrieval based on deep learning in grating interferometer.

Grating interferometry is a promising technique to obtain differential phase contrast images with illumination source of low intrinsic transverse coherence. However, retrieving the phase contrast image from the differential phase contrast image is difficult due to the accumulated noise and artifacts from the differential phase contrast image (DPCI) reconstruction. In this paper, we implemented a deep learning-based phase retrieval method to suppress these artifacts. Conventional deep learning based denoising requires noise/clean image pair, but it is not feasible to obtain sufficient number of clean images for grating interferometry. In this paper, we apply a recently developed neural network called Noise2Noise (N2N) that uses noise/noise image pairs for training. We obtained many DPCIs through combination of phase stepping images, and these were used as input/target pairs for N2N training. The application of the N2N network to simulated and measured DPCI showed that the phase contrast images were retrieved with strongly suppressed phase retrieval artifacts. These results can be used in grating interferometer applications which uses phase stepping method.

Analysis of a silicon comb structure using an inverse Talbot-Lau neutron grating interferometer.

We describe an inverse Talbot-Lau neutron grating interferometer that provides an extended autocorrelation length range for quantitative dark-field imaging. To our knowledge, this is the first report of a Talbot-Lau neutron grating interferometer (nTLI) with inverse geometry. We demonstrate a range of autocorrelation lengths (ACL) starting at low tens of nanometers, which is significantly extended compared to the ranges of conventional and symmetric setups. ACLs from a minimum of 44 nm to the maximum of 3.5 µm were presented for the designed wavelength of 4.4 Å in experiments. Additionally, the inverse nTLI has neutron-absorbing gratings with an optically thick gadolinium oxysulfide (Gadox) structure, allowing it to provide a visibility of up to 52% while maintaining a large field of view of approximately 100 mm × 100 mm. We demonstrate the application of our interferometer to quantitative dark-field imaging by using diluted polystyrene particles in an aqueous solution and silicon comb structures. We obtain quantitative structural information of the sphere size and concentration of diluted polystyrene particles and the period, height, and duty cycle of the silicon comb structures. The optically thick Gadox structure of the analyzer grating also provides improved characteristics for the correction of incoherent neutron scattering in an aqueous solution compared to the symmetric nTLI.

Quality Assessment and Relevant Clinical Impact of Randomized Controlled Trials of Varicocele: Next Step to Good-Quality Randomized Controlled Trial of Varicocele Treatment.

PURPOSE: To assess the quality of randomized controlled trials (RCTs) on varicocele published from 1979 to 2017. MATERIALS AND METHODS: We searched for original RCT on varicocele published between 1979 and 2017. Jadad scale, van Tulder scale, and Cochrane Collaboration Risk of Bias Tool were used to analyze RCT quality over time. Effects on RCT quality including funding source, Institutional Review Board (IRB) approval, and intervention were assessed. Treatment parameters of varicocele were also analyzed. RESULTS: Blinding and allocation concealment were described in 25.9% and 9.4% of RCT, respectively. Both tended to increase and a sharp dip in allocation concealment was observed in 2010-2017. Jadad scores increased steadily from 1979 to 2017 (1.28±0.59 to 2.19±1.10, p<0.01). Van Tulder scores tended to increase from 1979 to 2017 (4.21±0.94 to 5.58±1.58, p<0.01). RCTs with funding statements had higher Jadad (Yes vs. No, 3.25±0.50 vs. 1.70±0.97; p<0.01) and van Tulder (Yes vs. No, 7.25±1.26 vs. 4.81±1.26; p<0.01) scores than unfunded RCTs. IRB approval and intervention were associated with better quality. CONCLUSIONS: The number of RCTs on varicocele increased from 1979 to 2017. Also, quality improved over time with increasing IRB approval, funding, and multicenter trial. Most RCTs on varicocele reported the use of surgical treatment. RCTs of surgical treatments have limitations to satisfy the condition of RCT to conduct, but their quality has improved over time.

Efficacy and Safety of Mirodenafil Oro-Dispersible Film in Korean Patients with Erectile Dysfunction: A Double-Blind, Randomized, Placebo-Controlled, Parallel-Group, Multicenter, Phase IV Study.

PURPOSE: To investigate the efficacy, safety, and tolerability of oro-dispersible film (ODF) formulation of mirodenafil 50 mg and 100 mg for the treatment of patients with erectile dysfunction (ED) in Korea. MATERIALS AND METHODS: A multicenter, randomized, double-blind, placebo-controlled, parallel-group study of 129 subjects was performed. Subjects were randomized to either placebo or mirodenafil ODF 50 mg or 100 mg to be taken in an "on demand" manner for 8 weeks. The primary efficacy variable was the International Index of Erectile Dysfunction (IIEF)-5 questionnaire. The secondary efficacy variables comprised Sexual Encounter Profile questions 2 and 3 (SEP2 and SEP3), the Global Assessment Question (GAQ), and the Life Satisfaction Checklist (LSC). RESULTS: IIEF-5 was significantly increased in all groups after treatment. However, compared to the placebo group, only the mirodenafil ODF 100 mg group showed a significant difference. SEP2 and SEP3 were increased in both mirodenafil groups; however, the increase was not statistically significant for SEP2. In terms of GAQ and LSC, the mirodenafil ODF groups showed significant increases compared with the baseline. Most treatment-associated adverse events were mild and resolved spontaneously. CONCLUSIONS: Mirodenafil ODF is an effective and well-tolerated agent for the treatment of patients with ED in Korea.

Towards spatially resolved magnetic small-angle scattering studies by polarized and polarization-analyzed neutron dark-field contrast imaging.

In the past decade neutron dark-field contrast imaging has developed from a qualitative tool depicting microstructural inhomogeneities in bulk samples on a macroscopic scale of tens to hundreds of micrometers to a quantitative spatial resolved small-angle scattering instrument. While the direct macroscopic image resolution around tens of micrometers remains untouched microscopic structures have become assessable quantitatively from the nanometer to the micrometer range. Although it was found that magnetic structures provide remarkable contrast we could only recently introduce polarized neutron grating interferometric imaging. Here we present a polarized and polarization analyzed dark-field contrast method for spatially resolved small-angle scattering studies of magnetic microstructures. It is demonstrated how a polarization analyzer added to a polarized neutron grating interferometer does not disturb the interferometric measurements but allows to separate and measure spin-flip and non-spin-flip small-angle scattering and thus also the potential for a distinction of nuclear and different magnetic contributions in the analyzed small-angle scattering.

Relationship between workers' return to work, job retention and income in industrial accidents in Korea: a longitudinal study.

OBJECTIVE: This study aims to compare workers' income before and after an occupational injury, with regard to return to work and job retention, over a period of 5 years. DESIGN: This study was designed as a longitudinal study. SETTING: The Panel Study of Workers' Compensation Insurance (PSWCI) survey targeted workers involved in industrial accidents for which medical care was terminated in the year 2012. PARTICIPANTS: The panel study was conducted on a final sample of 2000 workers who were selected proportionally by region (nine regions) after priority assignment by disability rating (six levels). A total of 1458 workers were finally included in this study. METHODS: This study used data from the first to fifth PSWCI. To identify the effect on income after occupational injury considering return to work and job retention, we used the generalised estimating equation. RESULTS: In regard to workers' return to work, the OR that income after an occupational injury would be higher than that before an occupational injury was 3.17 (2.41-4.17) for those who returned to original work and 2.32 (1.81-2.97) for those re-employed as compared with who did not return to work and 1.27 (1.07-1.15) for those who retained their job as compared with those who did not. The ORs were 2.91 (2.26-3.75) for those who were re-employed and retained jobs and 2.96 (2.15-4.08) for those who returned to original work and did not retain jobs as compared with those who did not return to work and did not retain jobs. CONCLUSIONS: It is important for accident victims to retain their jobs to maintain their economic status.

Decomposing Magnetic Dark-Field Contrast in Spin Analyzed Talbot-Lau Interferometry: A Stern-Gerlach Experiment without Spatial Beam Splitting.

We have recently shown how a polarized beam in Talbot-Lau interferometric imaging can be used to analyze strong magnetic fields through the spin dependent differential phase effect at field gradients. While in that case an adiabatic spin coupling with the sample field is required, here we investigate a nonadiabatic coupling causing a spatial splitting of the neutron spin states with respect to the external magnetic field. This subsequently leads to no phase contrast signal but a loss of interferometer visibility referred to as dark-field contrast. We demonstrate how the implementation of spin analysis to the Talbot-Lau interferometer setup enables one to recover the differential phase induced to a single spin state. Thus, we show that the dark-field contrast is a measure of the quantum mechanical spin split analogous to the Stern-Gerlach experiment without, however, spatial beam separation. In addition, the spin analyzed dark-field contrast imaging introduced here bears the potential to probe polarization dependent small-angle scattering and thus magnetic microstructures.

An mHealth App (Speech Banana) for Auditory Training: App Design and Development Study.

BACKGROUND: With the growing adult population using electronic hearing devices such as cochlear implants or hearing aids, there is an increasing worldwide need for auditory training (AT) to promote optimal device use. However, financial resources and scheduling conflicts make clinical AT infeasible. OBJECTIVE: To address this gap between need and accessibility, we primarily aimed to develop a mobile health (mHealth) app called Speech Banana for AT. The app would be substantially more affordable and portable than clinical AT; would deliver a validated training model that is reflective of modern techniques; and would track users' progress in speech comprehension, providing greater continuity between periodic in-person visits. To improve international availability, our secondary aim was to implement the English language training model into Korean as a proof of concept for worldwide usability. METHODS: A problem- and objective-centered Design Science Research Methodology approach was adopted to develop the Speech Banana app. A review of previous literature and computer-based learning programs outlined current AT gaps, whereas interviews with speech pathologists and users clarified the features that were addressed in the app. Past and present users were invited to evaluate the app via community forums and the System Usability Scale. RESULTS: Speech Banana has been implemented in English and Korean languages for iPad and web use. The app comprises 38 lessons, which include analytic exercises pairing visual and auditory stimuli, and synthetic quizzes presenting auditory stimuli only. During quizzes, users type the sentence heard, and the app provides visual feedback on performance. Users may select a male or female speaker and the volume of background noise, allowing for training with a range of frequencies and signal-to-noise ratios. There were more than 3200 downloads of the English iPad app and almost 100 downloads of the Korean app; more than 100 users registered for the web apps. The English app received a System Usability Scale rating of "good" from 6 users, and the Korean app received a rating of "OK" from 16 users. CONCLUSIONS: Speech Banana offers AT accessibility with a validated curriculum, allowing users to develop speech comprehension skills with the aid of a mobile device. This mHealth app holds potential as a supplement to clinical AT, particularly in this era of global telemedicine.

Study on dark-field imaging with a laboratory x-ray source: Random stress variation analysis based on x-ray grating interferometry.

The dark-field image (DFI) in a grating interferometer involves the small-angle scattering properties of a material. The microstructure of the material can be characterized by an analysis of the auto-correlation length and the DFI. The feasibility of a DFI in a laboratory x-ray source with grating interferometry has been reported, but a follow-up study is needed. In this study, the random stress distribution was measured in the laboratory environment as an applied study. SiO2 mono-spheres as a cohesive powder with a 0.5 µm particle size were used as the sample. The microstructural changes according to the stresses on the particles were observed by acquiring a DFI along the auto-correlation length. In x-rays, a random two-phase media model was first used to analyze the characteristics of cohesive powder. This study showed that the microstructure of materials and x-ray images could be analyzed in a laboratory environment.

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Perineal involvement by metastatic renal cell carcinoma (RCC) is very rare, and there are only few reports on its radiological findings in the literature. Here, we present a case of a 76-year old female who presented with perineal pain caused by metastatic clear cell RCC. We discuss the radiological changes of the tumor before and after targeted therapy.

Neutron grating interferometer with an analyzer grating based on a light blocker.

We study an analyzer grating based on a scintillation light blocker for a Talbot-Lau grating interferometer. This is an alternative way to analyze the Talbot self-image without the need for an often difficult to fabricate absorption grating for the incident radiation. The feasibility of this approach using a neutron beam has been evaluated and experiments have been conducted at the cold neutron imaging facility of the NIST center for Neutron Research. The neutron grating interferometer with the proposed analyzer grating successfully produced attenuation, differential phase, and dark-field contrast images. In addition, numerical simulations were performed to simulate the Talbot pattern and visibility using scintillation screens of different thicknesses and there is good agreement with the experimental measurements. The results show potential for reducing the difficulty of fabricating analyzer grating, and a possibility for the so-called shadow effect to be eliminated and large-area gratings to be produced, especially when applied to X-rays. We report the performance of the analyzer grating based on a light blocker and evaluate its feasibility for the grating interferometer.

Spatio-temporal patterns of the minimum rest time for outdoor workers exposed to summer heat stress in South Korea.

In this study, the spatio-temporal characteristics of the minimum rest time for the safety of South Korean outdoor workers during hot summer months (June to August) are examined based on the hourly wet-bulb globe temperature (WBGT) across 27 weather stations in South Korea. The WBGT thresholds in the work-rest recommendation of the Korea Occupational Safety and Health Agency (KOSHA 2017) for the quantification of the minimum rest time are evaluated through a comparison of the given thresholds with the occurrences of occupational heat-related illness patients due to outdoor work during hot summer months in South Korea. The long-term (2009-2018) average of the hourly WBGT values during summer months shows that outdoor workers with a moderate workload are exposed to heat stress during approximately 30% of the entire daytime working hours (06:00-18:00). According to the WBGT thresholds modified from the KOSHA (2017) guidelines, the daily minimum rest time for a moderate workload noticeably increases up to 18% (11 min/h) in mid-summer (late July and early August). During mid-summer, the minimum rest time for a continuous moderate outdoor workload even increases up to 31% (18 min/h) between 12:00 and 13:00 and is regionally higher in the southwestern than in the southeastern regions of the Korean Peninsula. These results suggest that in summertime high-heat environments, a mandatory rest time must be provided according to appropriate heat management programs for the safety of workers.

Deep learning for high-resolution and high-sensitivity interferometric phase contrast imaging.

In Talbot-Lau interferometry, the sample position yielding the highest phase sensitivity suffers from strong geometric blur. This trade-off between phase-sensitivity and spatial resolution is a fundamental challenge in such interferometric imaging applications with either neutron or conventional x-ray sources due to their relatively large beam-defining apertures or focal spots. In this study, a deep learning method is introduced to estimate a high phase-sensitive and high spatial resolution image from a trained neural network to attempt to avoid the trade-off for both high phase-sensitivity and high resolution. To realize this, the training data sets of the differential phase contrast images at a pair of sample positions, one of which is close to the phase grating and the other close to the detector, are numerically generated and are used as the inputs for the training data set of a generative adversarial network. The trained network has been applied to the real experimental data sets from a neutron grating interferometer and we have obtained improved images both in phase-sensitivity and spatial resolution.