A machine learning approach to predicting dry eye-related signs, symptoms and diagnoses from meibography images.

Purpose: To use artificial intelligence to identify relationships between morphological characteristics of the Meibomian glands (MGs), subject factors, clinical outcomes, and subjective symptoms of dry eye. Methods: A total of 562 infrared meibography images were collected from 363 subjects (170 contact lens wearers, 193 non-wearers). Subjects were 67.2 % female and were 54.8 % Caucasian. Subjects were 18 years of age or older. A deep learning model was trained to take meibography as input, segment the individual MG in the images, and learn their detailed morphological features. Morphological characteristics were then combined with clinical and symptom data in prediction models of MG function, tear film stability, ocular surface health, and subjective discomfort and dryness. The models were analyzed to identify the most heavily weighted features used by the algorithm for predictions. Results: MG morphological characteristics were heavily weighted predictors for eyelid notching and vascularization, MG expressate quality and quantity, tear film stability, corneal staining, and comfort and dryness ratings, with accuracies ranging from 65 % to 99 %. Number of visible MG, along with other clinical parameters, were able to predict MG dysfunction, aqueous deficiency and blepharitis with accuracies ranging from 74 % to 85 %. Conclusions: Machine learning-derived MG morphological characteristics were found to be important in predicting multiple signs, symptoms, and diagnoses related to MG dysfunction and dry eye. This deep learning method illustrates the rich clinical information that detailed morphological analysis of the MGs can provide, and shows promise in advancing our understanding of the role of MG morphology in ocular surface health.

Multi-trait modeling and machine learning discover new markers associated with stem traits in alfalfa.

Alfalfa biomass can be fractionated into leaf and stem components. Leaves comprise a protein-rich and highly digestible portion of biomass for ruminant animals, while stems constitute a high fiber and less digestible fraction, representing 50 to 70% of the biomass. However, little attention has focused on stem-related traits, which are a key aspect in improving the nutritional value and intake potential of alfalfa. This study aimed to identify molecular markers associated with four morphological traits in a panel of five populations of alfalfa generated over two cycles of divergent selection based on 16-h and 96-h in vitro neutral detergent fiber digestibility in stems. Phenotypic traits of stem color, presence of stem pith cells, winter standability, and winter injury were modeled using univariate and multivariate spatial mixed linear models (MLM), and the predicted values were used as response variables in genome-wide association studies (GWAS). The alfalfa panel was genotyped using a 3K DArTag SNP markers for the evaluation of the genetic structure and GWAS. Principal component and population structure analyses revealed differentiations between populations selected for high- and low-digestibility. Thirteen molecular markers were significantly associated with stem traits using either univariate or multivariate MLM. Additionally, support vector machine (SVM) and random forest (RF) algorithms were implemented to determine marker importance scores for stem traits and validate the GWAS results. The top-ranked markers from SVM and RF aligned with GWAS findings for solid stem pith, winter standability, and winter injury. Additionally, SVM identified additional markers with high variable importance for solid stem pith and winter injury. Most molecular markers were located in coding regions. These markers can facilitate marker-assisted selection to expedite breeding programs to increase winter hardiness or stem palatability.

Factors associated with oropharyngeal dysphagia and unsuccessful nasogastric tube removal after endovascular thrombectomy for anterior circulation stroke.

PURPOSE: To identify the predictive variables for post-stroke dysphagia (PSD) among anterior circulation large vessel occlusion (LVO) stroke patients who underwent endovascular thrombectomy (EVT). METHODS: This retrospective cohort study enrolled hospitalized patients with anterior LVO stroke who underwent EVT between January 1, 2018 and October 31, 2022. PSD was defined as the unsuccessful removal of the nasogastric (NG) tube. Factors, such as premorbid characteristics, laboratory results, EVT, rehabilitation-related parameters, and neuro-imaging, were analyzed for correlations to PSD at 4 and 12 weeks. RESULTS: The study enrolled 136 patients, with a mean age of 72.9 ± 13.0 years, and 59 patients (43.4%) were male. At 4 weeks, 47.1% of the patients needed an NG tube, and at 12 weeks, 16.2% still required an NG tube. We found that lower albumin, lower body mass index (BMI), higher initial and 24-h post-EVT National Institute of Health Stroke Scale (NIHSS) scores, stroke-associated pneumonia, poor initial sitting balance and ability to sit up, insula or frontal operculum lesions, and bilateral hemisphere involvement were all associated with PSD at both 4 and 12 weeks in the univariate logistic regression. Multivariate analysis revealed that significant predictors of unsuccessful NG tube removal at 4 weeks included lower BMI (adjusted OR [aOR] 0.73, p = 0.005), hemorrhagic transformation (aOR 4.01, p = 0.0335), higher NIHSS scores at 24 h post-EVT (aOR 1.13, p = 0.0288), poor initial sitting ability (aOR 0.52, p = 0.0231), insular cortex ischemia (aOR 7.26, p = 0.0056), and bilateral hemisphere involvement (aOR 41.19, p < 0.0001). At 12 weeks, lower BMI (aOR 0.78, p = 0.0098), poor initial sitting balance (aOR 0.57, p = 0.0287), insular cortex lesions (aOR 4.83, p = 0.0092), and bilateral hemisphere involvement (aOR 4.07, p = 0.0139) remained significant predictors. CONCLUSIONS: In patients with anterior LVO following EVT, PSD was associated with lower BMI, higher NIHSS scores, poor initial sitting balance and sitting ability, insular lesions, and bilateral hemisphere involvement.

The importance of high total body water/fat free mass ratio and serial changes in body composition for predicting hospital mortality in patients with severe pneumonia: a prospective cohort study.

PURPOSE: This study aimed to investigate the impact of body composition variables on hospital mortality compared to other predictive factors among patients with severe pneumonia. Additionally, we aimed to monitor the dynamic changes in body composition variables over the course on days 1, 3, and 8 after intensive care unit (ICU) admission for each patient. METHODS: We conducted a prospective study, enrolling patients with severe pneumonia admitted to the medical intensive care unit at Kaohsiung Chang Gung Memorial Hospital from February 2020 to April 2022. We collected clinical data from all patients and assessed their body composition at 1, 3, and 8 days post-ICU admission. On day 1, we analyzed clinical and body composition variables to predict in-hospital mortality. RESULTS: Multivariate analysis identified the Modified Nutrition Risk in the Critically Ill (mNUTRIC) score and the ratio of total body water to fat-free mass (TBW/FFM) as independent factors associated with in-hospital mortality in severe pneumonia patients. Receiver operating characteristic analysis determined that the TBW/FFM ratio was the most reliable predictive parameter of in-hospital mortality, with a cutoff value of 0.74. General linear regression with repeated measures analysis showed that hospital non-survivors displayed notable fluctuations in body water, fat, and muscle variables over the course of days 1, 3, and 8 after ICU admission. CONCLUSIONS: The mNUTRIC score and TBW/FFM ratio emerged as independent factors for predicting hospital mortality, with the TBW/FFM ratio demonstrating the highest reliability as a predictive parameter.

Preoperative CT and Radiomics Nomograms for Distinguishing Bronchiolar Adenoma and Early-Stage Lung Adenocarcinoma.

RATIONALE AND OBJECTIVES: Evaluating the capability of CT nomograms and CT-based radiomics nomograms to differentiate between Bronchiolar Adenoma (BA) and Early-stage Lung Adenocarcinoma (LUAD). MATERIALS AND METHODS: In this retrospective study; we analyzed data from 226 patients who were treated at our institution and pathologically confirmed to have either BA or Early-stage LUAD. Patients were randomly divided into a training cohort (n=158) and a testing cohort (n=68). All CT images were independently analyzed and measured by two radiologists using conventional computed tomography. Clinical predictive factors were identified using logistic regression. Multivariable logistic regression analysis was used to construct differential diagnostic models for BA and early-stage LUAD, including traditional CT and radiomics models. The performance of the models was determined based on the area under the receiver operating characteristic curve, discrimination ability, and decision curve analysis (DCA). RESULTS: Lesion shape, tumor-lung interface, and pleural retraction signs were identified as independent clinical predictors. The areas under the curve for the CT nomogram, radiomic features, and radiomics nomogram were 0.854, 0.769, and 0.901, respectively. Both the CT nomogram and the radiomics nomogram demonstrated good generalizability in distinguishing between the two entities. DCA indicated that the nomograms achieved a higher net benefit compared to the use of radiomic features alone. CONCLUSION: The two preoperative nomograms hold significant value in differentiating between patients with BA and those with Early-stage LUAD, and they contribute to informed clinical treatment decision-making.

A robust inorganic binder against corrosion and peel-off stress in electrocatalysis.

Electrochemical binders used to immobilize electrocatalysts on electrodes are essential in all fields of electrochemistry. However, conventional organic-based binders like Nafion generally suffer from oxidative decomposition at high potentials on anodic electrodes and have high charge transport resistivity. This work proposes the use of acidic redox-assisted deposition to form cobalt manganese oxyhydroxides (CMOH) as a solid-state inorganic binder. CMOH remains stable under high oxidative currents and ensures catalyst adhesion even under significant peel-off stress as shown by experiments involving the alkaline oxygen evolution reaction (OER) using RuO2 as a catalyst immobilized on a rotating disc electrode. While the molecular structure of Nafion decays significantly after 45 minutes under OER conditions at 3.86 V, the CMOH binder is able to support the powder catalysts (RuO2 and NiO x ) showing stability around 1000 mA cm-2 without significant current decay over 24 hours. The robust catalyst adhesion is a result of the formation of chemical bonds between the electrode and the binder and it can be further improved by increasing the applied loading of CMOH. Unlike Nafion, both the OER activity and the diffusion kinetics are not significantly affected by the CMOH binder. It has also been shown that using CMOH as a binder leads to lower charge transfer resistances R ct and higher electrochemical surface areas compared to systems using Nafion. This is partially due to the presence of metal sites in different oxidation states which has been shown to increase intrinsic conductivity, facilitating the charge hopping at the binder/electrocatalyst interface. With this, the present work provides a proof-of-concept for inorganic metal oxides as promising solid-state binders for a wide range of applications in electrochemistry, demonstrating CMOH's outstanding characteristic of strong adhesion to support other highly active but adhesion-weak electrocatalysts.

Alkaline phosphatase-activated prodrug system based on a bifunctional CuO NP tandem nanoenzyme for on-demand bacterial inactivation and wound disinfection.

Nanozymes are promising antimicrobials, as they produce reactive oxygen species (ROS). However, the intrinsic lack of selectivity of ROS in distinguishing normal flora from pathogenic bacteria deprives nanozymes of the necessary selectivities of ideal antimicrobials. Herein, we exploit the physiological conditions of bacteria (high alkaline phosphatase (ALP) expression) using a novel CuO nanoparticle (NP) nanoenzyme system to initiate an ALP-activated ROS prodrug system for use in the on-demand precision killing of bacteria. The prodrug strategy involves using 2-phospho-L-ascorbic acid trisodium salt (AAP) that catalyzes the ALP in pathogenic bacteria to generate ascorbic acid (AA), which is converted by the CuO NPs, with intrinsic ascorbate oxidase- and peroxidase-like activities, to produce ROS. Notably, the prodrug system selectively kills Escherichia coli (pathogenic bacteria), with minimal influence on Staphylococcus hominis (non-pathogenic bacteria) due to their different levels of ALP expression. Compared to the CuO NPs/AA system, which generally depletes ROS during storage, CuO NPs/AAP exhibits a significantly higher stability without affecting its antibacterial activity. Furthermore, a rat model is used to indicate the applicability of the CuO NPs/AAP fibrin gel in wound disinfection in vivo with negligible side effects. This study reveals the therapeutic precision of this bifunctional tandem nanozyme platform against pathogenic bacteria in ALP-activated conditions.

Engineering a NanoBiT biosensor for detecting angiotensin-converting enzyme-2 (hACE2) interaction with SARS-CoV-2 spike protein and screening the inhibitors to block hACE2 and spike interaction.

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is facilitated by its trimeric surface spike protein, which binds to the human angiotensin-converting enzyme 2 (hACE2) receptor. This critical interaction facilitates viral entry and is a primary target for therapeutic intervention against COVID-19. However, it is difficult to fully optimize viral infection using existing protein-protein interaction methods. Herein, we introduce a nano-luciferase binary technology (NanoBiT)-based pseudoviral sensor designed to stimulate the dynamics of viral infection in both living cells and animals. Infection progression can be dynamically visualized via a rapid increase in luminescence within 3 h using an in vivo imaging system (IVIS). Inhibition of viral infection by baicalein and baicalin was evaluated using a NanoBiT-based pseudoviral sensor. These results indicate that the inhibitory efficacy of baicalein was strengthened by targeting the spike protein, whereas baicalin targeted the hACE2 protein. Additionally, under optimized conditions, baicalein and baicalin provided a synergistic combination to inhibit pseudoviral infection. Live bioluminescence imaging was used to evaluate the in vivo effects of baicalein and baicalin treatment on LgBiT-hACE2 mice infected with the BA.2-SmBiT spike pseudovirus. This innovative bioluminescent system functions as a sensitive and early-stage quantitative viral transduction in vitro and in vivo. This platform provides novel opportunities for studying the molecular biology of animal models.

The impact of emotion regulation strategies on disordered eating behavior in children and adolescents with type 1 diabetes: a cross-sectional study.

Objective: Difficulties in emotion regulation (DERs) can contribute to disordered eating behavior in children and adolescents with type 1 diabetes (T1D), although it is unknown how DERs may affect eating behavior in these children and adolescents. This study examined the relationship between disordered eating behaviors and emotion regulation in children and adolescents with T1D. Methods: For this cross-sectional study, 128 patients (aged 8-16 years) were recruited to complete the Diabetes Eating Problem Survey-Revised (DEPS-R) and Difficulties in Emotion Regulation Scale (DERs). Results: The mean age of the 128 patients (99 females) who completed the DEPS-R was 11.63 ± 2.27 years. The participants' mean DEPS-R score was 17.78 ± 8.56 points. Of the total sample, 61 participants' scores surpassed the established threshold, resulting in a DEPS-R positivity rate of 47.66%. The participants' mean total DERS score was 72.3 ± 21.15 points, and it was found that children and adolescents with T1D who had a positive DEPS-R screening result had significant differences in emotional regulation and that eating behavior disorders were positively correlated with emotional regulation and all dimensions scores. Conclusions: The prevalence of disordered eating behavior is high among children and adolescents with T1D. DERs are related to disordered eating behavior in children and adolescents with T1D. The novel finding that DERs may be a predictor of eating problems lends preliminary support for the inclusion of DERs in future risk models and as a potential target for intervention.

Heterozygous de novo dominant negative mutation of REXO2 results in interferonopathy.

Mitochondrial RNA (mtRNA) in the cytosol can trigger the innate immune sensor MDA5, and autoinflammatory disease due to type I IFN. Here, we show that a dominant negative mutation in the gene encoding the mitochondrial exonuclease REXO2 may cause interferonopathy by triggering the MDA5 pathway. A patient characterized by this heterozygous de novo mutation (p.T132A) presented with persistent skin rash featuring hyperkeratosis, parakeratosis and acanthosis, with infiltration of lymphocytes and eosinophils around small blood vessels. In addition, circulating IgE levels and inflammatory cytokines, including IFNα, are found consistently elevated. Transcriptional analysis highlights a type I IFN gene signature in PBMC. Mechanistically, REXO2 (T132A) lacks the ability to cleave RNA and inhibits the activity of wild-type REXO2. This leads to an accumulation of mitochondrial dsRNA in the cytosol, which is recognized by MDA5, leading to the associated type I IFN gene signature. These results demonstrate that in the absence of appropriate regulation by REXO2, aberrant cellular nucleic acids may accumulate and continuously trigger innate sensors, resulting in an inborn error of immunity.

Enhancing Outcomes in Chronic Fibrotic Interstitial Lung Disease Through Aggressive Management of Nintedanib-Induced Adverse Drug Reactions: A Retrospective Analysis.

BACKGROUND AND OBJECTIVES: Nintedanib, a tyrosine kinase inhibitor, is integral in slowing pulmonary fibrosis progression in chronic fibrotic interstitial lung disease (ILD). However, the occurrence of adverse drug reactions (ADRs) often limits its use, leading to treatment discontinuation, typically within 3-12 months. Discontinuation adversely affects patient outcomes. The study investigated whether aggressive ADR management can prolong nintedanib therapy and improve patient outcomes. METHODS: This retrospective, single-center study enrolled Taiwanese patients with chronic fibrotic ILD who were treated with nintedanib from January 2016 to December 2022 in Kaohsiung Chang Gung Memorial Hospital. Patients were categorized into those who discontinued treatment within 180 days and those continuing beyond. Management of ADRs was identified through concurrent prescriptions for symptoms such as nausea, vomiting, diarrhea, or hepatic dysfunction. Baseline demographics, comorbidities, pulmonary function tests, and instances of acute exacerbation were analyzed. RESULTS: The study enrolled 94 patients, with 71 (75.5%) experiencing ADRs. Among these, 41 (43.6%) discontinued nintedanib within 180 days. The administration of medications for managing nausea/vomiting [17 (41.5%) versus 36 (67.9%), p = 0.0103] and diarrhea [12 (29.3%) versus 33 (62.3%), p = 0.0015] was less frequent in the discontinued group compared with the continued group. Additionally, a higher incidence of acute exacerbation was observed in the discontinued group (34.1% versus 20.8%, p = 0.016). CONCLUSION: Aggressive management of ADRs may enhance patient tolerance to nintedanib, potentially prolonging treatment duration and improving outcomes in chronic fibrotic ILD.

Impacts of Matrix Metalloproteinase-2 Promoter Genotypes on Breast Cancer Risk.

BACKGROUND/AIM: Matrix metalloproteinase-2 (MMP-2) has been implicated in the pathogenesis of breast cancer (BC). However, there is limited research on the role of MMP-2 genotypes in BC risk. This study aimed to investigate the associations between two MMP-2 promoter polymorphisms, rs243865 and rs2285053, and BC risk. MATERIALS AND METHODS: MMP-2 genotypes were analyzed using PCR-based RFLP methodology in a cohort comprising 1,232 BC cases and 1,232 controls. RESULTS: Genotypic frequencies of MMP-2 rs243865 and rs2285053 in controls were consistent with Hardy-Weinberg equilibrium (p=0.3702 and 0.2036, respectively). There were no significant differences in the distribution of rs243865 and rs2285053 genotypes between BC cases and controls (p for trend=0.1602 and 0.2170, respectively). Variant genotypes at rs243865 and rs2285053 appeared to confer a protective effect, although not statistically significant (all p>0.05). Similarly, the variant T allele at rs243865 and rs2285053 showed a non-significant trend towards decreased BC risk (OR=0.84 and 0.89, 95%CI=0.69-1.02 and 0.78-1.02, p=0.0811 and 0.1043, respectively). There was no interaction observed between MMP-2 rs243865 or rs2285053 genotypes and age. Stratified analysis did not reveal significant associations between MMP-2 rs243865 or rs2285053 genotypes and triple-negative breast cancer (TNBC) (p=0.6458 and 0.8745, respectively). Among both TNBC and non-TNBC cases, none of the variant genotypes at rs243865 or rs2285053 showed significant associations with TNBC (all p>0.05). CONCLUSION: MMP-2 rs243865 and rs2285053 genotypes appear to have a minimal impact on individual susceptibility to BC or TNBC.

ROS-Responsive Nanoprobes for Bimodal Imaging-Guided Cancer Targeted Combinatorial Therapy.

Purpose: Chemotherapy mediated by Reactive oxygen species (ROS)-responsive drug delivery systems can potentially mitigate the toxic side effects of chemotherapeutic drugs and significantly enhance their therapeutic efficacy. However, achieving precise targeted drug delivery and real-time control of ROS-responsive drug release at tumor sites remains a formidable challenge. Therefore, this study aimed to describe a ROS-responsive drug delivery system with specific tumor targeting capabilities for mitigating chemotherapy-induced toxicity while enhancing therapeutic efficacy under guidance of Fluorescence (FL) and Magnetic resonance (MR) bimodal imaging. Methods: Indocyanine green (ICG), Doxorubicin (DOX) prodrug pB-DOX and Superparamagnetic iron oxide (SPIO, Fe3O4) were encapsulated in poly(lactic-co-glycolic acid) (PLGA) by double emulsification method to prepare ICG/ pB-DOX/ Fe3O4/ PLGA nanoparticles (IBFP NPs). The surface of IBFP NPs was functionalized with mammaglobin antibodies (mAbs) by carbodiimide method to construct the breast cancer-targeting mAbs/ IBFP NPs (MIBFP NPs). Thereafter, FL and MR bimodal imaging ability of MIBFP NPs was evaluated in vitro and in vivo. Finally, the combined photodynamic therapy (PDT) and chemotherapy efficacy evaluation based on MIBFP NPs was studied. Results: The multifunctional MIBFP NPs exhibited significant targeting efficacy for breast cancer. FL and MR bimodal imaging clearly displayed the distribution of the targeting MIBFP NPs in vivo. Upon near-infrared laser irradiation, the MIBFP NPs loaded with ICG effectively generated ROS for PDT, enabling precise tumor ablation. Simultaneously, it triggered activation of the pB-DOX by cleaving its sensitive moiety, thereby restoring DOX activity and achieving ROS-responsive targeted chemotherapy. Furthermore, the MIBFP NPs combined PDT and chemotherapy to enhance the efficiency of tumor ablation under guidance of bimodal imaging. Conclusion: MIBFP NPs constitute a novel dual-modality imaging-guided drug delivery system for targeted breast cancer therapy and offer precise and controlled combined treatment options.

Neuregulin 4 Attenuates Podocyte Injury and Proteinuria in Part by Activating AMPK/mTOR-Mediated Autophagy in Mice.

In this study, we investigate the effect of neuregulin 4 (NRG4) on podocyte damage in a mouse model of diabetic nephropathy (DN) and we elucidate the underlying molecular mechanisms. In vivo experiments were conducted using a C57BL/6 mouse model of DN to determine the effect of NRG4 on proteinuria and podocyte injury, and in vitro experiments were performed with conditionally immortalized mouse podocytes treated with high glucose and NRG4 to assess the protective effects of NRG4 on podocyte injury. Autophagy-related protein levels and related signaling pathways were evaluated both in vivo and in vitro. The involvement of the adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway was detected using chloroquine or AMPK inhibitors. The results showed that the AMPK/mTOR pathway was involved in the protective roles of NRG4 against high glucose-mediated podocyte injury. Also, NRG4 significantly decreased albuminuria in DN mice. PAS staining indicated that NRG4 mitigated glomerular volume and mesangium expansion in DN mice. Consistently, western blot and RT-PCR analyses confirmed that NRG4 decreased the expression of pro-fibrotic molecules in the glomeruli of DN mice. The immunofluorescence results showed that NRG4 retained expression of podocin and nephrin, whereas transmission electron microscopy revealed that NRG4 alleviated podocyte injury. In DN mice, NRG4 decreased podocyte apoptosis and increased expression of nephrin and podocin, while decreasing the expression of desmin and HIF1α. Overall, NRG4 improved albuminuria, glomerulosclerosis, glomerulomegaly, and hypoxia in DN mice. The in vitro experiments showed that NRG4 inhibited HG-induced podocyte injury and apoptosis. Furthermore, autophagy of the glomeruli decreased in DN mice, but reactivated following NRG4 intervention. NRG4 intervention was found to partially activate autophagy via the AMPK/mTOR signaling pathway. Consequently, when the AMPK/mTOR pathway was suppressed or autophagy was inhibited, the beneficial effects of NRG4 intervention on podocyte injury were diminished. These results indicate that NRG4 intervention attenuates podocyte injury and apoptosis by promoting autophagy in the kidneys of DN mice, in part, by activating the AMPK/mTOR signaling pathway.

The Relationship Between Carotid Artery Stenosis and the Development of Open-Angle Glaucoma: A Long-term Cohort Study in Taiwan.

PURPOSES: To determine the relationship between carotid artery stenosis (CAS) and the development of open-angle glaucoma (OAG) in the Taiwanese population. METHODS: This retrospective cohort study was conducted using Chang Gung Research Database. Cox-proportional hazards model was applied to calculate the hazard ratio for OAG between CAS and the control cohort. RESULTS: Among 19,590 CAS patients, 17,238 had mild CAS (<50%), 1,895 had moderate CAS (50-69%), and 457 had severe CAS (≥70%). The CAS cohort had a higher proportion of several comorbidities. After adjusting for comorbidities, no significant difference in OAG development was found between CAS and control cohorts. Matching for key comorbidities, no significant differences in OAG incidence were found between matched cohorts (P = .869). Subdividing the matched CAS cohort by stenosis severity: mild (<50%), moderate (50-69%), and severe (≥70%), a statistically significantly lower OAG risk was observed in patients with mild CAS stenosis (HR: 1.12, 95% CI = 1.03-1.21, P = .006). Kaplan-Meier analysis revealed reduced OAG incidence in CAS patients who underwent surgical intervention, compared to the control cohort (P <.001). Subgroup analysis revealed that patients in the mild CAS stenosis group, those who underwent surgical intervention exhibited a reduced OAG risk (HR: 0.29, 95% CI = 0.15-0.58, P = .001). CONCLUSIONS: No statistically significant differences in OAG risk were observed between patients with CAS and the control cohort. The severity of CAS appears to influence OAG risk, with surgical intervention potentially offering protective effects, particularly in patients with mild CAS stenosis (<50%), suggesting that enhanced ocular perfusion post-surgery may act as a protective factor against OAG development.

The association of temporalis muscle thickness with post-stroke dysphagia based on swallowing kinematic analysis.

BACKGROUND/PURPOSE: Post-stroke dysphagia (PSD) is a common functional deficit after stroke. Temporal muscle thickness (TMT) had been proven to be an independent factor for PSD. However, the relationship between TMT and PSD based on quantitative swallowing kinematic analysis remains unexplored. We aimed to investigate the association between TMT and PSD using videofluoroscopic swallow study (VFSS). METHOD: We retrospectively recruited stroke patients from May 2015 to March 2020 in the tertiary referral hospital. A total of 83 patients with dysphagia met all the enrollment criteria and were included in the study. TMT was measured by non-contrast brain computed tomography (CT) images. Parameters of VFSS were obtained, including penetration-aspiration scale (PAS), oral transit time (OTT), pharyngeal transit time (PTT) and swallowing trigger time (STT) in four standardized barium formulas respectively. The association between TMT and variables of VFSS were analyzed by adjusted linear and logistic multivariate regression models. Subgroup analysis based on age, sex, and premorbid modified Rankin Scale (mRS) stratification was conducted. RESULTS: TMT was significantly correlated with gender and premorbid mRS as the confounders. Univariate regression showed smaller TMT (p = 0.010) and poorer premorbid mRS (p = 0.018) was associated with prolonged PTT of the thick formula; lesser TMT was associated with prolonged PTT of the paste formula (p = 0.037). Multivariate analyses after confounder-adjustment demonstrated TMT was an independent indicator for PTT in the thick formula (p = 0.028). CONCLUSIONS: TMT was associated with swallowing kinematic changes in patients diagnosed with PSD. TMT is an independent indicator for delayed pharyngeal stage in the thick standardized formula during deglutition in PSD patients.

Localized Evaporative Cooling Explains Observed Ocular Surface-Temperature Patterns.

Purpose: We determined interblink corneal surface-temperature decline and tear-film evaporation rates of localized tear breakup cold regions (LCRs) and localized tear unbroken warm regions (LWRs) of the corneal surface, as well as that of the overall average corneal surface. Methods: Each subject underwent 4 inter-day visits where the interblink corneal surface-temperature history of the right eye was measured using a FLIR A655sc infrared thermographer. Corneal surface temperature history was analyzed to determine the overall, LCR, and LWR temperature-decline rates. Evaporation rates of LCR and LWR regions were determined from the measured LCR and LWR temperature data using the physical model of Dursch et al. Results: Twenty subjects completed the study. Mean (SD) difference of LCR temperature-decline rate was -0.08 (0.07)°C/s faster than LWR (P < 0.0001). Similarly, evaporation rates of LCR and LWR were statistically different (P < 0.0001). At ambient temperature, mean LCR and LWR evaporation rates were 76% and 27% of pure water evaporation flux, respectively. There was no statistically significant difference between the inter-day measured temperature-decline rates and the interblink starting temperature. Conclusions: Significant differences in corneal temperature-decline rate and evaporation rate between LCR and LWR were quantified using infrared thermography. In agreement with literature, LCRs and LWRs correlate directly with fluorescein break-up areas and unbroken tear areas, respectively. Because lipid-evaporation protection is diminished in breakup areas, higher local evaporation rates and faster local cooling rates occur in LCRs relative to LWRs. Our results confirm this phenomenon clinically for the first time.

Effect of dapagliflozin on uric acid in patients with chronic heart failure and hyperuricemia.

BACKGROUND: Patients with chronic heart failure (CHF) frequently develop hyperuricemia, an elevated serum uric acid level, associated with adverse outcomes. Dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, demonstrates reduction in cardiovascular mortality and hospitalization in patients with CHF and ejection fraction (HFrEF), irrespective of diabetes. However, dapagliflozin's effect on the uric acid levels in patients with CHF and hyperuricemia remain unclear. AIM: To investigate the effects of dapagliflozin on uric acid levels in CHF patients with hyperuricemia. METHODS: We conducted a randomized, double-blind, placebo-controlled trial in 200 patients with CHF and hyperuricemia, with HFrEF and serum uric acid levels ≥ 7 mg/dL (≥ 416 µmol/L). The participants were randomly assigned to receive a daily dose of 10 mg dapagliflozin or placebo for 24 months. The primary endpoint was the change in serum uric acid level from baseline to 24 months. Secondary endpoints included changes in left ventricular ejection fraction (LVEF), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and quality of life (QoL) scores, as well as the incidence of cardiovascular death and hospitalization for heart failure. RESULTS: At 24 months, dapagliflozin significantly reduced serum uric acid levels by 1.2 mg/dL (71 µmol/L) compared with placebo (95%CI: -1.5 to -0.9; P < 0.001). Dapagliflozin also significantly improved LVEF by 3.5% (95%CI: 2.1-4.9; P < 0.001), NT-proBNP by 25% (95%CI: 18-32; P < 0.001), and QoL scores by 10 points (95%CI: 7-13; P < 0.001) and reduced the risk of cardiovascular death and hospitalization for heart failure by 35% (95%CI: 15-50; P = 0.002) compared with the placebo. Adverse events were similar between the two groups, except for a higher rate of genital infections in the dapagliflozin group (10% vs 2%, P = 0.01). CONCLUSION: Dapagliflozin significantly lowered serum uric acid levels and improved the clinical outcomes in patients with CHF and hyperuricemia. Therefore, dapagliflozin may be a useful therapeutic option for this high-risk population.