Virtual reality skateboarding training for balance and functional performance in degenerative lumbar spine disease.

BACKGROUND: Degenerative lumbar spine disease (DLD) is a prevalent condition in middle-aged and elderly individuals. DLD frequently results in pain, muscle weakness, and motor impairment, which affect postural stability and functional performance in daily activities. Simulated skateboarding training could enable patients with DLD to engage in exercise with less pain and focus on single-leg weight-bearing. The purpose of this study was to investigate the effects of virtual reality (VR) skateboarding training on balance and functional performance in patients with DLD. METHODS: Fourteen patients with DLD and 21 age-matched healthy individuals completed a 6-week program of VR skateboarding training. The motion capture and force platform systems were synchronized to collect data during a single-leg stance test (SLST). Musculoskeletal simulation was utilized to calculate muscle force based on the data. Four functional performance tests were conducted to evaluate the improvement after the training. A Visual Analogue Scale (VAS) was also employed for pain assessment. RESULTS: After the training, pain intensity significantly decreased in patients with DLD (p = 0.024). Before the training, patients with DLD took longer than healthy individuals on the five times sit-to-stand test (p = 0.024). After the training, no significant between-group differences were observed in any of the functional performance tests (p > 0.05). In balance, patients with DLD were similar to healthy individuals after the training, except that the mean frequency (p = 0.014) was higher. Patients with DLD initially had higher biceps femoris force demands (p = 0.028) but shifted to increased gluteus maximus demand after the training (p = 0.037). Gluteus medius strength significantly improved in patients with DLD (p = 0.039), while healthy individuals showed consistent muscle force (p > 0.05). CONCLUSION: This is the first study to apply the novel VR skateboarding training to patients with DLD. VR skateboarding training enabled patients with DLD to achieve the training effects in a posture that relieves lumbar spine pressure. The results also emphasized the significant benefits to patients with DLD, such as reduced pain, enhanced balance, and improved muscle performance.

Tumor Location Is an Independent Prognostic Factor in Completely Resected Pathological Stage I Non-Small Cell Lung Cancer: A Multicenter Retrospective Study.

Previous studies suggested that the location of the primary tumor in non-small cell lung cancer (NSCLC) is associated with clinical features and prognosis, but results are conflicting. The purpose of this study was to explore tumor location as an independent risk factor of survival for patients with completely resected pathological stage I NSCLC. This was a multicenter retrospective study conducted in Taiwan. Included patients were diagnosed with stage I NSCLC and had undergone primary tumor resection. Variables including tumor location, pathological stage, histological differentiation, and International Association for the Study of Lung Cancer (IASLC) grade were evaluated for predictive ability for disease-free survival (DFS) and overall survival (OS). A total of 208 patients were included, with 123 (59.1%) patients having a primary tumor in the upper and middle lobes. The median duration of follow-up for survivors was 60.5 months. Compared to patients with IASLC Grade 3 disease, patients with Grade 1 disease had significantly longer DFS. Tumor location and IASLC grade were independent predictors for OS in multivariate analysis. Specifically, patients with NSCLC in the lower lobe and patients who are histologically classified as IASLC Grade 3 may have poorer prognosis and require greater attention to improve outcomes.

Physical function as a predictor of chemotherapy-induced peripheral neuropathy in patients with pancreatic cancer.

BACKGROUND: A growing body of research indicates that poor functional status before chemotherapy may be correlated with the severity of chemotherapy-induced peripheral neuropathy (CIPN) after the neurotoxic treatment. However, little is known about the associations between pre-chemotherapy physical function and CIPN in patients with pancreatic cancer. PURPOSE: To identify the predictors of CIPN in relation to pre-chemotherapy physical function in patients with pancreatic cancer. METHODS: This secondary analysis included data from patients with pancreatic cancer who participated in a longitudinal research study at National Cheng Kung University Hospital, Tainan, Taiwan. Four physical function tests (i.e., grip strength, Timed Up and Go (TUG), 2-minute step test (2MST), and Romberg test) and two questionnaires (The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 [EORTC QLQ-C30] and Chemotherapy-Induced Peripheral Neuropathy Module [CIPN20]) were assessed at baseline (i.e., before first chemotherapy session) and 2-, 3-, 4-, and 6-month follow-up. Multiple linear regression with adjustment for confounding factors was used to assess the associations between the four functional tests at baseline and the CIPN20 total score and individual subscale scores (sensory, motor, and autonomic) at 6-month follow-up. RESULTS: Data from a total of 209 pancreatic cancer patients (mean age: 64.4 years, 54.5% male) were analyzed. The findings showed that the severity of CIPN at 6-month follow-up was significantly associated with the baseline TUG completion time (ß = 0.684, p = 0.003). The TUG completion time was also positively correlated with the 6-month CIPN sensory and autonomic subscales. In addition, a baseline positive Romberg test (ß = 0.525, p = 0.009) was a significant predictor of the severity of motor neuropathy at 6-month follow-up. CONCLUSION: The TUG completion time and positive Romberg test before chemotherapy may be predictive factors of the CIPN severity 6 months after the commencement of chemotherapy. Accordingly, the incorporation of TUG and Romberg tests into the clinical assessment protocol emerges as imperative for individuals diagnosed with pancreatic carcinoma undergoing chemotherapy regimens.

Optimizing SARS-CoV-2 vaccine responses in kidney transplant recipients: an urgent need.

Kidney transplant recipients (KTRs) have been identified as a population at increased risk for severe SARS-CoV-2 infection outcomes. This study focused on understanding the immune response of KTRs post-vaccination, specifically examining both serological and cellular responses to the SARS-CoV-2 vaccine. Thirteen individuals, including seven KTRs and six healthy donors, were evaluated for antibody levels and T cell responses post-vaccination. The study revealed that KTRs had significantly lower serological responses, including reduced anti-receptor binding domain (RBD) binding antibodies and neutralizing antibodies against the Wuhan, Delta, and Omicron BA.2 strains. Additionally, KTRs demonstrated weaker CD8 T cell cytotoxic responses and lower Th1 cytokine secretion, particularly IFN-γ, after stimulation with variant spike peptide pools. These findings highlight the compromised immunity in KTRs post-vaccination and underscore the need for tailored strategies to bolster immune responses in this vulnerable group. Further investigations are warranted into the mechanisms underlying reduced vaccine efficacy in KTRs and potential therapeutic interventions. IMPORTANCE: Some studies have revealed that KTRs had lower serological response against SARS-CoV-2 than healthy people. Nevertheless, limited studies investigate the cellular response against SARS-CoV-2 in KTRs receiving SARS-CoV-2 vaccines. Here, we found that KTRs have lower serological and cellular responses. Moreover, we found that KTRs had a significantly lower IFN-γ secretion than healthy individuals when their PBMCs were stimulated with SARS-CoV-2 spike peptide pools. Thus, our findings suggested that additional strategies are needed to enhance KTR immunity triggered by the vaccine.

Identification of high sugar diet-induced dysregulated metabolic pathways in muscle using tissue-specific metabolic models in Drosophila.

Individual tissues perform highly specialized metabolic functions to maintain whole-body homeostasis. Although Drosophila serves as a powerful model for studying human metabolic diseases, a lack of tissue-specific metabolic models makes it challenging to quantitatively assess the metabolic processes of individual tissues and disease models in this organism. To address this issue, we reconstructed 32 tissue-specific genome-scale metabolic models (GEMs) using pseudo-bulk single cell transcriptomics data, revealing distinct metabolic network structures across tissues. Leveraging enzyme kinetics and flux analyses, we predicted tissue-dependent metabolic pathway activities, recapitulating known tissue functions and identifying tissue-specific metabolic signatures, as supported by metabolite profiling. Moreover, to demonstrate the utility of tissue-specific GEMs in a disease context, we examined the effect of a high sugar diet (HSD) on muscle metabolism. Together with 13C-glucose isotopic tracer studies, we identified glyceraldehyde 3-phosphate dehydrogenase (GAPDH) as a rate-limiting enzyme in glycolysis in response to HSD. Decreased GAPDH activity was linked to increased NADH/NAD+ ratio and oxidation of GAPDH. Furthermore, we introduced a pathway flux index to predict and validate additionally perturbed pathways, including fructose and butanoate metabolism. Altogether, our results represent a significant advance in generating quantitative tissue-specific GEMs and flux analyses in Drosophila, highlighting their use for identifying dysregulated metabolic pathways in a human disease model.

Effect of Cold Versus Hot Snare Polypectomy on Colon Postpolypectomy Bleeding in Patients with End-Stage Renal Disease: A Retrospective Cohort Study.

BACKGROUND: Patients with end-stage renal disease (ESRD) who undergo polypectomy may experience postpolypectomy bleeding. To reduce the risk of delayed postpolypectomy bleeding among the general population, cold snare polypectomy (CSP) is recommended for removing colon polyps smaller than 1 cm. Nevertheless, only few studies have examined the effect of CSP on patients with ESRD. METHODS: We retrospectively analyzed the data of patients with ESRD who underwent colonoscopic polypectomy for polyps larger than 5 mm at a Taiwanese university hospital from January 2014 to January 2023. The main outcome was delayed postpolypectomy bleeding within 30 days. Multivariate analysis was conducted to adjust for major confounders. RESULTS: A total of 557 patients with ESRD underwent colonoscopic polypectomy during the study period: 201 underwent CSP and 356 underwent hot snare polypectomy (HSP). Delayed postpolypectomy bleeding occurred in 27 patients (4.8%). The rate of delayed postpolypectomy bleeding was lower in patients with ESRD who underwent CSP than in those who underwent HSP (1.9% vs. 6.4%, P = 0.022). The percentage of patients who did not experience postpolypectomy bleeding within 30 days after CSP remained lower than that observed after HSP (P = 0.019, log-rank test). Multivariate analysis demonstrated immediate postpolypectomy bleeding and HSP to be independent risk factors for delayed postpolypectomy bleeding. A nomogram prognostic model was used to predict the potential of delayed postpolypectomy bleeding within 30 days in patients with ESRD. CONCLUSIONS: Compared with HSP, CSP is more effective in mitigating the risk of delayed postpolypectomy bleeding in patients with ESRD.

Fat loss and muscle gain: The possible role of cortical glutamate in determining the efficacy of physical exercise.

BACKGROUND: Physical exercise is widely acknowledged for its health benefits, but its effectiveness in treating obesity remains contentious due to variability in response. Owing to the roles of glutamate in appetite regulation, food addiction, and impulsivity, this observational cohort-study evaluated medial prefrontal cortex (mPFC) glutamate as a predictor of variability in exercise response, specifically in terms of fat loss and muscle gain. METHODS: Healthy non-exercising adult men (n = 21) underwent an 8-week supervised exercise program. Baseline glutamate levels in the mPFC were measured through magnetic resonance spectroscopy. For exercise-dependent changes in body composition (fat and muscle mass), basal metabolic rate (BMR), and blood metabolic biomarkers related to lipid and glucose metabolism, measurements were obtained through bioelectrical impedance and blood sample analyses, respectively. RESULTS: The exercise program resulted in significant improvements in body composition, including reductions in percentage body fat mass, body fat mass, and waist-to-hip ratio and an increase in mean muscle mass. Furthermore, BMR and metabolic indicators linked to glucose and lipids exhibited significant changes. Notably, lower baseline glutamate levels were associated with greater loss in percentage body fat mass (r = 0.482, p = 0.027), body fat mass (r = 0.441, p = 0.045), and increase in muscle mass (r = -0.409, p = 0.066, marginal) following the exercise program. CONCLUSION: These preliminary findings contribute to our understanding of the neurobiology of obesity and emphasize the significance of glutamate in regulating body composition. The results also highlight cortical glutamate as a potential predictor of exercise-induced fat loss and muscle gain.

Syndecan-4 is required for early-stage repair responses during zebrafish heart regeneration.

BACKGROUND: The healing process after a myocardial infarction (MI) in humans involves complex events that replace damaged tissue with a fibrotic scar. The affected cardiac tissue may lose its function permanently. In contrast, zebrafish display a remarkable capacity for scar-free heart regeneration. Previous studies have revealed that syndecan-4 (SDC4) regulates inflammatory response and fibroblast activity following cardiac injury in higher vertebrates. However, whether and how Sdc4 regulates heart regeneration in highly regenerative zebrafish remains unknown. METHODS AND RESULTS: This study showed that sdc4 expression was differentially regulated during zebrafish heart regeneration by transcriptional analysis. Specifically, sdc4 expression increased rapidly and transiently in the early regeneration phase upon ventricular cryoinjury. Moreover, the knockdown of sdc4 led to a significant reduction in extracellular matrix protein deposition, immune cell accumulation, and cell proliferation at the lesion site. The expression of tgfb1a and col1a1a, as well as the protein expression of Fibronectin, were all down-regulated under sdc4 knockdown. In addition, we verified that sdc4 expression was required for cardiac repair in zebrafish via in vivo electrocardiogram analysis. Loss of sdc4 expression caused an apparent pathological Q wave and ST elevation, which are signs of human MI patients. CONCLUSIONS: Our findings support that Sdc4 is required to mediate pleiotropic repair responses in the early stage of zebrafish heart regeneration.

Finding Your CAR: The Road Ahead for Engineered T Cells.

Adoptive cellular therapy using chimeric antigen receptors (CARs) has transformed immunotherapy by engineering T cells to target specific antigens on tumor cells. As the field continues to advance, pathology laboratories will play increasingly essential roles in the complicated multi-step process of CAR T-cell therapy. These include detection of targetable tumor antigens by flow cytometry or immunohistochemistry at the time of disease diagnosis and the isolation and infusion of CAR T cells. Additional roles include: i) detecting antigen loss or heterogeneity that renders resistance to CAR T cells as well as identifying alternative targetable antigens on tumor cells, ii) monitoring the phenotype, persistence, and tumor infiltration properties of CAR T cells and the tumor microenvironment for factors that predict CAR T-cell therapy success, and iii) evaluating side effects and biomarkers of CAR T-cell cytotoxicity such as cytokine release syndrome. This review highlights existing technologies that are applicable to monitoring CAR T-cell persistence, target antigen identification, and loss. Also discussed are emerging technologies that address new challenges such as how to put a brake on CAR T cells. Although pathology laboratories have already provided companion diagnostic tests important in immunotherapy (eg, programmed death-ligand 1, microsatellite instability, and human epidermal growth factor receptor 2 testing), we draw attention to the exciting new translational research opportunities in adoptive cellular therapy.

Subclass phenotypes in patients with unprovoked venous thromboembolisms using a latent class analysis.

BACKGROUND: Patients with unprovoked venous thromboembolisms (VTEs) can be sub-classified based on the different phenotypes using a latent class analysis (LCA), which might be useful for selecting individual management strategies. METHODS: In the COMMAND VTE Registry-2 database enrolling 5197 VTE patients, the current derivation cohort consisted of 1556 patients with unprovoked VTEs. We conducted clustering with an LCA, and the patients were classified into subgroups with the highest probability. We compared the clinical characteristics and outcomes among the developed subgroups. RESULTS: This LCA model proposed 3 subgroups based on 8 clinically relevant variables, and classified 592, 813, and 151 patients as Class I, II, and III, respectively. Based on the clinical features, we named Class I the younger, Class II the older with a few comorbidities, and Class III the older with many comorbidities. The cumulative 3-year anticoagulation discontinuation rate was highest in the older with many comorbidities (Class III) (39.9 %, 36.1 %, and 48.4 %, P = 0.02). There was no significant difference in the cumulative 5-year incidence of recurrent VTEs among the 3 classes (12.8 %, 11.1 %, and 4.0 % P = 0.20), whereas the cumulative 5-year incidence of major bleeding was significantly higher in the older with many comorbidities (Class III) (7.8 %, 12.7 %, and 17.8 %, P = 0.04). CONCLUSION: The current LCA revealed that patients with unprovoked VTEs could be sub-classified into further phenotypes depending on the patient characteristics. Each subclass phenotype could have different clinical outcomes risks especially a bleeding risk, which could have a potential benefit when considering the individual anticoagulation strategies. CLINICAL TRIAL REGISTRATION: URL: http://www.umin.ac.jp/ctr/index.htm COMMAND VTE Registry-2: Unique identifier, UMIN000044816 COMMAND VTE Registry: Unique identifier, UMIN000021132.

Neuromuscular electrical stimulation of humeral adductors in subjects with rotator cuff tear.

INTRODUCTION: In symptomatic patients with rotator cuff tear, MRI and radiographic studies have ascribed the pain symptom to insufficient humeral head depression during arm elevations. The arm adductors such as the teres major and pectoralis major may contribute to depression of the humerus head during arm elevations. Researchers have demonstrated that neuromuscular electrical stimulation (NMES) of the serratus anterior and lower trapezius can control scapular motions and improve acromiohumeral distance. It is unknown, however, if adductor neuromuscular training could help patients with rotator cuff tear. MATERIALS AND METHODS: A cross-sectional study of NMES of the teres major and pectoralis major was conducted on 30 symptomatic subjects with rotator cuff tear. We measured the acromiohumeral distance by ultrasonography and scapular kinematics during arm elevation with a three-dimensional motion tracking system. RESULTS: The acromiohumeral distance significantly increased during NMES of the teres major (0.73 mm, p < 0.001). However, the distance significantly decreased with NMES of the pectoralis major (0.78 mm, p < 0.001). Additionally, scapular upward rotation was greater during NMES of the teres major than during NMES of the pectoralis major (3.4°, p < 0.001). Scapular external rotation decreased significantly more during NMES of the pectoralis major than during NMES of the teres major (1.6°, p = 0.003). CONCLUSIONS: NMES of the teres major can increase acromiohumeral distance and scapular upward rotation during arm elevation. However, the decreased upward and external rotation of the scapula during arm elevation with NMES of the pectoralis major may be associated with subacromial impingement.

An electroencephalogram microdisplay to visualize neuronal activity on the brain surface.

Functional mapping during brain surgery is applied to define brain areas that control critical functions and cannot be removed. Currently, these procedures rely on verbal interactions between the neurosurgeon and electrophysiologist, which can be time-consuming. In addition, the electrode grids that are used to measure brain activity and to identify the boundaries of pathological versus functional brain regions have low resolution and limited conformity to the brain surface. Here, we present the development of an intracranial electroencephalogram (iEEG)-microdisplay that consists of freestanding arrays of 2048 GaN light-emitting diodes laminated on the back of micro-electrocorticography electrode grids. With a series of proof-of-concept experiments in rats and pigs, we demonstrate that these iEEG-microdisplays allowed us to perform real-time iEEG recordings and display cortical activities by spatially corresponding light patterns on the surface of the brain in the surgical field. Furthermore, iEEG-microdisplays allowed us to identify and display cortical landmarks and pathological activities from rat and pig models. Using a dual-color iEEG-microdisplay, we demonstrated coregistration of the functional cortical boundaries with one color and displayed the evolution of electrical potentials associated with epileptiform activity with another color. The iEEG-microdisplay holds promise to facilitate monitoring of pathological brain activity in clinical settings.

Evaluation of a Standard Dietary Regimen Combined with Heat-Inactivated Lactobacillus gasseri HM1, Lactoferrin-Producing HM1, and Their Sonication-Inactivated Variants in the Management of Metabolic Disorders in an Obesity Mouse Model.

This study investigated the impact of incorporating various inactivated probiotic formulations, with or without recombinant lactoferrin (LF) expression, into a standard chow diet on metabolic-related disorders in obese mice. After inducing obesity through a 13-week high-fat diet followed by a standard chow diet, mice received daily oral administrations of different probiotics for 6 weeks using the oral gavage approach. These probiotic formulations consisted of a placebo (MRS), heat-inactivated Lactobacillus gasseri HM1 (HK-HM1), heat-killed LF-expression HM1 (HK-HM1/LF), sonication-killed HM1 (SK-HM1), and sonication-killed LF-expression HM1 (SK-HM1/LF). The study successfully induced obesity, resulting in worsened glucose tolerance and insulin sensitivity. Interestingly, the regular diet alone improved glucose tolerance, and the addition of inactivated probiotics further enhanced this effect, with SK-HM1/LF demonstrating the most noticeable improvement. However, while regular dietary intervention alone improved insulin sensitivity, probiotic supplementation did not provide additional benefits in this aspect. Inflammation in perirenal and epididymal fat tissues was partially alleviated by the regular diet and further improved by probiotics, particularly by SK-HM1, which showed the most significant reduction. Additionally, HK-HM1 and HK-HM1/LF supplements could contribute to the improvement of serum total triglycerides or total cholesterol, respectively. Overall, incorporating inactivated probiotics into a regular diet may enhance metabolic indices, and recombinant LF may offer potential benefits for improving glucose tolerance.

Pyrroloquinoline quinone ameliorates PM2.5-induced pulmonary fibrosis through targeting epithelial-mesenchymal transition.

Pulmonary fibrosis is a lung disorder affecting the lungs that involves the overexpressed extracellular matrix, scarring and stiffening of tissue. The repair of lung tissue after injury relies heavily on Type II alveolar epithelial cells (AEII), and repeated damage to these cells is a crucial factor in the development of pulmonary fibrosis. Studies have demonstrated that chronic exposure to PM2.5, a form of air pollution, leads to an increase in the incidence and severity of pulmonary fibrosis by stimulation of epithelial-mesenchymal transition (EMT) in lung epithelial cells. Pyrroloquinoline quinone (PQQ) is a bioactive compound found naturally that exhibits potent anti-inflammatory and anti-oxidative properties. The mechanism by which PQQ prevents pulmonary fibrosis caused by exposure to PM2.5 through EMT has not been thoroughly discussed until now. In the current study, we discovered that PQQ successfully prevented PM2.5-induced pulmonary fibrosis by targeting EMT. The results indicated that PQQ was able to inhibit the expression of type I collagen, a well-known fibrosis marker, in AEII cells subjected to long-term PM2.5 exposure. We also found the alterations of cellular structure and EMT marker expression in AEII cells with PM2.5 incubation, which were reduced by PQQ treatment. Furthermore, prolonged exposure to PM2.5 considerably reduced cell migratory ability, but PQQ treatment helped in reducing it. In vivo animal experiments indicated that PQQ could reduce EMT markers and enhance pulmonary function. Overall, these results imply that PQQ might be useful in clinical settings to prevent pulmonary fibrosis.

Optimizing lipid control in Taiwanese diabetic patients: A collaborative consensus by the Diabetes Association of the Republic of China (Taiwan) and the Taiwanese Association of Diabetes Educators.

We present an in-depth analysis of dyslipidemia management strategies for patients with diabetes mellitus in Taiwan. It critically examines the disparity between established guideline recommendations and actual clinical practices, particularly in the context of evolving policies affecting statin prescriptions. The focus is on synthesizing the most recent findings concerning lipid management in patients with diabetes mellitus, with a special emphasis on establishing consensus regarding low-density lipoprotein cholesterol treatment targets. The article culminates in providing comprehensive, evidence-based recommendations tailored to the unique needs of those living with diabetes mellitus in Taiwan. It underscores the criticality of personalized care approaches, which incorporate multifaceted factors, and the integration of novel therapeutic options to enhance cardiovascular health outcomes.

Guizhi Fuling Wan ameliorates concanavalin A-induced autoimmune hepatitis in mice.

BACKGROUND: Autoimmune hepatitis (AIH) is an immune-mediated hepatic disease associated with intense complications. AIH is more common in females and needs effective drugs to treat. Guizhi Fuling Wan (GZFLW) is a traditional Chinese herbal formula used to treat various gynecologic diseases. In this study, we aim to extend the new use of GZFLW for AIH. METHODS: The tandem MS-based analysis was used to identify secondary metabolites in GZFLW. Therapeutic effects of GZFLW were tested in a concanavalin A (Con A)-induced AIH model in mice. Ethnopharmacological mechanisms underlying the antiapoptotic, antioxidant, and immunomodulatory protective effects were determined. RESULTS: Oral administration of GZFLW attenuates AIH in a Con A-induced hepatotoxic model in vivo. The tandem MS-based analysis identified 15 secondary metabolites in GZFLW. The Con A-induced AIH syndromes, including hepatic apoptosis, inflammation, reactive oxygen species accumulation, function failure, and mortality, were significantly alleviated by GZFLW in mice. Mechanistically, GZFLW restrained the caspase-dependent apoptosis, restored the antioxidant system, and decreased pro-inflammatory cytokine production in the livers of Con A-treated mice. Besides, GZFLW repressed the Con A-induced hepatic infiltration of inflammatory cells, splenic T cell activation, and splenomegaly in mice. CONCLUSIONS: Our findings demonstrate the applicable potential of GZFLW in treating AIH. It prompts further investigation of GZFLW as a treatment option for AIH and possibly other hepatic diseases.

Peripheral inflammation is associated with impaired sadness recognition in euthymic bipolar patients.

BACKGROUND: Inflammation impairs cognitive function in healthy individuals and people with psychiatric disorders, such as bipolar disorder (BD). This effect may also impact emotion recognition, a fundamental element of social cognition. Our study aimed to investigate the relationships between pro-inflammatory cytokines and emotion recognition in euthymic BD patients and healthy controls (HCs). METHODS: We recruited forty-four euthymic BD patients and forty healthy controls (HCs) and measured their inflammatory markers, including high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and TNF-α. We applied validated cognitive tasks, the Wisconsin Card-Sorting Test (WCST) and Continuous Performance Test (CPT), and a social cognitive task for emotion recognition, Diagnostic Analyses of Nonverbal Accuracy, Taiwanese Version (DANVA-2-TW). We analyzed the relationships between cytokines and cognition and then explored possible predictive factors of sadness recognition accuracy. RESULTS: Regarding pro-inflammatory cytokines, TNF-α was elevated in euthymic BD patients relative to HCs. In euthymic BD patients only, higher TNF-α levels were associated with lower accuracy of sadness recognition. Regression analysis revealed that TNF-α was an independent predictive factor of sadness recognition in patients with euthymic BD when neurocognition was controlled for. CONCLUSIONS: We demonstrated that enhanced inflammation, indicated by increased TNF-α, was an independent predictive factor of impaired sadness recognition in BD patients but not in HCs. Our findings suggested a direct influence of TNF-α on sadness recognition and indicated vulnerability to depression in euthymic BD patients with chronic inflammation.

Stacking architecture for collimated backlight using cylindrical lens sheet with linear light sources or edge-lit/direct-lit BLU.

Highly collimated and directional backlights are essential for realizing advanced display technologies such as autostereoscopic 3D displays. Previously reported collimated backlights, either edge-lit or direct-lit, in general still suffer unsatisfactory form factors, directivity, uniformity, or crosstalk etc. In this work, we report a simple stacking architecture for the highly collimated and uniform backlights, by combining linear light source arrays and carefully designed cylindrical lens arrays. Experiments were conducted to validate the design and simulation, using the conventional edge-lit backlight or the direct-lit mini-LED (mLED) arrays as light sources, the NiFe (stainless steel) barrier sheets, and cylindrical lens arrays fabricated by molding. Highly collimated backlights with small angular divergence of ±1.45°âˆ¼±2.61°, decent uniformity of 93-96%, and minimal larger-angle sidelobes in emission patterns were achieved with controlled divergence of the light source and optimization of lens designs. The architecture reported here provides a convenient way to convert available backlight sources into a highly collimated backlight, and the use of optically reflective barrier also helps recycle light energy and enhance the luminance. The results of this work are believed to provide a facile approach for display technologies requiring highly collimated backlights.

Edoxaban, Rivaroxaban or Apixaban for Cancer-Associated Venous Thromboembolism in the Real World: Insights from the COMMAND VTE Registry-2.

BACKGROUND: Real-world data on clinical characteristics and outcomes related to the use of different direct oral anticoagulants (DOACs) for cancer-associated venous thromboembolism (VTE) is lacking. METHODS: The COMMAND VTE Registry-2 is a multicenter registry enrolling 5,197 consecutive patients with acute symptomatic VTE from 31 centers in Japan from January 2015-August 2020. Our study population comprised 1,197 patients with active cancer who were divided into the edoxaban (N=643, 54%), rivaroxaban (N=297, 25%), and apixaban (N=257, 22%) groups. RESULTS: The cumulative 5-year incidence of recurrent VTE (9.3%, 10.2%, and 8.5%, respectively, P=0.82) and all-cause death (67.5%, 66.8%, and 63.8%, respectively, P=0.22) did not differ among the groups. Despite adjusting for confounders, the risks of recurrent VTE and all-cause death did not differ significantly among the groups. The cumulative 5-year incidence of major and clinically relevant bleeding was significantly lower in the rivaroxaban group than those in the other groups (22.6%, 14.0%, and 22.8%, P=0.04; and 37.6%, 26.8%, and 38.3%, P=0.01, respectively). After adjusting for confounders, in the rivaroxaban group, the risk for major bleeding was numerically lower (HR: 0.65, 95% CI: 0.40-1.01) and that of clinically relevant all bleeding was significantly lower (HR: 0.67, 95% CI: 0.48-0.92) than those in the edoxaban group. CONCLUSIONS: The risks of recurrent VTE and all-cause death did not differ significantly among the different DOACs ; however, the risk of bleeding events could differ, with a potentially lower risk of bleeding with rivaroxaban.

Health equity assessment of machine learning performance (HEAL): a framework and dermatology AI model case study.

Background: Artificial intelligence (AI) has repeatedly been shown to encode historical inequities in healthcare. We aimed to develop a framework to quantitatively assess the performance equity of health AI technologies and to illustrate its utility via a case study. Methods: Here, we propose a methodology to assess whether health AI technologies prioritise performance for patient populations experiencing worse outcomes, that is complementary to existing fairness metrics. We developed the Health Equity Assessment of machine Learning performance (HEAL) framework designed to quantitatively assess the performance equity of health AI technologies via a four-step interdisciplinary process to understand and quantify domain-specific criteria, and the resulting HEAL metric. As an illustrative case study (analysis conducted between October 2022 and January 2023), we applied the HEAL framework to a dermatology AI model. A set of 5420 teledermatology cases (store-and-forward cases from patients of 20 years or older, submitted from primary care providers in the USA and skin cancer clinics in Australia), enriched for diversity in age, sex and race/ethnicity, was used to retrospectively evaluate the AI model's HEAL metric, defined as the likelihood that the AI model performs better for subpopulations with worse average health outcomes as compared to others. The likelihood that AI performance was anticorrelated to pre-existing health outcomes was estimated using bootstrap methods as the probability that the negated Spearman's rank correlation coefficient (i.e., "R") was greater than zero. Positive values of R suggest that subpopulations with poorer health outcomes have better AI model performance. Thus, the HEAL metric, defined as p (R >0), measures how likely the AI technology is to prioritise performance for subpopulations with worse average health outcomes as compared to others (presented as a percentage below). Health outcomes were quantified as disability-adjusted life years (DALYs) when grouping by sex and age, and years of life lost (YLLs) when grouping by race/ethnicity. AI performance was measured as top-3 agreement with the reference diagnosis from a panel of 3 dermatologists per case. Findings: Across all dermatologic conditions, the HEAL metric was 80.5% for prioritizing AI performance of racial/ethnic subpopulations based on YLLs, and 92.1% and 0.0% respectively for prioritizing AI performance of sex and age subpopulations based on DALYs. Certain dermatologic conditions were significantly associated with greater AI model performance compared to a reference category of less common conditions. For skin cancer conditions, the HEAL metric was 73.8% for prioritizing AI performance of age subpopulations based on DALYs. Interpretation: Analysis using the proposed HEAL framework showed that the dermatology AI model prioritised performance for race/ethnicity, sex (all conditions) and age (cancer conditions) subpopulations with respect to pre-existing health disparities. More work is needed to investigate ways of promoting equitable AI performance across age for non-cancer conditions and to better understand how AI models can contribute towards improving equity in health outcomes. Funding: Google LLC.