Safety and efficacy of magnesium-rich artificial cerebrospinal fluid for subarachnoid hemorrhage.

Objectives: This study aimed to investigate the efficacy of using a newly formulated magnesium-rich artificial cerebrospinal fluid (MACSF) as an alternative to normal saline (NS) for intraoperative irrigation during aneurysm clipping in improving the prognosis of patients with Aneurysmal subarachnoid hemorrhage (aSAH). Methods: Patients with aSAH who underwent intraoperative irrigation with MACSF or NS during the clipping in the First Affiliated Hospital of Xi 'an Jiaotong University from March 2019 to March 2022 were selected as MACSF group and NS group, respectively. The primary prognostic indicators were the incidence of favorable outcomes (mRS 0-2). The secondary outcome measures included cerebral vasospasm (CVS), mortality, total hospital stay, and intensive care unit (ICU) stay. Safety was evaluated based on the occurrence rates of hypermagnesemia, meningitis, and hydrocephalus. Results: Overall, 34 and 37 patients were enrolled in the MACSF and NS groups, respectively. At 90 days after aSAH onset, the proportion of favorable prognosis in the MACSF group was significantly higher than that in the NS group (p = 0.035). The incidence of CVS within 14 days after surgery was significantly lower in the MACSF group than that in the NS group (p = 0.026). The mortality rate in the MACSF group was significantly lower than in the NS group (p = 0.048). The median lengths of hospital stay (p = 0.008) and ICU stay (p = 0.018) were significantly shorter in the MACSF group than in the NS group. No significant differences were observed in safety measures. Conclusion: Using MACSF as an irrigation fluid for aneurysm clipping can significantly improve the 90-day prognosis of patients with aSAH, which may be related to the reduced incidence of CVS. Clinical trial registration: https://www.clinicaltrials.gov, identifier NCT04358445.

Tailored apoptotic vesicles promote bone regeneration by releasing the osteoinductive brake.

Accumulating evidence has demonstrated that apoptotic vesicles (apoVs) derived from mesenchymal stem cells (MSCs; MSC-apoVs) are vital for bone regeneration, and possess superior capabilities compared to MSCs and other extracellular vesicles derived from MSCs (such as exosomes). The osteoinductive effect of MSC-apoVs is attributed to their diverse contents, especially enriched proteins or microRNAs (miRNAs). To optimize their osteoinduction activity, it is necessary to determine the unique cargo profiles of MSC-apoVs. We previously established the protein landscape and identified proteins specific to MSC-apoVs. However, the features and functions of miRNAs enriched in MSC-apoVs are unclear. In this study, we compared MSCs, MSC-apoVs, and MSC-exosomes from two types of MSC. We generated a map of miRNAs specific to MSC-apoVs and identified seven miRNAs specifically enriched in MSC-apoVs compared to MSCs and MSC-exosomes, which we classified as apoV-specific miRNAs. Among these seven specific miRNAs, hsa-miR-4485-3p was the most abundant and stable. Next, we explored its function in apoV-mediated osteoinduction. Unexpectedly, hsa-miR-4485-3p enriched in MSC-apoVs inhibited osteogenesis and promoted adipogenesis by targeting the AKT pathway. Tailored apoVs with downregulated hsa-miR-4485-3p exhibited a greater effect on bone regeneration than control apoVs. Like releasing the brake, we acquired more powerful osteoinductive apoVs. In summary, we identified the miRNA cargos, including miRNAs specific to MSC-apoVs, and generated tailored apoVs with high osteoinduction activity, which is promising in apoV-based therapies for bone regeneration.

Microcirculatory Impairment and Cerebral Injury in Hydrocephalus and the Effects of Cerebrospinal Fluid Diversion.

BACKGROUND AND OBJECTIVES: Hydrocephalus is characterized by progressive enlargement of cerebral ventricles, resulting in impaired microvasculature and cerebral hypoperfusion. This study aimed to demonstrate the microvascular changes in hydrocephalic rats and the effects of cerebrospinal fluid (CSF) release on cerebral blood flow (CBF). METHODS: On postnatal day 21 (P21), male Wistar rats were intracisternally injected with either a kaolin suspension or saline. On P47, Evan's ratio (ER) was measured using MRI. On P49, the arteriolar diameter and vascular density of the pia were quantified using a capillary video microscope. The CBF was measured using laser Doppler flowmetry. The expressions of NeuN and glial fibrillary acidic protein determined by immunochemical staining were correlated with the ER. The CBF and rotarod test performance were recorded before and after CSF release. The expressions of 4-hydroxynonenal (4-HNE) and c-caspase-3 were studied on P56. RESULTS: Ventriculomegaly was induced to varying degrees, resulting in the stretching and abnormal narrowing of pial arterioles, which regressed with increasing ER. Quantitative analysis revealed significant decreases in the arteriolar diameter and vascular density in the hydrocephalic group compared with those in the control group. In addition, the CBF in the hydrocephalic group decreased to 30%-50% of that in the control group. In hydrocephalus, the neurons appear distorted, and the expression of 4-HNE and reactive astrogliosis increase in the cortex. After CSF was released, improvements in the CBF and rotarod test performance were inversely associated with the ER. In addition, the levels of 4-HNE and c-caspase-3 were further elevated. CONCLUSION: Rapid ventricular dilatation is associated with severe microvascular distortion, vascular regression, cortical hypoperfusion, and cellular changes that impair the recovery of CBF and motor function after CSF release. Moreover, CSF release may induce reperfusion injury. This pathophysiology should be taken into account when treating hydrocephalus.

Shear Stress and Sub-Femtomolar Levels of Ligand Synergize to Activate ALK1 Signaling in Endothelial Cells.

Endothelial cells (ECs) respond to concurrent stimulation by biochemical factors and wall shear stress (SS) exerted by blood flow. Disruptions in flow-induced responses can result in remodeling issues and cardiovascular diseases, but the detailed mechanisms linking flow-mechanical cues and biochemical signaling remain unclear. Activin receptor-like kinase 1 (ALK1) integrates SS and ALK1-ligand cues in ECs; ALK1 mutations cause hereditary hemorrhagic telangiectasia (HHT), marked by arteriovenous malformation (AVM) development. However, the mechanistic underpinnings of ALK1 signaling modulation by fluid flow and the link to AVMs remain uncertain. We recorded EC responses under varying SS magnitudes and ALK1 ligand concentrations by assaying pSMAD1/5/9 nuclear localization using a custom multi-SS microfluidic device and a custom image analysis pipeline. We extended the previously reported synergy between SS and BMP9 to include BMP10 and BMP9/10. Moreover, we demonstrated that this synergy is effective even at extremely low SS magnitudes (0.4 dyn/cm2) and ALK1 ligand range (femtogram/mL). The synergistic response to ALK1 ligands and SS requires the kinase activity of ALK1. Moreover, ALK1's basal activity and response to minimal ligand levels depend on endocytosis, distinct from cell-cell junctions, cytoskeleton-mediated mechanosensing, or cholesterol-enriched microdomains. However, an in-depth analysis of ALK1 receptor trafficking's molecular mechanisms requires further investigation.

Age-period-cohort analysis of long-term trends in ischemic stroke mortality in China caused by specific risk factors from 1990 to 2019.

OBJECTIVE: To study the primary risk factors for the long-term trends of mortality rates in ischemic stroke (IS) in China. METHODS: Using the Global Burden of Disease Study 2019 (GBD 2019) database, research was conducted on the 11 primary risk factors for the mortality rates of IS in China from 1990 to 2019. This study employed Joinpoint regression software and the Age-Period-Cohort (APC) method to evaluate the trends of mortality rates divided by age, period, and cohort over time. RESULTS: From 1990 to 2019, the age-standardized mortality rate (ASMR) caused by a diet high in red meat and high body-mass index (BMI) in China showed an upward trend. ASMR increased first and then decreased due to smoking, diet high in sodium, particulate matter pollution, high fasting plasma glucose, and high systolic blood pressure. Low-density lipoprotein cholesterol (LDL-C), kidney dysfunction, low temperature, and lead exposure remained relatively stable during this period. In the 35-45 age group, the mortality rate of IS due to high LDL-C was up to about 60%, and smoking affected men more than women. Overall, high LDL-C, high systolic blood pressure, and particulate matter pollution were the most common risk factors in patients with IS. The risk of death rose with age. The period and cohort relative risks showed that metabolic risk factors had the greatest impact on the mortality of IS. CONCLUSION: Metabolic risk factors have become the primary risk factors for the ASMR of IS in China. Relevant authorities should pay attention to their long-term effects on IS. Effective public health policies and interventions should be implemented to reduce the burden of IS.

Remote ischemic postconditioning alleviates cerebral ischemic injury through SERCA2/endoplasmic reticulum stress-mediated apoptosis.

Remote ischemic postconditioning (RIPostC) alleviates brain ischemic injury through several pathways, including endoplasmic reticulum (ER) stress modulation. Sarco endoplasmic reticulum Ca2+ -ATPase(SERCA2) which plays vital role in calcium homeostasis regulation could modulate ER stress logically. This study aimed to investigate whether RIPostC exerts its neuroprotective effect by reducing ER stress mediated by SERCA2. Male SD rats underwent transient middle cerebral artery occlusion (tMCAO) for 2 h followed by reperfusion, with the RIPostC group undergoing 3 cycles of bilateral femoral artery clamping and reperfusion at the beginning of reperfusion. Stroke outcome was assessed based on infarct volume and neurological function evaluation. Protein levels of SERCA2 and other ER stress markers were measured using Western blotting, immunofluorescence, and immunohistochemistry techniques. Compared to the sham group, we observed that RIPostC can effectively reduce cerebral infarct volume after I/R (34.55%: 21.03%; p = .004) and improve neurological function deficit (9.67:12.5; p = .029). Additionally, RIPostC increased SERCA2 protein expression and decreased the protein level of glucose-regulated protein 78 (GRP78), phosphorylation of eukaryotic translation initiation factor 2α (p-eIF2α) and CCAAT/EBP homologous protein (CHOP). Furthermore, B-cell lymphoma-2 (Bcl-2) expression was increased, while Bcl-2-associated X protein (Bax) and cleaved-caspase-3 was decreased in response to application of RIPostC. Our results suggest that RIPostC improves the prognosis of tMCAO rats, possibly by inhibiting the ER stress mediated by SERCA2, facilitating apoptosis downregulation. The significance of this study is to provide a theoretical basis for further exploring the protective mechanism of ischemic stroke by RIPostC. RESEARCH HIGHLIGHTS: Our results suggest that RIPostC improves the prognosis of tMCAO rats, possibly by inhibiting the ER stress mediated by SERCA2, facilitating apoptosis downregulation, thus achieving a neuroprotective effect.

Association Between Retirement Age and Incidence of Depressive Disorders: A 19-Year Population-Based Study.

OBJECTIVE: To investigate the occurrence of depressive disorders spanning the transition to retirement, and explore the relationship between retirement age and depressive disorders. METHODS: We utilized a national population-based health insurance database encompassing 2 million Taiwanese individuals from 2000 to 2019. The study focused on individuals aged 50 years and older who were employed at the baseline, and 84,224 individuals had records of retirement during the follow-up period. Depressive disorders were identified using codes from the International Classification of Diseases. To assess the trend in the incidence of depressive disorders 7-year period before and after retirement, an interrupted time series analysis was performed. Cox-proportional hazard models were employed to investigate the association between retirement age and the occurrence of depressive disorders following retirement. RESULTS: The incidence of depression peaks at the time of retirement and shows a significant decrease after retirement. Incidence of depressive disorders was 6.4 and 7.6 per 1000 person-years among individuals who retired between the ages of 60-64 and 65-69. Comparing the two groups, those who retired between 65 and 69 exhibits a higher risk of developing depressive disorders (hazard ratio = 1.10, 95% confidence interval = 1.02-1.18). This association is particularly pronounced among women and individuals residing in areas with low urbanization levels. CONCLUSION: Retirement marks a crucial life milestone accompanied by a peak in depressive disorders. It is important to address the higher risk of depression associated with late retirement among socially disadvantaged groups.

Gender- and age-specific associations between psychosocial work conditions and perceived work sustainability in the general working population in Taiwan.

OBJECTIVES: One aspect of work sustainability pertains to workers' intention to remain in their current job until reaching retirement age. Various adverse working conditions are expected to diminish work sustainability among different social groups. This study aims to examine these associations across gender and age groups. METHODS: The study participants were 19,152 economically-active adults in a national survey conducted in Taiwan. Information concerning psychosocial working conditions were obtained through interviews, using the Job Content Questionnaire. Work sustainability was evaluated by one question that asked whether the participants felt they would be able to do their current job until the age of 60. The association between psychosocial work conditions and work sustainability was examined by logistic regression analysis. We further performed stratified analysis to explore age and gender-specific associations. RESULTS: We observed that 14.2% and 17.1% of male and female workers reported low work sustainability. Workers in the electronics industries and female workers in the healthcare and education sectors reported low work sustainability. Gender-specific analyses showed that low job control among men and shift work among women were significantly associated with low work sustainability. Age-specific analyses indicated that having poor health, shift work, and long working hours in younger workers, and having low job control in older workers were associated with low work sustainability. CONCLUSION: To retain older workers in the labor market, policies should aim at the improvement of psychosocial work conditions, and gender- and age-specific issues should be taken into consideration.

Work as a social determinant of health in high-income countries: past, present, and future.

This paper, the first in a three-part Series on work and health, provides a narrative review of research into work as a social determinant of health over the past 25 years, the key emerging challenges in this field, and the implications of these challenges for future research. By use of a conceptual framework for work as a social determinant of health, we identified six emerging challenges: (1) the influence of technology on the nature of work in high-income countries, culminating in the sudden shift to telework during the COVID-19 pandemic; (2) the intersectionality of work with gender, sexual orientation, age, race, ethnicity, migrant status, and socioeconomic status as codeterminants of health disparities; (3) the arrival in many Organisation for Economic Co-operation and Development countries of large migrant labour workforces, who are often subject to adverse working conditions and social exclusion; (4) the development of precarious employment as a feature of many national labour markets; (5) the phenomenon of working long and irregular hours with potential health consequences; and (6) the looming threat of climate change's effects on work. We conclude that profound changes in the nature and availability of work over the past few decades have led to widespread new psychosocial and physical exposures that are associated with adverse health outcomes and contribute to increasing disparities in health. These new exposures at work will require novel and creative methods of data collection for monitoring of their potential health impacts to protect the workforce, and for new research into better means of occupational health promotion and protection. There is also an urgent need for a better integration of occupational health within public health, medicine, the life sciences, and the social sciences, with the work environment explicitly conceptualised as a major social determinant of health.

Burden of ischemic stroke in mainland China and Taiwan province from 1990 to 2019: with forecast for the next 11 years.

Ischemic stroke is featured with high incidence, mortality, and disability. The aim of this study is to use Global Burden of Disease database to describe and compare the burden of ischemic stroke in mainland China and Taiwan province and to further predict the expected changes in the next 11 years using statistical modeling methods. Information on ischemic stroke incidence and mortality in China (mainland and Taiwan province) during 1990-2019 was obtained from the Global Burden of Disease database to analyze the effects of region, gender, and age on the incidence and mortality of ischemic stroke in China. The autoregressive integrated moving average model was used to predict the age-standardized incidence rate and age-standardized mortality rate of ischemic stroke in males and females in mainland China and Taiwan province in the next 11 years. The period from 1990 to 2019 witnessed an overall upward trend in the number of incidence and deaths in mainland China and Taiwan province. In 2019, there were nearly 2.87 million ischemic incidence cases with stroke in mainland China, with more female patients than male in the age group of over 60 years. Among the nearly 1.03 million deaths, the death toll of men under the age of 85 years was higher than that of women, while in Taiwan province, the number of incidence was 28 771, with more female patients of all ages than male. Among the 6788 deaths, the death toll of men under the age of 80 years was higher than that of women. In 2019, the age group with the highest number of patients in the two regions was 65-69 years, while the highest number of deaths was found in people aged 85 years and above. As our autoregressive integrated moving average model predicted, the age-standardized incidence rate value of ischemic stroke is expected to be 163.23/100 000 persons in mainland China by 2030, which would continue to increase, while the age-standardized mortality rate value of ischemic stroke is expected to be 16.41/100 000 persons in Taiwan province by 2030, which showed a decreasing trend. Disease burden of ischemic stroke is still increasing in mainland China and Taiwan province, and health resources should be deployed to implement effective prevention and control strategies, taking into account region, gender, and age.

Case report and literature review: fatal cerebral fat embolism following facial autologous fat graft.

Background: Severe cerebral artery embolism is a rare complication of facial autologous fat injection. However, its incidence has markedly increased with the recent rise in facial cosmetic procedures. Case presentation: We report a 31-year-old Chinese woman who presented with unconsciousness 6 h after having undergone a facial autologous fat injection. A neurological examination revealed stupor, bilaterally diminished pupillary light reflexes, right-sided central facial palsy, and no reaction to pain stimulation of right limbs. Diffusion-weighted imaging displayed patchy hyperintense lesions in the left frontal, parietal, and temporal lobes. Magnetic resonance angiography demonstrated fat embolism in the left internal carotid artery, anterior cerebral artery, and middle cerebral artery. We immediately performed mechanical thrombectomy under sufficient preoperative preparations but failed to achieve complete recanalization. Pathological examination of the embolus confirmed the presence of adipocytes. Although we actively administered symptomatic and supportive treatments, the patient eventually died due to the progression of cerebral herniation and systemic infection. Conclusion: Due to the ineffectiveness of current treatment and the inferior prognosis, fat embolism, a severe complication of autologous fat graft, should draw the attention of both plastic surgeons and neurologists so that actions may be taken for both its prevention and treatment.

Association between modifiable vascular risk factors and rapid progression of postradiation carotid artery stenosis.

BACKGROUND: Postradiotherapy carotid vasculopathy is a clinically relevant complication in patients with head and neck cancer receiving radiotherapy. In this study, we investigated the factors associated with the development and progression of carotid artery stenosis (CAS) in such patients. METHODS: Patients who received radiotherapy for head and neck cancers between October 2011 and May 2019 at a medical center in Taiwan were eligible for inclusion in this study. This study included patients who underwent two consecutive carotid duplex examinations within an interval of 1 to 3 years. The factors associated with ≥50% CAS at baseline and follow-up were analyzed. RESULTS: In total, 694 patients (mean age, 57.8 ± 9.9 years; men, 75.2%; nasopharyngeal cancer, 73.3%) were included. The mean interval between radiotherapy and carotid duplex examination was 9.9 ± 5.9 years. At baseline, 103 patients had ≥50% CAS, which was significantly associated with tobacco smoking, hypercholesterolemia, and a prolonged interval between radiotherapy and carotid duplex examination. A total of 586 patients did not have CAS at baseline; of them, 68 developed ≥50% CAS during follow-up. Hypertension and hypercholesterolemia were identified as independent risk factors for CAS progression. CONCLUSION: Modifiable vascular risk factors, such as hypertension and hypercholesterolemia, appear to be significantly associated with the rapid progression of postradiotherapy CAS in patients with head and neck cancer.

EEG-Channel-Temporal-Spectral-Attention Correlation for Motor Imagery EEG Classification.

In brain-computer interface (BCI) work, how correctly identifying various features and their corresponding actions from complex Electroencephalography (EEG) signals is a challenging technology. However, most current methods do not consider EEG feature information in spatial, temporal and spectral domains, and the structure of these models cannot effectively extract discriminative features, resulting in limited classification performance. To address this issue, we propose a novel text motor-imagery EEG discrimination method, namely wavelet-based temporal-spectral-attention correlation coefficient (WTS-CC), to simultaneously consider the features and their weighting in spatial, EEG-channel, temporal and spectral domains in this study. The initial Temporal Feature Extraction (iTFE) module extracts the initial important temporal features of MI EEG signals. The Deep EEG-Channel-attention (DEC) module is then proposed to automatically adjust the weight of each EEG channel according to its importance, thereby effectively enhancing more important EEG channels and suppressing less important EEG channels. Next, the Wavelet-based Temporal-Spectral-attention (WTS) module is proposed to obtain more significant discriminative features between different MI tasks by weighting features on two-dimensional time-frequency maps. Finally, a simple discrimination module is used for MI EEG discrimination. The experimental results indicate that the proposed text WTS-CC method can achieve promising discrimination performance that outperforms the state-of-the-art methods in terms of classification accuracy, Kappa coefficient, F1 score, and AUC on three public datasets.

Apoptotic Vesicles Regulate Bone Metabolism via the miR1324/SNX14/SMAD1/5 Signaling Axis.

Mesenchymal stem cells (MSCs) are widely used in the treatment of diseases. After their in vivo application, MSCs undergo apoptosis and release apoptotic vesicles (apoVs). This study investigates the role of apoVs derived from human bone marrow mesenchymal stem cells (hBMMSCs) in bone metabolism and the molecular mechanism of the observed effects. The results show that apoVs can promote osteogenesis and inhibit osteoclast formation in vitro and in vivo. ApoVs may therefore attenuate the bone loss caused by primary and secondary osteoporosis and stimulate bone regeneration in areas of bone defect. The mechanisms responsible for apoV-induced bone regeneration include the release of miR1324, which inhibit expression of the target gene Sorting Nexin 14 (SNX14) and thus activate the SMAD1/5 pathway in target cells. Given that MSC-derived apoVs are easily obtained and stored, with low risks of immunological rejection and neoplastic transformation, The findings suggest a novel therapeutic strategy to treat bone loss, including via cell-free approaches to bone tissue engineering.

Psychosocial Work Conditions During the COVID-19 Pandemic and Their Influences on Mental Health Risk and Intention to Leave Among Public Health Workers: A Cross-sectional and Follow-up Study in Taiwan.

Background: To examine the influences of psychosocial work conditions on mental health risk and intention to leave the public sector among workers of public health agencies in Taiwan. Methods: We surveyed 492 public health workers in March 2022 during the COVID-19 pandemic. Information on job demands, job control, workplace justice, experiences of workplace violence and its type and origin, and mental health status (assessed by the 5-item Brief Symptom Rating Scale, BSRS-5) was obtained. Of them, 192 participated in a follow-up survey conducted in May 2023 that assessed mental health status, employment changes, and intention to leave. Results: In the initial survey, 32.93% of participants reported poor mental health status, defined by having a score of BSRS-5 â‰§ 10, and 48.17% experienced some form of workplace violence over the past year. Notably, high psychosocial job demands (OR = 3.64, 95% CI = 1.93-6.87), low workplace justice (OR = 2.58, 95% CI = 1.45-4.58), and workplace violence (OR = 2.38, 95% CI = 1.51-3.77) were significantly associated with increased risk of mental disorders. Among those who participated in the follow-up survey, 22.40% had persistent poor mental health, and 30.73% considered leaving or have left the public sector. Longitudinal analyses indicated that job demands predicted persistent mental disorders and intention to leave the public sector, and the experience of workplace violence added additional mental health risks. Conclusion: The public health workforce is crucial for effective and resilient public health systems. Our findings that public health workers were at high mental health risk and had a high intention to leave the job warrant attention and policy interventions.

Influence of RBC Indices on HbA1c Measurement by Capillary Electrophoresis and HPLC Methods.

BACKGROUND: HbA1c is the gold standard of diabetic surveys to monitor the long-term glycemic control. Anemia is cited as a major confounder to HbA1c analysis; however, the effect of RBC indices influences on HbA1c analysis is not known. The aim of this study is to compare ion-exchange high-performance liquid chromatography, and capillary electrophoresis to evaluate the influence of RBC parameters on HbA1c values in anemia patients. METHODS: Erythrocyte parameters were collected from the 307 randomly selected specimens from the Hematology division. HbA1c was measured on the same specimen using Tosoh G8 and Capillarys 2 Flex Piercing on the same day. RESULTS: There is acceptable concordance between the results of capillary electrophoresis and HPLC methods (R2 = 0.953, p < 0.001). However, significant differences in HbA1c value between the two assay methods were obtained in the patients with abnormal RBC indices (p < 0.001). CONCLUSIONS: Our results demonstrated HbA1c differences were significantly different in the patients with low Hb (≤ 8 g/dL) and high RDW-CV (≥ 13.7%). It is suggested that in the analysis of HbA1c level in anemia patients, simultaneous testing for hemoglobin level is needed. In addition, development of a new reference value of HBA1c for patients with severe anemia should be considered.

An Effective Algorithm to Analyze the Optokinetic Nystagmus Waveforms from a Low-Cost Eye Tracker.

OBJECTIVE: Most neurological diseases are usually accompanied by changes in the oculomotor nerve. Analysis of different types of eye movements will help provide important information in ophthalmology, neurology, and psychology. At present, many scholars use optokinetic nystagmus (OKN) to study the physiological phenomenon of eye movement. OKN is an involuntary eye movement induced by a large moving surrounding visual field. It consists of a slow pursuing eye movement, called "slow phase" (SP), and a fast re-fixating saccade eye movement, called "fast phase" (FP). Non-invasive video-oculography has been used increasingly in eye movement research. However, research-grade eye trackers are often expensive and less accessible to most researchers. Using a low-cost eye tracker to quantitatively measure OKN eye movement will facilitate the general application of eye movement research. METHODS & RESULTS: We design an analytical algorithm to quantitatively measure OKN eye movements on a low-cost eye tracker. Using simple conditional filtering, accurate FP positions can be obtained quickly. The high-precision FP recognition rate is of great help for the subsequent calculation of eye movement analysis parameters, such as mean slow phase velocity (MSPV), which is beneficial as a reference index for patients with strabismus and other eye diseases. CONCLUSIONS: Experimental results indicate that the proposed method achieves faster and better results than other approaches, and can provide an effective algorithm to calculate and analyze the FP position of OKN waveforms.

Conditional knockout of Cdc20 attenuates osteogenesis in craniofacial bones.

Craniofacial bone defects cause significant problems to patients with harmful consequences. Mesenchymal stem cells (MSCs) can self-renew and exhibit multilineage differentiation, which could be applied to bone regeneration. However, craniofacial bone tissue MSCs have unique properties, differing in their characteristics to MSCs derived from long bones. CDC20 promotes osteogenic differentiation in long bones; however, its role in craniofacial bone tissues remains unknown. In this study, we found that Cdc20 conditional knockout in mice triggered distinctive cranial and mandibular bone loss. Moreover, the osteogenic differentiation potential of cranial suture-derived MSCs and mandibular bone marrow-derived MSCs was impaired in Cdc20 conditional knockout mice. The conditional knockout of Cdc20 impaired osteogenesis in craniofacial bones. Our findings provide new insights into craniofacial bone regeneration and the treatments of craniofacial bone-related diseases.

Repurposing of ingenol mebutate for treating human colorectal cancer by targeting S100 calcium-binding protein A4 (S100A4).

Colorectal cancer (CRC) is the world's second most common cause of cancer-related death. Novel treatments are still urgently needed. S100 calcium-binding protein A4 (S100A4) was demonstrated to be an anticancer therapeutic target. Herein, we found that higher S100A4 expression was associated with a poorer prognosis in publicly available cohorts and a Taiwanese CRC patient cohort. To identify repurposed S100A4 inhibitors, we mined the Connectivity Map (CMap) database for clinical drugs mimicking the S100A4-knockdown gene signature. Ingenol mebutate, derived from the sap of the plant Euphorbia peplus, is approved as a topical treatment for actinic keratosis. The CMap analysis predicted ingenol mebutate as a potent S100A4 inhibitor. Indeed, both messenger RNA and protein levels of S100A4 were attenuated by ingenol mebutate in human CRC cells. In addition, CRC cells with higher S100A4 expressions and/or the wild-type p53 gene were more sensitive to ingenol mebutate, and their migration and invasion were inhibited by ingenol mebutate. Therefore, our results suggest the repurposing of ingenol mebutate for treating CRC by targeting S100A4.

Explaining the Invisibility of Asbestos-Related Diseases in the Taiwan Workers' Compensation System.

Occupational asbestos exposure was prevalent in Taiwan, but asbestos-related diseases (ARDs) have rarely been recognized. We conducted in-depth face-to-face interviews with 16 patients with ARDs. All of them had worked in industries known for high asbestos exposure. However, only three patients had filed workers' compensation (WC) claims, and of them, only two patients were approved. Reasons for the low compensation rate of ARDs could be divided into institutional barriers related to the flaws of the WC system and non-institutional barriers related to the knowledge status, causal interpretation, and social situations of individual workers. The Labor Occupational Accident Insurance and Protection Act passed in April 2021 has responded to the under-compensation of occupational diseases. However, the new act's effects toward improving the recognition of ARDs remain questionable. Our findings indicated that additional efforts are needed to remove non-institutional barriers hindering workers' ability to ensure their compensation rights.