Developing Methods for Assessing Mental Activity Using Human-Smartphone Interactions: Comparative Analysis of Activity Levels and Phase Patterns in General Mental Activities, Working Mental Activities, and Physical Activities.

BACKGROUND: Human biological rhythms are commonly assessed through physical activity (PA) measurement, but mental activity may offer a more substantial reflection of human biological rhythms. OBJECTIVE: This study proposes a novel approach based on human-smartphone interaction to compute mental activity, encompassing general mental activity (GMA) and working mental activity (WMA). METHODS: A total of 24 health care professionals participated, wearing wrist actigraphy devices and using the "Staff Hours" app for more than 457 person-days, including 332 workdays and 125 nonworkdays. PA was measured using actigraphy, while GMA and WMA were assessed based on patterns of smartphone interactions. To model WMA, machine learning techniques such as extreme gradient boosting and convolutional neural networks were applied, using human-smartphone interaction patterns and GPS-defined work hours. The data were organized by date and divided into person-days, with an 80:20 split for training and testing data sets to minimize overfitting and maximize model robustness. The study also adopted the M10 metric to quantify daily activity levels by calculating the average acceleration during the 10-hour period of highest activity each day, which facilitated the assessment of the interrelations between PA, GMA, and WMA and sleep indicators. Phase differences, such as those between PA and GMA, were defined using a second-order Butterworth filter and Hilbert transform to extract and calculate circadian rhythms and instantaneous phases. This calculation involved subtracting the phase of the reference signal from that of the target signal and averaging these differences to provide a stable and clear measure of the phase relationship between the signals. Additionally, multilevel modeling explored associations between sleep indicators (total sleep time, midpoint of sleep) and next-day activity levels, accounting for the data's nested structure. RESULTS: Significant differences in activity levels were noted between workdays and nonworkdays, with WMA occurring approximately 1.08 hours earlier than PA during workdays (P<.001). Conversely, GMA was observed to commence about 1.22 hours later than PA (P<.001). Furthermore, a significant negative correlation was identified between the activity level of WMA and the previous night's midpoint of sleep (ß=-0.263, P<.001), indicating that later bedtimes and wake times were linked to reduced activity levels in WMA the following day. However, there was no significant correlation between WMA's activity levels and total sleep time. Similarly, no significant correlations were found between the activity levels of PA and GMA and sleep indicators from the previous night. CONCLUSIONS: This study significantly advances the understanding of human biological rhythms by developing and highlighting GMA and WMA as key indicators, derived from human-smartphone interactions. These findings offer novel insights into how mental activities, alongside PA, are intricately linked to sleep patterns, emphasizing the potential of GMA and WMA in behavioral and health studies.

Incidentally Discovered 99mTc-MDP Uptake on Bone Scan in Otosclerosis.

Otosclerosis is a poorly understood clinical entity causing progressive conductive hearing loss. Here we present the first known evidence of otosclerosis demonstrating 99mTc-MDP uptake on bone scan. This presents an opportunity to explore the role of nuclear medicine imaging in early detection, staging, and even informing treatment and prognosis of this condition. Laryngoscope, 2024.

Habitual Expressive Suppression of Positive, but not Negative, Emotions Consistently Predicts Lower Well-being across Two Culturally Distinct Regions.

Habitual expressive suppression (i.e., a tendency to inhibit the outward display of one's emotions; hereafter suppression) is often conceptualized as a maladaptive emotion regulation strategy. Yet, is this equally true for suppression of positive and of negative emotions? Across three studies and seven samples (total N > 1300 people) collected in two culturally distinct regions (i.e., Taiwan and the US), we examined the separability and distinct well-being effects of suppressing positive vs. negative emotions. Results consistently showed that (a) people suppressed their positive (vs. negative) emotions less, (b) the construct of suppression of positive (vs. negative) emotions was conceptually farther away from that of suppression of emotions in general, (c) suppression of positive and of negative emotions were only moderately correlated, and (d) only suppression of positive, but not negative, emotions, predicted lower well-being. An internal meta-analysis (k = 52 effect sizes) showed that these associations were robust to the inclusion of age, gender, and region as covariates. Future research may further probe the respective links between suppression of positive and of negative emotions and well-being across more cultural regions and across the life-span.

Believe, express, and enjoy: utility beliefs about social emotion expression consistently predict satisfactory outcomes.

The present study investigates the association between people's beliefs about emotion and their overall satisfaction with a social interaction. We focus on three specific aspects to examine this association: (a) utility beliefs-a dimension of emotion beliefs; (b) emotion expression-an emotion channel; and (c) four social emotions-anger, other-embarrassment, gratitude, and other-pride. We examine whether people's utility beliefs about expressing a social emotion can predict their evaluation of a social interaction when they express (vs. suppress) their social emotion. Results (N = 209) consistently show that when people express their social emotion, their utility beliefs positively predict their satisfaction with an event. However, when people suppress their gratitude, their utility beliefs negatively predict their satisfaction, an effect not observed in the other three emotion events. These findings corroborate the claim that emotion beliefs impact people's emotional lives. Implications for research on emotion beliefs and motivated emotion regulation are discussed.

Home-based rehabilitation versus hospital-based rehabilitation for stroke patients in post-acute care stage: Comparison on the quality of life.

BACKGROUND: This study focused on the integrated post-acute care (PAC) stage of stroke patients, and employed a retrospective study to examine the satisfaction with life quality in two groups, one that received home-based rehabilitation and one that received hospital-based rehabilitation. A secondary purpose was to analyze the correlations among the index and components concerning their quality of life (QOL) and compare the advantages and disadvantages of these two approaches to PAC. METHODS: This research was a retrospective study of 112 post-acute stroke patients. The home-based group received rehabilitation for one to two weeks, and two to four sessions per week. The hospital-based group received the rehabilitation for three to six weeks, and 15 sessions per week. The home-based group mainly received the training and guidance of daily activities at the patients' residence. The hospital-based group mainly received physical facilitation and functional training in the hospital setting. RESULTS: The mean scores of QOL assessment for both groups were found to be significantly improved after intervention. Between-group comparisons showed that the hospital-based group had better improvement than the home-based group in mobility, self-care, pain/discomfort and depression/anxiety. In the home-based group, the MRS score and the participant's age can explain 39.4% of the variance of QOL scores. CONCLUSION: The home-based rehabilitation was of lower intensity and duration than the hospital-based one, but it still achieved a significant improvement in QOL for the PAC stroke patients. The hospital-based rehabilitation offered more time and treatment sessions. Therefore hospital-based patients responded with better QOL outcomes than the home-based patients.

Colonization of nasal cavities by Staphylococcus epidermidis mitigates SARS-CoV-2 nucleocapsid phosphoprotein-induced interleukin (IL)-6 in the lung.

Infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can trigger excessive interleukin (IL)-6 signalling, leading to a myriad of biological effects including a cytokine storm that contributes to multiple organ failure in severe coronavirus disease 2019 (COVID-19). Using a mouse model, we demonstrated that nasal inoculation of nucleocapsid phosphoprotein (NPP) of SARS-CoV-2 increased IL-6 content in bronchoalveolar lavage fluid (BALF). Nasal administration of liquid coco-caprylate/caprate (LCC) onto Staphylococcus epidermidis (S. epidermidis)-colonized mice significantly attenuated NPP-induced IL-6. Furthermore, S. epidermidis-mediated LCC fermentation to generate electricity and butyric acid that promoted bacterial colonization and activated free fatty acid receptor 2 (Ffar2) respectively. Inhibition of Ffar2 impeded the effect of S. epidermidis plus LCC on the reduction of NPP-induced IL-6. Collectively, these results suggest that nasal S. epidermidis is part of the first line of defence in ameliorating a cytokine storm induced by airway infection of SARS-CoV-2.

The role of dialecticism in objective and subjective attitudinal ambivalence.

Although attitudes are often considered positive or negative evaluations, people often have both positive and negative associations with a target object or issue, and when people are ambivalent, they are typically presumed to find the experience aversive because they are motivated to hold clear, univalent attitudes. Cross-cultural research, however, has shown cultural variation in the propensity for dialectical thinking, which is characterized by a tolerance for contradiction. Two studies examined the role of dialectical thinking tendencies in the occurrence of attitudinal ambivalence and how much people subjectively experience their state of ambivalence. Study 1 measured individual differences in dialectical thinking within a culture, and Study 2 compared participants across two cultures (United States and Taiwan) that differ in dialecticism. Across studies, greater dialectical thinking was associated with holding both positive and negative evaluations of the same topic (objective ambivalence) and weaker correlations between objective ambivalence and subjective reports of being conflicted (subjective ambivalence).

The multiple mediating effects of cancer threat appraisal and quality of life on the association between mindfulness and depression for colorectal cancer survivors.

OBJECTIVE: This study explored the multiple mediating effects of cancer threat appraisal, functional status, and symptom distress on the association between mindfulness and depression in colorectal cancer (CRC) patients at the transition stage after completing cancer treatments. METHODS: A total of 90 CRC survivors who received cancer treatments within 3 months participated in this cross-sectional study. The functional status and symptom distress (EORTC-C30 and EORTC CR29), dispositional mindfulness (Five Facet Mindfulness Questionnaire), cancer threat appraisal ( Constructed Meaning Scale), and depressive symptoms (Beck Depression Inventory-II scale) were collected. The mediation and moderation analyses were conducted using the PROCESS macros for SPSS. RESULTS: Survivors' dispositional mindfulness (γ = -0.49, p < 0.001) and cancer threat appraisal (γ = -0.59, p < 0.001) were significantly associated with depressive symptoms. Simple mediation analysis indicated that cancer threat appraisal mediated the relationship between dispositional mindfulness and depression (ß = -0.02, 95% CI = -0.04 to -0.001). The multiple mediated analysis identified the path between dispositional mindfulness and depression via cancer threat appraisal and colorectal symptom distress (ß = -0.01, 95% CI = -0.03 to -0.01). In the mediated moderation model, the path between dispositional mindfulness and depression via colorectal function was moderated by cancer threat appraisal (ß = -0.02, 95% CI = -0.05 to -0.004). CONCLUSIONS: The two cognitive mechanisms of reducing CRC survivors' depression are as follows: (1) dispositional mindfulness reducing the appraisal of cancer as a threat and increasing positive perceptions of CRC symptoms and (2) the cancer threat appraisal buffered the impacts of CRC's mindfulness and colorectal function on depressive symptoms. Developing mindfulness with cognitive training is recommended for improving depressive symptoms among CRC patients in the transition period.

Skin Bacteria Mediate Glycerol Fermentation to Produce Electricity and Resist UV-B.

Bacteria that use electron transport proteins in the membrane to produce electricity in the gut microbiome have been identified recently. However, the identification of electrogenic bacteria in the skin microbiome is almost completely unexplored. Using a ferric iron-based ferrozine assay, we have identified the skin Staphylococcus epidermidis (S. epidermidis) as an electrogenic bacterial strain. Glycerol fermentation was essential for the electricity production of S. epidermidis since the inhibition of fermentation by 5-methyl furfural (5-MF) significantly diminished the bacterial electricity measured by voltage changes in a microbial fuel cell (MFC). A small-scale chamber with both anode and cathode was fabricated in order to study the effect of ultraviolet-B (UV-B) on electricity production and bacterial resistance to UV-B. Although UV-B lowered bacterial electricity, a prolonged incubation of S. epidermidis in the presence of glycerol promoted fermentation and elicited higher electricity to suppress the effect of UV-B. Furthermore, the addition of glycerol into S. epidermidis enhanced bacterial resistance to UV-B. Electricity produced by human skin commensal bacteria may be used as a dynamic biomarker to reflect the UV radiation in real-time.

Association between Anemia and Auditory Threshold Shifts in the US Population: National Health and Nutrition Examination Survey.

Existing evidence indicates that both iron deficiency anemia and sickle cell anemia have been previously associated with hearing loss. However, human data investigating the association between anemia and auditory threshold shifts at different frequencies in the adolescent, adult and elderly population are extremely limited to date. Therefore, this cross-sectional study used the dataset from the US National Health and Nutrition Examination Survey from 2005 to 2012 to explore differences in low- or high-frequency hearing thresholds and hearing loss prevalence between participants with and without anemia. A total of 918 patients with anemia and 8213 without anemia were included. Results indicated that low- and high-frequency pure tone average were significantly higher in patients with anemia than that in those without anemia in the elderly, but not in adult or adolescent population. In addition, the prevalence of low-frequency hearing loss but not high-frequency hearing loss was also higher in patients with anemia than in those without anemia in the elderly population. After adjusting various confounders, multiple regression models still indicated that patients with anemia tended to have larger threshold shift. In conclusion, anemia was associated with auditory threshold shifts in the elderly population, especially those vulnerable to low-frequency hearing loss.

CC12 Induces Apoptotic Cell Death and Cell Cycle Arrest in Human Glioblastoma Cell Lines and Mouse Xenograft Model.

Among central nervous system tumors, glioblastoma (GBM) is the most common and the most malignant type. Even under current standard treatments, the overall survival rate is still low and the recurrence rate is high. Therefore, developing novel and effective therapy is urgently needed. CC12, a synthesized small molecule, was evaluated for the potential anti-GBM effects in two GBM cell lines, U87MG and U118MG. The observations of cell morphology, MTT assay, flow cytometry-based apoptosis after CC12 treatment, were conducted. Western blot was performed for the investigation of the apoptotic mechanism. Positron emission tomography scan analysis and bioluminescent imaging assay using a mouse xenograft model were performed for the effect of CC12 in vivo. After treated by 10 µM CC12 for 24 h, both U118MG and U87MG cells showed tumor cell death. MTT assay results showed that the survival rates decreased when the CC12 concentrations or the treatment periods increased. Ki-67 expression and flow cytometry results indicated that the proliferation was inhibited in GBM cells, and G1 phase arrest was shown. The results of 7-AAD, Br-dUTP, and JC-1 staining all showed the apoptosis of GBM cells after CC12 treatment. Increased γH2AX, caspase-3, and poly (ADP-ribose) polymerase (PARP) levels meant the DNA damage, and increased Bcl2 family proteins after CC12 treatment indicated the intrinsic apoptotic pathway was involved in CC12 induced apoptosis. Furthermore, CC12 can induce the decrease of tumor prognostic marker DcR3. In vivo experiment results showed the effect of CC12 on tumor size reduction of CC12. In addition, the ability to cross the brain-blood barrier of CC12 was also confirmed. CC12 may have anti-tumor ability through the regulation of cell cycle and apoptosis in vitro and in vivo.

Author Correction: Investigating the relationship between district-level socioeconomic status and individual obesity in Taiwanese adolescents: A large-scale cross-sectional analysis.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Drosophila decapping protein 2 modulates the formation of cortical F-actin for germ plasm assembly.

In Drosophila, the deposition of the germ plasm at the posterior pole of the oocyte is essential for the abdomen and germ cell formation during embryogenesis. To assemble the germ plasm, oskar (osk) mRNA, produced by nurse cells, should be localized and anchored on the posterior cortex of the oocyte. Processing bodies (P-bodies) are cytoplasmic RNA granules responsible for the 5'-3' mRNA degradation. Evidence suggests that the components of P-bodies, such as Drosophila decapping protein 1 and Ge-1, are involved in the posterior localization of osk. However, whether the decapping core enzyme, Drosophila decapping protein 2 (dDcp2), is also involved remains unclear. Herein, we generated a dDcp2 null allele and showed that dDcp2 was required for the posterior localization of germ plasm components including osk. dDcp2 was distributed on the oocyte cortex and was localized posterior to the osk. In the posterior pole of dDcp2 mutant oocytes, osk was mislocalized and colocalized with F-actin detached from the cortex; moreover, considerably fewer F-actin projections were observed. Using the F-actin cosedimentation assay, we proved that dDcp2 interacted with F-actin through its middle region. In conclusion, our findings explored a novel function of dDcp2 in assisting osk localization by modulating the formation of F-actin projections on the posterior cortex.

Beyond the bones and joints: a review of ligamentous injuries of the foot and ankle on 99mTc-MDP-SPECT/CT.

99mTc-MDP-single photon emission computed tomography (SPECT)/CT has established itself as a useful modality in the assessment of the painful foot and ankle, owing to its ability to depict anatomical and functional information simultaneously. Despite its growing popularity, much of the literature describing the utility of 99mTc-MDP-SPECT/CT of the foot and ankle is limited to osseous and articular pathology, with descriptions of ligamentous pathology limited to just a handful of cases. Though assessment of soft tissues using a combination of bone tracer and CT is limited, with a sound understanding of the regional anatomy, it is certainly within the scope of 99mTc-MDP-SPECT/CT to accurately identify ligamentous injuries based on focal tracer uptake patterns and suspected ligamentous injuries should be reported as such. This article provides a case-based pictorial review of the 99mTc-MDP-SPECT/CT appearances of the various ligamentous injuries of the foot and ankle with case examples and MRI correlation where available, most of which have yet to be described. The typical patterns of bone tracer uptake and associated CT abnormalities that may be observed are discussed.

Investigating the relationship between district-level socioeconomic status and individual obesity in Taiwanese adolescents: A large-scale cross-sectional analysis.

The current study aimed to assess the prevalence of obesity and to explore the relationship between socioeconomic status and obesity among adolescents in Taiwan, a transitioning country. Data from the Taiwan School Physical Fitness Database on 1,875,627 Taiwanese adolescents aged 10-18 years were analyzed. The average family income per household in each district was collected from the national statistical institutional database. Descriptive statistics, Chi-square tests, Pearson correlation analysis, and mixed model analyses were used. The overall prevalence of combined overweight and obesity was 28.1%. The prevalence of overweight/obesity significantly differed according to gender and age. Furthermore, the average family income per household was negatively associated with the district-level prevalence of obesity. Additionally, when controlling for physical fitness, the average family income per household remained negatively associated with adolescent obesity. In addition, multilevel analysis was also applied to explore the relationship between district-level socioeconomic status and individual-level obesity to prevent the nested data structure from affecting the results. The results revealed that the average family income per household negatively correlated with individual obesity. These findings provide insight for public health officials into preventing and managing adolescent obesity.

The Need To Reform The Hospital Payment System In Indonesia

@#One of the crucial health policies in hospitals is about physician payment methods. Indonesia had implemented the National Health Assurance since 2014 to achieve Universal Health Coverage by 2019. Most of hospital revenue is packaging from the National Health Insurance Agent (called BPJS). However, Fee-for-service (FFS) payment method is still dominant in many hospitals. How can hospitals make policy to rearrange the payment method to attain hospital performance? The purpose of this research is to analyze the payment system that can improve employee satisfaction and performances. Mix method was used to collect data and make an interpretation. Data collected from 185 respondents and four key informants. The result showed that the policy in private and public hospitals in Indonesia of the physician payment is diverse. Most of the hospitals use the pure FFS for self-employee physicians (part timer employee). For full time employee, they applied FFS mixed with salary, or remuneration. To improve employee satisfaction and performance, the hospitals should make a policy to link the FFS to pay for performances. The hospital should make the tailoring program by involving the physician in a designing method of the hospital remuneration.

A Synergistic Anti-Cancer Effect of Troglitazone and Lovastatin in a Human Anaplastic Thyroid Cancer Cell Line and in a Mouse Xenograft Model.

Anaplastic thyroid cancer (ATC) is a malignant subtype of thyroid cancers and its mechanism of development remains inconclusive. Importantly, there is no effective strategy for treatment since ATC is not responsive to conventional therapies, including radioactive iodine therapy and thyroid-stimulating hormone suppression. Here, we report that a combinational approach consisting of drugs designed for targeting lipid metabolism, lovastatin (an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, HMGCR) and troglitazone (an agonist of peroxisome proliferator-activated receptor gamma, PPARγ), exhibits anti-proliferation in cell culture systems and leads to tumor regression in a mouse xenograft model. The composition contains a sub-lethal concentration of both drugs and exhibits low toxicity to certain types of normal cells. Our results support a hypothesis that the inhibitory effect of the combination is partly through a cell cycle arrest at G0/G1 phase, as evidenced by the induction of cyclin-dependent kinase inhibitors, p21cip and p27kip, and the reduction of hyperphosphorylated retinoblastoma protein (pp-Rb)-E2F1 signaling. Therefore, targeting two pathways involved in lipid metabolism may provide a new direction for treating ATC.

Simvastatin Inhibits Cell Proliferation and Migration in Human Anaplastic Thyroid Cancer.

Malignant human anaplastic thyroid cancer (ATC) is pertinacious to conventional therapies. The present study investigated the anti-cancer activity of simvastatin and its underlying regulatory mechanism in cultured ATC cells. Simvastatin (0-20 µM) concentration-dependently reduced cell viability and relative colony formation. Depletions of mevalonate (MEV) and geranylgeranyl pyrophosphate (GGpp) by simvastatin induced G1 arrest and increased apoptotic cell populations at the sub-G1 phase. Adding MEV and GGpp prevented the simvastatin-inhibited cell proliferation. Immunoblotting analysis illustrated that simvastatin diminished the activation of RhoA and Rac1 protein, and this effect was prevented by pre-treatment with MEV and GGpp. Simvastatin increased the levels of p21cip and p27kip proteins and reduced the levels of hyperphosphorylated-Rb, E2F1 and CCND1 proteins. Adding GGpp abolished the simvastatin-increased levels of p27kip protein, and the GGpp-caused effect was abolished by Skp2 inhibition. Introduction of Cyr61 siRNA into ATC cells prevented the epidermal growth factor (EGF)-enhanced cell migration. The EGF-induced increases of Cyr61 protein expression and cell migration were prevented by simvastatin. Taken together, these results suggest that simvastatin induced ATC proliferation inhibition through the deactivation of RhoA/Rac1 protein and overexpression of p21cip and p27kip, and migration inhibition through the abrogation of Cyr61 protein expression.

A Randomized, Double-Blind Clinical Study on Blood Pressure Reduction and Blood Lipid Profile Amelioration on Treatment with Ankascin 568.

Hypertension and cardiovascular complications are the leading causes of death worldwide. Antihypertensive drugs often cause various side effects, and improper use of antihypertensive medications can result in irreparable damage. Edible fungi of the Monascus species have been used as traditional Chinese medicines in Southeast Asia for several centuries. The fermented products of Monascus purpureus NTU 568 (ANKASCIN 568) possess a number of functional secondary metabolites including the anti-inflammatory pigments monascin (MS) and ankaflavin (AK). In this study, a double-blind, placebo-controlled clinical trial was performed in which patients with mild to moderate hypertension were randomly assigned to receive placebo or two 500-mg capsules of Ankascin 568 for 8 weeks. The effects of this treatment on the regulation of blood pressure (BP) were then examined. The results showed that systolic blood pressure (SBP) decreased from 141.6 ± 12.0 to 133.9 ± 14.4 mmHg (P < 0.05), and diastolic blood pressure (DBP) decreased from 91.7 ± 8.1 to 84.8 ± 7.4 mmHg (P < 0.05). Moreover, Ankascin 568 treatment effectively reduced serum triglycerides and total cholesterol (TC), increased high-density lipoprotein cholesterol (HDL-C), and reduced low-density lipoprotein cholesterol (LDL-C) levels, thereby improving the serum lipid profile. Additionally, administration of Ankascin 568 did not cause significant rhabdomyolysis nor impaired the metabolic or physiological functions of the liver or kidney. In conclusion, patients administered Ankascin 568 for 8 weeks exhibited significant in reduction of SBP, serum TC and LDL-C levels, which should contribute to better cardiovascular health.

Valproic acid inhibits glioblastoma multiforme cell growth via paraoxonase 2 expression.

We studied the potential mechanisms of valproic acid (VPA) in the treatment of glioblastoma multiforme (GBM). Using the human U87, GBM8401, and DBTRG-05MG GBM-derived cell lines, VPA at concentrations of 5 to 20 mM induced G2/M cell cycle arrest and increased the production of reactive oxygen species (ROS). Stress-related molecules such as paraoxonase 2 (PON2), cyclin B1, cdc2, and Bcl-xL were downregulated, but p27, p21 and Bim were upregulated by VPA treatment. VPA response element on the PON2 promoter was localized at position -400/-1. PON2 protein expression was increased in GBM cells compared with normal brain tissue and there was a negative correlation between the expression of PON2 and Bim. These findings were confirmed by the public Bredel GBM microarray (Gene Expression Omnibus accession: GSE2223) and the Cancer Genome Atlas GBM microarray datasets. Overexpression of PON2 in GBM cells significantly decreased intracellular ROS levels, and PON2 expression was decreased after VPA stimulation compared with controls. Bim expression was significantly induced by VPA in GBM cells with PON2 silencing. These observations were further shown in the subcutaneous GBM8401 cell xenograft of BALB/c nude mice. Our results suggest that VPA reduces PON2 expression in GBM cells, which in turn increases ROS production and induces Bim production that inhibits cancer progression via the PON2-Bim cascade.