Despite extensive research on the mental health effects of the COVID-19 pandemic, limited attention has been given to how pandemic-related stressors uniquely influence self-injury and suicidal ideation among global student populations. This cross-national study examines both psychological and pandemic-related determinants of self-harm in international and domestic Indonesian students, highlighting divergent drivers of self-injury across these groups. Conducted as a cross-sectional study from 2022 to 2023, the research involved 393 participants—200 studying overseas and 193 based in Indonesia. Data were collected via online questionnaires, including the Depression Anxiety Stress Scale (DASS) and the Self-Harm Inventory (SHI). Additional assessments captured social and educational factors such as living arrangements, marital status, family income, perceived study difficulties, academic performance, and financial concerns. Hierarchical clustering of correlation matrices was used to identify distinct patterns in mental health outcomes and associated drivers. No significant differences were observed between international and domestic students in overall levels of depression (10.1 ± 8.6 vs. 10.0 ± 8.4), anxiety (7.7 ± 6.4 vs. 8.6 ± 6.6), or loneliness (42.9 ± 8.9 vs. 42.7 ± 8.5; all pcorrected ≥ 0.98). However, the determinants of severe self-harm differed substantially between groups. Among domestic students, self-injury attempts were significantly associated with pandemic-related stressors, including COVID-19–related worry about family and friends (r = 0.26, puncorrected < 0.001) and worry about missing out on important experiences (r = 0.33, puncorrected < 0.001). These associations were not observed in international students (r ≤ 0.05, puncorrected ≥ 0.47), with between-group differences confirmed by Fisher’s z tests (p ≤ 0.039). In contrast, self-harm in international students was more strongly linked to broader psychological vulnerabilities rather than pandemic-specific concerns. Subcluster analyses supported these distinct contextual and psychological patterns. These findings highlight the need to address the unique psychological and social challenges faced by both international and domestic students. A holistic, culturally responsive approach to student mental health is critical, particularly in mitigating the risks of self-injury and suicidal ideation. These insights can support educators and institutions in identifying at-risk students and implementing effective support strategies, especially for global learners in times of crisis.

Leukemia progression is increasingly shaped by reciprocal interactions between leukemic cells and the bone marrow microenvironment, yet the extracellular regulatory networks associated with these interactions remain incompletely understood. Here, we investigated the biological context associated with the antileukemic activity of LCC-10 (NSC765599), a synthetic biphenyl benzamide derivative, using an integrated pharmacogenomic and structure-guided computational framework. Antiproliferative activity was first characterized using the NCI-60 screen and subsequently integrated with pharmacogenomic response similarity analysis, baseline transcriptomic profiling, similarity-based target prediction, systems-level network analysis, molecular docking, coarse-grained molecular dynamics simulations, comparative in silico ADMET evaluation, and zebrafish embryo developmental toxicity assessment. LCC-10 exhibited potent antiproliferative activity across leukemia cell lines, with submicromolar GI50 values in five of six models. Computational analyses converged on a matrix metalloproteinase (MMP)-associated extracellular matrix (ECM) regulatory network, with MMP2 and MMP9 among the recurrently implicated candidates. Structure-guided analyses suggested structural compatibility of LCC-10 with representative MMP catalytic domains but did not establish direct biochemical inhibition or target engagement. Comparative in silico ADMET analyses supported the predicted developability profile of LCC-10, whereas zebrafish embryo assays indicated concentration-dependent developmental tolerability within the tested range. Collectively, these findings associate LCC-10 with an MMP-associated ECM regulatory network in leukemia while defining this relationship as a hypothesis requiring direct experimental validation. This integrated framework provides a rationale for subsequent biochemical, target-engagement, and functional studies to clarify the molecular basis of LCC-10 activity.

BACKGROUND AND OBJECTIVE:Relevant research has provided valuable insights into risk factors for bicycle crashes at intersections. However, few studies have focused explicitly on three common types of bicycle crashes on road segments: overtaking, rear-end, and door crashes. This study aims to identify risk factors for overtaking, rear-end, and door crashes that occur on road segments. MATERIAL AND METHODS:We analysed British STATS19 accident records from 1991 to 2020. Using multivariate logistic regression models, we estimated adjusted odds ratios (AORs) with 95% confidence intervals (CIs) for multiple risk factors. The analysis included 127,637 bicycle crashes, categorised into 18,350 overtaking, 44,962 rear-end, 6,363 door, and 57,962 other crashes. RESULTS:Significant risk factors for overtaking crashes included heavy goods vehicles (HGVs) as crash partners (AOR = 1.30, 95% CI 1.27-1.33), and elderly crash partners (AOR = 2.01, 95% CI = 1.94-2.09), and decreased risk in rural area with speed limits of 20-30 miles per hour (AOR = 0.45, 95% CI = 0.43-0.47). For rear-end crashes, noteworthy risk factors included unlit darkness (AOR = 1.49, 95% CI = 1.40-1.57) and midnight hours (AOR = 1.28, 95% CI = 1.21-1.40). Factors associated with door crashes included urban areas (AOR = 16.2, 95% CI = 13.5-19.4) and taxi or private hire cars (AOR = 1.61, 95% CI = 1.57-1.69). Our joint-effect analysis revealed additional interesting results; for example, there were elevated risks for overtaking crashes in rural areas with elderly drivers as crash partners (AOR = 2.93, 95% CI = 2.79-3.08) and with HGVs as crash partners (AOR = 2.62, 95% CI = 2.46-2.78). CONCLUSIONS:The aforementioned risk factors remained largely unchanged since 2011, when we conducted our previous study. However, the present study concluded that the detrimental effects of certain variables became more pronounced in certain situations. For example, cyclists in rural settings exhibited an elevated risk of overtaking crashes involving HGVs as crash partners.

Recent scientific studies exploring the neuropsychological foundations of moral decision-making have shown that moral attitudes and evaluations are significantly influenced by emotion, particularly negative emotionality, as well as personality traits such as neuroticism. Further psychopharmacological research has observed that GABAergic agonists are capable of influencing moral decision-making by modifying anxiety-related emotional negativity and/or through cognitive modulation. The aim of this double-blind, crossover design, placebo-controlled study is to evaluate said GABAergic modulation on moral cognition. Importantly, unlike the aforementioned research, the present study not only utilizes explicit moral evaluation measures [e.g., the Justice Sensitivity Inventory (JSI) and evaluations of moral scenarios], but also uses the morality Implicit Association Test (mIAT) to assess unacknowledged attitudes towards morally charged scenarios. Our results indicate that acute lorazepam administration does not significantly alter moral judgments, including implicit moral attitudes, explicit justice sensitivity, and blame/praise evaluations. Lorazepam-induced changes in moral sensitivity appeared to vary with baseline levels, with individuals exhibiting higher baseline JSI or D scores tending to show greater reductions following administration. These findings support the involvement of GABAergic modulation in moral cognition, albeit without clear behavioral consequences.

INTRODUCTION:Patients with Type 2 diabetes experience cognitive and affective deficits linked to widespread functional brain alterations. However, previous meta-analyses of functional neuroimaging have primarily focused on the resting-state studies. While valuable, this approach may have overlooked the key neuronal mechanisms underlying these deficits. METHODS:To address this, we conducted a coordinate-level task-based meta-analysis of functional neuroimaging via a systematic search of Embase, PubMed, Medline, and Web of Science (December 2023), alongside task-based and task-free connectivity analyses using the BrainMap database. Activation likelihood estimations were applied to two task categories: that are, cognitive and affective. To control for biased results, we also conducted jackknife sensitivity analysis and within-paper combined experiments analysis as validation analyses. RESULTS:We identified a cluster of activation in cognitive paradigm (18 contrasts, 153 foci, 767 subjects), with the middle frontal gyrus, part of the medial frontal cortex, as the peak region. For the affective paradigm (18 contrasts, 181 foci, 951 subjects), we observed both increased and decreased activities. Two increased clusters peak in the amygdala and middle temporal gyrus, while the three decreased clusters were inferior frontal gyrus, insula, and putamen. Follow-up connectivity analyses showed that these brain alterations were both task-specific and task-generic. CONCLUSION:Despite the lack of uniformity across task, such domain-specific and domain-general patterns of alterations provide a more nuanced understanding of the cognitive and affective deficits in Type 2 diabetes patients. This highlights the varied neuronal mechanisms underlying these deficits.

Background:Although the association between neurodegenerative diseases, such as dementia, and traumatic brain injury (TBI) has long been known, the association between dementia and TBI with epilepsy has been controversial.Aim:This data-driven population-based study is designed to investigate the association between dementia and epilepsy after TBI within a 2-year period.Methods:This case-control cohort study was conducted using the Longitudinal Health Insurance Database 2000 (LHID2000). We included 784 individuals ambulatory or hospitalized for TBI with epilepsy from 2001 to 2011, compared with 2992 patients with TBI without epilepsy who were matched for characteristics including sex, age, and healthcare resource use index date. Every participant was followed up for 5 years to ascertain any dementia development. Data were stratified and analyzed using the Cox proportional hazards regression.Results:Through the 5-year follow-up period, 39 patients (5.21%) with TBI with epilepsy and 55 (1.53%) with TBI without epilepsy developed dementia. TBI with epilepsy was independently associated with a >3.03 times risk of dementia after correcting for age, sex, and comorbidities.Conclusion:These findings suggest an increased risk of dementia in patients with TBI with epilepsy. Our research recommends that individuals with TBI and epilepsy be monitored more intensively.

Moral attitudes and evaluations were once considered to emerge solely from rational thought. Nevertheless, recent neuropsychological studies show that these moral attributes are significantly influenced by emotion, particularly negative emotionality. Further psychopharmacological research has observed that GABAergic agonists are capable of influencing moral decision-making by modifying anxiety-related emotional negativity and/or through cognitive modulation. The aim of this double-blind, crossover design, placebo-controlled study is to evaluate said GABAergic modulation on moral cognition. Importantly, unlike the aforementioned research, the present study not only utilizes explicit moral evaluation measures (e.g., JSI and evaluations of moral scenarios), but also uses the morality Implicit Association Test (mIAT) to assess unacknowledged attitudes towards morally charged scenarios. Our results show that acute lorazepam administration significantly decreases mIAT D-scores in the High-D group, while having no effect on the Low-D group. Significant differences regarding the other-oriented JSI were observed between groups, with lorazepam administration exhibiting a marginal trend towards significance. These findings not only confirm GABAergic activity modulation on moral cognition (including implicit mechanisms), but also suggest such modulation promotes pro-social behavior. Altogether, this study supports the dynamic system model of moral cognition, where explicit rational deliberative operations interplay with implicit emotional processes during moral decision-making.

This study aimed to translate and validate the traditional Chinese version of the Community Integration Questionnaire-Revised (TC-CIQ-R) in patients with traumatic brain injury (TBI). We included participants aged ≥20 years and diagnosed as having TBI for ≥6 months from neurosurgical clinics. The 18-item TC-CIQ-R, Participation Measure – 3 Domains, 4 Dimensions (PM-3D4D), Extended Glasgow Outcome Scale (GOSE), and Taiwanese Quality of Life After Brain Injury (TQOLIBRI) were completed. The sample included 180 TBI survivors (54% male, mean age 47 years) of whom 87% sustained a mild TBI. Exploratory factor analysis extracted four factors – home integration, social integration, productivity, and electronic social networking – which explained 63.03% of the variation, after discarding the tenth item with a factor loading of 0.25. For criterion-related validity, the TC-CIQ-R was significantly correlated with the PM-3D4D; convergent validity was exhibited by demonstrating the associations between the TC-CIQ-R and TQOLIBRI. Known-group validity testing revealed significant differences in the subdomain and total scores of the TC-CIQ-R between participants with a mean GOSE score of ≤6 and >7 (all P < 0.001). The TC-CIQ-R exhibited acceptable Cronbach’s α values (0.68–0.88). We suggest the 17-item TC-CIQ-R as a valid tool for rehabilitation professionals, useful for both clinical practice and research in assessing community integration levels following TBI.

Glioblastoma multiforme (GBM) is the most aggressive and lethal primary brain tumor whose median survival is less than 15 months. The current treatment regimen comprising surgical resectioning, chemotherapy with Temozolomide (TMZ), and adjuvant radiotherapy does not achieve total patient cure. Stem cells’ presence and GBM tumor heterogeneity increase their resistance to TMZ, hence the poor overall survival of patients. A dysregulated cell cycle in glioblastoma enhances the rapid progression of GBM by evading senescence or apoptosis through an over-expression of cyclin-dependent kinases and other protein kinases that are the cell cycle’s main regulatory proteins. Herein, we identified and validated the biomarker and predictive properties of a chemoradio-resistant oncogenic signature in GBM comprising CDK1, PBK, and CHEK1 through our comprehensive in silico analysis. We found that CDK1/PBK/CHEK1 overexpression drives the cell cycle, subsequently promoting GBM tumor progression. In addition, our Kaplan–Meier survival estimates validated the poor patient survival associated with an overexpression of these genes in GBM. We used in silico molecular docking to analyze and validate our objective to repurpose Dapagliflozin against CDK1/PBK/CHEK1. Our results showed that Dapagliflozin forms putative conventional hydrogen bonds with CDK1, PBK, and CHEK1 and arrests the cell cycle with the lowest energies as Abemaciclib.

BACKGROUND:Cognitive impairment is common in patients with traumatic brain injury (TBI). Studies that have examined the effectiveness of neurofeedback (NFB) on cognitive function following TBI have had poor study designs and small sample sizes.OBJECTIVES:This randomized controlled trial assessed the effects of low-resolution tomography Z-score NFB (LZNFB) and theta/beta NFB on cognitive impairment, return to productive activity, and quality of life in patients with TBI.METHODS:We randomly assigned 87 patients with TBI with cognitive impairment to LZNFB, theta/beta NFB, or usual care (UC) groups. Patients in both NFB groups received weekly 60-minute treatment for 10 weeks, and those in the control group received UC and telephone interviews for 10 weeks. The primary outcome was cognitive function as measured by performance on cognitive tasks; the secondary outcomes included productive activity and quality of life based on the Community Integration Questionnaire-revised (CIQ-R) and the Quality of Life after Brain Injury (QOLIBRI), respectively, at baseline and immediately after the last intervention.RESULTS:The LZNFB group exhibited significantly greater improvements in immediate recall, delayed recall, recognition memory, and selective attention compared with the UC group; the theta/beta NFB group exhibited improvements in only immediate memory and selective attention (P < .05). The total CIQ-R scores of the LZNFB group after treatment were significantly improved than those of the UC group were.CONCLUSION:Consecutive LZNFB achieved therapeutic effects in memory, attention, and productive activity, whereas theta/beta NFB improved memory and attention in patients with TBI.This trial was prospectively registered at ClinicalTrial.gov (registration number: NCT03515317; https://clinicaltrials.gov/ct2/show/NCT03515317).

Purpose We performed a mediation analysis to investigate how mental fatigue mediates the relationship between cognitive functions and the return to productive activity following TBI. Methods One hundred and one people (>= 20 years) with first-time TBI more than 3 months who completed a series of cognitive tasks followed by Chinese versions of the Mental Fatigue Scale and Community Integration Questionnaire-Revised. Mediation analysis was used to test our hypotheses. Results Recognition memory and information processing speed were the only cognitive functions correlated with mental fatigue (B = -0.56 and -0.37, P = .04 and < 0.001) and the return to productive activity (B = 0.69 and 0.19, both P < .001) after controlling for confounders. Mental fatigue partially mediated the associations of recognition memory and information processing speed with the return to productive activity (B = 0.15 and 0.08, P = .001 and < 0.001, proportion of mediation = 22% and 46%) after the adjustment of confounders. Conclusions The findings suggest that mental fatigue can partially mediate the relationship between cognitive deficits and return to productive activity. Mental fatigue can be considered a crucial, treatable mediator of the adverse effects of cognitive impairment upon return to productive activity following TBI.

Objective: To investigate the effect of force applied during massage on relieving nonspecific low back pain (LBP). Methods: This single-blinded, randomized controlled trial enrolled 56 female patients with nonspecific LBP at a single medical center. For each participant, the therapist performed a 30 min massage session (20 min general massage and 10 min focal massage) using a special instrument with a force sensor inserted, for a total of six sessions in 3 weeks. During the 10 min focal massage, HF and LF groups received high force (HF, ≥2 kg) and low force (LF, ≤1 kg) massage, respectively. The primary outcome was pain intensity (i.e., visual analog scale (VAS), 0–10), and secondary outcomes comprised pain pressure threshold, trunk mobility, LBP-associated disability, and quality of life. Results: No significant between-group differences were observed in baseline characteristics. The HF group exhibited significantly lower VAS than did the LF group, with a mean difference of −1.33 points (95% CI: −2.17 to −0.5) at the end of the intervention, but no significant difference was noted at the end of the follow-up. A significant time effect (p < 0.05) was detected in all secondary outcomes except the pain pressure threshold and trunk mobility. A significant time × group interaction (p < 0.05) was found only for the VAS and pain pressure threshold. Conclusions: Compared with LF massage, HF massage exerted superior effects on pain relief in female patients with nonspecific LBP at the end of intervention. Applying different levels of force showed no effects on LBP-associated disabilities and quality of life.

Objective: Our aim was to evaluate the feasibility of our developed intelligent cardiopulmonary training system (ICTS) and of the percentage of time spent within the target HR range (%time) as an indicator of adherence to training intensity. Methods: In this noncontrolled trial, nine participants with sedentary lifestyles were recruited from the outpatient rehabilitation department of a teaching hospital. All participants received twelve 30 min sessions of cycling ergometer exercises (5 min warm up, 20 min training phase, and 5 min cool down) with the ICTS three times per week. Training intensity was determined at 60–80% heart rate reserve using cardiopulmonary exercise (CPET) pretests. During training, pedaling resistance was automatically adjusted by the ICTS to keep the user’s heart rate at the predetermined intensity range. Workload-peak and peak oxygen uptake (VO2-peak) were measured during the pretests and post-tests. We recorded the percentage of time spent within the target heart rate range (%time) during the 20 min training phase for each training session as an indicator of adherence. The correlation between %time and gains in VO2-peak was assessed. Results: After 4 weeks of training on the ICTS, workload-peak and VO2-peak significantly improved by 13.6 ± 7.2 w (mean ± SD, p = 0.008) and 1.5 ± 1.1 mL/kg/min (p = 0.011), respectively. The 12-session average %time ranged from 10.6% to 93.1% among the participants, and five participants achieved an average %time >80%. A positive correlation between average %time and training efficacy was found (rs = 0.85, p = 0.004). Conclusions: Cardiopulmonary training with an ICTS is feasible, and the percentage of time spent within the target heart rate range seems to be a reasonable indicator for monitoring training-intensity adherence.

Women during pregnancy and postpartum show high rates of obesity and metabolic diseases, especially women with excessive caloric intake. In the past, it was proved that individuals with high intrinsic aerobic exercise capacities showed higher lipid metabolism and lower fat production than those with low intrinsic aerobic exercise capacities. The purpose of this study was to determine whether mice with the low-fitness phenotype (LAEC) were more likely to develop metabolic abnormalities and obesity under dietary induction after delivery, and if mice with a high-fitness phenotype (HAEC) had a protective mechanism. After parturition and weaning, postpartum Institute of Cancer Research (ICR) mice received dietary induction for 12 weeks and were divided into four groups (n = 8 per group): high-exercise capacity postpartum mice with a normal chow diet (HAEC-ND); high-exercise capacity postpartum mice with a high-fat diet (HAEC-HFD); low-exercise capacity postpartum mice with a normal chow diet (LAEC-ND); and low-exercise capacity postpartum mice with a high-fat diet (LAEC-HFD). Obesity caused by a high-fat diet led to decreased exercise performance (p < 0.05). Although there were significant differences in body posture under congenital conditions, the LAEC mice gained more weight and body fat after high-fat-diet intake (p < 0.05). Compared with HAEC-HFD, LAEC-HFD significantly increased blood lipids, such as total cholesterol (TC), triacylglycerol (TG), low-density lipoprotein (LDL) and other parameters (p < 0.05), and the content of TG in the liver, as well as inducing poor glucose tolerance (p < 0.05). In addition, after HFD intake, excessive energy significantly increased glycogen storage (p < 0.05), but the LAEC mice showed significantly lower muscle glycogen storage (p < 0.05). In conclusion, although we observed significant differences in intrinsic exercise capacity, and body posture and metabolic ability were also different, high-fat-diet intake caused weight gain and a risk of metabolic disorders, especially in postpartum low-fitness mice. However, HAEC mice still showed better lipid metabolism and protection mechanisms. Conversely, LAEC mice might accumulate more fat and develop metabolic diseases compared with their normal rodent chow diet (ND) control counterparts.

ABSTRACT Background Hand massage therapies have been used to relieve anxiety and pain in various clinical situations. The effects of machine-based hand massage on preoperative anxiety in ambulatory surgery settings have not been evaluated. Purpose This prospective study was designed to investigate the effect of machine-based hand massage on preoperative anxiety and vital signs in ambulatory surgery patients. Methods One hundred ninety-nine patients aged 18 years and older who were scheduled to receive ambulatory surgery were recruited from the Taipei Municipal Wanfang Hospital in Taipei City, Taiwan. The patients were assigned randomly to the experimental group (n = 101), which received presurgical machine-based hand massage therapy, and the control group (n = 98), which received no intervention. The patients in both groups completed the Spielberger State-Trait Anxiety Inventory short form at preintervention (baseline) and postintervention. Results Within-group comparisons of Spielberger State-Trait Anxiety Inventory short form scores showed significant decreases between preintervention and postintervention scores in the experimental group (44.3 ± 11.2 to 37.9 ± 8.7) and no significant change in the control group. Within-group comparisons of vital signs revealed a significant increase in mean respiration rate between baseline and postintervention in both groups (both ps < .05). Blood pressure was found to have decreased significantly only in the control group at postintervention (p < .05). No significant preintervention to postintervention change in pulse was observed in either group. Conclusions The findings of this study indicate that machine-based hand massage reduces anxiety significantly in patients awaiting ambulatory surgery while not significantly affecting their vital signs.

Glioblastoma (GBM) is one of the most aggressive brain malignancies with high incidences of developing treatment resistance, resulting in poor prognoses. Glioma stem cell (GSC)-derived exosomes are important players that contribute to GBM tumorigenesis and aggressive properties. Herein, we investigated the inhibitory roles of GBM-N019, a novel small molecule on the transfer of aggressive and invasive properties through the delivery of oncogene-loaded exosomes from GSCs to naïve and non-GSCs. Our results indicated that GBM-N019 significantly downregulated the expressions of the mammalian target of rapamycin (mTOR), signal transducer and activator of transcription 3 (STAT3), and cyclin-dependent kinase 6 (CDK6) signaling networks with concomitant inhibitory activities against viability, clonogenicity, and migratory abilities of U251 and U87MG cells. Treatments with GBM-N019 halted the exosomal transfer of protein kinase B (Akt), mTOR, p-mTOR, and Ras-related protein RAB27A to the naïve U251 and U87MG cells, and rescued the cells from invasive and stemness properties that were associated with activation of these oncogenes. GBM-N019 also synergized with and enhanced the anti-GBM activities of palbociclib in vitro and in vivo. In conclusion, our results suggested that GBM-N019 possesses good translational relevance as a potential anti-glioblastoma drug candidate worthy of consideration for clinical trials against recurrent glioblastomas.

Background: Postconcussion symptoms (PCSs) are common complaints reported by patients after a mild traumatic brain injury (TBI), and these symptoms may lower quality of life. Previous investigations have primarily focused on PCSs in children, adults, and athletes. The frequency, and risk factors, and effects of PCSs for older adults with mild TBIs are unclear. Purpose: To investigate the frequency and risk factors of PCSs, and investigate their effects on quality of life over time after mild TBI in older adults. Methods: A prospective longitudinal study was performed. All participants were enrolled from the emergency department or neurosurgical outpatient clinics of a medical center. The measurement tools were the Rivermead Post-Concussion Symptoms Questionnaire and the Quality of Life after Traumatic Brain Injury. Measurements were performed on the seventh day, at the first month, and at the sixth month after the head injury. A generalized estimating equation model was used for data analyses. Results: One hundred and one older adults (mean age of 76.0 years) with mild TBIs with negative neuroimaging findings were included. Overall, 32.7%, 4%, and 15.8% of the sample reported PCS after 7 days, 1 month, and 6 months of head injury, respectively, revealing a U-shaped trend. We observed that comorbidity measured using the modified Charlson Comorbidity Index was associated with differences in PCSs (P < .05). PCSs were an independent predictor of changes in postinjury quality of life (P < .001). Conclusions: The results indicate that PCS after a mild TBI in older adults is prevalent, even in the chronic phase after a TBI, and PCSs significantly affected the quality of life of our cohort. Therefore, to improve patient quality of life, healthcare providers should employ effective interventions to manage PCSs at different phases after a TBI.

Alzheimer’s disease (AD) is the most frequent cause of neurodegenerative dementia and affects nearly 50 million people worldwide. Early stage diagnosis of AD is challenging, and there is presently no effective treatment for AD. The specific genetic alterations and pathological mechanisms of the development and progression of dementia remain poorly understood. Therefore, identifying essential genes and molecular pathways that are associated with this disease’s pathogenesis will help uncover potential treatments. In an attempt to achieve a more comprehensive understanding of the molecular pathogenesis of AD, we integrated the differentially expressed genes (DEGs) from six microarray datasets of AD patients and controls. We identified ATPase H+ transporting V1 subunit A (ATP6V1A), BCL2 interacting protein 3 (BNIP3), calmodulin-dependent protein kinase IV (CAMK4), TOR signaling pathway regulator-like (TIPRL), and the translocase of outer mitochondrial membrane 70 (TOMM70) as upregulated DEGs common to the five datasets. Our analyses revealed that these genes exhibited brain-specific gene co-expression clustering with OPA1, ITFG1, OXCT1, ATP2A2, MAPK1, CDK14, MAP2K4, YWHAB, PARK2, CMAS, HSPA12A, and RGS17. Taking the mean relative expression levels of this geneset in different brain regions into account, we found that the frontal cortex (BA9) exhibited significantly (p < 0.05) higher expression levels of these DEGs, while the hippocampus exhibited the lowest levels. These DEGs are associated with mitochondrial dysfunction, inflammation processes, and various pathways involved in the pathogenesis of AD. Finally, our blood–brain barrier (BBB) predictions using the support vector machine (SVM) and LiCABEDS algorithm and molecular docking analysis suggested that antrocin is permeable to the BBB and exhibits robust ligand–receptor interactions with high binding affinities to CAMK4, TOMM70, and T1PRL. Our results also revealed good predictions for ADMET properties, drug-likeness, adherence to Lipinskís rules, and no alerts for pan-assay interference compounds (PAINS) Conclusions: These results suggest a new molecular signature for AD parthenogenesis and antrocin as a potential therapeutic agent. Further investigation is warranted.

Objective: To compare the effects of computerized cognitive training (CCT) and tai chi (TC) with usual care (UC) on cognitive functions and secondary outcomes in older adults with traumatic brain injury. Participants and Settings: Ninety-six patients aged 55 years and older who had a diagnosis of traumatic brain injury requiring hospital admission. Design: Randomized controlled trial. Main Measures: The Mattis Dementia Rating Scale (MDRS), Mini-Mental State Examination, modified Telephone Interview of Cognitive Status, and Trail Making Tests A and B. Results: Compared with UC, CCT increased scores on the MDRS's total, attention, and memory and those on the Mini-Mental State Examination and Telephone Interview of Cognitive Status over the 6-month intervention; TC increased scores on the MDRS's total and conceptualization and those on the Mini-Mental State Examination over the 6-month intervention, while it also increased scores on the MDRS's total and initiation/preservation and those on the Telephone Interview of Cognitive Status and reduced the time to complete the Trail Making Test B over the 12-month study. Furthermore, compared with UC, CCT increased handgrip strength and TC reduced the time to complete 5 sit-to-stands over the 6-month intervention. Conclusion: Both CCT and TC may improve global cognition and different specific cognitive domains in older traumatic brain injury patients; the TC's effect may last for at least an additional 6 months.