Dueng-Yuan Hueng

Mild traumatic brain injury (mTBI) affects millions worldwide and frequently leads to secondary depression. Early identification of high-risk individuals is critical for targeted mental-health screening in this population. Data-driven phenotyping offers a promising avenue to unmask hidden symptom patterns, but few studies have combined unsupervised clustering of post-concussion profiles with established clinical and psychosocial metrics. We aimed to classify post-concussion symptom-severity profiles in adults with mTBI and to evaluate their association with secondary depression risk, adjusting for Glasgow Coma Scale (GCS) score, psychological resilience, age, sex, and time since injury. In this cross-sectional analysis, 249 adults with mTBI (GCS 13–15) were recruited from a tertiary hospital in northern Taiwan. We performed hierarchical clustering using Ward’s method with Euclidean distance (with BIC support) to derive three symptom-severity phenotypes from the Rivermead Post-Concussion Questionnaire items, then used k-means clustering to assign individuals to these by minizing within-cluster variance. Depression, defined as a Beck Depression Inventory-II ≥ 13, was modeled as an outcome in generalized linear models, adjusting for GCS and psychological resilience. Model discrimination was evaluated via area under the receiver operating characteristic curve (AUC). Three distinct symptom clusters (mild, moderate, severe) were identified. The severe cluster was characterized by prominent visual symptoms, including light sensitivity and double vision. Compared with the mild cluster, the moderate cluster had 5.06-fold higher depression odds (95% CI [2.08–12.31]; p < .001) and the severe cluster 17.17-fold higher odds (95% CI [5.66–52.14]; p < .001). Higher resilience was independently protective (OR = 0.95, 95% CI [0.93–0.96]; p < .001), as was each additional GCS score (OR = 0.20, 95% CI [0.06–0.62]; p = .005). The full model showed excellent discrimination with an AUC of 88%, 95% CI [0.83–0.92]. Our data-driven approach shows that distinct post-concussion symptom-severity phenotypes, when integrated with GCS and resilience metrics, yields a robust tool for identifying mTBI survivors at high risks of depression. These findings support early, targeted mental-health screening and lay the groundwork for prospective validation and personalized intervention strategies. NCT04243226. Registered on January 20. 2020.

Objective: Glioblastoma multiforme (GBM) is the most frequently occurring central nervous system tumor in adults. GBM patients exhibit poor survival outcomes following standard treatment, with drug resistance playing a critical role in disease progression. This study aimed to evaluate the effects of valsartan, a renin−angiotensin system inhibitor, on GBM cell lines with and without temozolomide (TMZ) resistance. Methods: TMZ-resistant GBM clones were established by repeatedly exposing LN229 and GBM8401 human glioma cells to high doses of TMZ, followed by selective culture of the surviving populations. Tumorigenic potential was assessed using viability, sphere formation, invasion, and apoptosis assays. Gene expression was examined by sequencing and validated by quantitative polymerase chain reaction. Results: Valsartan reduced the proportion of viable GBM cells regardless of TMZ sensitivity. Flow cytometry and western blotting revealed increased apoptosis in GBM following valsartan treatment. RNA sequencing revealed that valsartan regulates the cell cycle and induces G1-phase arrest, as evidenced by cell cycle flow cytometry. Moreover, APLN, an angiogenesis-related gene, was identified as a potential downstream target whose expression is significantly inhibited by valsartan. Conclusions: This study revealed that valsartan is a novel strategy for treating gliomas with drug resistance.

Glioblastoma multiforme (GBM) is an aggressive brain tumor with a poor prognosis, worsened by resistance to temozolomide (TMZ). TMZ-induced DNA damage is counteracted by the repair enzyme O-6-methylguanine-DNA methyltransferase (MGMT), promoting tumor recurrence. Targeting oxidative phosphorylation (OXPHOS), essential for cellular energy production, offers a potential therapeutic strategy to overcome TMZ resistance and improve GBM treatment outcomes. Gboxin, a small-molecule drug, selectively inhibits OXPHOS by targeting complex V, with minimal toxicity to normal cells. It accumulates in the mitochondria of GBM cells, exploiting their high membrane potential and pH, thereby inhibiting cell proliferation. This study evaluates Gboxin's efficacy in TMZ-resistant (TMZ-R) GBM. Results show that Gboxin suppresses the growth of both TMZ-sensitive and TMZ-R GBM cells by inhibiting proliferation, inducing apoptosis, and reducing OXPHOS activity. These findings were confirmed in an in vivo model, highlighting Gboxin as a promising therapeutic for both TMZ-sensitive and TMZ-R GBM.

The natural course of pineal germ cell tumors (GCTs), particularly their post-operative progression, is not well understood. We report a rare case of pineal region GCT showing rapid enlargement within 2 weeks following surgical resection. A young adult male presented with progressive headache and diplopia for several weeks. Although elevation of β-human chorionic gonadotropin (β-HCG) and α-fetoprotein (AFP) levels suggested that a large pineal mass lesion observed on magnetic resonance imaging (MRI) might be a β-HCG/AFP-producing tumor, whether the mass was truly a GCT remained unclear. We performed an endoscopy-assisted suboccipital infratentorial approach with removal of the tumor that was diagnosed as germinoma via histopathological investigation. During the week preceding chemotherapy, the patient’s consciousness rapidly worsened. MRI showed that the residual pineal germinoma had enlarged and even compressed the tectum and thalamus. Emergency chemotherapy and radiotherapy were prescribed, and the patient received invasive ventilation for respiratory failure. Unexpectedly, the patient recovered within a short period. Importantly, total regression of the pineal germinoma, accompanied by β-HCG and AFP levels returning to normal range, was observed 4 months after chemotherapy. These phenomena suggest that the rapid enlargement of the pineal germinoma, which might be induced by aggressive surgical cytoreduction, responds well to chemoradiotherapy.

"Letter to the Editor. Rotterdam CT score" published on 11 Aug 2023 by American Association of Neurological Surgeons.

Nuclear fission reactions can release massive amounts of energy accompanied by neutrons and γ photons, which create a mixed radiation field and enable a series of reactions in nuclear reactors. This study demonstrates a one-pot/one-step approach to synthesizing radioactive gold nanoparticles (RGNP) without using radioactive precursors and reducing agents. Trivalent gold ions are reduced into gold nanoparticles (8.6–146 nm), and a particular portion of ¹⁹⁷Au atoms is simultaneously converted to ¹⁹⁸Au atoms, rendering the nanoparticles radioactive. We suggest that harnessing nuclear energy to gold nanoparticles is feasible in the interests of advancing nanotechnology for cancer therapy. A combination of RGNP applied through convection-enhanced delivery (CED) and temozolomide (TMZ) through oral administration demonstrates the synergistic effect in treating glioblastoma-bearing mice. The mean survival for RGNP/TMZ treatment was 68.9 ± 9.7 days compared to that for standalone RGNP (38.4 ± 2.2 days) or TMZ (42.8 ± 2.5 days) therapies. Based on the verification of bioluminescence images, positron emission tomography, and immunohistochemistry inspection, the combination treatment can inhibit the proliferation of glioblastoma, highlighting the niche of concurrent chemoradiotherapy (CCRT) attributed to RGNP and TMZ.

Background: Proton pump inhibitor (PPI) lansoprazole acts as a liver X receptor agonist, which plays a crucial role in the crosstalk of osteoblasts and osteoclasts in vitro and during bone turnover in vivo. However, epidemiological studies on the association between the use of lansoprazole and osteoporosis risk are limited. We aimed to determine the risk of developing osteoporosis in patients with lansoprazole use. Methods: A retrospective cohort study was conducted using the National Health Insurance Research Database of Taiwan dated from 2000 to 2013. The study includes 655 patients with lansoprazole use (the exposed cohort) and 2620 patients with other PPI use (the comparison cohort). The main outcome was the primary diagnosis of osteoporosis. The hazard ratios (HRs) and 95% confidence intervals (CIs) were used to assess the association between the use of lansoprazole and risk of osteoporosis. Results: Patients receiving lansoprazole treatment had a reduced risk of osteoporosis as compared with those undergoing other PPI therapy (adjusted HR, 0.56; 95% CI, 0.46–0.68). Moreover, this inverse association is evident in both sexes and in various age groups. Conclusions: This population-based cohort study demonstrated that lansoprazole use was associated with a reduced risk of osteoporosis. The clinical implications of the present study need further investigations.

"Letter to the Editor. Outcome of malignant meningioma" published on 27 May 2022 by American Association of Neurological Surgeons.

Introduction: Hydrocephalus is a complication of spontaneous intracerebral hemorrhage; however, its predictive relationship with hydrocephalus in this patient cohort is not understood. Here, we evaluated the incidence and risk factors of hydrocephalus after craniectomy. Methods: Retrospectively studied data from 39 patients in the same hospital from 2016/01 to 2020/12 and analyzed risk factors for hydrocephalus. The clinical data recorded included patient age, sex, timing of surgery, initial Glasgow Coma Scale score, intracerebral hemorrhage (ICH) score, alcohol consumption, cigarette smoking, medical comorbidity, and blood data. Predictors of patient outcomes were determined using Student t test, chi-square test, and logistic regression. Results: We recruited 39 patients with cerebral herniation who underwent craniectomy for spontaneous supratentorial hemorrhage. Persistent hydrocephalus was observed in 17 patients. The development of hydrocephalus was significantly associated with the timing of operation, cigarette smoking, and alcohol consumption according to the Student t test and chi-square test. Univariate and multivariate analyses suggested that postoperative hydrocephalus was significantly associated with the timing of surgery (P = .031) and cigarette smoking (P = .041). Discussion: The incidence of hydrocephalus in patients who underwent delayed operation (more than 4 hours) was lower than that in patients who underwent an operation after less than 4 hours. nonsmoking groups also have lower incidence of hydrocephalus. Among patients who suffered from spontaneous supratentorial hemorrhage and need to receive emergent craniectomy, physicians should be reminded that postoperative hydrocephalus followed by ventriculoperitoneal shunting may be necessary in the future.

"Letter to the Editor. Prediction model of IDH wild-type glioblastoma" published on 03 Jun 2022 by American Association of Neurological Surgeons.