Speech decoding using cortical and subcortical electrophysiological signals.

Introduction: Language impairments often result from severe neurological disorders, driving the development of neural prosthetics utilizing electrophysiological signals to restore comprehensible language. Previous decoding efforts primarily focused on signals from the cerebral cortex, neglecting subcortical brain structures' potential contributions to speech decoding in brain-computer interfaces. Methods: In this study, stereotactic electroencephalography (sEEG) was employed to investigate subcortical structures' role in speech decoding. Two native Mandarin Chinese speakers, undergoing sEEG implantation for epilepsy treatment, participated. Participants read Chinese text, with 1-30, 30-70, and 70-150 Hz frequency band powers of sEEG signals extracted as key features. A deep learning model based on long short-term memory assessed the contribution of different brain structures to speech decoding, predicting consonant articulatory place, manner, and tone within single syllable. Results: Cortical signals excelled in articulatory place prediction (86.5% accuracy), while cortical and subcortical signals performed similarly for articulatory manner (51.5% vs. 51.7% accuracy). Subcortical signals provided superior tone prediction (58.3% accuracy). The superior temporal gyrus was consistently relevant in speech decoding for consonants and tone. Combining cortical and subcortical inputs yielded the highest prediction accuracy, especially for tone. Discussion: This study underscores the essential roles of both cortical and subcortical structures in different aspects of speech decoding.

Development and Validation of a Prediction Model for 30-Day Mortality and Functional Outcome in Patients with Primary Brainstem Hemorrhage.

INTRODUCTION: Primary brainstem hemorrhage (PBSH) is the most fatal subtype of intracerebral hemorrhage and is associated with poor prognosis. We aimed to develop a prediction model for predicting 30-day mortality and functional outcome in patients with PBSH. METHODS: We reviewed records of 642 consecutive patients with first-time PBSH from three hospitals between 2016 and 2021. Multivariate logistic regression was used to establish a nomogram in a training cohort. Cutoff points of the variables were determined by receiver operating characteristic curve analysis, and certain points were assigned to these predictors to produce the PBSH score. The nomogram and PBSH score were compared with other scoring systems for PBSH. RESULTS: Five independent predictors, comprised of temperature, pupillary light reflex, platelet-to-lymphocyte ratio, Glasgow Coma Scale (GCS) score on admission, and hematoma volume, were incorporated to construct the nomogram. The PBSH score consisted of 4 independent factors with individual points assigned as follows: temperature, ≥38°C (=1 point), <38°C (=0 points); pupillary light reflex, absence (=1 point), presence (=0 points); GCS score 3-4 (=2 points), 5-11 (=1 point), and 12-15 (=0 points); PBSH volume >10 mL (=2 points), 5-10 mL (=1 point), and <5 mL (=0 points). Results showed that the nomogram was discriminative in predicting both 30-day mortality (area under the ROC curve [AUC] of 0.924 in the training cohort, and 0.931 in the validation cohort) and 30-day functional outcome (AUC of 0.887). The PBSH score was discriminative in predicting both 30-day mortality (AUC of 0.923 in the training cohort and 0.923 in the validation cohort) and 30-day functional outcome (AUC of 0.887). The prediction performances of the nomogram and the PBSH score were superior to the intracranial hemorrhage (ICH) score, primary pontine hemorrhage (PPH) score, and new PPH score. CONCLUSIONS: We developed and validated two prediction models for 30-day mortality and functional outcome in patients with PBSH. The nomogram and PBSH score could predict 30-day mortality and functional outcome in PBSH patients.

Individualized targeting is warranted in subcallosal cingulate gyrus deep brain stimulation for treatment-resistant depression: A tractography analysis.

Subcallosal cingulate gyrus (SCG) is a target of deep brain stimulation (DBS) for treatment-resistant depression. However, previous randomized controlled trials report that approximately 42% of patients are responders to this therapy of last resort, and suboptimal targeting of SCG is a potential underlying factor to this unsatisfactory efficacy. Tractography has been proposed as a supplementary method to enhance targeting strategy. We performed a connectivity-based segmentation in the SCG region via probabilistic tractography in 100 healthy volunteers from the Human Connectome Project. The SCG voxels with maximum connectivity to brain regions implicated in depression, including Brodmann Area 10 (BA10), cingulate cortex, thalamus, and nucleus accumbens were identified, and the conjunctions were deemed as tractography-based targets. We then performed deterministic tractography using these targets in additional 100 volunteers to calculate streamline counts compassing to relevant brain regions and fibers. We also evaluated the intra- and inter-subject variance using test-retest dataset. Two tractography-based targets were identified. Tractography-based target-1 had the highest streamline counts to right BA10 and bilateral cingulate cortex, while tractography-based target-2 had the highest streamline counts to bilateral nucleus accumbens and uncinate fasciculus. The mean linear distance from individual tractography-based target to anatomy-based target was 3.2 ± 1.8 mm and 2.5 ± 1.4 mm in left and right hemispheres. The mean ± SD of targets between intra- and inter-subjects were 2.2 ± 1.2 and 2.9 ± 1.4 in left hemisphere, and 2.3 ± 1.4 and 3.1 ± 1.7 in right hemisphere, respectively. Individual heterogeneity as well as inherent variability from diffusion imaging should be taken into account during SCG-DBS target planning procedure.

Naphthalene Diimide-Based Donor-Acceptor-Donor Small Molecules as Metal-Free Organocatalysts for Photocatalytic CO2 Reaction.

The application of organic small molecules as metal-free photocatalysts for light-driven photoreduction of carbon dioxide (CO2) has seldom been explored. This work developed four naphthalene diimide (NDI)-derived donor-acceptor-donor small molecules with different numbers of thiophene units, namely, NDI-2T, NDI-TT, NDI-4T, and NDI-6T, as metal-free photocatalysts to catalyze the reduction of CO2 under irradiation with an air mass 1.5G solar simulator at one-sun intensity. The structure-property relationship was investigated by exploring the effects of the electron-donating ability of the donor units on the optical properties, redox potential, electron-hole distribution, and exciton lifetime. NDI-6T exhibited the most red-shifted absorption, longest exciton lifetime, and strongest electron-hole separation. However, the large upshift in oxidation potential because of the elevated electron-donating ability of the hexathiophene unit significantly reduced the driving force for catalyst regeneration, leading to poor catalytic performance. Alternatively, NDI-4T possessed proper redox potentials, reduced charge-transfer resistance, and excellent photocurrent intensity; therefore, it effectively converted CO2 to a single product of CO in the presence of water as an electron donor without a sacrificial reagent or cocatalyst with a product yield of 168.6 µmol gcat-1 24 h-1, which was considerably higher than those of NDI-TT (111.9 µmol gcat-1 24 h-1), NDI-2T (88.4 µmol gcat-1 24 h-1), and NDI-6T (40.5 µmol gcat-1 24 h-1). This study provides a practical guideline for the molecular design of conjugated organic molecules as promising photocatalysts for CO2 photoreduction.

Higher cystatin C level increases the risk of delayed cerebral ischemia after endovascular treatment of aneurysmal subarachnoid hemorrhage: a case-control study.

Cystatin C (CysC) has been found to be associated with hemorrhagic and ischemic stroke in many studies. However, the association between CysC level and the risk of delayed cerebral ischemia after endovascular treatment of aneurysmal subarachnoid hemorrhage has been reported rarely. Our study was proposed to explore this association. Consecutive patients from June 2015 to February 2021 in this single-center retrospective study were selected. Univariate and multivariate analyses were used to identify potential prognostic risk factors for delayed cerebral ischemia, and the stability of the association was demonstrated by several statistical methods, such as subgroup analysis, interaction testing, generalized linear models, and propensity score matching. A total of 424 patients were included in the analysis. Cystatin C was independently associated with delayed cerebral ischemia. The independent effects of CysC on delayed cerebral ischemia were shown in generalized linear models with a logit link, and the results were relatively stable in crude, partial, and full models with ORs (95% CIs) for delayed cerebral ischemia. Subgroup analysis showed no significant subgroup differences in the effect of CysC on delayed cerebral ischemia. There was also no interaction effect between CysC and other confounders. Patients in the high CysC group had a higher risk of delayed cerebral ischemia than those in the low CysC group before and after propensity score matching. CysC level could be an independent predictor for the risk of delayed cerebral ischemia after endovascular treatment of aneurysmal subarachnoid hemorrhage.

Drug delivery strategy in hepatocellular carcinoma therapy.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide, with high rates of recurrence and death. Surgical resection and ablation therapy have limited efficacy for patients with advanced HCC and poor liver function, so pharmacotherapy is the first-line option for those patients. Traditional antitumor drugs have the disadvantages of poor biological distribution and pharmacokinetics, poor target selectivity, high resistance, and high toxicity to nontargeted tissues. Recently, the development of nanotechnology has significantly improved drug delivery to tumor sites by changing the physical and biological characteristics of drugs and nanocarriers to improve their pharmacokinetics and biological distribution and to selectively accumulate cytotoxic agents at tumor sites. Here, we systematically review the tumor microenvironment of HCC and the recent application of nanotechnology in HCC. Video Abstract.

Outcomes of Ventriculoperitoneal Shunt in Patients With Idiopathic Normal-Pressure Hydrocephalus 2 Years After Surgery.

Objective: To evaluate the outcomes and prognostic factors of ventriculoperitoneal shunts (VP-shunts) in patients with idiopathic normal-pressure hydrocephalus (iNPH) at 6 months and 2 years after surgery. Method: We retrospectively analyzed 68 patients admitted to our institute and diagnosed with probable iNPH from January 2017 to March 2021. All patients underwent VP-shunt surgery with a programmable valve, and their outcomes were assessed via the Krauss index and modified Rankin scale (mRS) at 6 months and 2 years post-surgery. Univariate and multivariate regression analysis was performed to identify the prognostic factors. Results: The mean age of the patients was 71.1 ± 8.4 (mean ± standard deviation) years. On the Krauss improvement index, 6-month follow-up results were available for 68 patients. Of these patients, 91.2% experienced attenuation of their preoperative symptoms, with a mean Krauss index of 0.58 ± 0.27, and 48 patients (70.6%) had a Krauss index ≥0.5. Two-year follow-up results were available for 33 patients; 90.9% of them had sustained improvement, with a Krauss index of 0.54 ± 0.31, and 21 patients (66.3%) had a Krauss index ≥0.5. Thirty-three patients (58%) were living independently after 2 years (mRS 0-2). The outcomes were worse for patients with multiple comorbidities. Neither an increased patient age nor a prolonged history of illness was statistically significant prognostic factors for adverse outcomes of VP-shunt surgery. Conclusion: Surgical treatment was well-tolerated by patients with iNPH who received VP-shunts. Most patients experienced attenuation of their preoperative symptoms. Multiple concurrent comorbidities should be considered as adverse prognostic factors before shunt insertion in patients with iNPH.

Ventriculosternal Shunt for the Treatment of Idiopathic Normal Pressure Hydrocephalus: A Case Report.

Background: Conventional corticospinal fluid (CSF) diversion surgery for idiopathic normal pressure hydrocephalus (iNPH) includes ventriculoperitoneal shunt and ventriculoatrial shunt. Ventriculosternal (VS) shunt may be considered if both the abdominal cavity and atrium are not feasible. Methods: A 76-year-old woman was admitted to our hospital with gait disturbance and urinary incontinence for 2 years, and the condition aggravated in the last 1 month. Based on clinical assessment and imaging findings, the patient was diagnosed with iNPH, with surgical indications. She was on peritoneal dialysis for chronic renal failure, and a cardiac Doppler echocardiogram showed enlargement of the left atrium and decreased diastolic function of the left ventricle. Due to these conditions, we chose the sternum as the vessel for CSF absorption and performed VS shunt. Results: No swelling, exudation, and effusion were found in the suprasternal fossa. Gait disturbance and urinary incontinence improved significantly immediately and 1 week after surgery, respectively. No shunt-related complication was reported at 16 months follow-up. Conclusion: This case demonstrated VS shunting as a feasible and alternative for the management of hydrocephalus.

A connectomic analysis of deep brain stimulation for treatment-resistant depression.

OBJECTIVE: Deep brain stimulation (DBS) has been used as a treatment of last resort for treatment-resistant depression (TRD) for more than a decade. Many DBS targets have been proposed and tested clinically, but the underlying circuit mechanisms remain unclear. Uncovering white matter tracts (WMT) activated by DBS targets may provide crucial information about the circuit substrates mediating DBS efficacy in ameliorating TRD. METHODS: We performed probabilistic tractography using diffusion magnetic resonance imaging datas from 100 healthy volunteers in Human Connectome Project datasets to analyze the structural connectivity patterns of stimulation targeting currently-used DBS target for TRD. We generated mean and binary fiber distribution maps and calculated the numbers of WMT streamlines in the dataset. RESULTS: Probabilistic tracking results revealed that activation of distinct DBS targets demonstrated modulation of overlapping but considerably distinct pathways. DBS targets were categorized into 4 groups: Cortical, Striatal, Thalamic, and Medial Forebrain Bundle according to their main modulated WMT and brain areas. Our data also revealed that Brodmann area 10 and amygdala are hub structures that are associated with all DBS targets. CONCLUSIONS: Our results together suggest that the distinct mechanism of DBS targets implies individualized target selection and formulation in the future of DBS treatment for TRD. The modulation of Brodmann area 10 and amygdala may be critical for the efficacy of DBS-mediated treatment of TRD.

Tenofovir Disoproxil Fumarate Is Superior to Entecavir in Reducing Hepatitis B Surface Antigen for Chronic Hepatitis B in China: 2-Year Comprehensive Comparative Result of a Matched Comparative Study.

Aim: Tenofovir disoproxil fumarate (TDF) and entecavir (ETV) are equally recommended as the first-line antiviral treatments for chronic hepatitis B (CHB) at present. We aimed to compare the long-term efficacy and safety between ETV and TDF therapy in CHB patients who had not received nucleoside analog treatment. Method: In this single-center retrospective study, 414 patients who received ETV (290 patients) or TDF (124 patients) therapy at our center from January 2017 to May 2019 were included. To reduce the imbalance of baseline variables, propensity score matching (PSM) was employed to yield 124 pairs of patients at a ratio of 1:1 based on the treatment regimen. Result: After PSM, the cumulative rate of patients who achieved complete virological response (CVR) was not different by drug therapy at each inspection time (1, 3, 6, 12, 18, and 24 months). Subgroup analysis on HBeAg status and level of HBV DNA demonstrated that evolution of proportion of achieving CVR was not significantly different between groups. Despite the insignificant incidence of HBsAg seroclearance in either group, patients in TDF group achieved higher on-treatment HBsAg decline at each inspection time (1, 3, 6, 9, 12, 18, and 24 months), 0.39, 0.51, 0.61, 0.64, 0.68, 0.76, and 0.91 log IU/mL, respectively; while the corresponding reduction were 0.27, 0.37, 0.40, 0.45, 0.48, 0.55, and 0.66 log IU/mL in ETV group (p < 0.05). In subgroup analysis, we found that the significant difference still existed in patients with high baseline HBsAg level (>3 log IU/mL). Additionally, the proportion of patients who achieved on-treatment HBsAg decline >1 log IU/mL in TDF and ETV group was 33.3 and 17.1% (p < 0.01) at the 12th month, 44.4 and 29.5% (p = 0.03) at the 24th month, respectively. Mean increase in serum creatinine from baseline was 0.10 and 0.08 mg/dL in TDF and ETV group (p = 0.11), with no patient experienced acute kidney injury. Conclusions: TDF has higher potency in reducing HBsAg than ETV in this study. Considering the effect still existed in patients with high HBsAg level (>3 log IU/mL), TDF might be a superior therapeutic regimen combining with its relatively safety.

Oncogenic State and Cell Identity Combinatorially Dictate the Susceptibility of Cells within Glioma Development Hierarchy to IGF1R Targeting.

Glioblastoma is the most malignant cancer in the brain and currently incurable. It is urgent to identify effective targets for this lethal disease. Inhibition of such targets should suppress the growth of cancer cells and, ideally also precancerous cells for early prevention, but minimally affect their normal counterparts. Using genetic mouse models with neural stem cells (NSCs) or oligodendrocyte precursor cells (OPCs) as the cells-of-origin/mutation, it is shown that the susceptibility of cells within the development hierarchy of glioma to the knockout of insulin-like growth factor I receptor (IGF1R) is determined not only by their oncogenic states, but also by their cell identities/states. Knockout of IGF1R selectively disrupts the growth of mutant and transformed, but not normal OPCs, or NSCs. The desirable outcome of IGF1R knockout on cell growth requires the mutant cells to commit to the OPC identity regardless of its development hierarchical status. At the molecular level, oncogenic mutations reprogram the cellular network of OPCs and force them to depend more on IGF1R for their growth. A new-generation brain-penetrable, orally available IGF1R inhibitor harnessing tumor OPCs in the brain is also developed. The findings reveal the cellular window of IGF1R targeting and establish IGF1R as an effective target for the prevention and treatment of glioblastoma.

Efficacy and cost-effectiveness of antiviral regimens for entecavir-resistant hepatitis B: A systematic review and network meta-analysis.

BACKGROUND: Chronic hepatitis B (CHB) patients who had exposed to lamivudine (LAM) and telbivudine (LdT) had high risk of developing entecavir (ETV)-resistance after long-term treatment. We aimed to conduct a systematic review and a network meta-analysis on the efficacy and cost-effectiveness on antiviral regimens in CHB patients with ETV-resistance. DATA SOURCES: We searched PubMed, EMBASE and Web of Science for studies on nucleos(t)ide analogues (NAs) treatment [including tenofovir disoproxil fumarate (TDF)-based rescue therapies, adefovir (ADV)-based rescue therapies and double-dose ETV therapy] in CHB patients with ETV-resistance. The network meta-analysis was conducted for 1-year complete virological response (CVR) and biological response (BR) rates using GeMTC and ADDIS. A cost-effective analysis was conducted to select an economic and effective treatment regimen based on the 1-year CVR rate. RESULTS: A total of 6 studies were finally included in this analysis. The antiviral efficacy was estimated. On network meta-analysis, the 1-year CVR rate in ETV-TDF [odds ratio (OR)  = 22.30; 95 % confidence interval (CI): 2.78-241.93], LAM-TDF (OR  = 70.67; 95 % CI: 5.16-1307.45) and TDF (OR  = 16.90; 95 % CI: 2.28-186.30) groups were significantly higher than that in the ETV double-dose group; the 1-year CVR rate in the LAM-TDF group (OR  = 14.82; 95 % CI: 1.03-220.31) was significantly higher than that in the LAM/LdT-ADV group. The 1-year BR rate of ETV-TDF (OR = 28.68; 95 % CI: 1.70-1505.08) and TDF (OR = 21.79; 95 % CI: 1.43-1070.09) therapies were significantly higher than that of ETV double-dose therapy. TDF-based therapies had the highest possibility to achieve the CVR and BR at 1 year, in which LAM-TDF combined therapy was the most effective regimen. The ratio of cost/effectiveness for 1-year treatment was 8 526, 17 649, 20 651 Yuan in the TDF group, TDF-ETV group, and ETV-ADV group, respectively. CONCLUSIONS: TDF-based combined therapies such as ETV-TDF and LAM-TDF therapies were the first-line treatment if financial condition is allowed.

Sylvian Fissure Meningiomas: Case Report and Literature Review.

Meningiomas are primary intracranial tumors derived from arachnoid cap cells or meningothelial cells and usually display dural attachment. However, a small proportion of meningiomas that arise from the Sylvian fissure do not manifest dural attachment. Sylvian fissure meningiomas are relatively rare and have differential characteristics as compared with typical meningiomas. Herein, we reported a special case of atypical meningioma in the Sylvian fissure, that showed non-enhancement after contract management. The patient was a 30-year-old woman with a 2-year history of seizures. Preoperative computerized tomography and magnetic resonance imaging scans showed a calcific, non-enhancing lesion in the right insula lobe. The lesion was excised surgically for seizure control. Intraoperatively, the tumor was observed to be closely adhered to the middle cerebral artery (MCA), resulting in mild arterial damage. A case of Sylvian fissure meningioma was ultimately diagnosed by histopathological examination of the resected specimens. Sylvian fissure meningiomas are closely associated with the MCA and exhibit unusual imaging characteristics. Preoperative misdiagnosis may have serious adverse consequences and may result in incorrect surgery. To improve awareness of Sylvian fissure meningiomas on the differential diagnosis of Sylvian fissure lesions among clinicians, we present this report and briefly summarize previously reported cases to describe the clinical, pathological, radiological, and surgical features.