Dementia Assessment Using Mandarin Speech with an Attention-based Speech Recognition Encoder

Dementia diagnosis requires a series of different testing methods, which is complex and time-consuming. Early detection of dementia is crucial as it can prevent further deterioration of the condition. This paper utilizes a speech recognition model to construct a dementia assessment system tailored for Mandarin speakers during the picture description task. By training an attention-based speech recognition model on voice data closely resembling real-world scenarios, we have significantly enhanced the model's recognition capabilities. Subsequently, we extracted the encoder from the speech recognition model and added a linear layer for dementia assessment. We collected Mandarin speech data from 99 subjects and acquired their clinical assessments from a local hospital. We achieved an accuracy of 92.04% in Alzheimer's disease detection and a mean absolute error of 9% in clinical dementia rating score prediction.Comment: submitted to IEEE ICASSP 202

Evidence of d-phenylglycine as delivering tool for improving l-dopa absorption

<p>Abstract</p> <p>Background</p> <p><it>l</it>-Dopa has been used for Parkinson's disease management for a long time. However, its wide variety in the rate and the extent of absorption remained challenge in designing suitable therapeutic regime. We report here a design of using <it>d</it>-phenylglycine to guard <it>l</it>-dopa for better absorption in the intestine via intestinal peptide transporter I (PepT1).</p> <p>Methods</p> <p><it>d</it>-Phenylglycine was chemically attached on <it>l</it>-dopa to form <it>d</it>-phenylglycine-<it>l</it>-dopa as a dipeptide prodrug of <it>l</it>-dopa. The cross-membrane transport of this dipeptide and <it>l</it>-dopa via PepT1 was compared in brush-boarder membrane vesicle (BBMV) prepared from rat intestine. The intestinal absorption was compared by <it>in situ </it>jejunal perfusion in rats. The pharmacokinetics after i.v. and p.o. administration of both compounds were also compared in Wistar rats. The striatal dopamine released after i.v. administration of <it>d</it>-phenylglycine-<it>l</it>-dopa was collected by brain microdialysis and monitored by HPLC. Anti-Parkinsonism effect was determined by counting the rotation of 6-OHDA-treated unilateral striatal lesioned rats elicited rotation with (+)-methamphetamine (MA).</p> <p>Results</p> <p>The BBMV uptake of <it>d</it>-phenylglycine-<it>l</it>-dopa was inhibited by Gly-Pro, Gly-Phe and cephradine, the typical PepT1 substrates, but not by amino acids Phe or <it>l</it>-dopa. The cross-membrane permeability (Pm*) determined in rat jejunal perfusion of <it>d</it>-phenylglycine-<it>l</it>-dopa was higher than that of <it>l</it>-dopa (2.58 ± 0.14 vs. 0.94 ± 0.10). The oral bioavailability of <it>d</it>-phenylglycine-<it>l</it>-dopa was 31.7 times higher than that of <it>l-</it>dopa in rats. A sustained releasing profile of striatal dopamine was demonstrated after i. v. injection of <it>d</it>-phenylglycine-<it>l</it>-dopa (50 mg/kg), indicated that <it>d</it>-phenylglycine-<it>l</it>-dopa might be a prodrug of dopamine. <it>d</it>-Phenylglycine-<it>l</it>-dopa was more efficient than <it>l-</it>dopa in lowering the rotation of unilateral striatal lesioned rats (19.1 ± 1.7% vs. 9.9 ± 1.4%).</p> <p>Conclusion</p> <p>The BBMV uptake studies indicated that <it>d</it>-phenylglycine facilitated the transport of <it>l</it>-dopa through the intestinal PepT1 transporter. The higher jejunal permeability and the improved systemic bioavailability of <it>d-</it>phenylglycine-<it>l</it>-dopa in comparison to that of <it>l</it>-dopa suggested that <it>d-</it>phenylglycine is an effective delivery tool for improving the oral absorption of drugs like <it>l</it>-dopa with unsatisfactory pharmacokinetics. The gradual release of dopamine in brain striatum rendered this dipeptide as a potential dopamine sustained-releasing prodrug.</p

HBV replication is significantly reduced by IL-6

Interleukin-6 (IL-6) is a pleiotropic cytokine with pivotal functions in the regulation of the biological responses of several target cells including hepatocytes. The level of serum IL-6 has been reported to be elevated in patients with chronic hepatitis B, cirrhosis and hepatocellular carcinoma and represents the best marker of HBV-related clinical progression as compared with several other cytokines. In this study, we found that IL-6 was able to effectively suppress hepatitis B virus (HBV) replication and prevent the accumulation of HBV covalently closed circular DNA (cccDNA) in a human hepatoma cell line. We also demonstrated that the suppression of HBV replication by IL-6 requires concurrently a moderate reduction of viral transcripts/core proteins and a marked decrease in viral genome-containing nucleocapsids. Studies on the stability of existing viral capsids suggest that the IL-6 effect on the reduction of genome-containing nucleocapsids is mediated through the prevention of the formation of genome-containing nucleocapsids, which is similar to the effect of interferons. However, IFN-α/β and IFN-γ did not participate in the IL-6-induced suppression of HBV replication. Taken together, our results will provide important information to better understand the role of IL-6 in the course of HBV infection

Dynamics of HBV cccDNA expression and transcription in different cell growth phase

<p>Abstract</p> <p>Background</p> <p>The covalently closed-circular DNA (cccDNA) of hepatitis B virus (HBV) is associated with viral persistence in HBV-infected hepatocytes. However, the regulation of cccDNA and its transcription in the host cells at different growth stages is not well understood.</p> <p>Methods</p> <p>We took advantages of a stably HBV-producing cell line, 1.3ES2, and examine the dynamic changes of HBV cccDNA, viral transcripts, and viral replication intermediates in different cellular growth stages.</p> <p>Results</p> <p>In this study, we showed that cccDNA increased suddenly in the initial proliferation phase of cell growth, probably attributable to its nuclear replenishment by intracellular nucleocapsids. The amount of cccDNA then decreased dramatically in the cells during their exponential proliferation similar to the loss of extrachromosomal plasmid DNA during cell division, after which it accumulated gradually while the host cells grew to confluency. We found that cccDNA was reduced in dividing cells and could be removed when proliferating cells were subjected to long term of lamivudine (3TC) treatment. The amounts of viral replicative intermediates were rapidly reduced in these proliferating cells and were significantly increased after cells reaching confluency. The expression levels of viral transcripts were increased in parallel with the elevated expression of hepatic transcription factors (HNF4α, CEBPα, PPARα, etc.) during cell growth confluency. The HBV transcripts were transcribed from both integrated viral genome and cccDNA, however the transcriptional abilities of cccDNA was less efficient then that from integrated viral genome in all cell growth stages. We also noted increases in the accumulation of intracellular viral particles and the secretion of mature virions as the cells reached confluency and ceased to grow.</p> <p>Conclusions</p> <p>Based on the dynamics of HBV replication, we propose that HBV replication is modulated differently in the different stages of cell growth, and can be divided into three phases (initial proliferation phase, exponential proliferation phase and growth confluency phase) according to the cell growth curve. The regulation of cccDNA in different cell growth phase and its importance regarding HBV replication are discussed.</p

Moderate Ethanol Pre-treatment Mitigates ICH-Induced Injury via ER Stress Modulation in Rats

Intracerebral hemorrhage (ICH) is a life-threatening type of stroke that disrupts the normal neurological function of the brain. Clinical studies have reported a non-linear J-shaped association between alcohol consumption levels and the occurrence of cerebral stroke. Specifically, alcohol intoxication increases stroke incidence, while moderate alcohol pre-conditioning decreases stroke frequency and improves outcomes. Although alcohol pre-consumption is likely a crucial player in ICH, the underlying mechanism remains unclear. We performed 1-h alcohol pre-conditioning followed by ICH induction in Sprague-Dawley (SD) rats to investigate the role of alcohol pre-conditioning in ICH. Interestingly, behavioral test analysis found that ethanol intoxication (3 g/kg) aggravated ICH-induced neurological deficits, but moderate ethanol pre-conditioning (0.75 g/kg) ameliorated ICH-induced neurological deficits by reducing the oxidative stress and proinflammatory cytokines release. Moreover, we found that moderate ethanol pretreatment improved the striatal endoplasmic reticulum (ER) homeostasis by increasing the chaperone protein expression and reducing oxidative stress and apoptosis caused by ICH. Our findings show that the mechanism regulated by moderate ethanol pre-conditioning might be beneficial for ICH, indicating the importance of ER homeostasis, oxidative stress, and differential cytokines release in ICH

Life expectancies and incidence rates of patients under prolonged mechanical ventilation: a population-based study during 1998 to 2007 in Taiwan

[[abstract]]Introduction: The present study examined the median survival, life expectancies, and cumulative incidence rate (CIR) of patients undergoing prolonged mechanical ventilation (PMV) stratified by different underlying diseases.Methods: According to the National Health Insurance Research Database of Taiwan, there were 8,906,406 individuals who obtained respiratory care during the period from 1997 to 2007. A random sample of this population was performed, and subjects who had continuously undergone mechanical ventilation for longer than 21 days were enrolled in the current study. Annual incidence rates and the CIR were calculated. After stratifying the patients according to their specific diagnoses, latent class analysis was performed to categorise PMV patients with multiple co-morbidities into several groups. The life expectancies of different groups were estimated using a semiparametric method with a hazard function based on the vital statistics of Taiwan.Results: The analysis of 50,481 PMV patients revealed that incidence rates increased as patients grew older and that the CIR (17 to 85 years old) increased from 0.103 in 1998 to 0.183 in 2004 before stabilising thereafter. The life expectancies of PMV patients suffering from degenerative neurological diseases, stroke, or injuries tended to be longer than those with chronic renal failure or cancer. Patients with chronic obstructive pulmonary disease survived longer than did those co-morbid with other underlying diseases, especially septicaemia/shock.Conclusions: PMV provides a direct means to treat respiratory tract diseases and to sustain respiration in individuals suffering from degenerative neurological diseases, and individuals with either of these types of conditions respond better to PMV than do those with other co-morbidities. Future research is required to determine the cost-effectiveness of this treatment paradigm

A Macroporous TiO2 Oxygen Sensor Fabricated Using Anodic Aluminium Oxide as an Etching Mask

An innovative fabrication method to produce a macroporous Si surface by employing an anodic aluminium oxide (AAO) nanopore array layer as an etching template is presented. Combining AAO with a reactive ion etching (RIE) processes, a homogeneous and macroporous silicon surface can be effectively configured by modulating AAO process parameters and alumina film thickness, thus hopefully replacing conventional photolithography and electrochemical etch methods. The hybrid process integration is considered fully CMOS compatible thanks to the low-temperature AAO and CMOS processes. The gas-sensing characteristics of 50 nm TiO2 nanofilms deposited on the macroporous surface are compared with those of conventional plain (or non-porous) nanofilms to verify reduced response noise and improved sensitivity as a result of their macroporosity. Our experimental results reveal that macroporous geometry of the TiO2 chemoresistive gas sensor demonstrates 2-fold higher (∼33%) improved sensitivity than a non-porous sensor at different levels of oxygen exposure. In addition, the macroporous device exhibits excellent discrimination capability and significantly lessened response noise at 500 °C. Experimental results indicate that the hybrid process of such miniature and macroporous devices are compatible as well as applicable to integrated next generation bio-chemical sensors

Surface passivation effect by fluorine plasma treatment on ZnO for efficiency and lifetime improvement of inverted polymer solar cells

Zinc oxide (ZnO) is an important material for polymer solar cells (PSCs) where the characteristics of the interface can dominate both the efficiency and lifetime of the device. In this work we study the effect of fluorine (SF6) plasma surface treatment of ZnO films on the performance of PSCs with an inverted structure. The interaction between fluorine species present in the SF6 plasma and the ZnO surface is also investigated in detail. We provide fundamental insights into the passivation effect of fluorine by analyzing our experimental results and theoretical calculations and we propose a mechanism according to which a fluorine atom substitutes an oxygen atom or occupies an oxygen vacancy site eliminating an electron trap while it may also attract hydrogen atoms thus favoring hydrogen doping. These multiple fluorine roles can reduce both the recombination losses and the electron extraction barrier at the ZnO/fullerene interface improving the selectivity of the cathode contact. Therefore, the fabricated devices using the fluorine plasma treated ZnO show high efficiency and stable characteristics, irrespective of the donor : acceptor combinations in the photoactive blend. Inverted polymer solar cells, consisting of the P3HT:PC71BM blend, exhibited increased lifetime and high power conversion efficiency (PCE) of 4.6%, while the ones with the PCDTBT:PC71BM blend exhibited a PCE of 6.9%. Our champion devices with the PTB7:PC71BM blends reached a high PCE of 8.0% and simultaneously showed exceptional environmental stability when using the fluorine passivated ZnO cathode interlayers

Significance of Aurora B overexpression in hepatocellular carcinoma. Aurora B Overexpression in HCC

<p>Abstract</p> <p>Background</p> <p>To investigate the significance of Aurora B expression in hepatocellular carcinoma (HCC).</p> <p>Methods</p> <p>The <it>Aurora B </it>and <it>Aurora A </it>mRNA level was measured in 160 HCCs and the paired nontumorous liver tissues by reverse transcription-polymerase chain reaction. Mutations of the <it>p53 </it>and <it>β-catenin </it>genes were analyzed in 134 and 150 tumors, respectively, by direct sequencing of exon 2 to exon 11 of <it>p53 </it>and exon 3 of <it>β-catenin</it>. Anticancer effects of AZD1152-HQPA, an Aurora B kinase selective inhibitor, were examined in Huh-7 and Hep3B cell lines.</p> <p>Results</p> <p><it>Aurora B </it>was overexpressed in 98 (61%) of 160 HCCs and in all 7 HCC cell lines examined. The overexpression of <it>Aurora B </it>was associated with <it>Aurora A </it>overexpression (<it>P </it>= 0.0003) and <it>p53 </it>mutation (<it>P </it>= 0.002) and was inversely associated with <it>β</it>-<it>catenin </it>mutation (<it>P </it>= 0.002). <it>Aurora B </it>overexpression correlated with worse clinicopathologic characteristics. Multivariate analysis confirmed that <it>Aurora B </it>overexpression was an independent poor prognostic factor, despite its interaction with Aurora A overexpression and mutations of <it>p53 </it>and <it>β</it>-<it>catenin</it>. In Huh-7 and Hep3B cells, AZD1152-HQPA induced proliferation blockade, histone H3 (Ser10) dephosphorylation, cell cycle disturbance, and apoptosis.</p> <p>Conclusion</p> <p><it>Aurora B </it>overexpression is an independent molecular marker predicting tumor invasiveness and poor prognosis of HCC. Aurora B kinase selective inhibitors are potential therapeutic agents for HCC treatment.</p

Evaluation of Aerosol Delivery of Nanosuspension for Pre-clinical Pulmonary Drug Delivery

Asthma and chronic obstructive pulmonary disease (COPD) are pulmonary diseases that are characterized by inflammatory cell infiltration, cytokine production, and airway hyper-reactivity. Most of the effector cells responsible for these pathologies reside in the lungs. One of the most direct ways to deliver drugs to the target cells is via the trachea. In a pre-clinical setting, this can be achieved via intratracheal (IT), intranasal (IN), or aerosol delivery in the desired animal model. In this study, we pioneered the aerosol delivery of a nanosuspension formulation in a rodent model. The efficiency of different dosing techniques and formulations to target the lungs were compared, and fluticasone was used as the model compound. For the aerosol particle size determination, a ten-stage cascade impactor was used. The mass median aerodynamic diameter (MMAD) was calculated based on the percent cumulative accumulation at each stage. Formulations with different particle size of fluticasone were made for evaluation. The compatibility of regular fluticasone suspension and nanosuspension for aerosol delivery was also investigated. The in vivo studies were conducted on mice with optimized setting. It was found that the aerosol delivery of fluticasone with nanosuspension was as efficient as intranasal (IN) dosing, and was able to achieve dose dependent lung deposition