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

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology

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

Search for direct pair production of the top squark in all-hadronic final states in proton-proton collisions at s√=8 TeV with the ATLAS detector

The results of a search for direct pair production of the scalar partner to the top quark using an integrated luminosity of 20.1fb−1 of proton–proton collision data at √s = 8 TeV recorded with the ATLAS detector at the LHC are reported. The top squark is assumed to decay via t˜→tχ˜01 or t˜→ bχ˜±1 →bW(∗)χ˜01 , where χ˜01 (χ˜±1 ) denotes the lightest neutralino (chargino) in supersymmetric models. The search targets a fully-hadronic final state in events with four or more jets and large missing transverse momentum. No significant excess over the Standard Model background prediction is observed, and exclusion limits are reported in terms of the top squark and neutralino masses and as a function of the branching fraction of t˜ → tχ˜01 . For a branching fraction of 100%, top squark masses in the range 270–645 GeV are excluded for χ˜01 masses below 30 GeV. For a branching fraction of 50% to either t˜ → tχ˜01 or t˜ → bχ˜±1 , and assuming the χ˜±1 mass to be twice the χ˜01 mass, top squark masses in the range 250–550 GeV are excluded for χ˜01 masses below 60 GeV

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT

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

Search for R-parity-violating supersymmetry in events with four or more leptons in sqrt(s) =7 TeV pp collisions with the ATLAS detector

A search for new phenomena in final states with four or more leptons (electrons or muons) is presented. The analysis is based on 4.7 fb−1 of $\sqrt{s}=7\;\mathrm{TeV}$ proton-proton collisions delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in two signal regions: one that requires moderate values of missing transverse momentum and another that requires large effective mass. The results are interpreted in a simplified model of R-parity-violating supersymmetry in which a 95% CL exclusion region is set for charged wino masses up to 540 GeV. In an R-parity-violating MSUGRA/CMSSM model, values of m 1/2 up to 820 GeV are excluded for 10 < tan β < 40

Self-Limited Pneumoporta in the Era of Computed Tomography: A Case Report and Review of the Literature

Pneumoporta in patients with abdominal pain has been thought to be suggestive of fatal underlying conditions, such as mesenteric infarct, requiring emergency treatment. Widespread use of computed tomography (CT) has increased the frequency of detection of pneumoporta in patients with diseases other than mesenteric infarct. The natural course of resolution of pneumoporta has been rarely discussed in the literature and mainly focused on patients with iatrogenic diseases. Herein, we report the case of a 64-year-old woman who presented at our emergency department with positive peritoneal signs and pneumoporta. A 10 cm long segment of resolved ischemic bowel was detected on exploratory laparotomy, and bowel resection was not performed. Follow-up CT performed 62 hours later revealed complete resolution of pneumoporta. The patient was discharged uneventfully and was administered short-term prophylactic therapy with enoxaparin for thromboembolism. The epidemiology, etiology, and resolution of pneumoporta are also reviewed.</jats:p