Miracle-dz/UniFAR-FTUs huggingface dataset:
Utilisation willingness for institutional care by the elderly: a comparative study of empty nesters and non-empty nesters in Shandong, China

Introduction Institutional care has been strongly promoted in China to meet seniors’ long-term care needs. Empty-nest elderly, in comparison with their counterparts, have less social support and fewer caring networks. This study aimed to compare the utilisation willingness for institutional care and its predictors between empty-nest and non-empty-nest seniors. Methods A total of 3923 seniors were included in the analysis. Binary logistic regression models were used to understand the association between the living arrangements of the elderly households and willingness for institutional care and to identify the predictors of the utilisation willingness for institutional care among empty nesters and non-empty nesters. Results Our study found that approximately 8.5% of the seniors had a willingness for institutional care in Shandong, China. Empty-nest singles (OR 5.301; 95% CI 2.838 to 9.904) and empty-nest couples (OR 1.547; 95% CI 1.135 to 2.107) were found to be more willing to receive institutional care. Our results also showed that residence was a key determinant for institutionalisation willingness in empty-nest and non-empty-nest elderly. Among empty-nest singles, psychological stress was a positive determinant for institutional care. Factors, including education attainment, relationship with adult children, household income and per capita living space, were determinants for empty-nest couple willingness for institutionalisation. Age, number of children and self-reported health status were found to be associated factors for willingness among non-empty nesters. Conclusions The government should pay more attention to institutional care in rural areas where there is still a gap in elder care compared with that in urban areas. Targeted policies should be made for different types of seniors to offer appropriate institutional care.
Recent progress on biocompatible nanocarrier-based genistein delivery systems in cancer therapy

Abstract Diets with naturally occuring chemopreventive agents are showing good potentials in serving dual purposes: firstly, for maintaining health, and secondly, for emerging as most puissant cost-effective strategy against chronic diseases like cancer. Genistein, one of the active soy isoflavone, is gaining attention due to its ability to impede carcinogenic processes by regulating wide range of associated molecules and signalling mechanisms. Epidemiologic and preclinical evidences suggest that sufficient consumption of soy-based food having genistein can be correlated to the reduction of cancer risk. However, certain adverse effects like poor oral bioavailability, low aqueous solubility and inefficient pharmacokinetics have pushed it down in the list of phytoconstituents currently undergoing successful clinical trials. In order to maximise the utilisation of therapeutic benefits of this phytoestrogen, suitable drug carrier designs are required. Recently, nanocarriers, mainly composed of polymeric materials, are progressively and innovatively exploited with the aim to improve pharmacokinetics and pharmacodynamics of genistein. Here, we have briefly reviewed (a) the targeted molecular mechanisms of geinstein, (b) nanopolymeric approaches opted so far in designing carriers and (c) the reasons behind their restricted clinical applications. Finally, some mechanism-based approaches are proposed presenting genistein as the future paradigm in cancer therapy.
Predictors of Daily Adherence to Naltrexone for Alcohol Use Disorder Treatment During a Mobile Health Intervention.

Background Adherence to medications for treating alcohol use disorder (AUD) is poor. To identify predictors of daily naltrexone adherence over time, a secondary data analysis was conducted of a trial evaluating a mobile health intervention to improve adherence. Methods Participants seeking treatment for AUD (n = 58; Mage = 38 years; 71% male) were prescribed naltrexone for 8 weeks. Adherence was tracked using the Medication Event Monitoring System (MEMS). In response to daily text messages, participants reported the previous day's alcohol use, craving, and naltrexone side effects. Using multilevel structural equation modeling (MSEM), we examined baseline dispositional factors and within-person, time-varying factors as predictors of daily adherence. Results Naltrexone adherence decreased over time. Adherence was higher on days when individuals completed daily mobile assessments relative to days when they did not (odds ratio [OR] = 2.53, 95% confidence interval [CI] 1.61 to 3.98), irrespective of intervention condition. Days when individuals drank more than their typical amount were related to lower next-day adherence (OR = 0.93, 95% CI 0.88 to 0.99). A similar pattern was supported for craving (OR = 0.88, 95% CI 0.79 to 0.98). Weekend days were associated with lower adherence than weekdays (OR = 0.71, 95% CI 0.58 to 0.86); this effect was partly mediated by heavier daily drinking (indirect effect = -0.02, 95% CI -0.04 to -0.003) and stronger-than-usual craving (indirect effect = -0.01, 95% CI -0.02 to 0.00) on weekend days. Conclusions The results further demonstrate the need to improve adherence to AUD pharmacotherapy. The present findings also support developing interventions that target daily-level risk factors for nonadherence. Mobile health interventions may be one means of developing tailored and adaptive adherence interventions.
Trajectory assessment is useful when day-to-day esophageal acid exposure varies in prolonged wireless pH monitoring.

Acid exposure time commonly varies from day-to-day in prolonged wireless pH monitoring. Thus, diagnosis based on the number of days with abnormal acid burden may be misleading or inconclusive. We hypothesize that assessing longitudinal patterns of acid exposure may be diagnostically useful. Therefore, this study aims to describe acid exposure trajectories and evaluate agreement between identified trajectory patterns and conventional grouping. In this retrospective cohort study, we assessed patients with nonresponse to proton pump inhibitor therapy who underwent wireless pH monitoring (≥72 h) off therapy between August 2010 and September 2016. The primary outcome was esophageal acid exposure time. Subjects were grouped as 0, 1, 2, and 3+ days positive based on number of days with an acid exposure time >5.0%. Latent class group-based mixture model identified distinct longitudinal acid exposure trajectory groups. Of 212 subjects included 44%, 18%, 14%, and 24% had 0, 1, 2, 3+ days positive, respectively. Group-based modeling identified three significantly stable acid exposure trajectories: low (64%), middle (28%), and high (8%). Trajectory grouping and days positive grouping agreed substantially (weighted K 0.69; 95% CI: 0.63-0.76). Trajectory grouping identified 62% of subjects with conventionally inconclusive studies (one or two days positive) into the low trajectory. Agreement between trajectory groups when using three versus four days of monitoring was substantial (K 0.70; CI: 0.61-0.78). In summary, we found that patients with nonresponse to proton pump inhibitors follow three acid exposure trajectories over prolonged pH-monitoring periods: low, middle, and high. Compared to conventional day positive grouping, the trajectory modeling identified the majority of inconclusive days positive into the low trajectory group. Analyzing prolonged wireless pH data according to trajectories may be a complimentary method to conventional grouping, and may increase precision and accuracy in identifying acid burden.
Efficacy and safety of oral targeted therapies in pulmonary arterial hypertension: a meta-analysis of randomized clinical trials

Oral targeted therapies play an important role in the treatment of pulmonary arterial hypertension (PAH). Several new oral agents have emerged for PAH in recent years. However, whether they provide a survival advantage is still not clear. This meta-analysis aimed to assess the efficacy and safety of oral targeted therapies, especially on predefined clinical worsening events. Trials were searched in the Cochrane Library, EMBASE, and PUBMED databases through June 2018. We calculated risk ratios for dichotomous data and weighted mean differences with 95% confidence intervals (CI) for continuous data. Twenty-five trials with a total of 6847 participants were included in the meta-analysis. Oral targeted therapies were associated with significant risk reduction in clinical worsening compared with placebo (relative risk [RR] 0.64; 95% CI = 0.58–0.70; P < 0.001). This reduction in risk was driven by reduction in non-fatal endpoints, including PAH-related admissions to hospital (RR = 0.66; 95% CI = 0.56–0.76; P < 0.001), treatment escalation (RR = 0.43; 95% CI = 0.28–0.66; P < 0.001), and symptomatic progression (RR = 0.55; 95% CI = 0.48–0.64; P < 0.001), but not by reduction of mortality (RR = 0.87; 95% CI = 0.68–1.12; P = 0.215). Oral targeted therapies were also associated with improvement in 6-min walk distance (26.62 m; 95% CI = 20.54–32.71; P < 0.001) and World Health Organization functional class (RR = 1.36; 95% CI = 1.20–1.54; P < 0.001). The results of this meta-analysis showed the benefits of oral treatments on clinical worsening events in PAH. However, these oral agents did not show any survival benefit in the short-term follow-up.
Molecular dynamics simulation of biased agonists at the dopamine D2 receptor suggests the mechanism of receptor functional selectivity

Abstract The dopamine D2 receptor (D2R) is the primary target for antipsychotic drugs. Besides schizophrenia, this receptor is linked to dementia, Parkinson’s disease, and depression. Recent studies have shown that β-arrestin biased agonists at this receptor treat schizophrenia with less side effects. Although the high resolution structure of this receptor exists, the mechanism of biased agonism at the receptor is unknown. In this study, dopamine, the endogenous unbiased G-protein agonist, MLS1547, a G-protein biased agonist, and UNC9975, a G-protein antagonist and a β-arrestin biased agonist, were docked to a homology model of the whole D2R including all flexible loops, and molecular dynamics simulations were conducted to study the potential mechanisms of biased agonism. Our thorough analysis on the protein–ligand interaction, secondary structure, tertiary structure, structure dynamics, and molecular switches of all three systems indicates that ligand binding to transmembrane 3 might be essential for G-protein recruitment, while ligand binding to transmembrane 6 might be essential for β-arrestin recruitment. Our analysis also suggests changes in both the secondary and the tertiary structures of TM5 and TM7, molecular switches and ICL3 flexibility are important in biased signaling. Communicated by Ramaswamy H. Sarma
Short-term survival rates of branded Steller sea lion pups

Survival rates of western Steller sea lion (Eumetopias jubatus) pups (total N = 621) were estimated during 2000, 2002, and 2004 at one rookery on Marmot Island and during 2003 and 2005 at two rookeries on Ugamak Island for up to 73 days following hot-iron branding. Estimated daily apparent survival rates increased and standard errors of the estimates decreased with increasing durations of in-season monitoring. An asymptotic apparent survival rate (φa) of 0.9995 d-1 was estimated from sightings of marked pups on 7-30 occasions between 1 and 73 days after branding, as well as in subsequent years through 2015. Sex and pup mass at the time of branding were not strong factors affecting survival. Extrapolations of φ beyond the in-season period yielded 12-week and 1-year survival rates of 0.960 and 0.837, respectively. During six of the seven in-season monitoring periods, numbers of dead pups counted by observers following branding were less than those estimated to have died based on our calculated survival rate. Two more dead pups were counted than predicted at Marmot in 2000, but the actual cause(s) of any of the pup deaths are not known.
Adversarial Attacks Against Automatic Speech Recognition Systems via Psychoacoustic Hiding

Voice interfaces are becoming accepted widely as input methods for a diverse set of devices. This development is driven by rapid improvements in automatic speech recognition (ASR), which now performs on par with human listening in many tasks. These improvements base on an ongoing evolution of DNNs as the computational core of ASR. However, recent research results show that DNNs are vulnerable to adversarial perturbations, which allow attackers to force the transcription into a malicious output. In this paper, we introduce a new type of adversarial examples based on psychoacoustic hiding. Our attack exploits the characteristics of DNN-based ASR systems, where we extend the original analysis procedure by an additional backpropagation step. We use this backpropagation to learn the degrees of freedom for the adversarial perturbation of the input signal, i.e., we apply a psychoacoustic model and manipulate the acoustic signal below the thresholds of human perception. To further minimize the perceptibility of the perturbations, we use forced alignment to find the best fitting temporal alignment between the original audio sample and the malicious target transcription. These extensions allow us to embed an arbitrary audio input with a malicious voice command that is then transcribed by the ASR system, with the audio signal remaining barely distinguishable from the original signal. In an experimental evaluation, we attack the state-of-the-art speech recognition system Kaldi and determine the best performing parameter and analysis setup for different types of input. Our results show that we are successful in up to 98% of cases with a computational effort of fewer than two minutes for a ten-second audio file. Based on user studies, we found that none of our target transcriptions were audible to human listeners, who still understand the original speech content with unchanged accuracy.
On the Convergence of Adaptive Gradient Methods for Nonconvex Optimization

Adaptive gradient methods are workhorses in deep learning. However, the convergence guarantees of adaptive gradient methods for nonconvex optimization have not been sufficiently studied. In this paper, we provide a sharp analysis of a recently proposed adaptive gradient method namely partially adaptive momentum estimation method (Padam) (Chen and Gu, 2018), which admits many existing adaptive gradient methods such as RMSProp and AMSGrad as special cases. Our analysis shows that, for smooth nonconvex functions, Padam converges to a first-order stationary point at the rate of $O\big((\sum_{i=1}^d\|\mathbf{g}_{1:T,i}\|_2)^{1/2}/T^{3/4} + d/T\big)$, where $T$ is the number of iterations, $d$ is the dimension, $\mathbf{g}_1,\ldots,\mathbf{g}_T$ are the stochastic gradients, and $\mathbf{g}_{1:T,i} = [g_{1,i},g_{2,i},\ldots,g_{T,i}]^\top$. Our theoretical result also suggests that in order to achieve faster convergence rate, it is necessary to use Padam instead of AMSGrad. This is well-aligned with the empirical results of deep learning reported in Chen and Gu (2018).
Impact of adverse media reporting on public perceptions of the doctor–patient relationship in China: an analysis with propensity score matching method

Objectives Numerous studies indicate that the doctor–patient relationship in China is facing serious challenges. This study examined the impact of China Central Television’s negative coverage of high medicines prices on both doctors’ and patients’ opinions of the doctor–patient relationship. Setting Data were collected in a national survey conducted during 19 December 2016 to 11 January 2017 which targeted 136 public tertiary hospitals across the country. Participants All patients and doctors who submitted completed questionnaire were retrieved from the survey database. Intervention The study used propensity score matching method to match the respondents before and after China Central Television’s news report about high medicines prices which was given at 00:00 hours on 24 December 2016. Outcome measure Perception scores were calculated based on the five-point Likert scales to measure the opinions of the doctor–patient relationship. Results The perception scores of the doctor–patient relationship were significantly affected by the negative media coverage for hospitalised patients, who scored 1.18 lower on the doctor–patient relationship following the report (p=0.006, 95% CI 0.34 to 2.02), and doctors who scored 5.96 points lower on the same scale (p<0.001, 95% CI 4.11 to 7.82). Score for the ambulatory patients was unaffected by exposure to the adverse news report (p=0.05). Conclusion Chinese national media’s reporting of adverse news negatively affected the perceptions of the doctor–patient relationship among both inpatients and doctors. A better understanding of the role of mass media in the formation of opinion and trust between doctors and patients may permit strategies for managing the media, in order to improve public perceptions of the doctor–patient relationship.
Short-term Motion Prediction of Traffic Actors for Autonomous Driving using Deep Convolutional Networks

—Despite its ubiquity in our daily lives, AI is only just starting to make advances in what may arguably have the largest societal impact thus far, the nascent ﬁeld of autonomous driving. In this work we discuss this important topic and address one of crucial aspects of the emerging area, the problem of predicting future state of autonomous vehicle’s surrounding necessary for safe and efﬁcient operations. We introduce a deep learning-based approach that takes into account current world state and produces rasterized representations of each actor’s vicinity. The raster images are then used by deep convolutional models to infer future movement of actors while accounting for inherent uncertainty of the prediction task. Extensive experiments on real-world data strongly suggest beneﬁts of the proposed approach. Moreover, following successful tests the system was deployed to a ﬂeet of autonomous vehicles.
Inhibition of Nitric Oxide Production in Activated Macrophages Caused by Toxoplasma gondii Infection Occurs by Distinct Mechanisms in Different Mouse Macrophage Cell Lines

Toxoplasma gondii, the causative agent of toxoplasmosis, is a widespread intracellular parasite able to infect virtually any nucleated cell. T. gondii infection of activated macrophages inhibits nitric oxide (NO) production; however, parasite effectors responsible for this block have not been defined. Macrophage populations are extremely heterogeneous, responding differently to stimuli and to parasite infection. Here we evaluated the inhibition of NO production caused by T. gondii infection of J774-A1 and RAW 264.7 macrophages and assessed the role of several known parasite virulence factors in this phenotype. Infection of activated macrophages from both macrophage lines reduced NO production, however, the mechanism of this decrease was different. Consistent with previous reports, infected J774-A1 macrophages had reduced iNOS expression and lower number of iNOS positive cells. In contrast, T. gondii infection of RAW 264.7 macrophages did not alter iNOS expression or the number of iNOS positive cells, and yet it led to lower levels of NO production. Deletion of a number of previously defined virulence factors including ROP kinases that disrupt innate immune factors, TgIST which blocks STAT1 activation, as well as the secretory trafficking proteins ASP5 and MYR1, did not alter the phenotype of decreased NO production. Taken together our findings indicate that T. gondii infection inhibits NO production of activated macrophages by different mechanisms that involve reduction of iNOS expression vs. iNOS impairment, and suggest that a novel parasite effector is involved in modulating this important host defense pathway.
Expression and Localization of Cathepsins B, D and G in Cancer Stem Cells in Liver Metastasis From Colon Adenocarcinoma

Aim We have previously identified and characterized cancer stem cell (CSC) subpopulations in liver metastasis from colon adenocarcinoma (LMCA). In this study we investigated the expression and localization of cathepsins B, D and G, in relation to these CSCs. Methods 3,3-Diaminobenzidine (DAB) immunohistochemical (IHC) staining for cathepsins B, D and G was performed on 4μm-thick formalin-fixed paraffin-embedded LMCA sections from nine patients. Immunofluorescence (IF) IHC staining was performed on three representative samples of LMCA from the original cohort of nine patients, to determine the localization of these cathepsins in relation to the CSC subpopulations. NanoString mRNA analysis and Western Blotting (WB) were used to examine the transcript and protein expression of these cathepsins, respectively. Enzyme activity assays were utilized to determine their functional activity. Data acquired from counting of cells staining positively of the cathepsins on the DAB IHC-stained slides and from Nanostring mRNA analysis were subjected to statistical analyses to determine significance. Results DAB IHC staining demonstrated expression of cathepsins B, D and G within LMCA. IF IHC staining demonstrated the expression of both cathepsin B and cathepsin D by the OCT4− cells within the tumor nests and the OCT4+ CSC subpopulation within the peritumoral stroma. NanoString mRNA analysis showed significantly greater transcript expression of cathepsin B and cathepsin D, compared to cathepsin G. WB confirmed expression of cathepsin B and cathepsin D proteins, while cathepsin G was below detectable levels. Enzyme activity assays showed functional activity of cathepsin B and cathepsin D. Conclusion Our study demonstrated novel finding of the expression of cathepsin B, cathepsin D, and possibly cathepsin G by the putative CSC subpopulations within LMCA.
Co-Circulation of 4 Dengue Virus Serotypes among Travelers Entering China from Myanmar, 2017

We report 301 dengue virus infections among cross-border travelers entering Yunnan Province, China, from Myanmar during 2017. Phylogenetic analysis of 99 strains found all 4 serotypes co-circulating; genetic characteristics have also changed. This finding highlights the urgent need for monitoring dengue virus cross-border transmission as early warning of severe dengue fever.
Predictors of Sustained Employment Among Individuals With Serious Mental Illness: Findings From a 5-Year Naturalistic Longitudinal Study

Abstract Despite decades of research, understanding of the employment trajectories of individuals with serious mental illnesses remains elusive. We conducted a 5-year prospective, longitudinal study using a geographically broad sample of individuals who met established criteria for sustained competitive employment (N = 529). We collected data on an annual basis with a specifically designed survey instrument. Despite stable employment at study entry, more than half of the participants experienced work interruptions during the 5-year follow-up period. Predictors of sustained employment included the absence of a trauma diagnosis, Social Security disability income, psychiatric hospitalizations, and difficulties with daily functioning. The presence of a higher quality of life, workplace supports, and a flexible job were also predictive. Results dispel the myth that people with serious mental illnesses cannot be employed for prolonged periods. Interruptions in work trajectories, however, suggest that longer-term supports may increase individuals' capacity to maintain stable employment.