Miracle-dz/UniFAR-FTUs huggingface dataset:
Pharmacogenetics-guided dalcetrapib therapy after an acute coronary syndrome: the dal-GenE trial

Abstract Aims In a retrospective analysis of dal-Outcomes, the effect of dalcetrapib on cardiovascular events was influenced by an adenylate cyclase type 9 (ADCY9) gene polymorphism. The dal-GenE study was conducted to test this pharmacogenetic hypothesis. Methods and results dal-GenE was a double-blind trial in patients with an acute coronary syndrome within 1–3 months and the AA genotype at variant rs1967309 in the ADCY9 gene. A total of 6147 patients were randomly assigned to receive dalcetrapib 600 mg or placebo daily. The primary endpoint was the time from randomization to first occurrence of cardiovascular death, resuscitated cardiac arrest, non-fatal myocardial infarction, or non-fatal stroke. After a median follow-up of 39.9 months, the primary endpoint occurred in 292 (9.5%) of 3071 patients in the dalcetrapib group and 327 (10.6%) of 3076 patients in the placebo group [hazard ratio 0.88; 95% confidence interval (CI) 0.75–1.03; P = 0.12]. The hazard ratios for the components of the primary endpoint were 0.79 (95% CI 0.65–0.96) for myocardial infarction, 0.92 (95% CI 0.64–1.33) for stroke, 1.21 (95% CI 0.91–1.60) for death from cardiovascular causes, and 2.33 (95% CI 0.60–9.02) for resuscitated cardiac arrest. In a pre-specified on-treatment sensitivity analysis, the primary endpoint event rate was 7.8% (236/3015) in the dalcetrapib group and 9.3% (282/3031) in the placebo group (hazard ratio 0.83; 95% CI 0.70–0.98). Conclusion Dalcetrapib did not significantly reduce the risk of occurrence of the primary endpoint of ischaemic cardiovascular events at end of study. A new trial would be needed to test the pharmacogenetic hypothesis that dalcetrapib improves the prognosis of patients with the AA genotype. Clinical Trial Registration Trial registration dal-GenE ClinicalTrials.gov Identifier: NCT02525939
Autistic people outperform neurotypicals in a cartoon version of the Reading the Mind in the Eyes

Prior research suggests that while autistic people may demonstrate poorer facial emotion recognition when stimuli are human, these differences lessen when stimuli are anthropomorphic. To investigate this further, this work explores emotion recognition in autistic and neurotypical adults (n = 196). Groups were compared on a standard and a cartoon version of the Reading the Mind in the Eyes test. Results indicated that autistic individuals were not significantly different from neurotypicals on the standard version. However, autistic people outperformed neurotypicals on the cartoon version. The implications for these findings regarding emotion recognition deficits and the social motivation account of autism are discussed and support the view of socio‐cognitive differences rather than deficits in this population.
Adaptive RISE Control of Hydraulic Systems With Multilayer Neural-Networks

This paper focuses on developing an advanced nonlinear controller for hydraulic system to achieve asymptotic tracking with various disturbances. To accomplish this study, a multilayer neural-networks (NNs) estimator is first developed to improve the compensation accuracy of model-based feedforward control terms, which can greatly reduce the uncompensated disturbance, then a continuous robust integral of the sign of the error (RISE) control approach is effectively integrated with the multilayer NNs estimator to deal with the residual mismatched disturbance, in which the RISE feedback gain is adapted online to further decrease the high-gain feedback. At last, by considering the inwardness of matched disturbance in hydraulic systems, it is estimated by another multilayer NNs fully with the residual functional reconstruction inaccuracies handled by a novel adaptive term. As a result, theoretical analysis reveals that the proposed controller guarantees a semiglobal asymptotic stability. Extensively comparative experimental results verify the priority of the proposed control strategy, and a 0.2% dynamic tracking accuracy is achieved.
A Voting Ensemble Classifier for Wafer Map Defect Patterns Identification in Semiconductor Manufacturing

A wafer map contains a graphical representation of the locations about defect pattern on the semiconductor wafer, which can provide useful information for quality engineers. Various defect patterns occur due to increasing wafer sizes and decreasing features sizes, which makes it very complex and unreliable process to identify them. In this paper, we propose a voting ensemble classifier with multi-types features to identify wafer map defect patterns in semiconductor manufacturing. Our research contents can be summarized as follows. First, three distinctive features such as density-, geometry-, and radon-based features were extracted from raw wafer images. Then, we applied four machine learning classifiers, namely logistic regression (LR), random forests (RFs), gradient boosting machine (GBM), and artificial neural network (ANN), and trained them using extracted features of original data set. Then their results were combined with a soft voting ensemble (SVE) technique which assigns higher weights to the classifiers with respect to their prediction accuracy. Consequently, we got performance measures with accuracy, precision, recall, ${F}$ -measure, and AUC score of 95.8616%, 96.9326%, 96.9326%, 96.7124%, and 99.9114%, respectively. These results show that the SVE classifier with proposed multi-types features outperformed regular machine learning-based classifiers for wafer maps defect detection.
Analysis of ginseng in the treatment of Interstitial Cystitis/Bladder Pain Syndrome based on network pharmacology.

OBJECTIVE The network pharmacology is adopted in the paper to elaborate the active components, targets, and pathways of ginseng in the treatment of Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS). MATERIALS AND METHODS The active components and potential targets of ginseng were obtained through the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP). The OMIM, Disgenet, and Genecards databases for IC/BPS targets, and the STRING11.0 database were used for the protein-protein interaction (PPI) network. Meanwhile, the latter covers R language was used for the target of ginseng for IC/BPS, Bioconductor bioinformatics software for GO and KEGG functional enrichment analysis of key target genes, and the Cytoscape 3.8. 2 software for constructing the "component-target" network and the "component-target-pathway" network map. RESULTS The results are categorized into three camps: components, targets, and pathways. As for components, 22 active components of ginseng that perform biological activities in the cell membrane, cytoplasm, and nucleus were observed, among which kaempferol, girinimbin, suchilacton, arachidonate, and gomisin B are the main active ones. 650 targets were found, mainly represented by PTGS2, PTGS1, AR, SLC6A4, and CHRM2, 134 of which (especially AKT1, TNF, VEGFA, TP53, EGFR, STAT3, IL-1β, ESR1, and JUN) contribute to the treatment of IC/BPS. Moreover, the pathways that serve as major contributors are the PI3K-Akt signaling pathway, the HIF-1 signaling pathway, the STAT3 signaling pathway, the MAPK signaling pathway, the NF-κB signaling pathway, and the apoptosis-related pathway. CONCLUSIONS Ginseng can exert anti-inflammatory, anti-oxidative stress and anti-apoptotic effects on IC/BPS thanks to its multi-component, multi-target and multi-way functions.
An Experimental Human Colonization Model with Pneumococcal Serotype 3 has the Potential to be Used for Vaccine Studies

pollution and pediatric respiratory hospitalizations: effect modification by particle constituents and oxidative potential. Am J Respir Crit Care Med 2022;206:1370–1378. 13. WuY, Li S, Guo Y. Space-time-stratified case-crossover design in environmental epidemiology study.Health Data Science 2021;2021:1–3. 14. Bozigar M, Lawson AB, Pearce JL, Svendsen ER, Vena JA. Using Bayesian time-stratified case-crossover models to examine associations between air pollution and “asthma seasons” in a low air pollution environment. PLoS One 2021;16:e0260264. 15. Lu Y, Symons JM, Geyh AS, Zeger SL. An approach to checking casecrossover analyses based on equivalence with time-series methods. Epidemiology 2008;19:169–175.
Is non-occupational HIV Post Exposure Prophylaxis (nPEP) still used? An exploration of nPEP use since widespread availability of HIV PrEP

Background Non-occupational Post-Exposure Prophylaxis (nPEP) is an effective HIV prevention strategy in gay and bisexual men (GBM) taken after possible exposure. HIV Pre-Exposure Prophylaxis (PrEP) is also a highly effective HIV prevention strategy. Methods A retrospective audit of medical records of GBM presenting to a sexual health centre and provided with nPEP compared two periods to determine if nPEP usage changed following availability of PrEP. In the first period (P1) PrEP was available through extended trials. In the second period (P2) PrEP became more accessible through the Australian Pharmaceutical Benefits Scheme (PBS). Period comparisons were performed using a two-population test of proportions with one-tailed testing and significance set at P < . 05 using SPSS Statistics Version 25. Results There were 232 GBM provided with nPEP in P1, and 202 in P2. A two-population test of proportions demonstrated that GBM presentations for nPEP decreased significantly from 302/4779 (6.3%) of GBM visits in P1 to 221/7205 (3.1%) in P2 when PrEP was more accessible (Z=8.53, P < .001). PrEP uptake after presenting for nPEP increased from 30 (12.9%) of total GBM visits in P1 to 69 (34.2%) in P2 (Z=5.26, p < .001). Conclusions GBM accessing nPEP decreased with statistical significance post introduction of PBS PrEP.
The Self and alien self in psyche and soma

Abstract This paper compares presentations of disorders of the sense of body ownership and agency from psychoanalytic and neurological perspectives to demonstrate similarities in symptomatology proposing these similarities arise from adjustments in Friston’s generative model of self‐organization and selfhood. The implications for the analytic model of the Self, for clinical practice and for neuroscience research are considered. Patients with narcissistic disorders use projective defences resulting in a disordered sense of what belongs to whom. This applies to mind and body of self and other and is central to understanding transference and countertransference. Clinical observations of this disordered sense of ownership and agency mirror findings in neurological disorders. This paper proposes that in both neurological and psychological disorders Friston’s ‘internal generative model’ of selfhood is adjusted. Further to this whilst this adjustment may be either neurogenic or psychogenic, the final neural mechanism and symptomatic outcome are similar. On the basis of these observations the paper compares the concept of the Self from Jungian and psychoanalytic perspectives. Finally, the implications for the concept of the death instinct and Britton’s concept of Xenophobia are explored along with the implications of these observations for clinical practice.
Racial and ethnic differences in blood pressure before and after the 2016 United States general election

The 2016 U.S. presidential election was a major source of stress among many adults. Psychosocial stress can manifest physiologically in elevated blood pressure (BP). Little is known regarding the association of macro‐level sociopolitical events with BP changes at the population‐level. This study sought to characterize population‐level changes in BP following the 2016 U.S. presidential election.
Spinal Cord Injury: The Global Incidence, Prevalence, and Disability From the Global Burden of Disease Study 2019

Study Design. A retrospective cohort study. Objective. The authors aimed to estimate the incidence, prevalence and years lived with disability (YLDs) of spinal cord injury (SCI) by location, sex, age, injury site and socio-demographic index (SDI) based on the data of the Global Burden of Disease Study (GBD) 2019. Summary of Background Data. GBD 2019 estimates the burden of 369 diseases and injuries worldwide in 2019 and the temporal trends in the past 30 years. SCI is estimated as a result of injury from various causes. Methods. A Bayesian meta-regression tool, DisMod-MR2.1, was used to produce the estimates. Estimated annual percentage change (EAPC) was calculated based on a linear regression mode of the age standardized rates and the calendar year to represent the temporal trends of the age standardized rates. Spearman rank order correlation was used to determine the correlation between SDI and the incidence and burden of SCI. Results. Globally, there were 0.9 [95% uncertainty interval (UI), 0.7 to 1.2] million incident cases, 20.6 (95% UI, 18.9–23.6) million prevalent cases and 6.2 (95% UI, 4.5–8.2) million YLDs of total SCI in 2019. The ASPR increased (EAPC, 0.1; 95% confidence interval, −0.01 to 0.2), while the age standardized incidence rate (ASIR) (EAPC, −0.08; 95% UI, −0.24 to 0.09) and age standardized YLD rate (ASYR) (EAPC, −0.08; 95% confidence interval, −0.24 to 0.09) decreased. Males had higher ASIR and ASYR, and the rate of incidence, prevalence and YLD increased with age. Spinal injuries at neck level caused higher ASYR than injuries below neck level. A positive correlation existed between SDI and ASIR (ρ=0.1626, P<0.05), while a negative correlation was observed between SDI and EAPC of ASYR (ρ=−0.2421, P<0.01). Conclusion. Conclusively, the incidence and burden of SCI has increased over the last 30 years. Males and the elderly were affected to a greater degree than females and younger individuals. Level of Evidence. Level III.
Combinatorial approaches for novel cardiovascular drug discovery: a review of the literature

ABSTRACT Introduction In this article, authors report an inclusive discussion about the combinatorial approach for the treatment of cardiovascular diseases (CVDs) and for counteracting the cardiovascular risk factors. The mentioned strategy was demonstrated to be useful for improving the efficacy of pharmacological treatments and in CVDs showed superior efficacy with respect to the classical monotherapeutic approach. Areas covered According to this topic, authors analyzed the combinatorial treatments that are available on the market, highlighting clinical studies that demonstrated the efficacy of combinatorial drug strategies to cure CVDs and related risk factors. Furthermore, the review gives an outlook on the future perspective of this therapeutic option, highlighting novel drug targets and disease models that could help the future cardiovascular drug discovery Expert opinion The use of specifically designed and increasingly rational and effective drug combination therapies can therefore be considered the evolution of polypharmacy in cardiometabolic and CVDs. This approach can allow to intervene on multiple etiopathogenetic mechanisms of the disease or to act simultaneously on different pathologies/risk factors, using the combinations most suitable from a pharmacodynamic, pharmacokinetic, and toxicological perspective, thus finding the most appropriate therapeutic option.
Have beliefs in conspiracy theories increased over time?

The public is convinced that beliefs in conspiracy theories are increasing, and many scholars, journalists, and policymakers agree. Given the associations between conspiracy theories and many non-normative tendencies, lawmakers have called for policies to address these increases. However, little evidence has been provided to demonstrate that beliefs in conspiracy theories have, in fact, increased over time. We address this evidentiary gap. Study 1 investigates change in the proportion of Americans believing 46 conspiracy theories; our observations in some instances span half a century. Study 2 examines change in the proportion of individuals across six European countries believing six conspiracy theories. Study 3 traces beliefs about which groups are conspiring against “us,” while Study 4 tracks generalized conspiracy thinking in the U.S. from 2012 to 2021. In no instance do we observe systematic evidence for an increase in conspiracism, however operationalized. We discuss the theoretical and policy implications of our findings.
Dosage Frequency Effects on Treatment Outcomes Following Self-managed Digital Therapy: Retrospective Cohort Study

Background Although the efficacy of high-dose speech-language therapy (SLT) for individuals with poststroke aphasia has been established in the literature, there is a gap in translating these research findings to clinical practice. Therefore, patients continue to receive suboptimal amounts of SLT, with negative consequences for their functional communication recovery. Recent research has identified self-managed digital health technology as one way to close the dosage gap by enabling high-intensity therapy unrestricted by clinician availability or other practical constraints. However, there is limited empirical evidence available to rehabilitation professionals to guide dose prescriptions for self-managed SLT despite their increasing use in the COVID-19 era and likely beyond. Objective This study aims to leverage real-world mobile health data to investigate the effects of varied dosage frequency on performance outcomes for individuals with poststroke speech, language, and cognitive deficits following a 10-week period of self-managed treatment via a commercially available digital health platform. Methods Anonymized data from 2249 poststroke survivors who used the Constant Therapy app between late 2016 and 2019 were analyzed. The data included therapy tasks spanning 13 different language and cognitive skill domains. For each patient, the weekly therapy dosage was calculated based on the median number of days per week of app use over the 10-week therapy period, binned into groups of 1, 2, 3, 4, or ≥5 days per week. Linear mixed-effects models were run to examine change in performance over time as a function of dosage group, with post hoc comparisons of slopes to evaluate the performance gain associated with each additional day of practice. Results Across all skill domains, linear mixed-effects model results showed that performance improvement was significantly greater for patients who practiced 2 (β=.001; t15,355=2.37; P=.02), 3 (β=.003; t9738=5.21; P<.001), 4 (β=.005; t9289=7.82; P<.001), or ≥5 (β=.005; t6343=8.14; P<.001) days per week compared with those who only practiced for 1 day per week. Post hoc comparisons confirmed an incremental dosage effect accumulating with each day of practice (ie, 1 day vs 2 days, 2 days vs 3 days, and 3 days vs 4 days), apart from 4 days versus ≥5 days of practice per week. The result of greater improvement for higher versus lower dosage frequency groups was true not only across all domains but also within a majority of individual subdomains. Conclusions The findings from this study demonstrated that increased dosage frequency is associated with greater therapy gains over a 10-week treatment period of self-managed digital therapy. The use of real-world data maximizes the ecological validity of study results and makes the findings more generalizable to clinical settings. This study represents an important step toward the development of optimal dose recommendations for self-managed SLT.
The omega-3 hydroxy fatty acid 7(S)-HDHA is a high-affinity PPARα ligand that regulates brain neuronal morphology

The nuclear receptor peroxisome proliferator-activated receptor alpha (PPARα) is emerging as an important target in the brain for the treatment or prevention of cognitive disorders. The identification of high-affinity ligands for brain PPARα may reveal the mechanisms underlying the synaptic effects of this receptor and facilitate drug development. Here, using an affinity purification–untargeted mass spectrometry (AP-UMS) approach, we identified an endogenous, selective PPARα ligand, 7(S)-hydroxy-docosahexaenoic acid [7(S)-HDHA]. Results from mass spectrometric detection of 7(S)-HDHA in mouse and rat brain tissues, time-resolved FRET analyses, and thermal shift assays collectively revealed that 7(S)-HDHA potently activated PPARα with an affinity greater than that of other ligands identified to date. We also found that 7(S)-HDHA activation of PPARα in cultured mouse cortical neurons stimulated neuronal growth and arborization, as well as the expression of genes associated with synaptic plasticity. The findings suggest that this DHA derivative supports and enhances neuronal synaptic capacity in the brain. Description An endogenous ligand promotes PPARα-dependent activity in neurons that supports synaptic plasticity. Omega-3s for an active brain Activation of the nuclear receptor PPARα in mice is neuroprotective and boosts memory. Liu et al. found an endogenous ligand for PPARα in the brain that may promote these effects. Proteomic analysis of rodent brain lysates and biophysical assays revealed that 7(S)-HDHA, a hydroxylated derivative of the omega-3 fatty acid DHA, bound to PPARα with high affinity. Treating primary cortical neurons with 7(S)-HDHA promoted dendritic outgrowth and arborization, as well as the expression of PPARα target genes that are associated with synaptic plasticity. Supplementing the diet of young male rats with DHA increased the amount of 7(S)-HDHA in the cortex. The findings further support the notion that omega-3 fatty acids may support synaptic function in the brain and show a potential mechanism underlying such benefits from dietary DHA.
Multidomain concussion symptoms in adolescents: A network analysis

Abstract Concussion is a heterogeneous injury involving symptoms and impairment that represent multiple domains (e.g., anxiety, cognitive, vestibular). Network analysis, a modeling technique that estimates relationships among symptoms, provides a statistically sound and clinically practical method for evaluating these interrelationships. The purpose of this study was to examine, using network analysis, relationships among clinical assessments and multidomain symptom report within a sample of adolescent patients following a concussion. Participants included 326 patients (49.7% female) aged 10–21 years presenting to a concussion specialty clinic within 28 days of a diagnosed concussion. Participants completed the Post-Concussion Symptom Scale (PCSS) and Vestibular–Ocular Motor Screening (VOMS) tool at initial visit. Network models were applied to PCSS symptoms initially, and then applied to VOMS and PCSS symptom data together. Dizziness (Expected influence (EI) = 1.10) and sadness (EI = 1.91) were most central (i.e., highest cumulative partial correlations) to the symptom network. Numerous interdomain relationships were supported, including irritability with mental fogginess (edgeweight = 0.12), dizziness with headache (edgeweight = 0.16), and dizziness with vision problems (edgeweight = 0.13). Community analyses resulted in VOMS groupings by domain (e.g., vestibular) and symptom (e.g., dizziness). The findings suggest a more direct focus on symptom interrelationships, such as how dizziness contributes to emotional symptoms, may help guide and better target treatments. Also, results suggest grouping VOMS assessment by symptom (e.g., dizziness) and item (e.g., vestibular-ocular reflex) may better reflect underlying impairments reflected by these symptom-item combinations.