Miracle-dz/UniFAR-FTUs huggingface dataset:
Soluble α-synuclein–antibody complexes activate the NLRP3 inflammasome in hiPSC-derived microglia

Significance Release of oligomeric/fibrillar α-synuclein (αSyn) from damaged neurons contributes to neuronal cell death in Parkinson’s disease and other neurodegenerative disorders in part via microglial activation. Here, we show that αSyn activates the NLRP3 inflammasome in human induced pluripotent stem cell (hiPSC)-derived microglia (hiMG) via dual stimulation involving TLR2 engagement and mitochondrial damage. Oligomerized amyloid-β peptide (Aβ), as found in Alzheimer’s disease brains, exacerbates this neuroinflammation. Importantly, we found that misfolded proteins such as αSyn and Aβ, when bound to antibody and presented to hiMG, result in enhanced proinflammatory response of the NLRP3 inflammasome. These findings may have important implications for antibody therapies aimed at depleting misfolded/aggregated proteins from the human brain, as they may paradoxically trigger neuroinflammation in human microglia. Parkinson’s disease is characterized by accumulation of α-synuclein (αSyn). Release of oligomeric/fibrillar αSyn from damaged neurons may potentiate neuronal death in part via microglial activation. Heretofore, it remained unknown if oligomeric/fibrillar αSyn could activate the nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family pyrin domain-containing 3 (NLRP3) inflammasome in human microglia and whether anti-αSyn antibodies could prevent this effect. Here, we show that αSyn activates the NLRP3 inflammasome in human induced pluripotent stem cell (hiPSC)-derived microglia (hiMG) via dual stimulation involving Toll-like receptor 2 (TLR2) engagement and mitochondrial damage. In vitro, hiMG can be activated by mutant (A53T) αSyn secreted from hiPSC-derived A9-dopaminergic neurons. Surprisingly, αSyn–antibody complexes enhanced rather than suppressed inflammasome-mediated interleukin-1β (IL-1β) secretion, indicating these complexes are neuroinflammatory in a human context. A further increase in inflammation was observed with addition of oligomerized amyloid-β peptide (Aβ) and its cognate antibody. In vivo, engraftment of hiMG with αSyn in humanized mouse brain resulted in caspase-1 activation and neurotoxicity, which was exacerbated by αSyn antibody. These findings may have important implications for antibody therapies aimed at depleting misfolded/aggregated proteins from the human brain, as they may paradoxically trigger inflammation in human microglia.
Implementing Partnering for Change in Québec: Occupational Therapy Activities and Stakeholders’ Perceptions

Background. The occupational therapy school-based Partnering for Change (P4C) model has mostly been documented in Ontario. Purpose. This implementation study describes the implementation of P4C in two Québec elementary schools (P4C-Q), as well as therapy practices, their impacts, factors perceived to influence implementation, and recommendations. Method. A sequential mixed-methods design was applied. Therapists (n=2) completed daily journals, describing activities by P4C-Q level. Therapists and other school-stakeholders (n=11) participated in semi-structured interviews, analyzed through a content analysis framework. Findings. Daily journals illustrated that the majority of therapy time was spent on activities targeting the entire classroom, and on collaboration with educators. Interviews illustrated how coaching was used across different practices and the impact of these practices for schools (e.g., capacity-building) and children (e.g., increased functioning), and highlighted how relationship-building is key to facilitating the implementation of this model. Implications. Lessons learned may be helpful for others implementing P4C in their own contexts.
Centrosome‐mediated microtubule remodeling during axon formation in human iPSC‐derived neurons

Axon formation critically relies on local microtubule remodeling and marks the first step in establishing neuronal polarity. However, the function of the microtubule‐organizing centrosomes during the onset of axon formation is still under debate. Here, we demonstrate that centrosomes play an essential role in controlling axon formation in human‐induced pluripotent stem cell (iPSC)‐derived neurons. Depleting centrioles, the core components of centrosomes, in unpolarized human neuronal stem cells results in various axon developmental defects at later stages, including immature action potential firing, mislocalization of axonal microtubule‐associated Trim46 proteins, suppressed expression of growth cone proteins, and affected growth cone morphologies. Live‐cell imaging of microtubules reveals that centriole loss impairs axonal microtubule reorganization toward the unique parallel plus‐end out microtubule bundles during early development. We propose that centrosomes mediate microtubule remodeling during early axon development in human iPSC‐derived neurons, thereby laying the foundation for further axon development and function.
Unmet needs of the oldest old primary care patients with common somatic and psychiatric disorders—A psychometric evaluation

Unmet needs are common in older patients and should be assessed via suitable instruments. The adapted German version of the Camberwell Assessment of Need for the Elderly (CANE) represents an often used tool to determine the needs in older individuals. Evidence on the psychometric properties of the CANE is still pending.
The Impact of Patient Satisfaction on Patient Loyalty with the Mediating Effect of Patient Trust

This research is primarily focused on the issues of customer loyalty in the healthcare industry, particularly from the perspective of public hospitals in China. The research developed a theoretical model to test the relationship between patient satisfaction (PS), patient trust (PT), and patient loyalty (PL). The empirical data were collected from 1696 patients through the survey questionnaires from the public hospitals in Henan province. This research is an explanatory study, and adopts quantitative method. The measurement scales used in the survey were assessed and refined and the data analysis was performed using AMOS 19.0 to test the theoretical model and hypotheses developed. In addition, an exploratory factor analysis was used to identify the dimensions of PS, PT, and PL. Their reliability and validity were established through confirmatory factor analysis, and the structural equation modeling (SEM) was used in the related hypotheses. The findings indicate that PT is an important antecedent of PL, and PS has no direct relationship with PL. It is worth noting that PS can lead to PL with PT as the mediating variable. The survey results will help public hospital managers to formulate effective strategies and provide a basis for studying PL. The research will prompt hospital managers to pay attention to the factors which contribute to PS, PT, and PL, and maintain the loyalty of patients to medical institutions. This study is one of the few studies on the relationship between PS, PT, and PL in Chinese public hospitals, and it also explores the direct and indirect effects of PT on PL. The results have practical implications for the Chinese healthcare industry.
Punicalagin effect on total sleep deprivation memory deficit in male Wistar rats.

Sleep deprivation has deteriorating effects on cognitive functions and activation of brain inflammation mechanisms has been reported by some studies following total sleep deprivation. Some studies have reported the health benefits of punicalagin, a main abstract from Punica granatum L. , including those for the treatment of Alzheimer's disease. The antioxidant characteristic of punicalagin and the fact that sleep deprivation accelerates mediators of inflammation led us to further explore the possible neuroprotective role of punicalagin in total sleep deprivation memory impairment in a rat model. In this study, male Wistar rats were implanted with a canula in the lateral ventricle to receive intracerebroventricular injections (drug or vehicle). The animals were trained for the passive avoidance test and then received intracerebroventricular injections of different doses of punicalagin (0.001, 0.01, or 0.1 µg/rat). Then, they were placed in the sleep deprivation apparatus for 24 hours and tested afterwards for memory retrieval and locomotion. Our results indicated that 24 hours of total sleep deprivation impaired memory processes. PG microinjection before TSD did not prevent the deteriorating effect of total sleep deprivation on memory, and only showed a tendency of restoring the memory impairment. Comparison of the locomotor activity between the animals in different groups showed a significant increase in the total sleep deprivation sham groups that received two of the highest doses of punicalagin. Considering the reported beneficial actions of PG by other studies, further investigation is needed into the possible effects of PG in memory alterations.
Reduced anterior hippocampal and ventromedial prefrontal activity when repeatedly retrieving autobiographical memories

Research has reported that repeatedly retrieving a novel or imagined event representation reduces activity within brain regions critical for constructing mental scenarios, namely the anterior hippocampus and ventromedial prefrontal cortex (vmPFC). The primary aim of this investigation was to test if this pattern reported for imagined events would be found when repeatedly recollecting autobiographical memories. Twenty‐four participants retrieved 12 pre‐selected autobiographical memories four times while undergoing an fMRI scan. We used a region of interest approach to investigate how the anterior and posterior hippocampus as well as cortical regions critical for memory retrieval—the vmPFC and the posterior cingulate cortex (PCC)—are affected by repeated retrievals. This analysis revealed an effect in the bilateral anterior hippocampi and vmPFC, but not the posterior hippocampus nor the PCC, with activity decreasing in these regions as a function of repeated retrievals. A multivariate analytic approach (Partial Least Squares) was used to assess whole‐brain patterns of neural activity associated with repeated retrievals. This analysis revealed one pattern of neural activity associated with the initial retrieval of a memory (e.g., inferior frontal and temporal lobe regions) and a separate pattern of activity associated with later retrievals that was distributed primarily across the lateral parietal cortices. These findings suggest that the anterior hippocampus and the vmPFC support the episodic construction of an autobiographical memory the first time it is retrieved and that alternate nonconstructive processes support its subsequent retrieval shortly thereafter.
Over-Expression of Intestinal Alkaline Phosphatase Attenuates Atherosclerosis

Supplemental Digital Content is available in the text. Rationale: Intestinal alkaline phosphatase (IAP) is secreted by enterocytes and is present on the apical surface. It not only detoxifies bacterial endotoxin lipopolysaccharide (LPS) in the gut lumen and limits intestinal inflammation but also restricts translocation of LPS into systemic circulation. Diet-induced intestinal barrier dysfunction and subsequent development of metabolic endotoxemia seen in diabetes and heart disease is associated with reduced IAP levels. To examine the direct effects of increased IAP expression on barrier function and development of metabolic diseases, we developed intestine-specific IAP transgenic mice (IAPTg) overexpressing human chimeric IAP. Objective: The aim of this study was to evaluate the effects of intestine-specific IAP overexpression on Western-type diet (WD)–induced atherosclerosis in Ldlr−/− mice. Methods and Results: IAPTg mice crossed into Ldlr−/− background (Ldlr−/−IAPTg) and Ldlr−/− littermates were fed WD for 16 weeks. Intestinal barrier dysfunction was assessed by monitoring plasma LPS levels and histological examination of colon. Overexpression of IAP attenuated WD-induced disruption of the colonic mucous layer, reducing intestinal barrier dysfunction and plasma LPS levels. Significant reduction in body, liver, and adipose tissue weight was also seen in WD-fed Ldlr−/−IAPTg mice. Plasma and hepatic lipids were also significantly reduced in WD-fed Ldlr−/−IAPTg mice. Consistently, intestinal lipid absorption was attenuated in Ldlr−/−IAPTg mice with reduced expression of apical lipid transporters (CD [cluster of differentiation] 36, FATP4 [fatty acid transport protein 4], and NPC1L1 [Niemann-Pick C-like protein 1]) and intracellular lipid transport proteins (FABP [fatty acid binding protein] 1/2 and SCP2 [sterol carrier protein-2]). Attenuation of WD-induced atherosclerosis in Ldlr−/−IAPTg mice was demonstrated by significant reduction in arch and total aortic lesions as seen by enface analyses, as well as significantly reduced atherosclerotic lesions in the ascending aorta of these mice. Conclusions: IAP overexpression improves intestinal barrier function by maintaining the integrity of the mucin layer in WD-fed Ldlr−/−IAPTg mice and attenuates intestinal lipid absorption. Thus, by limiting translocation of gut-derived LPS or reducing plasma lipids, overexpression of IAP attenuates development of WD-induced atherosclerosis.
Nomograms incorporating preoperative RDW level for the prediction of postoperative complications and survival in colorectal liver metastases after resection.

BACKGROUND This study aimed to investigate the predictive significance of preoperative red cell volume distribution width (RDW) level for prognosis and to establish nomograms incorporating preoperative blood markers to predict postoperative complications and survival in patients with colorectal liver metastases (CRLM). METHODS This retrospective study included 380 enrolled CRLM patients who underwent hepatic resection. Predictors of postoperative complications were explored using binary logistic regression analysis. Covariates associated with overall survival (OS) and progression-free survival (PFS) were evaluated through univariate and multivariate Cox regression analyses. Only variables that reached statistical significance at P<0.1 in the univariate analysis were allowed to enter the multivariate analyses. The independent predictors that retained in the final multivariate model were incorporated into nomograms. RESULTS The optimal cut-off point of preoperative RDW-CV was 16%, and elevated RDW-CV was significantly associated with better prognosis (mPFS: 5.0 vs. 8.9 months, P=0.007; mOS: 59.0 vs. 42.0 months, P=0.041). The optimal cut-off point of preoperative RDW-SD was 43.9 fl, and elevated RDWSD was significantly associated with worse prognosis (mPFS: 8.0 vs. 13.0 months, P<0.001; mOS:36.8 vs. 70.2 months, P=0.001). A nomogram predicting postoperative complications was constructed based on preoperative gamma-glutamyl transpeptidase (GGT) ≥34.5 U/L, preoperative RDW-CV ≥14.1%, and intraoperative blood loss ≥200.0 mL, with AUROC of 0.658. The calibration curves and HosmerLemeshow test revealed desirable model calibration (chi-square: 3.99, P=0.91). A nomogram predicting PFS was constructed based on preoperative GGT ≥31.0 U/L, preoperative D-dimer ≥0.251 mg/L, preoperative RDW-CV <16.0%, preoperative RDW-SD ≥43.9 fl, positive lymph node metastasis, bilobar liver distribution, and R0 resection with good discrimination (C-index: 0.676±0.016) and calibration. A nomogram for the prediction of OS was constructed with favorable discrimination (C-index: 0.700±0.021) and calibration. Significant differences in PFS and OS were shown among patients stratified into three different risk groups (P<0.001) based on the nomograms. CONCLUSIONS This study first revealed the relationship between preoperative RDW-SD, RDW-CV, and prognosis in patients with CRLM. It also established nomograms especially considering preoperative blood markers to predict postoperative complications, PFS, and OS, which facilitated physicians to determine the optimal clinical management strategies.
Real-Time Volumetric Synthetic Aperture Software Beamforming of Row–Column Probe Data

Two delay-and-sum beamformers for 3-D synthetic aperture imaging with row–column addressed arrays are presented. Both beamformers are software implementations for graphics processing unit (GPU) execution with dynamic apodizations and third-order polynomial subsample interpolation. The first beamformer was written in the MATLAB programming language and the second was written in C/C++ with the compute unified device architecture (CUDA) extensions by NVIDIA. Performance was measured as volume rate and sample throughput on three different GPUs: a 1050 Ti, a 1080 Ti, and a TITAN V. The beamformers were evaluated across 112 combinations of output geometry, depth range, transducer array size, number of virtual sources, floating-point precision, and Nyquist rate or in-phase/quadrature beamforming using analytic signals. Real-time imaging defined as more than 30 volumes per second was attained by the CUDA beamformer on the three GPUs for 13, 27, and 43 setups, respectively. The MATLAB beamformer did not attain real-time imaging for any setup. The median, single-precision sample throughput of the CUDA beamformer was 4.9, 20.8, and 33.5 Gsamples/s on the three GPUs, respectively. The throughput of CUDA beamformer was an order of magnitude higher than that of the MATLAB beamformer.
Covid-19 and excess mortality in medicare beneficiaries

We estimated excess mortality in Medicare recipients with probable and confirmed Covid-19 infections in the general community and amongst residents of long-term care (LTC) facilities. We considered 28,389,098 Medicare and dual-eligible recipients from one year before February 29, 2020 through September 30, 2020, with mortality followed through November 30th, 2020. Probable and confirmed Covid-19 diagnoses, presumably mostly symptomatic, were determined from ICD-10 codes. We developed a Risk Stratification Index (RSI) mortality model which was applied prospectively to establish baseline mortality risk. Excess deaths attributable to Covid-19 were estimated by comparing actual-to-expected deaths based on historical comparisons and in closely matched cohorts with and without Covid-19. 677,100 (2.4%) beneficiaries had confirmed Covid-19 and 2,917,604 (10.3%) had probable Covid-19. 472,329 confirmed cases were community living and 204,771 were in LTC. Mortality following a probable or confirmed diagnosis in the community increased from an expected incidence of about 4% to actual incidence of 7.5%. In long-term care facilities, the corresponding increase was from 20.3% to 24.6%. The absolute increase was therefore similar at 3-4% in the community and in LTC residents. The percentage increase was far greater in the community (89%) than among patients in chronic care facilities (21%) who had higher baseline risk. The LTC population without probable or confirmed Covid-19 diagnoses experienced 38,932 excess deaths (35%) compared to historical estimates. Limitations in access to Covid-19 testing and disease under-reporting in LTC patients probably were important factors, although social isolation and disruption in usual care presumably also contributed. Remarkably, there were 31,360 fewer deaths than expected in community dwellers without probable or confirmed Covid-19 diagnoses, representing a 6% reduction. Disruptions to the healthcare system and avoided medical care were thus apparently offset by other factors, representing overall benefit. The Covid-19 pandemic had marked effects on mortality, but the effects were highly context-dependent.
Framing in Political Evaluations. An Empirical Study on the Role of Positive and Negative Comparisons in Affect and Preference Construction

Abstract The study focuses on framing which can be defined as a particular way of presenting information that affects how the message is understood and accepted. More precisely, in our research we investigate how comparisons to the concepts of an ideal politician (positive framing) and a bad politician (negative framing) influence affective evaluation and preference for a political candidate. The results of an experimental study showed that negative framing led to a higher affective evaluation and voting intention compared to positive framing. Furthermore, the juxtaposition of the candidate with the concept of a bad politician resulted in an increase in the preference for the candidate (compared to the initial measurement). The findings support the negativity effect and add to the discussion on comparative and negative advertising.
“What if…it never ends?”: Examining challenges in primary teachers' experience during the wholly online teaching

Abstract Since the outbreak of Covid-19, the Chinese government has issued strict policies for school operations. To meet the demands of normal school schedule while at home, teachers have been required to provide fully online classes regardless of their previous experience. Understanding and describing the authentic challenges teachers face during the wholly online learning and teaching period may not only allow stakeholders to make more informed decisions about subsequent practices, but also provide timely lessons for primary schools in other regions combating similar challenges. The present study was a phenomenological study, in which 26 Chinese primary school teachers were interviewed and provided photos that represented their typical online teaching experience. The essence of the study was “cautious adaptation,” and four themes were identified, including unpreparedness, concerns for at-risk students, constant change and diversity. Relevant issues and implications were discussed especially pertaining to technological innovation and advancement.
Social communication supports and services for adults with ASD: parents’ perceptions of barriers and needs

ABSTRACT Adults with autism spectrum disorder (ASD) experience significant social communication challenges that impact key areas of life, including relationship and employment success. Evidence points to great potential for social communication growth in adults with ASD; however, families’ access to supports and services is limited by lack of funding and accessibility. Scant research has been dedicated to unearthing the experiences of adults with ASD and their parents pertaining to social communication supports and services. This qualitative study gathered perceptions from 17 parents through focus groups aimed at determining barriers to and gaps in the system of social communication supports and services for adults with ASD. Using a phenomenological approach, conceptual content analysis was used to examine the parents’ perceptions and determine coding categories. Analyses revealed a number of barriers to effective use of such services and supports, and wishes for changes to facilitate services and supports in this area. Implications for professionals and policymakers are presented.