Miracle-dz/UniFAR-FTUs huggingface dataset:
Attentional Demand of a Movement Sequence Guided by Visual-Spatial and by Motor Representations

Abstract The objective of the experiment was to assess the change in attentional demands of a movement sequence guided by visual-spatial and motor representations across practice sessions in a dual-task probe paradigm. Participants were randomly assigned to either a 1-day or 2-day practice group. Following acquisition of the motor sequence task, participants first conducted a retention test and then four inter-manual transfer tests under single and dual-task conditions. The probe task was a simple reaction time. The inter-manual transfer tests, consisting of a mirror and non-mirror test, examined the development of the motor and visual-spatial representation, respectively. The results indicated that both representations guided the movement sequence and required attention. The attentional demands did not change with additional practice.
Cultural dimensions of individualism and collectivism and risk of opioid misuse: A test of Social Cognitive Theory

Abstract Background Despite the critical role social and cultural contexts play in pain experience, limited theoretical and empirical attention has been devoted to the interplay between social, cognitive, cultural, and psychological factors in chronic pain management and the risk of opioid misuse. Methods Using structural equation modeling, the present study tested the Social Cognitive Theory (SCT) of chronic pain management and risk of opioid misuse in the context of intraindividual cultural dimensions of individualism and collectivism among 316 ethnically diverse adults with chronic pain in the United States. Results Social cognitive predictors account for a significant amount of variance in pain dysfunction and risk of opioid misuse in adults with chronic pain. Satisfaction with pain support was positively associated with both greater pain acceptance and greater pain self‐efficacy. Individualism was found to be positively associated with satisfaction with pain support, pain self‐efficacy, and pain acceptance but negatively associated with the risk of opioid misuse. Collectivism was positively associated with the risk of opioid misuse. Conclusions The study findings not only empirically support using SCT for adults with chronic pain, but also provide a more thorough conceptual framework that highlights the intracultural diversity and interplay among social, cognitive, and psychological factors that affect pain experience and the risk of opioid misuse among adults with chronic pain.
Bladder-sparing (chemo)radiotherapy in elderly patients with muscle-invasive bladder cancer: a retrospective cohort study

Abstract Background Organ-sparing treatment for muscle-invasive bladder cancer by maximal transurethral removal of the tumor (TURB) followed by chemoradiation (CRT) has shown promising results in recent studies, and is therefore considered to be an acceptable alternative for the standard of radical cystectomy (RC) in selected patients. We report on outcomes in a single-center, retrospective CRT cohort in comparison to a RC and radiotherapy only (RT) cohort. Patients and methods The patient population included n = 84 CRT patients, n = 93 RC patients, and n = 95 RT patients. Primary endpoints were local control (LC) up to 2 years and overall survival (OS) up to 5 years. Cox regression was performed to determine risk factors for LC and OS in the CRT group. Acute genito-urinary (GU) and gastro-intestinal (GI) toxicity were scored with CTCAE version 4 for the RT and CRT cohort. Logistic regression was used to determine risk factors for toxicity. We followed the EQUATOR guidelines for reporting, using the STROBE checklist for observational research. Results Baseline characteristics were different between the treatment groups with in particular worse comorbidity scores and higher age in the RT cohort. The CRT schedule was completed by 96% of the patients. LC at 2 years was 83.4% (90% CI 76.0–90.8) for CRT vs. 70.9% (62.2–79.6) for RC and 67.0% (56.8–77.2) for RT. OS at 5 years was 48.9% (38.4–59.4) for CRT vs. 46.6% (36.4–56.8) for RC, and 27.6% (19.4–35.8) for RT. High T stage was significantly associated with worse LC and OS in the CRT group. GU/GI toxicity grade ≥2 occurred in 43 (48.3%) RT patients and 38 (45.2%) CRT patients. Conclusions The organ-preserving strategy with CRT was feasible and tolerable in this patient population, and the achieved LC and OS were satisfactory in comparison to the RC cohort and literature.
Explaining caregiver burden in a large sample of UK dementia caregivers: The role of contextual factors, behavioural problems, psychological resilience, and anticipatory grief

Abstract Objectives Dementia caregiver burden is a significant public health concern, affecting both the wellbeing of caregivers and their care-recipients. This study investigated a range of variables associated with caregiver burden in a large sample of UK dementia caregivers. Clinical characteristics and novel psychological constructs were used – including anticipatory grief and psychological resilience. Anticipatory grief refers to the process of experiencing loss prior to the death of a significant person. Method Caregivers of persons with dementia (N = 530) completed a survey obtaining the Zarit-Burden Interview (ZBI-SF) and other psychological and demographic/caregiving-related factors. Results Findings illustrate that 71% of the sample experienced high levels of caregiver burden and around 95% met the criteria for clinically significant levels of burden. A regression model explained 49% of the variance in subjective caregiver burden; contextual factors (care-recipients living situation, frequency of caregiving), behavioural challenges in the care-recipient (memory-related problem behaviours), caregiver psychological resilience and caregiver anticipatory grief (heartfelt long & sadness, worry & felt isolation) were all significant variables. Caregiver anticipatory grief, followed by psychological resilience, had the strongest association with burden Conclusion Caregiver anticipatory grief and psychological resilience, have a significant interaction with the clinical presentation of the dementia sufferer in explaining subjective caregiver burden. More grief and resilience-focused interventions targeting both the practical and emotional challenges are imperative to reduce burden and thus to ensure caregiver wellbeing.
A secretory form of Parkin‐independent mitophagy contributes to the repertoire of extracellular vesicles released into the tumour interstitial fluid in vivo

Abstract We characterized the in vivo interstitial fluid (IF) content of extracellular vesicles (EVs) using the GFP‐4T1 syngeneic murine cancer model to study EVs in‐transit to the draining lymph node. GFP labelling confirmed the IF EV tumour cell origin. Molecular analysis revealed an abundance of IF EV‐associated proteins specifically involved in mitophagy and secretory autophagy. A set of proteins required for sequential steps of fission‐induced mitophagy preferentially populated the CD81+/PD‐L1+ IF EVs; PINK1, TOM20, and ARIH1 E3 ubiquitin ligase (required for Parkin‐independent mitophagy), DRP1 and FIS1 (mitochondrial peripheral fission), VDAC‐1 (ubiquitination state triggers mitophagy away from apoptosis), VPS35, SEC22b, and Rab33b (vacuolar sorting). Comparing in vivo IF EVs to in vitro EVs revealed 40% concordance, with an elevation of mitophagy proteins in the CD81+ EVs for both murine and human cell lines subjected to metabolic stress. The export of cellular mitochondria proteins to CD81+ EVs was confirmed by density gradient isolation from the bulk EV isolate followed by anti‐CD81 immunoprecipitation, molecular sieve chromatography, and MitoTracker export into CD81+ EVs. We propose the 4T1 in vivo model as a versatile tool to functionally characterize IF EVs. IF EV export of fission mitophagy proteins has broad implications for mitochondrial function and cellular immunology.
Microscale pedestrian environment surrounding pedestrian injury sites in Washington state, 2015–2020

Abstract Objective While microscale pedestrian environment features such as sidewalks and crosswalks can affect pedestrian safety, it is challenging to assess microscale environment associated risk across locations or at scale. Addressing these challenges requires an efficient auditing protocol that can be used to assess frequencies of microscale environment features. For this reason, we developed an eight-item pedestrian environment virtual audit protocol and conducted a descriptive epidemiologic study of pedestrian injury in Washington State, USA. Methods We used data from police reports at pedestrian-automotive collision sites where the pedestrian was seriously injured or died. At each collision site, high school students participating in an online summer internship program virtually audited Google Street View imagery to assess the presence of microscale pedestrian environment features such as crosswalks and streetlighting. We assessed inter-rater reliability using Cohen’s kappa and explored prevalence of eight microscale environment features in relation to injury severity and municipal boundaries. Results There were 2248 motor vehicle crashes eliciting police response and resulting in death or serious injury of a pedestrian in Washington State between January 1, 2015 and May 8, 2020. Of the crashes resulting in serious injury or death, 498 (22%) resulted in fatalities and 1840 (82%) occurred within municipal boundaries. Cohen’s kappa scores for the eight pedestrian features that were audited ranged from 0.52 to 0.86. Audit results confirmed that features such as sidewalks and crosswalks were more common at collision sites within city limits. Conclusions High school student volunteers with minimal training can reliably audit microscale pedestrian environments using limited resources.
Patient safety culture in primary health care: Medical office survey on patient safety culture in a Brazilian family health strategy setting

Study objectives To assess the patient safety culture in Primary Health Care (PHC) setting after the transition to the Family Health Strategy (FHS) model in a Brazilian metropolitan area and compare the results between the categories of health care professionals. Methods A cross-sectional study including 246 workers from primary health care services in Federal District, Brazil. Data collection took place from October to December 2019 through the Medical Office Survey on Patient Safety Culture (MOSPSC) application. Patient safety culture was considered positive when the score was above 60%. For comparisons between the categories of health care professionals’, the ANOVA and Kruskal-Wallis test were used for composite percent positive scores, and Pearson’s chi-square or Fishers exact test for frequency and percentage of positive responses. Results The overall MOSPSC composite percent positive score was 49.9%. Among the 12 dimensions, only three showed a positive patient safety culture: Teamwork (73.1%), Organizational learning (62.9%), and Patient care tracking/follow-up (60.1%). The percentage of positive responses on overall quality assessment (78.1%) and overall patient safety assessment (78.0%) showed a positive evaluation. There was no significant difference in the composite percent positive score of overall MOSPSC (p = 0.135) and the percentage of positive responses on overall patient safety assessment (p = 0.156) between the categories of health care professionals. Overall quality assessment showed a significant difference between job roles (p < 0.001), in which nursing /health care technicians showed a significantly lower score than other job roles. Conclusion The patient safety culture assessment showed a weakness in the patient safety in the PHC services. The MOSPSC and nine of its dimensions presented a negative safety culture assessment, regardless of the high scores in the overall patient safety and quality assessments.
Effect of Chronic Cadmium Exposure on Brain and Liver Transporters and Drug-Metabolizing Enzymes in Male and Female Mice Genetically Predisposed to Alzheimer’s Disease

Cadmium (Cd) exposure is associated with increased Alzheimer’s disease (AD) risks. The human Apolipoprotein E (ApoE) gene encodes a lipid-transporting protein that is critical for brain functions. Compared with ApoE2 and E3, ApoE4 is associated with increased AD risk. Xenobiotic biotransformation-related genes have been implicated in the pathogenesis of AD. However, little is known about the effects of Cd, ApoE, and sex on drug-processing genes. We investigated the Cd-ApoE interaction on the transcriptomic changes in the brains and livers of ApoE3/ApoE4 transgenic mice. Cd disrupts the transcriptomes of transporter and drug-processing genes in brain and liver in a sex- and ApoE-genotype-specific manner. Proinflammation related genes were enriched in livers of Cd-exposed ApoE4 males, whereas circadian rhythm and lipid metabolism related genes were enriched in livers of Cd-exposed ApoE3 females. In brains, Cd up-regulated the arachidonic acid-metabolizing Cyp2j isoforms only in the brains of ApoE3 mice, whereas the dysregulation of cation transporters was male-specific. In livers, several direct target genes of the major xenobiotic-sensing nuclear receptor pregnane X receptor were uniquely upregulated in Cd-exposed ApoE4 males. There was a female-specific hepatic upregulation of the steroid hormone-metabolizing Cyp2 isoforms and the bile acid synthetic enzyme Cyp7a1 by Cd exposure. The dysregulated liver transporters were mostly involved in intermediary metabolism, with the most significant response observed in ApoE3 females. In conclusion, Cd dysregulated the brain and liver drug-processing genes in a sex- and ApoE-genotype specific manner, and this may serve as a contributing factor for the variance in the susceptibility to Cd neurotoxicity. SIGNIFICANCE STATEMENT Xenobiotic biotransformation plays an important role in modulating the toxicity of environmental pollutants. The human ApoE4 allele is the strongest genetic risk factor for AD, and cadmium (Cd) is increasingly recognized as an environmental factor of AD. Very little is known regarding the interactions between Cd exposure, sex, and the genes involved in xenobiotic biotransformation in brain and liver. The present study has addressed this critical knowledge gap.
Dynamic Nonlinear Behavior of Ionic Liquid-Based Reservoir Computing Devices

Herein, a physical reservoir device that uses faradaic currents generated by redox reactions of metal ions in ionic liquids was developed. Synthetic time-series data consisting of randomly arranged binary number sequences (“1” and “0”) were applied as isosceles-triangular voltage pulses with positive and negative voltage heights, respectively, and the effects of the faradaic current on short-term memory and parity-check task accuracies were verified. The current signal for the first half of the triangular voltage-pulse period, which contained a much higher faradaic current component compared to that of the second half of the triangular voltage-pulse period, enabled higher short-term memory task accuracy. Furthermore, when parity-check tasks were performed using a faradaic current generated by asymmetric triangular voltage-pulse levels of 1 and 0, the parity-check task accuracy was approximately eight times higher than that of the symmetric triangular voltage pulse in terms of the correlation coefficient between the output signal and target data. These results demonstrate the advantage of the faradaic current on both the short-term memory characteristics and nonlinear conversion capabilities and are expected to provide guidance for designing and controlling various physical reservoir devices that utilize electrochemical reactions.
Preferential Expansion of Foxp3+ T Regulatory Cells in CTLA-4–Deficient and CTLA-4–Haploinsufficient C57BL/6 Mice

Foxp3+ cells and CTLA-4 have been ascribed major roles in downregulating immune responses. To address the relationship between CTLA-4 expression and Foxp3+ cells, we generated littermate CTLA-4–sufficient (Ctla4+/+), CTLA-4–haploinsufficient (Ctla4+/−), and CTLA-4–deficient (Ctla4−/−) Foxp3-gfp knock-in C57BL/6 mice, permitting us to characterize the phenotype of Foxp3+ cells and to test their ex vivo T regulatory (Treg) suppressor activity. CD3+, CD4+, and CD8+ cells, but not CD19+ cells, were markedly expanded in Ctla4−/− mice compared with Ctla4+/+ or Ctla4+/− mice. In Ctla4−/− mice, the relative expansion of the Foxp3+ population was greater than that of the CD3+, CD4+, or CD8+ populations because of increased survival of Foxp3+ cells. Foxp3+ Treg cells from Ctla4−/− mice and Foxp3+ Treg cells from Ctla4+/+ mice exerted identical ex vivo suppressor function. This may be related to differential expression of GITR, CD73, and CD39 on Foxp3+ Treg cells from Ctla4−/− mice versus that on corresponding cells from littermate Ctla4+/+ or Ctla4+/− mice, with GITR and CD39 being upregulated and CD73 being downregulated on Foxp3+ Treg cells from Ctla4−/− mice. Moreover, CTLA-4 expression in Ctla4+/+, Ctla4+/−, and Ctla4−/− mice correlated with their percentages of Foxp3+ cells, suggesting an important role for CTLA-4 expression in Treg cell homeostasis. This may have vital ramifications for the treatment of patients for whom augmentation of suppressor function would be beneficial (e.g., patients with autoimmune diseases) and for whom diminution of suppressor function would be beneficial (e.g., patients with cancer).
Visual priming of two-step motion sequences

Perception of an ambiguous apparent motion is influenced by the immediately preceding motion. In positive priming, when an observer is primed with a slow-pace (1–3 Hz) sequence of motion frames depicting unidirectional drift (e.g., Right–Right–Right–Right), subsequent sequences of ambiguous frames are often perceived to continue moving in the primed direction (illusory Right–Right …). Furthermore, priming an observer with a slow-pace sequence of rebounding apparent motion frames that alternate between opponently coded motion directions (e.g., Right–Left–Right–Left) leads to an illusory continuation of the two-step rebounding sequence in subsequent random frames. Here, we show that even more arbitrary two-step motion sequences can be primed; in particular, two-step motion sequences that alternate between non-opponently coded directions (e.g., Up–Right–Up–Right; staircase motion) can be primed to be illusorily perceived in subsequent random frames. We found that staircase sequences, but not drifting or rebounding sequences, were primed more effectively with four priming frames compared with two priming frames, suggesting the importance of repeating the sequence element for priming arbitrary two-step motion sequences. Moreover, we compared the effectiveness of motion primes to that of symbolic primes (arrows) and found that motion primes were significantly more effective at producing prime-consistent responses. Although it has been proposed that excitatory and rivalry-like mechanisms account for drifting and rebounding motion priming, current motion processing models cannot account for our observed priming of staircase motion. We argue that higher order processes involving the recruitment and interaction of both attention and visual working memory are required to account for the type of two-step motion priming reported here.
Prognostic role of PD-L1 expression in patients with salivary gland carcinoma: A systematic review and meta-analysis

Background Although programmed cell death-ligand 1 (PD-L1) has been recognized as a potential marker in several cancers, the relationship between PD-L1 expression and survival in patients with salivary gland carcinoma (SGC) has remained unclear. We aimed to evaluate the association of PD-L1 expression with clinicopathological features and prognosis in SGC patients. Methods The databases Ovid Medline, PubMed, Scopus, and EMBASE were searched for relevant studies that detected PD-L1 expression in SGC. The meta-analysis was performed according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA), and the reporting recommendations for tumor marker prognostic studies (REMARK) was used to assess the quality of research eligible for this meta-analysis. Included studies were assessed using the Quality in Prognosis Studies (QUIPS) tool. Odds ratios (ORs) with 95% confidence interval (CI) were calculated to estimate the correlation between PD-L1 expression and clinicopathological features. Hazard ratios (HRs) with 95% CI were applied to assess the association between PD-L1 expression and survival outcomes of patients. Results A total of ten studies (including 952 patients with SGC) were evaluated. The meta-analysis showed that positive PD-L1 expression in SGC was significantly associated with male patients, older age, Tumor stage, lymph node metastasis, high pathological grade, and non-adenoid cystic carcinoma subtype. The pooled data demonstrated that high PD-L1 expression was associated with poor overall survival and disease-free survival. There was no significant correlation between PD-L1 expression and progression-free survival or disease-specific survival of SGC patients. Conclusion According to the meta-analysis, positive PD-L1 expression may play an important role as an effective marker of poor prognosis in patients with SGC. However, large-scale, prospective investigations are still needed to confirm the findings. The assessment of PD-L1 expression may aid in the personalized management of SGC.
Is myocardial strain an early marker of systolic dysfunction in obstructive sleep apnoea? Findings from a meta-analysis of echocardiographic studies

Aim: We investigated the association between obstructive sleep apnoea (OSA) and subclinical systolic dysfunction through a meta-analysis of echocardiographic studies that provided data on left ventricular (LV) mechanics as assessed by global longitudinal strain (GLS). Design: The PubMed, OVID-MEDLINE, and Cochrane library databases were systematically analyzed to search English-language articles published from inception to 31 December 2021. Studies were detected by using the following terms: ‘obstructive sleep apnea’, ‘sleep quality’, ‘sleep disordered breathing’, ‘cardiac damage’, ‘left ventricular hypertrophy’, ‘systolic dysfunction’, ‘global longitudinal strain’, ‘left ventricular mechanics’, ‘echocardiography’ and ‘speckle tracking echocardiography’. Results: The meta-analysis included 889 patients with OSA and 364 non-OSA controls from 12 studies. Compared with controls, GLS was significantly reduced in the pooled OSA group (SMD −1.24 ± 0.17, CI: −1.58 to −0.90, P < 0.0001), as well as in the normotensive OSA subgroup (SMD: −1.17 ± 0.12 CI:−1.40 to −0.95, P < 0.0001). Similar findings were obtained in sub-analyses performed separately in mild, moderate and severe OSA. This was not the case for LV ejection fraction (LVEF) (i.e. comparisons between controls vs. mild OSA, mild vs. moderate OSA, moderate vs. severe OSA). Conclusion: GLS is impaired in patients with OSA (independently from hypertension), worsening progressively from mild to moderate and severe forms, thus allowing to identify subclinical alterations of the systolic function not captured by LVEF. Therefore, myocardial strain assessment should be implemented systematically in the OSA setting to timely detect systolic dysfunction.