Miracle-dz/UniFAR-FTUs huggingface dataset:
Endothelial progenitor cell transplantation alleviated ischemic brain injury via inhibiting C3/C3aR pathway in mice

Endothelial progenitor cell transplantation is a potential therapeutic approach in brain ischemia. However, whether the therapeutic effect of endothelial progenitor cells is via affecting complement activation is unknown. We established a mouse focal ischemia model (n = 111) and transplanted endothelial progenitor cells into the peri-infarct region immediately after brain ischemia. Neurological outcomes and brain infarct/atrophy volume were examined after ischemia. Expression of C3, C3aR and pro-inflammatory factors were further examined to explore the role of endothelial progenitor cells in ischemic brain. We found that endothelial progenitor cells improved neurological outcomes and reduced brain infarct/atrophy volume after 1 to 14 days of ischemia compared to the control (p < 0.05). C3 and C3aR expression in the brain was up-regulated at 1 day up to 14 days (p < 0.05). Endothelial progenitor cells reduced astrocyte-derived C3 (p < 0.05) and C3aR expression (p < 0.05) after ischemia. Endothelial progenitor cells also reduced inflammatory response after ischemia (p < 0.05). Endothelial progenitor cell transplantation reduced astrocyte-derived C3 expression in the brain after ischemic stroke, together with decreased C3aR and inflammatory response contributing to neurological function recovery. Our results indicate that modulating complement C3/C3aR pathway is a novel therapeutic target for the ischemic stroke.
Effects of horse-riding therapy and rhythm and music-based therapy on functional mobility in late phase after stroke

BACKGROUND: Persons with stroke commonly have residual neurological deficits that seriously hamper mobility. OBJECTIVE: To investigate whether horse-riding therapy (H-RT) and rhythm and music-based therapy (R-MT) affect functional mobility in late phase after stroke. METHODS: This study is part of a randomized controlled trial in which H-RT and R-MT was provided twice weekly for 12 weeks. Assessment included the timed 10-meter walk test (10 mWT), the six-minute walk test (6 MWT) and Modified Motor Assessment Scale (M-MAS). RESULTS: 123 participants were assigned to H-RT (n = 41), R-MT (n = 41), or control (n = 41). Post-intervention, the H-RT group completed the 10 mWT faster at both self-selected (–2.22 seconds [95% CI, –3.55 to –0.88]; p = 0.001) and fast speed (–1.19 seconds [95% CI, –2.18 to –0.18]; p = 0.003), with fewer steps (–2.17 [95% CI, –3.30 to –1.04]; p = 0.002 and –1.40 [95% CI, –2.36 to –0.44]; p = 0.020, respectively), as compared to controls. The H-RT group also showed improvements in functional task performance as measured by M-MAS UAS (1.13 [95% CI, 0.74 to 1.52]; p = 0.001). The gains were partly maintained at 6 months among H-RT participants. The R-MT did not produce any immediate gains. However, 6 months post-intervention, the R-MT group performed better with respect to time; –0.75 seconds [95% CI, –1.36 to –0.14]; p = 0.035) and number of steps –0.76 [95% CI, –1.46 to –0.05]; p = 0.015) in the 10 mWT at self-selected speed. CONCLUSIONS: The present study supports the efficacy of H-RT in producing immediate gains in gait and functional task performance in the late phase after stroke, whereas the effectiveness of R-MT is less clear.
Interplay between orientation at electrodes and copper activation of Thermus thermophilus laccase for O2 reduction.

Multicopper oxidases (MCOs) catalyze the oxidation of a variety of substrates while reducing oxygen into water through four copper atoms. As an additional feature, some MCOs display an enhanced activity in solution in the presence of Cu2+. This is the case of the hyperthermophilic laccase HB27 from Thermus thermophilus, the physiologic role of which is unknown. As a particular feature, this enzyme presents a methionine rich domain proposed to be involved in copper interaction. In this work, laccase from T. thermophilus was produced in E. coli, and the effect of Cu2+ on its electroactivity at carbon nanotube modified electrodes was investigated. Direct O2 electroreduction is strongly dictated by carbon nanotube surface chemistry in accordance with the enzyme dipole moment. In the presence of Cu2+, an additional low potential cathodic wave occurs, which was never described earlier. Analysis of this wave as a function of Cu2+ availability allows us to attribute this wave to a cuprous oxidase activity displayed by the laccase and induced by copper binding close to the Cu T1 center. A mutant lacking the methionine-rich hairpin domain characteristic of this laccase conserves its copper activity suggesting a different site of copper binding. This study provides new insight into the copper effect in methionine rich MCOs, and highlights the utility of the electrochemical method to investigate cuprous oxidase activity and to understand the physiological role of these MCOs.
Improved therapeutic effects on diabetic foot by human mesenchymal stem cells expressing MALAT1 as a sponge for microRNA-205-5p

Diabetic foot (DF) is a common complication of high severity for diabetes, a prevalent metabolic disorder that affects billions of people worldwide. Mesenchymal stem cells (MSCs) have a demonstrative therapeutic effect on DF, through their generation of pro-angiogenesis factors, like vascular endothelial growth factor (VEGF). Recently, genetically modified MSCs have been used in therapy and we have shown that depletion of micoRNA-205-5p (miR-205-5p) in human MSCs promotes VEGF-mediated therapeutic effects on DF. Here, we showed that a long non-coding RNA (lncRNA), MALAT1, is a competing endogenous RNA (ceRNA) for miR-205-5p, and is low expressed in human MSCs. Ectopic expression of MALAT1 in human MSCs significantly decreased miR-205-5p levels, resulting in upregulation of VEGF production and improved in vitro endothelial cell tube formation. In a DF model in immunodeficient NOD/SCID mice, transplantation of human miR-205-5p-depleted MSCs exhibited better therapeutic effects on DF recovery than control MSCs. Moreover, MALAT1-expressing MSCs showed even better therapeutic effects on DF recovery than miR-205-5p-depleted MSCs. This difference in DF recovery was shown to be associated with the levels of on-site vascularization. Together, our data suggest that MALAT1 functions as a sponge RNA for miR-205-5p to increase therapeutic effects of MSCs on DF.
Development of a perioperative venous thromboembolism prophylaxis algorithm for pediatric orthopedic surgical patients

Abstract Venous thromboembolism (VTE) has been recognized as a rare but potentially serious complication in pediatric orthopedic patients. However, standardized guidelines for screening and management of at-risk patients do not exist. The aim of the study was to develop a VTE prophylaxis screening tool for postoperative orthopedic patients after conducting an institutional needs assessment survey. A needs assessment survey was conducted after institutional ethics board approval. Development of perioperative VTE prophylaxis algorithm for pediatric orthopedic surgical patients was planned after thorough literature review, consultation with national and international experts as well as using a modified nominal and consensus development conference (serial meetings) method for reaching a consensus. NAS as well as discussion with stakeholders indicated support for development of perioperative VTE prophylaxis algorithm for orthopedic patients. Using above methods, a VTE prophylaxis algorithm was developed and implemented at IWK Health Center. The present study involved development of a perioperative VTE prophylaxis algorithm for pediatric orthopedic surgical patients that could be easily and rapidly administered as a point of care assessment tool.
QKI regulates adipose tissue metabolism by acting as a brake on thermogenesis and promoting obesity

Adipose tissue controls numerous physiological processes, and its dysfunction has a causative role in the development of systemic metabolic disorders. The role of posttranscriptional regulation in adipose metabolism has yet to be fully understood. Here, we show that the RNA‐binding protein quaking (QKI) plays an important role in controlling metabolic homeostasis of the adipose tissue. QKI‐deficient mice are resistant to high‐fat‐diet (HFD)‐induced obesity. Additionally, QKI depletion increased brown fat energy dissipation and browning of subcutaneous white fat. Adipose tissue‐specific depletion of QKI in mice enhances cold‐induced thermogenesis, thereby preventing hypothermia in response to cold stimulus. Further mechanistic analysis reveals that QKI is transcriptionally induced by the cAMP‐cAMP response element‐binding protein (CREB) axis and restricts adipose tissue energy consumption by decreasing stability, nuclear export, and translation of mRNAs encoding UCP1 and PGC1α. These findings extend our knowledge of the significance of posttranscriptional regulation in adipose metabolic homeostasis and provide a potential therapeutic target to defend against obesity and its related metabolic diseases.
Single-cell analysis uncovers that metabolic reprogramming by ErbB2 signaling is essential for cardiomyocyte proliferation in the regenerating heart

While the heart regenerates poorly in mammals, efficient heart regeneration occurs in zebrafish. Studies in zebrafish have resulted in a model in which preexisting cardiomyocytes dedifferentiate and reinitiate proliferation to replace the lost myocardium. To identify which processes occur in proliferating cardiomyocytes we have used a single-cell RNA-sequencing approach. We uncovered that proliferating border zone cardiomyocytes have very distinct transcriptomes compared to the nonproliferating remote cardiomyocytes and that they resemble embryonic cardiomyocytes. Moreover, these cells have reduced expression of mitochondrial genes and reduced mitochondrial activity, while glycolysis gene expression and glucose uptake are increased, indicative for metabolic reprogramming. Furthermore, we find that the metabolic reprogramming of border zone cardiomyocytes is induced by Nrg1/ErbB2 signaling and is important for their proliferation. This mechanism is conserved in murine hearts in which cardiomyocyte proliferation is induced by activating ErbB2 signaling. Together these results demonstrate that glycolysis regulates cardiomyocyte proliferation during heart regeneration.
A feasibility study of a home-based lifestyle-integrated physical exercise training and home modification for community-living older people (Part 2): the FIT-at-Home fall prevention program

Abstract Purpose This study was conducted in a home-based context where trained occupational therapists delivered progressive physical exercise training and home modification intervention for preventing falls, namely the FIT-at-Home intervention. We assessed the feasibility of the intervention’s content and mode of delivery from the occupational therapists’ perspective as well as the feasibility of study procedures. Methods We used a mixed-methods approach, which generated qualitative data from 14 OTs’ after delivering the intervention via interviews and quantitative data of the study procedures via questionnaires and documentation sheets. Results In total, 16 of the 17 older people completed the intervention. Of 9 recorded falls, no serious physical problems occurred. Qualitative data suggested that the intervention content and mode was feasible. Only minor adaptations to the program are needed based on the users’ feedback. The main benefit was seen in the fact that simple exercises can be integrated into everyday life for older people with restricted mobility. Conclusion The FIT-at-Home intervention comprising lifestyle-integrated balance and strength exercises and home safety is feasible for occupational therapists to deliver. The findings will help to further refine the intervention and study procedures. Implications for rehabilitation Falling is a frequent and serious health problem for many community-living older people, and the incidence of injurious falls increases with advancing age. Home visiting programs comprising physical exercise training and home modification appear to be beneficial for older people with poor health, functional limitations, and limited mobility. This study indicates that it is feasible to introduce lifestyle-integrated balance and strength exercises, performed as part of daily routine for older people at risk of falling. Behavioural self-management strategies have the potential to improve the implementation of exercises during the course of rehabilitation treatment and afterward.
What are the Risk Factors for Deep Infection in AO/OTA 43C Pilon Fractures?

OBJECTIVES To determine the risk factors for deep infection in AO/OTA 43C pilon fractures DESIGN:: Retrospective, case control SETTING:: Single institution, Level 1 trauma center PARTICIPANTS:: All patients with 43C pilon fractures treated over a 5-year period with followup to bony union. One hundred fifty of 169 of identified patients met inclusion criteria. INTERVENTION Operative treatment of tibial pilon fracture MAIN OUTCOME MEASUREMENTS:: Deep infection; patient demographics, Gustilo-Anderson Classification, location of open fracture wounds, surgical approaches RESULTS:: The overall rate of deep infection was 16.7%. BMI, tobacco use, and diabetes were not associated with deep infection. The rate of Gustilo-Anderson type 3A and 3B fractures was significantly higher in those with infection, but the overall open fracture rate was not significantly different between the groups. Medial and anterior open fracture wound location were significantly associated with deep infection while lateral open fracture wound location was not. In closed fractures anteromedial and anterolateral approaches were not significantly associated with infection, but posterolateral approach was associated with deep infection. Segmental bone loss and the need for soft tissue coverage were the only independent risk factors for deep infection. CONCLUSIONS High grade open pilon fractures are at risk of deep infection, and medial/anterior open fracture wounds are particularly vulnerable to developing deep infection. The anteromedial/anterolateral surgical approaches should be selected based upon a complete understanding of the fracture pattern and soft tissue injury, however the posterolateral approach to the tibia should be used with some caution. Ultimately injury factors (Segmental bone loss, need for soft tissue coverage) appear to be the most important variables in driving deep infection and a complete understanding of the bone and soft tissue injury is needed to manage these injuries effectively.
Examining effects of mother and father warmth and control on child externalizing and internalizing problems from age 8 to 13 in nine countries

Abstract This study used data from 12 cultural groups in 9 countries (China, Colombia, Italy, Jordan, Kenya, Philippines, Sweden, Thailand, and United States; N = 1,315) to investigate bidirectional associations between parental warmth and control, and child externalizing and internalizing behaviors. In addition, the extent to which these associations held across mothers and fathers and across cultures with differing normative levels of parent warmth and control were examined. Mothers, fathers, and children completed measures when children were ages 8 to 13. Multiple-group autoregressive cross-lagged structural equation models revealed that evocative child-driven effects of externalizing and internalizing behavior on warmth and control are ubiquitous across development, cultures, mothers, and fathers. Results also reveal that parenting effects on child externalizing and internalizing behaviors, though rarer than child effects, extend into adolescence when examined separately in mothers and fathers. Father-based parent effects were more frequent than mother effects. Most parent- and child-driven effects appear to emerge consistently across cultures. The rare culture-specific parenting effects suggested that occasionally the effects of parenting behaviors that run counter to cultural norms may be delayed in rendering their protective effect against deleterious child outcomes.
Gastropathy in patients with Wilson disease

Abstract Background: Gastrointestinal symptoms are common in patients with Wilson disease (WD) and may be related to the disease itself or to adverse drug reactions (ADRs). Aim: To investigate gastroscopy findings in patients with WD and to analyze the risk of gastropathy in the context of different manifestations and treatments of WD as well as Helicobacter pylori infection status. Methods: This cross-sectional study included patients diagnosed or monitored for WD between 2007 and 2017. All enrolled patients were examined with gastroscopy and checked for infection with a urease test. Based on predominant manifestations, WD was classified as pre-symptomatic, hepatic (only liver symptoms) or neurological. Patients were divided into three treatment groups: untreated, treated with d-penicillamine (DPA) or zinc sulfate therapy. Results: Of 115 patients, 58 were male and the median age was 30 years. Gastropathy was observed in 65.2% of all patients. Factors that increased the risk of gastropathy were zinc sulfate (odds ratio [OR] = 3.01; 95% confidence interval [CI]: 1.12–8.09, p = .03), H. pylori infection (OR = 2.96; 95%CI: 1.34–6.56, p = .01) and neurological manifestations (OR = 2.55; 95%CI: 1.16–5.60, p = .02). In total, 9.6% of patients had gastric or duodenal ulcers and 29.6% had esophageal varices but no difference was seen by treatment status. In multivariate analysis, zinc sulfate remained associated with higher risk of gastropathy compared with no treatment (OR = 4.57; 95%CI: 1.21–17.19; p = .03) and DPA (OR = 6.28; 95%CI: 1.43–27.56; p = .01). Conclusions: Our results show that gastropathy in WD may be influenced by the treatment used. Keypoints In a retrospective study of 115 patients with Wilson’s disease, gastric injury was frequent. Patients receiving zinc sulfate had increased gastropathy risk compared with those receiving no treatment or d-penicillamine.
The SmoCar Study: A Caribbean-Based Multicenter Study on the Prevalence and Disparities Linked to Smoking and Gingival Health

The aim of the SmoCar (Smoking in the Caribbean) study was to estimate the prevalence of smoking and the disparities in the smoking practices of three regions in the Caribbean: Jamaica, Dominican Republic, and Puerto Rico. The secondary objective was to assess the prevalence and severity of gingivitis in relation to the smoking practices. The study population comprised 1,847 (weighted N = 1,830) individuals (18 years and older) who were volunteer participants from the capitals of Jamaica, Dominican Republic, and Puerto Rico. A structured interview was used to assess the participants’ smoking behaviors. The gingival index was used to determine the extent of gingival inflammation. Polytomous regression was used to estimate the adjusted odds ratios (aORs) for smoking status (current, past, or never), according to risk factors (sex, age-group, education, marital status, tooth-brushing frequency, and city of residence). Logistic regression models were used to assess the associations between different smoking status variables and mild to moderate/severe gingivitis. The majority of the participants were never-smokers, with current smokers being found most commonly in Kingston (33.22%), followed by San Juan (12.76%) and Santo Domingo (8.8%). Both current (aOR = 2.22, 95% confidence interval [1.45, 3.40]) and past (aOR = 1.87, 95% confidence interval [1.19, 2.93]) smoking (vs. never smoking) was strongly associated with severe gingivitis. Smoking was the most prevalent in Jamaicans and the least prevalent in Dominicans. The study population of current smokers was found to have a fourfold increased risk of severe gingivitis and a twofold increased risk of moderate gingivitis.
A modality‐specific dysfunction of pain processing in schizophrenia

Clinical observations showed that schizophrenia (SCZ) patients reported little or no pain under various conditions that are commonly associated with intense painful sensations, leading to a higher risk of morbidity and mortality. However, this phenomenon has received little attention and its underlying neural mechanisms remain unclear. Here, we conducted two experiments combining psychophysics, electroencephalography (EEG), and functional magnetic resonance imaging (fMRI) techniques to investigate neural mechanisms of pain insensitivity in SCZ patients. Specifically, we adopted a stimulus–response paradigm with brief stimuli of different sensory modalities (i.e., nociceptive, non‐nociceptive somatosensory, and auditory) to test whether pain insensitivity in SCZ patients is supra‐modal or modality‐specific, and used EEG and fMRI techniques to clarify its neural mechanisms. We observed that perceived intensities to nociceptive stimuli were significantly smaller in SCZ patients than healthy controls, whereas perceived intensities to non‐nociceptive somatosensory and auditory stimuli were not significantly different. The behavioral results were confirmed by stimulus‐evoked brain responses sampled by EEG and fMRI techniques, thus verifying the modality‐specific nature of the modulation of nociceptive information processing in SCZ patients. Additionally, significant group differences were observed in the spectral power of alpha oscillations in prestimulus EEG and the seed‐based functional connectivity in resting‐state fMRI (seeds: the thalamus and periaqueductal gray that are key nodes in ascending and descending pain pathways respectively), suggesting a possible contribution of cortical–subcortical dysfunction to the phenomenon. Overall, our study provides insight into the neural mechanisms of pain insensitivity in SCZ and highlights a need for systematic assessments of their pain‐related diseases.
Do Medicare and Medicaid Payer-Mix Change After the Privatization of Public Hospitals?

This study assessed the impact of public hospitals’ privatization on payer-mix. We used a national sample of nonfederal, acute care, public hospitals in 1997 and followed them through 2013, resulting in a cohort of 492 hospitals (8,335 hospital-year observations). Privatization to for-profit (FP) status was associated with a greater increase in Medicare payer-mix (β = 0.13; p ≤ .001), compared with a smaller increase for privatization to not-for-profit (NFP) status (β = 0.02; p ≤ .05). FP privatization was associated with a greater decrease in Medicaid payer-mix (β = −0.09; p ≤ .001), compared with NFP privatization (nonsignificant). There is a larger change in payer-mix after FP privatization than after NFP privatization.