Miracle-dz/UniFAR-FTUs huggingface dataset:
Mesenchymal Stromal Cell Secretome Is Affected by Tissue Source and Donor Age

Abstract Variation in mesenchymal stromal cell (MSC) function depending on their origin is problematic, as it may confound clinical outcomes of MSC therapy. Current evidence suggests that the therapeutic benefits of MSCs are attributed to secretion of biologically active factors (secretome). However, the effect of donor characteristics on the MSC secretome remains largely unknown. Here, we examined the influence of donor age, sex, and tissue source, on the protein profile of the equine MSC secretome. We used dynamic metabolic labeling with stable isotopes combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify secreted proteins in MSC conditioned media (CM). Seventy proteins were classified as classically secreted based on the rate of label incorporation into newly synthesized proteins released into the extracellular space. Next, we analyzed CM of bone marrow- (n = 14) and adipose-derived MSCs (n = 16) with label-free LC-MS/MS. Clustering analysis of 314 proteins detected across all samples identified tissue source as the main factor driving variability in MSC CM proteomes. Linear modelling applied to the subset of 70 secreted proteins identified tissue-related difference in the abundance of 23 proteins. There was an age-related decrease in the abundance of CTHRC1 and LOX, further validated with orthogonal techniques. Due to the lack of flow cytometry characterization of MSC surface markers, the analysis could not account for the potential effect of cell population heterogeneity. This study provides evidence that tissue source and donor age contribute to differences in the protein composition of MSC secretomes which may influence the effects of MSC therapy.
Improvement in quality of life and sexual function in patients affected by vulvar lichen sclerosus treated with combined autologous platelet-rich plasma and fat grafting

Vulvar lichen sclerosus (LS) severely impairs patients’ quality of life. To evaluate the impact of a combined application of autologous platelet-rich plasma (PRP) and fat grafting as treatment for vulvar LS on patient quality of life. We reviewed the clinical charts of 72 patients affected by LS, who underwent regenerative surgery. The patients’ quality of life was assessed using: the Dermatology Life Quality Index (DLQI), the Skindex-29, the Female Sexual Function Index (FSFI) and the patient-administered - Clinical Scoring System (CSS). After reconstructive surgery, all scores improved: Skindex-29 (−31.8 [IQR: 42.1, −21.8] points; p<0.001), FSFI (7.6 [IQR: 2.7, 14.7)] points; p<0.001), Patient-administered CSS (−24 [IQR: −30, −15] points; p<0.001), DLQI (−9 [IQR: −17, −7] points; p<0.001), Physician-administered CSS (−5 [IQR: −7, −5] points; p<0.001), and IGA (median ΔIGA: −4, IQR: −4, −3; p<0.001). Combined treatment with PRP and fat grafting proved to be effective in improving the quality of life of patients with vulvar LS.
NOVEL PS-OME MIRNA130B-3P REDUCES INFLAMMATION AND INJURY AND IMPROVES SURVIVAL AFTER RENAL ISCHEMIA-REPERFUSION INJURY

ABSTRACT Introduction: Acute kidney injury (AKI) is a prevalent medical disorder characterized by a sudden decline in kidney function, often because of ischemia/reperfusion (I/R) events. It is associated with significant chronic complications, and currently available therapies are limited to supportive measures. Extracellular cold-inducible RNA-binding protein (eCIRP) has been identified as a mediator that potentiates inflammation after I/R injury. However, it has been discovered that miRNA 130b-3p acts as an endogenous inhibitor of eCIRP. To address the inherent instability of miRNA in vivo, a chemically modified miRNA mimic called PS-OME miR130 was developed. We hypothesize that administration of PS-OME miR130 after renal I/R can lead to reduced inflammation and injury in a murine model of AKI. Methods: C57BL/6 male mice underwent renal I/R by clamping of bilateral renal hilum for 30 min or sham operation. Immediately after closure, mice were intravenously administered vehicle (phosphate-buffered saline) or PS-OME miR130 at a dose of 12.5 nmol/mouse. Blood and kidneys were collected after 24 h for further analysis. Separately, mice underwent renal I/R and administered vehicle or treatment and, survival was monitored for 10 days. Results: After renal I/R, mice receiving vehicle showed a significant increase in serum markers of kidney injury and inflammation including blood urea nitrogen, NGAL, KIM-1, and IL-6. After treatment with PS-OME miR130, these markers were significantly decreased. Kidney tissue mRNA expression for injury and inflammation markers including NGAL, KIM-1, KC, and MIP-2 were increased after renal I/R; however, these markers showed a significant reduction with PS-OME miR130 treatment. Histologically, treatment with PS-OME miR130 showed a significant decrease in neutrophil infiltration and injury severity score, and decreased apoptosis. In the 10-day survival study, mice in the treatment group showed a significant reduction in mortality as compared with vehicle group. Conclusion: In a murine renal I/R model, the administration of PS-OME miR130, a direct eCIRP antagonistic miRNA mimic, resulted in the reduction of kidney inflammation and injury, and improved survival. PS-OME miR130 holds promise to be developed as novel therapeutic for AKI as an adjunct to the standard of care.
Prevalence of cognitive impairment and cognitive improvement in patients with systemic lupus erythematosus during a 6-month follow-up study

Objectives The Montreal Cognitive Assessment (MoCA) is a simple and reliable screening tool for early detection for cognitive impairment in systemic lupus erythematosus (SLE). Most previous studies were cross-sectional with small samples. Research on long-term cognitive changes and reversibility is limited. This study aimed to establish the prevalence of cognitive impairment and changes in SLE patients after 6 months and the associated factors. Methods A prospective study was conducted in 200 patients with SLE between April 2021 and March 2022. Demographic data, disease activity, and medications were recorded. MoCA was administered at baseline and 6 months; for Thais, scores 17–24 indicate mild cognitive impairment, while ≤16 signifies severe impairment. Multivariate analysis identified factors associated with cognitive impairment and improvement. Results The patients’ median age was 44 years (range: 19–73), 96% were female, and 55% had < 12 years of education. The median disease duration was 11 years (range: 0–51.8), and 79% of patients had inactive disease. Cognitive impairment was found in 70% of patients (mild, 63%; severe, 7%). The most often affected domains were delayed recall (82%), abstraction (80.5%), language (76%) and visuospatial/executive function (70.5%), whereas orientation and naming were the least involved. Factors significantly associated with cognitive impairment were age > 40 years (OR, 3.71; 95% CI, 1.72–8.00), formal education < 12 years (OR, 3.11; 95% CI, 1.45–6.63), and prednisolone use (OR, 2.21; 95% CI, 1.08–4.51). Sixty-six (38.2%) of 173 patients completing the 6-month re-evaluation exhibited cognitive changes (52 [30.1%] improved; 14 [8.1%] deteriorated). Except for delayed recall, all commonly affected domains showed significant improvement. Disease activity, prednisolone, antimalarials, or immunosuppressant use did not predict cognitive improvement. Conclusions Mild cognitive impairment is prevalent among patients with SLE. Due to the possibility of reversibility, early recognition and additional research to identify relevant factors are required.
A Randomized Controlled Crossover Trial of Virtual Reality in Maintenance Cardiovascular Rehabilitation in a Low-Resource Setting: Impact on Adherence, Motivation, and Engagement.

OBJECTIVE The purpose of this study was to investigate the effects of adding virtual reality (VR) to maintenance cardiac rehabilitation (CR); it was hypothesized to increase adherence, motivation, and engagement. METHODS This study was a randomized, 1:1 concealed-allocation, single-blinded, 2 parallel-arm crossover trial. Blinded assessments were undertaken at baseline (mid-program), 12 weeks, and 24 weeks after baseline. The setting was a single CR program of unlimited duration in Brazil. Participants were patients with cardiovascular diseases or risk factors who had been in the program for ≥3 months. The CR program consisted of 3 supervised exercise sessions per week. In the VR arm, participants had 1 VR session of the 3 per week during the initial 12 weeks of the trial; this was withdrawn the subsequent 12 weeks. Measures were: program adherence (% of 3 sessions/week over 12 weeks; ascertained in all participants), motivation (Behavioral Regulation in Exercise Questionnaire 3), and engagement (User Engagement Scale, adapted; vigor, dedication, and absorption subscales); all 3 were primary outcomes. RESULTS Sixty-one (83.6%) patients were randomized (n = 30 to CR + VR); 54 (88.5%) were retained at 12 and 24 weeks. At baseline, participants had been in CR on average 7 years and had high engagement and motivation. CR + VR resulted in a significant increase in adherence at 12 weeks (baseline = 72.87%; 12 weeks = 82.80%), with significant reductions at 24 weeks when VR was withdrawn (65.48%); in the usual CR care arm, there were no changes over time. There was a significant effect for arm, with significantly higher adherence in the CR + VR arm than usual CR at 12 weeks (73.51%). Motivation decreased significantly from baseline to 12 weeks (4.32 [SD = 0.37] vs 4.02 [SD = 0.76]) and significantly increased from 12 to 24 weeks in the CR + VR arm (4.37 [SD = 0.36]). Absorption was significantly lower at 12 weeks in the CR + VR arm (6.79 [SD = 0.37] vs 6.20 [SD = 1.01]). CONCLUSION Although VR increased program adherence, interspersing it with usual CR sessions actually decreased patient motivation and absorption. IMPACT Supplementing a maintenance CR program with VR using "exergames" resulted in significantly greater adherence (8% increase or 3/36 sessions), and this was quite a robust effect given it was extinguished with the removal of VR. However, contrary to hypotheses, offering 1 session of VR per week and 2 of usual CR exercise was related to lower motivation and absorption, which has implications for how clinicians design programs for this patient population.
Pre-existing Interstitial Lung Abnormalities and Immune Checkpoint Inhibitor-Related Pneumonitis in Solid Tumors: A Retrospective Analysis

Abstract Background Immune checkpoint inhibitors (ICIs) have demonstrated efficacy over previous cytotoxic chemotherapies in clinical trials among various tumors. Despite their favorable outcomes, they are associated with a unique set of toxicities termed as immune-related adverse events (irAEs). Among the toxicities, ICI-related pneumonitis has poor outcomes with little understanding of its risk factors. This retrospective study aimed to investigate whether pre-existing interstitial lung abnormality (ILA) is a potential risk factor for ICI-related pneumonitis. Materials and Methods Patients with non-small cell lung cancer, malignant melanoma, renal cell carcinoma, and gastric cancer, who was administered either nivolumab, pembrolizumab, or atezolizumab between September 2014 and January 2019 were retrospectively reviewed. Information on baseline characteristics, computed tomography findings before administration of ICIs, clinical outcomes, and irAEs were collected from their medical records. Pre-existing ILA was categorized based on previous studies. Results Two-hundred-nine patients with a median age of 68 years were included and 23 (11.0%) developed ICI-related pneumonitis. While smoking history and ICI agents were associated with ICI-related pneumonitis (P = .005 and .044, respectively), the categories of ILA were not associated with ICI-related pneumonitis (P = .428). None of the features of lung abnormalities were also associated with ICI-related pneumonitis. Multivariate logistic analysis indicated that smoking history was the only significant predictor of ICI-related pneumonitis (P = .028). Conclusion This retrospective study did not demonstrate statistically significant association between pre-existing ILA and ICI-related pneumonitis, nor an association between radiologic features of ILA and ICI-related pneumonitis. Smoking history was independently associated with ICI-related pneumonitis. Further research is warranted for further understanding of the risk factors of ICI-related pneumonitis.
The Relationship Between Sea Breeze Forcing and HF Radar-Derived Surface Currents in Monterey Bay

Abstract : Despite the importance of sea breeze, only Hendrickson and MacMahan s research has been done to determine sea breeze effects in Monterey Bay; other than that not much research has been done. In this thesis, CODAR SeaSonde radars are used to map the surface current in Monterey Bay. Temperature, wind speed and wind direction are analyzed for five locations to establish the algorithm for determining the sea breeze days in Monterey Bay. Harmonic analysis is used to understand the relationship between sea breeze and high frequency (HF) radar-derived surface currents. To explain the cause of the peaks and lows in the amplitude of the sea breeze as shown by the harmonic analysis, coastal jet influences, boundary layer height changes, temperature gradient variations and cloudiness are investigated. Current patterns clearly respond to changing sea breeze strength with the strongest amplitudes corresponding to days with fully developed coastal jets. No coastal jet, lower amplitude sea breeze days, however, appear to have a more classical response in terms of wind direction changes. It is understood that rapid decrease of the amplitude of sea breeze in harmonic analysis is the day with sea breeze including obvious wind shifting, and rapid increase is the day when strong synoptic effect is seen obviously over the region.
Fluoxetine rescues the depressive-like behaviour induced by reserpine and the altered emotional behaviour induced by nicotine withdrawal in zebrafish: Involvement of tyrosine hydroxylase

Background: Nicotine cessation leads to anxiety and depression. Aims: The suitability of the zebrafish model of anhedonia using reserpine and fluoxetine was evaluated. Fluoxetine was also used to reduce nicotine withdrawal-induced anhedonic state. Methods: Zebrafish were exposed to reserpine (40 mg/l) and then to fluoxetine (0.1 mg/l) for 1 week. Anhedonia was evaluated in the Novel Tank Diving and Compartment Preference tests. Another group was exposed to nicotine (1 mg/l/2 weeks) and then exposed to fluoxetine. Anxiety and anhedonia were evaluated 2–60 days after. Tyrosine hydroxylase (TH) immunoreactivity and microglial morphology (labelled by 4C4 monoclonal antibody) in the parvocellular pretectal nucleus (PPN), dorsal part, and of calcitonin gene-related peptide (CGRP) in the hypothalamus were also analysed. Results: Less time in the top and increased latency to the top in reserpine compared to a drug-free group was found. Fluoxetine rescued reserpine-induced the reduced time in the top. Seven and 30 days after nicotine withdrawal more time in the bottom and similar time in the Compartment Preference test, rescued by fluoxetine, were shown. In the PPN, 30-day withdrawal induced an increase in TH immunoreactivity, but fluoxetine induced a further significant increase. No changes in PPN microglia morphology and hypothalamic CGRP were detected. Conclusions: Our findings validate the suitability of the zebrafish model of anhedonia using the reserpine-induced depression-like behaviour and the predictivity using fluoxetine. Fluoxetine rescued nicotine withdrawal-induced anhedonic state, opening the possibility to screen new drugs to alleviate anxiety and depression in smokers during abstinence.
Vicarious facilitation of facial responses to pain

Observing facial expressions of pain has been shown to lead to increased subjective, neural and autonomic pain responses. Surprisingly, these vicarious facilitation effects on its corresponding response channel, namely facial responses to pain have mostly been neglected. We aim to examine whether the prior exposure to facial expressions of pain leads to a facilitation of facial responses to experimental pain; and whether this facilitation is linked to the valence (pain vs. neutral expression) or also linked to specific motor‐features of the facial pain expressions (different facial muscle movements).
Total-Body Multiparametric PET Quantification of 18F-FDG Delivery and Metabolism in the Study of Coronavirus Disease 2019 Recovery

Visual Abstract Conventional whole-body static 18F-FDG PET imaging provides a semiquantitative evaluation of overall glucose metabolism without insight into the specific transport and metabolic steps. Here we demonstrate the ability of total-body multiparametric 18F-FDG PET to quantitatively evaluate glucose metabolism using macroparametric quantification and assess specific glucose delivery and phosphorylation processes using microparametric quantification for studying recovery from coronavirus disease 2019 (COVID-19). Methods: The study included 13 healthy subjects and 12 recovering COVID-19 subjects within 8 wk of confirmed diagnosis. Each subject had a 1-h dynamic 18F-FDG scan on the uEXPLORER total-body PET/CT system. Semiquantitative SUV and the SUV ratio relative to blood (SUVR) were calculated for different organs to measure glucose utilization. Tracer kinetic modeling was performed to quantify the microparametric blood-to-tissue 18F-FDG delivery rate K1 and the phosphorylation rate k3, as well as the macroparametric 18F-FDG net influx rate (Ki). Statistical tests were performed to examine differences between healthy subjects and recovering COVID-19 subjects. The effect of COVID-19 vaccination was also investigated. Results: We detected no significant difference in lung SUV but significantly higher lung SUVR and Ki in COVID-19 recovery, indicating improved sensitivity of kinetic quantification for detecting the difference in glucose metabolism. A significant difference was also observed in the lungs with the phosphorylation rate k3 but not with K1, which suggests that glucose phosphorylation, rather than glucose delivery, drives the observed difference of glucose metabolism. Meanwhile, there was no or little difference in bone marrow 18F-FDG metabolism measured with SUV, SUVR, and Ki but a significantly higher bone marrow K1 in the COVID-19 group, suggesting a difference in glucose delivery. Vaccinated COVID-19 subjects had a lower lung Ki and a higher spleen Ki than unvaccinated COVID-19 subjects. Conclusion: Higher lung glucose metabolism and bone marrow glucose delivery were observed with total-body multiparametric 18F-FDG PET in recovering COVID-19 subjects than in healthy subjects, implying continued inflammation during recovery. Vaccination demonstrated potential protection effects. Total-body multiparametric PET of 18F-FDG can provide a more sensitive tool and more insights than conventional whole-body static 18F-FDG imaging to evaluate metabolic changes in systemic diseases such as COVID-19.
A Rationale and Framework for Activating Employers as Agents of Change in the Implementation of Lifestyle as Medicine

Achieving the vision of human flourishing that Sundelius envisions will require a fundamental shift in our current approach to healthcare. Many would argue that the transformation is long overdue. Chronic diseases take an enormous toll on individuals’ quality of life and are a key driver of healthcare costs—in part because 40% of U.S. adults have 2 or more chronic conditions. The Centers for Disease Control reported that chronic health conditions account for 90% of our nation’s $4.1 trillion in annual healthcare costs. Even more troubling is the fact that the prevalence and burden of chronic diseases continues to rise, often disproportionately affecting individuals from Black and Brown communities. A recent study reported that, from 1999-2020, 1.63 million excess deaths and more than 80 million excess years of life lost were experienced by Black Americans compared to white Americans, with cardiovascular disease being the leading driver of excess mortality. Declining life expectancy in U.S.—now at lowest since 1996–is partially attributable to cardiovascular disease, and young adults represent growing proportion of cardiovascular disease events. The prevalence of cardiovascular risk factors (most notably diabetes and obesity) among adults aged 20-44 increased from 2009-2020 in the U.S.—and in particular among Black, Hispanic, and Mexican Americans. Recent modeling studies predict an increase in diabetes in the U.S. among individuals younger than 20 that is expected to disproportionately impact Black youth. Despite spending more per capita on healthcare than other developed nations, our current healthcare system is failing—and that failure is captured in Americans’ sentiment of widespread dissatisfaction. In a recent Harris Poll, 60% of U.S. adults gave the healthcare system a grade of C or worse. There is, therefore, an urgent need for increased implementation of lifestyle change as medicine, but barriers remain (eg, current reimbursement models). The predominantly fee-for-service healthcare model in the United States is riddled with perverse incentives that lead to a prioritization of pharmacological and procedure-based interventions rather than addressing root causes. What is clear is the need to redefine healthcare—to move away froma systemof sick care to a newmodel focused on centering equitable access to a healthy lifestyle as a key pillar of prevention, management, and treatment of chronic diseases that are consuming far too many healthcare dollars and robbing us of precious time with loved ones. Lifestyle modifications (eg, plant-based diets, physical activity, adequate sleep, strong social connections) can prevent, treat, and in some cases reverse chronic conditions. The quintuple aim for healthcare adds health equity to the prior priorities of improved patient experience, improved outcomes, lower costs, and clinician well-being—Lifestyle as Medicine has potential to help achieve all of those critical objectives. In This Issue
Management of Glomerular Proteinuria: A Commentary

It is widely accepted that proteinuria reduction is an appropriate therapeutic goal in chronic proteinuric kidney disease. Based on large randomized controlled clinical trials (RCT), ACE inhibitor (ACEI) and angiotensin receptor blocker (ARB) therapy have emerged as the most important antiproteinuric and renal protective interventions. However, there are numerous other interventions that have been shown to be antiproteinuric and, therefore, likely to be renoprotective. Un-fortunately testing each of these antiproteinuric therapies in RCT is not feasible. The nephrologist has two choices: restrict antiproteinuric therapies to those shown to be effective in RCT or expand the use of antiproteinuric therapies to include those that, although unproven, are plausibly effective and prudent to use. The goal of this work is to provide the documentation needed for the nephrologist to choose between these strategies. This work de-scribes 25 separate interventions that are either antiproteinuric or may block injurious mechanisms of proteinuria. Each intervention is assigned a level of recommendation (Level 1 is the highest; Level 3 is the lowest) according to the strength of the evidence supporting its antiproteinuric and renoprotective efficacy. Patho-physiologic mechanisms possibly involved are also discussed. The number of interventions at each level of recommendation are: Level 1, 2, Our experience we can in most patients the majority of