Miracle-dz/UniFAR-FTUs huggingface dataset:
Atrial myxomas arise from multipotent cardiac stem cells

Abstract Aims Cardiac myxomas usually develop in the atria and consist of an acid-mucopolysaccharide-rich myxoid matrix with polygonal stromal cells scattered throughout. These human benign tumours are a valuable research model because of the rarity of cardiac tumours, their clinical presentation and uncertain origin. Here, we assessed whether multipotent cardiac stem/progenitor cells (CSCs) give rise to atrial myxoma tissue. Methods and results Twenty-three myxomas were collected and analysed for the presence of multipotent CSCs. We detected myxoma cells positive for c-kit (c-kitpos) but very rare Isl-1 positive cells. Most of the c-kitpos cells were blood lineage-committed CD45pos/CD31pos cells. However, c-kitpos/CD45neg/CD31neg cardiac myxoma cells expressed stemness and cardiac progenitor cell transcription factors. Approximately ≤10% of the c-kitpos/CD45neg/CD31neg myxoma cells also expressed calretinin, a characteristic of myxoma stromal cells. In vitro, the c-kitpos/CD45neg/CD31neg myxoma cells secrete chondroitin-6-sulfate and hyaluronic acid, which are the main components of gelatinous myxoma matrix in vivo. In vitro, c-kitpos/CD45neg/CD31neg myxoma cells have stem cell properties being clonogenic, self-renewing, and sphere forming while exhibiting an abortive cardiac differentiation potential. Myxoma-derived CSCs possess a mRNA and microRNA transcriptome overall similar to normal myocardium-derived c-kitpos/CD45neg/CD31negCSCs , yet showing a relatively small and relevant fraction of dysregulated mRNA/miRNAs (miR-126-3p and miR-335-5p, in particular). Importantly, myxoma-derived CSCs but not normal myocardium-derived CSCs, seed human myxoma tumours in xenograft’s in immunodeficient NOD/SCID mice. Conclusion Myxoma-derived c-kitpos/CD45neg/CD31neg CSCs fulfill the criteria expected of atrial myxoma-initiating stem cells. The transcriptome of these cells indicates that they belong to or are derived from the same lineage as the atrial multipotent c-kitpos/CD45neg/CD31neg CSCs. Taken together the data presented here suggest that human myxomas could be the first-described CSC-related human heart disease.
Operationalization of the Brief ICF Core Set for Hearing Loss: An ICF-Based e-Intake Tool in Clinical Otology and Audiology Practice

Supplemental Digital Content is available in the text. Objectives: According to the International Classification of Functioning, Disability and Health (ICF), functioning reflects the interplay between an individual’s body structures and functions, activities, participation, environmental, and personal factors. To be useful in clinical practice, these concepts need to be operationalized into a practical and integral instrument. The Brief ICF Core Set for Hearing Loss (CSHL) provides a minimum standard for the assessment of functioning in adults with hearing loss. The objective of the present study was to operationalize the Brief CSHL into a digital intake tool that could be used in the otology–audiology practice for adults with ear and hearing problems as part of their intake assessment. Design: A three-step approach was followed: (1) Selecting and formulating questionnaire items and response formats, using the 27 categories of the Brief CSHL as a basis. Additional categories were selected based on relevant literature and clinical expertise. Items were selected from existing, commonly used disease-specific questionnaires, generic questionnaires, or the WHO’s official descriptions of ICF categories. The response format was based on the existing item’s response categories or on the ICF qualifiers. (2) Carrying out an expert survey and a pilot study (using the three-step test interview. Relevant stakeholders and patients were asked to comment on the relevance, comprehensiveness, and comprehensibility of the items. Results were discussed in the project group, and items were modified based on consensus. (3) Integration of the intake tool into a computer-based system for use in clinical routine. Results: The Brief CSHL was operationalized into 62 items, clustered into six domains: (1) general information, including reason for visit, sociodemographic, and medical background; (2) general body functions; (3) ear and hearing structures and functions; (4) activities and participation (A&P); (5) environmental factors (EF); and (6) personal factors (mastery and coping). Based on stakeholders’ responses, the instructions of the items on A&P and EF were adapted. The three-step test interview showed that the tool had sufficient content validity but that some items on EF were redundant. Overall, the stakeholders and patients indicated that the intake tool was relevant and had a logical and clear structure. The tool was integrated in an online portal. Conclusions: In the current study, an ICF-based e-intake tool was developed that aims to screen self-reported functioning problems in adults with an ear/hearing problem. The relevance, comprehensiveness, and comprehensibility of the originally proposed item list was supported, although the stakeholder and patient feedback resulted into some changes of the tool on item-level. Ultimately, the functioning information obtained with the tool could be used to promote patient-centered ear and hearing care taking a biopsychosocial perspective into account.
Single Radiotherapy Fraction with Local Anti-CD40 Therapy Generates Effective Abscopal Responses in Mouse Models of Cervical Cancer

Current treatment options for advanced cervical cancer are limited, especially for patients in poor-resource settings, with a 17% 5-year overall survival rate. Here, we report results in animal models of advanced cervical cancer, showing that anti-CD40 therapy can effectively boost the abscopal effect, whereby radiotherapy of a tumor at one site can engender therapeutically significant responses in tumors at distant untreated sites. In this study, two subcutaneous cervical cancer tumors representing one primary and one metastatic tumor were generated in each animal. Only the primary tumor was treated and the responses of both tumors were monitored. The study was repeated as a function of different treatment parameters, including radiotherapy dose and dosing schedule of immunoadjuvant anti-CD40. The results consistently suggest that one fraction dose of radiotherapy with a single dose of agonistic anti-CD40 can generate highly effective abscopal responses, with a significant increase in animal survival (p = 0.0004). Overall, 60% of the mice treated with this combination showed long term survival with complete tumor regression, where tumors of mice in other cohorts continued to grow. Moreover, re-challenged responders to the treatment developed vitiligo, suggesting developed immune memory for this cancer. The findings offer a potential new therapy approach, which could be further investigated and developed for the treatment of advanced cervical cancer, with major potential impact, especially in resource-poor settings.
Geospatial Mapping of Orthopaedic Surgeons Age 60 and Over and Confirmed Cases of COVID-19

Background: Although elective surgical procedures in the United States have been suspended because of the coronavirus disease 2019 (COVID-19) pandemic, orthopaedic surgeons are being recruited to serve patients with COVID-19 in addition to providing orthopaedic acute care. Older individuals are deemed to be at higher risk for poor outcomes with COVID-19. Although previous studies have shown a high proportion of older providers nationwide across medical specialties, we are not aware of any previous study that has analyzed the age distribution among the orthopaedic workforce. Therefore, the purposes of the present study were (1) to determine the geographic distribution of U.S. orthopaedic surgeons by age, (2) to compare the distribution with other surgical specialties, and (3) to compare this distribution with the spread of COVID-19. Methods: Demographic statistics from the most recent State Physician Workforce Data Reports published by the Association of American Medical Colleges were extracted to identify the 2018 statewide proportion of practicing orthopaedic surgeons ≥60 years of age as well as age-related demographic data for all surgical specialties. Geospatial data on the distribution of COVID-19 cases were obtained from the Environmental Systems Research Institute. State boundary files were taken from the U.S. Census Bureau. Orthopaedic workforce age data were utilized to group states into quintiles. Results: States with the highest quintile of orthopaedic surgeons ≥60 years of age included states most severely affected by COVID-19: New York, New Jersey, California, and Florida. For all states, the median number of providers ≥60 years of age was 105.5 (interquartile range [IQR], 45.5 to 182.5). The median proportion of orthopaedic surgeons ≥60 years of age was higher than that of all other surgical subspecialties, apart from thoracic surgery. Conclusions: To our knowledge, the present report provides the first age-focused view of the orthopaedic workforce during the COVID-19 pandemic. States in the highest quintile of orthopaedic surgeons ≥60 years old are also among the most overwhelmed by COVID-19. As important orthopaedic acute care continues in addition to COVID-19 frontline service, special considerations may be needed for at-risk staff. Appropriate health system measures and workforce-management strategies should protect the subset of those who are most potentially vulnerable. Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Earliest cases of coronavirus disease 2019 (COVID-19) identified in solid organ transplant recipients in the United States

With the rapidly expanding pandemic of SARS‐CoV‐2, there is concern that solid organ transplant recipients will be particularly vulnerable to infection and may experience a more severe clinical course. We report four cases of COVID‐19 in solid organ transplant recipients including recipients of kidney, liver, lung, and heart transplants. We describe each patient's medical history including transplantation history, their clinical presentation and workup, and their course from diagnosis to either hospital discharge or to improvement in symptoms. These reports demonstrate a range of symptoms, clinical severity, and disease course in solid organ transplant recipients with COVID‐19, including two hospitalized patients and two patients managed entirely in the outpatient setting.
An Alzheimer Disease Challenge Model: 24-Hour Sleep Deprivation in Healthy Volunteers, Impact on Working Memory, and Reversal Effect of Pharmacological Intervention

Supplemental digital content is available in the text. Abstract Purpose/Background Alzheimer disease (AD) is a public health issue because of the low number of symptomatic drugs and the difficulty to diagnose it at the prodromal stage. The need to develop new treatments and to validate sensitive tests for early diagnosis could be met by developing a challenge model reproducing cognitive impairments of AD. Therefore, we implemented a 24-hour sleep deprivation (SD) design on healthy volunteers in a randomized, double-blind, placebo-controlled, crossover study on 36 healthy volunteers. Methods/Procedure To validate the SD model, cognitive tests were chosen to assess a transient worsening of cognitive functions after SD and a restoration under modafinil as positive control (one dose of 200 mg). Then, the same evaluations were replicated after 15 days of donepezil (5 mg/d) or memantine (10 mg/d). The working memory (WM) function was assessed by the N-back task and the rapid visual processing (RVP) task. Findings/Results The accuracy of the N-back task and the reaction time of the RVP revealed the alteration of the WM with SD and its restoration with modafinil (changes in score after SD compared with baseline before SD), respectively, in the placebo group and in the modafinil group (−0.2% and +1.0% of satisfactory answers, P = 0.022; +21.3 and +1.9 milliseconds of reaction time, P = 0.025). Alzheimer disease drugs also tended to reverse this deterioration: the accuracy of the N-back task was more stable through SD (compared with −3.0% in the placebo group, respectively, in the memantine group and in the donepezil group: −1.4% and −1.6%, P = 0.027 and P = 0.092) and RVP reaction time was less impacted (compared with +41.3 milliseconds in the placebo group, respectively, in the memantine group and in the donepezil group: +16.1 and +29.3 milliseconds, P = 0.034 and P = 0.459). Implications/Conclusions Our SD challenge model actually led to a worsening of WM that was moderated by both modafinil and AD drugs. To use this approach, the cognitive battery, the vulnerability of the subjects to SD, and the expected drug effect should be carefully considered.
Diagnostic accuracy of an automated chemiluminescent immunoassay for anti‐SARS‐CoV‐2 IgM and IgG antibodies: an Italian experience

Abstract A pandemic of coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has been spreading throughout the world. Though molecular diagnostic tests are the gold standard for COVID‐19, serological testing is emerging as a potential surveillance tool, in addition to its complementary role in COVID‐19 diagnostics. Indubitably quantitative serological testing provides greater advantages than qualitative tests but today there is still little known about serological diagnostics and what the most appropriate role quantitative tests might play. Sixty‐one COVID‐19 patients and 64 patients from a control group were tested by iFlash1800 CLIA analyzer for anti‐SARS CoV‐2 antibodies IgM and IgG. All COVID‐19 patients were hospitalized in San Giovanni di Dio Hospital (Florence, Italy) and had a positive oro/nasopharyngeal swab reverse‐transcription polymerase chain reaction result. The highest sensitivity with a very good specificity performance was reached at a cutoff value of 10.0 AU/mL for IgM and of 7.1 for IgG antibodies, hence near to the manufacturer's cutoff values of 10 AU/mL for both isotypes. The receiver operating characteristic curves showed area under the curve values of 0.918 and 0.980 for anti‐SARS CoV‐2 antibodies IgM and IgG, respectively. iFlash1800 CLIA analyzer has shown highly accurate results for the anti‐SARS‐CoV‐2 antibodies profile and can be considered an excellent tool for COVID‐19 diagnostics.
Food Environment Typology: Advancing an Expanded Definition, Framework, and Methodological Approach for Improved Characterization of Wild, Cultivated, and Built Food Environments toward Sustainable Diets

The food environment is a critical place in the food system to implement interventions to support sustainable diets and address the global syndemic of obesity, undernutrition, and climate change, because it contains the total scope of options within which consumers make decisions about which foods to acquire and consume. In this paper, we build on existing definitions of the food environment, and provide an expanded definition that includes the parameter of sustainability properties of foods and beverages, in order to integrate linkages between food environments and sustainable diets. We further provide a graphical representation of the food environment using a socio-ecological framework. Next, we provide a typology with descriptions of the different types of food environments that consumers have access to in low-, middle-, and high-income countries including wild, cultivated, and built food environments. We characterize the availability, affordability, convenience, promotion and quality (previously termed desirability), and sustainability properties of food and beverages for each food environment type. Lastly, we identify a methodological approach with potential objective and subjective tools and metrics for measuring the different properties of various types of food environments. The definition, framework, typology, and methodological toolbox presented here are intended to facilitate scholars and practitioners to identify entry points in the food environment for implementing and evaluating interventions that support sustainable diets for enhancing human and planetary health.
Questionnaire on Perception of Threat from COVID-19

The ravages caused by the disease known as COVID-19 has led to a worldwide healthcare and social emergency requiring an effective combined effort from everyone to reduce contagion. Under these circumstances, the perception of the disease is going to have a relevant role in the individual’s psychological adjustment. However, at the present time there is no validated instrument for evaluating adult perception of threat from COVID-19. Considering the importance of perception or representation of the disease in a state of social alert, our study intended to validate an instrument measuring the psychological process of the disease caused by the coronavirus (COVID-19). In view of the above, this study evaluated the factor structure and reliability of the version of the Illness Perception Questionnaire (IPQ) for COVID-19 in a sample of adults. The sample consisted of 1014 Spanish adults (67.2% women and 32.8% men). The exploratory and confirmatory factor analyses supported a unidimensional model of the scale, which was the one that showed the best fit and explained 43.87% of the variance. This brief version has adequate psychometric properties and may be used to evaluate the perception of threat from COVID-19 in an adult Spanish population. The validation of this instrument contributes to progress in representation of COVID-19 in our culture.
Development of Abbreviated Versions of the Word Auditory Recognition and Recall Measure.

OBJECTIVES The objective of this study was to develop and evaluate abbreviated versions of the Word Auditory Recognition and Recall Measure (WARRM) as part of an iterative process in the development of a feasible test for potential future clinical use. DESIGN The three original WARRM (O-WARRM) randomizations were modified by altering the presentation paradigm. Instead of presenting 5 trials per set size with set size increasing from 2 to 6 as in the O-WARRM (n = 100 words), the experimental WARRM (E-WARRM) paradigm consisted of one trial from each of set sizes 2 to 6 to create a "run" (n = 20 words) with each randomization consisting of 5 runs (n = 100 words). A total of 24 younger listeners with normal hearing and 48 older listeners with hearing loss (OHL) were administered 1 randomization of the O-WARRM and 1 different randomization of the E-WARRM. RESULTS The recognition and recall performances on the O-WARRM and all versions of the E-WARRM (five individual runs and overall) were similar within each listener group, with the younger listeners with normal hearing outperforming the OHL listeners on all measures. Correlation analyses revealed moderate to strong associations between the abbreviated WARRM runs and the O-WARRM for the OHL listener group. Hierarchical regression modeling suggested that run 1 of the E-WARRM was a good predictor of O-WARRM performance and that adding additional runs did not improve the prediction. Taken together, these findings suggest that administering one run from the E-WARRM warrants further examination for clinical use. Additional analyses revealed equivalent scores on all five runs from the three E-WARRM randomizations for both listener groups. CONCLUSIONS Abbreviated versions of the O-WARRM were developed as part of this study. This was accomplished by modifying the original presentation paradigm and creating 15 unique "runs" among the original 3 randomizations. The resulting 15 runs could be considered 15 unique and abbreviated WARRM lists that have potential, in the future after further studies are conducted to establish important properties, for clinic use. The abbreviated WARRM lists may be useful for quantifying auditory working memory of listeners with hearing loss during the audiologic rehabilitation process.
Sorting Mechanisms for MicroRNAs into Extracellular Vesicles and Their Associated Diseases

Extracellular vesicles (EV) are secretory membranous elements used by cells to transport proteins, lipids, mRNAs, and microRNAs (miRNAs). While their existence has been known for many years, only recently has research begun to identify their function in intercellular communication and gene regulation. Importantly, cells have the ability to selectively sort miRNA into EVs for secretion to nearby or distant targets. These mechanisms broadly include RNA-binding proteins such as hnRNPA2B1 and Argonaute-2, but also membranous proteins involved in EV biogenesis such as Caveolin-1 and Neural Sphingomyelinase 2. Moreover, certain disease states have also identified dysregulated EV-miRNA content, shedding light on the potential role of selective sorting in pathogenesis. These pathologies include chronic lung disease, immune response, neuroinflammation, diabetes mellitus, cancer, and heart disease. In this review, we will overview the mechanisms whereby cells selectively sort miRNA into EVs and also outline disease states where EV-miRNAs become dysregulated.
Redox regulation of inflammation and immunity

Inflammation is a consequence of the activation of innate immunity and represents an important component of several pathological conditions, including not only the complication of infections but also sterile and autoimmune diseases. An early event in inflammation is represented by the production of proinflammatory cytokines and both their production and action have often been associated to oxidative stress. The redox status of the cell is therefore a key regulator of inflammation and glutathionylation (formation of mixed disulphides between cysteine residues of proteins and glutathione) is considered an important mechanism of this regulation.
The effects of dietary medium-chain fatty acids on ruminal methanogenesis and fermentation in vitro and in vivo: A meta-analysis.

The efficacy of methane (CH4 ) suppression using medium-chain fatty acids (MCFA) remains inconclusive, despite a number of studies on this topic are available. We thus carried out a meta-analysis to integrate the published data on different concentrations and types of MCFA such as lauric acid and myristic acid, which investigated ruminal methanogenesis and fermentation in in vitro and in vivo experiments. In vitro MCFA sources were classified either as pure MCFA (lauric acid, myristic acid and their combinations) or as natural MCFA-rich oils (canola oil enriched with lauric acids, coconut oil, krabok oil and palm kernel oil). The MCFA sources used in the in vivo studies were coconut oil, lauric acid, myristic acid and the combination of lauric and myristic acids. A total of 41 studies (20 in vitro and 21 in vivo studies) were compiled in our database, which included the data on CH4 emission, digestibility, ruminal fermentation products and microbial populations. The results showed that the amount of CH4 production per unit of digested organic matter decreased linearly under in vitro conditions (p < .01) and tended to decrease quadratically under in vivo conditions (p < .07) with increasing doses of MCFA. Populations of protozoa (p < .01) in both in vitro and in vivo responded negatively in a linear manner, whereas Archaea population diminished quadratically (p = .04) only in the in vitro conditions with increasing doses of MCFA. Increasing dietary MCFA concentrations also reduced the fibre digestibility linearly (p < .05) in both in vitro and in vivo conditions. CH4 production for different sources of MCFA decreased in following order: coconut oil > lauric acid > myristic acid > mixed lauric and myristic acids > palm kernel oil > canola oil enriched with lauric acids > krabok oil. It can be concluded that the effect of MCFA on ruminal methanogenesis depends on the amount and type of MCFA.