Miracle-dz/UniFAR-FTUs huggingface dataset:
To burn-out or not to burn-out: a cross-sectional study in healthcare professionals in Spain during COVID-19 pandemic

Objective To assess the prevalence of burn-out syndrome in healthcare workers working on the front line (FL) in Spain during COVID-19. Design Cross-sectional, online survey-based study. Settings Sampling was performed between 21st April and 3rd May 2020. The survey collected demographic data and questions regarding participants’ working position since pandemic outbreak. Participants Spanish healthcare workers working on the FL or usual ward were eligible. A total of 674 healthcare professionals answered the survey. Main outcomes and measures Burn-out syndrome was assessed by the Maslach Burnout Inventory-Medical Personnel. Results Of the 643 eligible responding participants, 408 (63.5%) were physicians, 172 (26.8%) were nurses and 63 (9.8%) other technical occupations. 377 (58.6%) worked on the FL. Most participants were women (472 (73.4%)), aged 31–40 years (163 (25.3%)) and worked in tertiary hospitals (>600 beds) (260 (40.4%)). Prevalence of burn-out syndrome was 43.4% (95% CI 39.5% to 47.2%), higher in COVID-19 FL workers (49.6%, p<0.001) than in non- COVID-19 FL workers (34.6%, p<0.001). Women felt more burn-out (60.8%, p=0.016), were more afraid of self-infection (61.9%, p=0.021) and of their performance and quality of care provided to the patients (75.8%, p=0.015) than men. More burn-out were those between 20 and 30 years old (65.2%, p=0.026) and those with more than 15 years of experience (53.7%, p=0.035). Multivariable logistic regression analysis revealed that, working on COVID-19 FL (OR 1.93; 95% CI 1.37 to 2.71, p<0.001), being a woman (OR 1.56; 95% CI 1.06 to 2.29, p=0.022), being under 30 years old (OR 1.75; 95% CI 1.06 to 2.89, p=0.028) and being a physician (OR 1.64; 95% CI 1.11 to 2.41, p=0.011) were associated with high risk of burn-out syndrome. Conclusions This survey study of healthcare professionals reported high rates of burn-out syndrome. Interventions to promote mental well-being in healthcare workers exposed to COVID-19 need to be immediately implemented.
Idecabtagene Vicleucel in Relapsed and Refractory Multiple Myeloma.

BACKGROUND Idecabtagene vicleucel (ide-cel, also called bb2121), a B-cell maturation antigen-directed chimeric antigen receptor (CAR) T-cell therapy, has shown clinical activity with expected CAR T-cell toxic effects in patients with relapsed and refractory multiple myeloma. METHODS In this phase 2 study, we sought to confirm the efficacy and safety of ide-cel in patients with relapsed and refractory myeloma. Patients with disease after at least three previous regimens including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody were enrolled. Patients received ide-cel target doses of 150 × 106 to 450 × 106 CAR-positive (CAR+) T cells. The primary end point was an overall response (partial response or better); a key secondary end point was a complete response or better (comprising complete and stringent complete responses). RESULTS Of 140 patients enrolled, 128 received ide-cel. At a median follow-up of 13.3 months, 94 of 128 patients (73%) had a response, and 42 of 128 (33%) had a complete response or better. Minimal residual disease (MRD)-negative status (<10-5 nucleated cells) was confirmed in 33 patients, representing 26% of all 128 patients who were treated and 79% of the 42 patients who had a complete response or better. The median progression-free survival was 8.8 months (95% confidence interval, 5.6 to 11.6). Common toxic effects among the 128 treated patients included neutropenia in 117 patients (91%), anemia in 89 (70%), and thrombocytopenia in 81 (63%). Cytokine release syndrome was reported in 107 patients (84%), including 7 (5%) who had events of grade 3 or higher. Neurotoxic effects developed in 23 patients (18%) and were of grade 3 in 4 patients (3%); no neurotoxic effects higher than grade 3 occurred. Cellular kinetic analysis confirmed CAR+ T cells in 29 of 49 patients (59%) at 6 months and 4 of 11 patients (36%) at 12 months after infusion. CONCLUSIONS Ide-cel induced responses in a majority of heavily pretreated patients with refractory and relapsed myeloma; MRD-negative status was achieved in 26% of treated patients. Almost all patients had grade 3 or 4 toxic effects, most commonly hematologic toxic effects and cytokine release syndrome. (Funded by bluebird bio and Celgene, a Bristol-Myers Squibb company; KarMMa ClinicalTrials.gov number, NCT03361748.).
Global Gene Expression of Cultured Human Dermal Fibroblasts: Focus on Cell Cycle and Proliferation Status in Improving the Condition of Face Skin

Chronological skin ageing is an inevitable physiological process that results in thin and sagging skin, fine wrinkles, and gradual dermal atrophy. The main therapeutic approaches to soft tissue augmentation involve using dermal fillers, where natural fillers, such as autologous fibroblasts, are involved in generating dermal matrix proteins. The aim of this study was to determine the global transcriptome profile of three passages of dermal autologous fibroblasts from a male volunteer, focusing on the processes of the cell cycle and cell proliferation status to estimate the optimal passage of the tested cells with respect to their reimplantation. We performed K-means clustering and validation of the expression of the selected mRNA by qRT-PCR. Ten genes were selected (ANLN, BUB1, CDC20, CCNA2, DLGAP5, MKI67, PLK1, PRC1, SPAG5, and TPX2) from the top five processes annotated to cluster 5. Detailed microarray analysis of the fibroblast genes indicated that the cell population of the third passage exhibited the highest number of upregulated genes involved in the cell cycle and cell proliferation. In all cases, the results of qRT-PCR confirmed the differences in expression of the selected mRNAs between fibroblasts from the primary culture (C0) and from the first (C1), second (C2), and third (C3) cell passage. Our results thus suggest that these cells might be useful for increasing fibroblast numbers after reimplantation into a recipient's skin, and the method used in this study seems to be an excellent tool for autologous transplantation allowing the rejuvenation of aging skin.
Clinical characteristics and histology of cholecystectomised dogs with nongravity-dependent biliary sludge: 16 cases (2014-2019).

OBJECTIVES To report the available histology, biochemistry and clinical progression of dogs without classic overt biliary tract signs that underwent cholecystectomy for nongravity-dependent biliary sludge. MATERIALS AND METHODS Case series of client-owned dogs for which a cholecystectomy was performed for nongravity-dependent biliary sludge. In six dogs, for which nongravity-dependent biliary sludge filled less than half of gall bladder volume, gall bladder ejection fractions were measured. Available histology, biochemistry, presenting clinical signs and post-surgical clinical progression were reported. RESULTS Sixteen dogs were included in this retrospective case series. No dogs met the histological criteria for gall bladder mucocoeles or had histological evidence of primary hepatitis or cholangitis. Biochemistry was normal for 11 dogs. Hypercholesterolaemia was not noted in any dog. Twelve dogs had cholecystitis (11 lymphoplasmacytic, one neutrophilic) and nine dogs had biliary mucosal hyperplasia. Thirteen dogs had enteritis (12 lymphoplasmacytic, one eosinophilic) and nine dogs had reactive hepatitis (eight lymphoplasmacytic, one neutrophilic). All six dogs with nongravity-dependent biliary sludge that filled less than half of gall bladder volume had sub-optimal gall bladder function. Presenting clinical signs, including diurnal inappetence in the morning and exercise intolerance, resolved in 86% (12/14) of dogs after cholecystectomy and clinical improvement was noted in 81% (13/16) of dogs overall. CLINICAL SIGNIFICANCE Duodenal inflammation could potentially impact gall bladder dysmotility in dogs with nongravity-dependent biliary sludge. Furthermore, diurnal inappetence in the morning and exercise intolerance could indicate symptomatic gall bladder disease in dogs with NDBS and can potentially precede more obvious systemic clinical signs associated with gall bladder mucocoeles.
Selecting the model for multiple imputation of missing data: Just use an IC!

Multiple imputation and maximum likelihood estimation (via the expectation‐maximization algorithm) are two well‐known methods readily used for analyzing data with missing values. While these two methods are often considered as being distinct from one another, multiple imputation (when using improper imputation) is actually equivalent to a stochastic expectation‐maximization approximation to the likelihood. In this article, we exploit this key result to show that familiar likelihood‐based approaches to model selection, such as Akaike's information criterion (AIC) and the Bayesian information criterion (BIC), can be used to choose the imputation model that best fits the observed data. Poor choice of imputation model is known to bias inference, and while sensitivity analysis has often been used to explore the implications of different imputation models, we show that the data can be used to choose an appropriate imputation model via conventional model selection tools. We show that BIC can be consistent for selecting the correct imputation model in the presence of missing data. We verify these results empirically through simulation studies, and demonstrate their practicality on two classical missing data examples. An interesting result we saw in simulations was that not only can parameter estimates be biased by misspecifying the imputation model, but also by overfitting the imputation model. This emphasizes the importance of using model selection not just to choose the appropriate type of imputation model, but also to decide on the appropriate level of imputation model complexity.
Isothiazolinones Common in Children's Toy Slime

Background Contact dermatitis to homemade slime has been frequently reported, with isothiazolinones as a likely sensitizer. Little is known on the presence of these preservatives in commercial, store-bought slime products. Objectives The aims of the study were to review the literature on “slime dermatitis” and to assess for the presence of isothiazolinones in commercially available slime products and homemade slime components. Methods An experimental, colorimetric spot test was used to verify the presence of isothiazolinones in 38 slime products of the 16 best-selling commercial slime kits, 1 finished homemade slime, and 4 common components of homemade slime. High-performance liquid chromatography with UV detection was performed on 8 commercial slime products. Results According to the spot test, 27 (71%) of the 38 commercial slime products contained isothiazolinones. High-performance liquid chromatography with UV detection analyses indicated, however, that false-positives and false-negatives readily occur: isothiazolinone content was correctly identified in only 4 (50%) of the 8 samples. Conclusions This study is the first to demonstrate the presence of isothiazolinones in commercial slime toys. Although the colorimetric spot test may have some utility as a screening assay, it is far from specific and likely not sensitive enough to reliably identify methylisothiazolinone.
Vesuvianite from Somma-Vesuvius volcano (southern Italy): chemical, X-ray diffraction and single-crystal polarized FTIR investigations

A suite of twelve vesuviante samples from skarn and syenitc ejecta from the Somma- Vesuvius volcanic complex was studied by means of a combination of energy dispersive spectrometry (EDS), inductively-coupled plasma-mass spectrometry (ICP-MS), powder and single-crystal X-ray diffraction, polarized radiation Fourier-transform infrared (FTIR) singlecrystal micro-spectrometry. Some thermo-gravimetric analyses (TGA) were also performed. Vesuvianite crystals are dark brown to honey yellow-brown, rarely reddish-brown, and up to 2 centimetres in dimension. Their major elements (SiO 2 , Al 2 O 3 , CaO and MgO) composition is rather constant, while Fe 2 O 3 , MnO and TiO 2 are slightly more variable . Light elements (B, Be and Li), Y, REE and actinides (Th, U) have been detected in all samples in minor to trace amounts, together with V, Zn, Zr, Sn, Co, Ga, Nb, Ta, Hf, Pb and Bi. Among the volatiles, fluorine is prevailing (in a range 1.41-2.25 wt. %). Water and chlorine are always observed, in the range 0.67-1.03 wt. % and 0.01-0.05 wt. %, respectively. Single-crystal X-ray diffraction analyses of vesuvianite gave P 4/ nnc as the most probable space group. Cell parameters vary from 15.542 A up to 15.576 A for a and 11.800 A up to 11.827 A for c . Polarized FTIR spectra of the OH fundamental measured parallel to the c -axis are dominated by absorption bands at 3638, 3567, 3452 and 3200 cm -1 , with two additional bands centred at 3590 and 3117 cm -1 . All bands show strong pleochroism with maximum absorption parallel to the c -axis and weak absorption components perpendicular to c . The spectra measured perpendicular to the c -axis are also dominated by the 3567, 3590 and 3638 cm -1 band group. OH amounts have been calculated using the total integrated absorption coefficient derived from the fitted spectra. These contents are in good agreement with the H 2 O values obtained by TGA. The formation temperature and the chemical environment of vesuvianite point to at least 800-890 °C and to the occurrence of chloride-fluoride-sulfate-carbonate-rich saline fluids, which are also rich in incompatible elements.
Responsiveness and Relationship Satisfaction in Couples Coping With Parkinson’s Disease: A Pilot Study

Parkinson’s disease (PD) is a neurodegenerative disorder which impacts the person’s physical, psychological and relational well-being, and the well-being of their romantic partner, who is often in a caregiving role. People with PD may struggle to empathize with and respond to their partner’s emotional states, which can hinder relationship satisfaction for both partners. Care partners, who may feel burnt out from caring for their partner’s physical and cognitive needs, may be limited in their ability to be responsive to their spouse’s relational needs, which can hinder satisfaction. Despite the challenges faced by couples coping with PD, little work has considered the interpersonal factors associated with relationship satisfaction for affected couples. In the current study, we investigated individual differences in the motivation to be responsive to a partner’s needs (i.e., communal strength), as well as perceptions of a partner’s responsiveness (i.e., the extent to which a person perceives their partner to care for, validate, and understand them). We recruited 20 couples in which one partner was diagnosed with PD and their romantic partner self-identified as a full-time caregiver, in order to examine how responsiveness is associated with both partners’ relationship satisfaction. When partners with PD reported higher communal strength, they reported higher relationship satisfaction and so did their care partner. When partners with PD perceived their care partner to be more responsive, they reported higher relationship satisfaction. These findings provide some preliminary evidence for responsiveness as one interpersonal factor worthy of further consideration for helping couples cope with PD.
Antidiabetic Activity of Widely Used Medicinal Plants in the Sri Lankan Traditional Healthcare System: New Insight to Medicinal Flora in Sri Lanka

The use of medicinal plant extracts and their isolated bioactive compounds for the management of diabetes mellitus has been tremendously increased in recent decades. The present study aimed at providing in-depth information on medicinal flora that has been widely used in the Sri Lankan traditional healthcare system for the management of diabetes mellitus. The data of this review article were obtained from published articles from January 2000 to September 2020 in scientific databases of PubMed, Web of Science, and Google Scholar. In this review, a total number of 18 medicinal plants with the antidiabetic activity were expressed, and their isolated antidiabetic active compounds were highlighted as new drug leads. Results of the reported studies revealed that medicinal plants exert a potent antidiabetic activity via both in vitro and in vivo study settings. However, bioactive compounds and antidiabetic mechanism (s) of action of many of the reported medicinal plants have not been isolated/elucidated the structure in detail, to date. Reported antidiabetic medicinal plants with other properties such as antioxidant and antihyperlipidemic activities deliver new entities for the development of antidiabetic agents with multiple therapeutic targets. This is a comprehensive review on potential antidiabetic activities of the Sri Lankan medicinal plants that have been widely used in the traditional healthcare system. The information presented here would fill the gap between the use of them by traditional healers in the traditional medicine healthcare system in Sri Lanka and their potency for development of new drug entities in future.
The Mediating Effects of Self-Esteem on Anxiety and Emotion Regulation

Individuals with anxiety disorders maladaptively appraise interpersonal threat cues leading to inaccurate interpretations of the self and others. However, little is known about the factors that mediate this association, therefore, the main aim of this study was to examine the relationship between state and trait anxiety, self-esteem, and emotion regulation strategies: reappraisal and suppression. Young adults aged between 18–26 years participated in the study. They completed a set of self-reports measuring emotion regulation, self-esteem, state-trait anxiety, and positive and negative attributes. Participants also completed an experimental task, using the dot-probe paradigm, which measures threat bias and response inhibition. The findings showed that trait and state anxiety predicted suppression, reappraisal, and internalising problems, and is linked to response inhibition. Importantly, low self-esteem, significantly mediated the relationship between increased anxiety and suppression. Taken together, these results show specific associations between emotion regulation and anxiety, highlighting the significant impact of self-esteem in young adults.
Rapid-prototyped collagen scaffolds reinforced with PCL/β-TCP nanofibres to obtain high cell seeding efficiency and enhanced mechanical properties for bone tissue regeneration

In this study, hierarchical collagen scaffolds consisting of micro-strut collagen and electrospun poly(e-caprolactone) (PCL)/β-tricalcium phosphate (TCP) nanofibres were fabricated to enhance cell seeding efficiency and mechanical properties compared to pure rapid-prototyped collagen scaffolds. To control the network of nanofibres, various deposition times (2, 5, 10, 20 s) of electrospun fibres were used to form one layer consisting of collagen struts. The tensile modulus of the hierarchical scaffolds, which have fibre networks electrospun for 20 s, was sevenfold higher than that of pure collagen scaffolds. Osteoblast-like cells (MG63) were seeded in the scaffolds to investigate cell seeding efficiency and various cellular activities. Cell seeding efficiency was measured; the efficiency increased from 55% for pure collagen scaffolds to 78% for hierarchical scaffolds (fibre deposition time: 20 s). In particular, even though for the low deposition time of fibres, 2 s, the seeding efficiency was about 64%. The hierarchical scaffold in which electrospun fibres were deposited for 10 s provided the highest proliferation rate of viable cells because the pores (11.6 ± 0.8 μm) of the fibre layer can effectively allow migration and proliferation of the injected cells. To observe the effect of bone tissue regeneration, the cellular activities including cell viability, ALP activity and calcium deposition were also evaluated. The results indicated that the activities were greatly enhanced due to the PCL/β-TCP nanofibres embedded in the collagen struts relative to pure collagen scaffolds.
Ultrasound May Suppress Tumor Growth, Inhibit Inflammation, and Establish Tolerogenesis by Remodeling Innatome via Pathways of ROS, Immune Checkpoints, Cytokines, and Trained Immunity/Tolerance

Background The immune mechanisms underlying low-intensity ultrasound- (LIUS-) mediated suppression of inflammation and tumorigenesis remain poorly determined. Methods We used microarray datasets from the NCBI GEO DataSet repository and conducted comprehensive data-mining analyses, where we examined the gene expression of 1376 innate immune regulators (innatome genes (IGs) in cells treated with LIUS. Results We made the following findings: (1) LIUS upregulates proinflammatory IGs and downregulates metastasis genes in cancer cells, and LIUS upregulates adaptive immunity pathways but inhibits danger-sensing and inflammation pathways and promote tolerogenic differentiation in bone marrow (BM) cells. (2) LIUS upregulates IGs encoded for proteins localized in the cytoplasm, extracellular space, and others, but downregulates IG proteins localized in nuclear and plasma membranes, and LIUS downregulates phosphatases. (3) LIUS-modulated IGs act partially via several important pathways of reactive oxygen species (ROS), reverse signaling of immune checkpoint receptors B7-H4 and BTNL2, inflammatory cytokines, and static or oscillatory shear stress and heat generation, among which ROS is a dominant mechanism. (4) LIUS upregulates trained immunity enzymes in lymphoma cells and downregulates trained immunity enzymes and presumably establishes trained tolerance in BM cells. (5) LIUS modulates chromatin long-range interactions to differentially regulate IGs expression in cancer cells and noncancer cells. Conclusions Our analysis suggests novel molecular mechanisms that are utilized by LIUS to induce tumor suppression and inflammation inhibition. Our findings may lead to development of new treatment protocols for cancers and chronic inflammation.
Videos of Sipuleucel-T Programmed T Cells Lysing Cells That Express Prostate Cancer Target Antigens

Abstract Sipuleucel-T, an autologous cellular immunotherapy, was approved to treat metastatic castration-resistant prostate cancer in 2010 in the United States. Treatment with sipuleucel-T primes the immune system to target prostate acid phosphatase, which is expressed by prostate cancer cells, potentially leading to lysis of cancer cells. Expanding on previously reported indirect evidence of cell killing with sipuleucel-T treatment, we sought to provide direct evidence of cell lysis through visualization. We used advanced video technology and available samples of peripheral blood mononuclear cells from subjects enrolled in the STAMP trial (NCT01487863). Isolated CD8+ T cells were used as effector cells and cocultured with autologous monocytes pulsed with control or target antigens. Differentially stained effector and target cells were then video recorded during coculture. Here, we present video recordings and analyses of T cells from sipuleucel-T–treated subjects showing—for the first time—direct lysis of cells that express prostate cancer target antigens, prostate acid phosphatase, or prostate-specific antigen.