Miracle-dz/UniFAR-FTUs huggingface dataset:
High power Q-switched 1064 nm / 532 nm Nd:YAG Laser in tattoo removal: A systematic review

ABSTRACT Q-switched 1064 nm/532 nm Nd: YAG Lasers present important characteristics which can contribute toward the removal of tattoos, for having the ability to reach only specific targets with minimal damage to the tissue. Despite reports of their clinical benefits, only a few scientific studies demonstrate the efficacy and safety of these types of lasers in the short and long term. To substantiate the effects, benefits, and safety of the application of Q-switched 1064 nm/532 nm Nd: YAG lasers, a systematic review was carried out from September to December of 2019, about the studies which report their use in the removal of tattoos, published in the last 20 years. Randomized clinical trials in humans were considered, as long as they evaluated the efficacy, safety, and benefits of the application of Q-switched 1064 nm/532 nm Nd: YAG lasers in the removal of black and color tattoos in different skin phototypes. One hundred and twenty-two articles were identified after the titles, abstracts were read, and duplicates were removed; six articles were left, which were included in the research (188 individuals). The Q-switched 1064 nm/532 nm Nd: YAG lasers seem promising in the short term, with minimal adverse effects; however, the efficacy and safety in the long term still present limitations. Consequently, future research is necessary, with better methodological standardization applied and with a follow-up for a longer period of evaluation of possible permanent adverse effects, to determine the standardization and safety of the therapy with the lasers Nd: YAG de 1064 nm/532 nm Q-switched.
Application of Age, Body Mass Index, Chronic Kidney Disease, Diabetes, and Genotyping Score for Efficacy of Clopidogrel: Secondary Analysis of the CHANCE Trial

Supplemental Digital Content is available in the text. Background and Purpose: The age, body mass index, chronic kidney disease, diabetes, and genotyping (ABCD-GENE) score is a validated risk score integrating CYP2C19 genotypes with clinical risk factors influencing clopidogrel response that would allow the more precise identification of subjects at risk for high platelet reactivity and adverse clinical outcomes. Our objective was to further verify application of the ABCD-GENE score and investigate appropriate cutoff value in patients with minor stroke or transient ischemic attack. Methods: In this post-analysis of the CHANCE trial (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events), the ABCD-GENE score was calculated for all patients enrolled in this study. By using the proposed cutoff of 10, patients were stratified as being at high risk for high platelet reactivity or not. We further categorized the ABCD-GENE score to 0 to 5, 6 to 24, and >24 to investigate the cutoff value of this scale in clinical application. Stroke recurrence at 3 months was considered as the primary outcome. Results: Among a total of 2923 patients with minor stroke/transient ischemic attack, there were 2273 (77.76%) with ABCD-GENE score <10 and 650 (22.24%) patients with ABCD-GENE score ≥10. Compared with the aspirin alone, hazard ratios (95% CIs) of the clopidogrel-aspirin therapy for stroke recurrence were 0.70 (0.54–0.91) and 0.76 (0.46–1.24), among patients of ABCD-GENE scores <10 and ABCD-GENE scores ≥10, respectively. Stratified analyses by ABCD-GENE score 0 to 5, 6 to 24, and >24, hazard ratios of the clopidogrel-aspirin therapy for stroke recurrence were 0.57 (95% CI, 0.38–0.85), 0.78 (0.58–1.06), and 1.20 (0.44–3.28) (P value for trend=0.0052). Conclusions: Among Chinese minor stroke/transient ischemic attack population, the efficacy of clopidogrel-aspirin therapy was decreased in patients with higher ABCD-GENE score. Our study suggests that CYP2C19 genotypes and clinical risk factors can be integrated by ABCD-GENE score to estimate the efficacy of clopidogrel-aspirin therapy.
Drug Repurposing to Identify Nilotinib as a Potential SARS-CoV-2 Main Protease Inhibitor: Insights from a Computational and In Vitro Study

COVID-19, an acute viral pneumonia, has emerged as a devastating pandemic. Drug repurposing allows researchers to find different indications of FDA-approved or investigational drugs. In this current study, a sequence of pharmacophore and molecular modeling-based screening against COVID-19 Mpro (PDB: 6LU7) suggested a subset of drugs, from the Drug Bank database, which may have antiviral activity. A total of 44 out of 8823 of the most promising virtual hits from the Drug Bank were subjected to molecular dynamics simulation experiments to explore the strength of their interactions with the SARS-CoV-2 Mpro active site. MD findings point toward three drugs (DB04020, DB12411, and DB11779) with very low relative free energies for SARS-CoV-2 Mpro with interactions at His41 and Met49. MD simulations identified an additional interaction with Glu166, which enhanced the binding affinity significantly. Therefore, Glu166 could be an interesting target for structure-based drug design. Quantitative structural–activity relationship analysis was performed on the 44 most promising hits from molecular docking-based virtual screening. Partial least square regression accurately predicted the values of independent drug candidates’ binding energy with impressively high accuracy. Finally, the EC50 and CC50 of 10 drug candidates were measured against SARS-CoV-2 in cell culture. Nilotinib and bemcentinib had EC50 values of 2.6 and 1.1 μM, respectively. In summary, the results of our computer-aided drug design provide a roadmap for rational drug design of Mpro inhibitors and the discovery of certified medications as COVID-19 antiviral therapeutics.
Daily stress and sleep associations vary by work schedule: A between‐ and within‐person analysis in nurses

Nurses experience poor sleep and high stress due to demanding work environments. Night shift work is common among nurses and may exacerbate stress–sleep associations. We examined bidirectional associations between daily stress and sleep, and moderation by recent shift worker status and daily work schedule among nurses. Participants were 392 nurses (92% female; 78% White, mean age = 39.54, SD = 11.15) who completed 14 days of electronic sleep diaries and actigraphy. They simultaneously completed assessments of daily stress and work schedule upon awakening (day shift vs. night shift [work between 9 p.m.–6 a.m.] vs. off work). Participants were classified as recent night shift workers if they worked at least one night shift during the past 14 days (n = 101; 26%). In the entire sample, greater daily stress predicted shorter self‐reported total sleep time and lower self‐reported sleep efficiency that night. Shorter self‐reported and actigraphy total sleep time and lower self‐reported sleep efficiency predicted higher next‐day stress. Compared with recent night shift workers, day workers reported higher stress after nights with shorter total sleep time. Stress‐sleep associations mostly did not vary by nurses’ daily work schedule. Sleep disturbances and stress may unfold in a toxic cycle and are prime targets for tailored interventions among nurses. Night shift workers may be less susceptible to the effects of short sleep on next‐day stress. Research is needed to understand the short‐ and long‐term effects of shift work and address the unique sleep challenges nurses face.
Tubulin polymerization promoting protein family member 3 (TPPP3) overexpression inhibits cell proliferation and invasion in nasopharyngeal carcinoma

ABSTRACT The function of tubulin polymerization promoting protein family member 3 (TPPP3) in tumor cells is complicated, and the role of TPPP3 in nasopharyngeal carcinoma (NPC) remains unclear. This study aims to explore the expression of TPPP3 in NPC and its effect on NPC cells. The expression of TPPP3 in NPC tissues and other cancers were analyzed by using the Oncomine and Gene Expression Omnibus (GEO) databases. The mRNA and protein of TPPP3 were detected in NPC tissues by quantitative real-time PCR and immunohistochemistry. Furthermore, TPPP3 was overexpressed in 5–8 F and HONE1 cell lines by lentivirus transfection, and functional analysis of TPPP3 in NPC was evaluated through in vitro experiments. The expression of TPPP3 was significantly down-regulated in NPC tissues and cells. Overexpression of TPPP3 significantly inhibited proliferation of 5–8 F and HONE1 cells in vitro. In addition, overexpression of TPPP3 significantly attenuated the invasion ability of 5–8 F, HONE1 cells in vitro, but have no significant effect on migration ability. Furthermore, TPPP3 overexpression diminished the expression of MMP-2 and MMP-9 mRNA. By analyzing dataset GSE12452, it was interesting that TPPP3 high expression group mainly functioned in B cell receptor signaling pathway, cell cycle and DNA replication. In conclusion, our results suggest that TPPP3 may be considered as an antioncogene, which plays an important role in the occurrence and progression of NPC. Abbreviations: TPPP3: tubulin polymerization promoting protein family member 3; NPC: nasopharyngeal carcinoma; GEO: Gene Expression Omnibus; qRT-PCR: quantitative real-time PCR; GFP: green fluorescence protein; MOI, transfected multiplicity of infection; CCK-8: cell counting kit-8; OD: optical density; GSEA: gene set enrichment analysis; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; MMP-2: matrix metalloproteinase-2; MMP-9: matrix metalloproteinase-9.
Clinical outcomes of all‐ceramic single crowns and fixed dental prostheses supported by ceramic implants: A systematic review and meta‐analyses

Abstract Objective To analyze the clinical outcomes of all‐ceramic single crowns (SCs) and fixed dental prostheses (FDPs) supported by ceramic implants. Materials and Methods Based on a focused question and customized PICO framework, electronic (Medline/EMBASE/Cochrane) and manual searches for studies reporting the clinical outcomes of all‐ceramic SCs and FDPs supported by ceramic implants ≥12 months were performed. The primary outcomes were reconstruction survival and the chipping proportion. The secondary outcomes were implant survival, technical complications, and patient‐related outcome measurements. Meta‐analyses were performed after 1, 2, and 5 years using random‐effect meta‐analyses. Results Eight of the 1,403 initially screened titles and 55 full texts were included. Five reported on monolithic lithium disilicate (LS2) SCs, one on veneered zirconia SCs, and two on veneered zirconia SCs and FDPs, which reported all on cement‐retained reconstructions (mean observation: 12.0–61.0 months). Meta‐analyses estimated a 5‐year survival rate of 94% (95% confidence interval [CI]: 82%–100%) for overall implant survival. Reconstruction survival proportions after 5 years were: monolithic LS2, 100% (95%CI: 95%–100%); veneered zirconia SCs, 89% (95%CI: 62%–100%); and veneered zirconia FDPs 94% (95%CI: 81%–100%). The chipping proportion after 5 years was: monolithic LS2, 2% (95%CI: 0%–11%); veneered zirconia SCs, 38% (95%CI: 24%–54%); and veneered zirconia FDPs, 57% (95%CI: 38%–76%). Further outcomes were summarized descriptively. Conclusions Due to the limited data available, only tendencies could be identified. All‐ceramic reconstructions supported by ceramic implants demonstrated promising survival rates after mid‐term observation. However, high chipping proportions of veneered zirconia SCs and, particularly, FDPs diminished the overall outcome. Monolithic LS2 demonstrated fewer clinical complications. Monolithic reconstructions could be a valid treatment option for ceramic implants.
Climate warming promotes deterministic assembly of arbuscular mycorrhizal fungal communities

Arbuscular mycorrhizal fungi (AMF) significantly contribute to plant resource acquisition and play important roles in mediating plant interactions and soil carbon (C) dynamics. However, it remains unclear how AMF communities respond to climate change. We assessed impacts of warming and precipitation alterations (30% increase or decrease) on soil AMF communities, and examined major ecological processes shaping the AMF community assemblage in a Tibetan alpine meadow. Our results showed that warming significantly increased root biomass, and available nitrogen (N) and phosphorus (P) in soil. While precipitation alterations increased AMF abundances, they did not significantly affect the composition or diversity of AMF communities. In contrast, warming altered the composition of AMF communities and reduced their Shannon–Wiener index and Pielou's evenness. In particular, warming shifted the AMF community composition in favor of Diversisporaceae over Glomeraceae, likely through its impact on soil N and P availability. In addition, AMF communities were phylogenetically random in the unwarmed control but clustered in warming plots, implying more deterministic community assembly under climate warming. Warming enhancement of root growth, N and P availability likely reduced plant C‐allocation to AMF, imposing stronger environmental filtering on AMF communities. We further proposed a conceptual framework that integrates biological and geochemical processes into a mechanistic understanding of warming and precipitation changes’ effects on AMF. Taken together, these results suggest that soil AMF communities may be more sensitive to warming than expected, highlighting the need to monitor their community structure and associated functional consequences on plant communities and soil C dynamics under the future warmer climate.
Combined seronegativity in Sjögren's syndrome.

OBJECTIVES To describe the clinical spectrum of Sjögren's syndrome (SS) patients with combined seronegativity. METHODS From a multicentre study population of consecutive SS patients fulfilling the 2016 ACR-EULAR classification criteria, patients with triple seronegativity [anti-Ro/SSA(-), anti-La/SSB(-), RF(-) and ANA(+)] and quadruple seronegativity [anti-Ro/SSA(-), anti-La/SSB(-), RF(-) and ANA(-)] were identified retrospectively. Both groups were matched in an 1:1 ratio with 2 distinct control SS groups: i) classic anti-Ro/SSA seropositive patients [SS(+)] and ii) classic anti-Ro/SSA seropositive patients with negative rheumatoid factor [SS(+)/RF(-)] to explore their effect on disease expression. Clinical, laboratory and, histologic features were compared. A comparison between triple and quadruple seronegative SS patients was also performed. REESULTS One hundred thirty-five SS patients (8.6%) were identified as triple seronegative patients and 72 (4.5%) as quadruple. Triple seronegative patients had lower frequency of peripheral nervous involvement (0% vs. 7.2% p=0.002) compared to SS(+) controls and lower frequency of interstitial renal disease and higher prevalence of dry mouth than SS(+)/RF(-) controls. Quadruple seronegative patients presented less frequently with persistent lymphadenopathy (1.5% vs. 16.9 p=0.004) and lymphoma (0% vs. 9.8% p=0.006) compared to SS(+) controls and with lower prevalence of persistent lymphadenopathy (1.5% vs. 15.3% p=0.008) and higher frequency of dry eyes (98.6% vs. 87.5% p=0.01) and autoimmune thyroiditis (44.1% vs. 17.1% p=0.02) compared to SS(+)/RF(-) SS controls. Study groups comparative analysis revealed that triple seronegative patients had higher frequency of persistent lymphadenopathy and lymphoma, higher focus score and later age of SS diagnosis compared to quadruple seronegative patients. CONCLUSIONS Combined seronegativity accounts for almost 9% of total SS population and is associated with a milder clinical phenotype, partly attributed to the absence of rheumatoid factor.
Drosophila Model for Gut-Mediated Horizontal Transfer of Narrow- and Broad-Host-Range Plasmids

Microbial evolution in the gut of animals due to horizontal gene transfer (HGT) is of significant interest for microbial evolution as well as within the context of human and animal health. Microbial populations evolve within the host, and factors from the bacteria and host interact to regulate this evolution. ABSTRACT Horizontal gene transfer (HGT) is a driving force of microbial evolution. The gut of animals acts as a potent reservoir for the lateral transfer of virulence, fitness, and antimicrobial resistance genes through plasmids. Reduced-complexity models for the examination of host-microbe interactions involved in plasmid transfer are greatly desired. Thus, this study identifies the use of Drosophila melanogaster as a model organism for the conjugation of plasmids of various incompatibility groups in the gut. Enterobacteriaceae conjugation pairs were identified in vitro and used for oral inoculation of the Drosophila gut. Flies were enumerated for the donor, recipient, and transconjugant populations. Each donor-recipient pair was observed to persist in fly guts for the duration of the experiment. Gut concentrations of the donors and recipients were significantly different between male and female flies, with females generally demonstrating increased concentrations. Furthermore, host genetics significantly altered the concentrations of donors and recipients. However, transconjugant concentrations were not affected by host sex or genetics and were detected only in the IncPε and IncI1 plasmid groups. This study demonstrates Drosophila melanogaster as a model for gut-mediated plasmid transfer. IMPORTANCE Microbial evolution in the gut of animals due to horizontal gene transfer (HGT) is of significant interest for microbial evolution as well as within the context of human and animal health. Microbial populations evolve within the host, and factors from the bacteria and host interact to regulate this evolution. However, little is currently known about how host and bacterial factors regulate plasmid-mediated HGT in the gut. This study demonstrates the use of Drosophila and the roles of sexual dimorphism as well as plasmid incompatibility groups in HGT in the gut.
Morphologic and Genomic Characteristics of Breast Cancers Occurring in Individuals with Lynch Syndrome

Purpose: Lynch syndrome is defined by germline pathogenic mutations involving DNA mismatch repair (MMR) genes and linked with the development of MMR-deficient colon and endometrial cancers. Whether breast cancers developing in the context of Lynch syndrome are causally related to MMR deficiency (MMRd), remains controversial. Thus, we explored the morphologic and genomic characteristics of breast cancers occurring in Lynch syndrome individuals. Experimental Design: A retrospective analysis of 20,110 patients with cancer who underwent multigene panel genetic testing was performed to identify individuals with a likely pathogenic/pathogenic germline variant in MLH1, MSH2, MSH6, or PMS2 who developed breast cancers. The histologic characteristics and IHC assessment of breast cancers for MMR proteins and programmed death-ligand 1 (PD-L1) expression were assessed on cases with available materials. DNA samples from paired tumors and blood were sequenced with Memorial Sloan Kettering–Integrated Mutation Profiling of Actionable Cancer Targets (≥468 key cancer genes). Microsatellite instability (MSI) status was assessed utilizing MSISensor. Mutational signatures were defined using SigMA. Results: A total of 272 individuals with Lynch syndrome were identified, 13 (5%) of whom had primary breast cancers. The majority of breast cancers (92%) were hormone receptor–positive tumors. Five (42%) of 12 breast cancers displayed loss of MMR proteins by IHC. Four (36%) of 11 breast cancers subjected to tumor-normal sequencing showed dominant MSI mutational signatures, high tumor mutational burden, and indeterminate (27%) or high MSISensor scores (9%). One patient with metastatic MMRd breast cancer received anti-PD1 therapy and achieved a robust and durable response. Conclusions: A subset of breast cancers developing in individuals with Lynch syndrome are etiologically linked to MMRd and may benefit from anti-PD1/PD-L1 immunotherapy.
Neoadjuvant In Situ Immunomodulation Enhances Systemic Antitumor Immunity against Highly Metastatic Tumors

Neoadjuvant induction and activation of cDC1s in primary tumors enhances systemic antitumor immunity, suppresses metastatic progression, improves survival, and synergizes with anti–PD-L1 therapy. Neoadjuvant immunotherapy, given before surgical resection, is a promising approach to develop systemic antitumor immunity for the treatment of high-risk resectable disease. Here, using syngeneic and orthotopic mouse models of triple-negative breast cancer, we have tested the hypothesis that generation of tumor-specific T-cell responses by induction and activation of tumor-residing Batf3-dependent conventional type 1 dendritic cells (cDC1) before resection improves control of distant metastatic disease and survival. Mice bearing highly metastatic orthotopic tumors were treated with a combinatorial in situ immunomodulation (ISIM) regimen comprised of intratumoral administration of Flt3L, local radiotherapy, and in situ TLR3/CD40 stimulations, followed by surgical resection. Neoadjuvant ISIM (neo-ISIM) generated tumor-specific CD8+ T cells that infiltrated into distant nonirradiated metastatic sites, which delayed the progression of lung metastases and improved survival after the resection of primary tumors. The efficacy of neo-ISIM was dependent on de novo adaptive T-cell immunity elicited by Batf3-dependent dendritic cells and was enhanced by increasing dose and fractionation of radiotherapy, and early surgical resection after the completion of neo-ISIM. Importantly, neo-ISIM synergized with programmed cell death protein-1 ligand-1 (PD-L1) blockade to improve control of distant metastases and prolong survival, while removal of tumor-draining lymph nodes abrogated the antimetastatic efficacy of neo-ISIM. Our findings illustrate the therapeutic potential of neoadjuvant multimodal intralesional therapy for the treatment of resectable tumors with high risk of relapse. Significance: Neoadjuvant induction and activation of cDC1s in primary tumors enhances systemic antitumor immunity, suppresses metastatic progression, improves survival, and synergizes with anti–PD-L1 therapy. Graphical Abstract
To Use or Not Use Complementary and Alternative Medicine (CAM) in Psychiatric Care: Interviews with Clinical Decision-Makers in Sweden

Abstract Complementary and alternative medicine (CAM) is used as a complementary intervention in psychiatric healthcare. The reasons for using or not using CAM in psychiatric care in Sweden, and how such decisions are taken, are largely unknown. The aim was to investigate arguments for and against the use of CAM in Swedish psychiatric care, and how decisions are made. Interviews with 10 persons in decision-making positions in psychiatric health care were analysed thematically. The result shows diverging understandings of the evidence base for CAM. Arguments against CAM referred to scepticism, the importance of evidence-based practice and the obligation to follow national guidelines. Arguments in favour of CAM were that CAM was person-centred, safe, cost-effective, nursing interventions with positive effects, appreciated and demanded by patients, providing space for non-verbal communication and reflection, supporting the therapeutic alliance. Decision paths were described as top-down through a hierarchical structure, or bottom-up, driven by committed staff members. We discuss how detailed national guidelines should be to achieve equal and evidence-based care, while still allowing clinics to make local exceptions, adjusting the care according to clinical expertise and patients’ preferences. Conclusion: Evidence-based, safe and cost-effective CAM methods may be relevant complementary interventions in psychiatric care, or as self-care, not to cure the psychiatric disease, but to reduce symptoms and promote sleep. With better knowledge of CAM, health professionals could guide patients through the jungle of CAM methods. Due to research problems on complex multicomponent interventions, high-quality pragmatic trials, including biomarkers, and qualitative studies are recommended.