Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of Abutment Geometry and Luting Agents on the Vertical Marginal Discrepancy of Cast Copings on Implant Abutments: An In Vitro Study

Aim Vertical marginal discrepancy (VMD) influences the success of implant-supported restorations. However, there is little literature that has investigated the influence of geometry and cementing agent on changes in VMD of metal copings on implant abutments. The objective was to evaluate the effect of the geometry of the abutment and cementing agents on VMD. Methods Cast copings were cemented on implant abutments customized cylindrical (4, 5.5, and 7 mm) and on hexagonal implant abutments (4 mm) cemented or uncemented molded copings were placed (n = 4, totally 64 samples) with different luting agents. The VMD of the copings were measured in the coping-abutment interface at three reference points using a stereomicroscope. The independent Student's t test was used for comparison between the two different abutment walls. The post hoc statistical analysis was performed by the Tukey test. Results There was a significant VMD increase between noncemented and cemented cast copings using different luting agents. Abutment geometry and luting agents significantly influenced the VMD (p ≤ 0.05). Cylindrical abutment at 7 mm in height cemented with different luting agent tested showed significantly higher VMD values than cylindrical abutments of 4 mm (p=0.019). Hexagonal abutments with a 4 mm height showed significantly higher VMD values than cylindrical 4 mm abutments using zinc oxide noneugenol and glass ionomer cements (p=0.032). Conclusions Abutment geometry and luting agents influence the VMD of cast copings cemented on implant abutment. The higher the cylindrical abutment, the greater the VMD, and hexagonal wall abutments promote greater marginal gap.
Clustering assessment in weighted networks

We provide a systematic approach to validate the results of clustering methods on weighted networks, in particular for the cases where the existence of a community structure is unknown. Our validation of clustering comprises a set of criteria for assessing their significance and stability. To test for cluster significance, we introduce a set of community scoring functions adapted to weighted networks, and systematically compare their values to those of a suitable null model. For this we propose a switching model to produce randomized graphs with weighted edges while maintaining the degree distribution constant. To test for cluster stability, we introduce a non parametric bootstrap method combined with similarity metrics derived from information theory and combinatorics. In order to assess the effectiveness of our clustering quality evaluation methods, we test them on synthetically generated weighted networks with a ground truth community structure of varying strength based on the stochastic block model construction. When applying the proposed methods to these synthetic ground truth networks’ clusters, as well as to other weighted networks with known community structure, these correctly identify the best performing algorithms, which suggests their adequacy for cases where the clustering structure is not known. We test our clustering validation methods on a varied collection of well known clustering algorithms applied to the synthetically generated networks and to several real world weighted networks. All our clustering validation methods are implemented in R, and will be released in the upcoming package clustAnalytics.
Knee Septic Arthritis after Palm Tree Thorn Injury: A Case Report

Introduction: A monoarthritic painful knee may have multiple etiologies, of which septic arthritis is commonly considered to be one of the most deleterious pathologies. This type of acute symptom is, in the literature, for some rare cases, related to an inflammatory process secondary to a penetrating plant thorn, which was considered an aseptic process and therefore treated by removing the foreign body. This work reports a recent case falling into that diagnosis, which due to its infrequent nature, could have been misevaluated and consequently mistreated. Case Report: Our goal is to bring to the attention of the orthopedic community that this type of deleterious pathology, which is today uncommon, must never be fully disregarded. We share a case of a 68-year-old male who was admitted 2 days after being injured by a palm tree (Arecaceae) thorn with acute inflammatory signs and effusion in the left knee. Although, ultrasound excluded pathway or intra-articular foreign bodies, in the arthroscopic procedure, a thorn was found and removed. Pantoea agglomerans was identified in the synovial fluid. Conclusion: Following the removal of the foreign body, empirical antibiotic treatment with coverage against Gram-negative pathogens was initiated and later on replaced by appropriate antibiotics, after susceptibility testing is obtained.
P2X7R in Mast Cells is a Potential Target for Salicylic Acid and Aspirin in Treatment of Inflammatory Pain

Background Mast cells are well known for their role in inflammatory pain. P2X7 receptor (P2X7R) has attracted much attention due to its prominent role in inflammatory diseases. Salicylates are commonly used anti-inflammatory and analgesic drugs. Until now, little has been known about whether P2X7R in mast cells is involved in inflammatory pain and whether it is a potential target for salicylates. Methods First, the expression of P2X receptors in mouse peritoneal mast cells was detected by using RT-PCR, immunofluorescence, calcium imaging and electrophysiological technique. In addition, the functions of P2X receptors, especially P2X7R, in mast cells were studied by using QPCR, ELISA and behavioral tests. Furthermore, P2X7R was used as a target to screen for some anti-inflammatory monomers that could inhibit its activity. At last, the effect of salicylic acid (SA) and aspirin (ASA) on the activity of P2X7R was studied by using calcium imaging, electrophysiological technique, ELISA, real-time PCR, behavioral tests, immunofluorescence and molecular docking. Results We found that P2X1, P2X3, P2X4 and P2X7 receptors were expressed in mouse peritoneal mast cells. The functions of different P2X receptors were various. Activation of P2X7R in mouse mast cells induced the release of inflammatory mediators, such as histamine, IL-1β, and CCL3. In addition, inflammation pain induced by high concentrations of ATP could be alleviated by P2X7R blockers or mast cell defects. Interestingly, SA or ASA could reduce high concentrations of ATP-induced inward current, P2X7R upregulation, mediators release, and inflammatory pain. SA or ASA also inhibited the inward current evoked by P2X7R agonist, BZATP. Molecular docking showed that SA or ASA had affinity for the cytoplasmic GDP-binding region of P2X7R. Conclusion P2X7R in mast cells was involved in inflammation pain by releasing inflammatory mediators, and P2X7R might be a potential target for SA and ASA analgesia.
Anti-CD22 CAR-T Cell Therapy as a Salvage Treatment in B Cell Malignancies Refractory or Relapsed After Anti-CD19 CAR-T therapy

Background To observe efficacy of the anti-CD22 chimeric antigen receptor modified (anti-CD22-CAR) T cell salvage therapy in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) and B cell acute lymphoid leukemia (B-ALL) patients whose disease did not reach CR or progressed again after anti-CD19-CAR T cell therapy. Methods In our study, seven R/R DLBCL patients reached stable disease (SD) or progression of disease (PD) after their anti-CD19-CAR T cell therapy. Only three in all the six R/R B-ALL patients obtained complete response (CR)/CR with incomplete count recovery (Cri) in their anti-CD19-CAR T cell therapy, but they relapsed again in the following three, six and one months. Then, all these thirteen R/R DLBCL and B-ALL patients received anti-CD22 CAR-T cell salvage therapy because their disease did not reach CR or progressed again. Results Four R/R DLBCL patients obtained CR, while two R/R DLBCL patients achieved PR and one patient achieved SD. But only two R/R B-ALL patients obtained Cri in their anti-CD22 CAR-T cell salvage therapy. The overall survival (OS) of R/R DLBCL patients after the anti-CD22 CAR-T cell therapy was 6.142±3.395 months until August 31, 2020. There was no different of the median expansion peaks of the two kinds of CAR T cells (P=0.920). The time of anti-CD22-CAR T cell proportion peak days was later than that of the time of anti-CD19-CAR T cell peak days post infusion (P=0.022). Their cytokine release syndrome (CRS) was graded 2–4 in their anti-CD19-CAR T cell therapy, while the notable CRS was graded 1–2 in their anti-CD22-CAR T cell therapy. But there was no difference in the CRS and the immune effect or cell associated neurotoxic syndrome (ICANS) grades in the two kinds of therapies. And there was no difference in the hematological toxicity grades in the two kinds of therapies. Conclusion The anti-CD22-CAR T cell salvage therapy is highly effective in R/R DLBCL patients than in R/R B-ALL patients who failed in anti-CD19-CAR T cell therapy before. We need to expand the number of R/R DLBCL or B-ALL patients and continue to observe. Trial Registration ChiCTR-ONN-16009862 and ChiCTR1800019298.
Early changes in the immune microenvironment of oral potentially malignant disorders reveal an unexpected association of M2 macrophages with oral cancer free survival

ABSTRACT Understanding the dynamics of the immune microenvironment is critical to the development of immuno-based strategies for the prevention of oral potentially malignant disorders transformation to oral squamous cell carcinoma (OSCC). We used laser capture microdissection and RNA-sequencing to profile the expression of 13 matched pairs of epithelial versus stromal compartments from normal mucosa, hyperplasia, dysplasia, and invasive tumors in the 4-nitroquinolein (4-NQO) murine model of oral carcinogenesis. Genes differentially expressed at each step of transformation were defined. Immune cell deconvolution and enrichment scores of various biological processes including immune-related ones were computed. Immunohistochemistry was also performed to characterize the immune infiltrates by T-cells (T-cells CD3+, helper CD4+, cytotoxic CD8+, regulatory FoxP3+), B-cells (B220+), and macrophages (M1 iNOS+, M2 CD163+) at each histological step. Enrichment of three independent M2 macrophages signatures were computed in 86 oral leukoplakia with available clinical outcome. Most gene expression changes were observed in the stromal compartment and related to immune biological processes. Immune cell deconvolution identified infiltration by the macrophage population as the most important quantitatively especially at the stage of dysplasia. In 86 patients with oral leukoplakia, three M2 macrophages signatures were independently associated with improved oral cancer-free survival. This study provides a better understanding of the dynamics of the immune microenvironment during oral carcinogenesis and highlights an unexpected association of M2 macrophages gene expression signatures with oral cancer free survival in patients with oral leukoplakia.
Kisspeptin and Hematologic Parameters as Predictive Biomarkers for First-Trimester Abortions

Abstract Objective Spontaneous abortion is the most common complication of early pregnancy, affecting up to 20% of recognized pregnancies. Kisspeptin is predominantly released by placental syncytiotrophoblasts, and regulates their placental invasion into the uterine matrices. We aimed to establish an association of serum kisspeptin levels with pregnancy outcomes during the early gestational stage of the first trimester. Method In this prospective study, 90 pregnant women in their 7 to 8 6/7 gestational weeks were classified into three groups: (i) The control group, consisting of healthy pregnant women (n=30), (ii) the threatened abortion group (n=30), and (iii) the spontaneous abortion group (n=30). The maternal serum samples were analyzed for complete blood count parameters and kisspeptin levels. Results There was no statistical difference regarding body mass index (BMI) and gestational age (p=0.370). Regarding detailed obstetric notations, including gravida, parity, abortion, and living children, socioeconomic levels, and employment rates, all study groups were comparable (p>0.05, for all). No significant association was found regarding the biochemical parameters of complete blood count, including neutrophil, lymphocyte, and platelet concentrations, as well as neutrophil-to-lymphocyte ratios (NLR) and platelet-to-lymphocyte ratios (PLR) (p>0.05, for all). The median serum kisspeptin levels of the study groups did not differ between the groups (p=0.153). Correlation analysis revealed no significant relationship between serum kisspeptin levels and other study parameters in any study groups (p>0.05, for all) Conclusion We found no statistically significant relationship between serum kisspeptin concentrations and pregnancy outcomes in the early gestational stage of the first trimester, and serum kisspeptin concentrations did not seem to be a reliable marker to distinguish abortion status from viable pregnancy.
Excess mortality analysis for Germany for all three COVID-19 waves in 2020 - 2021

Background and Aims: The reported case and death numbers of the coronavirus disease (COVID-19) are often used to estimate the impact of COVID-19. We observe that during the second half of the first and second waves, the COVID-19 deaths are significantly higher than the excess mortality. We attribute the difference to the pre-dying effect. We then compare the excess mortality to the official COVID-19 death numbers and calculate the infection fatality rates (IFRs) and the percentage of infected individuals from excess mortality for different age bands. We also compare the impact of COVID-19 to past influenza waves and analyze the vaccination effect on excess mortality. Methods: We forecast the baseline mortality from official data on deaths in Germany. Distributing a part of excess mortality into the near future, we lower the baseline simulating the pre-dying effect. From there, we compare the excess mortality to official COVID-19 deaths. From the observed mortality deficit, we estimate the percentage of infected individuals and then estimate the age-dependent IFRs. Results: In the first wave, we find an overall excess mortality of ca. 8 000. For the second wave, the overall excess mortality adds up to ca. 56 000. We find, that the pre-dying effect explains the difference between the official COVID-19 deaths and excess mortality in the second half of the waves to a high degree. Attributing the whole excess mortality to COVID-19, we find that the IFRs are significantly higher in the second wave. In the third wave, we find an excess mortality in mid-age bands which cannot be explained by the official COVID-19 deaths. For the senior band 80+, we find results in favor of a strong and positive vaccination effect for the third COVID-19 wave. Conclusions: We conclude that in the first and second COVID-19 waves, the COVID-19 deaths explain almost all excess mortality when the pre-dying effect is taken into account. In the third wave in 2021, the excess mortality is not very pronounced for the 80+ age band, probably due to vaccination. The partially unvaccinated 40-80 age group experiences a pronounced excess mortality in the third wave while there are too few official COVID-19 deaths to explain the excess. The no-vaccination scenario for the 80+ age band results in a similarly high excess mortality as for the more younger age bands, suggesting a very positive vaccination effect on reduction of COVID-19 deaths.
POST-COVID-19 SYNDROME, INFLAMMATORY MARKERS AND SEX DIFFERENCES

INTRODUCTION AND OBJECTIVE Post-COVID syndrome (PCS) is a poorly-known entity. Underlying low-grade inflammation (LGI) has been theorized as one of its pathophysiological mechanisms. We aimed to investigate a possible relationship between PCS and an increase in inflammation markers, in a sex-stratified analysis. PARTICIPANTS AND METHODS Mild cases of COVID-19 according to the WHO classification followed-up in a Primary Care Center, were included. We collected epidemiological data (age, sex, body mass index -BMI-, smoking, and comorbidities -Charlson index-), variables of the acute COVID-19 episode, and data at 3 months of follow-up (clinical manifestations and inflammatory markers). Serum C-reactive protein (CRP), neutrophil and lymphocyte counts, neutrophil/lymphocyte ratio (NLR), lactate dehydrogenase (LDH), ferritin, fibrinogen, and D-dimer levels were analyzed. Low-grade inflammation (LGI) was defined as serum CRP between >0.3 and <1.0 mg/dL. Five composite indices were built combining the upper ranges of 4 markers. Bivariate and multivariate analyses (logistic regression and general linear models) were performed, stratified by sex. RESULTS We analyzed 121 subjects with mild COVID-19 (56.2% women; mean age 46 years). The most common symptom in the acute episode was fever (60.3%), while it was fatigue in PCS (42.8%). Prevalence of PCS was 35.8% in women and 20.8% in men (p = 0.07). In women, after controlling for age, BMI, smoking, and comorbidities, the D1, D3, and D4 indices were consistently associated with PCS, with ORs of 5.14 (95% CI, 1.6-16.4), 4.20 (95% CI, 1.3- 13.3), and 4.12 (95% CI, 1.3-13.1), respectively; in patients with post-COVID anosmia and ageusia, neutrophils were significantly elevated (3.43 {+/-} 0.3 vs 2.58 {+/-} 0.1; p = 0.014, and 3.89 {+/-}0.3 vs 2.59 {+/-} 0.1; p = 0.002, respectively), after adjusting for confounders. In men, the D2 and D5 indices were associated with PCS, with adjusted ORs of 10.1 (95% CI, 1.2- 85) and 17.5 (95% CI, 2-153), respectively; furthermore, serum CRP in the LGI range was associated with PCS [adjusted OR=12.9 (95% CI, 1.3-121)], and in post-COVID persistent fatigue, the neutrophil count was significantly elevated (4.68 {+/-} 0.6 vs 3.37 {+/-} 0.1; p = 0.041), after controlling for confounders. CONCLUSIONS Consistent associations among PCS, anosmia, ageusia, and fatigue, with slight -but significant- elevated levels of inflammatory markers, have been observed. The neutrophil count was the most frequently involved marker. Sex-stratified analyses showed relevant differences between women and men concerning PCS and serum inflammatory markers.
Loss of MGA repression mediated by an atypical polycomb complex promotes tumor progression and invasiveness

MGA, a transcription factor and member of the MYC network, is mutated or deleted in a broad spectrum of malignancies. As a critical test of a tumor suppressive role, we inactivated Mga in two mouse models of non-small cell lung cancer using a CRISPR-based approach. MGA loss significantly accelerated tumor growth in both models and led to de-repression of non-canonical Polycomb ncPRC1.6 targets, including genes involved in metastasis and meiosis. Moreover, MGA deletion in human lung adenocarcinoma lines augmented invasive capabilities. We further show that MGA-MAX, E2F6, and L3MBTL2 co-occupy thousands of promoters and that MGA stabilizes these ncPRC1.6 subunits. Lastly, we report that MGA loss also induces a pro-growth effect in human colon organoids. Our studies establish MGA as a bona fide tumor suppressor in vivo and suggest a tumor suppressive mechanism in adenocarcinomas resulting from widespread transcriptional attenuation of MYC and E2F target genes mediated by MGA-MAX associated with a non-canonical Polycomb complex.
Multimodal single-cell analysis of cutaneous T cell lymphoma reveals distinct sub-clonal tissue-dependent signatures.

Cutaneous T cell lymphoma (CTCL) is a heterogeneous group of mature T cell neoplasms characterized by the accumulation of clonal malignant CD4+ T cells in the skin. The most common variant of CTCL, Mycosis Fungoides, is confined to the skin in early stages but can be accompanied by extracutaneous dissemination of malignant T cells to the blood and lymph nodes in advanced stages of disease. Sézary Syndrome, a leukemic form of disease is characterized by significant blood involvement. Little is known about the transcriptional and genomic relationship between skin and blood residing malignant T cells in CTCL. To identify and interrogate malignant clones in matched skin and blood from leukemic MF and SS patients, we combine T cell receptor clonotyping, with quantification of gene expression and cell surface markers at the single cell level. Our data reveals clonal evolution at a transcriptional and genetic level within the malignant populations of individual patients. We highlight highly consistent transcriptional signatures delineating skin-derived and blood-derived malignant T cells. Analysis of these two populations suggests that environmental cues, along with genetic aberrations, contribute to transcriptional profiles of malignant T cells. Our findings indicate that the skin microenvironment in CTCL promotes a transcriptional response supporting rapid malignant expansion, as opposed to the quiescent state observed in the blood, potentially influencing efficacy of therapies. These results provide insight into tissue-specific characteristics of cancerous cells and underscore the need to address the patients' individual malignant profiles at the time of therapy to eliminate all sub-clones.
The safety of morphine in patients with acute heart failure: A systematic review and meta‐analysis

While morphine has long been widely used in treating acute heart failure (AHF) due to its vasodilatory properties and anticipated anxiolysis, it remains unclear whether the application of morphine to those patients is reasonable. We aim to conduct a systematic review and meta‐analysis to assess the safety of morphine in patients with AHF. We searched PubMed, Cochrane Library, and Embase electronic databases from inception through March 2020. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the outcomes. Seven studies with 172, 226 patients were included. The results showed that morphine usage was not associated with increased in‐hospital mortality (OR: 1.94; 95% CI 0.93 to 4.03; p = 0.08). However, the use of morphine significantly increased the risk of invasive ventilation (OR: 2.72; 95% CI 1.09 to 6.80; p = 0.03). Furthermore, the subgroup analysis indicated that the application of morphine was not associated with increased 7‐day all‐cause mortality in patients with AHF (OR: 1.69; 95% CI 0.80 to 3.22; p = 0.11) but significantly increased the risk of 30‐day all‐cause mortality (OR: 1.59; 95% CI 1.16 to 2.17; p = 0.004). Based on current evidence, our results suggested that although morphine therapy did not significantly increase the risk of short‐term death (in the hospital or within 7 days) in patients with AHF, the risk of long‐term death and invasive ventilation were significantly increased. This result needs to be further confirmed by an ongoing randomized control trial.