Miracle-dz/UniFAR-FTUs huggingface dataset:
Mitochondrial Function in the Kidney and Heart, but not the Brain, is Mainly Altered in an Experimental Model of Endotoxaemia.

Significant impairments in mitochondrial function are associated with the development of multi-organ failure in sepsis/endotoxaemia, but the data on the dynamics of simultaneous mitochondrial impairment in multiple organs are limited. The aim of this study was to evaluate the changes in heart, brain and kidney mitochondrial function in an experimental model of lipopolysaccharide (LPS)-induced endotoxaemia.Samples were collected 4 and 24 h after single injection of LPS (10 mg/kg) in mice. Marked increases in inflammation-related gene expression were observed in all studied tissues 4 h after LPS administration. At 24 h post LPS administration, this expression of inflammation-related genes remained upregulated only in kidneys. Significantly increased concentrations of kidney function markers confirmed that kidneys were severely damaged. Echocardiographic measurements showed that the ejection fraction and fractional shortening were significantly reduced 4 h after LPS administration, whereas 24 h after LPS administration, the cardiac function was restored to baseline. A two-fold decrease in mitochondrial oxidative phosphorylation (OXPHOS) capacity in the kidney was observed 4 and 24 h after LPS administration. Significant decrease in mitochondrial fatty acid oxidation was observed in heart 4 h after LPS administration. Furthermore, 24 h after LPS administration, the respiration rates in cardiac fibres at OXPHOS and electron transport (ET) states were significantly increased, which resulted in increased ET coupling efficiency in the LPS-treated group, whereas four-fold increases in the H2O2 production rate and H2O2/O ratio were observed. The brain mitochondria demonstrated a slightly impaired mitochondrial functionality just 24 h after the induction of endotoxaemia.In conclusion, among studied tissues kidney mitochondria are the most sensitive to endotoxaemia and do not recover from LPS-induced damage, whereas in brain, mitochondrial function was not significantly altered. In heart, endotoxaemia induces a decrease in the mitochondrial fatty acid oxidation capacity, but during the phase of suppressed inflammatory response, the ET efficiency is improved despite the marked increase in reactive oxygen species production.
Facile and Green Synthesis of Graphene-Based Conductive Adhesives via Liquid Exfoliation Process

In this study, we report a facile and green process to synthesize high-quality and few-layer graphene (FLG) derived from graphite via a liquid exfoliation process. The corresponding characterizations of FLG, such as scanning electron microscopy (SEM), transmission electron microscope (TEM), atomic force microscopy (AFM) and Raman spectroscopy, were carried out. The results of SEM show that the lateral size of as-synthesized FLG is 1–5 μm. The results of TEM and AFM indicate more than 80% of graphene layers is <10 layers. The most surprising thing is that D/G ratio of graphite and FLG are 0.15 and 0.19, respectively. The result of the similar D/G ratio demonstrates that little structural defects were created via the liquid exfoliation process. Electronic conductivity tests and resistance of composite film, in terms of different contents of graphite/polyvinylidene difluoride (PVDF) and FLG/PVDF, were carried out. Dramatically, the FLG/PVDF composite demonstrates superior performance compared to the graphite/PVDF composite at the same ratio. In addition, the post-sintering process plays an important role in improving electronic conductivity by 85%. The composition-optimized FLG/PVDF thin film exhibits 81.9 S·cm−1. These results indicate that the developed FLG/PVDF composite adhesives could be a potential candidate for conductive adhesive applications.
Cu-Doped ZnO Electronic Structure and Optical Properties Studied by First-Principles Calculations and Experiments

The band structure, the density of states and optical absorption properties of Cu-doped ZnO were studied by the first-principles generalized gradient approximation plane-wave pseudopotential method based on density functional theory. For the Zn1-xCuxO (x = 0, x = 0.0278, x = 0.0417) original structure, geometric optimization and energy calculations were performed and compared with experimental results. With increasing Cu concentration, the band gap of the Zn1-xCuxO decreased due to the shift of the conduction band. Since the impurity level was introduced after Cu doping, the conduction band was moved downwards. Additionally, it was shown that the insertion of a Cu atom leads to a red shift of the optical absorption edge, which was consistent with the experimental results.
The methyltransferase SETD6 regulates Mitotic progression through PLK1 methylation

Significance The involvement of nonhistone protein methylation in cellular essential pathways is a rising field. Here we show evidence for the involvement of direct lysine methylation of the mitosis regulator PLK1 by SETD6 methyltransferase in cell cycle promotion. Our results reveal that this methylation occurs on two lysine residues and that lack of methylation leads to enhanced PLK1 catalytic activity, causing accelerated mitosis pace and thus faster proliferation rates. These findings suggest that PLK1 methylation by SETD6 controls the pace of mitotic progression, greatly enhancing our understanding of cell cycle complexity. The role of methylation in mitotic progression raises the possibility of its involvement in tumorigenic pathways by orchestrating cell division rates and might have insightful implications for the development of cancer-specific markers. Lysine methylation, catalyzed by protein lysine methyltransferases (PKMTs), is a key player in regulating intracellular signaling pathways. However, the role of PKMTs and the methylation of nonhistone proteins during the cell cycle are largely unexplored. In a recent proteomic screen, we identified that the PKMT SETD6 methylates PLK1—a key regulator of mitosis and highly expressed in tumor cells. In this study, we provide evidence that SETD6 is involved in cell cycle regulation. SETD6-deficient cells were observed to progress faster through the different mitotic steps toward the cytokinesis stage. Mechanistically, we found that during mitosis SETD6 binds and methylates PLK1 on two lysine residues: K209 and K413. Lack of methylation of these two residues results in increased kinase activity of PLK1, leading to accelerated mitosis and faster cellular proliferation, similarly to SETD6-deficient cells. Taken together, our findings reveal a role for SETD6 in regulating mitotic progression, suggesting a pathway through which SETD6 methylation activity contributes to normal mitotic pace.
The small RbcS-like domains of the β-carboxysome structural protein CcmM bind RubisCO at a site distinct from that binding the RbcS subunit

Carboxysomes are compartments in bacterial cells that promote efficient carbon fixation by sequestering RubisCO and carbonic anhydrase within a protein shell that impedes CO2 escape. The key to assembling this protein complex is CcmM, a multidomain protein whose C-terminal region is required for RubisCO recruitment. This CcmM region is built as a series of copies (generally 3–5) of a small domain, CcmMS, joined by unstructured linkers. CcmMS domains have weak, but significant, sequence identity to RubisCO's small subunit, RbcS, suggesting that CcmM binds RubisCO by displacing RbcS. We report here the 1.35-Å structure of the first Thermosynechococcus elongatus CcmMS domain, revealing that it adopts a compact, well-defined structure that resembles that of RbcS. CcmMS, however, lacked key RbcS RubisCO-binding determinants, most notably an extended N-terminal loop. Nevertheless, individual CcmMS domains are able to bind RubisCO in vitro with 1.16 μm affinity. Two or four linked CcmMS domains did not exhibit dramatic increases in this affinity, implying that short, disordered linkers may frustrate successive CcmMS domains attempting to simultaneously bind a single RubisCO oligomer. Size-exclusion chromatography–coupled right-angled light scattering (SEC-RALS) and native MS experiments indicated that multiple CcmMS domains can bind a single RubisCO holoenzyme and, moreover, that RbcS is not released from these complexes. CcmMS bound equally tightly to a RubisCO variant in which the α/β domain of RbcS was deleted, suggesting that CcmMS binds RubisCO independently of its RbcS subunit. We propose that, instead, the electropositive CcmMS may bind to an extended electronegative pocket between RbcL dimers.
Portable fibrobronchoscopic treatment for non-severe ischemic stroke-associated pneumonia patients with dysphagia: a pilot study

ABSTRACT Objective: To investigate the efficacy and safety of portable fibrobronchoscopy on the non-severe ischemic stroke-associated pneumonia (SAP) patients with dysphagia. Methods: A total of 86 non-severe ischemic SAP patients with dysphagia were randomly and equally divided into the treatment group and control group. The control group was given routine sputum suction, anti-infection drugs, and sputum-reducing drugs. The treatment group was treated with fiber-optic bronchoscopic sputum suction and alveolar lavage, and drug treatment same as the control group. The blood gases, inflammatory factors, clinical pulmonary infection score (CPIS), adverse reactions, and modified Rankin Scale (mRS) were compared. Results: The blood gases, serum inflammatory factors including procalcitonin (PCT), C-reactive protein (CRP), and tumor necrosis factor-α (TNF-α), and CPIS in the treatment group were superior to those in control group (P < 0.05). No significant difference was found in the incidence of adverse reactions between the two groups (P > 0.05). The mRS scores of the treatment group were significantly lower than those of control group 3 months after discharge. Conclusion: Sputum suction and alveolar lavage with portable fibrobronchoscope can significantly improve the hypoxia and pulmonary infections, reduce the inflammatory response, and thus improve the prognosis, rendering suction and alveolar lavage with portable fibrobronchoscope as a safe and effective treatment for non-severe ischemic SAP patients with dysphagia.
Integration of cell of origin into the clinical CNS International Prognostic Index improves CNS relapse prediction in DLBCL.

Central nervous system (CNS) relapse carries a poor prognosis in diffuse large B-cell lymphoma (DLBCL). Integrating biomarkers into the CNS-International Prognostic Index (CNS-IPI) risk model may improve identification of patients at high risk for developing secondary CNS disease. CNS relapse was analyzed in 1418 DLBCL patients treated with obinutuzumab or rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisone chemotherapy in the phase 3 GOYA study. Cell of origin (COO) was assessed using gene-expression profiling. BCL2 and MYC protein expression was analyzed by immunohistochemistry. The impact of CNS-IPI, COO, and BCL2/MYC dual-expression status on CNS relapse was assessed using a multivariate Cox regression model (data available in n = 1418, n = 933, and n = 688, respectively). High CNS-IPI score (hazard ratio [HR], 4.0; 95% confidence interval [CI], 1.3-12.3; P = .02) and activated B-cell‒like (ABC) (HR, 5.2; 95% CI, 2.1-12.9; P = .0004) or unclassified COO subtypes (HR, 4.2; 95% CI, 1.5-11.7; P = .006) were independently associated with CNS relapse. BCL2/MYC dual-expression status did not impact CNS relapse risk. Three risk subgroups were identified based on the presence of high CNS-IPI score and/or ABC/unclassified COO (CNS-IPI-C model): low risk (no risk factors, n = 450 [48.2%]), intermediate risk (1 factor, n = 408 [43.7%]), and high risk (both factors, n = 75 [8.0%]). Two-year CNS relapse rates were 0.5%, 4.4%, and 15.2% in the respective risk subgroups. Combining high CNS-IPI and ABC/unclassified COO improved CNS relapse prediction and identified a patient subgroup at high risk for developing CNS relapse. The study was registered at www.clinicaltrials. gov as #NCT01287741.
Caught in a vicious cycle? Explaining bidirectional spillover between parent-child relationships and peer victimization

Abstract Relationships with parents and peers are crucial for children's socialization, but how parent–child and peer relationships mutually affect each other is not well understood. Guided by spillover theory, we zoomed in on the bidirectional interplay between parental rejection and warmth on the one hand and peer victimization on the other, and examined whether children's maladjustment symptoms mediated hypothesized cross-domain spillover effects. Data stem from five waves of the longitudinal KiVa study among 9,770 children (50% boys; mean age = 9.16, standard deviation = 1.29). Results from random intercept cross-lagged panel models showed that higher parental rejection and lower parental warmth predicted increases in peer victimization and vice versa across waves, thus supporting the bidirectional model. Moreover, spillover from parent–child rejection and warmth to peer victimization was partially driven by children's depressive symptoms and bullying perpetration. Vice versa, spillover from peer victimization to parent–child rejection and warmth was partially driven by children's social anxiety, depressive symptoms, conduct problems, and bullying perpetration. Thus, children might get caught in persistent problems in two important social domains, and these two domains influence each other through children's maladjustment. Family and school interventions should be integrated to prevent a downwards spiral.
Tobacco screening and cessation efforts by dental providers: A quality measure evaluation.

OBJECTIVES The purpose of this study was to adapt, test, and evaluate the implementation of a primary care "Preventive care and Screening" meaningful use quality measure for tobacco use, in dental institutions. We determined the percentage of dental patients screened for tobacco use, and the percentage of tobacco users who received cessation counseling. METHODS We implemented the dental quality measure (DQM), in three dental schools and a large dental accountable care organization. An automated electronic health record (EHR) query identified patients 18 years and older who were screened for tobacco use one or more times within 24 months, and who received cessation counseling intervention if identified as a tobacco user. We evaluated EHR query performance with a manual review of a subsample of charts. RESULTS Across all four sites, in the reporting calendar year of 2015, a total of 143,675 patients met the inclusion criteria for the study. Within 24 months, including 2014 and 2015 calendar years, percentages of tobacco screening ranged from 79.7 to 99.9 percent, while cessation intervention percentages varied from 1 to 81 percent among sites. By employing DQM research methodology, we identified intervention gaps in clinical practice. CONCLUSIONS We demonstrated the successful implementation of a DQM to evaluate screening rates for tobacco use and cessation intervention. There is substantial variation in the cessation intervention rates across sites, and these results are a call for action for the dental profession to employ tobacco evidence-based cessation strategies to improve oral health and general health outcomes.
Comparison of metformin plus myoinositol vs metformin alone in PCOS women undergoing ovulation induction cycles: randomized controlled trial

Abstract The present study was planned to evaluate the benefit of synergetic effect of Metformin plus Myo-inositol versus Metformin alone in infertile polycystic ovarian syndrome (PCOS) women undergoing ovulation induction. One hundred and twenty infertile PCOS women were randomized: Group I (n = 60) received Metformin (500 mg) plus Myoinositol(600 mg) three times a day; Group II received Metformin 500 mg three times a day. Subjects were advised to try for spontaneous conception. Those who did not conceive after 3 months, were given three cycles of ovulation induction + intrauterine insemination. Hormonal and biochemical profile parameters were done at baseline and after 3 months of therapy. Primary outcome measure was live birth rate. Secondary outcomes were improvement in menstrual cycle, hormonal and biochemical parameters, spontaneous conception, abortions, multiple pregnancy, and ovarian hyperstimulation syndrome. Baseline demographic, hormonal and biochemical parameters were comparable in two groups. There was a significant improvement in menstrual cycles (cycle length and bleeding days) in Group I as compared to Group II. The improvement in biochemical and hormonal parameters were comparable in the two groups after 3 months. Live birth rate was significantly higher in the Group I as compared to Group II [55% (33/60); 26.67% (16/60); p = . 002]. The study concluded significantly higher live birth rate in women receiving the combination as compared to metformin alone.
Effects of glucocorticoids on B-cell subpopulations in patients with IgG4-related disease.

OBJECTIVES Glucocorticoids induce prompt clinical improvement in patients with IgG4-related disease (IgG4-RD) but their mechanisms of action in this specific condition are not fully understood. B lymphocytes appear central to IgG4-RD pathogenesis because B-cell depletion with rituximab leads to swift clinical responses. In the present work we aim to assess the effects of glucocorticoids on B-cell subpopulations in patients with IgG4-RD. METHODS Fifty patients with active untreated IgG4-RD and 20 healthy controls were enrolled in the present study. Flow cytometry analysis for total circulating CD19+ and CD20+ cells, naïve B cells, memory B cells, plasmablasts, and plasma cells was performed at baseline in all patients, and after 6 months of glucocorticoid treatment in 30 patients. Correlation studies with biomarkers of disease activity were also performed. RESULTS At baseline, patients with IgG4-RD showed reduced CD19+ and CD20+ B cells compared to healthy controls, but increased circulating plasmablasts and plasma cells. Circulating plasmablasts and plasma cells correlated with clinical and serological biomarkers of IgG4-RD activity. Glucocorticoid-induced disease remission was accompanied by a reduction of naïve B cell count, an increase of memory B cells, and by a depletion of circulating plasmablasts and plasma cells. CD19+ and CD20+ B cells, were not affected by glucocorticoids. CONCLUSIONS The efficacy of glucocorticoids in IgG4-RD is associated with selective effects on different B-cell subpopulations. Further studies are warranted to fully understand possible perturbations of the naïve and memory B-cell compartments in patients with IgG4-RD.
Comparative Analyses of Metabolomic Fingerprints and Cytotoxic Activities of Soft Corals from the Colombian Caribbean

Soft corals (Cnidaria, Anthozoa, Octocorallia) are a diverse group of marine invertebrates that inhabit various marine environments in tropical and subtropical areas. Several species are recognized as prolific sources of compounds with a wide array of biological activities. Recent advances in analytical techniques, supported by robust statistical analyses, have allowed the analysis and characterization of the metabolome present in a single living organism. In this study, a liquid chromatography-high resolution mass spectrometry metabolomic approach was applied to analyze the metabolite composition of 28 soft corals present in the Caribbean coast of Colombia. Multivariate data analysis was used to correlate the chemical fingerprints of soft corals with their cytotoxic activity against tumor cell lines for anticancer purpose. Some diterpenoids were identified as specific markers to discriminate between cytotoxic and non-cytotoxic crude extracts of soft corals against tumor cell lines. In the models generated from the comparative analysis of PLS-DA for tumor lines, A549 and SiHa, the diterpene 13-keto-1,11-dolabell-3(E),7(E),12(18)-triene yielded a high score in the variable importance in projection. These results highlight the potential of metabolomic approaches towards the identification of cytotoxic agents against cancer of marine origin. This workflow can be useful in several studies, mainly those that are time consuming, such as traditional bioprospecting of marine natural products.
Bone marrow transplantation for adolescents and young adults with sickle cell disease: Results of a prospective multicenter pilot study

We conducted a multicenter pilot investigation of the safety and feasibility of bone marrow transplantation (BMT) in adults with severe sickle cell disease (SCD) (NCT 01565616) using a reduced toxicity preparative regimen of busulfan (13.2 mg/kg), fludarabine (175 mg/m2) and thymoglobulin (6 mg/kg) and cyclosporine or tacrolimus and methotrexate for graft‐vs‐host disease (GVHD) prophylaxis. Twenty‐two patients (median age 22 years; range 17‐36) were enrolled at eight centers. Seventeen patients received marrow from an HLA‐identical sibling donor and five patients received marrow from an 8/8 HLA‐allele matched unrelated donor. Before BMT, patients had stroke, acute chest syndrome, recurrent pain events, were receiving regular red blood cell transfusions, or had an elevated tricuspid regurgitant jet (TRJ) velocity, which fulfilled eligibility criteria. Four patients developed grades II‐III acute GVHD (18%) and six developed chronic GVHD (27%) that was moderate in two and severe in one patient. One patient died of intracranial hemorrhage and one of GVHD. Nineteen patients had stable donor chimerism, 1‐year post‐transplant. One patient who developed secondary graft failure survives disease‐free after a second BMT. The one‐year overall survival and event‐free survival (EFS) are 91% (95% CI 68%‐98%) and 86% (95% CI, 63%‐95%), respectively, and 3‐year EFS is 82%. Statistically significant improvements in the pain interference and physical function domains of health‐related quality of life were observed. The study satisfied the primary endpoint of 1‐year EFS ≥70%. This regimen is being studied in a prospective clinical trial comparing HLA‐matched donor BMT with standard of care in adults with severe SCD (NCT02766465).
War on video: Combat footage, vernacular video analysis and military culture from within

In this article we present an ethnomethodological study of a controversial case of ‘friendly fire’ from the Iraq War in which leaked video footage, war on video, acquired particular significance. We examine testimony given during a United States Air Force (USAF) investigation of the incident alongside transcribed excerpts from the video to make visible the methods employed by the investigators to assess the propriety of the actions of the pilots involved. With a focus on the way in which the USAF investigators pursued their own analysis of language-in-use in their discussions with the pilots about what had been captured on the video, we turn attention to the background expectancies that analytical work was grounded in. These ‘vernacular’ forms of video analysis and the expectancies which inform them constitute, we suggest, an inquiry into military culture from within that culture. As such, attending to them provides insights into that culture.