Miracle-dz/UniFAR-FTUs huggingface dataset:
Management and outcome of primary CNS lymphoma in the modern era: An LOC network study.

OBJECTIVE Real-life studies on patients with primary CNS lymphoma (PCNSL) are scarce. Our objective was to analyze, in a nationwide population-based study, the current medical practice in the management of PCNSL. METHODS The French oculo-cerebral lymphoma network (LOC) database prospectively records all newly diagnosed PCNSL cases from 32 French centers. Data of patients diagnosed between 2011 and 2016 were retrospectively analyzed. RESULTS We identified 1,002 immunocompetent patients (43% aged >70 years, median Karnofsky Performance Status [KPS] 60). First-line treatment was high-dose methotrexate-based chemotherapy in 92% of cases, with an increasing use of rituximab over time (66%). Patients <60 years of age received consolidation treatment in 77% of cases, consisting of whole-brain radiotherapy (WBRT) (54%) or high-dose chemotherapy with autologous stem cell transplantation (HCT-ASCT) (23%). Among patients >60 years of age, WBRT and HCT-ASCT consolidation were administered in only 9% and 2%, respectively. The complete response rate to initial chemotherapy was 50%. Median progression-free survival was 10.5 months. For relapse, second-line chemotherapy, HCT-ASCT, WBRT, and palliative care were offered to 55%, 17%, 10%, and 18% of patients, respectively. The median, 2-year, and 5-year overall survival was 25.3 months, 51%, and 38%, respectively (<60 years: not reached [NR], 70%, and 61%; >60 years: 15.4 months, 44%, and 28%). Age, KPS, sex, and response to induction CT were independent prognostic factors in multivariate analysis. CONCLUSIONS Our study confirms the increasing proportion of elderly within the PCNSL population and shows comparable outcome in this population-based study with those reported by clinical trials, reflecting a notable application of recent PCNSL advances in treatment.
Clinical Applications, Pitfalls, and Uncertainties of Thrombin Generation in the Presence of Platelets

Platelet-dependent thrombin generation is a helpful tool to assess ex vivo the interaction between platelets and plasma coagulation factors in the initiation, amplification, and inhibition of thrombin generation (TG). This review article discusses the most relevant available data on the clinical applications of fluorogenic TG, the most widely used TG assay, performed in the presence of platelets, i.e., in platelet-rich plasma. With respect to prothrombotic states, arterial hypertension and obesity were the most prominent cardiovascular conditions linked to increased platelet-dependent TG. In addition, platelet-associated hypercoagulability, assessed by the TG assay, has been shown in individuals with active cancer. In terms of bleeding, platelet-dependent TG has been applied to assess bleeding risk in individuals with hemophilia, von Willebrand disease, and Glanzmann thrombasthenia as well as in subjects with other congenital or acquired coagulation factor deficiencies. In addition to risk prediction, a role of the TG assay has been suggested in monitoring antiplatelet therapy in prothrombotic conditions and replacement therapy in bleeding diathesis. Finally, for the routine clinical use and as a biomarker of disease development and progression, better standardization and clinical validation of platelet-dependent TG are still needed.
Bridging the Gap between Authentic Leadership and Employees Communal Relationships through Trust

Authentic leadership has emerged as a positive relational-leadership approach that has gained the attention of academicians and practitioners by stimulating a healthy work environment. This study examined the direct influence of authentic leadership on employees’ communal relationships. In addition, the study examined the mediating role of affective- and cognitive-based trust on these relationships. We adopted a cross-sectional study design and collected data from 200 employees working in the private banking sector in Pakistan. The findings indicated that authentic leadership was positively correlated with communal employee relationships. In addition, both affective- and cognitive-based trust were found to have a positive mediating effect on the relationship between authentic leadership and communal employee relationships. The practical implications, limitations and suggestions for future research are discussed.
Positron Emission Tomography (PET) Radiopharmaceuticals in Multiple Myeloma

Multiple myeloma (MM) is a plasma cell disorder, characterized by clonal proliferation of malignant plasma cells in the bone marrow. Bone disease is the most frequent feature and an end-organ defining indicator of MM. In this context, imaging plays a pivotal role in the management of the malignancy. For several decades whole-body X-ray survey (WBXR) has been applied for the diagnosis and staging of bone disease in MM. However, the serious drawbacks of WBXR have led to its gradual replacement from novel imaging modalities, such as computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography/computed tomography (PET/CT). PET/CT, with the tracer 18F-fluorodeoxyglucose (18F-FDG), is now considered a powerful diagnostic tool for the detection of medullary and extramedullary disease at the time of diagnosis, a reliable predictor of survival as well as the most robust modality for treatment response evaluation in MM. On the other hand, 18F-FDG carries its own limitations as a radiopharmaceutical, including a rather poor sensitivity for the detection of diffuse bone marrow infiltration, a relatively low specificity, and the lack of widely applied, established criteria for image interpretation. This has led to the development of several alternative PET tracers, some of which with promising results regarding MM detection. The aim of this review article is to outline the major applications of PET/CT with different radiopharmaceuticals in the clinical practice of MM.
Synthesis of La–Sr–Mn–O and La–Sr–Ca–Mn–O Perovskites Through Solution Combustion Using Urea at Fuel Deficient Conditions

La0.7 Sr0.3 MnO3 (LSMO) nanoparticles have been obtained via solution combustion synthesis (SCS) using urea and glycine as fuels. Also, La0.7 Sr0.27 Ca0.03 MnO3 (LSCMO) nanoparticles have been synthesized through solution combustion using urea as fuel. In this paper, the combustion process was carried out with a fuel to oxidant ratio giving fuel deficient conditions ( $\phi < {1}$ ). The thermal analysis (TGA) indicate that the organic residues from the urea-nitrates gel mixture are eliminated above 600 °C and the post-synthesis heat treatment yields the formation of the desired phase without impurities. The obtained phases were analyzed using X-ray diffraction. The infrared analysis confirms the purity of the samples obtained using urea. However, the sample obtained using glycine confirms the formation of SrCO3. The morphology was analyzed using a FE-SEM microscope, and it was found that the particles present a spherical shape with a mean size of around 45 nm in the selected samples. The samples’ energy dispersive X-ray spectra show that the desired elements (La, Sr, Ca, Mn and O) are present in the nanoparticles. The measured zero field cooled (ZFC) and field cooled (FC) magnetizations were recorded from 4.5 to 380 K at 105 A/m to obtain their blocking and Curie temperatures. Moreover, the hysteresis loops measured at room temperature confirm the superparamagnetic behavior of the elaborated samples. According to the results obtained, these nanoparticles have interesting properties that make them candidates to explore not only for their potential in biomedical applications but also in refrigeration and magnetic storage devices.
Isobolographic Analysis Demonstrates the Additive and Synergistic Effects of Gemcitabine Combined with Fucoidan in Uterine Sarcomas and Carcinosarcoma Cells

Background: Uterine sarcomas and carcinosarcoma are associated with unfavorable prognosis. The regimens that are used in chemotherapy are associated with high incidence of side effects and usually do not significantly increase patients’ survival rates. In this study we investigated the activity and interactions between gemcitabine and fucoidan, the natural compound known for its anti-tumor properties, in human sarcomas and carcinosarcoma cell models. Methods: SK-UT-1, SK-UT1-B (carcinosarcoma), MES-SA (leiomyosarcoma), and ESS-1 (endometrial stromal sarcoma) cell lines were used for the experiments. Cells were incubated in the presence of gemcitabine, fucoidan, and mixtures, after the incubation the MTT tests were performed. In order to assess the interactions between tested compounds isobolographic analysis was performed. Additional assessments of apoptosis and cell cycle were done. Results: Additive effect of combined treatment with gemcitabine and fucoidan was observed in ESS-1 and SK-UT-1 cell line. Although the supra-additive (synergistic) effect noticed in SK-UT-1B cell line. It was not possible to determine the interactions of fucoidan and gemcitabine in MES-SA cell line due to insufficient response to treatment. Addition of fucoidan to gemcitabine enhances its proapoptotic activity, what was observed especially in ESS-1 and SK-UT-1B cell lines. The arrest of cell cycle induced by mixture of gemcitabine and fucoidan, superior comparing gemcitabine alone was observed in SK-UT-1B. Conclusions: Obtained data showed that a combination of fucoidan and gemcitabine in uterine endometrial stromal sarcoma and carcinosarcoma cell lines has additive or even synergistic effect in decreasing cell viability. Furthermore, this drug combination induces apoptosis and arrest of cell cycle. The resistance of uterine leiomyosarcoma cell line, justifies searching for other drugs combinations to improve therapy efficacy.
Plasma neurofilament light chain: an early biomarker for hereditary ATTR amyloid polyneuropathy

Abstract Background: Transthyretin amyloidosis due to V30M mutation (ATTR-V30M) is the most frequent hereditary ATTR amyloidosis. Besides neurophysiological measures, there are no biomarkers to detect preclinical disease or monitor disease progression. CSF or plasma neurofilament light chain (pNfL) have recently been considered sensitive biomarkers to quantitate neuro-axonal damage in several disorders of the peripheral and central nervous system. Objective: Characterise plasma NfL levels in a series of untreated ATTR-V30M patients stratified by clinical severity using a cross-sectional retrospective study design. Methods: Sixty ATTR-V30M patients and 16 controls from 2 independent cohorts were analysed for pNfL by single-molecule array assay (SIMOA) technique. Disease severity was assessed with Polyneuropathy Disability Score. Results: pNfL is elevated in ATTR-V30M patients as a function of disease severity in both cohorts. Moreover, pNfL discriminates asymptomatic mutation carriers from early symptomatic patients (AUC = 0.97; p < .001) with high sensitivity (92.3%) and specificity (93.8%). pNfL elevation (>66.9 pg/mL) also discriminates patients with sensory neuropathy from patients with motor neuropathy (AUC = 0.91; p < .01) with a sensitivity of 61.5% and a specificity of 92.3%. Conclusion: pNfL is an easily accessible biomarker to establish ATTR-V30M disease conversion and to monitor disease progression. pNfL could be used as efficacy measure of disease-oriented therapies in clinical and pre-clinical trials.
Dose-response modeling of NLRP3 inflammasome-mediated diseases: asbestos, lung cancer, and malignant mesothelioma as examples

Abstract Can a single fiber of amphibole asbestos increase the risk of lung cancer or malignant mesothelioma (MM)? Traditional linear no-threshold (LNT) risk assessment assumptions imply that the answer is yes: there is no safe exposure level. This paper draws on recent scientific progress in inflammation biology, especially elucidation of the activation thresholds for NLRP3 inflammasomes and resulting chronic inflammation, to model dose-response relationships for malignant mesothelioma and lung cancer risks caused by asbestos exposures. The modeling integrates a physiologically based pharmacokinetics (PBPK) front end with inflammation-driven two-stage clonal expansion (I-TSCE) models of carcinogenesis to describe how exposure leads to chronic inflammation, which in turn promotes carcinogenesis. Together, the combined PBPK and I-TSCE modeling predict that there are practical thresholds for exposure concentration below which asbestos exposure does not cause chronic inflammation in less than a lifetime, and therefore does not increase chronic inflammation-dependent cancer risks. Quantitative examples using model parameter estimates drawn from the literature suggest that practical thresholds may be within about a factor of 2 of some past exposure levels for some workers. The I-TSCE modeling framework explains previous puzzling aspects of asbestos epidemiology, such as why age at first exposure is a better predictor of lifetime MM risk than exposure duration. It may be a valuable tool for risk analysts when LNT assumptions are not justified due to inflammation response thresholds mediating dose-response relationships.
Adherence to antiretroviral treatment and quality of life among transgender women living with HIV/AIDS in São Paulo, Brazil

ABSTRACT This study focused on factors associated with antiretroviral therapy (ART) adherence and quality of life among transgenderwomen in Sao Paulo, Brazil, using univariable and adjusted analysis. Adherence was evaluated with a self-report tool and with HIV viral load (VL) measurement. PROQOL-HIV was used to assess quality of life. 106 TGW with median 41 years old were included; most were white (56%) and had >10 years of education (57%). Median time since HIV/AIDS diagnosis was 10 years. Overall, participants had high T CD4+ counts (median 659 cells/mm3) and most (75%) had undetectable HIV VL. 85% were considered adherent using self-report (95%CI 77-91), whereas 72% (95%CI 62-80) were considered adherent when self-report and undetectable HIV VL were analyzed jointly. Older age was associated with higher ART adherence; each year increase in age was associated with 5% higher odds of adherence (p = 0.021). Quality of life ranged from good-excellent in 5 of 8 domains. Younger age, lower education, higher time since HIV diagnosis, comorbidities, illicit drugs use and depression were associated with lower PROQOL scores in specific domains in univariable analysis, while depression was also associated with lower total PROQOL score even after adjustment for age, comorbidities and time since HIV diagnosis (p = 0.048).
Normal-Appearing White Matter Integrity Is a Predictor of Outcome After Ischemic Stroke

Supplemental Digital Content is available in the text. Background and Purpose— The aim of the present study was to evaluate the relationship between normal-appearing white matter (NAWM) integrity and postischemic stroke recovery in 4 main domains including cognition, mood, gait, and dependency. Methods— A prospective study was conducted, including patients diagnosed for an ischemic supratentorial stroke on a 3T brain MRI performed 24 to 72 hours after symptom onset. Clinical assessment 1 year after stroke included a Montreal Cognitive Assessment, an Isaacs set test, a Zazzo cancelation task, a Hospital Anxiety and Depression scale, a 10-meter walking test, and a modified Rankin Scale (mRS). Diffusion tensor imaging parameters in the NAWM were computed using FMRIB (Functional Magnetic Resonance Imaging of the Brain) Diffusion Toolbox. The relationships between mean NAWM diffusion tensor imaging parameters and the clinical scores were assessed using linear and ordinal regression analyses, including the volumes of white matter hyperintensities, gray matter, and ischemic stroke as radiological covariates. Results— Two hundred seven subjects were included (66±13 years old; 67% men; median National Institutes of Health Stroke Scale score, 3; interquartile range, 2–6). In the models including only radiological variables, NAWM fractional anisotropy was associated with the mRS and the cognitive scores. After adjusting for demographic confounders, NAWM fractional anisotropy remained a significant predictor of mRS (β=−0.24; P=0.04). Additional path analysis showed that NAWM fractional anisotropy had a direct effect on mRS (β=−0.241; P=0.001) and a less important indirect effect mediating white matter hyperintensity burden. Similar results were found with mean diffusivity, axial diffusivity, and radial diffusivity. In further subgroup analyses, a relationship between NAWM integrity in widespread white matter tracts, mRS, and Isaacs set test was found in right hemispheric strokes. Conclusions— NAWM diffusion tensor imaging parameters measured early after an ischemic stroke are independent predictors of functional outcome and may be additional markers to include in studies evaluating poststroke recovery.
New Genotypes of Coxiella burnetii Circulating in Brazil and Argentina

Coxiella burnetii, the zoonotic agent of Q fever, has a worldwide distribution. Despite the vast information about the circulating genotypes in Europe and North America, there is a lack of data regarding C. burnetii strains in South America. Here, we show the presence of novel multispacer sequence typing (MST) genotypes of C. burnetii in two clusters detected in Brazil and Argentina that seem to be distant in parenthood. Argentinian strains isolated from a tick belongs to a new phylogenetic branch of C. burnetii, and the Brazilians strains may be related to MST 20 and 61. Multilocus variable number tandem repeats analysis (MLVA) typing provided a deeper resolution that may be related to host clusters of bovines, caprine, ovine, and ticks. Our results corroborate with the reports of geotypes of C. burnetii. Thus, we highlight the need for more genotyping studies to understand the genetic diversity of C. burnetii in South America and to confirm the hypothesis of host-related genotypes. We also emphasize the importance of virulence studies for a better understanding of Q fever in the region, which may help in surveillance and disease prevention programs.
LC-ICP-OES method for antimony speciation analysis in liquid samples

Abstract A method for the analysis of different species of antimony (Sb) that couples liquid chromatography with an inductively coupled plasma-optical emission spectrometry (LC-ICP-OES) system is presented. The method is simple and reliable to separate and quantify directly and simultaneously Sb(III) and Sb(V) in aqueous samples. The calibration curves showed high linearity at the three wavelengths tested. The limits of detection ranged from 24.9 to 32.3 μg/L for Sb(III) and from 36.2 to 46.0 μg/L for Sb(V), at the three wavelengths evaluated. The limit of detection for this method varied depending on the wavelength used. The lowest limit of quantification for Sb(V) (49.9 μg/L) and Sb(III) (80.7 μg/L) was obtained at a wavelength of 217.582 nm. The method sensitivity for Sb(V) was higher compared to Sb(III) at all the wavelengths considered. Samples containing different concentrations of Sb(III) and Sb(V) in three different matrices, i.e., water, basal culture medium, and anaerobic sludge plus basal medium, were analyzed. The coefficients of variation were low and ranged from 0.1 to 5.0 depending on the sample matrix. Recoveries of Sb(III) and Sb(V) were higher than 90% independently of the matrix analyzed and the wavelength used in the analysis.
Expression of Retinoid Acid Receptor-Responsive Genes in Rodent Models of Placental Pathology

In humans, retinoic acid receptor responders (RARRES) have been shown to be altered in third trimester placentas complicated by the pathologies preeclampsia (PE) and PE with intrauterine growth restriction (IUGR). Currently, little is known about the role of placental Rarres in rodents. Therefore, we examined the localization and expression of Rarres1 and 2 in placentas obtained from a Wistar rat model of isocaloric maternal protein restriction (E18.5, IUGR-like features) and from an eNOS-knockout mouse model (E15 and E18.5, PE-like features). In both rodent models, Rarres1 and 2 were mainly localized in the placental spongiotrophoblast and giant cells. Their placental expression, as well as the expression of the Rarres2 receptor chemokine-like receptor 1 (CmklR1), was largely unaltered at the examined gestational ages in both animal models. Our results have shown that RARRES1 and 2 may have different expression and roles in human and rodent placentas, thereby underlining immanent limitations of comparative interspecies placentology. Further functional studies are required to elucidate the potential involvement of these proteins in early placentogenesis.
Community Health Survey of Residents Living Near a Solid Waste Open Dumpsite in Sabak, Kelantan, Malaysia

The management of waste materials is a serious problem worldwide, especially in urbanizing countries like Malaysia. This study was conducted to compare the prevalence of health symptoms and diseases diagnosed among residents exposed to the solid waste open dumpsite in the suburb of Sabak with the non-exposed community. Research related to exposure to solid waste dumping with complete health problems has never been combined in one study. A comparative cross-sectional study was conducted. The exposed group included residents within a 1 km radius and the non-exposed group included residents between a 2.5 and 4.0 km radius from the dumpsite. The selected residents were interviewed using validated, structured questionnaires. A total of 170 residents from the exposed group and 119 residents from the non-exposed group were selected. The mean (SD) duration time of residence was 22.6 (18.9) years for the exposed group and 15.0 (12.0) years for the non-exposed group. Dumpsite exposure was significantly associated with sore throat (adjusted odd ratio (AOR) 1.88; 95% confidence interval (CI): 1.05, 3.38; p = 0.031), diabetes mellitus (AOR 2.84; 95% CI: 1.10, 7.30; p = 0.021) and hypertension (AOR 2.56; 95% CI: 1.27, 5.13; p = 0.006). This study provides evidence that the unsanitary solid waste disposal in Malaysia is hazardous to the health of residents in the surrounding 1 km, and efforts are needed to minimize the hazards.
Mainly Dimers and Trimers of Chinese Bayberry Leaves Proanthocyanidins (BLPs) are Utilized by Gut Microbiota: In Vitro Digestion and Fermentation Coupled with Caco-2 Transportation

Chinese bayberry leaf proanthocyanidins (BLPs) are Epigallocatechin gallate (EGCG) oligomers or polymers, which have a lot of health-promoting activity. The activity is closely related to their behavior during in vitro digestion, which remains unknown and hinders further investigations. To clarify the changes of BLPs during gastrointestinal digestion, further research is required. For in vitro digestion, including gastric-intestinal digestion, colon fermentation was applied. Caco-2 monolayer transportation was also applied to investigate the behavior of different BLPs with different degrees of polymerization. The trimers and the tetramers were significantly decreased during in vitro gastric-intestinal digestion resulting in a significant increase in the content of dimers. The dimers and trimers were the main compounds utilized by gut microbiota and they were assumed not to degrade through cleavage of the inflavan bond. The monomers and dimers were able to transport through the Caco-2 monolayer at a rate of 10.45% and 6.4%, respectively.