Miracle-dz/UniFAR-FTUs huggingface dataset:
Estimation of Radiation Absorbed Doses to the Red Marrow in Radioimmunotherapy

Myelotoxiclty is the dose-limiting factor in radioimmunotherapy. Traditional methods most commonly used to estimate the radiation adsorbed dose to the bone marrow of patients consider contributions from radionuclide in the blood and/or total body. Targeted therapies, such as radioimmunotherapy, add a third potential source for radiation to the bone marrow because the radiolabeled targeting molecules can accumulate specifically on malignant target cells infiltrating the bone marrow. A non-invasive method for estimating the radiation absorbed dose to the red marrow of patients who have received radiolabeled monoclonal antibodies (MoAb) has been developed and explored. The method depends on determining the cumulated activity in three contributing sources: 1) marrow; 2) blood; and 3) total body. The novel aspect of this method for estimating marrow radiation dose is derivation of the radiation dose for the entire red marrow from radiation dose estimates obtained by detection of cumulated activity in three lumbar vertebrae using a gamma camera. Contributions to the marrow radiation dose from marrow, blood, and total body cumulated activity were determined for patients who received an I-131 labeled MoAb, Lym-1, that reacts with malignant B-lymphocytes of chronic lymphocytic leukemia and nonHodgkin's iymphoma. Six patients were selected for illustrative purposes because their vertebrae were readily visualized on lumbar images. The radiation doses to the marrow contributed by nonpene-tratlng emissions in the marrow blood and penetrating emissions in the total body were similar in these patients with a mean of 0.2 and 0.3 rads per administered mCi from the blood and total body, respectively. However, the radiation doses to the marrow from nonpenetrating emissions of I-131 that targeted marrow malignancy varied greatly and ranged from 0.6–2.9 rads per administered mCi in these selected patients. The latter source of marrow radiation dose was often greater than the combined contribution of the blood and total body to marrow radiation dose; this source of marrow radiation dose is ignored by traditional approaches to bone marrow dosimetry and is important to consider for targeted therapies such as radioimmunotherapy. Although it is not appropriate to suggest that the marrow radiation doses estimated using the novel imaging method described are accurate, their use did predict greater hematologic toxicity in the 6 patients and this toxlcity was not anticipated from the marrow radiation doses estimated by using the traditional blood and total body contributions. The exact role of the imaging method remains to be determined and additional validation is required. Although further comparisons with data for hematologic toxicities and results from bone marrow biopsies are required, the method has the potential for providing the therapist with a predictor of greater likelihood of myelotoxicity. Imaging studies with the intended therapeutic agent can be obtained for an individual patient so that predictions can be made before the implementation of therapy.
Magnetic resonance imaging and cerebrovascular hemodynamics in (pre)-eclampsia

Hoge bloeddruk tijdens de zwangerschap is gevaarlijk. De mogelijke gevolgen, zoals hersenoedeem, stuipen en hersenbloedingen, eisen jaarlijks wereldwijd 50 tot 65 duizend vrouwenlevens. Ook in Nederland is deze zogeheten 'preeclampsie' de hoofdoorzaak van moedersterfte. Toch grijpen artsen vaak te laat in volgens Gerda Zeeman. Dit omdat er te weinig bekend is in de medische wetenschap over veranderingen in de hersendoorbloeding. Ook leren de handboeken dat vrouwen in principe geheel herstellen. Zeeman bracht als eerste de veranderingen in de hersenen in beeld en constateert onder meer dat er wel degelijk blijvende schade kan zijn. Hoge bloeddruk komt ongeveer bij vijf tot tien procent van de zwangerschappen voor. Bij een patient met preeclampsie (ook wel zwangerschapsvergiftiging of toxicose genoemd) kunnen stuipen ontstaan, soms gevolgd door een hersenbloeding. Dit komt omdat de bloeddruk dan acuut stijgt. Zeeman heeft tijdens haar opleiding veel ervaring opgedaan met de behandeling van deze patienten: ‘Een stuipende vrouw zorgt voor een angstaanjagend moment voor artsen en verpleegkundigen en het is een drama wanneer je een moeder daarna ziet overlijden. ’ Medische handboeken onderwijzen dat een vrouw geheel herstelt na stuipen en dat hersenbloedingen zeldzaam zijn. Daarom wordt er momenteel vaak veel te laat gestart met bloeddrukverlagende medicatie. Maar een groot deel van de vrouwen lijkt jarenlang verschijnselen over te houden aan de stuipen, zoals geheugenverlies en gebrek aan concentratievermogen. Blijvende schade Het is bekend dat zwangerschap voor grote veranderingen zorgt in de belasting van hart en bloedvaten, maar de veranderingen in de doorbloeding van de hersenen zijn tot nu toe nagenoeg niet onderzocht. Daarom zijn artsen onzeker welke preventie of behandeling toe te passen. Met moderne MRI-technieken bracht Zeeman in beeld dat bij gezonde zwangere vrouwen de bloeddoorstroming in de hersenen afneemt, terwijl er juist een toename is bij vrouwen met zwangerschapshypertensie. Waarschijnlijk leidt dit mechanisme uiteindelijk tot stuipen. Verder ontdekte de promovendus dat een kwart van de patienten in meer of mindere mate blijvende hersenschade overhoudt aan stuipen. Stuipen en hersenbloedingen zijn in veel gevallen te voorkomen door tijdig de bloeddruk te verlagen en magnesiumsulfaat toe te dienen. Dat gebeurt helaas nog veel te weinig in Nederland. Hoe het magnesiumsulfaat werkt is niet bekend. Men denkt dat het samentrekking van de hersenvaten tegengaat, maar Zeeman ontdekte dat het gunstige effect van magnesiumsulfaat daar niet aan toe te schrijven is.
Up-regulation of serum miR-4262 predicts clinical outcome of patients with acute myeloid leukemia.

OBJECTIVE The aim of this study was to investigate whether miR-4262 was associated with the prognosis of acute myeloid leukemia (AML) patients. PATIENTS AND METHODS Serum and bone marrow miR-4262 expression were investigated in 186 AML patients and 115 healthy normal controls by using Real-time PCR. Associations between miR-4262 expressions and various clinicopathological characteristics were analyzed. Overall survival and relapse-free survival were evaluated using the Kaplan-Meier method. Univariate and multivariate analysis were performed using the Cox proportional hazard analysis. RESULTS Expression levels of miR-4262 in the bone marrow and serum of AML patients were both significantly higher than those in healthy controls (both p<0.01). Moreover, increased miR-4262 expression was significantly associated with FAB classification (p=0.001) and cytogenetics (p=0.001). Patients with high miR-4262 expression had poorer overall survival time and relapse-free survival time than those with low miR-4262 expression. Finally, multivariate analysis identified high miR-4262 expression as an independent prognostic factor for AML (p<0.001). CONCLUSIONS Our data revealed that the evaluation of miR-4262 expression in the bone marrow and serum was an ideal tool for predicting the progression of AML and prognosis.
Hyperaccumulation of Nickel by Hairy Roots of AlyssumSpecies: Comparison with Whole Regenerated Plants

Hairy roots were used to investigate nickel uptake by the hyperaccumulator species, Alyssum bertolonii, A. tenium, and A. troodii. The Ni biosorption capacity of A. tenium hairy roots was lower than for other types of biomass such as bacteria and algae; in short‐term (9‐h) equilibrium studies, the highest Ni content measured in the roots was 17 500 μg g−1 dry weight at a liquid concentration of about 4000 ppm. Using long‐term hairy root cultures, it was demonstrated that Ni tolerance and hyperaccumulation do not necessarily depend on the presence of shoots or root‐shoot translocation. A. bertolonii hairy roots remained healthy in appearance and continued to grow in the presence of 20−100 ppm Ni, accumulating up to 7200 μg g−1 dry weight Ni. In contrast, hairy roots of Nicotiana tabacum turned dark brown at 20 ppm Ni and growth was negligible. The ability to grow at high external Ni concentrations allowed hyperaccumulator hairy roots to remove much greater amounts of heavy metals from the culture liquid than nonhyperaccumulator hairy roots, even though biomass Ni concentrations were similar. Although hairy roots proved to be a useful tool for investigating Ni hyperaccumulation, there were significant differences in the Ni uptake capacity of hairy roots and whole plants. Regenerated plants of A. tenium were much more tolerant of Ni and capable of accumulating higher Ni concentrations than hairy roots of this species.
Mining a MOOC: What our MOOC taught us about professional learning, teaching, and assessment

In July 2014, a massive open online course (MOOC) entitled The Assessment and Teaching of 21st Century Skills (ATC21S) was offered within the University of Melbourne's programme. Designed as a research engagement and dissemination initiative, the ATC21S MOOC enrolled 18,000 education practitioners, predominantly interested in teaching and assessment of complex 21st century skills. This chapter describes the experience of developing and teaching in the MOOC, and of learning through it. The authors suggest areas for ongoing research, and highlight areas in which MOOCs may stimulate broader change. This chapter commences the dialogue for the opening book section – policy issues in MOOCs Design, and responds to the topic of ‘emerging technology and change management issues for eLearning in the MOOCS environment. '
Ablation of lesions or no treatment in minimal-mild endometriosis in infertile women: a randomized trial. Gruppo Italiano per lo Studio dell'Endometriosi.

In order to analyse the efficacy of resection/ablation of minimal/mild endometriotic lesions for improving fertility, we conducted a randomized clinical trial. Eligible patients were women aged </=36 years who were trying to conceive and had a laparoscopically confirmed diagnosis of minimal/mild endometriosis (stage I or II of the revised American Fertility Society classification) and otherwise unexplained infertility for >/=2 years. Eligible women were randomly assigned to resection or ablation of visible endometriosis (54 patients) or diagnostic laparoscopy only (47 patients). After laparoscopy women tried to conceive spontaneously for 1 year (follow-up period). A total of five women withdrew from the study: three for personal reasons, and two were lost to follow-up. Considering 51 women in the resection/ablation and 45 in the no-treatment group who ended the follow-up period, 12 (24%) in the resection/ablation group and 13 (29%) in the no treatment group conceived; the difference was not significant. Two spontaneous abortions were observed in the resection/ablation group and three in the no-treatment one. Thus the 1 year birth rate was 10 out of 51 women (19.6%) in the resection/ablation group and 10 out of 45 women (22.2%) in the no-treatment group. In conclusion, the results of this study do not support the hypothesis that ablation of endometriotic lesions markedly improves fertility rates.
22q11.2 Deletion Syndrome is under-recognised in adult patients with tetralogy of Fallot and pulmonary atresia

Background Three quarters of patients with 22q11.2 Deletion Syndrome (22q11.2DS) have congenital heart disease (CHD), typically conotruncal heart defects. Although it is currently common practice to test all children with typical CHD for 22q11.2DS, many adult patients have not been tested in the past and therefore 22q11.2DS might be under-recognised in adults. Objectives To determine the prevalence of 22q11.2DS in adults with tetralogy of Fallot (TOF) and pulmonary atresia (PA)/ventricular septal defect (VSD) and to assess the level of recognition of the syndrome in adult patients. Methods Patients were identified from CONCOR, a nationwide registry for adult patients with CHD. Inclusion criteria were diagnosis of TOF or PA/VSD and the availability of DNA. Patients with syndromes other than 22q11.2DS were excluded. Multiplex ligation-dependent probe amplification was used to detect 22q11.2 microdeletions. Results 479 patients with TOF and 79 patients with PA/VSD (56% male, median age 34.7 years) were included and analysed. Twenty patients were already known to have 22q11.2DS. A 22q11.2 microdeletion was detected in a further 24 patients. Thirty-one patients with TOF (6.5%) had 22q11.2DS, whereas 13 patients with PA/VSD had 22q11.2DS (16.5%). Of all 22q11.2 microdeletions, 54% (24/44) were unknown before this study. Conclusion This study shows that although the prevalence of 22q11.2DS in adults with TOF and PA/VSD is substantial, it is unrecognised in more than half of patients. As the syndrome has important clinical and reproductive implications, a diagnostic test should be considered in all adult patients with TOF and PA/VSD.
Etiologic Diagnosis of Corneal Ulceration at a Tertiary Eye Center in Kathmandu, Nepal

Purpose: To determine the etiologic diagnosis of infectious corneal ulcers at Tilganga Institute of Ophthalmology, a tertiary teaching hospital in Kathmandu Nepal, from 2006-2009. Methods: This study involved a review of all microbiology records at Tilganga Institute of Ophthalmology from August 2006 through July 2009. Microbiologic records from the corneal scrapings of all patients suspected of having infectious corneal ulcers were included. Results: Corneal scrapings were obtained from 468 patients. The average patient age was 52 years, and 55% of the affected cases were males. Microorganisms were grown from 185 of the corneal scrapings (40%). Pure bacterial cultures were obtained from 72 patients (39%), and pure fungal cultures were obtained from 113 patients (61%). Gram stain was 75% sensitive (95% confidence interval, 0.632-0.841) in identifying bacterial infection, whereas KOH prep was 80.5% sensitive (95% confidence interval, 0.718-0.871) in identifying fungal organisms. Of 72 bacterial isolates, 50 isolates (69%) were Streptococcus pneumoniae, the most common organism isolated in this study. Of 113 fungal isolates, 40 of isolates (35%) were identified as Aspergillus sp. Conclusions: Fungal organisms (61%) are the most common cause of infectious keratitis in this patient population. Of all organisms, S. pneumoniae was the most common organism identified. Smear microscopy is reliable in rapidly determining the etiology of the corneal infection and can be used to help guide initial therapy in this setting.
Subinhibitory Clindamycin Differentially Inhibits Transcription of Exoprotein Genes in Staphylococcus aureus

ABSTRACT It has long been known that certain antibiotics, at subinhibitory concentrations, differentially inhibit the synthesis of α-hemolysin and other staphylococcal virulence factors. In this report, we show that subinhibitory clindamycin (SBCL) eliminates production of nearly all exoproteins by Staphylococcus aureus but has virtually no effect on cytoplasmic proteins. The effect was abolished by a gene conferring resistance to macrolides-lincosamides-streptogramin B, showing that differential inhibition of protein synthesis is responsible; remarkably, however, subinhibitory clindamycin blocked production of several of the individual exoprotein genes, including spa(encoding protein A), hla (encoding α-hemolysin), andspr (encoding serine protease), at the level of transcription, suggesting that the primary effect must be differential inhibition of the synthesis of one or more regulatory proteins. In contrast to earlier reports, however, we found that subinhibitory clindamycin stimulates synthesis of coagulase and fibronectin binding protein B, also at the level of transcription.agr and sar expression was minimally affected by subinhibitory clindamycin. These effects varied from strain to strain and do not seem to be responsible for the effects of subinhibitory clindamycin on the overall exoprotein pattern.
Perforin and Gamma Interferon Expression Are Required for CD4+ and CD8+ T-Cell-Dependent Protective Immunity against a Human Parasite, Trypanosoma cruzi, Elicited by Heterologous Plasmid DNA Prime-Recombinant Adenovirus 5 Boost Vaccination

ABSTRACT A heterologous prime-boost strategy using plasmid DNA, followed by replication-defective recombinant adenovirus 5, is being proposed as a powerful way to elicit CD4+ and CD8+ T-cell-mediated protective immunity against intracellular pathogens. We confirmed this concept and furthered existing research by providing evidence that the heterologous prime-boost regimen using the gene encoding amastigote surface protein 2 elicited CD4+ and CD8+ T-cell-mediated protective immunity (reduction of acute parasitemia and prolonged survival) against experimental infection with Trypanosoma cruzi. Protective immunity correlated with the presence of in vivo antigen-specific cytotoxic activity prior to challenge. Based on this, our second goal was to determine the outcome of infection after heterologous prime-boost immunization of perforin-deficient mice. These mice were highly susceptible to infection. A detailed analysis of the cell-mediated immune responses in immunized perforin-deficient mice showed an impaired gamma interferon (IFN-γ) secretion by immune spleen cells upon restimulation in vitro with soluble recombinant antigen. In spite of a normal numeric expansion, specific CD8+ T cells presented several functional defects detected in vivo (cytotoxicity) and in vitro (simultaneous expression of CD107a/IFN-γ or IFN-γ/tumor necrosis factor alpha) paralleled by a decreased expression of CD44 and KLRG-1. Our final goal was to determine the importance of IFN-γ in the presence of highly cytotoxic T cells. Vaccinated IFN-γ-deficient mice developed highly cytotoxic cells but failed to develop any protective immunity. Our study thus demonstrated a role for perforin and IFN-γ in a number of T-cell-mediated effector functions and in the antiparasitic immunity generated by a heterologous plasmid DNA prime-adenovirus boost vaccination strategy.
Overexpression of dopamine D2 receptors reduces alcohol self‐administration

The mechanism(s) underlying predisposition to alcohol abuse are poorly understood but may involve brain dopamine system(s). Here we used an adenoviral vector to deliver the dopamine D2 receptor (DRD2) gene into the nucleus accumbens of rats, previously trained to self‐administer alcohol, and to assess if DRD2 levels regulated alcohol preference and intake. We show that increases in DRD2 (52%) were associated with marked reductions in alcohol preference (43%), and alcohol intake (64%) of ethanol preferring rats, which recovered as the DRD2, returned to baseline levels. In addition, this DRD2 overexpression similarly produced significant reductions in ethanol non‐preferring rats, in both alcohol preference (16%) and alcohol intake (75%). This is the first evidence that overexpression of DRD2 reduces alcohol intake and suggests that high levels of DRD2 may be protective against alcohol abuse.
Overproduction of monocyte derived tumor necrosis factor alpha, interleukin (IL) 6, IL-8 and increased neutrophil superoxide generation in Behçet's disease. A comparative study with familial Mediterranean fever and healthy subjects.

OBJECTIVE The etiopathogenesis of Behçet's disease (BD) has not yet been clarified but might involve immune dysfunction. As cytokines are involved in the regulation of immune responses and inflammatory reactions, we investigated whether they may play a role in the pathogenesis of BD. METHODS We investigated spontaneous and lipopolysaccharide (LPS) stimulated production of tumor necrosis factor alpha (TNF alpha), interleukin (IL) 1, IL-6, IL-8 and granulocyte monocyte macrophage colony stimulating factor (GM-CSF) by peripheral blood monocytes from 21 patients with BD, 10 healthy controls and 10 patients with familial Mediterranean fever (FMF), another chronic inflammatory disease. We also studied superoxide generation and surface antigen expression by polymorphonuclear neutrophils (PMN). RESULTS The spontaneous secretion of TNF alpha, IL-6 and IL-8 by monocytes was significantly increased in patients with active BD. The secretion of TNF alpha, IL-1, IL-6 and IL-8 was found to be in normal range in asymptomatic patients with FMF. The LPS stimulated production of TNF alpha, IL-6, IL-1 and IL-8 was significantly increased in patients with BD, without any correlation with BD activity. In vitro, PMN spontaneously generated significant amounts of superoxide in patients with active BD. CONCLUSION Taken together, our results suggest that monocyte and PMN dysfunctions may play a role in the pathogenesis of BD.
Stability of Genetic and Environmental Effects from Adolescence to Young Adulthood: Results of Croatian Longitudinal Twin Study of Personality

Abstract The primary aim of this study was to conduct a bivariate genetic analysis investigating the extent to which genetic and environmental factors contribute to stability and change in personality factors in the period from adolescence to young adulthood on a sample of Croatian twins. The sample used in this research was formed in 1992 based on a register of citizens of Zagreb and data was collected for 160 twin pairs (75 monozygotic and 85 dizygotic twin pairs). Twins were tested twice, 4 years apart with the Eysenck Personality Questionnaire (mean age at first time point was 17 years). Univariate analyses indicate that the best fitting model for extraversion, neuroticism, psychoticism and lie scale at both time points includes additive genetic (A) and nonshared environmental (E) influences, with heritability estimates in the . 40 to . 50 range. Longitudinal analyses using AE correlated factors model indicate that genetic factors contribute mainly to stability, while environmental factors contribute mainly to change in personality during that 4-year period of transition from adolescence to young adulthood.
MicroRNA-22 Regulates Smooth Muscle Cell Differentiation From Stem Cells by Targeting Methyl CpG–Binding Protein 2

Objective— In this study, we attempted to uncover the functional impact of microRNA-22 (miR-22) and its target gene in smooth muscle cell (SMC) differentiation and delineate the molecular mechanism involved. Approach and Results— miR-22 was found to be significantly upregulated during SMC differentiation from embryonic stem cells and adventitia stem/progenitor cells. Enforced expression of miR-22 by its mimic, while knockdown of miR-22 by its antagomiR, promotes or inhibits SMC differentiation from embryonic stem cells and adventitia stem/progenitor cells, respectively. Expectedly, miR-22 overexpression in stem cells promoted SMC differentiation in vivo. Methyl CpG–binding protein 2 (MECP2) was predicted as one of the top targets of miR-22. Interestingly, the gene expression levels of MECP2 were significantly decreased during SMC differentiation, and MECP2 was dramatically decreased in miR-22 overexpressing cells but significantly increased when miR-22 was knockdown in the differentiating stem cells. Importantly, luciferase assay showed that miR-22 substantially inhibited wild-type, but not mutant MECP2-3′ untranslated region-luciferase activity. In addition, modulation of MECP2 expression levels affects multiple SMC-specific gene expression in differentiated embryonic stem cells. Mechanistically, our data showed that MECP2 could transcriptionally repress SMC gene expression through modulating various SMC transcription factors, as well as several proven SMC differentiation regulators. Evidence also revealed that enrichment of H3K9 trimethylation around the promoter regions of the SMC differentiation regulators genes were significantly increased by MECP2 overexpression. Finally, miR-22 was upregulated by platelet-derived growth factor-BB and transforming growth factor-&bgr; through a transcriptional mechanism during SMC differentiation. Conclusions— miR-22 plays an important role in SMC differentiation, and epigenetic regulation through MECP2 is required for miR-22 mediated SMC differentiation.