Miracle-dz/UniFAR-FTUs huggingface dataset:
Vγ9Vδ2 T Lymphocytes Efficiently Recognize and Kill Zoledronate-Sensitized, Imatinib-Sensitive, and Imatinib-Resistant Chronic Myelogenous Leukemia Cells

Imatinib mesylate (imatinib), a competitive inhibitor of the BCR-ABL tyrosine kinase, is highly effective against chronic myelogenous leukemia (CML) cells. However, because 20–30% of patients affected by CML display either primary or secondary resistance to imatinib, intentional activation of Vγ9Vδ2 T cells by phosphoantigens or by agents that cause their accumulation within cells, such as zoledronate, may represent a promising strategy for the design of a novel and highly innovative immunotherapy capable to overcome imatinib resistance. In this study, we show that Vγ9Vδ2 T lymphocytes recognize, trogocytose, and efficiently kill imatinib-sensitive and -resistant CML cell lines pretreated with zoledronate. Vγ9Vδ2 T cell cytotoxicity was largely dependent on the granule exocytosis- and partly on TRAIL-mediated pathways, was TCR-mediated, and required isoprenoid biosynthesis by zoledronate-treated CML cells. Importantly, Vγ9Vδ2 T cells from patients with CML can be induced by zoledronate to develop antitumor activity against autologous and allogeneic zoledronate-treated leukemia cells, both in vitro and when transferred into immunodeficient mice in vivo. We conclude that intentional activation of Vγ9Vδ2 T cells by zoledronate may substantially increase their antileukemia activities and represent a novel strategy for CML immunotherapy.
Chromogranin A is a sensitive marker of progression or regression in ileo-cecal neuroendocrine tumors

Abstract Objective. The correlation between plasma Chromogranin A concentrations and changes in tumor size evaluated by computed tomography (CT) – as a gold standard - was evaluated. Material and methods. One hundred and sixteen patients with CgA-producing ileo-cecal neuroendocrine tumors were evaluated by events, which were recorded when a CT was followed by another CT 1 - 12 months later. Change in tumor size was defined as regression, progression, or stable disease using RECIST criteria 1.1. Of 426 events, there were 97 with progression, 279 with stable disease, and 50 with regression. Based on the ROC curves a cutoff value of 25% change was selected to discriminate between increased, decreased, or unchanged CgA concentrations in plasma, using a sensitive radioimmunoassay with well-defined epitope specificity. Results. In the 97 events showing tumor progression diagnostic sensitivity and specificity of an increased CgA concentration were 86% and 86%, respectively. The positive and negative predictive values were 64% and 85%, respectively. In the 279 events with unchanged tumor size the diagnostic sensitivity and specificity of an unchanged CgA concentration were 73% and 86%, and the positive and negative predictive values were 91% and 63%, respectively. In the 50 events showing tumor regression, diagnostic sensitivity and specificity of a decrease in CgA concentration were 78% and 91%, the positive and negative predictive values being 55% and 97%. Conclusions. CgA concentrations in plasma have a high diagnostic accuracy in monitoring patients with ileo-cecal neuroendocrine tumors. In particular, an increase in plasma CgA concentration was useful to indicate tumor progression.
What works to improve teacher attendance in developing countries? A systematic review

i This material has been funded by the Department for International Development. The views expressed do not necessarily reflect the views of the Department for International Development. The authors are part GRADE and Penn State University and were supported by the International Initiative for Impact Evaluation (3ie) and the Evidence for Policy and Practice Information and Co-ordinating Centre (EPPICentre). The EPPI-Centre reference number for this report is 2010. This report should be cited as: Guerrero G, Leon J, Zapata M, Sugimaru C, Cueto S (2012) What works to improve teacher attendance in developing countries? A systematic review. London: EPPICentre, Social Science Research Unit, Institute of Education, University of London. ISBN: 978-1-907345-39-5
Peptide Vaccine Induces Enhanced Tumor Growth Associated with Apoptosis Induction in CD8+ T Cells

CD8+ CTLs play a critical role in antitumor immunity. However, vaccination with synthetic peptide containing CTL epitopes has not been generally effective in inducing protective antitumor immunity. In this study, we addressed the detailed mechanism(s) involved in this failure using a new tumor model of BALB/c transplanted tumors expressing NY-ESO-1, an extensively studied human cancer/testis Ag. Whereas peptide immunization with an H2-Dd–restricted CTL epitope derived from NY-ESO-1 (NY-ESO-1 p81–88) induced NY-ESO-181–88–specific CD8+ T cells in draining lymph nodes and spleens, tumor growth was significantly enhanced. Single-cell analysis of specific CD8+ T cells revealed that peptide immunization caused apoptosis of >80% of NY-ESO-181–88–specific CD8+ T cells at tumor sites and repetitive immunization further diminished the number of specific CD8+ T cells. This phenomenon was associated with elevated surface expression of Fas and programmed death-1. When peptide vaccination was combined with an adjuvant, a TLR9 ligand CpG, the elevated Fas and programmed death-1 expression and apoptosis induction were not observed, and vaccine with peptide and CpG was associated with strong tumor growth inhibition. Selection of appropriate adjuvants is essential for development of effective cancer vaccines, with protection of effector T cells from peptide vaccine-induced apoptosis being a prime objective.
Von Willebrand Factor Antigen and Factor XI Activity Levels As Predictors of Bleeding Tendency in Israeli Patients with Von Willebrand's Disease

Previous preliminary data and case reports have suggested an association of von Willebrand's disease (vWD) with factor XI deficiency and platelet abnormalities. We have analyzed the prevalence of factor XI deficiency and thrombocytopathy in a cohort of Israeli patients with vWD. Decreased factor XI levels (<67 U/dl) were documented in 35 of 63 (36%) vWD subjects; factor XI levels were <30 U/dl in five of 60 (8%). A significant decline in ADP-induced platelet aggregation (<30% of control) was found in 48% of vWD patients. Likewise, epinephrine-induced aggregation was reduced in 41%, and collagen-induced aggregation was decreased in 7% of vWD patients. Logistic regression analysis showed that while Ivy bleeding time, ristocetin cofactor, and ristocetin-induced platelet aggregation did not predict bleeding, both von Willebrand factor antigen and factor XI activity levels predict bleeding in patients with vWD. These findings suggest that mild factor XI deficiency and thrombocytopathy are common in Israeli subjects with vWD and that associated factor XI deficiency can result in clinical bleeding in these patients. Key Words: Von Willebrand' s disease—Factor XI deficiency—Thrombocytopathy.
Neonatal outcome and congenital malformations in children born after in-vitro fertilization

This population-based cohort study compared children conceived through in vitro fertilization (IVF) with those conceived spontaneously with regard to neonatal outcomes, the need for hospitalization, and congenital malformations. The two groups were matched for maternal age, parity, social class, gender, year of birth, area of residence, and fetal plurality. The study group included 306 live-born infants born during 1990-1995, 154 singletons and 152 from multiple pregnancies. Control infants were born after completed week 22 of gestation or weighed at least 500 g at birth. In addition to a group of 569 control infants representing the general population in the proportion of multiple births, 103 infants served as plurality-matched controls, and 153 IVF singleton infants were compared with 287 singleton controls. Most mortality rates were twice as high as national figures for the general Finnish population. Compared with control infants representing the general population, odds ratios in the IVF group were 5.6 for preterm birth, 6.2 for very low birth weight (<1500 g), 9.8 for low birth weight (1500-2499 g), 2.4 for neonatal morbidity, and 3.2 for hospitalization. All of these findings were statistically significant. Children in the IVF group not only were hospitalized more often in the neonatal period, but were more frequently intubated. There was no significant difference in low 5-minute Apgar scores. The rate of major or minor congenital malformations or syndromes in the IVF group was 6.6%. Cardiac malformations were increased 4-fold in the IVF population compared with control infants representing the general population. There were no significant differences in central nervous system, limb, or visceral malformations. IVF children in this study had compromised neonatal outcomes that seemed to arise mostly from multiplicity. Analyses stratified for plurality yielded no significant differences between IVF and control infants. In addition, cardiac septal defects were more prevalent in the IVF group. The most productive means of improving neonatal outcomes would be to limit the number of embryos transferred and therefore the number of multiple pregnancies.
Students' use of the internet and social networking sites for learning at Sultan Qaboos University

Students increasingly use the internet and social networking sites but there is little research evidence of its use in fields of learning, specifically in the Arab educational environment. This study therefore investigates students' use of the internet and social networking sites for learning activities and games at the Omani Sultan Qaboos University. To achieve the purpose of the study, a survey questionnaire was developed as the main research instrument. The tests for validity and reliability were conducted during a pilot study. The questionnaire was then administered to the study sample, which was purposive and included (73) educational technology course students who were aware of advanced media including social networking sites. Findings show that the internet and e-mail are frequently used by students, wireless connections and mobile technologies spread quickly among the students and students use search engines for educational purposes. Two research hypotheses were rejected and a third one was accepted. Conclusions and recommendations were then drawn.
Effect of inflammatory bowel disease therapies on immunogenicity of Mycobacterium paratuberculosis proteins

Abstract Background and aims. The link between Mycobacterium avium subsp. paratuberculosis (MAP) and Crohn's disease (CD) is supported by several studies that have reported the detection and isolation of MAP from human tissues, but causation has not yet been proven. Preliminary studies have shown higher levels of antibodies in sera from CD patients against secreted protein from MAP within human macrophages when compared to healthy controls. The immunogenicity of this protein in CD patients under different treatment regimes was evaluated. Materials and methods. Sera of 110 CD patients, 82 ulcerative colitis (UC), and 150 healthy controls were collected and the presence of antibodies against the mycobacterial protein tyrosine phosphatase PtpA was assayed using ELISA. Results. A statistically significant difference in the level of antibodies against PtpA was measured in untreated CD patients versus healthy controls, but variation in the antibody levels was observed when patients were subjected to different treatment regimens. UC patients showed no differences in the levels of antibodies against PtpA when compared to healthy controls. Conclusions. CD patients under different drug treatments show a clear difference in the levels of antibodies against a protein secreted by MAP, suggesting that if MAP is active in the progress of CD, some treatments can be detrimental to its survival.
Elder abuse in long-term care residences and the risk indicators

ABSTRACT The aim of the study was to assess the prevalence of abuse among the residents of long-term care facilities in Israel, and its associations with risk indicators. Seventy-one such residents aged 70 or more years were assessed in the internal and orthopaedic departments of two university medical centres for possible abuse by carers at the long-term facilities from which they were admitted. The study collected socio-demographic and health profiles and a list of maltreatment or abusive acts, and administered the Signs of Abuse Inventory and the Expanded Indicators of Abuse Questionnaire. Among the 71 residents, 31 per cent reported some form of maltreatment, most being instances of disrespectful behaviour. Signs of abuse, mostly of neglect, were detected in 22.5 per cent of the sample. Hierarchical regression analysis revealed that higher scores on risk indicators and higher dependence on others for the activities of daily living significantly associated with reported abuse, while age, gender, risk indicators and lower blood albumin level (being an indicator of worse nutritional and health status) significantly associated with identified signs of abuse. It is concluded that direct questioning mainly discloses instances of disrespectful behaviours and humiliation, while the assessment of signs of abuse is more sensitive to cases of neglect. Risk indicators were found to be reliable indicators of abuse. Routine screening for these indicators is recommended to improve detection and thereby to prevent abuse in long-term care facilities.
Measuring the Effectiveness of Adult Day Care as a Facility to Support Family Caregivers of Dementia Patients

This study reports findings from an evaluation of adult day care that are drawn from ANOVAs based on a comparative longitudinal design. To obtain a suitable outcome measure considering all relevant dimensions of caregiver stress, qualitative data from semistructured caregiving interviews were analyzed using content analytical techniques. Response scales were developed to assess the intensity of caregiving stress to allow for further statistical analyses. Results from the ANOVAs showed that use of day care significantly reduced conflicts between caregiving and job requirements, caregiving and family needs, and recreational constrictions. It is important to note that day care is effective in reducing specific, but not all, aspects of caregiving stress. For an adequate assessment of interventions meant to alleviate caregiving stress, the different dimensions of the concept must be considered.
NF-κB RelA Subunit Is Crucial for Early IFN-β Expression and Resistance to RNA Virus Replication

RNA virus infection results in expression of type 1 IFNs, especially IFN-α/β, which play a crucial role in host antivirus responses. Type 1 IFNs are induced in a cell type-specific manner through TLR and RIG-I–like receptor pathways, both of which activate IFN regulatory factors (IRFs) and NF-κB transcription factors. Although NF-κB activation and association with the IFN-β promoter after RNA virus infection is well documented, our previous work showed that, surprisingly, NF-κB is not essential for IFN-β gene expression. Thus, the actual function of NF-κB in IFN-β expression and virus replication is not clear. In this study, we found Newcastle disease virus and vesicular stomatitis virus replication is enhanced in mouse embryonic fibroblasts (MEFs) lacking the NF-κB RelA subunit. Increased virus replication was traced to a specific requirement for RelA in early virus-induced IFN-β expression. At these time points, when IFN-β expression is ~100-fold less than peak levels, impaired IFN-β production delayed IFN-induced gene expression, resulting in increased virus replication in RelA−/− MEFs. Importantly, our results show that RelA requirement is crucial only when IRF3 activation is low. Thus, high levels of activated IRF3 expression are sufficient for induction of IFN-β in RelA−/− MEFs, transcriptional synergism with the coactivator CREB-binding protein, and rescue of susceptibility to virus. Together, these findings indicate that NF-κB RelA is not crucial for regulating overall IFN-β production, as previously believed; instead, RelA is specifically required only during a key early phase after virus infection, which substantially impacts the host response to virus infection.
IL-17 Enhancement of the IL-6 Signaling Cascade in Astrocytes

Astrocytes have important physiological roles in CNS homeostasis and serve as a bridge between the CNS and immune system. IL-17 and IL-6 are important in many CNS disorders characterized by neuroinflammation. We examined the role of IL-17 on the IL-6 signaling cascade in primary astrocytes. IL-17 functioned in a synergistic manner with IL-6 to induce IL-6 expression in astrocytes. The synergistic effect involved numerous signaling pathways including NF-κB, JNK MAPK, and p38 MAPK. The NF-κB pathway inhibitor BAY-11, JNK inhibitor JNKi II, and p38 inhibitor SB203580 suppressed the synergistic effect of IL-6 and IL-17 on IL-6 expression. IL-17 synergized with IL-6 to enhance the recruitment of activated NF-κB p65, c-Fos, c-Jun, and the histone acetyltransferases CREB-binding protein and p300 to the IL-6 promoter in vivo to induce IL-6 transcription. This was accompanied by enhanced acetylation of histones H3 and H4 on the IL-6 promoter. Moreover, we elucidated an important role for suppressor of cytokine signaling (SOCS) 3 in IL-17 enhancement of IL-6 signaling in astrocytes. SOCS3 small interfering RNA knockdown and SOCS3 deletion in astrocytes augmented the synergistic effect of IL-6 and IL-17 due to an enhancement of activation of the NF-κB and MAPK pathways. These results indicate that astrocytes can serve as a target of Th17 cells and IL-17 in the CNS, and SOCS3 participates in IL-17 functions in the CNS as a negative feedback regulator.
Prolonged N200 is the early neurophysiologic change in the patient with minimal hepatic encephalopathy

Abstract Background. In neurophysiological studies, P300, is well known for reflecting early cognitive impairment in minimal hepatic encephalopathy (MHE). Although P300 is investigated extensively, other early event-related potential (ERP) parameters have not been studied in MHE. Methods. The subjects were 21 adult cirrhotic patients without clinical encephalopathy and 29 normal controls. For neuropsychological testing, number connection tests, A and B (NCT-A, NCT-B), the line tracing test, the serial dotting test (SDT), and the digit symbol test (DST) were performed. For ERP testing, auditory oddball paradigms were used. The N100, P200, N200, and P300 parameters were measured. Results. Cirrhosis had longer neuropsychological performance scores on NCT-A, SDT, and DST than the control group. In neurophysiological test, cirrhotic patients showed longer latencies for N100, P200, N200, and P300 than the control group. Although P300 alteration was not seen in patients without MHE compared to the control group (325.4 ± 43.3 vs. 345.21 ± 35.1, p = 0.25), N200 latency was significantly prolonged in cirrhotic patients without MHE compared to the healthy group (242.1 ± 30.3 vs. 259.58 ± 33.3, p = 0.006). N200 also showed good correlation with psychometric hepatic encephalopathy score and critical flicker frequency. Conclusions. N200 is a useful tool for assessing early changes of cognitive dysfunction in cirrhosis. It suggests that slower auditory cortical processing is the first sign of cerebral deterioration in patients with hepatic encephalopathy.
International Conference on Virtual and Augmented Reality in Education Fun Learning with AR Alphabet Book for Preschool Children

This paper describes the design and evaluation of an AR alphabet book, an Augmented Reality based book for teaching the alphabet to preschool children. Used together with camera and computer, children could view the superimposed virtual alphabet in a fun and interactive manner using the pattern markers as an interaction tool. Generally, teaching young children could be difficult this is due to the focus of young children is different from elderly since they could only focus on something for short period of time. Introducing the fun and interactive learning could grab the attention therefore enhance teaching and learning for young learner. Fun-learning emphasized interactive learning through play, songs; dance, drama and the use of information and communication technology (ICT). Researches showed that fun learning also increase the ability to memorize and understanding of the user. Flashcard is one of the learning approaches to teach children the alphabet. The tangible manner of flashcard introduce the interaction of learning therefore it could create the joyful learning. However, the potential of flash-card could be further enhance through the use of AR technology. Therefore, introducing the use of AR could encompass fun learning since AR offer rich media learning. Besides displaying each alphabet upon presentation of its corresponding pattern marker, children have the options to see 3D models of objects that begin with each alphabet character. Additional book features includes pattern markers for children to view animation of how each letter is drawn and jigsaw puzzle game for each letter to test children understanding. An informal study was conducted among 15 preschool children aged between 5-6 years old to examine user perception of the book. The preliminary results indicate the children reacted positively towards the books; most reported they like and enjoy using the AR book. Observation of the children behaviors during study corroborates this finding. Most students requested to use the AR book repeatedly. These results suggest the potential of AR book as a tool to create fun learning environment especially for preschool children. Furthermore, the brief interview with the teacher of the preschool also suggested that the system seem to grab the attention of the children. © 2013 The Authors. Published by Elsevier B.V. Selection and/or peer-review under responsibility of the programme committee of the 2013 International Conference on Virtual and Augmented Reality in Education.
The long-term outcome of anti-tumor necrosis factor-α therapy related to fecal calprotectin values during induction therapy in pediatric inflammatory bowel disease

Abstract Objective. Monitoring fecal calprotectin (FC) could assist in the assessment of the therapeutic response of inflammatory bowel disease (IBD). There are few studies on long-term prognosis related to the FC value response to infliximab induction therapy, thus providing the aim of this study on pediatric patients. Methods. FC levels were measured during the induction and maintenance phase of infliximab therapy (5 mg/kg) in 76 pediatric IBD patients introduced to maintenance therapy. The long-term outcomes and clinical disease activity were retrospectively related to the FC response to induction. Results. The median pretreatment FC level of 817 μg/g stool (range <5–24,000) declined to 372 μg/g (range 5–2430) by week 6, with a low level (<100 μg/g) in 35% (pooled comparable data for ulcerative colitis and Crohn’s). Clinical activity indices showed remission in 59% (pediatric Crohn's disease activity index: <10, n = 33; pediatric ulcerative colitis activity index: <10 n = 12). In 49 patients (64%), infliximab therapy was discontinued (inadequate effect/surgery = 27; remission/bridging to azathioprine = 12; adverse effect = 6; antibodies to infliximab n = 4) during the study period with a median follow up of 1.1 years (interquartile range [IQR]: 0.71–4.4). Those who discontinued the therapy within the first year due to an inadequate effect had higher median FC level during induction than the other patients (median 633 µg/g, IQR: 197–819 and median 219 µg/g, IQR: 71–508, respectively; p < 0.025) and were less frequently in clinical remission at week 6 (p < 0.01). Conclusions. The long-term prognosis of infliximab therapy is related to the response to induction therapy in pediatric IBD and reflected in low FC values between weeks 2 and 6 and clinical remission.