Miracle-dz/UniFAR-FTUs huggingface dataset:
PET/CT and MIBG scans in diagnosis and management of Neuroblastoma

Introduction and aim: Several studies report conflicting results about 18 F-FDG/PET and MIBG scans and their diagnostic as well as prognostic significance in children with neuroblastoma. The current study was meant to evaluate both modalities and to compare them in relation to standardized modes of evaluation. Patients and Methods: Paired evaluation ( 18 F-PET/CT and MIBG) was carried out prospectively (within a time interval of 1 month) at diagnosis and at different points of therapy, between June 2012 and April 2013. Thirty patients (14 males and 16 females), aged (0-18 years), diagnosed with Neuroblastoma at Children’s Cancer Hospital-Egypt. They were treated according to COG A3973 for high risk patients and COG A3961 for intermediate risk patients. Results: FDG/PET showed good results in detecting NB at all sites. FDG/PET also showed a higher sensitivity and specificity, and a better PPV/NPV than MIBG which was not statistically significant. Concordance between paired scans (MIBG, and PET) was found in 55.7% of cases (Kappa=0.001) for primary tumor site, and in 7% for bone and 19.4% for bone marrow. The significance of concordance between both modalities was only demonstrated for metastatic boney lesions. There were 13 patients having stage III neuroblastoma (43.3%) while 17 patients (56.7%) were having stage IV disease. 23 Patients were categorized as high risk (76.7%) while 7 patients (23.3%) were intermediate risk. Both, PET/CT scan and MIBG were more sensitive in detecting disease at stage IV than stage III. Conclusion: 18 F-FDG/PET scan can be used effectively in both diagnosis and management decisions for children with neuroblastoma, it is a good complementary tool especially in detecting bone metastasis, although further clinical trials must agree on definite analytical aspects between both modalities.
Hypoplastic presentation of acute lymphoblastic leukemia

A 37-year-old man presented with fever, lethargy and headache followed in two days by abdominal pain and high fever (408C). Swine flu was initially suspected but a blood count showed a white cell count (WBC) of 0.3 3 10/l, hemoglobin concentration (Hb) 4.5 g/dl, platelet count 18 3 10/l and neutrophil count 0.1 3 10/l. A blood film showed toxic changes in neutrophils; there were atypical lymphocytes, which appeared reactive. Liver function was impaired. The patient required an urgent right hemicolectomy for perforation of the colon as a result of neutropenic enterocolitis. A bone marrow aspirate was hypocellular with no abnormal cells being seen and normal cytogenetic analysis. Peripheral blood immunophenotyping showed no abnormal population. A trephine biopsy (left) was hypocellular with an increase of small T and B lymphocytes. There was no increase in CD34-positive cells but cells expressing terminal deoxynucleotidyl transferase (TdT) were increased. The findings were interpreted as toxic damage to the bone marrow with the increased TdT-positive cells possibly representing hematogones and presaging recovery. The patient suffered a further episode of sepsis but then made an uneventful recovery with blood counts showing spontaneous recovery (right). However four months after the initial presentation he developed fatigue. The Hb was found to have fallen to 9.5 g/dl, the platelet count to 31 3 10/l and the neutrophil count to 0.2 3 10/l. A blood film now showed numerous lymphoblasts and these had largely effaced the bone marrow. The immunophenotype was that of common ALL (CD10, CD19, cytoplasmic CD22 and CD79a positive, cytoplasmic l chain negative). The patient entered complete remission with combination chemotherapy (UKALL XII regime) and successfully completed allogeneic stem cell transplantation. An aplastic presentation of ALL occurs in about 2% of childhood ALL and is also sometimes seen in adults. As in our patient, neutropenia is often more severe than thrombocytopenia. Leukemia has followed after an interval varying from 5 weeks to 9 months but the interval is usually less than 6 months. Sometimes a lymphoid infiltrate is present during the aplastic phase and increased reticulin and fibroblasts may provide evidence of stromal damage. In at least five reported patients retrospective molecular analysis has shown the presence of the leukemic clone during the aplastic phase. The pathogenesis of this rare presentation of ALL remains unknown although in a single patient leukemic lymphoblasts were shown to inhibit hematopoiesis.
Gender differences in colorectal cancer incidence, mortality, hospitalizations and surgical procedures in Canada.

BACKGROUND Over the past few decades there have been changes in incidence and mortality of colorectal cancer. OBJECTIVE To examine gender differences in incidence, hospitalization, hospital-based procedures and mortality for colorectal cancer. METHODS Data were derived from the Hospital Morbidity Database, Canadian Cancer Registry and the Canadian Mortality Database. RESULTS Overall incidence and mortality rates for colorectal cancer are decreasing, but remain substantially higher for males. Absolute numbers of cases are similar for men and women. The top subsite for men was rectal cancer, which was third highest for women, whereas right colon cancer was highest for women. Male/female ratios for incidence and surgeries were highest for distal cancer and are increasing with time. CONCLUSIONS Although overall incidence rates have shown a decline, absolute numbers of new colorectal cancer cases have increased. While men have higher colorectal cancer rates, women have similar numbers and screening should target both equally. Over the years, colorectal cancer subsites are showing a rightward shift, i.e. an increase in proximal subsites, but a leftward shift in male/female ratios, i.e. a greater decrease for the more distal subsites in females. The lower rates for women for distal cancer are compatible with a degree of hormonal protection based on oral contraceptive and hormone replacement therapy. Colorectal cancer will continue to be a considerable public health problem in the foreseeable future.
Physiopathology of haemophilic arthropathy

Summary. Haemophilic arthropathy, which shares some clinical and biological injury characteristics with rheumatoid arthritis, is characterized by two main features: chronic proliferative synovitis and cartilage destruction. It is the consequence of repeated extravasation of blood into joint cavities, but its exact pathogenesis, particularly with regard to early changes in the joint, is still incompletely understood. This review presents recent findings obtained in experiments performed in vitro and using animal models, which have improved our knowledge of the pathogenesis of haemophilic arthropathy. These experimental studies show that haemophilic arthropathy is a multifactorial event in which the deposit of iron in the joints appears to exert a central role. First, iron may promote the apoptosis of chondrocytes by catalysing the formation of oxygen metabolites; this may explain the fact that intra‐articular blood exerts a directly harmful effect on cartilage before, and independent of synovial changes. Secondly, iron may also act on the synovial membrane by favouring its proliferation through the induction of proto‐oncogenes involved in cellular proliferation and stimulation of inflammatory cytokines as well as abrogation of apoptosis. These two processes, one degenerative and cartilage‐mediated, the other inflammatory and synovium‐mediated could occur in parallel or sequentially. Overall, it may be expected that these experimental results will yield new therapeutic strategies capable of effectively preventing the occurrence of this still serious and common complication in patients with severe haemophilia.
One‐stage and chromogenic FVIII:C assay discrepancy in mild haemophilia A and the relationship with the mutation and bleeding phenotype

Summary. The discrepancy of the levels of factor VIII activity (FVIII:C) by different assays in some mild and moderate haemophilic A patients has been long known. Specific mutations affecting FVIII:C discrepancies have been described. No consensus exit as to which method most accurately represents the FVIII cofactor function in vivo and which has a better correlation with the haemorrhagic clinical expression. We studied 163 mild A haemophiliacs, and detected discrepancies in 20% of the patients, most of whom presented higher levels of FVIII:C with the one‐stage assay. In nine families, the FVIII mutation was found, while three showed mutations not previously described (Leu1978Phe and Ser1791Pro associated with higher levels of FVIII:C by one‐stage method; Arg1639His in a patient with low level of FVIII:C by the one‐stage, but normal, chromogenic assay). Assessing the level of FVIII:C by different methods could help to learn the possible haemorrhagic expressions of patients.
Students' attitudes to the communications employed during an outbreak of meningococcal disease in a UK school: a qualitative study.

BACKGROUND Following an outbreak of meningococcal disease in a school in the North West of England, the communication methods employed by the Health Protection Agency (HPA) were evaluated in order to explore ways of improving communication with the public. METHODS Qualitative questionnaires were distributed to Year 12 (sixth form) students. The Framework approach was used to analyse the data, which were coded, and emergent themes identified. RESULTS In the absence of clear communication from official sources, many participants suggested that circulating rumours caused confusion and anxiety in the student population. Rumours were spread through informal networks in person or through text and MSN messaging. It was generally perceived that accurate information in this period would have been useful to allay potentially unfounded anxiety. Most students surveyed reported that they were sufficiently aware of the situation prior to receiving official announcements. The information provided by the HPA through the school was generally perceived as being useful, but it came too late. CONCLUSION In outbreak situations, rumours will spread rapidly in the absence of early communication, and this can be a significant cause of anxiety. The use of digital communication strategies should be considered, since they can seed dependable information that will disseminate rapidly through peer groups.
Structure and Function of the Intracellular Region of the Plexin-B1 Transmembrane Receptor*

Members of the plexin family are unique transmembrane receptors in that they interact directly with Rho family small GTPases; moreover, they contain a GTPase-activating protein (GAP) domain for R-Ras, which is crucial for plexin-mediated regulation of cell motility. However, the functional role and structural basis of the interactions between the different intracellular domains of plexins remained unclear. Here we present the 2.4 Å crystal structure of the complete intracellular region of human plexin-B1. The structure is monomeric and reveals that the GAP domain is folded into one structure from two segments, separated by the Rho GTPase binding domain (RBD). The RBD is not dimerized, as observed previously. Instead, binding of a conserved loop region appears to compete with dimerization and anchors the RBD to the GAP domain. Cell-based assays on mutant proteins confirm the functional importance of this coupling loop. Molecular modeling based on structural homology to p120GAP·H-Ras suggests that Ras GTPases can bind to the plexin GAP region. Experimentally, we show that the monomeric intracellular plexin-B1 binds R-Ras but not H-Ras. These findings suggest that the monomeric form of the intracellular region is primed for GAP activity and extend a model for plexin activation.
Towards a public health approach to parenting programmes for parents of adolescents.

BACKGROUND Poor parenting practices have been associated with adolescent emotional and behavioural problems which are potentially preventable. Parenting interventions that are based on behavioural and social learning theories have been repeatedly shown to be effective. However, few evidence-based parenting programmes are implemented and sustained at a population level. Little research is available on supporting the general population of parents during the adolescent years. Further, a substantial research-practice gap exists regarding the impact of a universal approach to parenting programmes for parents of adolescents. METHOD This article will first examine the effects of parenting practices on adolescent outcome. Afterwards, it addresses the effectiveness of parenting programmes for parents of adolescents. Finally, it discusses the need for a public health approach to parenting programmes.
Periphere Endothelfunktionsmessung - Anwendung in der täglichen klinischen Praxis gerechtfertigt?

Assessment of Peripheral Endothelial Function – Justified Use in Daily Clinical Practice? Endothelial dysfunction represents an early step in atherogenesis, and can be non-invasively measured in peripheral vessels. The most common used technique to assess peripheral endothelial function is the ultrasound-based measurement of flow mediated di-
Evaluation of the role of secretory sphingomyelinase and bioactive sphingolipids as biomarkers in hemophagocytic lymphohistiocytosis

Hemophagocytic lymphohistiocytosis (HLH) is a rare systemic inflammatory syndrome that results from unrestrained immune cell activation. Despite significant advances in the understanding of the pathophysiology of HLH, interventions remain limited for this often‐fatal condition. Secretory sphingomyelinase (S‐SMase) is a pro‐inflammatory lipid hydrolase that is upregulated in several inflammatory conditions, including HLH. S‐SMase promotes the formation of ceramide, a bioactive lipid implicated in several human disease states. However, the role of the S‐SMase/ceramide pathway in HLH remains unexplored. To further evaluate the role of S‐SMase upregulation in HLH, we tested the serum of patients with HLH (n = 16; primary = 3, secondary = 13) and healthy control patients (n = 25) for serum S‐SMase activity with tandem sphingolipid metabolomic profiling. Patients with HLH exhibited elevated levels of serum S‐SMase activity, with concomitant elevations in several ceramide species and sphingosine, while levels of sphingosine‐1‐phosphate were significantly decreased. Importantly, the ratio of C16‐ceramide:sphingosine was uniquely elevated in HLH patients that died despite appropriate treatment, but remained low in HLH patients that survived, suggesting that this ratio may be of prognostic significance. Together, these results demonstrate upregulation of the S‐SMase/ceramide pathway in HLH, and suggest that the balance of ceramide and sphingosine determine clinical outcomes in HLH. Am. J. Heamtol. 88:E265–E272, 2013. © 2013 Wiley Periodicals, Inc.
Safety and efficacy of upfront plerixafor + G‐CSF versus placebo + G‐CSF for mobilization of CD34+ hematopoietic progenitor cells in patients ≥60 and <60 years of age with non‐Hodgkin's lymphoma or multiple myeloma

The efficacy and safety of plerixafor + G‐CSF in enhancing hematopoietic stem cell mobilization and collection has been demonstrated in two phase III studies involving patients with NHL or MM. In these pivotal studies, plerixafor + G‐CSF significantly increased the proportion of patients achieving target stem cell yields, compared to placebo + G‐CSF. In this analysis, we compare the efficacy and safety of plerixafor + G‐CSF versus placebo + G‐CSF in patients enrolled in the two phase III studies, stratified by age: ≥60 years of age and <60 years of age. The proportion of older patients who achieved target stem cell yields was significantly higher in the plerixafor group than in placebo group (NHL: 50.9 vs. 25.4%, P < 0.001; MM: 69.6 vs. 23.7%, P < 0.001). In this older cohort, the median times to neutrophil and to platelet engraftment following autologous stem cell transplant were comparable between the plerixafor and placebo groups. Similar efficacy findings were observed in the younger age group. The most common adverse events (all grades) reported among older patients in the plerixafor group included diarrhea (41.3%), nausea (38.9%), fatigue (30.2%), and injection‐site reaction (29.4%). The frequency of adverse events was similar between the older and the younger age groups. Taken together, our subanalysis demonstrate that plerixafor + G‐CSF can be safely and effectively used in adult patients of all ages, including those ≥60 years, to support optimal stem cell mobilization for autologous stem cell transplantation. Am. J. Hematol. 88:1017–1023, 2013. © 2013 Wiley Periodicals, Inc.
Sites of initial bleeding episodes, mode of delivery and age of diagnosis in babies with haemophilia diagnosed before the age of 2 years: a report from The Centers for Disease Control and Prevention’s (CDC) Universal Data Collection (UDC) project

Summary. Lack of detailed natural history and outcomes data for neonates and toddlers with haemophilia hampers the provision of optimal management of the disorder. We report an analysis of prospective data collected from 580 neonates and toddlers aged 0–2 years with haemophilia enrolled in the Universal Data Collection (UDC) surveillance project of the Centers for Disease Control and Prevention (CDC). This study focuses on a cohort of babies with haemophilia whose diagnosis was established before the age of two. The mode of delivery, type and severity of haemophilia, onset and timing of haemorrhages, site(s) of bleeding, provision of prophylaxis with coagulation factor replacement therapy, and the role played by the federally funded Haemophilia Treatment Centers (HTC) in the management of these infants with haemophilia were evaluated. Seventy‐five per cent of haemophilic infants were diagnosed early, in the first month of life, especially those with a family history or whose mothers were known carriers; infants of maternal carriers were more likely to be delivered by C‐section. Involvement of an HTC prior to delivery resulted in avoidance of the use of assisted deliveries with vacuum and forceps. Bleeding from the circumcision site was the most common haemorrhagic complication, followed by intra‐ and extra‐cranial haemorrhages and bleeding from heel stick blood sampling. Eight per cent of the infants were administered factor concentrate within 24 h of birth; more than half were treated to prevent bleeding. This study highlights the significant rate and the sites of initial bleeding unique to very young children with haemophilia and underscores the need for research to identify optimal evidence‐based recommendations for their management.
Pro-hormone Secretogranin II Regulates Dense Core Secretory Granule Biogenesis in Catecholaminergic Cells*

Processes underlying the formation of dense core secretory granules (DCGs) of neuroendocrine cells are poorly understood. Here, we present evidence that DCG biogenesis is dependent on the secretory protein secretogranin (Sg) II, a member of the granin family of pro-hormone cargo of DCGs in neuroendocrine cells. Depletion of SgII expression in PC12 cells leads to a decrease in both the number and size of DCGs and impairs DCG trafficking of other regulated hormones. Expression of SgII fusion proteins in a secretory-deficient PC12 variant rescues a regulated secretory pathway. SgII-containing dense core vesicles share morphological and physical properties with bona fide DCGs, are competent for regulated exocytosis, and maintain an acidic luminal pH through the V-type H+-translocating ATPase. The granulogenic activity of SgII requires a pH gradient along this secretory pathway. We conclude that SgII is a critical factor for the regulation of DCG biogenesis in neuroendocrine cells, mediating the formation of functional DCGs via its pH-dependent aggregation at the trans-Golgi network.
Intra- and Interdomain Effects Due to Mutation of Calcium-binding Sites in Calmodulin*

The IQ-motif protein PEP-19, binds to the C-domain of calmodulin (CaM) with significantly different kon and koff rates in the presence and absence of Ca2+, which could play a role in defining the levels of free CaM during Ca2+ transients. The initial goal of the current study was to determine whether Ca2+ binding to sites III or IV in the C-domain of CaM was responsible for affecting the kinetics of binding PEP-19. EF-hand Ca2+-binding sites were selectively inactivated by the common strategy of changing Asp to Ala at the X-coordination position. Although Ca2+ binding to both sites III and IV appeared necessary for native-like interactions with PEP-19, the data also indicated that the mutations caused undesirable structural alterations as evidenced by significant changes in amide chemical shifts for apoCaM. Mutations in the C-domain also affected chemical shifts in the unmodified N-domain, and altered the Ca2+ binding properties of the N-domain. Conversion of Asp93 to Ala caused the greatest structural perturbations, possibly due to the loss of stabilizing hydrogen bonds between the side chain of Asp93 and backbone amides in apo loop III. Thus, although these mutations inhibit binding of Ca2+, the mutated CaM may not be able to support potentially important native-like activity of the apoprotein. This should be taken into account when designing CaM mutants for expression in cell culture.
Factors associated with the uptake of seasonal influenza vaccination in adults: a systematic review.

Studies on different populations have shown that a variety of factors influence attitudes and decision in the general population on vaccine uptake. This study explores factors associated with the uptake of influenza vaccination among adults. A systematic literature review was performed on literature searched in databases EMBASE, MEDLINE, Cochrane Library and Electronic Theses Online Service up until November 2013. A critical appraisal framework was designed to assess the methodological quality of the studies. Twenty-three articles met the inclusion criteria and were selected for outcome analysis and 21 were quantitative observational studies. Advancement in age (OR 1.06-23.7) and having chronic diseases (OR 1.38-13.7) were strongly indicative of vaccine uptake. Perceptions on vaccine efficacy (OR 2.7-10.55) and vaccine safety and adverse events (OR 10.5) were more influential than the level of knowledge on influenza and its vaccination. Advice from doctors/health professionals/family and/or close friends and free vaccination were also key factors in association with uptake of vaccination. This review highlighted the finding that perception on vaccine efficacy, perception on vaccine safety and adverse events, advice from doctors/health professionals/family/close friends and free vaccination are changeable factors that are strongly associated with influenza vaccination in adults aged 18-64.
Red blood cell nitric oxide synthase activation is increased in patients with sickle cell hemoglobin C disease

low number of patients in the DNR90 group leads to low statistical power hiding a potential difference between the two groups. However, hazard ratio in the multivariate model (0.91 for RFS and 0.84 for OS) do not support a dramatic influence of DNR dose in our series. Moreover, improvements of AML therapy results over time might confound the results of historical control comparison as previously shown [12,13], but in our analysis, this would have favor the DNR90 group. Although these limitations, our results are important to give the basis of a potential prospective comparison of these regimens with the objectives of confirming our retrospective data but more importantly to try to define subgroups of patients for which dose intensification may be beneficial.