Miracle-dz/UniFAR-FTUs huggingface dataset:
Stem cell transplantation in Malaysia and future directions.

279 There is a website named EDGE (www.edge.org) which explores unconventional ideas in this rapidly changing world. In 2006, this site had invited many eminent scientists and thinkers to write about “What is your dangerous idea? ” An idea considered dangerous now may in future turn out to be beneficial to mankind. In the early seventies, Dr ED Thomas not only toyed with such a dangerous idea, but also was able to convince his colleagues to carry out the first clinical trial in allogeneic (donor-recipient) bone marrow transplantation in humans. This study showed a plateau in the survival curve suggesting that a cure is possible in endstage acute leukemia. It became a major milestone in clinical transplantation research and therapy. In the mid seventies, Dr NC Gorin performed the first autologous (patient’s own) bone marrow transplantation (BMT) for patients who had no family donor for allogeneic transplant. Since then, BMT has progressed considerably and benefited patients with not only blood disorders but also other systemic diseases such as solid tumours and autoimmune disorders.
Wing folding and the functional morphology of the wing base in Coleoptera.

The wing unfolding of Pachnoda marginata was examined using digital video (50 half-fps) and high speed video sequences (1000 fps), and the skeleto-muscular apparatus of the metathorax was described. Left and right hind wing are able to promote independently of each other. The hind wings do not unfold instantly when the elytra are lifted and may also reach the flight position (and beat) while still folded. Wing promotion is exhaustible and the time needed for unfolding varies considerably. These observations strongly suggest a muscular control. Wing unfolding is probably triggered by contraction of M. pleura alaris and a resulting proximad movement of the 3rd axillary sclerite, pulling the Media posterior backwards, while the Radius anterior is held by the basalar muscle as the antagonist. Our findings are in clear contrast to the earlier assumption that the hind wings of Coleoptera either unfold or fold due to intrinsic elasticity. The specific wing folding and unfolding mechanisms are autapomorphic character states of Coleoptera. They were maintained during evolution even though considerable variations of skeletal thoracic structures, musculature and venation occurred. (Additional material is available from the Zoology web page: http://www.urbanfischer.de/journals/zoology).
Human Placental MicroRNAs and Preeclampsia1

ABSTRACT MicroRNAs are a class of noncoding small RNAs that regulate the expression of nearly 30% of all the human genes and participate in all fundamental cell processes. Genome-wide analysis has revealed that human placenta expresses more than 600 miRNA species, including placenta-specific ones with high levels of expression. Comparative analysis also has revealed many differentially expressed miRNAs with either high or low levels of expression in human placentas from normal versus preeclamptic pregnancies, indicating an important role of miRNAs in normal and pathological placental physiology. Although limited information is currently available as to how miRNA regulates human placental development and function, there are studies suggesting that preeclampsia-associated differentially expressed miRNAs possess critical roles in regulating placental development and function via targeting specific genes with diverse known functions. Herein we summarize the current findings regarding the expression of placental miRNAs and their function, especially in the trophoblast cells. We have recently found that the angiogenesis-associated miR-17-family miRNAs are upregulated in preeclamptic compared with normotensive placentas and they target the ephrin-B2/Eph receptor B4 (EPHB4) system. Because ephrin-B2 and EPHB4 has been previously shown to play a crucial role in trophoblast invasion into maternal spiral artery and vascular patterning during early human placental development, the miR-17-ephrin-B2/EPHB4 pathway seems to be a novel miRNA pathway for regulating normal and aberrant placental development during preeclampsia.
Religious Coping Style as a Predictor of the Severity of Anorectic Symptomology

A review of the literature concerning the relationship between anorexia nervosa (AN) and religion reveals two disparate themes: religion as a cultivator of AN, and religion as a recovery benefactor. The purpose of the present study was to address this discrepancy by exploring one factor—religious coping style—suspected to influence the role religion assumes in the lives of individuals with AN. A sample of 134 women who self-identified as having received an AN diagnosis completed measures of religious coping style and anorectic symptomology. Analyses revealed that religious coping style significantly predicted severity of anorectic symptomology.
Hydration: Special issues for playing football in warm and hot environments

The high metabolic rates and body temperatures sustained by football players during training and matches causes sweating – particularly when in warm or hot environments. There is limited published data on the effects of this sweat loss on football performance. The limited information available, together with knowledge of the effects of sweat loss in other sports with skill components as well as endurance and sprint components, suggests that the effects of sweating will be similar as in these other activities. Therefore, the generalization that, on average, a body mass reduction equivalent to 2% should be the acceptable limit of sweat losses seems reasonable. This magnitude and more, of sweat loss is a common occurrence for some players. Sodium is the main electrolyte lost in sweat but there is large variability in sodium losses between players. However, the extent of sodium losses in some players may be such that its replacement is warranted for these players. Although football is a team sport, the great individual variability in sweat and electrolyte losses of players in the same training session or match dictates that individual monitoring to determine individual water and electrolyte requirements should be an essential part of a player's nutrition strategy.
BAHA®: The Direct Bone Conductor

The BAHA® device uses the principle of direct bone conduction (DBC) to overcome several of the drawbacks of conventional air-conduction (AC) and bone-conduction (BC) hearing aids for patients with conductive or mixed hearing loss. Recent developments of the BAHA system have made it more user friendly and the device has been further miniaturized. The FDA has cleared the device for both adults and pediatrics (from age 5 and up) and also for bilateral fitting. With the BAHA system, a vibrating transducer is directly connected to the skull bone, of which the cochlea is an integrated part. This principle of DBC provides a more or less direct and clear transmission pathway to the cochlea. The BAHA surgery is, however, a minor surgical procedure and does not in any way interfere with the hearing organ so there are no risks of damaging the ear or the residual hearing. Scientific papers about BAHA from around the world report high performance, safety, and patient satisfaction. (Tjellstrom and Granstrom, 1995; Powell et al., 1996; Hartland et al., 1996; Papsin et al., 1997; Tietze et al., 2001; Tjellstrom and Hakansson, 2001; Snik et al., 2001; Lustig et al., 2001). Today, more than 9000 patients around the world have been treated with BAHA.
Comparing active and repressed expression states of genes controlled by the Polycomb/Trithorax group proteins

Drosophila Polycomb group (PcG) and Trithorax group (TrxG) proteins are responsible for the maintenance of stable transcription patterns of many developmental regulators, such as the homeotic genes. We have used ChIP-on-chip to compare the distribution of several PcG/TrxG proteins, as well as histone modifications in active and repressed genes across the two homeotic complexes ANT-C and BX-C. Our data indicate the colocalization of the Polycomb repressive complex 1 (PRC1) with Trx and the DNA binding protein Pleiohomeotic (Pho) at discrete sequence elements as well as significant chromatin assembly differences in active and inactive regions. Trx binds to the promoters of active genes and noncoding transcripts. Most strikingly, in the active state, Pho covers extended chromatin domains over many kilobases. This feature of Pho, observed on many polytene chromosome puffs, reflects a previously undescribed function. At the hsp70 gene, we demonstrate in mutants that Pho is required for transcriptional recovery after heat shock. Besides its presumptive function in recruiting PcG complexes to their site of action, our results now uncover that Pho plays an additional role in the repression of already induced genes.
Ketamine for the treatment of chronic non-cancer pain

Importance of the field: Worldwide the number of patients affected by chronic pain is growing and conventional treatment is often insufficient. Recently the importance of the N-methyl-d-aspartate receptor (NMDAR) in the mechanisms and maintenance of chronic pain was established. Ketamine (introduced in the 1960s as an anesthetic) is the most studied NMDAR antagonist in the treatment of various chronic pain syndromes. Areas covered in this review: The pharmacology, safety and toxicology of ketamine are discussed. Further, electronic databases were scanned for prospective, randomized controlled trials that assessed ketamine's analgesic effect in patients with chronic pain. The focus of this review is on trials published after 2008 that applied long-term intravenous infusions. What the reader will gain: While most studies on intravenous ketamine show acute analgesic effects, three recent trials on long-term ketamine treatment (days to weeks) demonstrate the effectiveness of ketamine in causing long-term (months) relief of chronic pain. Despite these positive results, further studies are needed on safety/toxicity issues. Other administration modes are less effective in causing long-term pain relief. Take home message: There is now evidence form a limited number of studies that pain relief lasting for months is observed after long-term intravenous ketamine infusion, suggesting a modulatory effect of ketamine in the process of chronic pain, possibly via blockade of upregulated NMDAR.
Integration of discrete manufacturing field devices data and services based on OPC UA

The importance of information availability from field device to management level is continuously growing against the background for meeting the demands on competitive and flexible production systems in discrete manufacturing. Service-oriented Architecture (SOA) paradigm seems to promise to fulfill this requirement. However, SOA will not be applicable to every field device due to e.g. computational limitations. Therefore this paper presents an approach for the integration of manufacturing field devices based on fieldbus information models and services. This is done by a controller-based SOA gateway and a semantic transformation of fieldbus information models and services into OPC Unified Architecture (OPC UA). An on-the-fly transformation of data and services based on OPC UA is proposed and validated using sercos III as Real-Time-Ethernet (RTE)-based fieldbus.
Demonstration of Lignin-to-Peroxidase Direct Electron Transfer

Background: Ligninolytic peroxidases are often studied using simple model substrates. Results: Reaction of versatile peroxidase with the lignin polymer is shown by a combination of directed mutagenesis, chromatographic, and spectroscopic techniques. Conclusion: The main reaction implies direct electron transfer to a surface tryptophanyl radical responsible for lignin oxidation. Significance: This is the first time that this central mechanistic aspect is shown for a ligninolytic peroxidase. Versatile peroxidase (VP) is a high redox-potential peroxidase of biotechnological interest that is able to oxidize phenolic and non-phenolic aromatics, Mn2+, and different dyes. The ability of VP from Pleurotus eryngii to oxidize water-soluble lignins (softwood and hardwood lignosulfonates) is demonstrated here by a combination of directed mutagenesis and spectroscopic techniques, among others. In addition, direct electron transfer between the peroxidase and the lignin macromolecule was kinetically characterized using stopped-flow spectrophotometry. VP variants were used to show that this reaction strongly depends on the presence of a solvent-exposed tryptophan residue (Trp-164). Moreover, the tryptophanyl radical detected by EPR spectroscopy of H2O2-activated VP (being absent from the W164S variant) was identified as catalytically active because it was reduced during lignosulfonate oxidation, resulting in the appearance of a lignin radical. The decrease of lignin fluorescence (excitation at 355 nm/emission at 400 nm) during VP treatment under steady-state conditions was accompanied by a decrease of the lignin (aromatic nuclei and side chains) signals in one-dimensional and two-dimensional NMR spectra, confirming the ligninolytic capabilities of the enzyme. Simultaneously, size-exclusion chromatography showed an increase of the molecular mass of the modified residual lignin, especially for the (low molecular mass) hardwood lignosulfonate, revealing that the oxidation products tend to recondense during the VP treatment. Finally, mutagenesis of selected residues neighboring Trp-164 resulted in improved apparent second-order rate constants for lignosulfonate reactions, revealing that changes in its protein environment (modifying the net negative charge and/or substrate accessibility/binding) can modulate the reactivity of the catalytic tryptophan.
Clinical characteristics and management of a Greek female patient cohort with breast ductal carcinoma in situ.

PURPOSE The purpose of this retrospective single-centre study was to examine the histopathological characteristics of breast ductal carcinoma in situ (DCIS) lesions in a cohort of Greek female patients and describe our experience regarding the clinical management of the disease. METHODS The medical records from 1995 up to mid-2014 were scanned in order to trace DCIS cases. One hundred and seventy two patients (6.8% of all breast cancer cases) were diagnosed with pure DCIS and no invasive components; 32.0% underwent a second surgery, mainly due to first surgery positive margins. RESULTS Age at first surgery ranged from 27 to 79 years (mean±SD 50±11) and median tumor size was 10mm (interquartile range/IQR7equals;12mm). Comedo necrosis (CN) was identified in 28.5% of the cases. The detection of CN was significantly associated with older age at diagnosis, larger tumor size and lower probability of highly differentiated tumors. Radiotherapy (RT) and hormonotherapy (HT) were applied to 44.8% and 63.4% of the patients, respectively. CONCLUSIONS We implemented international practices (surgery, radiotherapy and prophylactic hormonal therapy) to patients diagnosed with DCIS and have observed only two relapses. It is our belief that DCIS requires a multidisciplinary approach and patient-tailored therapy which can potentially contribute to minimization of the local recurrence risk.
Heme oxygenase-1 induction through p 38 MAPK / Nrf 2 activation by ethanol extract of Artemisia capillaries inhibits LPS-activated iNOS , COX-2 , and HMGB 1 in RAW 264 . 7 cells

Heme oxygenase-1 (HO-1) negatively regulates inflammatory cytokines in lipopolysaccharide (LPS)-activated RAW 264.7 cells. The purpose of the study was to know whether anti-inflammatory effect of the extract of Artemisia capillaries (EAC) is responsible for HO-1 protein expression in RAW264.7 cells. EAC increased HO-1 expression in a time and concentration-dependent manner and inhibited the expression of iNOS (NO) and COX-2 (PGE2), and release of high mobility group box 1 (HMGB1) in LPS-activated RAW 264.7 cells, respectively. EAC also inhibited NF-kB activity in LPS-activated cells. Finally, the induction of HO-1 as well as inhibition of iNOS and COX-2 by EAC was inhibited by SB203580 but not by SP600125, PD98059, nor LY294002. These results suggest that p38 MAPK/Nrf2-dependent HO-1 induction by EAC is at least rationalized for traditional use of this herb to treat in inflammatory disorders.
Antiphosphorylcholine Antibody Levels Are Elevated in Humans with Periodontal Diseases

ABSTRACT Human immunoglobulin G2 (IgG2) serum concentrations and the IgG2 antibody response to Actinobacillus actinomycetemcomitanscan be influenced by genes, by environmental factors such as smoking, and by periodontal disease status. Examination of the IgG2 response to phosphorylcholine (PC), a response thought to be mainly induced by the C polysaccharide of Streptococcus pneumoniae, suggested that periodontal disease status was also associated with this response. This prompted the hypothesis that PC is an important oral antigen associated with organisms in the periodontal flora and that anti-PC antibody is elevated as a consequence of periodontal disease. Subjects in various periodontal disease diagnostic categories in which attachment loss is exhibited were tested for anti-PC in serum. Those with adult periodontitis, localized juvenile periodontitis, generalized early-onset periodontitis, and gingival recession all had similar levels of anti-PC IgG2 serum antibody which were significantly greater than in the group of subjects with no attachment loss. Analysis of plaque samples from subgingival and supragingival sites in all diseases categories for reactivity with the anti-PC specific monoclonal antibody TEPC-15 revealed that a substantial proportion of the bacteria in dental plaque (30 to 40%) bear PC antigen; this antigen was not restricted to morphotypes resembling only cocci but was also present on rods and branched filamentous organisms. We found that S. mitis, S. oralis, and S. sanguis, as well as oral actinomycetes, including A. viscosus, A. odontolyticus, and A. israelii, incorporated substantial amounts of [3H]choline from culture media. Further analysis of antigens derived from these organisms by Western blot indicated that S. oralis, S. sanguis,A. viscosus, A. odontolyticus, and A. israelii contained TEPC-15-reactive antigens. The data show that many commonly occurring bacterial species found in dental plaque contain PC antigen and that immunization with plaque-derived PC antigens as a consequence of inflammation and periodontal attachment loss may influence systemic anti-PC antibody concentrations.
Growth Factors, Cytokines, Cell Cycle Molecules Suppressor of Cytokine Signaling-2 Gene Disruption Promotes Apc Tumorigenesis and Activator Protein-1 Activation

Epigenetic in vitro and in vivo studies suggest that suppressor of cytokine signaling-2 (SOCS2) may normally limit tumorigenesis in the intestine; however, this theory has not been directly tested. We hypothesized that SOCS2 deficiency promotes spontaneous intestinal tumorigenesis in Apc mice. Therefore, we quantified tumor number, size, and load in the small intestine and colon using SOCS2 / /Apc , SOCS2 / /Apc , and SOCS2 / /Apc mice and assayed hematocrit as an indirect marker of disease severity. Biochemical and histological assays were used to assess mechanisms. Heterozygous and homozygous disruption of SOCS2 alleles promoted 166 and 441% increases in tumor load in the small intestine, respectively, accelerated development of colon tumors, and caused severe anemia. SOCS2 deletion promoted significant increases in intestinal insulinlike growth factor-I mRNA but did not affect plasma insulin-like growth factor-I. Western blots and immunohistochemical analysis demonstrated that tumor and nontumor intestinal tissue of SOCS2 / /Apc mice had increased serine 727 phosphorylation of signal transducer and activator of transcription 3 compared with SOCS2 / /Apc mice. Moreover, electromobility shift assays showed that SOCS2 deletion did not alter signal transducer and activator of transcription 3 DNA binding. However, tumors and small intestine from SOCS2 / /Apc showed dramatic increases in activator protein-1 (AP-1) DNA binding, and SOCS2 overexpression in vitro reduced levels of AP-1. These studies indicate that SOCS2 deletion promotes the spontaneous development of intestinal tumors driven by mutations in the adenomatous polyposis coli/ -catenin pathway and activates AP-1. Therefore, reduced expression or epigenetic silencing of SOCS2 may serve as a useful biomarker for colorectal cancer risk. (Am J Pathol 2010, 176:2320–2332; DOI: 10.2353/ajpath.2010.090684)
Disease phenotype and genotype are associated with shifts in intestinal‐associated microbiota in inflammatory bowel diseases

Background: Abnormal host–microbe interactions are implicated in the pathogenesis of inflammatory bowel diseases. Previous 16S rRNA sequence analysis of intestinal tissues demonstrated that a subset of Crohn's disease (CD) and ulcerative colitis (UC) samples exhibited altered intestinal‐associated microbial compositions characterized by depletion of Bacteroidetes and Firmicutes (particularly Clostridium taxa). We hypothesize that NOD2 and ATG16L1 risk alleles may be associated with these alterations. Methods: To test this hypothesis, we genotyped 178 specimens collected from 35 CD, 35 UC, and 54 control patients for the three major NOD2 risk alleles (Leu 1007fs, R702W, and G908R) and the ATG16L1T300A risk allele, that had undergone previous 16S rRNA sequence analysis. Our statistical models incorporated the following independent variables: 1) disease phenotype (CD, UC, non‐IBD control); 2) NOD2 composite genotype (NOD2R = at least one risk allele, NOD2NR = no risk alleles); 3) ATG16L1T300A genotype (ATG16L1R/R, ATG16L1R/NR, ATG16L1NR/NR); 4) patient age at time of surgery and all first‐order interactions. The dependent variable(s) were the relative frequencies of bacterial taxa classified by applying the RDP 2.1 classifier to previously reported 16S rRNA sequence data. Results: Disease phenotype, NOD2 composite genotype and ATG16L1 genotype were significantly associated with shifts in microbial compositions by nonparametric multivariate analysis of covariance (MANCOVA). Shifts in the relative frequencies of Faecalibacterium and Escherichia taxa were significantly associated with disease phenotype by nonparametric ANCOVA. Conclusions: These results support the concept that disease phenotype and genotype are associated with compositional changes in intestinal‐associated microbiota. (Inflamm Bowel Dis 2011;)
Capturing circulating endothelial progenitor cells: a new concept tested in the HEALING studies.

Cardiology Practice and Hospital, Munich, Germany S has become a standard procedure in percutaneous coronary interventions (PCI). 1 The Achilles’ heel of stenting—the stent-related restenosis—has been almost (but not totally) resolved by many drug-eluting stents (DES). Today, DES are used in over 80% in the USA and in Switzerland with lower penetration rates in other countries. The new Achilles’ heel of stenting with DES, however, seems to be late stent thrombosis:2-4 due to delayed healing, DES require longer addition of clopidogrel to acetylsalicylic acid drug. If clopidogrel is discontinued too early, stent thrombosis with its inherent high mortality, is a possible threat. Therefore, a new concept was developed, enhancing the speed of stent healing by capturing circulating endothelial progenitor cells from the blood stream onto a specially designed stent.5-7