Miracle-dz/UniFAR-FTUs huggingface dataset:
Biocontrol of aflatoxin in corn by inoculation with non-aflatoxigenic Aspergillus flavus isolates

Abstract The ability of two non-aflatoxigenic Aspergillus flavus Link isolates (CT3 and K49) to reduce aflatoxin contamination of corn was assessed in a 4-year field study (2001–2004). Soil was treated with six wheat inoculant treatments: aflatoxigenic isolate F3W4; two non-aflatoxigenic isolates (CT3 and K49); two mixtures of CT3 or K49 with F3W4; and an autoclaved wheat control, applied at 20 kg ha−1. In 2001, inoculation with the aflatoxigenic isolate increased corn grain aflatoxin levels by 188% compared to the non-inoculated control, while CT3 and K49 inoculation reduced aflatoxin levels in corn grain by 86 and 60%, respectively. In 2002, the non-toxigenic CT3 and K49 reduced aflatoxin levels by 61 and 76% compared to non-inoculated controls, respectively. In 2001, mixtures of aflatoxigenic and non-aflatoxigenic isolates had little effect on aflatoxin levels, but in 2002, inoculation with mixtures of K49 and CT3 reduced aflatoxin levels 68 and 37% compared to non-inoculated controls, respectively. In 2003 and 2004, a low level of natural aflatoxin contamination was observed (8 ng g−1). However, inoculation with mixtures of K49 + F3W4 and CT3 + F3W4, reduced levels of aflatoxin 65–94% compared to the aflatoxigenic strain alone. Compared to the non-sclerotia producing CT3, strain K49 produces large sclerotia, has more rapid in vitro radial growth, and a greater ability to colonize corn when artificially inoculated, perhaps indicating greater ecological competence. Results indicate that non-aflatoxigenic, indigenous A. flavus isolates, such as strain K49, have potential use for biocontrol of aflatoxin contamination in southern US corn.
Malignant melanoma of the skin occurring during pregnancy

The clinical course of melanoma of the skin diagnosed during pregnancy was compared with a control population of women with melanoma that occurred during the childbearing years, as recorded by the Connecticut Tumor Registry. The survival at three and five years for the 12 patients whose melanoma developed during pregnancy was significantly worse than for 175 nonpregnant controls (five‐year survival 55% for pregnant women compared with 83% for nonpregnant women, P < 0.05). Melanoma during pregnancy tended to occur more often on the trunk, a prognostically poor site, and at more advanced stage of disease than in nonpregnant women. However, when pregnant patients were matched to random, nonpregnant case‐controls by age, anatomic site of primary lesion, and stage at diagnosis, three‐ and five‐year survivals were not different. The number of pregnant women observed among this group of women was not substantially higher than expected, when estimated from Connecticut live birth rates: 13.3 pregnancies were expected and 12 pregnant women were actually observed. However, an unknown number of pregnancies end in abortion, making more exact estimates impossible. Melanoma occurring during pregnancy usually carries a poor prognosis, but once the disease is diagnosed, the course is not worse than expected considering stage of disease and primary site.
Design of optimized integrated optical phase modulators with graphene

Integrated optical phase modulators based on silicon waveguides with graphene are optimized through the design of the waveguide for operation with quasi-TE or quasi-TM modes using numerical simulations. Higher performance is achieved for quasi-TM mode operation with V<inf>π</inf>L=0.5 V.mm and for the quasi-TE mode V<inf>π</inf>L=0.9 V.mm, electro-optical bandwidths of up to 2.85 GHz is achieved.
The effect of pancreatic enzyme supplementation in patients with steatorrhoea after total gastrectomy.

OBJECTIVE To assess the influence of pancreatic enzyme supplementation on symptoms, energy intake, bowel habits, and fat malassimilation in patients after total gastrectomy. DESIGN A prospective, double-blind, randomized, parallel, placebo-controlled, multi-centre trial. SETTING Institutionalized patients in three gastroenterological rehabilitation clinics. PARTICIPANTS 52 institutionalized patients with a faecal fat output > or = 14 g/day, operated on for malignant gastric disease a median of 198 days (interquartile range (IQR) 47-608) previously, and free from recurrence and/or metastasis. INTERVENTIONS Nine sachets of pancreatic enzymes per day (each containing lipase 36,000, amylase 27,000, protease 2400 FIP (Federation International Pharmaceutique)) or identical-looking placebo were given for 14 days. MAIN OUTCOME MEASURES Abdominal symptoms, energy intake, bowel habits and fat malassimilation. RESULTS After treatment, patients on enzyme therapy felt better overall (P = 0.006), but no improvement of a specific symptom could be identified. During the intervention, the median kilojoule intake per kilogram body weight was 9% higher in the placebo group (170.8 (IQR 146.9-202.6)) than in the enzyme-treated group (157.0 (IQR 134.8-170.4)) (P = 0.03). Enzyme treatment did not result in a significant difference between the placebo and the enzyme-treated group regarding bowel habits or fat malassimilation. CONCLUSIONS The effect of high-dose pancreatic enzymes supplementation on symptoms and steatorrhoea after total gastrectomy is marginal and does not justify its routine use.
Interplay of Sp1 and Egr-1 in the Proximal Platelet-derived Growth Factor A-Chain Promoter in Cultured Vascular Endothelial Cells (*)

The platelet-derived growth factor (PDGF) A-chain has been implicated in the initiation and progression of vascular occlusive lesions. The elements in the human PDGF-A promoter that mediate increased expression of the gene in vascular endothelial cells have not been identified. A potent inducer of PDGF-A expression in endothelial cells is phorbol 12-myristate 13-acetate (PMA). 5′-Deletion and transfection analysis revealed that a G+C-rich region in the proximal PDGF-A promoter is required for PMA-inducible gene expression. This region bears overlapping consensus recognition sequences for Sp1 and Egr-1. PMA induces Egr-1 mRNA expression within 1 h, whereas PDGF-A transcript levels increase after 2-4 h. Constitutive levels of Sp1 are not altered over 24 h. A specific nucleoprotein complex is formed when an oligonucleotide bearing the G+C-rich element is incubated with nuclear extracts from PMA-treated cells. The temporal appearance of this complex is consistent with the transient increase in Egr-1 transcripts. Antibodies to Egr-1 completely supershift the PMA-induced complex. Interestingly, increased nuclear levels of Egr-1 attenuate the ability of Sp1 to interact with the oligonucleotide, implicating competition between Egr-1 and Sp1 for the G+C-rich element. Binding studies with recombinant proteins demonstrate that Egr-1 can displace Sp1 from this region. Insertion of the G+C-rich element into a hybrid promoter-reporter construct confers PMA inducibility on the construct. Mutations that abolish Egr-1 binding also abrogate expression induced by PMA or overexpressed Egr-1. These findings demonstrate that PMA-induced Egr-1 displaces Sp1 from the G+C-rich element and activates expression driven by the PDGF-A proximal promoter in endothelial cells. The Sp1/Egr-1 displacement mechanism may be an important regulatory circuit in the control of inducible gene expression in vascular endothelial cells.
The Biological Embedding of Early Experience and Its Effects on Health in Adulthood

Abstract: Explanations of the socioeconomic gradient in health status must account for the observations that the gradient cuts across a wide range of disease processes and is capable of replicating itself on new disease processes as they emerge in society. Understanding this pattern requires an understanding of how human organisms can become generally vulnerable or resilient to disease over time: a huge collation task across different disciplines. The hypothesis that best fits current evidence is that the gradient is an “emergent property” of the interaction between the developmental status of people and the material and psychosocial conditions they encounter over their life course. Within this broad formulation, special attention is given to child development, and the prospect that socioeconomic differences in the quality of early life experiences contribute to subsequent gradients in health status through socioeconomic differences in brain sculpting and the conditioning of host defense systems that depend on communication with the developing brain. The contribution to the gradient in health is theorized to occur through a combination of latent effects, pathway effects, and cumulative disadvantage.
Lymphatic Mapping Establishes the Role of BRAF Gene Mutation in Papillary Thyroid Carcinoma

Objective:To define the role of BRAF gene mutation in the progression of papillary thyroid carcinoma. Summary Background Data:BRAF gene mutation is frequently detected in papillary thyroid carcinoma. Its role in pathogenesis or progression is under investigation. Methods:Patients who underwent thyroidectomy and sentinel lymph node biopsy for papillary thyroid cancer were accrued. BRAF mutation was assessed in primary tumors and matched sentinel lymph nodes by a quantitative real-time PCR assay. Results:Tissue specimens from 103 consecutive patients were evaluated. BRAF mutation of the primary tumor was detected in 34 (33%) patients. In 26 of 34 (76%) patients with BRAF mutation, concomitant lymph node metastasis was detected. On the contrary, in 69 patients with BRAF mutation-negative primary tumors, only 12 (17%) patients had lymph node metastasis (&khgr;2, P < 0.0001). BRAF mutation was detected in 20 of 26 (77%) lymph node metastases matched to BRAF mutation-positive primary tumors; it was not detected in lymph node metastases matched to BRAF mutation-negative primary tumors. Univariate analysis identified age, stage, tumor size, and BRAF mutation as prognostic factors for lymph node metastasis. In multivariate analysis, only BRAF mutation remained a significant prognostic factor for lymph node metastasis (odds ratio = 10.8, 95% confidence interval, 3.5–34.0, P < 0.0001). Conclusions:BRAF mutation may be a key genetic factor for the metastatic progression of papillary thyroid carcinoma. The study demonstrates that this gene mutation is a significant risk factor for locoregional lymph node metastasis and has potential utility as a surrogate marker.
Improving glycaemic control of insulin-treated diabetic patients--a structured audit of specialist nurse intervention.

Insulin-treated diabetic patients with poor glycaemic control are frequently referred to diabetes specialist nurses, but little data exist as to the effectiveness of this practice. We therefore analysed the progress of 43 prospectively referred insulin-treated patients with glycosylated haemoglobin (HbA1c) levels > 7.5%. Diabetes nurse intervention involved re-education, dietary advice and insulin dose adjustment. Improvement in control was defined as a final HbA1c < 7.0% or a fall of HbA1c of > 1.0% at 6 months post-intervention. Almost two-thirds (63%) of patients achieved improvement status, with no increase in body weight or hypoglycaemic episodes. Disappointingly, however, the 'non-improver' group (37%) showed a mean deterioration in HbA1c. In conclusion, diabetes nurse intervention for poorly controlled insulin-treated diabetic patients is generally effective, but intervention may be best targeted to responsive patients. The factors which influence diabetic patients' 'responsiveness to change' require further investigation.
Review of 336 patients with hepatocellular carcinoma at Songklanagarind Hospital.

AIM:To determine the clinical presentations, survival and prognostic factors of hepatocellular carcinoma (HCC) in Southern Thailand.METHODS:Retrospective analysis was performed on the 336 hepatocellular carcinoma patients treated at Songklanagarind hospital between 1 January 1991 and 31 January 1999.RESULTS:Of these 336 patients, 276 were males and 60 were females. The mean age was 54.4 years. The common symptoms and signs were abdominal pain and hepatomegaly. The most common presentation of tumor was a dominant mass with daughter nodules. Portal vein involvement was found in 50% of total. Extrahepatic metastasis was found in 13%, and the lung was the most common site. There were 65.4% with evidence of cirrhosis and half of them were in Child's class B. HBsAg was positive in 72.6%. Regarding a(c)Okuda's tumor staging, 15%, 61% and 24% were stage I, II and III, respectively. Overall median survival was 2.1 months (11.5 2.6 and 0.7 months for stage I, II and III respectively). Treatments of HCC improved patient survival (5.5 months vs 1.6 months for untreated patients). Most common causes of death were hepatic failure. Using multivariate analysis, the prognostic factors identified were tumor staging, alpha-fetoprotein level above 10000&mgr;gcenter dotL(-1), extrahepatic metastasis, portal vein thrombosis and treatment.CONCLUSION:HCC in Thailand is a fatal disease with poor outcome due to late presentation and high prevalence of liver cirrhosis. Early detection and proper management may improve outcome.
Helix Capping in RNA Structure

Helices are an essential element in defining the three-dimensional architecture of structured RNAs. While internal basepairs in a canonical helix stack on both sides, the ends of the helix stack on only one side and are exposed to the loop side, thus susceptible to fraying unless they are protected. While coaxial stacking has long been known to stabilize helix ends by directly stacking two canonical helices coaxially, based on analysis of helix-loop junctions in RNA crystal structures, herein we describe helix capping, topological stacking of a helix end with a basepair or an unpaired nucleotide from the loop side, which in turn protects helix ends. Beyond the topological protection of helix ends against fraying, helix capping should confer greater stability onto the resulting composite helices. Our analysis also reveals that this general motif is associated with the formation of tertiary structure interactions. Greater knowledge about the dynamics at the helix-junctions in the secondary structure should enhance the prediction of RNA secondary structure with a richer set of energetic rules and help better understand the folding of a secondary structure into its three-dimensional structure. These together suggest that helix capping likely play a fundamental role in driving RNA folding.
Chronic Morphine-Induced Changes in μ-Opioid Receptors and G Proteins of Different Subcellular Loci in Rat Brain

Prolonged exposure to opioid agonists can induce adaptive changes resulting in tolerance and dependence. Here, rats were rendered tolerant by subcutaneous injections of increasing doses of morphine from 10 to 60 mg/kg for 3, 5, or 10 consecutive days. Binding parameters of the μ-opioid receptor in subcellular fractions were measured with [3H]DAMGO ([d-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin). Although the density of surface μ-sites did not change after the 5-day morphine treatment, up-regulation of synaptic plasma membrane binding was detected after the 10-day drug administration. In contrast, the number of μ-binding sites in a light vesicle or microsomal fraction (MI) was elevated by 68 and 30% after 5 and 10 days of morphine exposure, respectively. The up-regulated MI μ-sites displayed enhanced coupling to G proteins compared with those detected in saline-treated controls. Pertussis toxin catalyzed ADP ribosylation, and Western blotting with specific antisera was used to quantitate chronic morphine-induced changes in levels of various G protein α-subunits. Morphine treatment of 5 days and longer induced significant increases in levels of Gαo, Gαi1, and Gαi2 in MI fractions that are part of an adaptation process. Up-regulation of intracellular μ-sites may be the result of post-translational changes and in part de novo synthesis. The results provide the first evidence that distinct regulation of intracellular μ-opioid receptor G protein coupling and G protein levels may accompany the development of morphine tolerance.
Gene silencing by DNA methylation in haematological malignancies

The past decade has seen an explosion of interest in the epigenetics of cancer, with an increasing understanding that this form of genomic modification plays a critical role in pathogenesis. The malignant phenotype results from a step‐wise increase of both genetic abnormalities and epigenetic modifications, leading to dysregulation of critical genes controlling cell growth, differentiation and apoptosis. The methylation of CpG islands within gene promoters is a major epigenetic transcriptional control mechanism that is frequently dysregulated in human cancer. This phenomenon (methylation of CpG islands) plays a critical role in the transcriptional silencing of tumour suppressor genes in cancer and has prompted the development and testing of several demethylating agents aimed at reversing this process. Clinical trials using epigenetically targeted therapies have yielded particularly promising results in the myelodysplastic syndromes (MDS), in which tumour suppressor gene silencing by promoter methylation is a frequent event. Several genes and gene pathways disrupted by aberrant CpG island methylation have now been identified in haematological malignancies, the most frequently studied being the cell cycle inhibitors p16 (now termed CDKN2A; mostly methylated in lymphoid malignancy) and p15 (now termed CDKN2B; commonly methylated in lymphoid and myeloid malignancies). This review will discuss the role that aberrant gene silencing by promoter hypermethylation plays in the molecular pathogenesis of haematological malignancies and assess the clinical potential of demethylating agents for the management of patients.
Immunoproteomic analysis of the protein repertoire of unsporulated Eimeria tenella oocysts

The apicomplexan protozoans Eimeria spp. cause coccidioses, the most common intestinal diseases in chickens. Coccidiosis is associated with significant animal welfare issues and has a high economic impact on the poultry industry. Lack of a full understanding of immunogenic molecules and their precise functions involved in the Eimeria life cycles may limit development of effective vaccines and drug therapies. In this study, immunoproteomic approaches were used to define the antigenic protein repertoire from the total proteins of unsporulated Eimeria tenella oocysts. Approximately 101 protein spots were recognized in sera from chickens infected experimentally with E. tenella. Forty-six spots of unsporulated oocysts were excised from preparative gels and identified by matrix-assisted laser desorption ionization time-of-flight MS (MALDI-TOF-MS) and MALDI-TOF/TOF-MS. For unsporulated oocysts, 13 known proteins of E. tenella and 17 homologous proteins to other apicomplexan or protozoan parasites were identified using the ‘Mascot’ server. The remaining proteins were searched against the E. tenella protein sequence database using the ‘Mascot in-house’ search engine (version 2.1) in automated mode, and 12 unknown proteins were identified. The amino acid sequences of the unknown proteins were searched using BLAST against non-redundant sequence databases (NCBI), and 9 homologous proteins in unsporulated oocyst were found homologous to proteins of other apicomplexan parasites. These findings may provide useful evidence for understanding parasite biology, pathogenesis, immunogenicity and immune evasion mechanisms of E. tenella.
Recent successes of the energy landscape theory of protein folding and function

Protein folding and binding can be understood using energy landscape theory. When seeming deviations from the predictions of the funnel hypothesis are found, landscape theory helps us locate the cause. Sometimes the deviation reflects symmetry effects, allowing extra degeneracies to occur. Such effects seem to explain some kinetic anomalies in helical bundles. When binding processes were found to use apparently non-funneled landscapes this was traced to an inadequate understanding of biomolecular forces. The discrepancy allowed the discovery of new water-mediated forces – some of which act between hydrophilic residues. Introducing such forces into the algorithms greatly improves the quality of structure predictions.
Refractory Status Epilepticus: Is EEG Burst Suppression an Appropriate Treatment Target during Drug-Induced Coma? What is the Holy Grail?

Refractory Status Epilepticus: Effect of Treatment Aggressiveness on Prognosis Rossetti AO, Logroscino G, Bromfield EB Arch Neurol 2005;62(11):1698–1702 Background Administration of antiepileptic drugs for coma induction in refractory status epilepticus (RSE) has not been widely studied. Moreover, the effect on outcome of electroencephalographic (EEG) burst suppression remains unclear. Objective To investigate whether various coma-inducing options are associated with different prognoses after RSE. Design Retrospectively assessed case series. Setting Two tertiary referral hospitals in Boston, Massachusetts. Patients Among 127 consecutive episodes (107 patients) of status epilepticus, we identified episodes that were refractory to first-line and second-line antiepileptic drugs, needing induced coma with barbiturates, propofol, or midazolam for clinical management. Main Outcome Measures Short-term mortality and prevalence of return to functional baseline after the acute episode of status epilepticus were analyzed in relation to demographic and clinical variables and to treatment option (antiepileptic agents and EEG burst suppression). Results Forty-nine episodes of RSE (47 patients) were found, occurring more frequently in incident than in recurrent episodes of status epilepticus (p = .06). Mortality was 23% for patients with RSE and 8% for those without RSE (p = .05). Return to baseline occurred more often in the non-RSE group (p = .04). In 20 (61%) of 33 monitored episodes, EEG burst suppression was achieved. Demographic data, clinical variables, and outcome did not differ significantly with the various coma-inducing agents or between episodes with and without EEG burst suppression. Conclusions Refractory status epilepticus is more prevalent in incident than in recurrent status epilepticus and is associated with higher mortality; clinical status is less likely to return to baseline than with non-RSE. Outcome was independent of the specific coma-inducing agents used and the extent of EEG burst suppression, suggesting that the underlying cause represents its main determinant.
MiR-148a increases glioma cell migration and invasion by downregulating GADD45A in human gliomas with IDH1 R132H mutations

High-grade gliomas are severe tumors with poor prognosis. An R132H mutation in the isocitrate dehydrogenase (IDH1) gene prolongs the life of glioma patients. In this study, we investigated which genes are differentially regulated in IDH1 wild type (IDH1WT) or IDH1 R132H mutation (IDH1R132H) glioblastoma cells. Growth arrest and DNA-damage-inducible protein (GADD45A) was downregulated and microRNA 148a (miR-148a) was upregulated in in IDH1R132H human glioblastomas tissues. The relationship between GADD45A and miR-148a is unknown. In vitro experiments showed that GADD45A negatively regulates IDH1R132H glioma cell proliferation, migration, and invasion, and neurosphere formation in IDH1R132H glioblastoma stem cells (GSC). In addition, a human orthotopic xenograft mouse model showed that GADD45A reduced tumorigenesis in vivo. Our findings demonstrated that miR-148a promotes glioma cell invasion and tumorigenesis by downregulating GADD45A. Our findings provide novel insights into how GADD45A is downregulated by miR-148a in IDH1R132H glioma and may help to identify therapeutic targets for the effective treatment of high-grade glioma.