Miracle-dz/UniFAR-FTUs huggingface dataset:
Systems biology and modeling in neuroblastoma: practicalities and perspectives

Neuroblastoma (NB) is a common pediatric malignancy characterized by clinical and biological heterogeneity. A host of prognostic markers are available, contributing to accurate risk stratification and appropriate treatment allocation. Unfortunately, outcome is still poor for many patients, indicating the need for a new approach with enhanced utilization of the available biological data. Systems biology is a holistic approach in which all components of a biological system carry equal importance. Systems biology uses mathematical modeling and simulation to investigate dynamic interactions between system components, as a means of explaining overall system behavior. Systems biology can benefit the biomedical sciences by providing a more complete understanding of human disease, enhancing the development of targeted therapeutics. Systems biology is largely contiguous with current approaches in NB, which already employ an integrative and pseudo-holistic approach to disease management. Systems modeling of NB offers an optimal method for continuing progression in this field, and conferring additional benefit to current risk stratification and management. Likewise, NB provides an opportunity for systems biology to prove its utility in the context of human disease, since the biology of NB is comprehensively characterized and, therefore, suited to modeling. The purpose of this review is to outline the benefits, challenges and fundamental workings of systems modeling in human disease, using a specific example of bottom-up modeling in NB. The intention is to demonstrate practical requirements to begin bridging the gap between biological research and applied mathematical approaches for the mutual gain of both fields, and with additional benefits for clinical management.
Integrating LTE broadband system in PMR band: OFDM vs. FBMC coexistence capabilities and performances

This paper focuses on the use of Long Term Evolution (LTE) broadband system in coexistence with currently deployed Professional Mobile Radio (PMR) communication systems. The coexistence capabilities are analyzed using of an LTE like based system with Orthogonal Frequency Division Multiplexing (OFDM) and Filter Bank MultiCarrier (FBMC) physical layers. Obtained results show that, in order to achieve the LTE-PMR coexistence, we need to filter the synthesized OFDM signal. This filtering is made to protect the PMR (TETRA, TETRAPOL, TETRA TEDS standards, etc.) systems by reducing the sidelobes levels due the use of modulated OFDM scheme. On the other hand, the FBMC signal fits perfectly the LTE-TEDS harmful interference protection requirements starting from the minimum frequency offset allowed by the TEDS standard mask. This can be explained by the fact that a good frequency localization is achieved by the prototype filter used in the FBMC scheme.
Gene-smoking interactions identify several novel blood pressure loci in the Framingham Heart Study.

BACKGROUND Cardiovascular diseases are among the most significant health problems in the United States. Blood pressure (BP) variability has a genetic component, and most of the genetic variance remains to be identified. One promising strategy for gene discovery is genome-wide analysis of interactions between single nucleotide polymorphisms (SNPs) and environmental factors related to cardiovascular diseases. METHODS We investigated SNP-smoking interaction effects on BP in genome-wide data in 6,889 participants from the Framingham Heart Study. We performed the standard 1 degree of freedom (df) test of the interaction effect and the joint 2 df test of main and interaction effects. Three smoking measures were used: cigarettes per day (CPD), pack years of smoking, and smoking status. RESULTS We identified 7 significant and 21 suggestive BP loci. Identified through the joint 2 df test, significant SBP loci include: rs12149862 (P = 3.65×10(-9)) in CYB5B, rs2268365 (P = 4.85×10(-8)) in LRP2, rs133980 (P = 1.71×10(-8) with CPD and P = 1.07×10(-8) with pack-years) near MN1, and rs12634933 (P = 4.05×10(-8)) in MECOM. Through 1 df interaction analysis, 1 suggestive SBP locus at SNP rs8010717 near NRXN3 was identified using all 3 smoking measures (P = 3.27×10(-7) with CPD, P = 1.03×10(-7) with pack-years, and P = 1.19×10(-7) with smoking status). CONCLUSIONS Several of these BP loci are biologically plausible, providing physiological connection to BP regulation. Our study demonstrates that SNP-smoking interactions can enhance gene discovery and provide insight into novel pathways and mechanisms regulating BP.
A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial to Test Efficacy and Safety of Magnetic Resonance Imaging-Based Thrombolysis in Wake-up Stroke (WAKE-UP)

Rationale In about 20% of acute ischemic stroke patients stroke occurs during sleep. These patients are generally excluded from intravenous thrombolysis. MRI can identify patients within the time-window for thrombolysis (≤4·5 h from symptom onset) by a mismatch between the acute ischemic lesion visible on diffusion weighted imaging (DWI) but not visible on fluid-attenuated inversion recovery (FLAIR) imaging. Aims and hypothesis The study aims to test the efficacy and safety of MRI-guided thrombolysis with tissue plasminogen activator (rtPA) in ischemic stroke patients with unknown time of symptom onset, e.g., waking up with stroke symptoms. We hypothesize that stroke patients with unknown time of symptom onset with a DWI-FLAIR-mismatch pattern on MRI will have improved outcome when treated with rtPA compared to placebo. Design WAKE-UP is an investigator initiated, European, multicentre, randomized, double-blind, placebo-controlled clinical trial. Patients with unknown time of symptom onset who fulfil clinical inclusion criteria (disabling neurological deficit, no contraindications against thrombolysis) will be studied by MRI. Patients with MRI findings of a DWI-FLAIR-mismatch will be randomised to either treatment with rtPA or placebo. Study outcome The primary efficacy endpoint will be favourable outcome defined by modified Rankin Scale 0–1 at day 90. The primary safety outcome measures will be mortality and death or dependency defined by modified Rankin Scale 4–6 at 90 days. Discussion If positive, WAKE-UP is expected to change clinical practice making effective and safe treatment available for a large group of acute stroke patients currently excluded from specific acute therapy.
From genomics to proteomics: new directions in molecular neuropsychiatry

Neuropsychiatry, like many other biomedical sciences, has been revolutionized by the advances in genomic technologies over the years. The advent of PCR (polymerase chain reaction) and the sequencing of the human genome have provided invaluable insights into the molecular genetics of the various psychiatric disorders through the study of candidate genes and linkage analyses. However, biological phenotype is dictated by protein expression, which has been shown to stray from the genetic blueprint designated by the genome. Consequently, the field of proteomics has recently emerged as a powerful means of exploring protein structure, function, and expression patterns. The ability to study disease at the gene and protein levels presents a tremendous opportunity for neuropsychiatric research, particularly in terms of the potential for developing therapeutic agents for novel protein targets.
Objectively Measured Physical Activity and Health-Related Physical Fitness in Secondary School-Aged Male Students With Autism Spectrum Disorders

Background Recent evidence suggests that childhood obesity is increasing in children with typical development (TD) and in children with autism spectrum disorders (ASD). The associations between physical activity (PA) levels and physical fitness components have not yet been objectively examined in this population but may have clinical implications for the development of secondary health complications. Objective The aims of this study were: (1) to compare PA and physical fitness between secondary school-aged male students with ASD and their peers with TD and (2) to assess possible interrelationships between PA and physical fitness levels in each group. Design This was a cross-sectional study. Methods Physical activity was recorded every 10 seconds by using accelerometry in 70 male students with (n=35) and without (n=35) ASD for up to 5 weekdays and 2 weekend days. The Brockport Physical Fitness Test was used to assess physical fitness. Results The primary findings were: (1) participants with ASD were less physically active overall and engaged in moderate-to-vigorous PA for a lower percentage of time compared with participants with TD during weekdays; (2) participants with ASD had significantly lower scores on all physical fitness measures, except body composition; and (3) group-dependent relationships existed between physical fitness profiles and PA levels. Limitations The study design limits causal inference from the results. Conclusion Specific interventions for maximizing PA and physical fitness levels in secondary school-aged male students with ASD are urgently needed.
Google Scholar: Warum eine (akademische) Suchmaschine nicht aus- reicht

WissenschaftlerInnen stehen heute eine Vielzahl unterschiedlichster Suchmaschinen fur die Suche nach wissenschaftlichen Dokumenten zur Verfugung. Neben den klassischen Informationsanbietern Bibliothek, Fachinformation und Verlag sind Web-Suchmaschinen inzwischen fester Bestandteil bei der Recherche nach frei zuganglichen Dokumenten. Scirus [1] und Google Scholar [2] sind zwei Beispiele fur Suchdienste kommerzieller SuchmaschinenUnternehmen, die eine Einschrankung auf den wissenschaftlichen Dokumentenraum anstreben und nennenswerte Dokumentzahlen in allen Disziplinen generieren. Der Vergleich der Treffermengen fur beliebige Suchthemen zeigt deutlich, dass es mengenmasig einen grosen Unterschied macht, mit welchem Suchsystem, in welchem Dokumentenpool und nach welchen Dokumenttypen gesucht wird. Tabelle 1 verdeutlicht dies am Beispiel der Trefferergebnisse fur die Suchbegriffe search engines bzw. Suchmaschinen in der allgemeinen Internetsuchmaschine Google, der wissenschaftlichen Suchmaschine Google Scholar (GS) und der grosten fachubergreifenden bibliographischen Literaturdatenbank Web of Science (WoS) [3]. Der Anteil der Dokumente, die in diesem Fall der Wissenschaft zu zuordnen sind (siehe GS und WoS in Tabelle 1), liegt gegenuber der allgemeinen Websuche lediglich im PromilleBereich.
RANGE EXPANSION OF THE FIRE ANT DECAPITATING FLY, PSEUDACTEON TRICUSPIS, EIGHT TO NINE YEARS AFTER RELEASES IN NORTH FLORIDA

In the fall of 2005 and the spring of 2006, the fire ant decapitating fly Pseudacteon tricuspis (Diptera: Phoridae) was observed 145-275 km out from the original release sites in northern Florida, occupying an area of about 86,500 km2. Average expansion rates of 26-57 km/year were considerably faster than previous observations. Considering these rates and other releases, we estimate that almost all of the state of Florida will harbor resident populations of P. tricuspis in the next 3 to 5 years.
Electrically Driven Single-Cell Photonic Crystal Laser

We report the experimental demonstration of an electrically driven, single-mode, low threshold current (∼260 μA) photonic band gap laser operating at room temperature. The electrical current pulse is injected through a sub-micrometer-sized semiconductor wire at the center of the mode with minimal degradation of the quality factor. The actual mode of interest operates in a nondegenerate monopole mode, as evidenced through the comparison of the measurement with the computation based on the actual fabricated structural parameters. As a small step toward a thresholdless laser or a single photon source, this wavelength-size photonic crystal laser may be of interest to photonic crystals, cavity quantum electrodynamics, and quantum information communities.
Differential distribution of hypocretin (orexin) and melanin‐concentrating hormone in the goldfish brain

The orexigenic peptides hypocretin (orexin) and melanin‐concentrating hormone (MCH) are involved in the control of food intake and in other homeostatic functions including sleep and arousal. In this article we study the distribution of these peptides in the brain of the goldfish (Carassius auratus), focusing on those regions particularly related to feeding, sleep, and arousal. Although the general distribution of these peptides in goldfish shows many similarities to those described previously in other species, we observed some noteworthy differences. As in other vertebrates, the peptidergic somata lie in the anterolateral hypothalamus. In goldfish, both hypocretin and MCH immunoreactive cell bodies project fibers to the ventral telencephalon, thalamus, and hypothalamus. At mesencephalic levels fibers reach the deep layers of the optic tectum and also course sparsely through the mesencephalic tegmentum. In contrast to the strong innervation of locus coeruleus and raphe in mammal, the MCH and hypocretin systems in goldfish barely innervate these aminergic populations related to the regulation of sleep and arousal. MCH, but not hypocretin, immunoreactive fibers terminate substantially in the sensory layer of the vagal gustatory lobe of goldfish, while both peptidergic systems distribute to the primary visceral sensory areas of the medulla and pons. The strong involvement of these peptidergic systems with the hypothalamus and general visceral nuclei, but not with locus coeruleus or raphe nuclei support the view that these peptides originally played a role in regulation of energy balance and evolved secondarily to influence sleep‐wakefulness systems in amniote vertebrates. J. Comp. Neurol. 488:476–491, 2005. © 2005 Wiley‐Liss, Inc.
Evaluation of cerebral vasospasm after early surgical and endovascular treatment of ruptured intracranial aneurysms.

OBJECTIVE To document the influence of the treatment modality (early surgery versus early endovascular treatment) on measures of cerebral vasospasm in a nonrandomized series of 156 patients treated within 72 hours of aneurysmal subarachnoid hemorrhage. METHODS The following parameters were prospectively collected in a computerized data base and retrospectively analyzed for association with vasospasm-related ischemic infarctions: 1) Hunt and Hess (H&H) grade, 2) Fisher grade, 3) highest mean cerebral blood flow velocity (CBFVMAX) and maximum percent change in mean CBFV (%deltaCBFV) as recorded by transcranial Doppler ultrasound, 4) incidence of repeat subarachnoid hemorrhage, 5) incidence of delayed ischemic neurological deficits, 6) incidence of delayed ischemic infarctions, and 7) Glasgow Outcome Scale score. RESULTS Forty-one patients (26.3%) suffered ischemic infarctions. The ischemic infarction rate was correlated with higher H&H grade (P = 0.002), higher Fisher grade (P = 0.05), higher CBFVMAX (P < 0.001) and %deltaCBFV (P = 0.01), occurrence of repeat subarachnoid hemorrhage, occurrence of delayed ischemic neurological deficits, and endovascular treatment (P = 0.02). CONCLUSION The infarction rate was higher with endovascular treatment versus surgery (37.7 versus 21.6%), as a result of a skewed Fisher Grade 4 infarction pattern in the endovascular treatment group versus the surgery treatment group (66.7 versus 24.5%). We suspect that unremoved subarachnoid/intracerebral clots contributed to the higher infarction rate with endovascular treatment. When patients with Fisher Grade 4 and H&H Grade V were excluded from analysis, the difference in infarct incidence between the treatment groups no longer reached statistical significance (Fisher Grades 1-3, P = 0.49; H&H Grades I-IV, P = 0.96).
On disaster information gathering in a complex shanty town terrain

Information gathering during a disaster management has a crucial role in designing the disaster response mechanism. Several factors such as geography, infrastructure, and population influence the information gathering process. The task is particularly complex when disasters strike a shanty town. A shanty town terrain is characterized by its high population density, considerable level of under-development, and poor infrastructure. Mobile Data Collection agents (MDCs) can be assigned with the task of data collection in the aftermath of a disaster. In this paper, we study the difficulty of data gathering process using two movement models, Path Type Based Movement and Path Memory Based Movement in combination with data hand-off strategies No Hand-off, Superior-Only Hand-off and Superior-Peer Hand-off. We use the metrics such as percentage data collected, percentage way coverage, and the number of inter-MDC meetings for analyzing the performance of MDCs in the data gathering process. The low values of data collected and way coverage show the difficulty in obtaining disaster-data from a complex shanty town terrain.
Effect of Chronic Mild Stress on AT1 Receptor Messenger RNA Expression in the Brain and Kidney of Rats

Objective The purpose of the study was to determine whether exposure to chronic mild stress (CMS) affects expression of angiotensin II Type 1a receptor (AT1aR) messenger RNA (mRNA) in the brain and kidney. Methods Male Sprague-Dawley rats were divided into an unchallenged control group, which remained at rest, and an experimental group, exposed to CMS produced by a series of unexpected, disturbing stimuli applied at random over a period of 4 weeks. After sacrificing the animals, samples of the septal/accumbal and hypothalamic/thalamic diencephalon, brain medulla, cerebellum, and the renal medulla were harvested for determination of AT1aR mRNA. Results Expression of AT1a receptor mRNA was significantly greater in the rats in the CMS condition than in the controls (septal/accumbal diencephalon: 1.689 [0.205] versus 0.027 [0.004], hypothalamic/thalamic diencephalon: 1.239 [0.101] versus 0.003 [0.001], brain medulla: 2.694 [0.295] versus 0.028 [0.003], cerebellum: 0.013 [0.002] versus 0.005 [0.001; p < .001 for all comparisons], and renal medulla: 409.92 [46.92] versus 208.06 [30.56; p < .01]). There was a significant positive correlation between AT1a mRNA expression in the septal/accumbal diencephalon and brain medulla (p < .025). Conclusions The results provide evidence that CMS significantly enhances expression of the AT1aR gene in the brain and kidney and indicate that changes in expression of AT1aR mRNA in different brain regions during CMS may be causally related. It is suggested that the up-regulation of AT1a receptors by chronic stress may potentiate negative effects of angiotensin II in pathologies associated with activation of the renin-angiotensin system.
An aggressive medical approach for inflammatory bowel disease: clinical challenges and therapeutic profiles in a retrospective hospital-based series.

BACKGROUND We studied the toxicity of cyclosporin (CsA), azathioprine, and mesalamine in 94 patients with inflammatory bowel disease (IBD). METHODS 63 treatments with CsA (2mg/kg intravenously or 5 mg/kg orally); 57 with azathioprine (2 mg/kg); and 44 with mesalamine (3.2-4.8 gr) were included. After induction, oral CsA was continued for 6 months, azathioprine for a median of 14 months (range 1-201 mos), mesalamine until tolerated. RESULTS CsA toxicity frequency 25%: withdrawal and colectomy in 3 cases. AZA toxicity rate: 43% with an overall time-to-onset of a median of 6 months (range 1-60 mos); withdrawal and colectomy in 7 cases; 62% of the events were other than leukopenia. Mesalamine toxicity rates: (13.6%) with one colectomy. CONCLUSION Toxicity-related withdrawal of conventional IBD treatments is significant and leads to colectomy in ulcerative colitis. 50% of the thiopurine toxicities outrange the predicting power of the available pharmacogenomic assays; mesalamine often causes allergic lung dysfunction. Efforts are warranted to optimize this conventional treatment of IBD.
The analysis of the risks for the development of tumour lysis syndrome in children.

BACKGROUND Acute renal failure (ARF) during the course of cytostatic therapy is a serious complication. ARF can be isolated or became as component of tumour lysis syndrome (TLS). TLS comprises a number of metabolic abnormalities (hyperuricemia, hyperphosphatemia, hyperkalemia, azotemia and hypocalcemia) which are associated with lymphoproliferative malignancies following spontaneous or chemotherapy-induced cytolysis. There exist probably no clear prediction for the development of TLS that could enable early detection of manifestation of this severe condition. SUBJECTIVE Conventional management with aggressive hydration, alkalization of the urine, administration of allopurinol, and the slow introduction of chemotherapy is often unable to prevent metabolic instability and ARF. Recent studies define a subgroup of patients at higher risk of renal failure during induction chemotherapy. ARF was encountered during initial therapy of patients with a lactate dehydrogenase (LDH) index greater than 3.3. METHODS AND MATERIAL A retrospective analysis of 10 children (3 girls, 7 boys, average age 9.7 years) with LDII index greater than 3.3 has been done. All children were treated for lymphoproliferative malignancy with conventional preventive measures. RESULTS Three children needed haemodialysis--2 boys had fully expressed TLS with ARF shortly after starting chemotherapy, in 1 boy the dialysis was indicated because of extreme hyperuricemia and high creatinine level presented before chemotherapy. We consider that LDH index is not specific criterium for prediction of TLS. In conclusion, our cases demonstrate the pathophysiologic spectrum of ARF in TLS between hyperuricemia and hyperphosphatemia. CONCLUSION The LDH index, urine output, and hyperphosphatemia could be used to identify those paediatric patients who would benefit from the prospective use some of extracorporeal elimination methods. Further investigation of this techniques in a larger number of patients is warranted. (Tab. 5, Ref. 12.)
Tacrolimus and steroid treatment for acute exacerbation of idiopathic pulmonary fibrosis.

OBJECTIVE Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) occurs during the chronic progressive course of idiopathic pulmonary fibrosis. Mortality is estimated to be >70%, because no effective treatment has been established. We evaluated the effectiveness of combination therapy of tacrolimus and methylprednisolone for AE-IPF. METHODS Patients of AE-IPF treated with methylprednisolone pulse therapy with or without tacrolimus (targeting 20 ng/mL) during the period between January 2001 and April 2010 were retrospectively reviewed. The primary endpoints were survival rate and duration. We also observed lactate dehydrogenase levels, partial pressure of arterial oxygen/fraction of inspired oxygen ratio (P/F ratio), KL-6, occurrence of re-exacerbation, and computed tomography score. RESULTS Fifteen Japanese patients [tacrolimus group aged 74.2±6.0 years old (n=5), non-tacrolimus group aged 75.1±12.8 years old (n=10)] were identified. Pre-treatment clinical parameters were not significantly different between the two groups. Four of 5 tacrolimus group patients and 1 of 10 non-tacrolimus group patients survived (p<0.05). The median survival durations were >92 days (tacrolimus group) and 38 days (non-tacrolimus group) (p<0.05). Lactate dehydrogenase levels and the P/F ratio were also significantly favorable in the tacrolimus group. KL-6 and CT score were not significantly different in both groups. Four re-acute exacerbations were observed only in the non-tacrolimus group. CONCLUSION Combined tacrolimus and methylprednisolone pulse therapy mitigates AE-IPF, prevents re-acute exacerbation, and contributes to a better prognosis.