Miracle-dz/UniFAR-FTUs huggingface dataset:
Modelling Neuroinflammation In Vitro: A Tool to Test the Potential Neuroprotective Effect of Anti-Inflammatory Agents

Neuron-microglia co-cultures treated with pro-inflammatory agents are a useful tool to study neuroinflammation in vitro, where to test the potential neuroprotective effect of anti-inflammatory compounds. However, a great diversity of experimental conditions can be found in the literature, making difficult to select the working conditions when considering this approach for the first time. We compared the use of neuron-primary microglia and neuron-BV2 cells (a microglial cell line) co-cultures, using different neuron:microglia ratios, treatments and time post-treatment to induce glial activation and derived neurotoxicity. We show that each model requires different experimental conditions, but that both neuron-BV2 and neuron-primary microglia LPS/IFN-γ-treated co-cultures are good to study the potential neuroprotective effect of anti-inflammatory agents. The contribution of different pro-inflammatory parameters in the neurotoxicity induced by reactive microglial cells was determined. IL-10 pre-treatment completely inhibited LPS/IFN-γ-induced TNF-α and IL-6 release, and COX-2 expression both in BV2 and primary microglial cultures, but not NO production and iNOS expression. However, LPS/IFN-γ induced neurotoxicity was not inhibited in IL-10 pre-treated co-cultures. The inhibition of NO production using the specific iNOS inhibitor 1400 W totally abolished the neurotoxic effect of LPS/IFN-γ, suggesting a major role for NO in the neurotoxic effect of activated microglia. Consequently, among the anti-inflammatory agents, special attention should be paid to compounds that inhibit NO production.
Loss of heterozygosity of the RB gene is a poor prognostic factor in patients with osteosarcoma.

PURPOSE The usual therapy of osteosarcoma is neoadjuvant chemotherapy, followed by surgery, then by postoperative chemotherapy. There is no prognostic factor to predict, at diagnosis, the histologic response and final outcome. Inactivation of the retinoblastoma-susceptibility gene RB is associated with the pathogenesis of several human cancers. In primary osteosarcomas, loss of heterozygosity (LOH) at the RB locus has been found in greater than 60% of cases. The aim of this study was to determine the potential early prognostic value of LOH of RB gene on the biopsy material at diagnosis. PATIENTS AND METHODS Forty-seven patients with primary osteosarcoma, treated in four French institutions, were studied. LOH was studied by polymerase chain reaction (PCR) of an informative RB DNA polymorphism. RESULTS Assessment of LOH at the RB gene could be completed on 34 heterozygous patients only. LOH was found in 24 cases (70%). The event-free survival (EFS) rate at 60 months is 100% for patients without LOH, 43% for all patients with RB LOH, and 65% for nonmetastatic patients with RB LOH. The difference in EFS is highly significant at P = . 008 and P = . 024, respectively. Histologic response after preoperative chemotherapy did not show significant correlation with LOH status. CONCLUSION RB gene LOH appears to be an early predictive feature for osteosarcomas that indicates a potential unfavorable outcome. RB LOH study might shortly help to identify high-risk patients earlier. If this is verified, therapy could then be adapted earlier to the individual's real risk of relapse.
Risks of Carcinogenesis from Urethane Exposure

ABSTRACT. BACKGROUND. Physical and Chemical Properties. Production, Use, and Exposure. Regulatory Standards and Guidelines. PHARMACOKINETICS AND METABOLISM. Introduction. Absorption. Distribution. Metabolism. Elimination. Interactions Between Urethane and Other Compounds. Kinetics of Metabolism. GENOTOXICITY. Introduction. The Salmonella Test. Mammalian Cell Tests In Vitro. Mammalian Tests In Vivo. Biochemical Markers. Summary. CARCINOGENIC EFFECTS. Humans. Animals. MODE OF ACTION OF URETHANE TUMORIGENESIS. Introduction. Evidence that Urethane Acts as a Complete Carcinogen. Mode of Genotoxic Action of Urethane. Evidence for Involvement of Metabolic Activation. Suspect Active Metabolites of Urethane. The Effects of Alterations in Metabolism on Urethane Carcinogenesis. Mouse Strain Susceptibility to Urethane and Vinyl Carbamate. Alternative Hypotheses. Summary. CANCER POTENCY ESTIMATION. Derivations from Animal Data. Results of Analyses of Urethane Dose Response Data. Conclusion. APPENDIX 1. Introduction. FIGURES. TABLES. REFERENCES.
ABCB1 Genetic Effects on Antidepressant Outcomes: A Report From the iSPOT-D Trial.

OBJECTIVE The ABCB1 gene encodes P-glycoprotein, which limits brain concentrations of certain antidepressants. ABCB1 variation has been associated with antidepressant efficacy and side effects in small-sample studies. Cognitive impairment in major depressive disorder predicts poor treatment outcome, but ABCB1 genetic effects in patients with cognitive impairment are untested. The authors examined ABCB1 genetic variants as predictors of remission and side effects in a large clinical trial that also incorporated cognitive assessment. METHOD The authors genotyped 10 ABCB1 single-nucleotide polymorphisms (SNPs) in 683 patients with major depressive disorder treated for at least 2 weeks, of whom 576 completed 8 weeks of treatment with escitalopram, sertraline, or extended-release venlafaxine (all substrates for P-glycoprotein) in a large randomized, prospective, pragmatic trial. Antidepressant efficacy was assessed with the 16-item Quick Inventory of Depressive Symptomatology-Self-Rated (QIDS-SR), and side effects with a rating scale for frequency, intensity, and burden of side effects. General and emotional cognition was assessed with a battery of 13 tests. RESULTS The functional SNP rs10245483 upstream from ABCB1 had a significant effect on remission and side effect ratings that was differentially related to medication and cognitive status. Common homozygotes responded better and had fewer side effects with escitalopram and sertraline. Minor allele homozygotes responded better and had fewer side effects with venlafaxine, with the better response most apparent for patients with cognitive impairment. CONCLUSIONS The functional polymorphism rs10245483 differentially affects remission and side effect outcomes depending on the antidepressant. The predictive power of the SNP for response or side effects was not lessened by the presence of cognitive impairment.
Predicting Improvement in Urinary and Bowel Incontinence for Home Health Patients Using Electronic Health Record Data

PURPOSE: The purpose of the study was to discover which patient and support system characteristics and interventions documented by home health clinicians were associated with improvement in urinary and bowel incontinence contrasting logistic regression and data mining approaches. SUBJECTS AND SETTING: Seventeen hundred ninety-three patients in this study experienced 2072 episodes of care. The study sample comprised all nonmaternity patients aged 18 years or older receiving skilled home health services in 2004. Subjects were drawn from a convenience sample of 15 home health agencies. DESIGN: We completed a secondary analysis of data from 15 home health agencies' electronic health records. Data for this study were documented by home care clinicians using the Outcome and Assessment Information Set (OASIS) structured assessment form and the Omaha System interventions, which is a standardized terminology. RESULTS: There were 684 patients with urinary incontinence and 187 with bowel incontinence. By discharge 38% improved in urinary incontinence and 45% improved their bowel incontinence. Using logistic regression, no patient or support system characteristics were identified that associated with improvement in either urinary or bowel incontinence, only a limited number of interventions were significant. A data mining decision tree was producible only for bowel incontinence, demonstrating a combination of patient and support system factors as well as selected interventions were important in determining whether patients would improve in bowel incontinence. CONCLUSIONS: Home health patients have complex comorbid conditions requiring home care nurses to have broad, generalized knowledge. Future research is needed to determine if the inclusion of a certified WOC nurse would improve outcomes.
Cloning, Genomic Organization, and Characterization of a Human Cholinephosphotransferase*

A cholinephosphotransferase activity catalyzes the final step in the de novo synthesis of phosphatidylcholine via the transfer of a phosphocholine moiety from CDP choline to diacylglycerol. Ethanolaminephosphotransferase activity catalyzes a similar reaction substituting CDP ethanolamine as the phosphobase donor. We report the identification and cloning of a human cDNA (human cholinephosphotransferase (hCPT1)) that codes for a cholinephosphotransferase-specific enzyme. This was demonstrated usingin vitro enzyme assays and in vivo measurement of the reconstitution of the phosphatidylcholine and phosphatidylethanolamine biosynthetic pathways in yeast cells devoid of their own endogenous cholinephosphotransferase and ethanolaminephosphotransferase activities. This contrasted with our previously cloned human choline/ethanolaminephosphotransferase cDNA that was demonstrated to code for a dual specificity choline/ethanolaminephosphotransferase. The hCPT1 and human choline/ethanolaminephosphotransferase (hCEPT1) predicted amino acid sequences possessed 60% overall identity and had only one variation in the amino acid residues within the CDP-alcohol phosphotransferase catalytic motif. In vitro assessment of hCPT1 and hCEPT1 derived cholinephosphotransferase activities also revealed differences in diradylglycerol specificities including their capacity to synthesize platelet-activating factor and platelet-activating factor precursor. Expression of the hCPT1 mRNA varied greater than 100-fold between tissues and was most abundant in testis followed by colon, small intestine, heart, prostate, and spleen. This was in marked contrast to the hCEPT1 mRNA, which has been found in similar abundance in all tissues tested to date. Both the hCPT1 and hCEPT1 enzymes were able to reconstitute the synthesis of PC in yeast to levels provided by the endogenous yeast cholinephosphotransferase; however, only hCEPT1-derived activity was able to complement the yeastCPT1 gene in its interaction with SEC14 and affect cell growth.
More pain, more tender points: is fibromyalgia just one end of a continuous spectrum?

OBJECTIVES: To investigate the hypothesis that fibromyalgia represents one end of a spectrum in which there is a more general association between musculoskeletal pain and tender points. METHODS: The subjects studied were 177 individuals selected from a population based screening survey for musculoskeletal pain. All subjects completed a pain mannikin and were examined for the presence of tender points at the nine American College of Rheumatology bilateral sites. RESULTS: There were moderately strong associations (odds ratios range 1.3-3.1) between the reported presence of pain in a body segment and the presence of a tender point within that segment. Further, there was evidence of a trend of increasing number of tender points with increasing number of painful segments. The reporting of non-specific pain, aching, or stiffness, was also associated with high tender point counts. CONCLUSION: This study illustrates that the association between tender points and pain is not restricted to the clinically defined subgroup with chronic widespread pain. Given that widespread pain and tender points have previously been linked with distress, this might reflect lesser degrees, or earlier phases of the somatisation of distress.
Meta-Analysis of Dose-Response Relationships for Hydrochlorothiazide, Chlorthalidone, and Bendroflumethiazide on Blood Pressure, Serum Potassium, and Urate

Thiazide and thiazide-like diuretics are widely used in the management of hypertension, but recently the equivalence of hydrochlorothiazide and chlorthalidone for blood pressure (BP) lowering and prevention of cardiovascular disease has been questioned. We performed a meta-analysis to characterize the dose-response relationships for 3 commonly prescribed thiazide diuretics, hydrochlorothiazide, chlorthalidone, and bendroflumethiazide, on BP, serum potassium, and urate. Randomized, double-blind, parallel placebo-controlled trials meeting the following criteria, ≥2 different monotherapy dose arms, follow-up duration ≥4 weeks, and baseline washout of medication ≥2 weeks, were identified using Embase (1980–2010 week 50), Medline (1950–2010 November week 3), metaRegister of Controlled Trials, and Cochrane Central. A total of 26 trials examined hydrochlorothiazide, 3 examined chlorthalidone, and 1 examined bendroflumethiazide. Studies included a total of 4683 subjects in >53 comparison arms. Meta-regression of the effect of thiazides on systolic BP showed a log-linear relationship with a potency series: bendroflumethiazide>chlorthalidone>hydrochlorothiazide. The estimated dose of each drug predicted to reduce systolic BP by 10 mm Hg was 1.4, 8.6, and 26.4 mg, respectively, and there was no evidence of a difference in maximum reduction of systolic BP by high doses of different thiazides. Potency series for diastolic BP, serum potassium, and urate were similar to those seen for systolic BP. Hydrochlorothiazide, chlorthalidone, and bendroflumethiazide have markedly different potency. This may account for differences in the antihypertensive effect between hydrochlorothiazide and chlorthalidone using standard dose ranges.
The relationship between management control system usage and planned change achievement: An exploratory study

Abstract Although the relevance of management control systems to successful change achievement has been conceptually acknowledged, empirical matters such as measuring the contribution of control systems to effective change implementation lack practical investigation. Using data obtained from managers in 22 organizations, we explore the extent to which managers believe their management control systems are employed when implementing planned change. Relationships between commonly employed management controls and implementation success are also estimated. Results indicated that managers used management control systems less extensively than other elements of change process, although usage of control systems increased with implementation. A strong relationship was found between the use of control systems based on outcomes monitoring and implementation success. However, there was no significant relationship between the use of behavior-based controls and implementation success. Overall, the findings suggest that many organizations may underutilize formal controls, particularly those related to outcomes monitoring, when managing change.
Adjacent segment degeneration following spinal fusion for degenerative disc disease.

Fusion has become the standard of care for numerous pathologic conditions of the spine over the past 50 years. Instrumented thoracolumbar fusion for adolescent and adult spinal deformity has enjoyed great success in arresting the progression of and correcting scoliotic deformity. In the cervical spine, decompression and fusion have provided a greater than 90% likelihood of relieving radicular symptoms and stabilizing or improving myelopathy. Decompression and posterolateral fusion of the lumbar spine have been shown to be the superior form of surgical management for degenerative spondylolisthesis in prospective randomized studies. Given the high clinical success recognized in using fusion for deformity and stenosis of the cervical and lumbar spine, the long-term sequelae of these procedures has been considered of secondary importance. However, as spinal fusion is being performed on younger patients and as the rates of cervical and lumbar spine surgery have increased over the past two decades, concern regarding the effect on adjacent motion segments has been increasing. Furthermore, as indications for fusion have expanded to include mechanical back and neck pain with more variable success rates, concern for adjacent segment degeneration has been amplified. Adjacent level degeneration, following cervical, lumbar, and lumbosacral fusions, has been well documented in recent literature, yet there remains considerable controversy as to when adjacent level radiographic degeneration becomes clinically relevant. It has also become evident that maintenance of sagittal alignment of the spine has important clinical implications when treating and preventing adjacent segment degeneration and flat back syndrome. Numerous studies have demonstrated in properly selected patients that decompression and fusion can yield marked improvement with respect to pain and outlook for various conditions of the spine. However, there are also numerous articles that suggest otherwise, with the results of spinal fusion described as unpredictable, if not unsatisfactory, and often precipitating further surgical intervention. It is important, therefore, to understand the long-term consequences of cervical, lumbar, and lumbosacral fusions, and their impact on adjacent segment degeneration.
Modular Toolkit for Data Processing (MDP): A Python Data Processing Framework

Modular toolkit for Data Processing (MDP) is a data processing framework written in Python. From the user's perspective, MDP is a collection of supervised and unsupervised learning algorithms and other data processing units that can be combined into data processing sequences and more complex feed-forward network architectures. Computations are performed efficiently in terms of speed and memory requirements. From the scientific developer's perspective, MDP is a modular framework, which can easily be expanded. The implementation of new algorithms is easy and intuitive. The new implemented units are then automatically integrated with the rest of the library. MDP has been written in the context of theoretical research in neuroscience, but it has been designed to be helpful in any context where trainable data processing algorithms are used. Its simplicity on the user's side, the variety of readily available algorithms, and the reusability of the implemented units make it also a useful educational tool.
Hormones and Sexuality During Transition to Menopause

OBJECTIVE: To examine the relationship between reproductive hormonal dynamics and sexual dysfunction assessed in a cohort of women approaching menopause. METHODS: Women in the Penn Ovarian Aging Study were assessed at yearly intervals for 3 years with early follicular hormone measurements (estradiol, follicle-stimulating hormone, luteinizing hormone [LH], sex hormone binding globulin, dehyroepiandrosterone sulfate [DHEAS], total testosterone), anthropometric measures, and extensive questionnaires including the Female Sexual Function Index. Univariable analyses were performed to determine the association between hormones, menopausal status, and sexual dysfunction. Multivariable linear and logistic regression models were created to examine the influence of hormones on sexual function adjusting for the effect of potential confounders. RESULTS: The final multivariable model indicated that sexual dysfunction increased with advanced menopausal status, with postmenopausal women being 2.3 times as likely to experience sexual dysfunction compared with premenopausal women (odds ratio 2.3, 95% confidence interval [CI] 1.3–4.1). Low DHEAS serum concentrations were associated with decreased sexual function (odds ratio 1.59, 95% CI 1.19–2.14). Additional risk factors associated with sexual dysfunction included absence of a sexual partner (11.2, 95% CI 6.9–18.1), high anxiety (3.8, 95% CI 1.6–9.2), and children under the age of 18 living at home (1.6, 95% CI 1.1–5.5). Lubrication, orgasm, and pain were specific aspects of sexuality negatively affected by menopause. CONCLUSION: This study confirms the observation that sexual dysfunction increases over the menopausal transition. Several factors associated with sexual dysfunction include low DHEAS, absence of a sexual partner, anxiety, and children under the age of 18 living at home. LEVEL OF EVIDENCE: II
Inhibition of Sodium Channel Gating by Trapping the Domain II Voltage Sensor with Protoxin II

ProTx-II, an inhibitory cysteine knot toxin from the tarantula Thrixopelma pruriens, inhibits voltage-gated sodium channels. Using the cut-open oocyte preparation for electrophysiological recording, we show here that ProTx-II impedes movement of the gating charges of the sodium channel voltage sensors and reduces maximum activation of sodium conductance. At a concentration of 1 μM, the toxin inhibits 65.3 ± 4.1% of the sodium conductance and 24.6 ± 6.8% of the gating current of brain Nav1.2a channels, with a specific effect on rapidly moving gating charge. Strong positive prepulses can reverse the inhibitory effect of ProTx-II, indicating voltage-dependent dissociation of the toxin. Voltage-dependent reversal of the ProTx-II effect is more rapid for cardiac Nav1.5 channels, suggesting subtype-specific action of this toxin. Voltage-dependent binding and block of gating current are hallmarks of gating modifier toxins, which act by binding to the extracellular end of the S4 voltage sensors of ion channels. The mutation L833C in the S3-S4 linker in domain II reduces affinity for ProTx-II, and mutation of the outermost two gating-charge-carrying arginine residues in the IIS4 voltage sensor to glutamine abolishes voltage-dependent reversal of toxin action and toxin block of gating current. Our results support a voltage-sensor-trapping model for ProTx-II action in which the bound toxin impedes the normal outward gating movement of the IIS4 transmembrane segment, traps the domain II voltage sensor module in its resting state, and thereby inhibits channel activation.
Free Vibration Analysis of Multiple Delaminated Beams under Axial Compressive Load

Analytical solutions are developed to study the free vibrations of multiple delaminated beams under axial compressive loadings. The Euler—Bernoulli beam theory and both the `free mode' and the `constrained mode' assumption in delamination buckling and vibration are used. In addition, a parametric study is performed to study the influence of the axial compressive load on the vibration characteristics of the multiple-delaminated beam. Results show a monotonic relation between the natural frequency and the axial compressive load. Furthermore, the axial compressive load is shown to significantly influence the first vibration mode shape of the beam. However, the influence on the second vibration mode shape is less significant. The present `free mode' solution is also used to investigate the first mode and the second mode buckling of the delaminated beams. For certain delamination lengths and locations, the second mode buckling load is lower that the first mode.
A simple adaptive procedure leading to correlated equilibrium

We propose a new and simple adaptive procedure for playing a game: ‘‘regret-matching. ’’ In this procedure, players may depart from their current play with probabilities that are proportional to measures of regret for not having used other strategies in the past. It is shown that our adaptive procedure guarantees that, with probability one, the empirical distributions of play converge to the set of correlated equilibria of the game.