Miracle-dz/UniFAR-FTUs huggingface dataset:
SyGMa: Combining Expert Knowledge and Empirical Scoring in the Prediction of Metabolites

Predictions of potential metabolites based on chemical structure are becoming increasingly important in drug discovery to guide medicinal chemistry efforts that address metabolic issues and to support experimental metabolite screening and identification. Herein we present a novel rule‐based method, SyGMa (Systematic Generation of potential Metabolites), to predict the potential metabolites of a given parent structure. A set of reaction rules covering a broad range of phase 1 and phase 2 metabolism has been derived from metabolic reactions reported in the Metabolite Database to occur in humans. An empirical probability score is assigned to each rule representing the fraction of correctly predicted metabolites in the training database. This score is used to refine the rules and to rank predicted metabolites. The current rule set of SyGMa covers approximately 70 % of biotransformation reactions observed in humans. Evaluation of the rule‐based predictions demonstrated a significant enrichment of true metabolites in the top of the ranking list: while in total, 68 % of all observed metabolites in an independent test set were reproduced by SyGMa, a large part, 30 % of the observed metabolites, were identified among the top three predictions. From a subset of cytochrome P450 specific metabolites, 84 % were reproduced overall, with 66 % in the top three predicted phase 1 metabolites. A similarity analysis of the reactions present in the database was performed to obtain an overview of the metabolic reactions predicted by SyGMa and to support ongoing efforts to extend the rules. Specific examples demonstrate the use of SyGMa in experimental metabolite identification and the application of SyGMa to suggest chemical modifications that improve the metabolic stability of compounds.
Interventions to address sexual problems in people with cancer.

BACKGROUND Sexual dysfunction in people with cancer is a significant problem. The present clinical practice guideline makes recommendations to improve sexual function in people with cancer. METHODS This guideline was undertaken by the Interventions to Address Sexual Problems in People with Cancer Expert Panel, a group organized by the Program in Evidence-Based Care (pebc). Consistent with the pebc standardized approach, a systematic search was conducted for existing guidelines, and the literature in medline and embase for the years 2003-2015 was systematically searched for both systematic reviews and primary literature. Evidence found for men and for women was evaluated separately, and no restrictions were placed on cancer type or study design. Content and methodology experts performed an internal review of the resulting draft recommendations, which was followed by an external review by targeted experts and intended users. RESULTS The search identified 4 existing guidelines, 13 systematic reviews, and 103 studies with relevance to the topic. The present guideline provides one overarching recommendation concerning the discussion of sexual health and dysfunction, which is aimed at all people with cancer. Eleven additional recommendations made separately for men and women deal with issues such as sexual response, body image, intimacy and relationships, overall sexual functioning and satisfaction, and vasomotor and genital symptoms. CONCLUSIONS To our knowledge this clinical practice guideline is the first to comprehensively evaluate interventions for the improvement of sexual problems in people with cancer. The guideline will be a valuable resource to support practitioners and clinics in addressing sexuality in cancer survivors.
The Steady-State Internal Redox State (NADH/NAD) Reflects the External Redox State and Is Correlated with Catabolic Adaptation in Escherichia coli

ABSTRACT Escherichia coli MC4100 was grown in anaerobic glucose-limited chemostat cultures, either in the presence of an electron acceptor (fumarate, nitrate, or oxygen) or fully fermentatively. The steady-state NADH/NAD ratio depended on the nature of the electron acceptor. Anaerobically, the ratio was highest, and it decreased progressively with increasing midpoint potential of the electron acceptor. Similarly, decreasing the dissolved oxygen tension resulted in an increased NADH/NAD ratio. As pyruvate catabolism is a major switch point between fermentative and respiratory behavior, the fluxes through the different pyruvate-consuming enzymes were calculated. Although pyruvate formate lyase (PFL) is inactivated by oxygen, it was inferred that the in vivo activity of the enzyme occurred at low dissolved oxygen tensions (DOT ≤ 1%). A simultaneous flux from pyruvate through both PFL and the pyruvate dehydrogenase complex (PDHc) was observed. In anaerobic cultures with fumarate or nitrate as an electron acceptor, a significant flux through the PDHc was calculated on the basis of the redox balance, the measured products, and the known biochemistry. This result calls into question the common assumption that the complex cannot be active under these conditions. In vitro activity measurements of PDHc showed that the cellular content of the enzyme varied with the internal redox state and revealed an activity for dissolved oxygen tension of below 1%. Whereas Western blots showed that the E3 subunit of PDHc (dihydrolipoamide dehydrogenase) did not vary to a large extent under the conditions tested, the E2 subunit (dihydrolipoamide acetyltransferase) amount followed the trend that was found for the in vitro PDHc activity. From this it is concluded that regulation of the PDHc is exerted at the E1/E2 operon (aceEF). We propose that the external redox state (measured as the midpoint potentials of those terminal acceptors with which the cell has sufficient capacity to react) is reflected by the internal redox state. The latter may subsequently govern both the expression and the activity of the two pyruvate-catabolizing enzymes.
Los riesgos de las entidades aseguradoras en el marco del Enterprise Risk Management (ERM) y el control interno

Los sistemas integrales de gestion del riesgo, en particular el Enterprise Risk Management (ERM), se han convertido en una practica fundamental de la gestion de empresas para la mitigacion y control de los riesgos. La crisis financiera actual ha estimulado a las empresas aseguradoras a dar mayor importancia a la gestion de los riesgos, alentadas ademas por la nueva regulacion europea Solvencia II; por ello el objetivo principal de este trabajo ha sido proponer un marco conceptual de los riesgos a los que se enfrentan las empresas internacionales de seguros desde una perspectiva global, cuya actividad presenta peculiaridades especificas que hacen que el proceso de control interno y gestion de riesgos adquieran una especial relevancia, y que puede ser aplicado a empresas de otros sectores economicos.
Medical management of advanced heart failure.

CONTEXT Advanced heart failure, defined as persistence of limiting symptoms despite therapy with agents of proven efficacy, accounts for the majority of morbidity and mortality in heart failure. OBJECTIVE To review current medical therapy for advanced heart failure. DATA SOURCES We searched MEDLINE for all articles containing the term advanced heart failure that were published between 1980 and 2001; EMBASE was searched from 1987-1999, Best Evidence from 1991-1998, and Evidence-Based Medicine from 1995-1999. The Cochrane Library also was searched for critical reviews and meta-analyses of congestive heart failure. STUDY SELECTION Randomized controlled trials of therapy for 150 patients or more were included if advanced heart failure was represented. Other common clinical situations were addressed from smaller trials as available, trials of milder heart failure, consensus guidelines, and both published and personal clinical experience. DATA EXTRACTION Data quality was determined by publication in peer-reviewed literature or inclusion in professional society guidelines. DATA SYNTHESIS A primary focus for care of advanced heart failure is ongoing identification and treatment of the elevated filling pressures that cause disabling symptoms. While angiotensin-converting enzyme inhibitors and beta-adrenergic agents can slow disease progression and prolong survival, titration and tolerability often present challenges. Most patients are not eligible for surgical intervention but do benefit from a medical regimen tailored to individual clinical and hemodynamic profiles and from heart failure management programs that reduce rehospitalization. Survival ranges from 80% at 2 years for patients rendered free of congestion to less than 50% at 6 months for patients with refractory symptoms, in whom end-of-life options may include hospice care and inactivation of implantable defibrillators. CONCLUSIONS Current management of advanced heart failure is based more on consensus than on randomized trials. Systematic investigation should address not only new therapies but also strategies for selecting and optimizing therapies already available.
PREVALENCE OF PSYCHIATRIC MORBIDITY AMONG MEDICAL IN-PATIENTS*

SUMMARY One hundred patients admitted in medical wards of G. G. S. Medical College, Faridkot, were examined for presence of Psychiatric illness. 31 cases were found to be suffering from some sort of psychiatric illness. Out of 31, 16 patients were found to be suffering from primary affective disorders and physical symptoms in them appeared to be direct consequences of depression. Other psychiatric morbidity was constituted by hysteria (6), organic bran syndrome (5), anxiety neuroses (3) and schizophrenia (l). Psychiatric cases were found to be maximum in age group of 31-60 years and more patients belonged to middle class. Relationship of psychiatric illness with duration and type of medical illness is also discussed.
Uma Abordagem para Identificação de Padrões de Ocorrência de Eventos Solares Transientes Baseada no Fluxo de Múons

The muon is an elementary particle with a negative charge, and is the most abundant charged component of cosmic radiation that penetrates deep into the Earth's soil. Analyzing the flow of muons that reaches our planet is important to identify solar eruptions that can cause harm to the population. This paper presents an approach based on sequence mining algorithms to automate the process of identifying frequent patterns in the captured muon stream. Experiments carried out show that the approach is capable of identifying eruptions by means of the identified frequent patterns.
Human biodistribution and dosimetry of the PET perfusion agent copper-62-PTSM.

UNLABELLED Copper-62-pyruvaldehyde bis(N4-methyl)thiosemicarbazone (PTSM) has been proposed as a generator-produced radiopharmaceutical for perfusion imaging using PET. Several clinical studies have demonstrated the ability of 62Cu-PTSM to quantitate myocardial and cerebral perfusion in humans. Because 62Cu-PTSM is generator-produced, it can be provided to clinical centers without cyclotron availability and, therefore, represents a cost-effective, practical PET perfusion tracer for clinical applications. To assess the safety, time-dependent biodistribution, and whole-body and organ-specific absorbed radiation dose estimates of this tracer, a Phase I study of 62Cu-PTSM was performed using whole-body imaging with PET in 10 healthy volunteers and with the radiopharmaceutical delivered by a compact modular generator unit. METHODS Five male and five female subjects underwent a series of clinical tests and head-to-midthigh, whole-body PET scans at three time points over 1 hr after intravenous injection of 62Cu-PTSM. Before injection of the tracer, PET transmission scans were performed and used to correct the emission data for attenuation. Final image data were expressed in units of mCi/cc. Using standard organ weights, the percent injected dose per organ was calculated. Biodistribution data were obtained at three different time points and from these data biological half-lives in different organs were determined for calculation of radiation absorbed dose estimates. RESULTS The liver was seen as the critical organ receiving a dose of 0.0886 rad/mCi. This organ defined the maximum single injected dose at 56 mCi using the limit of 5 rads to a critical organ per study per year. The whole-body dose is 0.0111 rad/mCi, resulting in a 0.622 rad exposure with a maximum single injection dose. Only trace levels of activity were found in the urine, which suggests low levels of urinary excretion and bladder exposure. No significant clinical, electrocardiographic or laboratory abnormalities were seen after the injection of 62Cu-PTSM. CONCLUSION Copper-62-PTSM is a clinically safe radiopharmaceutical with favorable dosimetry for human studies at injected doses significantly above those projected for use in clinical studies.
Artificial neural network computation on graphic process unit

Artificial neural network (ANN) is widely used in pattern recognition related area. In some case, the computational load is very heavy, in other case, real time process is required. So there is a need to apply a parallel algorithm on it, and usually the computation for ANN is inherently parallel. In this paper, graphic hardware is used to speed up the computation of ANN. In recent years, graphic processing unit (GPU) grows faster than CPU. Graphic hardware venders provide programmability on GPU. In this paper, application of commodity available GPU for two kinds of ANN models was explored. One is the self-organizing maps (SOM); the other is multi layer perceptron (MLP). The computation result shows that ANN computing on GPU is much faster than on standard CPU when the neural network is large. And some design rules for improve the efficiency on GPU are given.
Retrospective, longitudinal analysis of serum human herpesvirus‐8 viral DNA load in AIDS‐related kaposi's sarcoma patients before and after diagnosis

Human herpesvirus 8 (HHV‐8) is detected more often in patients progressing towards Kaposi's sarcoma (KS) than in patients who do not develop the disease, suggesting that the level of viremia might be associated with Kaposi's sarcoma disease and progression. Longitudinal serum samples from 19 AIDS‐Kaposi's sarcoma patients, ranging from 2 years before KS till 2 years after KS diagnosis were tested. No correlation was found between viral load and progression to KS, or disease stage. J. Med. Virol. 74:390–396, 2004. © 2004 Wiley‐Liss, Inc.
Congressional Behavior and Electoral Marginality

The "marginality" hypothesis maintains that members of Congress from marginal districts will display more moderation in their voting behavior than will those from safe districts. We give two alternative interpretations to the hypothesis: Candidates from more marginal districts will: (1) tend to converge to the positions of their constituents; and (2) tend to converge to the positions of their opponents. Employing policy opinion data on both party candidates for 299 districts for which valid competition figures could be obtained, and simulated constituency opinions for the same districts, we find a general tendency for candidates to diverge from each other in marginal districts. However, we find that in the more marginal districts, candidates closest to the constituency opinion are considerably more likely to win than their opponent-although quite the contrary is the case for the noncompetitive districts. Incumbents are found to have greater probability of winning reelection than their challengers even when the latter are closer to constituency opinion.
The Effects of Call Options on Exit Strategies in Private Equity Shareholder Agreements

1. David Sonius 1. is a consultant with hww Unternehmensberater GmbH in Berlin, Germany. (david.sonius{at}hww.eu) 2. Uwe Kehrel 1. is an assistant professor at the Institute of Business Administration at the University of Munster in Munster, Germany. (uwe.kehrel{at}uni-muenster.de
Cognitive Decline in Chronic Migraine with Nonsteroid Anti-inflammation Drug Overuse: A Cross-Sectional Study

Background Chronic migraine with medication overuse headache (CM-MOH) is the most common type of chronic migraine, and it increases risk of stroke and white matter lesions. These pathologic changes could induce cognitive decline. However, the alteration of cognitive function in CM-MOH patients is not established. Therefore, we took this study to reveal the cognitive performances in CM-MOH. Methods This cross-sectional study was conducted between December 2015 and January 2017. Patients were divided into CM-MOH, CMwoMOH (chronic migraine without medication overuse), and MO (migraine without aura) groups. Cognitive function was assessed in all cases during interictal periods using Addenbrooke's Cognitive Examination Test (ACE-R), Trail Making Test A/B (TMT A/B), and Digit Symbol Test (DST). Detailed headache characteristics and evaluation of anxiety, depression, and living and sleep quality were collected. Results 116 patients were included in this study. There were 21 CM-MOHs, 20 CMwoMOHs, 35 MOs, and 40 controls. Age and education were the independent risk factors of cognitive decline (P < 0.05). After adjusting, the risk of cognitive decline was higher in CM compared with control in ACE-R score and language fluency (P < 0.05). In addition, CM-MOH sufferers were in higher risk of memory and executive dysfunction (P < 0.05). The cognitive function had no difference between CM-MOH and CMwoMOH (P > 0.05). Meanwhile, CM-MOH got significantly higher scores than MO in anxiety and depression, with poorer performances in sleep and life quality (P < 0.05). Conclusion The risk of cognitive decline increased in chronic migraine patients. Nonsteroid anti-inflammatory drugs overuse had no influence on cognitive performances among chronic migraine sufferers.
Cross-frequency information transfer from EEG to EMG in grasping

This paper presents an investigation into the cortico-muscular relationship during a grasping task by evaluating the information transfer between EEG and EMG signals. Information transfer was computed via a non-linear model-free measure, transfer entropy (TE). To examine the cross-frequency interaction, TEs were computed after the times series were decomposed into various frequency ranges via wavelet transform. Our results demonstrate the capability of TE to capture the direct interaction between EEG and EMG. In addition, the cross-frequency analysis revealed instantaneous decrease in information transfer from EEG to the high frequency component of EMG (100-200Hz) during the onset of movement.
Prospective Computed Tomographic Analysis of Osteochondral Lesions of the Ankle Joint Associated With Ankle Fractures

Background: Osteochondral lesions (OCLs) associated with ankle fracture correlate with unfavorable outcome. The goals of this study were to detect OCLs following ankle fracture, to associate fracture type to OCLs and to investigate whether OCLs affect clinical outcome. Methods: 100 ankle fractures requiring operative treatment were prospectively included (46 men, 54 women; mean age 44 ± 14 years, range 20-77). All ankle fractures (conventional radiography; 71 Weber B, 22 Weber C, 1 Weber A, 4 isolated medial malleolus and 2 isolated posterior malleolus fractures) were treated by open reduction and internal fixation. Multidetector computed tomography (CT) was performed postoperatively. For each OCL, the location, size, and Loomer OCL classification (CT modified Berndt and Harty classification) were determined. The subjective Foot and Ankle Outcome Scoring (FAOS) was used for clinical outcome at 1 year. Results: OCLs were found in 10/100 ankle fractures (10.0%). All OCLs were solitary talar lesions. Four OCLs were located posteromedial, 4 posterolateral, 1 anterolateral, and 1 anteromedial. There were 2 type I OCLs (subchondral compression), 6 type II OCLs (partial, nondisplaced fracture) and 2 type IV OCLs (displaced fracture). Mean OCL size (largest diameter) was 4.4 ± 1.7 mm (range, 1.7 mm to 6.2 mm). Chi-square analysis showed no significant association between ankle fracture type and occurrence of OCLs. OCLs did occur only in Lauge-Hansen stage III/IV ankle fractures. There were no significant differences in FAOS outcome between patients with or without OCLs. Conclusions: Ten percent of investigated ankle fractures had associated OCLs on CT. Although no significant association between fracture type and OCL was found, OCLs only occurred in Lauge-Hansen stage III/IV ankle fractures. With the numbers available, OCLs did not significantly affect clinical outcome at 1 year according to FAOS. Level of Evidence: Level IV, observational study.
Long-Term Gain, Short-Term Pain: Assessing the Potential Impact of Structural Reforms in Chile

In this paper, I study the potential economic impact of the 2015-18 structural reform agenda in Chile, using the IMF dynamic general equilibrium model (GIMF). I find that the agenda has the potential to significantly increase Chile's long-run GDP, although it may have some negative effects in the short term. Ensuring a smooth transition to a higher productive potential depends on three key dimensions: the credibility of the reforms, their effectiveness in closing structural gaps, and their speed of implementation. Badly designed reforms that remove only a very small fraction of the existing structural gaps, at a slow speed, and with little credibility, can greatly reduce the positive impact of the reform agenda on GDP.
Activation of Interferon Response Factor-3 in Human Cells Infected with Herpes Simplex Virus Type 1 or Human Cytomegalovirus

ABSTRACT Activation of cellular interferon-stimulated genes (ISGs) after infection with herpes simplex virus type 1 (HSV-1) or human cytomegalovirus (HCMV) was investigated. The level of ISG54-specific RNA in human fetal lung (HFL) or human foreskin (BJ) fibroblasts increased substantially after infection with either virus in the presence of cycloheximide. HSV-1 particles lacking glycoprotein D or glycoprotein H failed to induce ISG54-specific RNA synthesis, demonstrating that entry of virus particles rather than binding of virions to the cell surface was required for the effect. A DNA-binding complex that recognized an interferon-responsive sequence motif was induced upon infection with HSV-1 or HCMV in the presence of cycloheximide, and the complex was shown to contain the cell proteins interferon response factor 3 (IRF-3) and CREB-binding protein. IRF-3 was modified after infection with HSV-1 or HCMV to a form of lower electrophoretic mobility, consistent with phosphorylation. De novo transcription of viral or cellular genes was not required for the activation of IRF-3, since the effect was not sensitive to inhibition by actinomycin D. Infection of HFL fibroblasts with HSV-1 under conditions in which viral replication proceeded normally resulted in severely reduced levels of the IRF-3-containing complex, defining the activation of IRF-3 as a target for viral interference with ISG induction. In BJ fibroblasts, however, significant activation of IRF-3 was detected even when the viral gene expression program progressed to later stages, demonstrating that the degree of inhibition of the response was dependent on host cell type. As a consequence of IRF-3 activation, endogenous interferon was released from BJ cells and was capable of triggering the appropriate signal transduction pathway in both infected and uninfected cells. Activation of ISG54-specific RNA synthesis was not detected after infection of human U-373MG glioblastoma cells, showing that the induction of the response by infection is cell type dependent.