Miracle-dz/UniFAR-FTUs huggingface dataset:
Exploiting Answer Set Programming with External Sources for Meta-Interpretive Learning

Abstract Meta-Interpretive Learning (MIL) learns logic programs from examples by instantiating meta-rules, which is implemented by the Metagol system based on Prolog. Viewing MIL-problems as combinatorial search problems, they can alternatively be solved by employing Answer Set Programming (ASP), which may result in performance gains as a result of efficient conflict propagation. However, a straightforward ASP-encoding of MIL results in a huge search space due to a lack of procedural bias and the need for grounding. To address these challenging issues, we encode MIL in the HEX-formalism, which is an extension of ASP that allows us to outsource the background knowledge, and we restrict the search space to compensate for a procedural bias in ASP. This way, the import of constants from the background knowledge can for a given type of meta-rules be limited to relevant ones. Moreover, by abstracting from term manipulations in the encoding and by exploiting the HEX interface mechanism, the import of such constants can be entirely avoided in order to mitigate the grounding bottleneck. An experimental evaluation shows promising results.
Could peripartum antibiotics have delayed health consequences for the infant?

Antibiotics are increasingly prescribed in the peripartum period, for both maternal and fetal indications. Their effective use undoubtedly reduces the incidence of specific invasive infections in the newborn, such as group B streptococcal septicaemia. However, the total burden of infectious neonatal disease may not be reduced, particularly if broad‐spectrum agents are used, as the pattern of infections has been shown to alter to allow dominance of previously uncommon organisms. This area has been relatively understudied, and there are almost no studies of long‐term outcome. Recent findings suggest that such long‐term data should be sought. First, there is evidence that organisms initially colonising the gut at birth may establish chronic persistence in many children, in contrast to prompt clearance if first encountered in later infancy, childhood or adulthood. Second, there is a rapidly advancing basic scientific data showing that individual members of the gut flora specifically induce gene activation within the host, modulating mucosal and systemic immune function and having an additional impact on metabolic programming. We thus review the published data on the impact of perinatal antibiotic regimens upon composition of the flora and later health outcomes in young children and summarise the recent scientific findings on the potential importance of gut flora composition on immune tolerance and metabolism.
Characterization of Lead Precipitate Following Uptake by Roots of Brassica juncea

Seedlings of Brassica juncea (L.) Czern. were grown in solution culture for 14 d prior to exposure to Pb2+ at an activity of 31 μM for 72 h. Electron‐dense deposits found within the apoplast and symplast were analyzed using scanning transmission electron microscopy/energy dispersive spectroscopy to determine the chemical identity of the deposits and potential toxicity resistance mechanisms. Irrespective of the cellular compartment in which they were found, the deposits contained Pb, O, P, and Cl. For the extracellular deposits, the average Pb:P:O atomic ratio was 1:0.54:3.0, which together with the hexagonal crystal system suggests that Pb is present as chloropyromorphite (Pb5(PO4)3Cl). A weak Ca signal also was detected in approximately half of the spectra, possibly indicating the presence of small concentrations of phosphohedyphane (Pb3Ca2(PO4)3Cl). The evidence suggests that B. juncea resists Pb toxicity by storing precipitated Pb in the vacuole.
Protein microarrays using liquid phase fractionation of cell lysates

We describe an approach in which protein microarrays are produced using a two‐dimensional (2‐D) liquid phase fractionation of cell lysates. The method involves a pI‐based fractionation using chromatofocusing in the first dimension followed by nonporous reversed‐phase high‐performance liquid chromatography (HPLC) of each pI fraction in the second dimension. This allows fractionation of cellular proteins in the liquid phase that could then be arrayed on nitrocellulose slides and used to study humoral response in cancer. Protein microarrays have been used to identify potential serum biomarkers for prostate cancer. It is shown that specific fractions are immunoreactive against prostate cancer serum but not against serum from healthy individuals. These proteins could serve as sero‐diagnostic markers for prostate cancer. Importantly, this method allows for use of post‐translationally modified proteins as baits for detection of humoral response. Proteins eliciting an immune response are identified using the molecular mass and peptide sequence data obtained using mass spectrometric analysis of the liquid fractions. The fractionation of proteins in the liquid phase make this method amenable to automation.
[Postoperative analgesia in herniated disk surgery. Comparative study of diclofenac , lysine acetylsalicylate, and ketorolac].

INTRODUCTION Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective in treating musculoskeletal pain and are theoretically ideal for treating postoperative pain of the lumbar column. OBJECTIVES To compare the analgesic efficacy and side effects of treatment with 3 NSAIDs (lysine acetylsalicylate, ketorolac and diclofenac) in the treatment of pain after surgery for lumbar disc hernia. PATIENTS AND METHODS We enrolled 75 ASA I-II patients undergoing discectomy because of lumbar disc hernia; balanced general anesthesia was used in all cases. The patients were randomly distributed in 3 groups based on type of analgesia given in the immediate postoperative period. Group A received lysine acetylsalicylate (1800 mg), group B received ketorolac (30 mg) and group C received diclofenac (75 mg). The analgesics were diluted in 100 mg of saline solution and administered through a peripheral vein over 10 min. We evaluated the analgesia attained on a visual analog scale (VAS) and the physiological response to pain was assessed by monitoring changes in arterial pressure, heart rate and breathing frequency. If analgesia was insufficient 30 min after administration of the drug, 200 mg of lysine cloximate was given as a top-up. The side effects of each drug were also recorded. RESULTS VAS evaluation showed significant reductions in pain 60 min after administration in groups A and B and after 120 min in group C. Nine patients in each group required lysine cloximate. There were no significant differences in physiological response among the 3 groups. No patient suffered major side effects. Mild side effects were reported most often in group B. CONCLUSIONS The NSAIDs studied were inadequately for treating pain after surgery for lumbar disc hernia. Ketorolac was no better than the other analgesics studied but was associated with a higher number of mild side effects.
Factor Structure of the Halstead-Reitan Neuropsychological Battery: A Review and Integration

The Halstead-Reitan Neuropsychological Battery (HRNB) was the first factor-analyzed neuropsychological battery. It was based on a series of tests studied in Ward Halstead's laboratory at the University of Chicago, was accomplished in collaboration with a group of eminent statisticians, and was published in 1947. Four factors were extracted based on Halstead's tests called central integrative field, abstraction, power, and directional and constituted what was described as biological intelligence. Since this original analysis, Reitan's additions to the battery, and the proposal of Reitan and Wolfson's model of neuropsychological functioning, this factor-analytic research continued. This article reviews factor-analytic research concluding that Halstead's analysis has held up reasonably well and there is support for the Reitan and Wolfson model. However, Reitan's revisions of the battery added tests that form a distinct language factor and the sensory-perceptual tests that generally form a separate factor. Other tests and scoring methods used in individual studies modified the core battery and produced somewhat differing solutions. The complexity of the tests prevents the HRNB from being a factorially pure battery, and simple structure is rarely, if ever, reached. Current versions of the HRNB appear to evaluate both “biological” and “psychometric” intelligence, which appear to load on separate factors.
Molecular Changes in the Polymerase Genes (PA and PB1) Associated with High Pathogenicity of H5N1 Influenza Virus in Mallard Ducks

ABSTRACT The highly pathogenic (HP) influenza viruses H5 and H7 are usually nonpathogenic in mallard ducks. However, the currently circulating HP H5N1 viruses acquired a different phenotype and are able to cause mortality in mallards. To establish the molecular basis of this phenotype, we cloned the human A/Vietnam/1203/04 (H5N1) influenza virus isolate that is highly pathogenic in ferrets, mice, and mallards and found it to be a heterogeneous mixture. Large-plaque isolates were highly pathogenic to ducks, mice, and ferrets, whereas small-plaque isolates were nonpathogenic in these species. Sequence analysis of the entire genome revealed that the small-plaque and the large-plaque isolates differed in the coding of five amino acids. There were two differences in the hemagglutinin (HA) gene (K52T and A544V), one in the PA gene (T515A), and two in the PB1 gene (K207R and Y436H). We inserted the amino acid changes into the wild-type reverse genetic virus construct to assess their effects on pathogenicity in vivo. The HA gene mutations and the PB1 gene K207R mutation did not alter the HP phenotype of the large-plaque virus, whereas constructs with the PA (T515A) and PB1 (Y436H) gene mutations were nonpathogenic in orally inoculated ducks. The PB1 (Y436H) construct was not efficiently transmitted in ducks, whereas the PA (T515A) construct replicated as well as the wild-type virus did and was transmitted efficiently. These results show that the PA and PB1 genes of HP H5N1 influenza viruses are associated with lethality in ducks. The mechanisms of lethality and the perpetuation of this lethal phenotype in ducks in nature remain to be determined.
Functional epitope analysis of the human CD4 molecule: antibodies that inhibit human immunodeficiency virus type 1 gene expression bind to the immunoglobulin CDR3-like region of CD4

We recently demonstrated that monoclonal antibody (MAb) 13B8-2, specific for the immunoglobulin (Ig) complementary determining region 3 (CDR3)-like region of the CD4 molecule, inhibits viral transcription in human immunodeficiency virus (HIV)-infected CEM cells and HIV type 1 (HIV-1) promoter activity. Here, we have studied the capacity of several MAb specific for the D1 domain of CD4, including anti-CDR2-like (Leu-3a and ST4) and anti-CDR3-like (13B8-2 and ST40) MAb, and for the D2 domain of CD4 (BL4) to inhibit both provirus transcription in HIV-1LAI-infected CEM cells and transcription of the chloramphenicol acetyltransferase (CAT) gene under control of the HIV-1 long terminal repeat in transiently transfected CEM cells. We found that HIV-1 promoter activity and provirus transcription are inhibited only by MAb that bind to the CDR3-like region in domain 1 of CD4. Moreover, we demonstrated that the Fab fragment of an anti-CDR3-like region-specific anti-CD4 MAb is a powerful inhibitor of HIV-1 promoter activity. These results have implications for understanding the role of the CDR3-like region in CD4 T-cell signaling, which controls provirus transcription.
Structure Function Correlates in the Pulmonary Vasculature during Acute Lung Injury and Chronic Pulmonary Hypertension 1 2

Arteries, veins, and capillaries comprise the pulmonary vasculature. Three structural types of artery and vein are identified, the most muscular vessels being the largest. For example, arteries that accompany the preacinar arteries are muscular in structure while those within the acinus may be either, muscular, partially muscular or non-muscular. These small intraacinar arteries contribute much to the hemodynamic behavior of the lung. Pulmonary edema results from damage to the capillary endothelium while chronic pulmonary hypertension is characterized by structural alterations in the pulmonary arteries. Correlation of the structural and functional changes of chronic pulmonary hypertension suggest that the increases in medial and adventitial thickness of the muscular preacinar arteries are secondary to the onset of this disease, while the changes in the peripheral arteries—appearance of muscle in smaller intraacinar arteries than normal and reduction in arterial volume—contribute to the rise in pulmonary artery pressure and pulmonary vascular resistance. Such correlations of structure and hemodynamic measurements demand that the lung be fixed in a simple and standardized manner. Available methodology to evaluate the structural changes that occur during the development of pulmonary edema and chronic pulmonary hypertension are described.
Incremental cost-effectiveness of combined therapy vs medication only for youth with selective serotonin reuptake inhibitor-resistant depression: treatment of SSRI-resistant depression in adolescents trial findings.

CONTEXT Many youth with depression do not respond to initial treatment with selective serotonin reuptake inhibitors (SSRIs), and this is associated with higher costs. More effective treatment for these youth may be cost-effective. OBJECTIVE To evaluate the incremental cost-effectiveness over 24 weeks of combined cognitive behavior therapy plus switch to a different antidepressant medication vs medication switch only in adolescents who continued to have depression despite adequate initial treatment with an SSRI. DESIGN Randomized controlled trial. SETTING Six US academic and community clinics. PATIENTS Three hundred thirty-four patients aged 12 to 18 years with SSRI-resistant depression. INTERVENTION Participants were randomly assigned to (1) switch to a different medication only or (2) switch to a different medication plus cognitive behavior therapy. MAIN OUTCOME MEASURES Clinical outcomes were depression-free days (DFDs), depression-improvement days (DIDs), and quality-adjusted life-years based on DFDs (DFD-QALYs). Costs of intervention, nonprotocol services, and families were included. RESULTS Combined treatment achieved 8.3 additional DFDs (P = .03), 0.020 more DFD-QALYs (P = .03), and 11.0 more DIDs (P = .04). Combined therapy cost $1633 more (P = .01). Cost per DFD was $188 (incremental cost-effectiveness ratio [ICER] = $188; 95% confidence interval [CI], -$22 to $1613), $142 per DID (ICER = $142; 95% CI, -$14 to $2529), and $78,948 per DFD-QALY (ICER = $78,948; 95% CI, -$9261 to $677,448). Cost-effectiveness acceptability curve analyses suggest a 61% probability that combined treatment is more cost-effective at a willingness to pay $100,000 per QALY. Combined treatment had a higher net benefit for subgroups of youth without a history of abuse, with lower levels of hopelessness, and with comorbid conditions. CONCLUSIONS For youth with SSRI-resistant depression, combined treatment decreases the number of days with depression and is more costly. Depending on a decision maker's willingness to pay, combined therapy may be cost-effective, particularly for some subgroups. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00018902.
Calcium regulation of parathyroid and C cell function in familial benign hypercalcemia

The roles of parathyroid hormone (PTH) and calcitonin (CT) in the pathogenesis of familial benign hypercalcemia (FBH, or hypocalciuric hypercalcemia) are uncertain. Thus we performed studies in 26 patients with FBH, 12 patients with primary hyperparathyroidism (HPT), and 20 normal volunteers, to answer these questions: are plasma levels of intact or biologically active PTH frequently elevated in FBH? Is plasma intact PTH nonsuppressible during calcium infusion? Is there blunting of the C cell CT response to calcium infusion as occurs in primary HPT? We used three methods for measurement of PTH: a mid region‐specific radioimmunoassay (iPTH, antiserum GP‐1M), an extraction‐concentration bioassay (bioPTH, stimulation of cAMP generation in osteoblastlike cells), and a two‐site immunoradiometric assay (IRMA) for intact PTH. PTH levels were significantly elevated in primary HPT by all three methods, but mean PTH was normal in FBH and 85–92% of values overlapped the normal range. During 5 minute calcium infusions (2 mg Ca2+ per kg) iPTH values fell little, but bioPTH and intact PTH fell sharply in all three groups. Mean calcium‐induced decreases of intact and bioPTH were indistinguishable from normal in FBH, but PTH levels generally remained elevated at 5 minutes in primary HPT. In FBH basal and postinfusion CT levels were normal. The data show that, in the majority of patients with FBH, PTH concentrations and bioactivity in blood are within the normal range and are suppressed rapidly to very low levels with further increases of calcium. The data suggest that the abnormality of parathyroid function in FBH differs from that in primary HPT. There was no deficiency of CT or C cell responsiveness in FBH, another difference from primary HPT. Nonetheless, in 8–15% of cases, measurement of PTH could not discriminate FBH from primary HPT.
DIFFERENTIAL EFFECTS ON ACTION POTENTIAL DURATION OF CLASS IA, B AND C ANTIARRHYTHMIC DRUGS: MODULATION BY STIMULATION RATE AND EXTRACELLULAR K+ CONCENTRATION

1. Standard microelectrode techniques were used to study the effects on the action potential duration (APD) of canine Purkinje fibres of a therapeutic concentration of nine Class I antiarrhythmic drugs. At an extracellular K+ concentration of 5.6 mmol/L all nine agents reduced APD at all drive rates studied (range of interstimulus intervals = 200–1000 ms). At lower levels of K+, quinidine (5 μmol/L) and disopyramide (10 μmol/L) (Class Ia agents) revealed dual effects on APD. At the lowest levels of K+ (2 mmol/L) and the longest interstimulus interval used (2000 ms), both agents significantly prolonged APD. Under all other conditions, APD was either unchanged or reduced. Lignocaine, 15 μmol/L (Class Ib agent) reduced APD at all rates and all K+ concentrations and this effect was greatest at the slowest rates.
Systematic Review of Epigenetic Effects of Pharmacological Agents for Bipolar Disorders

Epigenetic effects of medications are an evolving field of medicine, and can change the landscape of drug development. The aim of this paper is to systematically review the literature of the relationship between common medications used for treatment of bipolar disorders and epigenetic modifications. MedLine/PubMed searches were performed based on pre-specified inclusion criteria from inception to November 2017. Six animal and human studies met the inclusion criteria. These studies examined the epigenetic changes in the main classes of medications that are used in bipolar disorders, namely mood stabilizers and antipsychotics. Although these initial studies have small to moderate sample size, they generally suggest an evolving and accumulating evidence of epigenetic changes that are associated with several of the medications that are used in bipolar I and II disorders. In this manuscript, we describe the specific epigenetic changes that are associated with the medications studied. Of the studies reviewed, five of the six studies revealed epigenetic changes associated with the use of mood stabilizers or antipsychotic medications. This review contributes to future research directions. Further understanding of the complexities of the epigenome and the untangling of the effects and contributions of disease states versus medications is crucial for the future of drug design and the development of new therapeutics. Epigenetic therapeutics hold great promise for complex disease treatment and personalized interventions, including psychiatric diseases.
The influence of emotion clarity on emotional prosody identification in paranoid schizophrenia

Background Identification of emotional facial expression and emotional prosody (i.e. speech melody) is often impaired in schizophrenia. For facial emotion identification, a recent study suggested that the relative deficit in schizophrenia is enhanced when the presented emotion is easier to recognize. It is unclear whether this effect is specific to face processing or part of a more general emotion recognition deficit. Method We used clarity-graded emotional prosodic stimuli without semantic content, and tested 25 in-patients with paranoid schizophrenia, 25 healthy control participants and 25 depressive in-patients on emotional prosody identification. Facial expression identification was used as a control task. Results Patients with paranoid schizophrenia performed worse than both control groups in identifying emotional prosody, with no specific deficit in any individual emotion category. This deficit was present in high-clarity but not in low-clarity stimuli. Performance in facial control tasks was also impaired, with identification of emotional facial expression being a better predictor of emotional prosody identification than illness-related factors. Of those, negative symptoms emerged as the best predictor for emotional prosody identification. Conclusions This study suggests a general deficit in identifying high-clarity emotional cues. This finding is in line with the hypothesis that schizophrenia is characterized by high noise in internal representations and by increased fluctuations in cerebral networks.
Dilated cardiomyopathy associated with deficiency of the cytoskeletal protein metavinculin.

BACKGROUND The cytoskeleton plays an important role in maintaining cell structure and integrity. Defects in cytoskeletal proteins can cripple cell strength and may cause cardiomyopathy. We analyzed heart tissues from subjects with dilated cardiomyopathy for abnormalities in the cardiac cytoskeleton. Metavinculin, a cardiac isoform of the cytoskeletal protein vinculin, connects actin microfilaments to the intercalated disk and membrane costameres of the heart. METHODS AND RESULTS Metavinculin and vinculin transcripts and protein were analyzed by polymerase chain reaction (PCR) and Western blotting. Thirty-three human heart specimens were studied, including 5 normal controls, 4 subjects with ischemic cardiomyopathy, 1 with X-linked cardiomyopathy, and 23 with idiopathic dilated cardiomyopathy (IDC). PCR of cardiac cDNA detected absence of the metavinculin transcript in cardiac tissue from a subject with IDC. PCR of genomic DNA showed that the metavinculin exon was present but not utilized in the cardiac transcript. Western blot analysis demonstrated absence of metavinculin protein in the heart from this subject. Immunostaining of cardiac vinculin in this heart showed disorganized intercalated disk structures. Metavinculin deficiency was associated with normal cardiac expression of the cytoskeletal proteins vinculin, alpha-actinin, and dystrophin. Normal metavinculin expression in the other heart specimens suggests that the defect is specific in the IDC subject identified. CONCLUSIONS These results demonstrate an association between metavinculin deficiency and dilated cardiomyopathy due to a defect in alternative mRNA splicing.