Miracle-dz/UniFAR-FTUs huggingface dataset:
How do we treat life‐threatening anemia in a Jehovah's Witness patient?

The refusal of allogeneic human blood and blood products by Jehovah's Witness (JW) patients complicates the treatment of life‐threatening anemia. For JW patients, when hemoglobin (Hb) levels decrease beyond traditional transfusion thresholds (<7 g/dL), alternative methods to allogeneic blood transfusion can be utilized to augment erythropoiesis and restore endogenous Hb levels. The use of erythropoietin‐stimulating agents and intravenous iron has been shown to restore red blood cell and Hb levels in JW patients, although these effects may be significantly delayed. When JW patients have evidence of life‐threatening anemia (Hb <5 g/dL), oxygen‐carrying capacity can be supplemented with the administration of Hb‐based oxygen carriers (HBOCs). Although HBOCs are not Food and Drug Administration (FDA) approved, they may be obtained and administered with FDA, institutional review board, and patient approval. We describe a protocol‐based algorithm to the management of life‐threatening anemia in JW patients and review time to anemia reversal and patient outcomes using this approach.
A comparative evaluation of properties and clinical efficacy of the echinocandins

With the increase in prevalence of fungal infections, newer antifungal agents are needed to effectively treat invasive disease, and at the same time minimize adverse effects from therapy. The echinocandins comprise a novel class of antifungals; their mechanism of action involves inhibiting 1,3-β-D-glucan synthase, which is essential in cell wall synthesis for certain fungi. All three echinocandins are US FDA-approved for the treatment of esophageal candidiasis. Caspofungin and anidulafungin are licensed for the treatment of candidemia, and other select forms of invasive candidiasis. Micafungin is at present the only echinocandin approved for prophylaxis of fungal infections in hematopoietic stem cell transplants; whereas caspofungin is approved for empiric therapy of febrile neutropenia. Although all three echinocandins are active against Aspergillus, only caspofungin is presently approved for salvage therapy in invasive aspergillosis. Combination therapy with echinocandins plus other licensed antifungal therapy shows promise in treating invasive aspergillosis. This article will explore the similarities and differences among the echinocandins.
Entrepreneurial round-tripping

Purpose The purpose of this paper is to develop and empirically test the theory that new industry entrants hold advantages over incumbents in the shift from unidirectional to multi-directional revenue streams. Design/methodology/approach Using a Cobb-Douglas production function, modified to isolate returns to innovation, the authors examine data from three separate contexts: steamships on Western US rivers (1810-1860), satellite-based internet services (1962-2010) and food waste recycling (1995-2015). Findings The results reveal that while incumbents often attempt to stretch existing technologies to fit emerging circumstances, entrepreneurial innovators achieve greater success by approaching multi-directional value creation as a distinct challenge, one requiring new technologies, organizational forms and business models. Existing theories have primarily attributed incumb ent inertia to a firm’s inability perceive and pursue radical innovations, the results also suggest that existing firms are unwilling to pursue innovations that are likely to erode the marginal profitability of their respective business models. Ironically, rather than protecting incumbents’ financial interests, the authors find that “marginal reasoning” can lead to diminished performance and even extinction. Research limitations/implications The proposed framework and empirical findings have implications for numerous multi-directional frontiers, including: social networking, commercial space travel, distance education and medical treatments using nanoscale technologies. Practical implications While incumbents often lament the destabilizing effects of multi-directionality, new and small firms enjoy a compelling array of entry points and opportunities. Originality/value Scholars, incumbent firms and start-ups both benefit from insights stemming from the novel formulation of multi-directionality challenges and opportunities.
Primary Hepatocytes: Current Understanding of the Regulation of Metabolic Enzymes and Transporter Proteins, and Pharmaceutical Practice for the Use of Hepatocytes in Metabolism, Enzyme Induction, Transporter, Clearance, and Hepatotoxicity Studies

This review brings you up-to-date with the hepatocyte research on: 1) in vitro–in vivo correlations of metabolism and clearance; 2) CYP enzyme induction, regulation, and cross-talk using human hepatocytes and hepatocyte-like cell lines; 3) the function and regulation of hepatic transporters and models used to elucidate their role in drug clearance; 4) mechanisms and examples of idiosyncratic and intrinsic hepatotoxicity; and 5) alternative cell systems to primary human hepatocytes. We also report pharmaceutical perspectives of these topics and compare methods and interpretations for the drug development process.
Fast-Onset Long-Term Open-State Block of Sodium Channels by A-type FHFs Mediates Classical Spike Accommodation in Hippocampal Pyramidal Neurons

Classical accommodation is a form of spike frequency adaptation in neurons whereby excitatory drive results in action potential output of gradually decreasing frequency. Here we describe an essential molecular component underlying classical accommodation in juvenile mouse hippocampal CA1 pyramidal neurons. A-type isoforms of fibroblast growth factor homologous factors (FHFs) bound to axosomatic voltage-gated sodium channels bear an N-terminal blocking particle that drives some associated channels into a fast-onset, long-term inactivated state. Use-dependent accumulating channel blockade progressively elevates spike voltage threshold and lengthens interspike intervals. The FHF particle only blocks sodium channels from the open state, and mutagenesis studies demonstrate that this particle uses multiple aliphatic and cationic residues to both induce and maintain the long-term inactivated state. The broad expression of A-type FHFs in neurons throughout the vertebrate CNS suggests a widespread role of these sodium channel modulators in the control of neural firing.
Rapid prescreening is as effective at reducing screening error as postscreening with the FocalPoint automated screening device

Both manual (rapid prescreening) and automated methods have been devised to reduce screening error compared with routine review of 10% of negative gynecologic cases. To date these two methods have not been compared. A total of 5,139 liquid‐based (SurePath Pap Test, BD Diagnostics) cases were subjected to 100% rapid prescreening and routine manual screening. All cases diagnosed as negative on routine screening were placed on the FocalPoint (BD Diagnostics, Franklin Lakes, NJ) automated screening device. All cases that were negative on routine screening and abnormal on rapid prescreening or in the top 15% of cases by FocalPoint were rescreened and a final diagnosis obtained. Cases were blinded during rapid prescreening and routine manual screening. Abnormal was defined as any diagnosis of atypical squamous cells (ASC) or worse. A total of 427 (8%) of cases were abnormal on routine screening. The sensitivity of rapid prescreening was 44.6%. Rapid prescreening identified an additional 14 abnormal cases (13 ASC and 1 LSIL) and FocalPoint identified nine cases (eight ASC, one LSIL) that were not detected by routine screening. Three of these cases were detected by both methods. The sensitivity of routine screening was 93.1%. Rapid prescreening increased the overall sensitivity significantly (96.0%, P = 0.04); FocalPoint increased the sensitivity but this change was not significant (95.0%, P = 0.21). Estimated screening time was 30 seconds for rapid prescreening and 6 minutes for routine screening with the result that rapid prescreening required 2,570 minutes while review of the FocalPoint Slides required 2,694 minutes. The sensitivity of routine screening in the second half of the study (95.3%) was higher than that in the first half of the study (91.6%) but the difference was not significant (P = 0.11). Rapid prescreening is as effective as directed review using FocalPoint at reducing screening errors and requires no additional screening time. Continued use of these methods may improve the sensitivity of routine screening. Diagn. Cytopathol. 2011. © 2010 Wiley‐Liss, Inc.
ALK‐positive primary cutaneous T‐cell‐lymphoma (CTCL) with unusual clinical presentation and aggressive course

Anaplastic lymphoma kinase (ALK) expression is uncommon in primary cutaneous T‐cell‐lymphomas (CTCL). We report the case of a patient who was initially diagnosed with small plaque parapsoriasis, and eventually developed an unusual manifestation of CTCL 6 years later. The disease was characterized by aggressively ulcerating plaques and tumors of the entire skin. Histopathology revealed monoclonal proliferation of atypical T‐lymphocytes and CD30‐positive blasts with expression of ALK and identification of an ATIC‐ALK fusion protein. Extensive staging confirmed the primary cutaneous origin of the lymphoma. After failure of several conventional treatments including polychemotherapy, the patient finally achieved remission after receiving brentuximab‐vedotin, alemtuzumab and subsequent allogeneic stem cell transplantation. In the following, the patient developed inflammatory cutaneous lesions that pathologically showed no evidence for lymphoma relapse or classical cutaneous graft‐versus‐host disease. The patient responded to immunosuppression, but finally died from multi‐organ failure due to sepsis 8 months after stem cell transplantation. This is a rare instance of ALK positivity in a CTCL, most likely resembling CD30+ transformed mycosis fungoides, because it was not typical for cutaneous anaplastic large cell lymphoma (ALCL). In contrast to its role in systemic ALCL as favorable prognostic marker, ALK expression here was associated with an aggressive course.
Genetic variation in DNMT3B and increased global DNA methylation is associated with suicide attempts in psychiatric patients

Recently, a significant epigenetic component in the pathology of suicide has been realized. Here we investigate candidate functional SNPs in epigenetic‐regulatory genes, DNMT1 and DNMT3B, for association with suicide attempt (SA) among patients with co‐existing psychiatric illness. In addition, global DNA methylation levels [5‐methyl cytosine (5‐mC%)] between SA and psychiatric controls were quantified using the Methylflash Methylated DNA Quantification Kit. DNA was obtained from blood of 79 suicide attempters and 80 non‐attempters, assessed for DSM‐IV Axis I disorders. Functional SNPs were selected for each gene (DNMT1; n = 7, DNMT3B; n = 10), and genotyped. A SNP (rs2424932) residing in the 3′ UTR of the DNMT3B gene was associated with SA compared with a non‐attempter control group (P = 0.001; Chi‐squared test, Bonferroni adjusted P value = 0.02). Moreover, haplotype analysis identified a DNMT3B haplotype which differed between cases and controls, however this association did not hold after Bonferroni correction (P = 0.01, Bonferroni adjusted P value = 0.56). Global methylation analysis showed that psychiatric patients with a history of SA had significantly higher levels of global DNA methylation compared with controls (P = 0.018, Student's t‐test). In conclusion, this is the first report investigating polymorphisms in DNMT genes and global DNA methylation quantification in SA risk. Preliminary findings suggest that allelic variability in DNMT3B may be relevant to the underlying diathesis for suicidal acts and our findings support the hypothesis that aberrant DNA methylation profiles may contribute to the biology of suicidal acts. Thus, analysis of global DNA hypermethylation in blood may represent a biomarker for increased SA risk in psychiatric patients.
A confirmatory factor analysis of the Brief Psychiatric Rating Scale in a homeless sample

This study used a confirmatory factor analysis procedure, the Oblique Multiple Group Method (OMG), with the Brief Psychiatric Rating Scale (BPRS) on a sample of homeless individuals who had both a severe mental illness and a substance use disorder. The hypothesized five‐factor model of Guy (1976) accounted for 93% of the possible variance, and all the appropriate scales had their highest loading on their respective hypothesized factor. In addition, the Guy model accounted for more variance than did an alternative model. The five factors were labelled: thinking disorder, anergia, anxiety‐depression, hostility‐suspicion, and activity. Copyright © 2003 Whurr Publishers Ltd.
Guidance for developing ethical research projects involving children

In this the third master class of the Children's Research Network for Ireland and Northern Ireland, participants will have an opportunity to respond to the Guidance and to discuss ethical issues in their work. The workshop will also provide participants with the opportunity to discuss the challenges facing the community and voluntary sector in applying and monitoring ethical standards in their work in the absence of formal/institutional ethics committees
Exploring Indonesia-Paraguay trade potentials:A revealed comparative advantage approach

This paper attempts to identify and analyze the Indonesia-Paraguay bilateral trade potentials based on their respective export competitiveness. The analysis uses the Revealed Comparative Advantage Index for year 2012 obtained from World Integrated Trade Solution (WITS). The paper reveals that there are huge opportunities for both countries to further strengthen bilateral trade relations.Based on the RCA Index analysis, the paper revealed that in general both countrieshave exported their commodities based on theirrespective comparative advantages, but however both countries current exports still do not reflect their potentials as most for Indonesia (none for Paraguay) of the top ten commodities with the strongest comparative advantagewereunable to penetrate both sides market. This study suggests both countries should remove trade barriers starting by providing access for the top 10 export commodities with the strongest comparative advantage to penetrate in both countries. This step could be a stepping stone towards strengthening bilateral trade relations. Keywords: Comparative Advantage, Export Competitiveness, Bilateral Trade Relation JEL classification numbers: F14, F15, F17
The use of the probiotic Lactobacillus rhamnosus GG and viral findings in the nasopharynx of children attending day care

Limited data are available on the effects of probiotics on the nasopharyngeal presence of respiratory viruses in children attending day care. In this substudy of a randomized, double‐blinded, placebo‐controlled 28‐week intervention study, nasopharyngeal swab samples were collected, on visits to a physician due to symptoms of infection, from children receiving control milk (N = 97) and children receiving the same milk supplemented with probiotic Lactobacillus rhamnosus GG (N = 97). The presence of 14 respiratory viruses was assessed by PCR methods, and viral findings were compared with symptom prevalences in the intervention groups. Rhinovirus was identified in 28.6% of 315 swab samples, followed by respiratory syncytial virus (12.4%), parainfluenza virus 1 (12.1%), enterovirus (8.9%), influenza A(H1N1)pdm09 (7.9%), human bocavirus 1 (3.8%), parainfluenza virus 2 (3.2%), adenovirus (2.9%), and influenza A(H3N2) (0.6%). The children in the probiotic group had less days with respiratory symptoms per month than the children in the control group (6.48 [95% CI 6.28–6.68] vs. 7.19 [95% CI 6.98–7.41], P < 0.001). Probiotic intervention did not reduce significantly the occurrence of the examined respiratory viruses, or have an effect on the number of respiratory symptoms observed at the time of a viral finding. Rhinovirus, respiratory syncytial virus, and parainfluenza virus 1 were the most common respiratory viruses in symptomatic children. Children receiving Lactobacillus rhamnosus GG had fewer days with respiratory symptoms than children in the control group, although probiotic intervention was not effective in reducing the amount of viral findings or the respiratory symptoms associated with viral findings. J. Med. Virol. 85:1632–1638, 2013. © 2013 Wiley Periodicals, Inc.
Individual and contextual effects of education on proximate fertility determinants and life time fertility in Kenya

The main aim of the paper is to verify to what extent the impact of schooling for women on life time fertility and various proximate determinants of fertility will vary across the contextual levels of female education and across region. Data are from the Kenyan Fertility Survey of 1977-1978. "The main [finding] of this paper is that the fertility transition in Kenya is clearly advancing and moving to a crucial stage. This however evolves along an intricate pattern. [because] the elasticities of the intermediate fertility variables with respect to individual schooling are definitely a function of the macro-variables that capture regional patterns of culture and of social and economic development; the elasticities are furthermore differentiated with respect to each of the intermediate fertility variables.There is evidence pointing in the direction of an imminent net fertility decline in large parts of Nairobi Mombasa and the Central [and] Eastern provinces. " (EXCERPT)
Electricity Consumption and Economic Growth in Botswana: A Vector Error Correction Approach

Emerging economies are still faced with need to improve economic growth. OneÂ of the main drivers of growth in literature has been found to be electricityÂ consumption. However literature fails to explain the relationship betweenÂ economic growth and electricity consumption. It is against this background thatÂ the study examines the presence of the long run relationship between economicÂ growth and electricity consumption in Botswana. The study use annual time seriesÂ data for the period 1980 â€“ 2014. Using the Vector Error Correction Model, theÂ study shows that there is a positive long run relationship between the twoÂ variables. Electricity consumption drives long term growth and it is an importantÂ input in the countryâ€™s production function. Human capital and inflation areÂ important control variables in explaining this long run relationship. InflationaryÂ pressures on the economy should be kept low and human capital developmentÂ should be industry relevant for the country to advance its growth efforts. Â Policymakers should continue with and rather develop instruments that encourageÂ more electricity consumption. In this case electricity subsidies should be given toÂ firms in areas that are critical for countryâ€™s growth prospects, like mining andÂ agriculture. Policy makers need to make a cost benefit analysis as they design theÂ subsidies to benefit all the targeted economic agents.JEL classification numbers: O11, E31, E24, F43Keywords: Economic Growth, Electricity Consumption, Botswana, Vector errorcorrection model
Confabulation based recomender system

A recommender system helps users to make choices among alternative candidates based on their previous behaviors. These systems employ data mining tasks to analyze user data and extract useful information for the prediction of user preferences. Collaborative filtering based approaches recommend to each user according to his/her most similar users. A similarity measure used in these recommender systems affects their performance. In this paper, a new recommender system is proposed that does not need the similarity measure. It recommends using confabulation theory, the user's previous rating values and other users' rating values. We compare our system with a collaborative filtering based recommender system which uses Pearson similarity measure. Our experiments on MovieLense dataset show the superiority of the proposed algorithm in term of MAE.
Combined use of sphenoidal electrodes and the dipole localization method for the identification of the mesial temporal focus

We attempted to sub‐classify four cases who show temporal spikes on standard scalp electroencephalogram (EEG), using sphenoidal electrodes and the dipole localization method. In a case with mesial temporal epilepsy, spikes showed phase reversal in a sphenoidal electrode, and the spike dipoles were estimated to be in the mesial temporal lobe. In a case with lateral temporal epilepsy, spikes showed no phase reversal in a sphenoidal electrode, and the spike dipoles were estimated to be in the lateral temporal lobe. In two cases out of four, spikes showed phase reversal in sphenoidal electrodes, whilst the dipoles were estimated to be in the frontal lobe. Clinical features also suggested a diagnosis of frontal lobe epilepsy. In one of the two cases in which frontal lobe epilepsy was suspected, ictal dipoles as well as interictal spike dipoles indicated participation of the frontal lobe in the genesis of seizures. Nevertheless, only mesial temporal lobectomy was performed based on results obtained by invasive subdural electrodes. As a result, seizures were not controlled. Although sphenoidal electrodes were useful for differentiating between mesial and lateral temporal lobe foci, it is advisable to use them in combination with the dipole localization method to identify frontal lobe foci.
Evaluation of Specific Stabilizing Exercise in the Treatment of Chronic Low Back Pain With Radiologic Diagnosis of Spondylolysis or Spondylolisthesis

Study Design. A randomized, controlled trial, test‐retest design, with a 3‐, 6‐, and 30‐month postal questionnaire follow‐up. Objective. To determine the efficacy of a specific exercise intervention in the treatment of patients with chronic low back pain and a radiologic diagnosis of spondylolysis or spondylolisthesis. Summary of Background Data. A recent focus in the physiotherapy management of patients with back pain has been the specific training of muscles surrounding the spine (deep abdominal muscles and lumbar multifidus), considered to provide dynamic stability and fine control to the lumbar spine. In no study have researchers evaluated the efficacy of this intervention in a population with chronic low back pain where the anatomic stability of the spine was compromised. Methods. Forty‐four patients with this condition were assigned randomly to two treatment groups. The first group underwent a 10‐week specific exercise treatment program involving the specific training of the deep abdominal muscles, with co‐activation of the lumbar multifidus proximal to the pars defects. The activation of these muscles was incorporated into previously aggravating static postures and functional tasks. The control group underwent treatment as directed by their treating practitioner. Results. After intervention, the specific exercise group showed a statistically significant reduction in pain intensity and functional disability levels, which was maintained at a 30‐month follow‐up. The control group showed no significant change in these parameters after intervention or at follow‐up. Summary. A "specific exercise" treatment approach appears more effective than other commonly prescribed conservative treatment programs in patients with chronically symptomatic spondylolysis or spondylolisthesis.