Miracle-dz/UniFAR-FTUs huggingface dataset:
Glucose-Induced Time-Dependent Potentiation of Insulin Release, but not Islet Blood Perfusion, in Anesthetized Rats

Background: Repeated administration of glucose in vivo leads to a time-dependent potentiation of insulin release. Glucose is also known to stimulate pancreatic islet blood flow, but whether this is associated with a time-dependent potentiation is unknown. We therefore repeatedly administered glucose to anesthetized rats and evaluated effects on insulin release and islet blood flow. Methods: Male Wistar-Furth rats, anesthetized with thiobutabarbital, were injected intravenously with 1 ml of saline or glucose at times 0, 30 and 60 min. The combinations used were saline + saline + saline (SSS), glucose + saline + saline (GSS), saline + saline + glucose (SSG) and glucose + glucose + glucose (GGG). Regional organ blood flow values were measured 3 min after the final injection with a microsphere technique, and at this time also serum insulin concentrations were determined with ELISA. Results: Serum insulin concentrations as well as total pancreatic, pancreatic islet and duodenal blood flow were higher in SSG and GGG-treated rats when compared to those given SSS and GSS. However, only insulin concentrations, not blood flow values, were higher in GGG rats when compared to SSG animals. Conclusions: Glucose-induced time-dependent potentiation of insulin release occurs in vivo in thiobutabarbital-anesthetized rats, but is not associated with a further increase in islet blood flow.
Partial-brain radiotherapy for primary central nervous system lymphoma: multi-institutional experience

Whole-brain radiotherapy (WBRT) has been an important component of treatment for primary central nervous system lymphoma (PCNSL), but delayed neurotoxicity has been a matter of concern. We have employed partial-brain radiotherapy (PBRT) with wide margins for PCNSL patients with a single lesion or a few lesions. In this study, we evaluated the treatment outcome in PCNSL patients undergoing PBRT. Between 2003 and 2014, 24 patients were treated with PBRT; 16 received high-dose-methotrexate (MTX) –containing chemotherapy before PBRT. Conventional fractionation with a median dose of 54 Gy was used. For reference, 15 patients undergoing MTX-based chemotherapy and WBRT were also analyzed. The 3-year overall survival rate was 60% for all 24 patients undergoing PBRT and 68% for the 16 patients undergoing MTX-based chemotherapy plus PBRT. The 3-year progression-free survival rate was 41% for all 24 patients undergoing PBRT and 36% for the 16 patients undergoing MTX-based chemotherapy. The in-field recurrence rate was 26% and the out-of-field recurrence rate was 15% at 3 years for all 24 patients undergoing PBRT. The rates for in-field recurrence and the out-of-field recurrence were 27% and 21%, respectively, for the 16 patients undergoing MTX-based chemotherapy. CNS-recurrence rates were similar in patients undergoing MTX-based chemotherapy and PBRT to the rates in those undergoing MTX-based chemotherapy and WBRT. Neurocognitive dysfunction developed in 3 of the 16 patients undergoing MTX + PBRT and in 4 of 15 patients undergoing MTX + WBRT (P = 0.68). PBRT seems to be a feasible treatment option for solitary PCNSL. Further investigations are warranted to evaluate the advantages of PBRT over WBRT.
Climate change and permafrost thaw-induced boreal forest loss in northwestern Canada

Permafrost distribution throughout the western Canadian subarctic is not well understood due to the remoteness and size of the region, its spatial and temporal heterogeneity, limited data availability, and sparse monitoring networks. These factors severely challenge investigations of how climate warming might affect the distribution of permafrost and provide strong justification for new methods of evaluating permafrost extent using remote sensing platforms. This study quantifies forest loss at ten subarctic boreal sites in the southern Northwest Territories and northeastern British Columbia between 1970 and 2010. Historical air photos and optical remote sensing images were assessed using a change detection approach over the ten sites, each 10 km2 spanning a north/south transect of 200 km. This study is the first to apply change detection methods to a large-scale gradient and spans the southern margin of discontinuous permafrost where results demonstrate variable patterns of net forest loss at each site ranged from 6.9% to 11.6% over the 40 year study period. Here we show that these differential rates of landcover change can be explained in part through climatic and environmental factors that vary latitudinally across the selected sites. Change statistics—net change, forest gain and forest loss were significantly correlated with an assortment of factors that varied across the ten-site transect.
The Impact of Type, Dosage and Time of Prenatal Steroid Administration on Neonatal Outcome

Background: In 1972, Liggins and Howie demonstrated that antenatal steroid administration reduced the incidence of respiratory distress syndrome and perinatal mortality in neonates. Since the publication of these findings, perinatal and long-term results of steroid therapy have been evaluated in numerous studies. The aim of the study was to compare the impact of prenatal steroid dosage on perinatal outcomes in neonates and in mothers. Summary: Although the results of the studies are ambiguous, one should consider the potential benefits of dexamethasone in cases of risk of preterm delivery due to abnormalities in fetal health assessments. Dexamethasone may also lead to better results when preterm neonates are burdened with cardiovascular defects or diseases. The opposite holds true for abnormal flows within UA or fetal MCA, i.e., one should consider whether betamethasone is the appropriate drug of choice. Steroid treatment after 34 weeks of gestation is not beneficial. Administration of the full course of steroid treatment (24 mg) in lower single doses is probably more favorable for the mother. On the other hand, a shorter time interval between the doses may allow more women in preterm birth to receive the full course of steroids. Further studies are required to answer these questions, and better methods for predicting preterm birth should be determined.
A Hierarchical Bayesian Model for Combining Multiple 2 × 2 Tables Using Conditional Likelihoods

Summary. This paper introduces a hierarchical Bayesian model for combining multiple 2×2 tables that allows the flexibility of different odds ratio estimates for different tables and at the same time allows the tables to borrow information from each other. The proposed model, however, is different from a full Bayesian model in that the nuisance parameters are eliminated by conditioning instead of integration. The motivation is a more robust model and a faster and more stable Gibbs algorithm. We work out a Gibbs scheme using the adaptive rejection sampling for log concave density and an algorithm for the mean and variance of the noncentral hypergeometric distribution. The model is applied to a multicenter ulcer clinical trial.
Goal Salience Affects Infants’ Goal-Directed Gaze Shifts

Around their first year of life, infants are able to anticipate the goal of others’ ongoing actions. For instance, 12-month-olds anticipate the goal of everyday feeding actions and manual actions such as reaching and grasping. However, little is known whether the salience of the goal influences infants’ online assessment of others’ actions. The aim of the current eye-tracking study was to elucidate infants’ ability to anticipate reaching actions depending on the visual salience of the goal object. In Experiment 1, 12-month-old infants’ goal-directed gaze shifts were recorded as they observed a hand reaching for and grasping either a large (high-salience condition) or a small (low-salience condition) goal object. Infants exhibited predictive gaze shifts significantly earlier when the observed hand reached for the large goal object compared to when it reached for the small goal object. In addition, findings revealed rapid learning over the course of trials in the high-salience condition and no learning in the low-salience condition. Experiment 2 demonstrated that the results could not be simply attributed to the different grip aperture of the hand used when reaching for small and large objects. Together, our data indicate that by the end of their first year of life, infants rely on information about the goal salience to make inferences about the action goal.
Protein Kinase CK2 Protects Multiple Myeloma Cells from ER Stress–Induced Apoptosis and from the Cytotoxic Effect of HSP90 Inhibition through Regulation of the Unfolded Protein Response

Purpose: Protein kinase CK2 promotes multiple myeloma cell growth by regulating critical signaling pathways. CK2 also modulates proper HSP90-dependent client protein folding and maturation by phosphorylating its co-chaperone CDC37. Because the endoplasmic reticulum (ER) stress/unfolded protein response (UPR) is central in myeloma pathogenesis, we tested the hypothesis that the CK2/CDC37/HSP90 axis could be involved in UPR in myeloma cells. Experimental Design: We analyzed CK2 activity upon ER stress, the effects of its inactivation on the UPR pathways and on ER stress–induced apoptosis. The consequences of CK2 plus HSP90 inhibition on myeloma cell growth in vitro and in vivo and CK2 regulation of HSP90-triggered UPR were determined. Results: CK2 partly localized to the ER and ER stress triggered its kinase activity. CK2 inhibition reduced the levels of the ER stress sensors IRE1α and BIP/GRP78, increased phosphorylation of PERK and EIF2α, and enhanced ER stress–induced apoptosis. Simultaneous inactivation of CK2 and HSP90 resulted in a synergic anti-myeloma effect (combination index = 0.291) and in much stronger alterations of the UPR pathways as compared with the single inhibition of the two molecules. Cytotoxicity from HSP90 and CK2 targeting was present in a myeloma microenvironment model, on plasma cells from patients with myeloma and in an in vivo mouse xenograft model. Mechanistically, CK2 inhibition led to a reduction of IRE1α/HSP90/CDC37 complexes in multiple myeloma cells. Conclusions: Our results place CK2 as a novel regulator of the ER stress/UPR cascades and HSP90 function in myeloma cells and offer the groundwork to design novel combination treatments for this disease. Clin Cancer Res; 18(7); 1888–900. ©2012 AACR.
Novel developments in genetic and epigenetic mechanisms of anxiety

Purpose of review The present review aims to deliver a systematic overview of current developments and trends in (epi)genetics of anxiety and to identify upcoming challenges and opportunities. Recent findings Genes related to peptide and hormone signaling have been suggested for anxiety-related phenotypes, e.g., the NPSR1 gene, which has been associated predominantly with panic disorder in women, and shown to interact with environmental factors and to influence psychometric, neurophysiological, and neuroimaging correlates of anxiety. Similar multi-level results have been reported for genetic and epigenetic variation in the OXTR gene, especially in social anxiety disorder (SAD), and for CRHR1 gene variation in women with panic disorder. Variants in RGS2 and ASIC1 genes were linked to panic disorder, with the latter also being implicated in SAD treatment response. Finally, monoaminergic ‘risk’ genes (SLC6A4, MAOA, HTR1A) were related to SAD, generalized anxiety disorder and women with panic disorder, anxiety traits and response to psychopharmacological and psychotherapeutic interventions. Summary Converging evidence for potential genetic and epigenetic risk markers has been gathered and future studies call for independent replications and multi-level integration of dimensional approaches, environmental factors, and biological readouts, while considering sex-specific substratification. Particularly, epigenetic variation appears promising for disease course and treatment response predictions.
Compared with Younger Peritoneal Dialysis Patients, Elderly Patients Have Similar Peritonitis-Free Survival and Lower Risk of Technique Failure, But Higher Risk of Peritonitis-Related Mortality

♦ Background: The number of elderly patients with end-stage kidney disease (ESKD) is increasing worldwide, but the proportion of elderly patients commencing peritoneal dialysis (PD) is falling. The reluctance of elderly ESKD patients to consider PD may be related to a perception that PD is associated with greater rates of complications. In the present study, we compared outcomes between younger and older PD patients. ♦ Methods: Using Australia and New Zealand Dialysis Registry data, all adult ESKD patients commencing PD between 1991 and 2007 were categorized into under 50, 50 – 64.9, and 65 years of age or older groups. Time to first peritonitis, death-censored technique failure, and peritonitis-associated and all-cause mortality were evaluated by multivariate Cox proportional hazards model analysis. ♦ Results: Of the 12 932 PD patients included in the study, 3370 (26%) were under 50 years of age, 4386 (34%) were 50 – 64.9 years of age, and 5176 (40%) were 65 years of age or older. Compared with younger patients (<50 years), elderly patients (≥65 years) had a similar peritonitis-free survival and a lower risk of death-censored technique failure [hazard ratio (HR): 0.85; 95% confidence interval (CI): 0.79 to 0.93], but they had higher peritonitis-related (HR: 2.31; 95% CI: 1.68 to 3.18) and all-cause mortality (HR: 2.90; 95% CI: 2.60 to 3.23). ♦ Conclusions: Not unexpectedly, elderly patients have higher peritonitis-related and all-cause mortality, which is likely a consequence of a greater prevalence of comorbid disease. However, compared with younger patients, elderly patients have superior technique survival and similar peritonitis-free survival, suggesting that PD is a viable renal replacement therapy in this group of patients.
Obstacles and Opportunities for Sustaining Performance Management Systems

ABSTRACT Measuring performance in public organizations has been a growing trend for several decades. Designing, adopting, and implementing this style of management system have been the topic of much practitioner and academic deliberation. One struggle those determined to adopt performance measurement and management systems have faced, though, is the ability to sustain them over time and actually engrain them into their decision-making frameworks. Countless barriers to long-term success exist for public organizations and this article seeks to identify and categorize them. Using a mixed-method survey design, this research shows which factors are the most important to organizations hoping to build a performance system that can stand the test of time. Capacity, knowledge, and buy-in limitations pose serious threats to these reforms and it takes a concerted effort to cultivate not only support from employees and management to pursue performance management but the technical and conceptual capacity to design the right system for the organization.
Working Algorithms: Software Automation and the Future of Work

While some argue that the rise of software automation threatens workers with obsolescence, others assert that new complementarities between humans and software systems are likely to emerge. This study draws on 19 months of participant-observation research at a software firm to investigate how relations between workers and technology evolved over three phases of the company’s development. The author finds two forms of human–software complementarity: computational labor that supports or stands in for software algorithms and emotional labor aimed at helping users adapt to software systems. Instead of perfecting software algorithms that would progressively push people out of the production process, managers continually reconfigured assemblages of software and human helpers, developing new forms of organization with a dynamic relation to technology. The findings suggest how the dynamism of the organizations in which software algorithms are produced and implemented will contribute to labor’s enduring relevance in the digital age.
The 10-D assessment and evidence-based medicine tool for authors and peer reviewers in clinical pharmacology

Background: Peer reviewers and authors of clinical pharmacology manuscripts need to meet the standards for Evidence-Based Medicine (EBM) and Good Publication Practices (GPP), and editors of clinical pharmacology journals have to maintain an overview of the peer review process. Methods and results: The peer review process can be monitored and facilitated using the 10-D assessment, which comprises peer review criteria to determine if: 1. design of the study, 2. diagnoses employed, 3. drug molecules involved, 4. dosages applied, 5. data collected, 6. discussion of the findings, 7. deductions made, 8. documentation, 9. declarations, and 10. dHS (drug hypersensitivity syndrome) risk assessment is in accord with the objectives of the study and meet the requirements of EBM and GPP. Conclusions: The 10-D assessment tool, although easy to apply, requires a high level of clinical pharmacology expertise, especially in the fields of drug disposition, pharmacokinetics, and drug action. Its application will facilitate the peer review of clinical research and clinical trial reports and thus promote safety in drug development and pharmacotherapy and meet the needs of Good Publication Practices.
The Method of Planning Green Infrastructure System with the Use of Landscape-Functional Units (Method LaFU) and its Implementation in the Wrocław Functional Area (Poland)

Green infrastructure (GI) is planned at various scales, including a regional one: city-regions. Strategic GI planning included in the city-regions spatial development policy can contribute to their sustainable development through, among others, providing a range of ecosystem services. In order to meet the challenge of planning GI on a regional scale, the authors present the Method of Landscape-Functional Units (Method LaFU), which is used for the planning and evaluation of such systems. This method was tested in the Wrocław Functional Area (WFA), which is characterized by many negative processes, primarily uncontrolled development of built-up areas, fragmentation of landscape, and declining natural and semi-natural areas. The presented results show the effectiveness of the Method LaFU in GI planning and, above all, in its assessment, which makes it possible to identify problem areas that are at risk but still important for the functioning of the GI system. This allows for quick decision making by entities responsible for spatial planning in the region. The proposed method can also be used in other city-regions.
Ewing's sarcoma: Ten‐year experience with adjuvant chemotherapy

Since May 1970, 67 consecutive patients with primary (nonmetastatic) Ewing's sarcoma were treated with adjuvant chemotherapy (CT) in addition to radiation therapy (RT) or surgery for the primary tumor. The first 19 patients were treated with four‐drug sequential CT (T‐2). The second protocol was a seven‐drug induction combination CT (T‐6) followed by T‐2 maintenance CT; in both protocols CT was continued for 18 months. The current protocol (T‐9) consists of combination CT given continuously for a period of 9 months. Of the entire group of 67 patients, 47 (70%) had axial and proximal lesions (pelvis, spine, rib, humerus, and femur) and 20 (30%) had distal lesions (forearm, leg, and foot); 53/67 (79%) are surviving free of disease 12–118 months (median 41 months) from the start of treatment. Fifteen of 23 (65%) patients with axial lesions, 19/24 (79%) patients with proximal lesions, and 19/20 (95%) patients with distal lesions are free of disease. Disease‐free survivors include 28/39 (72%) male patients and 25/28 (89%) female patients. Thirty‐four patients had RT, and 33 had surgery or surgery and RT, in addition to chemotherapy, for local treatment. The disease‐free survival rate was 76% in the RT group and 82% in the surgery group; failure in the RT group was attributable to local recurrence in 7/34 (21%) patients. Recent experience with T‐9 CT has demonstrated that CT given prior to RT or surgery can cause a great reduction in the size of the primary tumor while allowing the pathologicallyeroded bone to heal prior to the initiation of RT; this also allows the high‐risk patient with an axial primary (pelvis or spine) to tolerate the aggressive CT needed to prevent distant metastases. In addition to dramatically increasing survival in patients with Ewing's sarcoma, combination CT has helped achieve permanent local control. The superior survival rates for all sites of primary tumor are attributable to the early use of aggressive combination CT.
Site‐specific factor involved in the editing of the psbL mRNA in tobacco plastids.

In tobacco plastids, functional psbL mRNA is created by editing an ACG codon to an AUG translation initiation codon. To determine if editing may occur in a chimeric mRNA, the N‐terminal part of psbL containing the editing site was translationally fused with the aadA and kan bacterial genes. The chimeric constructs were introduced into the tobacco plastid genome by targeted gene insertion. Editing of the chimeric mRNAs indicated that the 98 nt fragment spanning the psbL editing site contains all cis information required for editing. Expression of the chimeric gene transcripts led to a significant decrease in the editing efficiency of the endogenous psbL mRNA. However, the efficiency of editing in the transplastomic lines was unchanged for four sites in the rpoB and ndhB mRNAs. Reduced efficiency of psbL editing, but not of the other four sites, in the transplastomic lines indicates depletion of psbL‐specific editing factor(s). This finding implicates the involvement of site‐specific factors in editing of plastid mRNAs in higher plants.
Influence of different prophylactic antibiotic regimens on implant survival rate: a retrospective clinical study.

BACKGROUND The routine use of antibiotics in oral implant treatment seems to be widespread. The pre- or postoperative use of antibiotics in conjunction with implant surgery and its correlation with failure and success rates are poorly documented in the literature. The debate regarding overprescription of antibiotics raises the need for a critical evaluation of proper antibiotic coverage in association with implant treatment. PURPOSE The purpose of this study was to compare the implant survival rate following a 1-day single-dose preoperative antibiotic regimen with that following a 1-week postoperative antibiotic protocol. MATERIALS AND METHODS The study included 868 consecutively treated patients. A total of 3,021 implants were placed. The population was split into two categories, either receiving a 1-day single-dose administration only, or a 1-week postoperative administration of antibiotics. Healing was evaluated at second-stage surgery (6 months for the upper jaw, 3 months for the lower jaw). Failure was defined as removal of implants because of non-osseointegration. Statistical analyses were performed with analysis of variance and the Scheffé test, with a significance level of 5% for comparison of data. RESULTS No significant differences with regard to complications and implant survival were found in the study. CONCLUSION Based on the present data, a more restrictive regimen consisting of a 1-day dose of prophylactic antibiotic in conjunction with routine implant procedures is recommended.