Miracle-dz/UniFAR-FTUs huggingface dataset:
Expression of proinflammatory cytokines by human mesenchymal stem cells in response to cyclic tensile strain

Mesenchymal stem cells produce proinflammatory cytokines during their normal growth. Direct or indirect regulation of bone resorption by these cytokines has been reported. However, the effects of osteogenic conditions—chemical and/or mechanical—utilized during in vitro bone tissue engineering on expression of cytokines by hMSCs have not been studied. In this study, we investigated the effects of cyclic tensile strain, culture medium (with and without dexamethasone), and culture duration on the expression of tumor necrosis factor‐α (TNF‐α), interleukin‐1β (IL‐1β), interleukin‐6 (IL‐6), and interleukin‐8 (IL‐8) by bone marrow derived human mesenchymal stem cells (hMSCs). Human MSCs seeded in three‐dimensional Type I collagen matrices were subjected to 0%, 10%, and 12% uniaxial cyclic tensile strains at 1 Hz for 4 h/day for 7 and 14 days in complete growth or dexamethasone‐containing osteogenic medium. Viability of hMSCs was maintained irrespective of strain level and media conditions. Expression of either TNF‐α or IL‐1β was not observed in hMSCs under any of the conditions investigated in this study. Expression of IL‐6 was dependent on culture medium. An increase in IL‐6 expression was caused by both 10% and 12% strain levels. Both 10% and 12% strain levels caused an increase in IL‐8 production by hMSCs that was dependent on the presence of dexamethasone. IL‐6 and IL‐8 expressions by hMSCs were induced by cyclic tensile strain and osteogenic differentiating media, indicating that IL‐6 and IL‐8 may be functioning as autocrine signals during osteogenic differentiation of hMSCs. J. Cell. Physiol. 219: 77–83, 2009. © 2008 Wiley‐Liss, Inc.
Learning-induced sharpening of neuronal tuning and adaptation: Not “mixed”

Abstract Gotts et al. present an attractive model of how priming can arise from neuronal adaptation effects. Their very satisfying account helps to demystify adaptation effects. In fact, adaptation effects are even less mysterious than portrayed: While Gotts et al. state that “fMRI studies in humans that have attempted to evaluate sharpening of visual object representations with experience have … generated mixed results”, referring to fMRI adaptation (fMRI-A) studies by our group and others, the results described in the cited papers are in fact entirely compatible, further establishing the usefulness of fMRI-A to probe neuronal tuning in humans.
Nonfactual Know-How and the Boundaries of Semantics

Know-how and expressivism are usually regarded as disjoint topics, belonging to distant areas of philosophy. This paper argues that, despite obvious differences, the two debates have important similarities. In particular, semantic and conceptual tools developed by expressivists can be exported to the know-how debate. On the one hand, some of the expressivists' semantic resources can be used to deflect Stanley and Williamson's influential argument for factualism about know-how: the claim that knowing how to do something consists in knowing a fact. On the other, expressivism provides the resources to formulate a nonfactualist account of know-how. On this account, know-how has a kind of nonpropositional content and plays the role of guiding performance of action, rather than recording information from the environment.
Antibody-based delivery of interleukin-9 to neovascular structures: Therapeutic evaluation in cancer and arthritis

Interleukin-9 is a cytokine with multiple functions, including the ability to activate group 2 innate lymphoid cells, which has been postulated to be therapeutically active in mouse models of arthritis. Similarly, interleukin-9 has been suggested to play an important role in tumor immunity. Here, we describe the cloning, expression, and characterization of three fusion proteins based on murine interleukin-9 and the F8 antibody, specific to the alternatively spliced EDA domain of fibronectin. EDA is strongly expressed in cancer and in various arthritic conditions, while being undetectable in the majority of healthy organs. Interleukin-9-based fusion proteins with an irrelevant antibody specific to hen egg lysozyme served as negative control in our study. The fusion proteins were characterized by quantitative biodistribution analysis in tumor-bearing mice using radioiodinated protein preparations. The highest tumor uptake and best tumor:organ ratios were observed for a format, in which the interleukin-9 moiety was flanked by two units of the F8 antibody in single-chain Fv format. Biological activity of interleukin-9 was retained when the payload was fused to antibodies. However, the targeted delivery of interleukin-9 to the disease site resulted in a modest anti-tumor activity in three different murine models of cancer (K1735M2, CT26, and F9), while no therapeutic benefit was observed in a collagen induced model of arthritis. Collectively, these results confirm the possibility to deliver interleukin-9 to the site of disease but cast doubts about the alleged therapeutic activity of this cytokine in cancer and arthritis, which has been postulated in previous publications.
Genetic expression of aryl hydrocarbon hydroxylase induction. Evidence for the involvement of other genetic loci.

Abstract The intraperitoneal administration of aromatic hydrocarbons such as 3-methylcholanthrene or β-naphthoflavone stimulates aryl hydrocarbon (benzo[a]pyrene) hydroxylase activity in C57BL/6N, C57BL/6J, C3H/HeN, BALB/cAnN, CBA/HN, and PL/J inbred mice but not in the DBA/2N, 129/J, RF/J, AKR/N, AKR/J, or AU/SsJ inbred strains. By means of genetic crosses between a "responsive" and a "nonresponsive" strain, the hydroxylase induction appears to segregate as an autosomal dominant trait in the C57BL/6N x RF/J cross, the C57BL/6N x 129/J cross, the C3H/HeN x AKR/N cross, the BALB/cAnN x AKR/N cross, the CBA/HN x AKR/N cross, the BALB/cAnN x DBA/2N cross, the C57BL/6N x AU/SsJ cross, the PL/J x AU/SsJ cross, the C57BL/6J x AKR/J cross, the C57BL/6N x AKR/J cross, and the C57BL/6J x AKR/N cross. The absence of hydroxylase induction appears to segregate in an autosomal dominant fashion in the C57BL/6N x AKR/N cross. The induction process in offspring from the C3H/HeN x DBA/2N cross is inherited additively. In mice from many of the above mentioned crosses, there exists a positive, significant correlation between the induced hepatic hydroxylase activity and (a) new formation of hepatic microsomal cytochrome P1-450; (b) higher inducible hydroxylase activities in lung, kidney, bowel, and skin; and (c) induction of hepatic microsomal 7-ethoxycoumarin O-deethylase, p-nitroanisole-O-demethylase, and 3-methyl-4-methylaminoazobenzene N-demethylase activities. We have found no exceptions to this general observation. The basal hydroxylase activity appears to be inherited additively, within the limits of individual variation. From data involving more than 2200 individual mice of these 12 inbred strains, the induction of the monooxygenase activities and the stimulation of cytochrome P1-450 formation by aromatic hydrocarbons appear to be regulated by at least three alleles at each of two nonlinked genetic loci.
Evaluation of an every-other-day palonosetron schedule to control emesis in multiple-day high-dose chemotherapy.

AIM Efficacy of intermittent palonosetron dosing in patients undergoing multiple-day, high-dose chemotherapy (HDC) was investigated. PATIENTS & METHODS Fifty-eight patients received palonosetron (0.25 mg intravenous [iv.]) every other day plus daily dexamethasone (8 mg iv. twice daily) dosing. The primary end point was complete control (CC; no emesis, no rescue anti-emetics, and no more than mild nausea) in the overall acute-period (until 24 h after chemotherapy completion). RESULTS Acute-period CC occurred in 81% and 50% of patients receiving palonosetron and ondansetron (historical control cohort), respectively. Palonosetron (odds ratio [OR]: 4.37; p = 0.001) and a longer duration of HDC regimen (OR: 3.47; p = 0.011) independently predicted a better anti-emetic outcome. CONCLUSION Palonosetron every other day plus daily dexamethasone is an effective anti-emetic coverage in patients undergoing HDC.
Does applying technology throughout the medication use process improve patient safety with antineoplastics?

Purpose Medical errors, in particular medication errors, continue to be a troublesome factor in the delivery of safe and effective patient care. Antineoplastic agents represent a group of medications highly susceptible to medication errors due to their complex regimens and narrow therapeutic indices. As the majority of these medication errors are frequently associated with breakdowns in poorly defined systems, developing technologies and evolving workflows seem to be a logical approach to provide added safeguards against medication errors. Summary This article will review both the pros and cons of today's technologies and their ability to simplify the medication use process, reduce medication errors, improve documentation, improve healthcare costs and increase provider efficiency as relates to the use of antineoplastic therapy throughout the medication use process. Several technologies, mainly computerized provider order entry (CPOE), barcode medication administration (BCMA), smart pumps, electronic medication administration record (eMAR), and telepharmacy, have been well described and proven to reduce medication errors, improve adherence to quality metrics, and/or improve healthcare costs in a broad scope of patients. The utilization of these technologies during antineoplastic therapy is weak at best and lacking for most. Specific to the antineoplastic medication use system, the only technology with data to adequately support a claim of reduced medication errors is CPOE. In addition to the benefits these technologies can provide, it is also important to recognize their potential to induce new types of errors and inefficiencies which can negatively impact patient care. Conclusion The utilization of technology reduces but does not eliminate the potential for error. The evidence base to support technology in preventing medication errors is limited in general but even more deficient in the realm of antineoplastic therapy. Though CPOE has the best evidence to support its use in the antineoplastic population, benefit from many other technologies may have to be inferred based on data from other patient populations. As health systems begin to widely adopt and implement new technologies it is important to critically assess their effectiveness in improving patient safety.
Emergency contraception over‐the‐counter: Practices and attitudes of pharmacists and pharmacy assistants in far North Queensland

Background: Emergency contraception (EC) has been available as a Schedule 3 (over‐the‐counter, OTC) medication through Australian pharmacies since 2004. This study aimed to describe OTC EC dispensing services in pharmacies in the Cairns and Hinterland Health Service District and to explore the knowledge and attitudes of pharmacy staff. The study findings will assist in developing resources to support pharmacy staff in their OTC EC provision role.
University of Groningen Bioenergetic cues shift FXR splicing towards FXR 2 to modulate hepatic lipolysis and fatty acid metabolism

Objective: Farnesoid X receptor (FXR) plays a prominent role in hepatic lipid metabolism. The FXR gene encodes four proteins with structural differences suggestive of discrete biological functions about which little is known. Methods: We expressed each FXR variant in primary hepatocytes and evaluated global gene expression, lipid profile, and metabolic fluxes. Gene delivery of FXR variants to Fxr / mouse liver was performed to evaluate their role in vivo. The effects of fasting and physical exercise on hepatic Fxr splicing were determined. Results: We show that FXR splice isoforms regulate largely different gene sets and have specific effects on hepatic metabolism. FXRa2 (but not a1) activates a broad transcriptional program in hepatocytes conducive to lipolysis, fatty acid oxidation, and ketogenesis. Consequently, FXRa2 decreases cellular lipid accumulation and improves cellular insulin signaling to AKT. FXRa2 expression in Fxr / mouse liver activates a similar gene program and robustly decreases hepatic triglyceride levels. On the other hand, FXRa1 reduces hepatic triglyceride content to a lesser extent and does so through regulation of lipogenic gene expression. Bioenergetic cues, such as fasting and exercise, dynamically regulate Fxr splicing in mouse liver to increase Fxra2 expression. Conclusions: Our results show that the main FXR variants in human liver (a1 and a2) reduce hepatic lipid accumulation through distinct mechanisms and to different degrees. Taking this novel mechanism into account could greatly improve the pharmacological targeting and therapeutic efficacy of FXR agonists. 2015 The Authors. Published by Elsevier GmbH. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Late Antibody-Mediated Rejection in Renal Allografts: Outcome After Conventional and Novel Therapies

Background Although several strategies for treating early antibody-mediated rejection (AMR) in kidney transplants have been investigated, evidence on treatment of late AMR manifesting after 6 months is sparse. In this single-center series, we present data on 23 consecutive patients treated for late AMR. Methods Late AMR was diagnosed using Banff 2007 criteria along with presence of donor-specific antibodies (DSA) and acute rise in serum creatinine (SCr). Response to therapy was assessed by improvement in SCr, histologic improvement, and decline in DSA strength. Results Overall, 17% (4/23) had documented nonadherence while 69% (16/23) had physician-recommended reduction in immunosuppression before AMR. Eighteen patients (78%) were treated with plasmapheresis or low-dose IVIg+rituximab; 11 (49%) with refractory AMR also received one to three cycles of bortezomib. While there was an improvement (P=0.02) in mean SCr (2.4 mg/dL) at the end of therapy compared with SCr at the time of diagnosis (2.9 mg/dL), this improvement was not sustained at most recent follow-up. Eleven (48%) patients had no histologic resolution on follow-up biopsy. Lack of histologic response was associated with older patients (odds ratio [OR]=3.17; P=0.04), presence of cytotoxic DSA at time of diagnosis (OR=200; P=0.04), and severe chronic vasculopathy (cv≥2) on index biopsy (OR=50; P=0.06). Conclusions A major setting in which late AMR occurred in our cohort was reduction or change in immunosuppression. Our data demonstrate an inadequate response of late AMR to current and novel (bortezomib) therapies. The benefits of therapy need to be counterweighed with potential adverse effects especially in older patients, large antibody loads, and chronic allograft vasculopathy.
Reasons for adolescent suicide attempts: associations with psychological functioning.

OBJECTIVE To determine reasons for suicide attempts in adolescents and to examine the relationship between these reasons and psychological functioning. METHOD Self-reported reasons for suicide attempts and psychological functioning were examined in 120 adolescent suicide attempters who presented to a pediatric general hospital. RESULTS Consistent with prior research, the most frequently endorsed motives for self-harm were to die, to escape, and to obtain relief. More manipulative reasons for overdose (such as making people sorry) were endorsed less frequently. Adolescents who cited death as a reason for their suicide attempt reported more hopelessness, socially prescribed perfectionism, depression, and anger expression. Discriminant function analyses indicated that high levels of depression and anger expression predicted a self-reported wish to die, and high levels of depression and socially prescribed perfectionism predicted death as the primary reason reported for the suicide attempt. CONCLUSIONS Systematic assessment of the reasons for a suicide attempt is a useful tool for clinicians in determining recommendations for follow-up treatment.
Improving patients' beliefs about antidepressants in primary care: a cluster-randomized controlled trial of the effect of a depression care program.

OBJECTIVE Many depressed patients have negative beliefs about antidepressants, leading to poor adherence, unfavorable depression outcome, and low perceived well-being, role functioning, and quality of life. Interventions to ameliorate beliefs are therefore needed. METHOD In a cluster-randomized controlled trial conducted from September 1999 to January 2001, 2 interventions to improve management of major depressive disorder in primary care were compared: (1) a depression care program (DCP), providing enhanced patient education, stimulation of active participation of general practitioners and patients in the treatment process, discussion of benefits and costs of taking antidepressant medication, and systematic follow-up and (2) a systematic follow-up program (SFP). Thirty general practitioners were randomly assigned, and 211 patients with current major depressive disorder (diagnosed according to DSM-IV) were included. All patients were prescribed a selective serotonin reuptake inhibitor. Beliefs were assessed at baseline, at week 10, and at week 26. Differences in change of beliefs between DCP and SFP groups were analyzed. RESULTS Changes in patients' beliefs were more favorable in the DCP condition at week 10 and week 26, compared with SFP only (beliefs concerning appropriate medication-taking, week 10: effect size = 0.39, p = .012; week 26: effect size = 0.55, p = .001; beliefs concerning harmfulness, week 10: effect size = 0.45, p = .011; week 26: effect size = 0.62, p = .002). CONCLUSION The depression care program ameliorates beliefs about antidepressants in primary care patients with major depressive disorder. The study results encourage the implementation of a depression care program in order to improve beliefs about antidepressant medication in primary care patients diagnosed with major depressive disorder.
Ventricular arrhythmias and diazepam.

To the Editor. — Barrett and Hey's description of ventricular arrhythmias associated with the intravenous use of diazepam ( 214 :1323, 1970) illustrates some of the difficulties in drawing conclusions from uncontrolled isolated case reports. Their first patient had a short burst of ventricular tachycardia after direct current shock, a not infrequent observation regardless of the nature of the premedication. In their second case however ventricular tachyarrhythmia occurred following administration of diazepam, but before shock. Although the patient had also been receiving quinidine which may cause paradoxical ventricular arrhythmias, the temporal relationship to administration of diazepam would seem to implicate the latter as the cause. Diazepam has been extensively investigated and cardiac arrhythmias related to its use have rarely been encountered. It is difficult to interpret data from different series because of varying patient populations, clinical settings, doses, and methods of administration. Cardiac arrest in one patient treated with diazepam for seizures
The W43-MM1 mini-starburst ridge, a test for star formation efficiency models ?

Context. Star formation e ciency (SFE) theories are currently based on statistical distributions of turbulent cloud structures and a simple model of star formation from cores. They remain poorly tested, especially at the highest densities. Aims. We investigate the e ects of gas density on the SFE through measurements of the core formation e ciency (CFE). With a total mass of 2 10 4 M , the W43-MM1 ridge is one of the most convincing candidate precursors of Galactic starburst clusters and thus one of the best places to investigate star formation. Methods. We used high-angular resolution maps obtained at 3 mm and 1 mm within the W43-MM1 ridge with the IRAM Plateau de Bure Interferometer to reveal a cluster of 11 massive dense cores, and, one of the most massive protostellar cores known. A Herschel column density image provided the mass distribution of the cloud gas. We then measured the “instantaneous” CFE and estimated the SFE and the star formation rate (SFR) within subregions of the W43-MM1 ridge. Results. The high SFE found in the ridge ( 6% enclosed in 8 pc 3 ) confirms its ability to form a starburst cluster. There is, however, a clear lack of dense cores in the eastern part of the ridge, which may be currently assembling. The CFE and the SFE are observed to increase with volume gas density, while the SFR per free fall time steeply decreases with the virial parameter, vir. Statistical models of the SFR may describe the outskirts of the W43-MM1 ridge well, but struggle to reproduce its inner part, which corresponds to measurements at low vir. It may be that ridges do not follow the log-normal density distribution, Larson relations, and stationary conditions forced in the statistical SFR models.
Association of bovine DGAT1 and leptin genes polymorphism with milk production traits and energy balance indicators in primiparous Holstein cows

This study investigated the impact and significance of two polymorphisms located in the DGAT1 and LEP genes on selected milk production traits during the first six months of lactation, with respect to the course of the Holstein primiparous cows’ body condition. A total of 278 primiparous Holstein cows were tested for the DGAT1-K232A and LEP C(-963)T mutations using the PCR-RFLP technique. The following allele frequencies were found: K232A 0.74 (A) and 0.26 (K), C(-963)T 0.58 (C) and 0.42 (T). The statistically significant influences (P<0.01-0.05) were found for both polymorphisms. Homozygotes AA for DGAT1 were characterized by the highest daily milk production and lowest percentage content of fat during almost all observed months (P<0.01-0.05), which is related to statistically significantly (P<0.01) the lowest fat-to-protein ratio. Cows with CC genotype in LEP gene were characterized by the lowest content of fat during the second month of lactation which affected corresponding fat-to-protein ratio in milk. Body condition score (BCS) level and BCS changes during the first six months of lactations were not influenced by any mutation evaluated.
The role of insightful disclosure in outcomes for women in peer‐directed breast cancer groups: a replication study

This study was stimulated by the recent publication (Health Commun 2006;19(2):133–142) who reported the effects of insightful disclosure on outcomes in' peer‐led internet breast cancer support groups. The present study attempted to replicate their hypotheses using the same methods for coding insightful disclosure as well as parallel outcome measures. Four hypotheses are tested; writing a higher percentage of insightful disclosure words will be associated with: (1) fewer BC concerns; (2) reduction in the emotional distress; (3) better physical health; and (4) few functional limitations. New members (N = 77) to BC bulletin boards (BB) were recruited through BB postings and/or e‐mails. We asked them to fill out questionnaires measuring depression and quality of life, when they joined the BB, and again six months later. Two questionnaires (CESD and FACTB [Functional Well being, Physical well being, and Breast cancer Concerns]) were administered and repeated six months later. For two of the four outcome measures (Functional Well being and Breast Cancer Concerns), insightful disclosure played a crucial and significant role, the other two showed a trend toward significance (CESD and Physical well being). The three control variables, stages, years of cancer and level of participation all had effects on the outcomes, varying with the type of outcome measure. The findings, in this study, support Shaw et al. hypotheses. In their study, only one outcome measure, reduction of emotional distress was significant. Copyright © 2007 John Wiley & Sons, Ltd.