Miracle-dz/UniFAR-FTUs huggingface dataset:
Radial arm maze performance of rats following repeated low level microwave radiation exposure

We examined the possibility of changes in “working” memory of rats following whole body exposure to microwave (MW) radiation. During each of 10 days, we exposed rats within circularly polarized waveguides for 45 min to 2450 MHz fields at whole body SARs of 0.6 W/kg (2 μs pulses, 500 pps), followed by testing in a 12 arm, radial arm maze (RAM). Rats received a preexposure injection of one of three psychoactive compounds or saline, to determine whether a compound would interact with MW exposure to affect performance in the maze. Error rate, i.e., reentry into arms already visited, and time to criterion data for 10 consecutive days of testing were analyzed by a three way analysis of variance (ANOVA) using main effects of “exposure” and “drug” and a repeated factor of “test day. ” Our alpha limit for significance was P < . 05. Analyzes of error rates revealed no significant exposure effect, no significant drug effect and no significant interaction between the two main factors. There was a significant difference in test days, as expected, with repeated test‐trial days, which indicates that learning was accomplished. There was no significant interaction of test day and the other two factors. The results of our analyzes of time to criterion data included no significant exposure effect, a significant drug effect, a significant test day effect, and a significant interaction between drug and test day factors. Post hoc analyzes of the drug factor revealed that rats treated with either physostigmine or nalrexone hydrochloride, took significantly longer to complete the maze task than rats pretreated with saline or with naloxone methodide. We conclude that there is no evidence from the current study that exposure to of MW radiation under parameters examined caused decrements in the ability of rats to learn the spatial memory task. Bioelectromagnetics 25:49–57, 2004. Published 2003 Wiley‐Liss, Inc.
Altered microstructure integrity of the amygdala in schizophrenia: a bimodal MRI and DWI study

Background The amygdala plays a central role in the fronto-limbic network involved in the processing of emotions. Structural and functional abnormalities of the amygdala have recently been found in schizophrenia, although there are still contradictory results about its reduced or preserved volumes. Method In order to address these contradictory findings and to further elucidate the possibly underlying pathophysiological process of the amygdala, we employed structural magnetic resonance imaging (MRI) and diffusion weighted imaging (DWI), exploring amygdalar volume and microstructural changes in 69 patients with schizophrenia and 72 matched healthy subjects, relating these indices to psychopathological measures. Results Measuring water diffusivity, the apparent diffusion coefficients (ADCs) for the right amygdala were found to be significantly greater in patients with schizophrenia compared with healthy controls, with a trend for abnormally reduced volumes. Also, significant correlations between mood symptoms and amygdalar volumes were found in schizophrenia. Conclusions We therefore provide evidence that schizophrenia is associated with disrupted tissue organization of the right amygdala, despite partially preserved size, which may ultimately lead to abnormal emotional processing in schizophrenia. This result confirms the major role of the amygdala in the pathophysiology of schizophrenia and is discussed with respect to amygdalar structural and functional abnormalities found in patients suffering from this illness.
Cardiovascular and Cerebrovascular Aging – New Mechanisms and Insights Dantrolene suppresses spontaneous Ca 2 release without altering excitation-contraction coupling in cardiomyocytes of aged mice

Domeier TL, Roberts CJ, Gibson AK, Hanft LM, McDonald KS, Segal SS. Dantrolene suppresses spontaneous Ca release without altering excitation-contraction coupling in cardiomyocytes of aged mice. Am J Physiol Heart Circ Physiol 307: H818–H829, 2014. First published July 18, 2014; doi:10.1152/ajpheart.00287. 2014. —Cardiac dysfunction in the aged heart reflects abnormalities in cardiomyocyte Ca homeostasis including altered Ca cycling through the sarcoplasmic reticulum (SR). The ryanodine receptor antagonist dantrolene exerts antiarrhythmic effects by preventing spontaneous diastolic Ca release from the SR. We tested the hypothesis that dantrolene prevents spontaneous Ca release without altering excitation-contraction coupling in aged myocardium. Left ventricular cardiomyocytes isolated from young (3 to 4 mo) and aged (24–26 mo) C57BL/6 mice were loaded with the Ca indicator fluo-4. Amplitudes of action potential-induced Ca transients at 1-Hz pacing were similar between young and aged mice, yet cell shortening was impaired in aged mice. Isoproterenol (1 M) increased Ca transient amplitude and cell shortening to identical levels in young and aged; dantrolene (1 M) had no effect on Ca transients or cell shortening during pacing. Under Ca overload conditions induced with 10 mM extracellular Ca concentration, spontaneous Ca waves were of diminished amplitude and associated with lower SR Ca content in aged versus young mice. Despite no effect in young mice, dantrolene increased SR Ca content and Ca wave amplitude in aged mice. In the presence of isoproterenol following rest from 1-Hz pacing, Ca spark frequency was elevated in aged mice, yet the time to spontaneous Ca wave was similar between young and aged mice; dantrolene decreased Ca spark frequency and prolonged the time to Ca wave onset in aged mice with no effect in young mice. Thus dantrolene attenuates diastolic Ca release in the aged murine heart that may prove useful in preventing cardiac dysfunction.
Early intervention service eligibility: implications of using the Peabody Developmental Motor Scales.

OBJECTIVE Occupational therapists, as members of early intervention (El) teams, are responsible for contributing to equitable decision making regarding service eligibility. Because the two editions of the Peabody Developmental Motor Scales (PDMS) are often used in this process, it is important to study these measures. Therefore, the purpose of this study was to examine the implications of using different editions of the PDMS (PDMS versus PDMS-2) and different types of scores (standard deviation versus percent delay) when determining children's eligibility for El. METHOD With testing order counterbalanced, 30 candidates for El evaluation, between 11 months and 34 months corrected age, were tested using both the PDMS and the PDMS-2. RESULTS Support for El eligibility often differed depending on the edition of the PDMS used and the type of score used. When the PDMS was used, as opposed to the PDMS-2, disagreements occurred 23% to 43% of the time. For all disagreements, scores on the PDMS supported El eligibility, whereas scores on the PDMS-2 did not. When support for service eligibility was compared using percent delay scores versus standard deviation scores, disagreements occurred more often for the PDMS (Gross Motor: 17%; Fine Motor: 23%) than for the PDMS-2 (Gross Motor: 7%; Fine Motor: 3%). CONCLUSIONS It is important that occupational therapists within a facility, and ideally within a state, identify a single test edition to use as part of the process for determining El eligibility. Also, if standard scores and percent delay scores point to conflicting decisions (eligibility vs. noneligibility), further evaluation and greater reliance on clinical judgment are advised.
Protocol biopsies after kidney transplantation

Numerous studies have investigated features of allograft injury in renal biopsies obtained in stable kidney transplants. Evaluation of protocol biopsies has revealed a considerably high prevalence of subclinical acute rejection (SAR) and chronic allograft nephropathy (CAN) already in early phases after transplantation. The meanwhile well‐established association of SAR and CAN in protocol biopsy with long‐term allograft failure and the finding of superior allograft outcome after treatment of SAR in a randomized prospective study may point to clinical relevance of this procedure. In this review, potential benefits and risks associated with kidney allograft biopsy in stable renal transplant recipients are discussed.
Progranulin promotes tumour necrosis factor‐induced proliferation of suppressive mouse CD4+ Foxp3+ regulatory T cells

Progranulin (PGRN) is a pleiotropic growth factor with immunosuppressive properties. Recently, it was reported that PGRN was an antagonist of tumour necrosis factor (TNF) receptors, preferentially for TNFR2. However, we and others showed that TNF–TNFR2 interaction was critical for the activation and expansion of functional CD4+ Foxp3+ regulatory T (Treg) cells. We therefore examined the effect of PGRN on the proliferation of naturally occurring murine suppressive Treg cells induced by TNF. Consistent with our previous reports, TNF overcame the hyporesponsiveness of highly purified Treg cells to T‐cell receptor stimulation. Furthermore, in the presence of interleukin‐2, TNF preferentially stimulated proliferation of Treg cells contained in unfractionated CD4 cells. These effects of TNF on suppressive Treg cells were markedly increased by exogenous PGRN. TNF and TNFR2 interactions are required for this effect of PGRN, because the PGRN by itself did not stimulate Treg cell proliferation. The effect of PGRN on Treg cells was abrogated by antibody against TNFR2, and Treg cells deficient in TNFR2 also failed to respond to PGRN. Furthermore, PGRN also enhanced the proliferative responses of effector T cells to TNF, but to a lesser extent than that of Treg cells, presumably caused by the different levels of TNFR2 expression on these two subsets of CD4 cells. Hence, our data clearly show that PGRN promotes, rather than inhibits, the functional consequence of TNF–TNFR2 interaction on Treg cells.
Multiple Myeloma Patients Have a Specific Serum Metabolomic Profile That Changes after Achieving Complete Remission

Purpose: Multiple myeloma remains an incurable disease. New approaches to develop better tools for improving patient prognostication and monitoring treatment efficacy are very much needed. In this study, we aimed to evaluate the potential of metabolomics by 1H-NMR to provide information on metabolic profiles that could be useful in the management of multiple myeloma. Experimental Design: Serum samples were collected from multiple myeloma patients at the time of diagnosis and after achieving complete remission. A matched control set of samples was also included in the study. The 1H-NMR measurements used to obtain the metabolic profile for each patient were followed by the application of univariate and multivariate statistical analyses to determine significant differences. Results: Metabolic profiles of multiple myeloma patients at diagnosis exhibited higher levels of isoleucine, arginine, acetate, phenylalanine, and tyrosine, and decreased levels of 3-hydroxybutyrate, lysine, glutamine, and some lipids compared with the control set. A similar analysis conducted in multiple myeloma patients after achieving complete remission indicated that some of the metabolic changes (i.e., glutamine, cholesterol, lysine) observed at diagnosis displayed a variation in the opposite direction upon responding to treatment, thus contributing to multiple myeloma patients having a closer metabolic profile to those of healthy individuals after the disappearance of major disease manifestations. Conclusions: The results highlight the potential of metabolic profiles obtained by 1H-NMR in identifying multiple myeloma biomarkers that may be useful to objectively discriminate individuals with and without multiple myeloma, and monitor response to treatment. Clin Cancer Res; 19(17); 4770–9. ©2013 AACR.
Accepted Manuscript A Model to Predict the Severity of Acute Pancreatitis Based on Serum Level of Amylase and Body Mass Index

Background & Aims: Most patients with acute pancreatitis (AP) develop mild disease but up to 20% develop severe disease. Many clinicians monitor serum levels of amylase and lipase in an attempt to predict the disease course, but this strategy has not been recommended by practice guidelines. We performed a retrospective analysis to determine whether the percent changes in amylase and lipase were associated with the severity of disease that developed in patients with AP. Methods: We analyzed data collected from 182 consecutive patients with AP (21 with severe AP) admitted at the Cleveland Clinic from January 2008 through May 2010 (discover cohort). The association between 11 different factors and severity of AP were assessed by univariable analysis; multivariable models were explored through stepwise selection regression. The percent change in serum level of amylase was calculated as follows: [(amylase day1 – amylase day2)/amylase day1 * 100]. The percent change in amylase and body mass index (BMI) were combined to generate a z-score [z = −5.9 + (0.14*BMI) + (0.01* percent change in amylase)], which was converted into a probability distribution called the change in amylase and BMI (CAB) score. The CAB score was validated using the AP database at the University of Pittsburgh Medical Center (140 patients, 35 with severe AP); we calculated p-scores for each patient and estimated the area under the receiver operating characteristics (AUROC) curve values. Results: Univariable analysis identified percent change in serum level of amylase and other factors to be significantly associated with severity of AP ( P=.017). The CAB score was best at identifying patients who developed severe AP, with an AUROC values of 0.79 in the discovery cohort (95% confidence interval, 0.71−0.87) and 0.731 (95% confidence interval, 0.61 −0.84) in the validation cohort Conclusion: We developed a model to identify patients most likely to develop severe AP based on percent changes in serum level of amylase during the first 2 days after admission to the hospital and BMI.
Systematic review evaluating the timing of thoracic radiation therapy in combined modality therapy for limited-stage small-cell lung cancer.

PURPOSE We employed meta-analytic techniques to evaluate early (E) versus late (L) timing of thoracic radiation therapy (RT) in limited-stage small-cell lung cancer (LS-SCLC). In addition, we assessed the impact of radiation fractionation and chemotherapeutic regimen on timing. METHODS Randomized trials published after 1985 addressing timing of RT relative to chemotherapy in LS-SCLC were included. Trials were analyzed by risk ratio (RR), risk difference, and number-needed-to-treat methods. RESULTS Overall survival (OS) RRs for all studies were 1.17 at 2 years (95% CI, 1.02 to 1.35; P = .03) and 1.13 at 3 years (95% CI, 0.92 to 1.39; P = .2), indicating a significantly increased 2-year survival for ERT versus LRT patients and suggestive of a similar trend at 3 years. Subset analysis of studies using hyperfractionated RT revealed OS RR for ERT versus LRT of 1.44 (95% CI, 1.17 to 1.77; P = .001) and 1.39 (95% CI, 1.02 to 1.90; P = .04) at 2 and 3 years, respectively, indicating a survival benefit of ERT versus LRT. Studies using once-daily fractionation showed no difference in 2- and 3-year OS RRs for ERT compared with LRT. Studies using platinum-based chemotherapy had OS RRs of 1.30 (95% CI, 1.10 to 1.53; P = .002) and 1.35 (95% CI, 1.07 to 1.70; P = .01) at 2 and 3 years, respectively, favoring ERT. Studies using nonplatinum-based chemotherapy regimens had nonsignificant differences in OS. CONCLUSION A small but significant improvement in 2-year OS for ERT versus LRT in LS-SCLC was observed, similar to the benefit of adding RT to chemotherapy or prophylactic cranial irradiation. A greater difference was evident for hyperfractionated RT and platinum-based chemotherapy.
MicroRNA‐455 suppresses non‐small cell lung cancer through targeting ZEB1

MicroRNA‐455 (miRNA‐455), which is downregulated in human cancer, potently mediates the multiple steps of carcinogenesis. However, the role of miR‐455 in non‐small cell lung cancer (NSCLC) carcinogenesis remains unclear. In present study, we determined the mature miRNA‐455 expression in NSCLC tissues and cells by real‐time PCR. Follow‐up studies examined the effects of a miR‐455 mimic (gain of function) on cell proliferation, migration, and invasion. Our data indicate that miR‐455 was significantly down‐regulated in NSCLC cell lines and tissues. In functional assays, overexpression of miR‐455 suppressed the proliferation, migration, and invasion of NSCLC cell lines. Data from reporter assays showed that miR‐455 directly binds to 3′UTR of ZEB1 and suppresses the endogenous level of ZEB1 protein expression. Furthermore, overexpression of ZEB1 reverses miR‐455‐suppressed malignant phenotype of NSCLC cells. Moreover, we found that upregulation of ZEB1 expression is inversely associated with miR‐455 expression in NSCLC tissues. Taken together, miR‐455 as an anti‐oncogene in non‐small cell lung cancer through up‐regulation of ZEB1 and serve as a potential therapeutic target in NSCLC.
Outcomes and Predictors of Mortality and Stroke after On-Pump and Off-Pump Coronary Artery Bypass Surgery in Octogenarians

Objective Octogenarians, as the fastest growing stratum of the population and with the highest prevalence of coronary artery disease, are being increasingly referred for coronary artery bypass grafting (CABG). The general perception is that the presence of comorbidities and the propensity for neurological injury expose them to a higher risk for mortality and morbidity after conventional on-pump CABG, and therefore, off-pump CABG should be preferentially offered to octogenarians to improve outcomes. This study evaluates the in-hospital outcomes and predictors of mortality and stroke in octogenarians undergoing on- and off-pump CABG at our institution. Methods From January 2000 to December 2010, a total of 290 octogenarians underwent off-pump (n = 217) and on-pump (n = 73) CABG. Their data were prospectively entered into the cardiac surgery database (Patients Analysis & Tracking System; Dendrite Clinical Systems, Ltd, Oxford, England, United Kingdom) and analyzed retrospectively. Outcome measures included in-hospital mortality, major complications, and length of stay. Multivariate analysis was performed to identify predictors of combined outcome of in-hospital mortality and stroke. Results The mean ± SD age of the patients was 82 ± 2.0 years. Preoperative demographics were similar for the on-pump and off-pump groups. The patients who underwent off-pump CABG had a lower number of distal anastomoses performed compared with the patients who underwent on-pump CABG [mean difference, 0.2; 95% confidence interval (CI), 0.02–0.4; P = 0.03]. However, the ratio of grafts (received/needed) was the same in both groups. In-hospital mortality for the entire cohort was 7.2%, with no significant difference between the groups for death (6.0% vs 11.0%; P = 0.08), stroke (2.8% vs 2.8%; P = 1.0), other major complications, and length of hospital stay. Independent predictors of combined outcome identified from the multiple logistic model included heart failure [odds ratio (OR), 4.4; 95% CI, 1.5–13.0; P = 0.008], diabetes (OR, 2.6; 95% CI, 1.0–6.0; P = 0.046), nitrate infusion (OR, 2.9; 95% CI, 1.1–8.0; P = 0.04), postoperative renal failure requiring hemofiltration (OR, 8.6; 95% CI, 3.5–21.1; P < 0.001), and postoperative ventricular arrhythmias (OR, 7.3; 95% CI, 1.9–27.8; P = 0.009). Conclusions Both on-pump and off-pump CABG are reasonable revascularization strategies in octogenarians. Careful patient selection and individualized treatment decisions can minimize postoperative mortality and morbidity in octogenarians undergoing on- and off-pump CABG.
Carbon assimilation pathways during growth of Pseudomonas AM1 on methylamine and Pseudomonas MS on methylamine and trimethylsulphonium salts.

SUMMARY: A study was made of the incorporation of carbon from [14C]methylamine by cultures of Pseudomonas AMI growing on methylamine. The distribution of radioactivity within the non-volatile constituents of the ethanol-soluble fractions of the bacteria, after incubation for periods of up to 38 s, was analysed by chromato-graphy and autoradiography. Most of the radioactivity fixed at the earliest times of sampling appeared in serine, phosphorylated compounds and malate. These results contrasted with previous studies of the incorporation of labelled growth substrates by cultures of Pseudomonas MS growing on methylamine or trimethyl-sulphonium salts and correlated with the specific activities of hydroxypyruvate reductase, phosphoenolpyruvate carboxylase, N-methyl glutamate synthetase and γ-glutamylmethylamide synthetase in bacterial extracts. No hydroxypyruvate reductase was detectable in extracts of Pseudomonas MS grown either on methylamine or on trimethylsulphonium nitrate. The assimilation pathway for methylamine in Pseudomonas AMI appears essentially the same as that for methanol and different from that in Pseudomonas MS.
Periapical status and quality of root fillings and coronal restorations in a Danish population.

AIM The aim of this study was to investigate the quality of endodontic and coronal restorations and the association with periapical status in a Danish population. METHODOLOGY A total of 614 randomly selected individuals (20-60+ years of age) from Aarhus County had a full-mouth radiographic examination. The quality of endodontic and coronal restorations and the periapical status of endodontically treated teeth were assessed by radiographic criteria. Root fillings were categorized as 'adequate' or 'inadequate' with regard to root filling length and lateral seal. Coronal restorations were categorized into 'adequate' and 'inadequate', defined by the absence or presence of radiographic signs of overhangs or open margins. Results were analysed statistically using the chi-squared test. RESULTS The total number of endodontically treated teeth was 773, and 52.3% had apical periodontitis (AP). Root-filled teeth with an adequate lateral seal had a lower incidence of AP than teeth with an inadequate seal (44.3% vs. 57.8%), and teeth with an adequate root filling length were associated with a better periapical status than teeth with inadequate length of the root filling (42.0% vs. 67.6%). Similarly, adequate coronal restorations were associated with better periapical status than inadequate restorations (48.0% vs. 63.9%). When both root filling and coronal restoration quality were assessed, the incidence of AP ranged from 31.2% (optimal quality) to 78.3% (all parameters scored as inadequate). CONCLUSIONS Inadequate root canal and coronal restorations were associated with an increased incidence of AP.
Minimal Residual Disease in Multiple Myeloma: Current Landscape and Future Applications With Immunotherapeutic Approaches

The basic principle that deeper therapeutic responses lead to better clinical outcomes in cancer has emerged technologies capable of detecting rare residual tumor cells. The need for ultra-sensitive approaches for minimal residual disease (MRD) detection is particularly evident in Multiple Myeloma (MM), where patients will ultimately relapse despite the achievement of complete remission, which is commonplace due to remarkable therapeutic advances. Consequently, current response criteria on MM have been amended based on MRD status and MRD negativity is now considered the most dominant prognostic factor and the most valuable indicator for a subsequent relapse. However, there are particular limitations and several aspects for MRD assessment that remain open. This review summarizes current data on MRD in the clinical management of MM, highlights open issues and discusses the challenges and the endless opportunities arising for both patients and clinicians. Furthermore, it focuses on the current status of MRD in clinical trials, its dynamics in addressing debatable aspects in the clinical handling and its potential role as the prevailing factor for future MRD-driven tailored therapies.