Miracle-dz/UniFAR-FTUs huggingface dataset:
Activity of trifluorothymidine against cytomegalovirus

Trifluorothymidine (TFT) was tested for antiviral activity against mouse cytomegalovirus (MCMV) and human cytomegalovirus (HCMV) in one-step replication assays. The TFT concentration required to reduce virus yield by 50% (ID50) was 0.22 microM for MCMV and 0.012 microM for HCMV. The antiviral activity of TFT against MCMV was reversed by addition of equimolar thymidine, and no antiviral activity was demonstrable in a host cell line lacking thymidine kinase. Thus, TFT's anti-MCMV activity is dependent on a host cell TK since this herpesvirus lacks thymidine kinase. A continuous subcutaneous infusion of TFT achieving a serum concentration of 1 microM failed to protect mice from lethal MCMV infection, perhaps because serum levels of thymidine were comparable to the drug level. Comparison of the ID50 against HCMV and the ID50 against human bone marrow progenitor cells resulted in an in vitro therapeutic ratio of 108, suggesting that TFT might offer some promise as a clinically useful anti-HCMV agent.
Temporal Transcriptional Response during Infection of Type II Alveolar Epithelial Cells with Francisella tularensis Live Vaccine Strain (LVS) Supports a General Host Suppression and Bacterial Uptake by Macropinocytosis*

Background: The mechanism of Francisella LVS entry into A549 cells is unknown. Results: Microarrays were performed at early infection time points, supported by phenotypic observations and inhibition experiments. Conclusion: Francisella LVS may enter A549 cells by macropinocytosis and quiets the host infection response. Significance: Francisella LVS induces significant host cell signaling at very early time points after the bacteria's interaction with the cell. Pneumonic tularemia is caused by inhalation of Francisella tularensis, one of the most infectious microbes known. We wanted to study the kinetics of the initial and early interactions between bacterium and host cells in the lung. To do this, we examined the infection of A549 airway epithelial cells with the live vaccine strain (LVS) of F. tularensis. A549 cells were infected and analyzed for global transcriptional response at multiple time points up to 16 h following infection. At 15 min and 2 h, a strong transcriptional response was observed including cytoskeletal rearrangement, intracellular transport, and interferon signaling. However, at later time points (6 and 16 h), very little differential gene expression was observed, indicating a general suppression of the host response consistent with other reported cell lines and murine tissues. Genes for macropinocytosis and actin/cytoskeleton rearrangement were highly up-regulated and common to the 15 min and 2 h time points, suggesting the use of this method for bacterial entry into cells. We demonstrate macropinocytosis through the uptake of FITC-dextran and amiloride inhibition of Francisella LVS uptake. Our results suggest that macropinocytosis is a potential mechanism of intracellular entry by LVS and that the host cell response is suppressed during the first 2–6 h of infection. These results suggest that the attenuated Francisella LVS induces significant host cell signaling at very early time points after the bacteria's interaction with the cell.
Radiotoxicity after iodine-131 therapy for thyroid cancer using the micronucleus assay.

UNLABELLED The purpose of the present study was to evaluate the degree of cytological radiation damage to lymphocytes after 131I therapy using the cytokinesis-blocked micronucleus assay. The chromosomal damage to lymphocytes induced by 131I in vivo should result in augmentation of the cells with micronuclei. METHODS We studied 25 patients with differentiated thyroid carcinoma who were treated with 3.7 GBq of 131I. Isolated lymphocytes collected from patients 1 wk after therapy were harvested and treated according to the cytokinesis-blocked method of Fenech and Morley. The micronucleus number of micronuclei per 500 binucleated cells were scored by visual inspection. As controls, lymphocytes from the same patients before therapy were also studied. In an in vitro study, lymphocytes from three patients at least 3 mo after therapy were exposed to doses varying from 0.25 to 1 Gy and studied with the same method. RESULTS The mean number (mean +/- s.d.) of micronuclei after treatment was significantly increased (p < 0.05) as compared to control subjects (15.7 +/- 2.7 vs. 5.4 +/- 1.4). Since there was an interval ranging from 6 to 20 mo (mean 11.8 mo) between the present and the last radioiodine therapy, no significant effect on the frequency of micronucleus with cumulative radiation exposure of 131I to lymphocytes was detected. Internal radiation absorbed doses estimated for 25 patients were 0.33 +/- 0.09 Gy in this external irradiation study. CONCLUSION The relatively low frequency of lymphocyte micronuclei induced by 131I in vivo and lack of significant effect on the frequency of lymphocyte micronuclei with cumulative 131I supported the contention that short-term nonstochastic damage of this therapy with 3.7 GBq of 131I in thyroid cancer patients is minimal and reversible.
Dynamics of regional brain activity in epilepsy: a cross-disciplinary study on both intracranial and scalp-recorded epileptic seizures

Objective. Recent cross-disciplinary literature suggests a dynamical analogy between earthquakes and epileptic seizures. This study extends the focus of inquiry for the applicability of models for earthquake dynamics to examine both scalp-recorded and intracranial electroencephalogram recordings related to epileptic seizures. Approach. First, we provide an updated definition of the electric event in terms of magnitude and we focus on the applicability of (i) a model for earthquake dynamics, rooted in a nonextensive Tsallis framework, (ii) the traditional Gutenberg and Richter law and (iii) an alternative method for the magnitude–frequency relation for earthquakes. Second, we apply spatiotemporal analysis in terms of nonextensive statistical physics and we further examine the behavior of the parameters included in the nonextensive formula for both types of electroencephalogram recordings under study. Main results. We confirm the previously observed power-law distribution, showing that the nonextensive formula can adequately describe the sequences of electric events included in both types of electroencephalogram recordings. We also show the intermittent behavior of the epileptic seizure cycle which is analogous to the earthquake cycles and we provide evidence of self-affinity of the regional electroencephalogram epileptic seizure activity. Significance. This study may provide a framework for the analysis and interpretation of epileptic brain activity and other biological phenomena with similar underlying dynamical mechanisms.
Estimating uncompensated care charges at rural hospital emergency departments.

CONTEXT Rural hospitals face multiple financial burdens. Due to federal law, emergency departments (ED) provide a gateway for uninsured and self-pay patients to gain access to treatment. It is unknown how much uncompensated care in rural hospitals is due to ED visits. PURPOSE To develop a national estimate of uncompensated care from patients utilizing the ED in rural hospitals. METHODS Clinical data from the National Hospital Ambulatory Medical Care Survey-ED (NHAMCS-ED) from 1999 and 2000 were linked to billing data from South Carolina. National estimates of utilization and charges were calculated, with rurality and self-pay status being the variables of focus. FINDINGS Applying South Carolina billing data to national clinical data yields a national estimate for 1999-2000 of nearly $441 billion in charges being generated through emergency departments, with self-pay patients representing 9.0% of total charges. Rural self-pay patients accounted for an estimated $3.5 billion in charges in 1999 and $5.3 billion in 2000. These charges may represent a total financial burden of more than $4 billion to rural hospitals. CONCLUSIONS Efforts should be made to reduce the uncompensated care burden on rural hospitals to ensure their viability. These efforts may include Medicaid/SCHIP expansions, FQHCs or RHCs, Critical Access Hospital Designation, or other indigent care programs that would reduce the need for self-pay patients to utilize EDs.
Comparsion analysis of data mining models applied to clinical research in traditional Chinese medicine.

OBJECTIVE To help researchers selecting appropriate data mining models to provide better evidence for the clinical practice of Traditional Chinese Medicine (TCM) diagnosis and therapy. METHODS Clinical issues based on data mining models were comprehensively summarized from four significant elements of the clinical studies: symptoms, symptom patterns, herbs, and efficacy. Existing problems were further generalized to determine the relevant factors of the performance of data mining models, e.g. data type, samples, parameters, variable labels. Combining these relevant factors, the TCM clinical data features were compared with regards to statistical characters and informatics properties. Data models were compared simultaneously from the view of applied conditions and suitable scopes. RESULTS The main application problems were the inconsistent data type and the small samples for the used data mining models, which caused the inappropriate results, even the mistake results. These features, i.e. advantages, disadvantages, satisfied data types, tasks of data mining, and the TCM issues, were summarized and compared. CONCLUSION By aiming at the special features of different data mining models, the clinical doctors could select the suitable data mining models to resolve the TCM problem.
Cutting Edge: Administration of Anti-CD40 Ligand and Donor Bone Marrow Leads to Hemopoietic Chimerism and Donor-Specific Tolerance Without Cytoreductive Conditioning1

Transplantation tolerance, defined as allograft acceptance by an immunocompetent recipient in the absence of long-term immunosuppression, has remained an elusive goal in clinical transplantation. Robust experimental tolerance induction strategies have in common methods to induce mixed hemopoietic chimerism. To date, however, chimerism induction across allogeneic barriers has required recipient conditioning with irradiation or cytoablative agents. In this paper we show that B6 recipients of fully allogeneic BALB/c skin grafts treated with repeated doses of donor bone marrow and anti-CD40 ligand (CD40L) develop durable (>300 days), readily detectable (6–12%) multilineage hemopoietic chimerism, indefinite allograft acceptance (>300 days), and donor-specific tolerance to secondary skin grafts. Analysis of the TCR repertoire of treated mice indicates that the underlying mechanisms of tolerance are in part mediated by deletion of donor-reactive T cells. These data demonstrate that durable hemopoietic chimerism and robust transplantation tolerance can be achieved without cytotoxic conditioning using a potentially clinically applicable regimen.
Toxicity of dietary methylmercury to fish: Derivation of ecologically meaningful threshold concentrations

Threshold concentrations associated with adverse effects of dietary exposure to methylmercury (MeHg) were derived from published results of laboratory studies on a variety of fish species. Adverse effects related to mortality were uncommon, whereas adverse effects related to growth occurred only at dietary MeHg concentrations exceeding 2.5 µg g−1 wet weight. Adverse effects on behavior of fish had a wide range of effective dietary concentrations, but generally occurred above 0.5 µg g−1 wet weight. In contrast, effects on reproduction and other subclinical endpoints occurred at dietary concentrations that were much lower (<0.2 µg g−1 wet wt). Field studies generally lack information on dietary MeHg exposure, yet available data indicate that comparable adverse effects have been observed in wild fish in environments corresponding to high and low MeHg contamination of food webs and are in agreement with the threshold concentrations derived here from laboratory studies. These thresholds indicate that while differences in species sensitivity to MeHg exposure appear considerable, chronic dietary exposure to low concentrations of MeHg may have significant adverse effects on wild fish populations but remain little studied compared to concentrations in mammals or birds. Environ. Toxicol. Chem. 2012; 31: 1536–1547. © 2012 SETAC
Comparison by electron microscopy of intracellular events and survival of Burkholderia pseudomallei in monocytes from normal subjects and patients with melioidosis.

INTRODUCTION Burkholderia pseudomallei (B. pseudomallei) has been shown to persist intracellularly in patients with melioidosis, until reactivated by decreasing immunocompetence. We have previously demonstrated by transmission electron microscopy, the internalisation of B. pseudomallei by human macrophages and the occurrence of phagosome-lysosome fusion. METHODS Phagocytosis and electron microscopy were used to compare the rate of phagosome-lysosome fusion and the intracellular survival of B. pseudomallei using monocytes obtained from five patients with melioidosis and five normal healthy adults. RESULTS Ingested bacilli were seen in various stages of degradation, with a few remaining viable within phagolysosomes, and the proliferation of these viable bacteria was observed. Phagocytosis of B. pseudomallei by normal macrophages was two-fold higher than uptake by the melioidosis macrophages (p-value is less than 0.001). Three times more phagolysosomes were present in the normal macrophages, indicating that fusion occurred slowly and inefficiently in the melioidosis macrophages (p-value is less than 0.001), resulting in higher number of organisms within the melioidosis macrophages (p-value is less than 0.001). Both variables were inversely related to each other. CONCLUSION Our observations suggest that phagolysosome fusion occurred slowly and inefficiently in monocytes of patients with melioidosis, leading to an increased number of intracellular organisms compared to monocytes obtained from healthy donors.
Efficacy and tolerability of duloxetine treatment in elderly patients with major depressive disorder and concurrent anxiety symptoms.

OBJECTIVE To compare the efficacy and tolerability of duloxetine 60mg/day versus placebo in treating elderly patients with major depressive disorder (MDD) and concurrent anxiety symptoms. METHODS Patients (>/=65) were randomized to eight weeks of treatment with duloxetine 60mg/day (n=207) or placebo (n=104). Anxiety measures were analyzed for all patients, by age (<75 and >/=75), and in patients having concurrent high anxiety (HAMD(17), item 10; Psychic Anxiety baseline score of 2, 3, or 4). Psychic Anxiety, Somatic Anxiety item 11, and the Anxiety/Somatization subscale were analyzed for all patients and subgroups by mean change from baseline to endpoint and repeated measures. Tolerability was assessed via treatment-emergent adverse events (TEAEs), and adverse events were reported as the reason for discontinuation. The analyses presented are primarily post hoc in nature. RESULTS Duloxetine produced significantly greater reductions than placebo in Psychic Anxiety (least-squares mean change: -0.62 vs. -0.18, p<0.001) and the Anxiety/Somatization subscale (-1.88 vs. -0.99, p=0.002). Repeated measures analyses showed separation between the treatment groups beginning at Week 1 for Psychic Anxiety and Week 4 for the Anxiety/Somatization subscale. Significant improvement occurred in the <75 and >/=75 age groups for Psychic Anxiety, but only the <75 group for the Anxiety/Somatization subscale. Duloxetine-treated patients with high anxiety showed significant improvement compared with placebo-treated patients on Psychic Anxiety, Anxiety/Somatization subscale, the 17-item Hamilton Depression Rating Scale (HAMD(17)) total score, and several other measures. Duloxetine and placebo had similar TEAE rates and discontinuation rates due to adverse events. CONCLUSION Duloxetine (60mg/day) was efficacious and tolerable in elderly patients with MDD and concurrent anxiety symptoms.
Evaluation of chemotherapy response in pediatric bone sarcomas by [F‐18]‐fluorodeoxy‐D‐glucose positron emission tomography

Response to neoadjuvant chemotherapy is a significant prognostic factor for osteosarcoma (OS) and the Ewing sarcoma family of tumors (ESFT). Conventional radiographic imaging does not discriminate between responding and nonresponding osseous tumors. [F‐18]‐fluorodeoxy‐D‐glucose (FDG) positron emission tomography (PET) is a noninvasive imaging modality that accurately predicts histopathologic response in patients with various malignancies. To describe the FDG PET imaging characteristics and to determine the correlation between FDG PET imaging and chemotherapy response in children with bone sarcomas, we reviewed our single institution experience.
Hypergravity does not affect testicular function.

BACKGROUND A previous study revealed that exposure of rats to microgravity for 14 d on Cosmos 2044 reduced production of testosterone by > 80%, although spermatogenesis remained essentially normal. METHODS To ascertain if testicular function was altered in hypergravity, 60-d-old rats were randomly assigned to 2 groups (10 per group) and subjected to 14 d of centrifugation to expose them to a total of 2G, or held at unit gravity in similar cages without centrifugation (control). RESULTS After 14 d, body weight of 2G rats was essentially unchanged, whereas that of control rats had increased; 310 vs. 377 g (p < 0.05). Testes weight, production and secretion of testosterone, diameters of seminiferous tubules and their lumina, data from subjective evaluation of spermatogenesis, and counts of homogenization-resistant spermatids all were similar for 2G and control rats. CONCLUSION It was concluded that exposure of male rats to 2G for 14 d had no major effect on testicular function whereas, based on earlier studies, exposure to microgravity (< 10(-3) x gravity) for 11-14 d suppressed production of testosterone by Leydig cells and reduced concentrations of anabolic steroids available to peripheral tissues.
New insights into Eastern Beringian mortuary behavior: A terminal Pleistocene double infant burial at Upward Sun River

Significance Two interred infants with associated grave goods and a third cremated child represent the earliest known human remains from the North American subarctic, and they provide evidence for novel mortuary behaviors at the end of the last Ice Age. Two bifacial points with decorated foreshafts represent hafted projectiles, confirming earlier conclusions about Paleoindian weapon system form and function. Excellent faunal and other contextual data indicate broad-spectrum foraging behaviors. Here we report on the discovery of two infant burials dating to ∼11,500 calibrated years (cal) B.P. at the Upward Sun River site in central Alaska. The infants were interred in a pit feature with associated organic and lithic grave goods, including the earliest known North American hafted bifaces with decorated antler foreshafts. Skeletal and dental analyses indicate that Individual 1 died shortly after birth and Individual 2 was a late-term fetus, making these the youngest-aged late Pleistocene individuals known for the Americas and the only known prenate, offering, to our knowledge, the first opportunity to explore mortuary treatment of the youngest members of a terminal Pleistocene North American population. This burial was situated ∼40 cm directly below a cremated 3-y-old child previously discovered in association with a central hearth of a residential feature. The burial and cremation are contemporaneous, and differences in body orientation, treatment, and associated grave goods within a single feature and evidence for residential occupation between burial episodes indicate novel mortuary behaviors. The human remains, grave goods, and associated fauna provide rare direct data on organic technology, economy, seasonality of residential occupations, and infant/child mortality of terminal Pleistocene Beringians.
Shoulder muscle isometric strength and active range of motion in patients with frozen shoulder syndrome after manipulation under anesthesia.

BACKGROUND AND OBJECTIVE Frozen shoulder syndrome (FSS) causes pain and restriction of movement in the shoulder. The aim was to assess changes in shoulder muscle isometric maximal voluntary contraction (MVC) force and active range of motion (AROM) in patients with frozen shoulder syndrome (FSS) after manipulation under general anesthesia (MUA). MATERIAL AND METHODS In total, 18 patients with FSS (9 women and 9 men) with a mean age of 53.6 years (SD, 9.7) participated in this study. MVC force of shoulder flexors, adductors, and internal and external rotators was measured by a handheld dynamometer. AROM in the same directions was measured goniometrically. The patients were screened according to the intensity of pain by day and at night. The data were collected before MUA and 1 and 6 months after MUA. A significant reduction in MVC force and AROM was noted before MUA in the involved extremity as compared with the uninvolved extremity (P<0.05). These parameters for the involved extremity were significantly increased 1 month after MUA (P<0.05). However, 6 months after MUA, MVC force and AROM did not differ significantly compared with the uninvolved extremity (P>0.05), whereas AROM of flexion and external rotation remained significantly reduced (P<0.05). A significant reduction in shoulder pain by day and at night was recorded 1 and 6 months after MUA (P<0.05). CONCLUSIONS In the patients with FSS, the fastest improvement of MVC force and AROM occurred following the first month after MUA. However, 6 months after MUA, shoulder muscle MVC force for the involved extremity did not differ significantly as compared with the uninvolved extremity, whereas the shoulder AROM in flexion and external rotation remained lower.
ENDOTOXIN‐ AND CYTOKINE‐MEDIATED EFFECTS ON LIVER CELL PROLIFERATION AND LIPID METABOLISM AFTER PARTIAL HEPATECTOMY: A STUDY WITH RECOMBINANT N‐TERMINAL BACTERICIDAL/PERMEABILITY‐INCREASING PROTEIN AND INTERLEUKIN‐1 RECEPTOR ANTAGONIST

This study was performed to clarify the mechanisms underlying post‐resection changes in liver cell proliferation and metabolism. To assess the role of gut‐derived endotoxaemia and endogenous cytokines in these changes, the effects of peri‐operative treatment with either the lipopolysaccharide‐neutralizing bactericidal/permeability‐increasing protein or interleukin‐1 receptor antagonist were investigated at 24 h after two‐thirds hepatectomy in rats. Peri‐operative treatment with either agent caused enhanced expression of proliferating cell nuclear antigen (PCNA) and reduced lipid accumulation. Activity of the hexose monophosphate shunt was significantly decreased after partial hepatectomy and restored by interleukin‐1 receptor antagonist only. After partial hepatectomy, bile canalicular alkaline phosphatase activity was significantly increased in pericentral zones and redistributed to both bile canalicular and sinusoidal membranes of hepatocytes. These effects were not significantly influenced by either treatment. It is concluded that endotoxin restricts liver cell proliferation and leads to lipid accumulation following partial hepatectomy, and that interleukin‐1 is a principal mediator in these processes. Furthermore, interleukin‐1 mediates a repression of the pentose phosphate pathway. These changes may be of significance with respect to liver function, at least in the early phase after partial hepatectomy.