Miracle-dz/UniFAR-FTUs huggingface dataset:
Toxicity of Subacute Intravenous Manganese Chloride Administration in Beagle Dogs

Manganese (Mn), a naturally occurring essential trace element, is currently being used as a metal complex for pharmaceutical and magnetic resonance imaging agents. Despite its popularity in these practices, minimal attention has focused on possible toxicity of released free Mn ions, which could occur if these agents decomplexed. There is especially limited information available regarding acute toxicity of Mn in dogs. In this study, we performed an in-depth evaluation of acute toxicologic potential of manganese chloride (MnCl2) when administered as a 4-hr/day intravenous infusion to male beagle dogs. The dose of MnCl2 used (16 mg/kg/day) was equivalent to approximately 3-5 times the daily dose of Mn typically administered in some of the Mn-complexed agents. All routine toxicologic endpoints were evaluated, including cardiovascular parameters. This dosing regimen resulted in the death or moribund sacrifice of all the animals within 4 days of initiation of treatment. Clinical evidence of toxicity included loss of appetite, reduction in blood pressure with reflex tachycardia, and a marked increase in liver enzymes, beginning with the first dose and increasing in severity with successive doses. Gross and histopathologic evaluations confirmed severe hepatotoxicity, which was characterized by massive hepatocellular necrosis, periportal hemorrhages, and mild biliary epithelial hyperplasia. These results indicate that acute treatment of beagle dogs with MnCl2 causes severe hepatotoxicity and hypotension with reflex tachycardia and suggest that dogs are very sensitive to toxic effects of Mn.
Behavior of Mycobacterium leprae in Human Macrophages In Vitro

Attempts have been made to cultivate Mycobacterium leprae in human macrophages in vitro. In 27 out of 55 experiments a two- to ninefold increase (mean 2.31 ± 1.46) in acid-fast organisms were observed over a period of 1.5 to 3 months of cultivation. No such increase was observed with heat-killed bacilli (mean fold increase 0.88 ± 0.19). Macrophages were necessary for obtaining increases. No multiplication was observed on artificial media. A close correlation between increases of acid-fast organisms and changes in viability as determined by the morphology of the bacilli (morphologic index) was found. The increases in acid-fast organisms could be inhibited by anti-leprosy drugs. It is concluded that multiplication of M. leprae may take place inside human macrophages in vitro. Multiplication appears not to be dependent on whether the macrophages are derived from lepromatous or tuberculoid patients or healthy individuals. Moreover, multiplication took place both at 33 and 37 C. The applicability of this method is at present limited by the restricted survival of human macrophages in vitro.
Distribution of PCDDs/PCDFs and Co-PCBs in Human Maternal Blood, Cord Blood, Placenta, Milk, and Adipose Tissue: Dioxins Showing High Toxic Equivalency Factor Accumulate in the Placenta

To assess levels of dioxin background contamination and transfer of dioxins from mothers to unborn children and infants, concentrations of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and coplanar-polychlorinated biphenyls (Co-PCBs) were measured in human samples from expectant and nursing mothers living in Nara, Japan. The average toxic equivalency quantities (TEQs) of PCDDs/PCDFs and Co-PCBs from circulating maternal blood, cord blood, placenta, milk taken 3–10 d after delivery, milk taken one month after delivery, and adipose tissue were 26 and 9.3, 15 and 2.3, 31 and 1.2, 16 and 5.4, 18 and 8.8, and 16 and 7.7 pg-TEQ/g-fat, respectively. Among the various PCDD/PCDF congeners, 1,2,3,7,8-PeCDD and 2,3,4,7,8-PeCDF contributed most heavily to the TEQs of all maternal samples. Among the various Co-PCB congeners, 3,3′,4,4′,5-PeCB (#126), 2,3,3′,4,4′,5-HxCB (#156), and 2,3′,4,4′,5-PeCB (#118) contributed most heavily to the TEQs of all maternal samples. But, the concentrations and relative percentages of congeners differed among the various samples, suggesting that congeners showing high toxic equivalency factor accumulate in the placenta.
Impact of Family Efficacy Beliefs on Quality of Family Functioning and Satisfaction with Family Life

The present study tested with 142 families a structural model of the interplay of perceived dyadic and collective forms of efficacy within the interdependent family system, and how these different forms of efficacy are structurally related to quality of family functioning and satisfaction with family life. Dyadic parent-child efficacy, dyadic spousal efficacy, and filial efficacy were linked to family satisfaction through the mediating impact of collective family efficacy. A high sense of collective family efficacy was accompanied by open family communication and candid disclosure by adolescents of their activities outside the home. Collective family efficacy contributed to parents' and adolescents' satisfaction with their family life both directly and through its impact on quality of family functioning. An alternative structural model in which quality of family functioning affects the different forms of perceived family efficacy and family satisfaction provided a poorer fit to the data.
Floor plate-derived neuropilin-2 functions as a secreted semaphorin sink to facilitate commissural axon midline crossing

Secreted semaphorins signal through neuropilin-2/plexin-A1 receptor complexes on post-crossing commissural axons to mediate floor plate repulsion in the mouse spinal cord. Hernandez-Enriquez et al. show that floor plate-derived neuropilin-2 is developmentally regulated, functioning as a molecular sink to sequester semaphorins, preventing premature repulsion of precrossing axons prior to subsequent down-regulation, and allowing for semaphorin-mediated repulsion of post-crossing axons.
Amygdala–midbrain connectivity indicates a role for the mammalian parental care system in human altruism

Costly altruism benefitting a stranger is a rare but evolutionarily conserved phenomenon. This behaviour may be supported by limbic and midbrain circuitry that supports mammalian caregiving. In rodents, reciprocal connections between the amygdala and the midbrain periaqueductal grey (PAG) are critical for generating protective responses toward vulnerable and distressed offspring. We used functional and structural magnetic resonance imaging to explore whether these regions play a role in supporting costly altruism in humans. We recruited a rare population of altruists, all of whom had donated a kidney to a stranger, and measured activity and functional connectivity of the amygdala and PAG as altruists and matched controls responded to care-eliciting scenarios. When these scenarios were coupled with pre-attentive distress cues, altruists' sympathy corresponded to greater activity in the left amygdala and PAG, and functional connectivity analyses revealed increased coupling between these regions in altruists during this epoch. We also found that altruists exhibited greater fractional anisotropy within the left amygdala–PAG white matter tract. These results, coupled with previous evidence of altruists' increased amygdala-linked sensitivity to distress, are consistent with costly altruism resulting from enhanced care-oriented responses to vulnerability and distress that are supported by recruitment of circuitry that supports mammalian parental care.
A prospective study of cholesterol, apolipoproteins, and the risk of myocardial infarction.

BACKGROUND The independent contributions of subfractions of high-density lipoprotein (HDL) cholesterol (HDL2 and HDL3) and apolipoproteins in predicting the risk of myocardial infarction are unclear. Prospective data are sparse, but HDL2 is widely believed to be a more important predictor than HDL3. METHODS Blood samples were collected at base line from 14,916 men (ages, 40 to 84 years) who were participants in the Physicians' Health Study. After five years of follow-up, plasma samples from 246 men with new myocardial infarction (case subjects) were analyzed together with specimens from 246 men matched to them for age and smoking status who had not had a myocardial infarction. RESULTS The levels of total cholesterol and apolipoprotein B-100 were significantly associated with an increased risk of myocardial infarction (data on levels of low-density lipoprotein cholesterol were unavailable). Both HDL cholesterol and HDL2 levels were associated with a substantially decreased risk of myocardial infarction, but the HDL3 level was the strongest predictor; the relative risk was 0.3 (95 percent confidence interval, 0.2 to 0.6) for those in the fifth of the group with the highest HDL3 levels, as compared with the fifth with the lowest levels. The benefit of a higher HDL cholesterol level was most pronounced among those with lower total cholesterol levels. Levels of apolipoprotein A-I and apolipoprotein A-II were also associated with decreased risk. However, the levels of HDL subfractions and apolipoproteins did not add significantly to the value of a multivariate model that included the ratio of total to HDL cholesterol in predicting myocardial infarction, whereas that ratio remained a significant independent predictor of risk. After adjustment for other risk factors, a change of one unit in the ratio of total to HDL cholesterol was associated with a 53 percent change in risk (95 percent confidence interval, 26 percent to 85 percent). CONCLUSIONS This study underscores the importance of HDL cholesterol in predicting the risk of myocardial infarction and demonstrates protective effects of both the HDL3 and HDL2 subfractions of HDL cholesterol. We found little or no predictive value for the levels of apolipoproteins A-I, A-II, and B or HDL subfractions after conventional risk factors and the ratio of total to HDL cholesterol were considered.
Follicular Fluid or Serum Level of Inhibin-B: Which One is an Effective Marker of Follicular Development in IVF Patients?

Materials and Methods: This prospective study was performed on 70 patients undergoing controlled ovarian hyperstimulation and followed by the IVF Department between February 2009-June 2009. Age, body mass index (BMI), basal levels of folliclestimulating hormone (FSH), estradiol (E2), luteinizing hormone (LH), ovarian volume, and number of antral follicles were compared between the good responders and poor responders. Blood samples of inhibin-B were collected before the treatment, on the day of human chorionic gonadotropin (hCG) administration, and on the day of oocyte pick-up. Follicular fluid samples were obtained from dominant follicles during oocyte retrieval. These parameters and characteristics of the cycles were compared between the good responders and poor responders.
Current source density analysis of linear and non‐linear components of the primate electroretinogram.

1. We have used the method of current source density analysis to locate the generators of harmonic electroretinogram (ERG) responses to contrast‐modulated pattern and uniform‐field stimuli in the primate retina. 2. Sinusoidal steady‐state analysis was used, with a stimulus temporal frequency of 8 Hz. Fundamental and second‐harmonic response components were measured for the uniform‐field response. The second harmonic of the average of contrast‐reversal pattern responses obtained at a series of spatial phases was also determined in the same experiments. In addition, retinal tissue resistance was measured. All of these measurements were obtained at a series of equally spaced depths in the retina. 3. Retinal resistivity was not observed to vary systematically with depth. In addition, any plausible undetected inhomogeneities of resistivity with depth were found to slightly affect the relative magnitudes of estimated current sources and sinks, but to have little effect on their localization. 4. In a given penetration, the phase lag of each harmonic component was relatively constant with depth in most cases; however the magnitude of this phase lag sometimes varied in different penetrations. To compare data from different penetrations, the constant phase lag for each harmonic was estimated, and the response data phase‐shifted so as to bring all data into a standard (cosine) phase. 5. The resulting current source density analyses were found to be quite consistent in overall form for different penetrations and in different animals. These data were averaged to obtain a final estimate of the depth profiles for generators of different ERG components. 6. The uniform‐field fundamental response was found to have a predominant source‐sink pair in the distal half of the retina (receptor layer to outer plexiform layer). The pattern (second‐harmonic) response generators had a quite different depth profile, consisting mainly of a source‐sink pair in the proximal 20% of the retina (encompassing the nerve fibre layer to the middle of the inner plexiform layer). The uniform‐field second‐harmonic response showed a current source density (CSD) depth profile with multiple sources/sinks, as if it contained contributions from the other two.
High expression levels of the mammalian target of rapamycin inhibitor DEPTOR are predictive of response to thalidomide in myeloma

Constitutive activation of the phosphoinositide 3kinase (PI3K)/Akt pathway is an important molecular event that contributes to the malignant phenotype of many human cancers, including myeloma. In general, this activation of PI3K is a result of genetic abnormalities of key components of the pathway, with the most common event being mutation or deletion of PTEN (phosphatase and tensin homolog gene) [1]. In contrast, down-regulation of PTEN by mutation has not been reported in myeloma, yet activation of the PI3K pathway remains important [2,3]. The cause of this activation in myeloma was uncertain, but was thought to be the result of extrinsic cytokine stimulation by interleukin-6 (IL6) and insulin-like growth factor-1 (IGF-1), as opposed to intrinsic abnormalities of PI3K pathway components. However, recently DEPTOR (DEPDC6) has been identified as a regulator of the PI3K pathway that appears to have a specific role in up-regulating PI3K signaling in myeloma [4]. DEPTOR is a negative regulator of mammalian target of rapamycin complex 1 (mTORC1), an inhibitor of PI3K, which when overexpressed relieves the negative feedback of mTORC1 on insulin receptor substrate-1 (IRS1), resulting in increased PI3K signaling. High DEPTOR expression therefore results in activated PI3K and Akt. The level of expression of DEPTOR has been studied in a variety of human cancers, where it has been found to be low, potentially as a consequence of negative feedback from the constitutively activated PI3K signaling. In myeloma, however, DEPTOR has been found to be overexpressed in about 25% of samples, and can mediate activation of the PI3K pathway in these cases [4]. Thus, cases with high DEPTOR expression may constitute a specific myeloma subgroup suitable for targeted therapy. In this context, thalidomide treatment has been shown to increase PTEN expression and to suppress Akt signaling [5–7]. As cases of myeloma characterized by high DEPTOR expression may depend on PI3K/ Akt signaling for survival, we hypothesized that they may benefit from exposure to thalidomide more than cases lacking such expression, and have examined this hypothesis in the context of a phase III randomized trial comparing a thalidomide-based induction regimen with conventional chemotherapy. In total, 154 bone marrow samples from patients with newly presenting myeloma treated on the Intensive Pathway of the MRC Myeloma IX trial (ISRCTN68454111) were available for analysis. The samples were purified for plasma cells using CD138 magnetic microbeads (Miltenyi Biotech, Bisley, UK) before extraction of RNA and DNA (Allprep kit; Qiagen, Crawley, UK). RNA and DNA were prepared for hybridization to the U133 Plus 2.0 expression GeneChip or the 500K Mapping GeneChip (Affymetrix, Santa Clara, USA) respectively, following the manufacturer’s guidelines as previously described [8–10]. Expression levels were generated
Therapist affect focus and patient outcomes in psychodynamic psychotherapy: a meta-analysis.

OBJECTIVE The authors systematically examined the relationship between therapist facilitation of patient emotional experience/expression and outcome in psychodynamic psychotherapy. METHOD Computer and manual searches were conducted for relevant publications, and 10 independent samples of short-term dynamic psychotherapy were included in a meta-analysis. Data analysis included calculation of an overall effect size of the relationship between therapist affect focus and outcome, statistical significance, and test for homogeneity. In addition, moderator analyses were conducted to examine the potential impact of type of outcome construct used and the methodological quality of individual studies. RESULTS The overall average weighted effect size across all outcome types was statistically significant (r=0.30), and the homogeneity statistic was nonsignificant. Moderator analyses indicated a statistically significant relationship between therapist facilitation of patient emotional experience/expression and outcome when more than one outcome construct was included but not when either a single or an unclear outcome construct was used. There were no significant relationships between methodological quality and the size of the effects, although use of audio- or videotaping for supervision demonstrated a moderate effect. CONCLUSIONS These data indicate that therapist facilitation of patient affective experience/expression is associated with patient improvement over the course of psychodynamic psychotherapy. Although the size of this relationship was not significantly related to methodological quality, results suggest the importance of close supervision of actual techniques through the use of audio- or videotapes. Additionally, results highlight the importance of defining outcome in a multidimensional way to properly assess theoretically relevant effects.
The environmental Kuznets curve in a world of irreversibility

This paper develops an overlapping generations model where consumption is the source of polluting emissions. Pollution stock accumulates with emissions but is partially assimilated by nature at each period. The assimilation capacity of nature is limited and vanishes beyond a critical level of pollution. We first show that multiple equilibria exist. More importantly, some exhibit irreversible pollution levels although an abatement activity is operative. Thus, the simple engagement of maintenance does not necessarily suffice to protect an economy against convergence toward a steady state having the properties of an ecological and economic poverty trap. In contrast with earlier related studies, the emergence of the environmental Kuznets curve is no longer the rule. Instead, we detect a sort of degenerated environmental Kuznets curve that corresponds to the equilibrium trajectory leading to the irreversible solution.
Definition of a subset of human peripheral blood mononuclear cells that are permissive to human cytomegalovirus infection

The identity of cells responsible for transmission of human cytomegalovirus (HCMV) in blood products or bone marrow transplants is unknown. We have tested the capacity of HCMV to in vitro infect human peripheral blood mononuclear cells (PBMC) from healthy donors and found that certain PBMC are permissive to HCMV infection. In vitro-infected viable cells were double stained for surface expression of different HMCV proteins and for cell-type-specific antigens to allow the identification of sensitive cells. All analysis were performed on viable cells, using HCMV-specific monoclonal antibodies and automated flow cytofluorimetry. PBMC were infected either with the laboratory-adapted HCMV strain AD169 or with a virus isolate obtained from a viremic patient. Up to 25% of all PBMC could express the major immediate-early antigen as well as the pp65 antigen, known at the lower matrix protein. Infected cells were mainly CD14+ monocytes, but also a small population of large CD8+ cells were susceptible to HCMV infection. CD19+ B lymphocytes were resistant to HCMV infection. Different populations of infected cells were enriched by using Dynabeads coated with cell-type-specific antibodies, and the presence of infectious virus was demonstrated by incubating the selected and sonicated cell material on human fibroblasts. Only material from infected monocytes and from CD3+ CD8+ cells gave rise to HCMV-specific plaques. The presence of HCMV mRNA as a sign of active viral transcription of the major immediate-early and late pp150 genes in infected cells was demonstrated by using nested reversed polymerase chain reaction. A common denominator was found for all cells that could be infected with HCMV. The CD13 antigen, a 130- to 150-kDa integral membrane protein identical to the enzyme aminopeptidase N, was expressed on all HCMV-permissive cells.
Velocity patterns in the aorta.

Hot-film constant temperature probes, evaluated in regimes of pipe-flow, have been used to explore velocity distributions across diameters at various sites in the aorta of dogs. Velocity profiles at all levels were blunt, with boundary-layers less than 2 mm thick; marked skews occurred in the profiles at certain sites in the proximal aorta. The major factors influencing flow in these regions are discussed, and possible causative factors identified. Fully-developed turbulence occurred in only one case, which is described.
MDSC-decreasing chemotherapy increases the efficacy of cytokine-induced killer cell immunotherapy in metastatic renal cell carcinoma and pancreatic cancer

Adoptive immunotherapy using cytokine-induced killer (CIK) cells is a promising cancer treatment, but its efficacy is restricted by various factors, including the accumulation of myeloid-derived suppressor cells (MDSCs). In this study, we determine whether chemotherapeutic drugs that reduce MDSC levels enhance the efficacy of CIK cell therapy in the treatment of solid tumors. Fifty-three patients were included in this study; 17 were diagnosed with metastatic renal cell carcinoma (MRCC), 10 with advanced pancreatic cancer (PC), and 26 with metastatic melanoma (MM). These patients were divided into two groups: CIK cell therapy alone and CIK cell therapy combined with chemotherapy. Combining CIK cell therapy and chemotherapy increased 1-year survival rates and median survival times in MRCC and PC patients, but not in MM patients. The disease control rate did not differ between treatment groups for MRCC or MM patients, but was higher in PC patients receiving combined treatment than CIK cell treatment alone. These data suggest that addition of MDSC-decreasing chemotherapy to CIK cell therapy improves survival in MRCC and PC patients.
Red & black or black & white? Phylogeny of the Araschnia butterflies (Lepidoptera: Nymphalidae) and evolution of seasonal polyphenism

Phylogeny of the butterfly genera Araschnia, Mynes, Symbrenthia and Brensymthia (Lepidoptera: Nymphalidae: Nymphalini) is reconstructed, based on 140 morphological and ecological characters. The resulting tree shows that Araschnia is a sister group of the clade including Symbrenthia, Mynes and Brensymthia (Symbrenthia is paraphyletic in the respect of remaining genera; Symbrenthia hippalus is a derived species of Mynes). The species‐level relationships within Araschnia are robustly supported as follows: (A. davidis (prorsoides ((zhangi doris) (dohertyi (levana burejana))))). Analysis of the wing colour‐pattern characters linked with the seasonal polyphenism in the Araschnia species suggests that the black and white coloration of the long‐day (summer) generation is apomorphic. Biogeographically, the origin of polyphenism in Araschnia predates the dispersal of some Araschnia species towards the Palaearctic temperate zone, and the ecological cause of the polyphenism itself is then probably not linked with thermoregulation. The possible mimetic/cryptic scenarios for the origin of Araschnia polyphenism are discussed.