Miracle-dz/UniFAR-FTUs huggingface dataset:
Constant, cycling, hot and cold thermal environments: strong effects on mean viability but not on genetic estimates

It has frequently been suggested that trait heritabilities are environmentally sensitive, and there are genetic trade‐offs between tolerating different environments such as hot and cold or constant and fluctuating temperatures. Future climate predictions suggest an increase in both temperatures and their fluctuations. How species will respond to these changes is uncertain, particularly as there is a lack of studies which compare genetic performances in constant vs. fluctuating environments. In this study, we used a nested full‐sib/half‐sib breeding design to examine how the genetic variances and heritabilities of egg‐to‐adult viability differ at high and low temperatures with and without daily fluctuations in temperatures using Drosophila melanogaster as a model organism. Although egg‐to‐adult viability was clearly sensitive to developmental temperatures, heritabilities were not particularly sensitive to developmental temperatures. Moreover, we found that egg‐to‐adult viabilities at different developmental temperatures were positively correlated, suggesting a common genetic background for egg‐to‐adult viability at different temperatures. Finding both a uniform genetic background coupled with rather low heritabilities insensitive to temperatures, our results suggest evolutionary responses are unlikely to be limited by temperature effects on genetic parameters or negative genetic correlations, but by the direct effects of stressful temperatures on egg‐to‐adult viability accompanied with low heritabilities.
NMDA and Non‐NMDA Ionotropic Glutamate Receptors Modulate Striatal Acetylcholine Release via Pre‐ and Postsynaptic Mechanisms

Abstract: The effects of NMDA and α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionic acid (AMPA) on endogenous acetylcholine release from rat striatal slices and synaptosomes were investigated. Both agonists (1–300 µM) facilitated acetylcholine release from slices in a dose‐dependent manner. NMDA (100–300 µM) and AMPA (30–300 µM), however, subsequently inhibited acetylcholine release. NMDA (100 µM)‐induced facilitation was antagonized by 3‐(2‐carboxypiperazin‐4‐yl)propyl‐1‐phosphonic acid (CPP) and dizocilpine (both 1–10 µM), whereas the 10 µM AMPA effect was antagonized by 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (CNQX; 1–30 µM). NMDA (100 µM)‐induced inhibition was counteracted by CPP, but not dizocilpine, and by the nitric oxide synthase inhibitor l‐nitroarginine (1–100 µM). Tetrodotoxin (0.5 µM) prevented the facilitatory effect of 3 µM NMDA and AMPA, but left unchanged that of 30 µM NMDA and 100 µM AMPA. Acetylcholine release from synaptosomes was stimulated by KCI (7.5–100 mM) in a dose‐dependent manner. NMDA and AMPA maximally potentiated the 20 mM KCl effect at 1 µM and 0.01 µM, but were ineffective at 100 µM and 10 µM, respectively. Inhibition of acetylcholine release was never found in synaptosomes. The effects of 1 µM NMDA and 0.01 µM AMPA were antagonized by CPP (0.0001–1 µM) or dizocilpine (0.0001–10 µM) and by CNQX (0.001–1 µM), respectively. These data suggest that glutamatergic control of striatal acetylcholine release is mediated via both pre‐ and post‐synaptic NMDA and non‐NMDA ionotropic receptors.
Analysis of Salvage Operation in Head and Neck Microsurgical Reconstruction

In this study, we examined salvage operations after reexploration in head and neck reconstruction and analyzed ways to solve problems. Free flap reconstruction of the head and neck lesion was carried out for 513 cases in our hospital over the past 12 years. Twenty‐one cases of reexploration were caused by postoperative thrombosis (4.1%). We could only salvage seven cases (33.3%) of 21 cases from flap thrombosis. All seven cases were included in the category of venous thrombosis, and they were undertaken within 3 days postoperatively. Our results have shown that once thrombosis occurs, there is little possibility of flap salvage, particularly 3 days after operation and in infectious cases. When no flow phenomena are observed and no flap salvage is deemed possible, aggressive treatment such as a second free flap or next pedicle flap should be chosen as soon as possible to avoid any delay in postoperative treatment.
Signal Transduction Inhibition of APCs Diminishes Th17 and Th1 Responses in Experimental Autoimmune Encephalomyelitis1

IL-17- and IFN-γ-secreting T cells play an important role in autoimmune responses in multiple sclerosis and the model system experimental autoimmune encephalomyelitis (EAE). Dendritic cells (DCs) in the periphery and microglia in the CNS are responsible for cytokine polarization and expansion of this T cell subset. Our results indicate that in vivo administration of a signal transduction inhibitor that targets DCs to mice with EAE led to a decrease in CNS infiltration of pathogenic Ag-specific T cells. Since this approach does not target T cells directly, we assessed the effects on the APCs that are involved in generating the T cell responses. Since in EAE and multiple sclerosis, both microglia and peripheral DCs are likely to contribute to disease, we utilized a bone marrow chimera system to distinguish between these two populations. These studies show that peripheral DCs are the primary target but that microglia are also modestly affected by CEP-701, as numbers and activation states of the cells in the CNS are decreased after therapy. Our results also showed a decrease in secretion of TNF-α, IL-6, and IL-23 by DCs as well as a decrease in expression of costimulatory molecules. We further determined that levels of phospho-Stat1, Stat3, Stat5, and NF-κB, which are signaling molecules that have been implicated in these pathways, were decreased. Thus, use of this class of signal transduction inhibitors may represent a novel method to treat autoimmunity by dampening the autoreactive polarizing condition driven by DCs.
Adjunctive fluoxetine in the treatment of negative symptoms in chronic schizophrenic patients

The effect of adjunctive fluoxetine on negative schizophrenic symptoms was evaluated in 34 chronic schizophrenic in-patients on maintenance therapy with neuroleptics. They received randomly, on a double-blind basis, fluoxetine (20 mg/day) or placebo for 12 weeks. In the fluoxetine group, three patients dropped out because of side effects. Negative symptoms, as measured by change on the Scale for Assessment of Negative Symptoms at the end point compared to baseline values, were significantly improved in fluoxetine-treated patients (p < 0.001), but not in the placebo group. Fluoxetine treatment did not influence positive schizophrenic symptoms, while it induced a slight, but statistically significant, decrease (p < 0.05) in depressive symptoms, as measured by the Hamilton Rating Scale for Depression. Unwanted effects were more common among patients receiving fluoxetine. These data suggest that the addition of fluoxetine to neuroleptic treatment may be beneficial in some schizophrenic patients with negative symptoms.
Calcium‐activated potassium channels in the endothelium of intact rat aorta.

1. Single K+ channel currents and membrane potential were recorded in the endothelium of excised intact rat aorta. 2. Two types of K+ channel were found in excised patches, KCh and KAp. With Na+ and K+ as the main external and internal cations, outward conductances were 6.7 pS (KCh) and 2.8 pS (KAp). In symmetric 150 mM K+, the inward conductances were 18 and 9.1 pS. 3. Activation by Ca2+ was concentration dependent. KCh channels were activated by [Ca2+] > 0.1 microM and KAp by [Ca2+] > 0.5 microM. 4. Apamin at concentrations > 1 nM inhibited KAp Channels. Block was complete at 10 nM. KAp channels were insensitive to charybdotoxin. KCh channels were inhibited by charybdotoxin at concentrations > 50 nM, but were insensitive to apamin. 5. d‐Tubocurarine (dTC) evoked flickering activity of KAp channels at concentrations > 5 microM and complete block at 100 microM. At these doses, dTC did not affect KCh channels, but at concentrations > 1 mM it decreased the single channel amplitude. 6. Hyperpolarization evoked by acetylcholine was unaffected by apamin or dTC at low concentrations ( < or = 100 microM), but inhibited by high concentrations of charybdotoxin ( > 50 nM) or dTC ( > 1 mM). 7. These data suggest that KCh channels are novel Ca(2+)‐activated K+ channels responsible for the ACh‐evoked hyperpolarization in the endothelium of rat aorta.
Direct Susceptibility Testing of Positive Blood Cultures by Using Sensititre Broth Microdilution Plates

ABSTRACT Traditional susceptibility testing of blood cultures requires overnight incubation in order to obtain isolated colonies. Susceptibility results can be reported up to 24 h sooner by using a bacterial pellet from the blood culture broth. This study evaluated the accuracy of direct susceptibility testing from positive ESP blood culture broths by using Sensititre broth microdilution plates compared to testing with isolated colonies. Practical inclusion criteria were applied to gram-positive organisms to avoid reporting susceptibilities for probable contaminants. All gram-negative organisms were tested directly. An aliquot of the blood culture was centrifuged, and the resulting pellet was used to make a 0.5 McFarland suspension. Microdilution plates were inoculated and interpreted according to the manufacturer's instructions. Colony counts were performed to ensure proper colony density was achieved. A total of 199 patient and seeded blood cultures were evaluated for both essential (within ±1 twofold dilution) and categorical (sensitive, intermediate, or resistant) agreement. Testing of 93 gram-positive isolates (1,214 antimicrobial agent-organism combinations) yielded 98% essential agreement and categorical error rates of 0.3% minor, no major (false resistance), and 1.7% very major (false susceptibility) errors. For 106 gram-negative isolates (1,828 antimicrobial agent-organism combinations), the essential agreement was 99%. Categorical error rates were 0.5, 0, and 2.0% for minor, major, and very major errors, respectively. Performance was comparable for both gram-positive and gram-negative isolates, as well as for both aerobic and anaerobic media. Using this direct testing methodology, reliable susceptibility results can be reported to physicians 24 h sooner, allowing earlier appropriate modification of antimicrobial therapy.
Korean Ethnicity as Compared with White Ethnicity Is an Independent Favorable Prognostic Factor for Overall Survival in Non-small Cell Lung Cancer before and after the Oral Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Era

Background: We have previously demonstrated, using a regional California Cancer Registry database, that Asian ethnicity is an independent favorable prognostic factor for overall survival (OS) in non-small cell lung cancer (NSCLC). Methods: Retrospective population-based analysis of Korean and US white patients with NSCLC with known smoking status from Samsung Cancer Center, Seoul, South Korea, and a Southern California Regional Cancer Registry between 1998 and 2005 with follow-up through February 2008 to allow for even case ascertainment periods before and after 2002, when epidermal growth factor receptor tyrosine kinase inhibitors were introduced in Korea and considered as the year of reference. Results: A total of 4622 Korean and 8846 US white patients were analyzed. Median age of diagnosis was 63 years versus 71 years for Korean and white patients, respectively (P < 0.0001). A total of 34.5% of Korean compared with 8.2% white patients were never-smokers. There was significant OS improvement in never-smokers when compared with ever-smokers among either Korean patients (p < 0.0141) or US white (p < 0.0397), respectively. There was significant improvement in OS among Korean patients from 2002 to 2005 compared with 1998–2001 (p < 0.0001) but not among US white patients (p = 0.5641). Except for stage II patients (p = 0.0723), univariate analysis revealed Korean patients had improved OS compared with US white patients among stages I, III, and IV, respectively (all p < 0.0001). Multivariate analysis revealed Korean ethnicity (versus white; hazard ratio (HR) = 0.869; p < 0.0001) was an independent favorable factor for OS. The adjusted HR for OS Korean ethnicity when compared with white ethnicity improved during 2002–2005 (HR = 0.795; p < 0.0001) compared with 1998–2001 (HR = 0.889; p = 0.0013). Conclusions: These results suggest that Korean ethnicity compared with US white ethnicity is an independent favorable prognostic factor for OS in NSCLC. In addition, greater survival benefit among Korean patients with NSCLC was noted in the postepidermal growth factor receptor tyrosine kinase inhibitor era (2002 and after) compared with US white ethnicity.
Study on the First Appearance of Social Studies in the Elementary School Program in Turkey

This article describes the nature of the Social Studies program taught in the form of a class in Turkey. We use the 1968 elementary school program, where social studies were mentioned for the first time in an official program. For this purpose, we formally explained the interpretation of the concept of social studies for the first time in elementary school programs by using a document analysis showing what social studies are, where they stand in the program, what they consist of, and what the pedagogical understanding regarding Social Studies teaching and education processes is. The study used document analysis, a qualitative research method, to analyze data collected from the 1968 elementary school program, which is a primary source. Moreover, we created categories in line with the questions posed in this project and interpreted the data accordingly. Results reveal that Social Studies teaching began as a separate class at elementary schools in 1968 and the nature of social studies is clouded with the pedagogical concern that 9–10-year-old individuals could comprehend teaching topics only with an interdisciplinary approach. When Social Studies classes first appeared in elementary schools in Turkey, individuals’ needs and involvement with the environment was emphasized, focusing on subject and citizenship. Remarkably, the methods, techniques, and resources to be used in teaching the classes were diverse. It is observed that the Social Studies class embodied the goals of becoming patriotic, economically productive, and socially harmonic individuals.
Assessment of disease activity in rheumatoid arthritis using a novel folate targeted radiopharmaceutical Folatescan.

OBJECTIVES Development of a simple and accurate technique for detecting active inflammation in the joints and other tissues of patients with inflammatory disorders is an unmet need in rheumatic diseases. This study is a preliminary assessment of the safety and usage of a radiopharmaceutical, FolateScan (Technetium-99m EC20; 99mTc-EC20), for detecting disease activity in patients with rheumatoid arthritis. METHODS EC20 is a folate-targeted diagnostic radiopharmaceutical which binds to the folate receptor and is preferentially taken up by activated macrophages. In this open-label, cross-sectional study, a total of 40 patients with RA (26 with one or more swollen joints, 14 with clinically quiescent joint disease; 0/66 joint count) as well as 6 patients with osteoarthritis, 12 patients with other inflammatory conditions and 5 healthy subjects received 0.1 mg of EC20 labeled with 20-25mCi of technetium-99m. Disease activity was scored in each joint and other target tissues by a radiologist blinded to the clinical assessment, and results were compared to the rheumatologist's physical examination, which served as the test standard. RESULTS The 40 patients (78% female) with RA had a mean age of 56.9 years. Assessment of uptake of 99mTc-EC20 in joints of patients with RA based on image analysis was compared to the clinical examination. FolateScan detected more actively involved joints in 27 patients (68%) than joints recorded as "swollen", and more actively involved joints in 25 patients (63%) than joints recorded as "painful and/or swollen". The number of swollen joints by clinical exam was correlated with ESR (r=0.43; p=0.006) and C-rp (r=0.35; p=0.03). The number of actively involved joints by FolateScan was also correlated with ESR (r=0.47; p=0.002) and C-rp (r=0.36; p=0.02). Joint uptake was also seen in patients with osteoarthritis. CONCLUSION FolateScan is a potentially useful tool for detection of disease activity in patients with RA and may be more sensitive than the physical examination.
Recent Advances on the Spherical Tokamak Route to Fusion Power

Stambaugh developed the Peng-Hicks concept of a fusion reactor based on a solid copper center-post spherical tokamak (ST). Using the promising results from the START experiment, they produced a vision for a path to fusion power. This path had two elements such as the ability to produce high fusion gain from an ST and of equal importance, the ability to demonstrate this in a small (and therefore relatively low cost) pilot plant device. In this paper, we review various attempts to pursue this vision, and try to elucidate the reason why success has not yet been achieved. However, we show that the advent of high temperature superconductors may overcome some of the problems, and we suggest a revised version of the small, low entry cost route to fusion power.
Diametric Role of the Latency-Associated Protein Acr1 of Mycobacterium tuberculosis in Modulating the Functionality of Pre- and Post-maturational Stages of Dendritic Cells

It is instrumental for the Mycobacterium tuberculosis (Mtb) to persist within its host in dormancy. Mtb represses most of its metabolic machinery during latency, but upregulates the expression of latency-associated protein alpha-crystallin protein (Acr1). Therefore, it is imperative to understand how throughout dormancy, Mtb employs Acr1 to regulate the host immunity. This study reveals that Acr1 exhibits divergent effect on the pre- and post-maturation stages of dendritic cells (DCs). In the current study, we demonstrate that early encounter of bone marrow cells with Acr1 while differentiating into DCs (AcrDCpre), leads to impairment in their maturation. In contrast, when exposed to Acr1 after maturation (AcrDCpost), DCs show augmentation in their activity, secretion of TNF-α, IL-12, IL-6, and activation of T cells. Additionally, AcrDCpost promoted the polarization of naïve CD4 T cells to Th1 cells and Th17 cells and restricted the intracellular growth of Mtb. Furthermore, these DCs upregulated the expression of CCR7 and exhibited enhanced migratory capabilities. The discrete impact of Acr1 on DCs is mediated through a mechanism involving STAT-1, SOCS-3, ERK, TLR-4, and NF-κB signaling pathways. This study reveals the unprecedented role of Acr1 in distinctly modulating the function of DCs at different stages of maturation.
Incidence and clinical significance of hepatitis B virus precore gene translation initiation mutations in e antigen‐negative patients

Hepatitis Be antigen (HBeAg)‐negative chronic hepatitis B (CHB) is associated with hepatitis B virus (HBV) variants harbouring changes in the precore region. Most commonly, a G to A point mutation at nucleotide 1896 (m1896) creates a novel translation stop codon that prevents HBeAg production. In the Mediterranean region the m1896 mutation prevails in greater than 98% of HBeAg‐negative CHB patients. In this study the prevalence of additional mutations in the precore region was investigated among patients with chronic HBV infection. Precore sequences were determined by sequencing serum HBV DNA amplified by polymerase chain reaction (PCR) with primers flanking the precore/core region. Thirty‐one HBeAg‐negative and five HBeAg‐positive individuals were studied. All HBeAg‐negative patients (100%) harboured the m1896 mutation and 20 (64.5%) also had a G to A mutation at nucleotide 1899 (m1899). Additional mutations affecting the translation initiation of the precore gene were found in seven (22.5%) patients, all with active liver disease, five of whom had episodes of HBV reactivation. HBeAg‐positive patients had no mutations in these positions and neither did any of the five HBeAg‐negative patients with normal levels of liver enzymes, representing the healthy carrier state of HBV infection. Serial sample analysis from one patient revealed that the initiation codon mutation developed following HBeAg seroconversion and the appearance of m1896. During periods of high HBV replication, the ratio of mutant to wild‐type ATG was found to increase in parallel with HBV DNA levels. These data show that a significant proportion of HBeAg‐negative patients who already harbour the 1896 stop codon mutation may subsequently develop precore translation initiation mutations, which appear to be associated with enhanced HBV replication and severe liver disease.
From hand twister to mind twister: computer-aided treatment in traumatic wrist fracture.

OBJECTIVE The use of computers as a treatment modality in the occupational therapy hand clinic is, as yet, not common practice. A computer interface for wrist movements was developed, and a study to justify the application of such a device is presented. METHOD Forty-seven patients in a day hand clinic who had traumatic fracture of one hand with limitation of wrist mobility participated in the study. Participants were divided into two treatment groups: computer-aided treatment (high technology) and traditional brush machine treatment (low technology). A device was developed based on the brush machine in which the brush machine's mechanism was converted into a medial-lateral joystick. Right-to-left movements were digitally transformed for the use of a computer game. Participants were treated for 5 weeks, and outcome measures included range of motion (ROM), grip strength, edema, and level of interest. RESULTS Results showed significant improvement in ROM, grip strength, and edema across 5 weeks for all participants. Although no significant differences were found between the two groups in ROM, grip strength, and edema, the computer-aided group showed significantly more interest in treatment than did the brush machine group. Finally, the interaction between treatment group and the attitude toward computers was not significant. CONCLUSIONS These results indicate the potential for more interesting motor treatment and rehabilitation of the wrist through the use of computer games. The efficacy of using computers in occupational therapy clinics needs further investigation.