Miracle-dz/UniFAR-FTUs huggingface dataset:
Lenalidomide Enhances Natural Killer Cell and Monocyte-Mediated Antibody-Dependent Cellular Cytotoxicity of Rituximab-Treated CD20+ Tumor Cells

Purpose: Lenalidomide has significant activity in myelodysplastic syndromes, multiple myeloma, and non-Hodgkin's lymphoma (NHL). In previous studies, natural killer (NK) cell expansion by lenalidomide was shown to enhance the cytotoxic effect of rituximab. This study assessed the ability of lenalidomide to enhance antibody-dependent cellular cytotoxicity (ADCC) in rituximab-treated NHL cell lines and primary tumor cells from patients with B-cell chronic lymphocytic leukemia (B-CLL) in vitro. Experimental Design: An in vitro ADCC system was used to assess the ability of lenalidomide to enhance human NK cell and monocyte function in response to rituximab. Results: Lenalidomide directly enhanced IFN-γ production via Fc-γ receptor-mediated signaling in response to IgG. It was also a potent enhancer of NK cell-mediated and monocyte-mediated tumor cell ADCC for a variety of rituximab-treated NHL cell lines in vitro, an effect that was dependent on the presence of antibody and either interleukin-2 or interleukin-12. Lenalidomide also enhanced the ability of NK cells to kill primary tumor cells derived from three patients with B-CLL who have been treated previously with fludarabine plus cyclophosphamide. Enhanced NK cell ADCC was associated with enhanced granzyme B and Fas ligand expression and could be inhibited by a granzyme B inhibitor and partially inhibited by antibody to FasL. Enhanced NK cell Fc-γ receptor signaling is associated with enhanced phosphorylated extracellular signal-related kinase levels leading to enhanced effector function. Conclusions: These findings suggest that lenalidomide has the potential to enhance the rituximab-induced killing of NHL cell lines and primary B-cell chronic lymphocytic leukemia cells via a NK cell-mediated and monocyte-mediated ADCC mechanism in vitro, providing a strong rationale for the combination of lenalidomide with IgG1 antibodies to target tumor-specific antigens in patients with cancer.
Bacteriological Assessment and Antibiotics Susceptibility Profile of Bacteria Recovered from Pond Water, Fish Skin, and Gut in Ile-Ife, Osun State, Nigeria

Fish currently provide 6.7% of all protein consumed by humans globally, nevertheless, aquaculture system has been linked to fish and environmental contamination and disease outbreak. This study aims to isolate, identify, and characterise, bacteria in fish and pond water as well as the antibiotic profile of detected Coliforms. The susceptibility of the isolates was tested using the Kirby-Bauer disc diffusion method on Mueller Hinton agar. A total of forty (40) isolates were isolated from the water samples of which (5) species were Gram Positive bacteria and 35 species of Gram Negative bacteria. The temperature for all ponds ranged from 25°C to 28°C. The mean bacteria count for pond C1 to T2 were 4.9 × 102, 4.9 × 102, 5.4 × 102, 2.5 × 102, 2.2 × 102, and 1.9 × 102 CFU/ml respectively. All isolates were 100% resistant to ceftazidime, cefuroxime and augmentin. More resistance to cefixime (80%) and gentamicin (73.3%) and nitrofurantoin (66.7%) was recorded. However, only 16.6% and 8.3% of the isolates were resistant to ciprofloxacin and ofloxacin respectively. The multiple antimicrobial resistance index (MARI) ranged from 0.5 to 0.9. The water quality parameters (temperature and pH) and the type of bacteria detected in all pond type did not differ significantly. The Multi-drug resistance bacteria detected could be pathogenic to fish and consumers.
Social barriers to optimal pain management in infants and children.

OBJECTIVE To examine the social barriers that lead to less than optimal management of pain in children. DESIGN Recognizing the vulnerabilities of infants and children and their dependence on caring adults, a model of pain communication is proposed. The model examines (a) the pain experiences of children, including social determinants; (b) developmental variations in the capacity to encode the severity and qualities of pain as expressive behavior; (c) adult skills and deficiencies in decoding pain; and (d) the actions of adults predicated on the meaning and significance attached to children's actions. Limitations in care were examined. DATA SOURCES The current research and professional literature were accessed through searches of the Psyclit and Medline databases for relevant investigations on the basis of our working knowledge of the literature. CONCLUSION Numerous deterrents to optimal care are identified in the domains of commonplace beliefs about the nature of pain in infants and children: failure to recognize the impact of socialization in familial and cultural modes of experience and expression; needs for age-specific assessment instruments; the limited capacity to use available evidence concerning pain; the need to employ clinicians, parents, and other adults more effectively in delivering care; and structural problems in the health care system.
Cytomembranic PD-L1 expression in locoregionally advanced nasopharyngeal carcinoma

Background and objective The aim of this study was to evaluate the expression of cytomembranic programmed death-ligand 1 (PD-L1) and its clinical significance in locoregionally advanced nasopharyngeal carcinoma (NPC). Patients and methods Formalin-fixed, paraffin-embedded tissue biopsies from 85 patients with histological diagnosis of locoregionally advanced NPC treated with radical intensity-modulated radiotherapy and concurrent cisplatin-based chemotherapy were studied. By using immunohistochemistry staining, expressions of cytomembranic PD-L1 on tumor cells were detected. Results After a median follow-up duration of 65.8 months, 7 (8.2%), 5 (5.9%), and 5 (5.9%) patients suffered from local failure, regional failure, and distant metastases, respectively. The 5-year local failure-free survival, regional failure-free survival, distant failure-free survival, and overall survival (OS) rates were 90.9%, 94.8%, 94.0%, and 92.2%, respectively. Our results revealed that a high expression of cytomembranic PD-L1 was correlated with shorter OS (5y-OS: 82.5% vs 97.6%, P=0.022). In the multivariate analysis, only the cytomembranic PD-L1 was an independent prognostic factor for OS (hazard ratio: 6.176, 95% confidence interval, 1.166–32.710, P=0.032). Conclusion Cytomembranic PD-L1 expression levels correlated with OS in locoregionally advanced NPC. Agreement between different methods is needed for further application of PD-L1 biomarker assays in NPC.
A staging system for forelimb regeneration in the axolotl, Ambystoma mexicanum

A staging system has been devised for normal regeneration from the upper arm in the mature axolotl. It consists of seven externally definable stages: (1) Wound healing (WH); (2) Dedifferentiation (DD); (3) Early bud (EB); (4) Medium bud (MB); (5) Late bud (LB); (6) Palette (Pal), and (7) Digital outgrowth (DO). Serial histological sections of 38 regenerating limbs were used to correlate gross stages with microscopic events in the regenerative process.
Bird assemblage vulnerability depends on the diversity and biogeographic histories of islands

Significance Biodiversity is broadly thought to be positively associated with a wide array of ecosystem functions and properties. Because these properties may reduce extinction risk, for example, by making functioning more stable and ecosystems less prone to invasion, biodiverse islands have the potential to accumulate species over evolutionary time that are more vulnerable to extinction. We find that bird diversity is positively related to the collective vulnerability of species in a set of assemblages. This relationship is highly contingent on biogeographic history, a factor often overlooked in biodiversity and ecosystem-functioning studies. Our findings expose a paradox: biodiverse systems, as more robust systems, may experience greater biodiversity loss over ecological time because they accumulate more vulnerable species over evolutionary time. Biodiversity is widely acknowledged to influence the magnitude and stability of a large array of ecosystem properties, with biodiverse systems thought to be more functionally robust. As such, diverse systems may be safer harbors for vulnerable species, resulting in a positive association between biodiversity and the collective vulnerability of species in an assemblage, or “assemblage vulnerability. ” We find that, for 35 islands across Northern Melanesia, bird assemblage vulnerability and biodiversity are positively associated. This relationship is highly contingent on Pleistocene connectivity, suggesting that biogeographic history—a factor often overlooked in biodiversity and ecosystem-functioning studies—may influence contemporary ecological processes. In the face of biodiversity loss attributable to anthropogenic drivers, reduced ecosystem functioning may erode the safe harbors of vulnerable assemblages. Paradoxically, these results suggest that biodiverse systems, as more robust systems, may experience greater biodiversity loss over ecological time because they harbor more vulnerable species accumulated over evolutionary time.
Sloppy Bypass of an Abasic Lesion Catalyzed by a Y-family DNA Polymerase*

DNA damage that eludes cellular repair pathways can arrest the replication machinery and stall the cell cycle. However, this damage can be bypassed by the Y-family DNA polymerases. Here, Dpo4, an archetypal Y-family member from the thermophilic Sulfolobus solfataricus, was used to extend our kinetic studies of the bypass of an abasic site, one of the most mutagenic and ubiquitous cellular lesions. A short oligonucleotide sequencing assay is developed to directly sequence DNA bypass products synthesized by Dpo4. Our results show that incorporation upstream of the abasic lesion is replicated error-free; yet dramatically, once Dpo4 encounters the lesion, synthesis became sloppy, with bypass products containing a myriad of mutagenic events. Incorporation of dAMP (29%) and dCMP (53%) opposite the abasic lesion at 37 °C correlates exceptionally well with our kinetic results and demonstrates two dominant bypass pathways via the A-rule and the lesion loop-out mechanism. Interestingly, the percentage of overall frameshift mutations increased from 71 (37 °C) to 87% (75 °C). Further analysis indicates that lesion bypass via the A-rule is strongly preferred over the lesion loop-out mechanism at higher temperatures and concomitantly reduces the occurrence of “-1 deletion” mutations observed opposite the lesion at lower temperatures. The bypass percentage via the latter pathway is confirmed by an enzymatic digestion assay, verifying the reliability of our sequencing assay. Our results demonstrate that an abasic lesion causes Dpo4 and possibly all Y-family members to switch from a normal to a very mutagenic mode of replication.
Clinical course correlates poorly with muscle pathology in nemaline myopathy

Objective: To report pathologic findings in 124 Australian and North American cases of primary nemaline myopathy. Methods: Results of 164 muscle biopsies from 124 Australian and North American patients with primary nemaline myopathy were reviewed, including biopsies from 19 patients with nemaline myopathy due to α-actin (ACTA1) mutations and three with mutations in α-tropomyosinSLOW (TPM3). For each biopsy rod number per fiber, percentage of fibers with rods, fiber-type distribution of rods, and presence or absence of intranuclear rods were documented. Results: Rods were present in all skeletal muscles and diagnosis was possible at all ages. Most biopsies contained nemaline bodies in more than 50% of fibers, although rods were seen only on electron microscopy in 10 patients. Rod numbers and localization correlated poorly with clinical severity. Frequent findings included internal nuclei and increased fiber size variation, type 1 fiber predominance and atrophy, and altered expression of fiber type specific proteins. Marked sarcomeric disruption, increased glycogen deposition, and intranuclear rods were associated with more severe clinical phenotypes. Serial biopsies showed progressive fiber size variation and increasing numbers of rods with time. Pathologic findings varied widely in families with multiple affected members. Conclusions: Very numerous nemaline bodies, glycogen accumulation, and marked sarcomeric disruption were common in nemaline myopathy associated with mutations in skeletal α-actin. Nemaline myopathy due to mutations in α-tropomyosinSLOW was characterized by preferential rod formation in, and atrophy of, type 1 fibers. Light microscopic features of nemaline myopathy correlate poorly with disease course. Electron microscopy may correlate better with disease severity and genotype.
Modulation of Central Synapses by Astrocyte-Released ATP and Postsynaptic P2X Receptors

Communication between neuronal and glial cells is important for neural plasticity. P2X receptors are ATP-gated cation channels widely expressed in the brain where they mediate action of extracellular ATP released by neurons and/or glia. Recent data show that postsynaptic P2X receptors underlie slow neuromodulatory actions rather than fast synaptic transmission at brain synapses. Here, we review these findings with a particular focus on the release of ATP by astrocytes and the diversity of postsynaptic P2X-mediated modulation of synaptic strength and plasticity in the CNS.
H3 Histamine Receptor–Mediated Activation of Protein Kinase Cα Inhibits the Growth of Cholangiocarcinoma In vitro and In vivo

Histamine regulates functions via four receptors (HRH1, HRH2, HRH3, and HRH4). The d-myo-inositol 1,4,5-trisphosphate (IP3)/Ca2+/protein kinase C (PKC)/mitogen-activated protein kinase pathway regulates cholangiocarcinoma growth. We evaluated the role of HRH3 in the regulation of cholangiocarcinoma growth. Expression of HRH3 in intrahepatic and extrahepatic cell lines, normal cholangiocytes, and human tissue arrays was measured. In Mz-ChA-1 cells stimulated with (R)-(α)-(−)-methylhistamine dihydrobromide (RAMH), we measured (a) cell growth, (b) IP3 and cyclic AMP levels, and (c) phosphorylation of PKC and mitogen-activated protein kinase isoforms. Localization of PKCα was visualized by immunofluorescence in cell smears and immunoblotting for PKCα in cytosol and membrane fractions. Following knockdown of PKCα, Mz-ChA-1 cells were stimulated with RAMH before evaluating cell growth and extracellular signal–regulated kinase (ERK)-1/2 phosphorylation. In vivo experiments were done in BALB/c nude mice. Mice were treated with saline or RAMH for 44 days and tumor volume was measured. Tumors were excised and evaluated for proliferation, apoptosis, and expression of PKCα, vascular endothelial growth factor (VEGF)-A, VEGF-C, VEGF receptor 2, and VEGF receptor 3. HRH3 expression was found in all cells. RAMH inhibited the growth of cholangiocarcinoma cells. RAMH increased IP3 levels and PKCα phosphorylation and decreased ERK1/2 phosphorylation. RAMH induced a shift in the localization of PKCα expression from the cytosolic domain into the membrane region of Mz-ChA-1 cells. Silencing of PKCα prevented RAMH inhibition of Mz-ChA-1 cell growth and ablated RAMH effects on ERK1/2 phosphorylation. In vivo, RAMH decreased tumor growth and expression of VEGF and its receptors; PKCα expression was increased. RAMH inhibits cholangiocarcinoma growth by PKCα-dependent ERK1/2 dephosphorylation. Modulation of PKCα by histamine receptors may be important in regulating cholangiocarcinoma growth. (Mol Cancer Res 2009;7(10):1704–13)
Influence of nutrient limitation and low pH on serogroup B Neisseria meningitidis capsular polysaccharide levels: correlation with virulence for mice

Neisseria meningitidis strain M986, which possesses a polyanionic sialic acid capsular polysaccharide, was resistant to the bactericidal effects of normal rabbit serum, but sensitive when immune serum and complement were present. An isogenic strain PRM102, deficient in the ability to produce capsular polysaccharide, was sensitive to normal serum. Strain M986, when grown under conditions of low pH or nutrient limitation, synthesized increased levels of capsular polysaccharide. This was accompanied by an increase in cell surface hydrophilicity and virulence for mice. Cells grown in low-pH, iron-limited medium synthesized the highest concentration of polysaccharide and exhibited the highest cell surface hydrophilicity and virulence among the cases examined. The increase in capsular polysaccharide was partly explained by a decrease in the specific activity of a membrane-bound cytidine monophosphate-N acetylneuraminic acid hydrolase. The results suggest that conditions of nutrient limitation and low pH exert profound effects on the physicochemical nature of the meningococcal cell surface which, in turn, cumulate in enhanced virulence of this organism for mice.
Japan and Labor Migration: Theoretical and Methodological Implications of Negative Cases

Migration scholars have frequently emphasized the tremendous increase in international migration in recent years. But several advanced industrial countries — Japan in particular — have relatively small numbers of foreign workers. Most of the literature on labor migration relates only to “positive cases,” i.e., countries that have actually experienced significant inflows of foreign workers. This article proposes considering Japan as a “negative case” of labor migration in the post-World War II period. There has been much recent interest in the growing numbers of foreign workers in Japan, but what is most interesting about Japan is the fact that the numbers are relatively small (as a percentage of the labor force) and that they began to increase so late, in comparison to other countries. The main goal of the paper is to advocate consideration of negative cases in migration research; a proper theory of labor migration would distinguish between positive and negative cases.
Double-Blind Placebo-Controlled Treatment Trial of Chlamydia trachomatis Endocervical Infections in Pregnant Women

Objective: The purpose of this study was to determine if treatment of pregnant women with Chlamydia trachomatis infection would lower the incidence of preterm delivery and/or low birth weight. Methods: Pregnant women between the 23rd and 29th weeks of gestation were randomized in double-blind fashion to receive either erythromycin 333 mg three times daily or an identical placebo. The trial continued until the end of the 35th week of gestation. Results: When the results were examined without regard to study site, erythromycin had little impact on reducing low birth weight (8% vs. 11%, P = 0.4) or preterm delivery (13% vs. 15%, P = 0.7). At the sites with high persistence of C. trachomatis in the placebo-treated women, low birth weight infants occurred in 9 (8%) of 114 erythromycin-treated and 18 (17%) of 105 placebo-treated women (P = 0.04) and delivery <37 weeks occurred in 15 (13%) of 115 erythromycin-treated and 18 (17%) of 105 placebo-treated women (P = 0.4). Conclusions: The results of this trial suggest that the risk of low birth weight can be decreased by giving erythromycin to some women with C. trachomatis. Due to the high clearance rate of C. trachomatis in the placebo group, these data do not provide unequivocal evidence that erythromycin use in all C. trachomatis-infected women prevents low birth weight.
Self-attention Based Model for Punctuation Prediction Using Word and Speech Embeddings

This paper proposes to use self-attention based model to predict punctuation marks for word sequences. The model is trained using word and speech embedding features which are obtained from the pre-trained Word2Vec and Speech2Vec, respectively. Thus, the model can use any kind of textual data and speech data. Experiments are conducted on English IWSLT2011 datasets. The results show that the self-attention based model trained using word and speech embedding features outperforms the previous state-of-the-art single model by up to 7.8% absolute overall F1-score. The results also show that it obtains performance improvement by up to 4.7% absolute overall F1-score against the previous best ensemble model.
Modeling of species distributions with Maxent: new extensions and a comprehensive evaluation

Accurate modeling of geographic distributions of species is crucial to various applications in ecology and conservation. The best performing techniques often require some parameter tuning, which may be prohibitively time-consuming to do separately for each species, or unreliable for small or biased datasets. Additionally, even with the abundance of good quality data, users interested in the application of species models need not have the statistical knowledge required for detailed tuning. In such cases, it is desirable to use “default settings”, tuned and validated on diverse datasets. Maxent is a recently introduced modeling technique, achieving high predictive accuracy and enjoying several additional attractive properties. The performance of Maxent is influenced by a moderate number of parameters. The first contribution of this paper is the empirical tuning of these parameters. Since many datasets lack information about species absence, we present a tuning method that uses presence-only data. We evaluate our method on independently collected high-quality presence-absence data. In addition to tuning, we introduce several concepts that improve the predictive accuracy and running time of Maxent. We introduce “hinge features” that model more complex relationships in the training data; we describe a new logistic output format that gives an estimate of probability of presence; finally we explore “background sampling” strategies that cope with sample selection bias and decrease model-building time. Our evaluation, based on a diverse dataset of 226 species from 6 regions, shows: 1) default settings tuned on presence-only data achieve performance which is almost as good as if they had been tuned on the evaluation data itself; 2) hinge features substantially improve model performance; 3) logistic output improves model calibration, so that large differences in output values correspond better to large differences in suitability; 4) “target-group” background sampling can give much better predictive performance than random background sampling; 5) random background sampling results in a dramatic decrease in running time, with no decrease in model performance.
Segmentation of Vehicles and Roads by a Low-Channel Lidar

An effective method to segment vehicles and roads is proposed for autonomous vehicles using low-channel 3D lidar. The distance-view transformation is newly proposed to overcome the low density of top-view data of lidar. In addition, a dilated convolution structure is proposed to expand the receptive field of a convolutional neural network. The proposed network improves the accuracy of segmentation. The experimental results are presented to verify the usefulness of the proposed method.
Does Education matter for convergence in carbon dioxide per capita emissions

Recent papers have debated the existence of converg ence in carbon dioxide per capita. This paper improves on existing work and examines the im portance of education on the convergence in carbon dioxide per capita emissions ver the period 1970-2004 for 85 countries. We use panel data and apply GMM-System. This rigorous approach takes into account observed and unobserved heterogeneity of co untries and solves the endogeneity of some variables. Our results suggest a divergence in carbon dioxide per capita emissions and education doesn’t matter. Contrary to common intuition, in developing countries there is no convergence and education doesn’t matter for carbon dioxide growth. In developed countries, education favours convergence in carbon dioxide per capita on ly if it interacts with good political institutions. Without interaction to political inst itutions, education increases carbon dioxide per capita growth and handicaps carbon dioxide per capita convergence.