Miracle-dz/UniFAR-FTUs huggingface dataset:
Neutrophils Contribute to Excess Serum BAFF Levels and Promote CD4+ T Cell and B Cell Responses in Lupus-Prone Mice

Despite increased frequencies of neutrophils found in autoimmune diseases such as systemic lupus erythematosus (SLE), how they contribute to disease pathogenesis and the mechanisms that affect the accumulation of neutrophils are poorly understood. The aim of this study was to identify factors in autoantibody-mediated autoimmunity that controls the accumulation of spleen resident neutrophils and to determine whether neutrophils contribute to abnormal B cell responses. Increased levels of the cytokine BAFF have been linked to loss of B cell tolerance in autoimmunity, but the cellular source responsible for excess BAFF is unknown. B cell maturation antigen (BCMA) is a receptor for BAFF and is critical for the survival of bone marrow plasma cells. Paradoxically, BCMA deficiency exacerbates the formation of autoantibody-secreting plasma cells in spleens of lupus-prone mice and the reasons for this effect are not understood. Here we analyzed the phenotype, localization and function of neutrophils in spleens of healthy mice and congenic lupus-prone mice, and compared mice sufficient or deficient in BCMA expression. Neutrophils were found to be significantly increased in frequency and activation status in spleens of lupus-prone mice when BCMA was absent. Furthermore, neutrophils localized within T cell zones and enhanced CD4+ T cell proliferation and IFNγ production through the production of BAFF. Reduced BAFF and IFNγ serum levels, decreased frequencies of IFNγ-producing T cells, germinal center B cells, and autoantibody production after neutrophil depletion indicated the involvement of neutrophils in these autoimmune traits. Thus, we have identified a novel role for BCMA to control excess BAFF production in murine lupus through restraining the accumulation of BAFF-producing neutrophils. Our data suggests that devising therapeutic strategies to reduce neutrophils in autoimmunity may decrease BAFF levels and ameliorate disease.
To Cyberloaf or Not to Cyberloaf: The Impact of the Announcement of Formal Organizational Controls

Abstract We investigate the changing causal relationships between cyberloafing behavior and its antecedents after the announcement of formal organizational controls that, unlike informal controls, are officially imposed by organizations. Drawing on Akers’s social learning theory, we first propose neutralization, perceived risk, past cyberloafing, and peer cyberloafing as antecedents of cyberloafing. We then develop a theoretical account of how their impacts change from before to after the announcement of formal controls. The proposed model was empirically tested using data collected from two separate surveys administered a month apart. The first survey captured the preannouncement state of cyberloafing among respondents; the follow-up survey was administered after the respondents were asked to assume that their company had just announced anti-cyberloafing controls that used explicit monitoring and sanctions. We show that preannouncement, employees’ intentions to cyberloaf are mostly influenced by their past tendencies to cyberloaf and by others’ cyberloafing, but their neutralization and perceived risk play no significant role. In contrast, postannouncement, the impacts of individuals’ neutralization and perceived risk on their cyberloafing suddenly become significant. Theoretically, we demonstrate that to accurately predict noncompliant behavior, it is important to account for all four antecedents and incorporate the announcement of formal controls. Practically, understanding how this announcement affects the relationships between cyberloafing and its antecedents suggests different areas managers need to target, pre- and postannouncement, to curb cyberloafing.
Homozygous Survival Motor Neuron 2 Gene Deletion and Sporadic Lower Motor Neuron Disease in Children

A case of lower motor neuron disease with homozygous survival motor neuron 2 (SMN2) gene deletion is reported in this article. A 7-year-old boy was admitted to our hospital with main complaints of lower extremity weakness and difficulty squatting for the past year. SMN gene copies were quantified by multiplex ligation-dependent probe amplification. Exons 7 and 8 of the SMN1 gene were normal, but homozygous deletion of exons 7 and 8 of the SMN2 gene was identified. Homozygous deletion of exons 7 and 8 of the SMN centromeric gene was detected, and exons 7 and 8 of the SMN1 gene were found to be normal in the proband. Two copies of exons 7 and 8 of the SMN1 gene were identified, and zero copies of exons 7 and 8 of the SMN2 gene were found. We consider that this case represents a previously unrecognized type of lower motor neuron disease that resulted from homozygous deletion of the SMN2 gene.
Fornix Microstructure Correlates with Recollection But Not Familiarity Memory

The fornix is the main tract between the medial temporal lobe (MTL) and medial diencephalon, both of which are critical for episodic memory. The precise involvement of the fornix in memory, however, has been difficult to ascertain since damage to this tract in human amnesics is invariably accompanied by atrophy to surrounding structures. We used diffusion-weighted imaging to investigate whether individual differences in fornix white matter microstructure in neurologically healthy participants were related to differences in memory as assessed by two recognition tasks. Higher microstructural integrity in the fornix tail was found to be associated with significantly better recollection memory. In contrast, there was no significant correlation between fornix microstructure and familiarity memory or performance on two non-mnemonic tasks. Our findings support the idea that there are distinct MTL–diencephalon pathways that subserve differing memory processes.
Pax-6 and Cdx-2/3 Interact to Activate Glucagon Gene Expression on the G1 Control Element*

The promoter element G1, critical for α-cell-specific expression of the glucagon gene, contains two AT-rich sequences important for transcriptional activity. Pax-6, a paired homeodomain protein previously shown to be required for normal α-cell development and to interact with the enhancer element G3 of the glucagon gene, binds as a monomer to the distal AT-rich site of G1. However, although the paired domain of Pax-6 is sufficient for interaction with the G3 element, the paired domain and the homeodomain are required for high affinity binding to G1. In addition to monomer formation, Pax-6 interacts with Cdx-2/3, a caudal-related homeodomain protein binding to the proximal AT-rich site, to form a heterodimer on G1. Both proteins are capable of directly interacting in the absence of DNA. In BHK-21 cells, Pax-6 activates glucagon gene transcription both through G3 and G1, and heterodimerization with Cdx-2/3 on G1 leads to more than additive transcriptional activation. In glucagon-producing cells, both G1 and G3 are critical for basal transcription, and the Pax-6 and Cdx-2/3 binding sites are required for activation. We conclude that Pax-6 is not only critical for α-cell development but also for glucagon gene transcription by its independent interaction with the two DNA control elements, G1 and G3.
Energy balance and body composition in cancer patients.

Abstract Energy balance and body composition were studied in 10 cancer patients to investigate the interrelationship between energy expenditure and energy intake in the development of cancer cachexia. These data were compared to the findings in control patients of similar age with diseases affecting physical activities to about the same extent. The measurements of energy expenditure and intake were repeated when possible during progression of the malignant disease. Body composition in a larger group of cancer patients (n = 29) was compared to data from a group of healthy subjects within the same age range (n = 164). The cancer patients were below normal in body weight and body cell mass. Body fat was reduced in women with cancer. Energy intake (mean, 1270 kcal/day), although varying greatly, was not significantly different from the intake in the controls (mean, 1470 kcal/day). Both the daily energy expenditure (mean, 2020 kcal/24 hr) and the resting metabolic rate (mean, 1630 kcal/24 hr) were significantly greater in the cancer patients than they were in the controls (mean, 1420 and 1170 kcal/24 hr, respectively). Parallel to exacerbation of the disease and reduced energy intake, the energy expenditure and the resting metabolic rate increased in relation to body cell mass in two patients. After curative surgery both intake and expenditure of energy returned to normal levels in one patients. For a more accurate interpretation of the higher daily energy expenditure and resting metabolic rate found in the cancer patients, the influences of body weight, body cell mass, and height were ruled out. The results suggest that one of the reasons for the development of cancer cachexia is an increasing resting metabolic rate and daily energy expenditure.
JExtract: An Eclipse Plug-in for Recommending Automated Extract Method Refactorings

Although Extract Method is a key refactoring for improving program comprehension, refactoring tools for such purpose are often underused. To address this shortcoming, we present JExtract, a recommendation system based on structural similarity that identifies Extract Method refactoring opportunities that are directly automated by IDE-based refactoring tools. Our evaluation suggests that JExtract is far more effective (w.r.t. recall and precision) to identify misplaced code in methods than JDeodorant, a state-of-the-art tool
Interferon-Gamma Release Assay Performance of Pleural Fluid and Peripheral Blood in Pleural Tuberculosis

Background The diagnosis of pleural tuberculosis (TB) remains to be difficult. Interferon-gamma release assay (IGRA) is a promising method for diagnosing TB in low TB burden countries. The release of interferon-gamma (IFN-γ) by T lymphocytes increases at a localized site of infection with Mycobacterium tuberculosis antigen. This study aimed to examine the clinical accuracy of T-SPOT.TB on pleural fluid and peripheral blood for the diagnosis of pleural TB in high TB burden country. Methods 168 subjects with pleural effusion were enrolled prospectively and examined with T-SPOT.TB on pleural fluid and peripheral blood samples simultaneously. Results The receiver operating characteristic (ROC) curve and cut-off value of pleural fluid T-SPOT.TB was established according to spot forming cells (SFC) between culture/biopsy-confirmed pleural TB group and no pleural TB group. The sensitivity of pleural fluid T-SPOT.TB and peripheral blood T-SPOT.TB was similar (96.3% and 92.7%, respectively) (P= 0.691). In contrast, the specificity of pleural fluid T-SPOT.TB (94.5%) was significantly higher than that of peripheral blood T-SPOT.TB (76.1%) (P=0.002). 2% (2/98) of pleural fluid T-SPOT.TB results were indeterminate. Conclusion The diagnostic accuracy of peripheral blood T-SPOT.TB is low in high TB burden countries due to latent tuberculosis infection. Pleural fluid T-SPOT.TB is a relatively useful and supplementary test to explore pleural TB in high TB burden countries, but its diagnostic accuracy needs to be validated in further large scale research.
Extensive composite molar restorations: 3 years clinical evaluation

Abstract Objective. To evaluate the clinical performance of extensive direct composite restorations in molars after 1 and 3 years and to find out the importance of extent of the restorations and other factors related to their performance. Materials and methods. Seventy-four patients with a molar tooth in need of a restoration covering at least three surfaces and one cusp were selected. Patient-related factors were registered and the tooth was prepared and restored by using a nano-filled composite. A topographic system for classification of extensive posterior restorations was developed. At baseline, the operator recorded a clinical evaluation, using modified USPHS-criteria. After 1 and 3 years, an independent observer evaluated the restorations. Post-operative problems arising during the observation period were registered. Results. A change in clinical score from baseline to the 1 and 3 year recall was recorded for all clinical criteria. A total of nine restorations were graded as unacceptable after 3 years (3-year survival rate of 87.7% and a mean annual failure rate of 4.2%). Except for gender (p = 0.022), none of the patient-related factors investigated (age, caries risk, extension of the restoration and presence of cervical enamel) had a significant influence on the survival of the restorations. Conclusions. Extensive direct posterior composite restorations showed an acceptable clinical performance after 3 years. Men had a significantly greater restoration failure rate than women.
Effect Of Permethrin, Pirimiphos Methyl And Bendiocarb On The Osmotic Resistance Of Rat Erythrocytes

Environmental pollution by insecticides is one of the most important problems in the world. Some of the pesticides were found to exert carcinogenic, teratogenic and/or mutagenic effects even following normal agricultural use (U.S.Geological Survey, 1997). On the other hand residues from insecticides, herbicides and insect growth hormones are known to represent the most common food contaminants particularly in developing countries. Thus the wide spread use of insecticides in agriculture stimulated our interest for studying their possible toxic effect(s) in man and animals. The aim of the present work was to study the effect of short term (for 2 weeks) oral daily feeding with diet containing 10 times the human maximum acceptable daily intake (a concentration that may be faced by human) of either permethrin, pirimiphos-methyl or bendiocarb on osmotic fragility of rat erythrocytes. Sprague Dawley male rats were divided into four groups, each consists of 10 animals. Animals of each group were fed either normal diet (control group), permethrin (21.7 ppm), pirimiphos-methyl (4.4 ppm) or bendiocarb (2.0 ppm) for 2 weeks. Twenty four hours later, blood samples were withdrawn and osmotic fragility was determined. The obtained results indicated that permethrin, pirimiphos-methyl and bendiocarb increase the osmotic fragility.
Retinoblastoma. A study of two cases by electron microscopy.

The ultrastructure of two retinoblastomas includes cytologic features which are characteristic of neoplasia. Unusual degenerative changes were observed in both tumors. Rosettes xoere present in one case, and the cells which formed them showed some characteristics of ependyma of the primitive neural tube, and also of developing vision receptor cells. Structures resembling pericentriolar bodies xoere associated with basal bodies of cilia in rosettes.
Human Dendritic Cell DC-SIGN and TLR-2 Mediate Complementary Immune Regulatory Activities in Response to Lactobacillus rhamnosus JB-1

The microbiota is required for optimal host development and ongoing immune homeostasis. Lactobacilli are common inhabitants of the mammalian large intestine and immunoregulatory effects have been described for certain, but not all, strains. The mechanisms underpinning these protective effects are beginning to be elucidated. One such protective organism is Lactobacillus rhamnosus JB-1 (Lb. rhamnosus JB-1). Lb. murinus has no such anti-inflammatory protective effects and was used as a comparator organism. Human monocyte-derived dendritic cells (MDDCs) were co-incubated with bacteria and analysed over time for bacterial adhesion and intracellular processing, costimulatory molecule expression, cytokine secretion and induction of lymphocyte polarization. Neutralising antibodies were utilized to identify the responsible MDDC receptors. Lb. rhamnosus JB-1 adhered to MDDCs, but internalization and intracellular processing was significantly delayed, compared to Lb. murinus which was rapidly internalized and processed. Lb. murinus induced CD80 and CD86 expression, accompanied by high levels of cytokine secretion, while Lb. rhamnosus JB-1 was a poor inducer of costimulatory molecule expression and cytokine secretion. Lb. rhamnosus JB-1 primed MDDCs induced Foxp3 expression in autologous lymphocytes, while Lb. murinus primed MDDCs induced Foxp3, T-bet and Ror-γt expression. DC-SIGN was required for Lb. rhamnosus JB-1 adhesion and influenced IL-12 secretion, while TLR-2 influenced IL-10 and IL-12 secretion. Here we demonstrate that the delayed kinetics of bacterial processing by MDDCs correlates with MDDC activation and stimulation of lymphocytes. Thus, inhibition or delay of intracellular processing may be a novel strategy by which certain commensals may avoid the induction of proinflammatory responses.
Modeling of Interactions between the Zebrafish Hatching Enzyme ZHE1 and A Series of Metal Oxide Nanoparticles: Nano-QSAR and Causal Analysis of Inactivation Mechanisms

The quantitative relationships between the activity of zebrafish ZHE1 enzyme and a series of experimental and physicochemical features of 24 metal oxide nanoparticles were revealed. Vital characteristics of the nanoparticles’ structure were reflected using both experimental and theoretical descriptors. The developed quantitative structure–activity relationship model for nanoparticles (nano-QSAR) was capable of predicting the enzyme inactivation based on four descriptors: the hydrodynamic radius, mass density, the Wigner–Seitz radius, and the covalent index. The nano-QSAR model was calculated using the non-linear regression tree M5P algorithm. The developed model is characterized by high robustness R2bagging = 0.90 and external predictivity Q2EXT = 0.93. This model is in agreement with modern theories of aquatic toxicity. Dissolution and size-dependent characteristics are among the key driving forces for enzyme inactivation. It was proven that ZnO, CuO, Cr2O3, and NiO nanoparticles demonstrated strong inhibitory effects because of their solubility. The proposed approach could be used as a non-experimental alternative to animal testing. Additionally, methods of causal discovery were applied to shed light on the mechanisms and modes of action.
Brain microvessel cross-presentation is a hallmark of experimental cerebral malaria

Cerebral malaria is a devastating complication of Plasmodium falciparum infection. Its pathogenesis is complex, involving both parasite‐ and immune‐mediated events. CD8+ T cells play an effector role in murine experimental cerebral malaria (ECM) induced by Plasmodium berghei ANKA (PbA) infection. We have identified a highly immunogenic CD8 epitope in glideosome‐associated protein 50 that is conserved across rodent malaria species. Epitope‐specific CD8+ T cells are induced during PbA infection, migrating to the brain just before neurological signs manifest. They are functional, cytotoxic and can damage the blood–brain barrier in vivo. Such CD8+ T cells are also found in the brain during infection with parasite strains/species that do not induce neuropathology. We demonstrate here that PbA infection causes brain microvessels to cross‐present parasite antigen, while non‐ECM‐causing parasites do not. Further, treatment with fast‐acting anti‐malarial drugs before the onset of ECM reduces parasite load and thus antigen presentation in the brain, preventing ECM death. Thus our data suggest that combined therapies targeting both the parasite and host antigen‐presenting cells may improve the outcome of CM patients.
Sex Differences in the Adult Human Brain: Evidence from 5216 UK Biobank Participants

Sex differences in human brain structure and function are of substantial scientific interest because of sex-differential susceptibility to psychiatric disorders [1,2,3] and because of the potential to explain sex differences in psychological traits [4]. Males are known to have larger brain volumes, though the patterns of differences across brain subregions have typically only been examined in small, inconsistent studies [5]. In addition, despite common findings of greater male variability in traits like intelligence [6], personality [7], and physical performance [8], variance differences in the brain have received little attention. Here we report the largest single-sample study of structural and functional sex differences in the human brain to date (2,750 female and 2,466 male participants aged 44-77 years). Males had higher cortical and sub-cortical volumes, cortical surface areas, and white matter diffusion directionality; females had thicker cortices and higher white matter tract complexity. Considerable overlap between the distributions for males and females was common, and subregional differences were smaller after accounting for global differences. There was generally greater male variance across structural measures. The modestly higher male score on two cognitive tests was partly mediated via structural differences. Functional connectome organization showed stronger connectivity for males in unimodal sensorimotor cortices, and stronger connectivity for females in the default mode network. This large-scale characterisation of neurobiological sex differences provides a foundation for attempts to understand the causes of sex differences in brain structure and function, and their associated psychological and psychiatric consequences.
Automatically Generating Game Tactics through Evolutionary Learning

The decision-making process of computer-controlled opponents in video games is called game AI. Adaptive game AI can improve the entertainment value of games by allowing computer-controlled opponents to ix weaknesses automatically in the game AI and to respond to changes in human-player tactics. Dynamic scripting is a reinforcement learning approach to adaptive game AI that learns, during gameplay, which game tactics an opponent should select to play effectively. In previous work, the tactics used by dynamic scripting were designed manually. We introduce the evolutionary state-based tactics generator (ESTG), which uses an evolutionary algorithm to generate tactics automatically. Experimental results show that ESTG improves dynamic scripting's performance in a real-time strategy game. We conclude that high-quality domain knowledge can be automatically generated for strong adaptive game AI opponents. Game developers can bene it from applying ESTG, as it considerably reduces the time and effort needed to create adaptive game AI.