Miracle-dz/UniFAR-FTUs huggingface dataset:
Whole-Body 12C Irradiation Transiently Decreases Mouse Hippocampal Dentate Gyrus Proliferation and Immature Neuron Number, but Does Not Change New Neuron Survival Rate

High-charge and -energy (HZE) particles comprise space radiation and they pose a challenge to astronauts on deep space missions. While exposure to most HZE particles decreases neurogenesis in the hippocampus—a brain structure important in memory—prior work suggests that 12C does not. However, much about 12C’s influence on neurogenesis remains unknown, including the time course of its impact on neurogenesis. To address this knowledge gap, male mice (9–11 weeks of age) were exposed to whole-body 12C irradiation 100 cGy (IRR; 1000 MeV/n; 8 kEV/µm) or Sham treatment. To birthdate dividing cells, mice received BrdU i.p. 22 h post-irradiation and brains were harvested 2 h (Short-Term) or three months (Long-Term) later for stereological analysis indices of dentate gyrus neurogenesis. For the Short-Term time point, IRR mice had fewer Ki67, BrdU, and doublecortin (DCX) immunoreactive (+) cells versus Sham mice, indicating decreased proliferation (Ki67, BrdU) and immature neurons (DCX). For the Long-Term time point, IRR and Sham mice had similar Ki67+ and DCX+ cell numbers, suggesting restoration of proliferation and immature neurons 3 months post-12C irradiation. IRR mice had fewer surviving BrdU+ cells versus Sham mice, suggesting decreased cell survival, but there was no difference in BrdU+ cell survival rate when compared within treatment and across time point. These data underscore the ability of neurogenesis in the mouse brain to recover from the detrimental effect of 12C exposure.
Warped Hypertime Representations for Long-Term Autonomy of Mobile Robots

This letter presents a novel method for introducing time into discrete and continuous spatial representations used in mobile robotics, by modeling long-term, pseudo-periodic variations caused by human activities or natural processes. Unlike previous approaches, the proposed method does not treat time and space separately, and its continuous nature respects both the temporal and spatial continuity of the modeled phenomena. The key idea is to extend the spatial model with a set of wrapped time dimensions that represent the periodicities of the observed events. By performing clustering over this extended representation, we obtain a model that allows the prediction of probabilistic distributions of future states and events in both discrete and continuous spatial representations. We apply the proposed algorithm to several long-term datasets acquired by mobile robots and show that the method enables a robot to predict future states of representations with different dimensions. The experiments further show that the method achieves more accurate predictions than the previous state of the art.
Babesia gibsoni cytochrome b mutations in canine blood samples submitted to a US veterinary diagnostic laboratory

Background: Babesiosis caused by Babesia gibsoni is recognized throughout the world and can be difficult to treat. Resistance to atovaquone is associated with mutations in the B. gibsoni mitochondrial genome, specifically the M128 position of cytochrome b (cytb). The prevalence of cytb mutations in North America has not been reported. Hypothesis/Objectives: The objective of our study was to describe the prevalence of cytb M128 mutations in B. gibsoni in canine blood samples submitted to a US veterinary diagnostic laboratory. A secondary objective was to determine whether or not some dogs had wild‐type cytb in our initial samples then had M128 mutations detected in follow‐up samples. Animals: One‐Hundred seventy‐four dogs that tested positive for the presence of B. gibsoni between 2012 and 2017. Methods: Case series of consecutive samples submitted to a veterinary diagnostic laboratory. Partial B. gibsoni cytb genes were amplified by polymerase chain reaction and screened for the presence of mutations at the M128 position. Results: The overall prevalence of M128 mutants was 3.5% (6/173 dogs) in the initial samples. The incidence of new cytb mutants in dogs that tested positive for B. gibsoni, which then had follow‐up testing, was 12.1% (5/41). Conclusions and Clinic Importance: Our study reaffirms that B. gibsoni infection is widespread and most commonly detected in American Staffordshire Terrier/American Pit Bull Terrier dogs (128/174, 74% of the infected dogs in our study). The prevalence of cytb mutations does not warrant pretreatment genotyping.
Computational insights into pH‐dependence of structure and dynamics of pyrazinamidase: A comparison of wild type and mutants

The mycobacterial enzyme pyrazinamidase (PZase) is the target of key tuberculosis drug, pyrazinamide. Mutations in PZase cause drug resistance. Herein, three point mutations, W68G, L85P, and V155G, were investigated through over 8 µs of molecular dynamics simulations coupled with essential dynamics and binding pocket analysis at neutral (pH = 7) and acidic (pH = 4) ambient conditions. The 51‐71 flap region exhibited drastic displacement leading to enlargement of binding cavity, especially at the lower pH. Accessibility of solvent to the active site of the mutant enzymes was also reduced. The protonation of key surface residues at low pH results in more contribution of these residues to structural stability and integrity of the enzyme and reduced interactions with solvent molecules, which acts as a cage, keeping the enzyme together. The observed results suggest a pattern of structural alterations due to point mutations in PZase, which is consistent with other experimental and theoretical investigations and, can be harnessed for drug design purposes.
Profiling of B-Cell Factors and Their Decoy Receptors in Rheumatoid Arthritis: Association With Clinical Features and Treatment Outcomes

Introduction: B-cell activation is pivotal in rheumatoid arthritis (RA) pathogenesis and represents a relevant therapeutic target. The main aim of this study was to characterize the profiles of B-cell factors and their decoy receptors in RA and evaluate their clinical relevance. Methods: sBLyS, sAPRIL, sBCMA, sTACI, sBLyS-R, and several cytokines' serum levels were measured by immunoassays in 104 RA patients and 33 healthy controls (HC). An additional group of 42 systemic lupus erythematosus (SLE) patients were enrolled as disease controls. Whole blood IFI44, IFI44L, IFI6, and MX1 gene expression was measured and averaged into an IFN-score. BLyS membrane expression (mBLyS) was assessed on blood cell subsets by flow cytometry. Results: increased sAPRIL and sBCMA levels were found in RA, whereas BLyS was elevated in very early RA (VERA). No differences were observed for sTACI and sBLyS-R. An increased sBLyS/sBLyS-R ratio was associated with poor clinical outcome at 6 and 12 months in VERA, whereas a positive association with disease activity was observed in established disease. Increased mBLyS expression was found on monocytes, mDCs, neutrophils and B-cells in RA, to a similar extent that in SLE patients. Cluster analysis identified a specific B-cell factors profile overrepresented in RA and associated with autoantibodies, elevated proinflammatory cytokines (IFNα, MIP1α, TNFα, IL-37, and GM-CSF) and increased type-I IFN signature. Increasing sBCMA and sBLyS serum levels upon treatment and mBLyS expression at baseline on monocytes and mDCs, but not B-cells, were associated with poor clinical outcome upon TNFα-blockade. Conclusions: profound and complex alterations of soluble and membrane-bound B-cell factors are observed in RA associated with clinical outcomes, thus supporting its applicability to guide patient stratification along disease course.
GDP-l-fucose synthase is a CD4+ T cell–specific autoantigen in DRB3*02:02 patients with multiple sclerosis

GDP-l-fucose synthase is an autoantigen recognized by cerebrospinal fluid–infiltrating CD4+ T cells from HLA-DRB3* patients with multiple sclerosis. Move over myelin Although it is well established that autoreactive lymphocytes induce demyelination in multiple sclerosis, the exact antigenic targets that initiate disease are undefined. Planas et al. studied CD4+ T cells from the cerebrospinal fluid of patients with multiple sclerosis. One CD4+ T cell clone was reactive to the human enzyme GDP-l-fucose synthase; T cells from other patients were then identified, as well as myelin-reactive cells. Intriguingly, some of the GDP-l-fucose synthase–reactive cells could also be stimulated by a bacterial version of the enzyme. These tantalizing results identify a new autoantigen and suggest that one possible trigger of disease could be cross-reactivity to microbiota-derived peptides. Multiple sclerosis is an immune-mediated autoimmune disease of the central nervous system that develops in genetically susceptible individuals and likely requires environmental triggers. The autoantigens and molecular mimics triggering the autoimmune response in multiple sclerosis remain incompletely understood. By using a brain-infiltrating CD4+ T cell clone that is clonally expanded in multiple sclerosis brain lesions and a systematic approach for the identification of its target antigens, positional scanning peptide libraries in combination with biometrical analysis, we have identified guanosine diphosphate (GDP)–l-fucose synthase as an autoantigen that is recognized by cerebrospinal fluid–infiltrating CD4+ T cells from HLA-DRB3*–positive patients. Significant associations were found between reactivity to GDP-l-fucose synthase peptides and DRB3*02:02 expression, along with reactivity against an immunodominant myelin basic protein peptide. These results, coupled with the cross-recognition of homologous peptides from gut microbiota, suggest a possible role of this antigen as an inducer or driver of pathogenic autoimmune responses in multiple sclerosis.
Molecular Mechanisms Directing Migration and Retention of Natural Killer Cells in Human Tissues

A large body of data shows that Natural Killer (NK) cells are immune effectors exerting a potent cytolytic activity against tumors and virus infected cells. The discovery and characterization of several inhibitory and activating receptors unveiled most of the mechanisms allowing NK cells to spare healthy cells while selectively attacking abnormal tissues. Nevertheless, the mechanisms ruling NK cell subset recirculation among the different compartments of human body have only lately started to be investigated. This is particularly true for pathological settings such as tumors or infected tissues but also for para-physiological condition like pregnant human uterine mucosa. It is becoming evident that the microenvironment associated to a particular clinical condition can deeply influence the migratory capabilities of NK cells. In this review we describe the main mechanisms and stimuli known to regulate the expression of chemokine receptors and other molecules involved in NK cell homing to either normal or pathological/inflamed tissues, including tumors or organs such as lung and liver. We will also discuss the role played by the chemokine/chemokine receptor axes in the orchestration of physiological events such as NK cell differentiation, lymphoid organ retention/egress and recruitment to decidua during pregnancy.
Rapid and low-cost multiplex synthesis of chemokine analogs

Peptides represent a promising source of new medicines, but improved technologies are needed to facilitate discovery and optimization campaigns. In particular, longer peptides with multiple disulfide bridges are challenging to produce, and producing large numbers of structurally related variants is dissuasively costly and time-consuming. The principal cost and time drivers are the multiple column chromatography purification steps that are used during the multistep chemical synthesis procedure, which involves both ligation and oxidative refolding steps. In this study, we developed a method for multiplex parallel synthesis of complex peptide analogs in which the structurally variant region of the molecule is produced as a small peptide on a 384-well synthesizer with subsequent ligation to the longer, structurally invariant region and oxidative refolding carried out in-well without any column purification steps. To test the method, we used a panel of 96 analogs of the chemokine RANTES (regulated on activation normal T cell expressed and secreted)/CCL5 (69 residues, two disulfide bridges), which had been synthesized using standard approaches and characterized pharmacologically in an earlier study. Although, as expected, the multiplex method generated chemokine analogs of lower purity than those produced in the original study, it was nonetheless possible to closely match the pharmacological attributes (anti-HIV potency, capacity to elicit G protein signaling, and capacity to elicit intracellular receptor sequestration) of each chemokine analog to reference data from the earlier study. This rapid, low-cost approach has the potential to support discovery and optimization campaigns based on analogs of other chemokines as well as those of other complex peptide and small protein targets of a similar size.
The use of stem cells in ischemic heart disease treatment

Ischemic heart disease is a major cause of death and disabilities worldwide. Unfortunately, not all patients are suitable for direct revascularization. Cell-based therapies may be alternative options because of their potential to promote neovascularisation and endothelial repair, improving myocardial perfusion. The success of cell-based therapies depends on the type of implanted stem cells, delivery method and underlying disease. Several different cell populations including bone marrow-derived mononuclear cells (MNCs), mesenchymal stromal cells (MSCs), CD34+, CD133+, endothelial progenitor cells, adipose-derived mesenchymal stromal cells (ASCs) and stem cells from placenta and umbilical cord have been investigated. Presently, no consensus exists about the best cell type for clinical regenerative therapy. Because the system of coronary arteries in the ischemic area is poor and most of the coronary artery is significantly narrowed or closed, direct implantation of stem cells in the ischemic area of the heart muscle appears an attractive method.
Intra-abdominal Sepsis After Ileocolic Resection in Crohn’s Disease: The Role of Combination Immunosuppression

BACKGROUND: Intra-abdominal sepsis complicates <10% of ileocolic resections for Crohn’s disease, but the impact of combination immunosuppression and repeat resection on its development remains unknown. OBJECTIVE: The purpose of this study was to determine risk factors for intra-abdominal sepsis after ileocolic resection, specifically examining the role of combination immunosuppression and repeat intestinal resection. DESIGN: This was a retrospective review of patient records from 2007 to 2017. SETTINGS: The study was conducted at a single-institution IBD tertiary referral center. PATIENTS: Patients with a diagnosis of Crohn’s disease who were undergoing ileocolic resection with primary anastomosis were included. Diverted patients were excluded. MAIN OUTCOME MEASURES: Preoperative and intraoperative variables, including preoperative immunosuppressive regimens and previous intestinal resection, were evaluated as potential risk factors for intra-abdominal sepsis. RESULTS: A total of 621 patients (55% women) underwent ileocolic resection for Crohn’s disease; 393 (63%) were first-time resections. The rate of 30-day intra-abdominal sepsis was 8% (n = 50). On univariate analysis, triple immunosuppression (combination of a corticosteroid, immunomodulator, and biological) and previous intestinal resection were significantly associated with intra-abdominal sepsis. Both risk factors remained significant on multivariable analysis (OR for triple immunosuppression (vs none) = 3.53 (95% CI, 1.27–9.84); previous intestinal resection OR = 2.27 (95% CI, 1.25–4.13)). A significant trend was seen between an increasing number of these risk factors (triple immunosuppression and previous intestinal resection) and rate of intra-abdominal sepsis (5%, 12%, and 22% for 0, 1, and 2 risk factors; p < 0.01). A trend was observed between increasing number of previous intestinal resections and the rate of intra-abdominal sepsis (p < 0.01). LIMITATIONS: This study is limited by its single-institution tertiary referral center scope. CONCLUSIONS: Combination immunosuppression and previous intestinal resection were both associated with the development of intra-abdominal sepsis. In light of these results, surgeons should consider the effects of combination immunosuppression and a history of previous intestinal resection, in addition to other risk factors, when deciding which patients warrant temporary intestinal diversion. See Video Abstract at http://links.lww. com/DCR/A664.
Sleep Quality in Patients with Rheumatoid Arthritis and Associations with Pain, Disability, Disease Duration, and Activity

We aimed to assess the subjective sleep quality in patients with rheumatoid arthritis (RA) and its correlation with disease activity, pain, inflammatory parameters, and functional disability. In a cross-sectional study, patients with confirmed RA diagnosis responded to a questionnaire (consisting of socio-demographic data, the Health Assessment Questionnaire Disability Index, and the Medical Outcome Study Sleep Scale). Disease activity was assessed with the Clinical Disease Activity Index, and pain levels using the visual analogue scale. In addition, inflammatory markers (C-reactive protein, interleukin-6, and tumor necrosis factor alpha) were analyzed. Ninety-five patients were analyzed, predominantly female, with an average age of 50.59 (9.61) years. Fifty-seven percent reported non-optimal sleep duration, where functional disability (92.7% vs. 69.8%; p = 0.006) and higher median pain levels (3.75 (2.3–6.0) vs. 2.5 (2.0–3.5); p = 0.003) were also more prevalent. No differences in sociodemographic variables, disease duration or activity, inflammatory parameters, or use of biological and corticosteroid therapy were observed. The multivariate regression analysis showed that more intense pain was associated with a lower likelihood of optimal sleep (odds ratio (OR) = 0.68, 95% confidence interval (CI) 0.47–0.98, p = 0.038). Patients with RA report a high prevalence of non-optimal sleep, which is linked to pain level. Clinicians need to be aware of this issue and the potential effects on health and functional status.
Pathogenic Role of Immune Cells in Rheumatoid Arthritis: Implications in Clinical Treatment and Biomarker Development

Rheumatoid arthritis (RA) is a chronic, autoimmune, systemic, inflammatory disorder that affects synovial joints, both small and large joints, in a symmetric pattern. This disorder usually does not directly cause death but significantly reduces the quality of life and life expectancy of patients if left untreated. There is no cure for RA but, patients are usually on long-term disease modifying anti-rheumatic drugs (DMARDs) to suppress the joint inflammation, to minimize joint damage, to preserve joint function, and to keep the disease in remission. RA is strongly associated with various immune cells and each of the cell type contributes differently to the disease pathogenesis. Several types of immunomodulatory molecules mainly cytokines secreted from immune cells mediate pathogenesis of RA, hence complicating the disease treatment and management. There are various treatments for RA depending on the severity of the disease and more importantly, the patient’s response towards the given drugs. Early diagnosis of RA and treatment with (DMARDs) are known to significantly improve the treatment outcome of patients. Sensitive biomarkers are crucial in early detection of disease as well as to monitor the disease activity and progress. This review aims to discuss the pathogenic role of various immune cells and immunological molecules in RA. This review also highlights the importance of understanding the immune cells in treating RA and in exploring novel biomarkers.
T-cell lymphoma with rhabdomyolysis: case report and literature review

Rhabdomyolysis refers to the destruction or disintegration of striated muscles. This syndrome is characterized by muscle breakdown and necrosis, resulting in the leakage of intracellular muscle constituents into the circulation and extracellular fluid. We report a rare case of rhabdomyolysis complicating multi-organ failure caused by T-cell lymphoma in a 32-year-old woman. The final diagnosis was rhabdomyolysis caused by peripheral T-cell lymphoma based on bone marrow aspirate and biopsy.
Environmental Ethics Awareness of Teachers.

The environment can be described as 'the environment in which the living things live, are connected by vital bonds and interact with each other in various forms' (Yıldız & et al., 2005: 14). There is a balance between the living and non-living factors that make up the environment. However, Scientists have pointed out that human-induced activities after the Industrial Revolution led to the destruction of the balance in the periphery (Legget, 2007: 19). People's thoughts and behaviors are also influential in the formation of environmental problems (Watson & Halse, 2005; Kahyaoğlu, 2011; Şenyurt, Temel & Özkahraman, 2011). Mankind has adopted the concept of excessive consumption and destruction, as opposed to benefiting from nature at the rate of its own needs. Moreover, mankind regarded itself as the "master of nature"(Armstrong & Botzler, 1993: 53) and thought that other beings had no value other than their utility (Karaca, 2007). This has resulted in serious degradation of natural balance and serious environmental problems. People are now faced with environmental problems that have previously been ignored (Ertan, 2004). Human nature needs to learn that it is part of nature, not ownership. This will ensure that the person is aware of their responsibilities towards nature. Human is not the owner of nature. He has to learn that human beings are part of nature. This will ensure that the person is aware of their responsibilities towards natüre (Özer & Keleş, 2016). It is very important that the individual is aware of the environment ethics. Individuals who are aware of environmental ethics are actively involved in the protection of the environment. Environmental ethics is concerned with the resolution of environmental problems faced by individuals (Freiman, 2006). Environmental ethics is a theoretical discipline that examines all kinds of attitudes and behaviors that people consider important when making decisions about nature, factors that make up nature, or the environment (Karaca, 2007). The environmental ethic evaluates the relationship of people to nature Abstract
Aggregated Dilated Convolutions for Efficient Motion Deblurring

Blind motion deblurring is a challenging computer vision problem due to its ill-posed nature. Moreover, this problem becomes more challenging when blur varies spatially over the entire image. Meanwhile, the efficiency of blind motion deblurring algorithms is also very important. In this work, we propose a convolutional neural network (CNN) to solve this problem in an end-to-end manner. The network architecture is based on conditional Generative Adversarial Network (cGAN) integrated with stacked encoder-decoder architecture and skip connections. We use a residual block which aggregates dilated convolutions to construct our network. With experiments on the benchmark dataset, we demonstrate that the proposed method achieves competitive performance compared with the state-of-the-art blind motion deblurring methods, and in the meanwhile reduces time and memory overhead.