Miracle-dz/UniFAR-FTUs huggingface dataset:
Infection with Host-Range Mutant Adenovirus 5 Suppresses Innate Immunity and Induces Systemic CD4+ T Cell Activation in Rhesus Macaques

Ad5 is a common cause of respiratory disease and an occasional cause of gastroenteritis and conjunctivitis, and seroconversion before adolescence is common in humans. To gain some insight into how Ad5 infection affects the immune system of rhesus macaques (RM) 18 RM were infected with a host-range mutant Ad5 (Ad5hr) by 3 mucosal inoculations. There was a delay of 2 to 6 weeks after the first inoculation before plasmacytoid dendritic cell (pDC) frequency and function increased in peripheral blood. Primary Ad5hr infection suppressed IFN-γ mRNA expression, but the second Ad5hr exposure induced a rapid increase in IFN-gamma mRNA in peripheral blood mononuclear cells (PBMC). Primary Ad5hr infection suppressed CCL20, TNF and IL-1 mRNA expression in PBMC, and subsequent virus exposures further dampened expression of these pro-inflammatory cytokines. Primary, but not secondary, Ad5hr inoculation increased the frequency of CXCR3+ CD4+ T cells in blood, while secondary, but not primary, Ad5hr infection transiently increased the frequencies of Ki67+, HLADR+ and CD95+/CCR5+ CD4+ T cells in blood. Ad5hr infection induced polyfunctional CD4 and CD8+ T cells specific for the Ad5 hexon protein in all of the animals. Thus, infection with Ad5hr induced a complex pattern of innate and adaptive immunity in RM that included transient systemic CD4+ T cell activation and suppressed innate immunity on re-exposure to the virus. The complex effects of adenovirus infection on the immune system may help to explain the unexpected results of testing Ad5 vector expressing HIV antigens in Ad5 seropositive people.
Role of Maternal Dietary Peanut Exposure in Development of Food Allergy and Oral Tolerance

Background The impact of maternal ingestion of peanut during pregnancy and lactation on an offspring’s risk for peanut allergy is under debate. Objective To investigate the influence of maternal dietary peanut exposure and breast milk on an offspring’s allergy risk. Methods Preconceptionally peanut-exposed C3H/HeJ females were either fed or not fed peanut during pregnancy and lactation. The offsprings’ responses to peanut sensitization or oral tolerance induction by feeding antigen prior to immunization were assessed. We also assessed the impact of immune murine milk on tolerance induction pre- or post-weaning. For antigen uptake studies, mice were gavaged with fluorescent peanut in the presence or absence of immune murine milk; Peyer’s patches were harvested for immunostaining. Results Preconceptional peanut exposure resulted in the production of varying levels of maternal antibodies in serum (and breast milk), which were transferred to the offspring. Despite this, maternal peanut exposure either preconceptionally or during pregnancy and lactation, when compared to no maternal exposure, had no impact on peanut allergy. When offspring were fed peanut directly, dose-dependent tolerance induction, unaltered by maternal feeding of peanut, was seen. Although peanut uptake into the gut-associated lymphoid tissues was enhanced by immune milk as compared to naïve milk, tolerance induction was not affected by the co-administration of immune milk either pre- or post-weaning. Conclusion Maternal peanut exposure during pregnancy and lactation has no impact on the development of peanut allergy in the offspring. Tolerance to peanut can be induced early, even pre-weaning, by giving moderate amounts of peanut directly to the infant, and this is neither enhanced nor impaired by concurrent exposure to immune milk.
Continued Care in Palliative Bowel Surgery: An Invited Brief Commentary on “Long-Term Functional Outcome After Internal Delorme's Procedure for Obstructed Defecation Syndrome and the Role of Post-Operative Rehabilitation”

In Long-term functional outcome after Internal Delorme’s Procedure for Obstructed Defecation Syndrome and the role of postoperative rehabilitation, the authors and investigators aim to examine the role of postoperative rehabilitation on the outcomes of patients who did not respond to conservative treatment [1]. This study focused specifically on the Internal Delorme’s Procedure (IDP), a modified rectosigmoidectomy which removes prolapsed or intussuscepted portions of the rectum, to provide relief from Obstructed Defecation Syndrome (ODS). While rarely life-threatening, ODS is a form of functional constipation which can burden one’s quality of life [2, 3]. The root cause of ODS is often an anatomical defect and therefore conservative treatment methods may not be effective. These conservative treatments generally consist of bulking agents and fiber supplements added to the diet of the patient, or laxatives and stool softeners [4]. Since the cause is anatomical in nature, patients would have to either consistently and continuously adhere to the conservative therapy or undergo surgery to repair the defect [5]. Ultimately, due to the fact that the participants selected did not have any life-threatening conditions [1], this study may be viewed as an examination of the effectiveness of IDP as a palliative treatment. In these circumstances, IDP falls within the American College of Surgeon’s (ACS) definition of palliative treatment, especially considering the expansion of its meaning to include all interventions aiming “to relieve physical pain and psychological, social and spiritual suffering”
Evolutionary origin of Tbr2‐expressing precursor cells and the subventricular zone in the developing cortex

The subventricular zone (SVZ) is greatly expanded in primates with gyrencephalic cortices and is thought to be absent from vertebrates with three‐layered, lissencephalic cortices, such as the turtle. Recent work in rodents has shown that Tbr2‐expressing neural precursor cells in the SVZ produce excitatory neurons for each cortical layer in the neocortex. Many excitatory neurons are generated through a two‐step process in which Pax6‐expressing radial glial cells divide in the VZ to produce Tbr2‐expressing intermediate progenitor cells, which divide in the SVZ to produce cortical neurons. We investigated the evolutionary origin of SVZ neural precursor cells in the prenatal cerebral cortex by testing for the presence and distribution of Tbr2‐expressing cells in the prenatal cortex of reptilian and avian species. We found that mitotic Tbr2+ cells are present in the prenatal cortex of lizard, turtle, chicken, and dove. Furthermore, Tbr2+ cells are organized into a distinct SVZ in the dorsal ventricular ridge (DVR) of turtle forebrain and in the cortices of chicken and dove. Our results are consistent with the concept that Tbr2+ neural precursor cells were present in the common ancestor of mammals and reptiles. Our data also suggest that the organizing principle guiding the assembly of Tbr2+ cells into an anatomically distinct SVZ, both developmentally and evolutionarily, may be shared across vertebrates. Finally, our results indicate that Tbr2 expression can be used to test for the presence of a distinct SVZ and to define the boundaries of the SVZ in developing cortices. J. Comp. Neurol. 524:433–447, 2016. © 2015 Wiley Periodicals, Inc.
Metabolic Characterization of the Common Marmoset (Callithrix jacchus)

High-resolution metabolomics has created opportunity to integrate nutrition and metabolism into genetic studies to improve understanding of the diverse radiation of primate species. At present, however, there is very little information to help guide experimental design for study of wild populations. In a previous non-targeted metabolomics study of common marmosets (Callithrix jacchus), Rhesus macaques, humans, and four non-primate mammalian species, we found that essential amino acids (AA) and other central metabolites had interspecies variation similar to intraspecies variation while non-essential AA, environmental chemicals and catabolic waste products had greater interspecies variation. The present study was designed to test whether 55 plasma metabolites, including both nutritionally essential and non-essential metabolites and catabolic products, differ in concentration in common marmosets and humans. Significant differences were present for more than half of the metabolites analyzed and included AA, vitamins and central lipid metabolites, as well as for catabolic products of AA, nucleotides, energy metabolism and heme. Three environmental chemicals were present at low nanomolar concentrations but did not differ between species. Sex and age differences in marmosets were present for AA and nucleotide metabolism and warrant additional study. Overall, the results suggest that quantitative, targeted metabolomics can provide a useful complement to non-targeted metabolomics for studies of diet and environment interactions in primate evolution.
Flaxseed Oil Attenuates Intestinal Damage and Inflammation by Regulating Necroptosis and TLR4/NOD Signaling Pathways Following Lipopolysaccharide Challenge in a Piglet Model

SCOPE Flaxseed oil is a rich source of α-linolenic acid (ALA), which is the precursor of the long-chain n-3 polyunsaturated fatty acids (PUFAs), including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). This study investigates the protective effect of flaxseed oil against intestinal injury induced by lipopolysaccharide (LPS). MATERIALS AND RESULTS Twenty-four weaned pigs were used in a 2 × 2 factorial experiment with dietary treatment (5% corn oil vs 5% flaxseed oil) and LPS challenge (saline vs LPS). On day 21 of the experiment, pigs were administrated with LPS or saline. At 2 h and 4 h post-administration, blood samples were collected. After the blood harvest at 4 h, all piglets were slaughtered and intestinal samples were collected. Flaxseed oil supplementation led to the enrichment of ALA, EPA, and total n-3 PUFAs in intestine. Flaxseed oil improved intestinal morphology, jejunal lactase activity, and claudin-1 protein expression. Flaxseed oil downregulated the mRNA expression of intestinal necroptotic signals. Flaxseed oil also downregulated the mRNA expression of intestinal toll-like receptors 4 (TLR4) and its downstream signals myeloid differentiation factor 88 (MyD88), nuclear factor kappa B (NF-κB), and nucleotide-binding oligomerization domain proteins 1, 2 (NOD1, NOD2) and its adapter molecule, receptor-interacting protein kinase 2 (RIPK2). CONCLUSION These results suggest that dietary addition of flaxseed oil enhances intestinal integrity and barrier function, which is involved in modulating necroptosis and TLR4/NOD signaling pathways.
Endoscopic submucosal dissection for early rectal neoplasia: experience from a European center

Abstract Background and study aims Endoscopic resection is a curative treatment option for large nonpedunculated colorectal polyps (LNPCPs). Endoscopic submucosal dissection (ESD) allows en bloc resection but ESD experience is still limited outside Asia. The aim of our study was to evaluate the role of ESD in the treatment of early rectal neoplasia in a European center. Patients and methods 330 patients referred for endoscopic resection of rectal LNPCPs were included prospectively. Results ESD was performed for 302 LNPCPs (median diameter 40 mm). Submucosal invasive cancer (SMIC) was present in 17.2 % (n = 52). SMIC was associated with Paris type (54.5 % among type 0-Is lesions, 100 % of 0-Is-IIc type, 0 % of 0-IIa, 14.9 % of 0-IIa-Is, and 59.3 % of 0-IIa-IIc type; P < 0.001) and with surface pattern (71.4 % among nongranular plus mixed surface lesions, 17.9 % of lesions with granular surface and nodule ≥ 10 mm). For SMICs, resection rates were en bloc 81.4 %, R0 65.1 %, and curative 30.2 %. Curative resection rate improved from 13.6 % to 47.6 % over the study period (P = 0.036). The reason for 83.3 % (25/30) of noncurative resections was submucosal invasion exceeding 1000 µm. For benign lesions (n = 250, 82.8 %), the R0 resection increased from 55.2 % to 84.8 % over the study period (P < 0.001). Recurrence rate was 4.8 %, bleeding rate 5.2 %, and perforation rate 0.8 % (all complications managed conservatively). Median follow-up was 35 months. Conclusions The majority of rectal LNPCPs are benign lesions. ESD offers high R0 resection and low recurrence rates but EMR may be appropriate. In lesions with a risk for SMIC, ESD should be offered to achieve R0 resection. Despite high rates of R0 resection the curative resection rate of ESD for rectal SMIC is < 50 %. Pretherapeutic lesion selection needs improvement.
Effects of Concomitant Conventional and Previous Biological Disease Modifying Anti-Rheumatic Drugs Treatment on the Efficacy of Tocilizumab to Induce Remission in Patients with Rheumatoid Arthritis An Observational Real-Life Study

Objectives: To investigate remission rates in rheumatoid arthritis patients exposed to tocilizumab treatment in real life clinical practice and to test whether concomitant conventional and previous biological disease modifying anti-rheumatic drugs treatment affects the efficacy of tocilizumab to reach remission. Methods: Between January 2009 and December 2012 disease activity was analyzed in 272 rheumatoid arthritis patients exposed to tocilizumab at the onset of treatment and sequentially thereafter, i.e. every four weeks at the time of infusion. Aside from demographic and disease-specific variables, previous and concomitant conventional and biologic disease modifying anti-rheumatic drugs therapy was documented in all patients. Multivariate logistic regression analyses were conducted to identify factors influencing Disease Activity Score 28 remission and attrition to tocilizumab treatment. Results: 219 (80.5%) of all patients were female. Mean Age was 55.48 ± 13.23 years and our patients had mean disease duration of 12.48 ± 9.30 years. Disease Activity Score 28 significantly decreased from 5.00 ± 1.52 at baseline to 3.09 ± 1.49 at the latest infusion. Mean treatment period was 58.28 ± 43.95 weeks. A total of 101 patients (42.8%) achieved Disease Activity Score 28 remission, which was significantly associated to the length of tocilizumab exposure. Achievement of Disease Activity Score 28 remission was independent from the concomitant use of conventional disease modifying anti-rheumatic drugs. Previous exposure to tumour necrosis factor inhibitors but not rituximab significantly reduced the likelihood to achieve Disease Activity Score 28 remission. Two logistic regression analyses revealed baseline disease activity and duration of tocilizumab therapy as independent factors for Disease Activity Score 28 remission, whereas age and concomitant methotrexate therapy were linked to attrition to tocilizumab treatment. Conclusion: Remission rates found in this observational study are comparable to those of randomized controlled trials and those of big post-marketing surveillance studies. Remission rates of rheumatoid arthritis patients treated with tocilizumab in clinical practice are not influenced by concomitant disease modifying anti-rheumatic drugs use. Previous exposure to tumour necrosis factor inhibitors but not to rituximab decreases the chance to reach remission with tocilizumab.
Prophylactic antibiotics before cord clamping in cesarean delivery: a systematic review

The number of clinical trials investigating the optimal timing of prophylactic antibiotics in cesarean section has increased rapidly over the last few years. We conducted a systematic review to inform up‐to‐date evidence‐based guidelines to prevent postpartum infectious morbidity in the mother and rule out any safety issues related to antepartum antibiotic exposure in infants.
Laminar analysis of the slow wave activity in the somatosensory cortex of anesthetized rats

Rhythmic slow waves characterize brain electrical activity during natural deep sleep and under anesthesia, reflecting the synchronous membrane potential fluctuations of neurons in the thalamocortical network. Strong evidence indicates that the neocortex plays an important role in the generation of slow wave activity (SWA), however, contributions of individual cortical layers to the SWA generation are still unclear. The anatomically correct laminar profiles of SWA were revealed under ketamine/xylazine anesthesia, with combined local field potential recordings, multiple‐unit activity (MUA), current source density (CSD) and time‐frequency analyses precisely co‐registered with histology. The up‐state related negative field potential wave showed the largest amplitude in layer IV, the CSD was largest in layers I and III, whereas MUA was maximal in layer V, suggesting spatially dissociated firing and synaptic/transmembrane processes in the rat somatosensory cortex. Up‐state related firing could start in virtually any layers (III–VI) of the cortex, but were most frequently initiated in layer V. However, in a subset of experiments, layer IV was considerably active in initiating up‐state related MUA even in the absence of somatosensory stimulation. Somatosensory stimulation further strengthened up‐state initiation in layer IV. Our results confirm that cortical layer V firing may have a major contribution to the up‐state generation of ketamine/xylazine‐induced SWA, however, thalamic influence through the thalamorecipient layer IV can also play an initiating role, even in the absence of sensory stimulation.
Extending Existential Quantification in Conjunctions of BDDs

We introduce new approaches intended to speed up determining the satisabilit y of a given Boolean formula ’ expressed as a conjunction of Boolean functions. A common practice in such cases, when using constraint-oriented methods, is to represent the functions as BDDs, then repeatedly cluster BDDs containing one or more variables, and nally existentially quantify those variables away from the cluster. Clustering is essential because, in general, existential quantication cannot be applied unless the variables occur in only a single BDD. But, clustering incurs signican t overhead and may result in BDDs that are too big to allow the process to complete in a reasonable amount of time. There are two signican t contributions in this paper. First, we identify elementary conditions under which the existential quantication of a subset of variables V 0 may be distributed over all BDDs without clustering. We show that when these conditions are satised, safe assignments to the variables of V 0 are automatically generated. This is signican t because these assignments can be applied, as though they were inferences, to simplify ’. Second, some ecien t operations based on these conditions are introduced and can be integrated into existing frameworks of both search-oriented and constraint-oriented methods of satisabilit y. All of these operations are relaxations in the use of existential quantication and therefore may fail to nd one or more existing safe assignments. Finally, we compare and contrast the relationship of these operations to autarkies and present some preliminary results.
Adaptive Range Estimation in Perspective Vision System Using Neural Networks

This paper proposes an adaptive range estimation method in a perspective vision system using neural networks (NN). With a universal function approximation property of the NN, this study first defines the NN-based range value and the adaptive observer to determine the distance is designed with the known object motion, i.e., translational and rotational velocities. To remove the uncertainty between the true range and the estimated value, the proposed estimator utilizes a saturation function with a time-varying gain. The adaptive rules of the weight parameters of the NN and time-varying gain are derived using Lyapunov stability theory and the overall closed-loop stability is proven by introducing a deadzoned estimation error, which is composed of the estimation error and the saturation function. Finally, to validate the performance of the proposed method, experiments are conducted for the estimation of the relative distance between a target and a camera mounted on a multirotor unmanned aerial vehicle with an inertial measurement unit and a motion capture system.
Functions of Nonsuicidal Self‐Injury Are Differentially Associated with Suicide Ideation and Past Attempts among Childhood Trauma Survivors

Research into factors for suicide has revealed relations between trauma exposure and suicidality (e.g., Bridge, Goldstein, & Brent, ; Joiner, Sachs-Ericson, Wingate, Brown, Anestis, & Selby, ) wherein painful and provocative experiences (e.g., nonsuicidal self-injury [NSSI]) are an important link (e.g., Van Orden, Witte, Cukrowicz, Braithwaite, Selby, & Joiner, ; Smith, ). No prior research has assessed the relationship between functions of NSSI and suicidality among childhood trauma survivors. Participants who endorsed childhood trauma exposure (N = 121; Mage = 18.69, range 18-22) completed measures of posttraumatic stress disorder (PTSD) symptoms, NSSI, and suicidality. Multiple regressions assessing whether the four functions of NSSI predicted suicide ideation and past attempts after controlling for PTSD symptom severity found that only social negative reinforcement was associated with SI (β = .304, SE = .243, t = 2.23, p = .028), while only automatic negative reinforcement was associated with past attempts (β = .470, SE = .066, t = 2.25, p = .028). Findings highlight the importance of assessing NSSI functions when assessing suicidality among trauma survivors.
Preparatory Engagement of Cognitive Control Networks Increases Late in Childhood

Abstract The ability to engage task control flexibly, especially in anticipation of task demands, is beneficial when juggling different tasks. We investigated whether children in late childhood or early adolescence engaged preparatory task control similar to adults in a trial‐wise cued task‐switching paradigm. Twenty‐eight children (aged 9‐15 years) and 30 adults (aged 21‐30 years) participated in an fMRI study in which the Cue (preparatory) period across 2 tasks was analyzed separately from the execution of the tasks (the Target period). Children performed more slowly and less accurately than adults, and showed behavioral improvement within the child group age range of 9‐15 years. Children exhibited weaker Cue period activation than adults within a number of putative cognitive control regions. In contrast, children exhibited greater activity than adults in several regions, including sensorimotor areas, during the Target period. Children who activated cognitive control‐related regions more during the Cue period tended to activate the Target signal age‐related regions less, and this correlated with improved accuracy and reaction time on the task, as well as age. The results endorse previous findings that preparatory cognitive control systems are still developing in late childhood, but add new evidence of age‐related shifts in activity at the trial level.