Miracle-dz/UniFAR-FTUs huggingface dataset:
Imaging the Impact of Cortical Microcirculation on Synaptic Structure and Sensory-Evoked Hemodynamic Responses In Vivo

In vivo two-photon microscopy was used to image in real time dendrites and their spines in a mouse photothrombotic stroke model that reduced somatosensory cortex blood flow in discrete regions of cortical functional maps. This approach allowed us to define relationships between blood flow, cortical structure, and function on scales not previously achieved with macroscopic imaging techniques. Acute ischemic damage to dendrites was triggered within 30 min when blood flow over >0.2 mm2 of cortical surface was blocked. Rapid damage was not attributed to a subset of clotted or even leaking vessels (extravasation) alone. Assessment of stroke borders revealed a remarkably sharp transition between intact and damaged synaptic circuitry that occurred over tens of μm and was defined by a transition between flowing and blocked vessels. Although dendritic spines were normally ~13 μm from small flowing vessels, we show that intact dendritic structure can be maintained (in areas without flowing vessels) by blood flow from vessels that are on average 80 μm away. Functional imaging of intrinsic optical signals associated with activity-evoked hemodynamic responses in somatosensory cortex indicated that sensory-induced changes in signal were blocked in areas with damaged dendrites, but were present ~400 μm away from the border of dendritic damage. These results define the range of influence that blood flow can have on local cortical fine structure and function, as well as to demonstrate that peri-infarct tissues can be functional within the first few hours after stroke and well positioned to aid in poststroke recovery.
A Cross-Sectional Study of the Relationship between Cortical Bone and High-Impact Activity in Young Adult Males and Females

Context: The factors that govern skeletal responses to physical activity remain poorly understood. Objective: The aim of this study was to investigate whether gender or fat mass influences relationships between cortical bone and physical activity, after partitioning accelerometer outputs into low (0.5–2.1 g), medium (2.1–4.2 g), or high (>4.2 g) impacts, where g represents gravitational force. Design/Setting: We conducted a cross-sectional analysis in participants from the Avon Longitudinal Study of Parents and Children. Participants: We studied 675 adolescents (272 boys; mean age, 17.7 yr). Outcome Measures: We measured cortical bone parameters from peripheral quantitative computed tomography scans of the mid-tibia, adjusted for height, fat mass, and lean mass. Results: High-impact activity was positively associated with periosteal circumference (PC) in males but not females [coefficients (95% confidence intervals), 0.054 (0.007, 0.100) and 0.07 (−0.028, 0.041), respectively; showing sd change per doubling in activity]. There was also weak evidence that medium impacts were positively related to PC in males but not females (P = 0.03 for gender interaction). On stratifying by fat mass, the positive relationship between high-impact activity and PC was greatest in those with the highest fat mass [high impact vs. PC in males, 0.01 (−0.064, 0.085), 0.045 (−0.040, 0.131), 0.098 (0.012, 0.185), for lower, middle, and upper fat tertiles, respectively; high impact vs. PC in females, −0.041 (−0.101, 0.020), −0.028 (−0.077, 0.022), 0.082 (0.015, 0.148), P = 0.01 for fat mass interaction]. Similar findings were observed for strength parameters, cross-sectional moment of inertia, and strength-strain index. Conclusions: In late adolescence, associations between high-impact activity and PC are attenuated by female gender and low body fat, suggesting that the skeletal response to high-impact activity is particularly reduced in young women with low fat mass.
Multiomic disease signatures converge to cytotoxic CD8 T cells in primary Sjögren’s syndrome

Objectives Multiomics study was conducted to elucidate the crucial molecular mechanisms of primary Sjögren’s syndrome (SS) pathology. Methods We generated multiple data set from well-defined patients with SS, which includes whole-blood transcriptomes, serum proteomes and peripheral immunophenotyping. Based on our newly generated data, we performed an extensive bioinformatic investigation. Results Our integrative analysis identified SS gene signatures (SGS) dysregulated in widespread omics layers, including epigenomes, mRNAs and proteins. SGS predominantly involved the interferon signature and ADAMs substrates. Besides, SGS was significantly overlapped with SS-causing genes indicated by a genome-wide association study and expression trait loci analyses. Combining the molecular signatures with immunophenotypic profiles revealed that cytotoxic CD8 T cells were associated with SGS. Further, we observed the activation of SGS in cytotoxic CD8 T cells isolated from patients with SS. Conclusions Our multiomics investigation identified gene signatures deeply associated with SS pathology and showed the involvement of cytotoxic CD8 T cells. These integrative relations across multiple layers will facilitate our understanding of SS at the system level.
Predicting persistence of eating disorder compensatory weight control behaviors

OBJECTIVE The study aimed to identify variables that predicted persistence versus desistence of eating disorder-related compensatory behaviors in a high-risk factor sample of women who reported repeated compensatory behaviors at baseline. Data came from a randomized trial evaluating two brief obesity prevention interventions for college students with weight concerns. METHOD Two hundred and sixty one young women (Mean age = 19.1, 79% European American) with weight concerns were randomly assigned to one of two brief obesity prevention interventions or educational video control. Participants were assessed at baseline, post-intervention, 6- and 12-month follow-up by interview, survey, and physical measurements on 6 eating disorder features and 13 psychosocial variables hypothesized to predict onset or maintenance of eating pathology. RESULTS Approximately half (48%) reported engaging in recurrent compensatory behaviors in the year preceding study involvement. Among this subset, 61% reported persistent compensatory behaviors over 12-month follow-up. Neither study condition and adjunctive treatment, nor eating disorder features predicted persistence. Persistent compensatory behavior was significantly associated with greater sociocultural pressure to be thin, impulsivity, and substance use, and lower perceived sexual attractiveness. DISCUSSION Perceived pressure to be thin is an established risk factor for the initiation of disorder eating behaviors but also may serve as a maintenance factor for unhealthy compensatory behaviors. Impulsivity, either as a trait factor or resulting from substance misuse may contribute to poor judgment and ongoing compensatory behaviors. Additional research on factors that predict persistence of eating disordered behaviors is needed. © 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2017; 50:561-568).
RT-Fall: A Real-Time and Contactless Fall Detection System with Commodity WiFi Devices

This paper presents the design and implementation of RT-Fall, a real-time, contactless, low-cost yet accurate indoor fall detection system using the commodity WiFi devices. RT-Fall exploits the phase and amplitude of the fine-grained Channel State Information (CSI) accessible in commodity WiFi devices, and for the first time fulfills the goal of segmenting and detecting the falls automatically in real-time, which allows users to perform daily activities naturally and continuously without wearing any devices on the body. This work makes two key technical contributions. First, we find that the CSI phase difference over two antennas is a more sensitive base signal than amplitude for activity recognition, which can enable very reliable segmentation of fall and fall-like activities. Second, we discover the sharp power profile decline pattern of the fall in the time-frequency domain and further exploit the insight for new feature extraction and accurate fall segmentation/detection. Experimental results in four indoor scenarios demonstrate that RT-fall consistently outperforms the state-of-the-art approach WiFall with 14 percent higher sensitivity and 10 percent higher specificity on average.
Working Memory and Consciousness: The Current State of Play

Working memory (WM), an important posit in cognitive science, allows one to temporarily store and manipulate information in the service of ongoing tasks. WM has been traditionally classified as an explicit memory system—that is, as operating on and maintaining only consciously perceived information. Recently, however, several studies have questioned this assumption, purporting to provide evidence for unconscious WM. In this article, we focus on visual working memory (VWM) and critically examine these studies as well as studies of unconscious perception that seem to provide indirect evidence for unconscious WM. Our analysis indicates that current evidence does not support an unconscious WM store, though we offer independent reasons to think that WM may operate on unconsciously perceived information.
INNOVATION PLATFORMS: EXPERIENCES WITH THEIR INSTITUTIONAL EMBEDDING IN AGRICULTURAL RESEARCH FOR DEVELOPMENT

SUMMARY Innovation Platforms (IPs) are seen as a promising vehicle to foster a paradigm shift in agricultural research for development (AR4D). By facilitating interaction, negotiation and collective action between farmers, researchers and other stakeholders, IPs can contribute to more integrated, systemic innovation that is essential for achieving agricultural development impacts. However, successful implementation of IPs requires institutional change within AR4D establishments. The objective of this paper is to reflect on the implementation and institutionalisation of IPs in present AR4D programmes. We use experiences from sub-Saharan Africa to demonstrate how the adoption and adaptation of IPs creates both opportunities and challenges that influence platform performance and impact. Niche-regime theory is used to understand challenges, and anticipate on how to deal with them. A key concern is whether IPs in AR4D challenge or reinforce existing technology-oriented agricultural innovation paradigms. For example, stakeholder representation, facilitation and institutional embedding determine to a large extent whether the IP can strengthen systemic capacity to innovate that can lead to real paradigm change, or are merely ‘old wine in new bottles’ and a continuation of ‘business as usual’. Institutional embedding of IPs and – more broadly – the transition from technology-oriented to system-oriented AR4D approaches requires structural changes in organisational mandates, incentives, procedures and funding, as well as investments in exchange of experiences, learning and capacity development.
UvA-DARE ( Digital Academic Repository ) Mortality and morbidity of surgery for unruptured intracranial aneurysms : a meta-analysis

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How to make a primordial germ cell

Primordial germ cells (PGCs) are the precursors of sperm and eggs, which generate a new organism that is capable of creating endless new generations through germ cells. PGCs are specified during early mammalian postimplantation development, and are uniquely programmed for transmission of genetic and epigenetic information to subsequent generations. In this Primer, we summarise the establishment of the fundamental principles of PGC specification during early development and discuss how it is now possible to make mouse PGCs from pluripotent embryonic stem cells, and indeed somatic cells if they are first rendered pluripotent in culture.
Detection of Superoxide in Vascular Tissue

Abstract—During the past decade, it has become apparent that reactive oxygen species play a critical role in the genesis of many vascular diseases. The superoxide anion is among the most important of these, not only because of its rapid reaction with NO but also because it serves as a progenitor for many other reactive oxygen species. Although there are many approaches to detecting and quantifying superoxide in chemical systems, its detection in intact tissues is more difficult. The validity of the most popular and frequently used assay for this purpose, lucigenin-enhanced chemiluminescence, has been recently questioned. It has been suggested that lucigenin itself, especially at high concentrations (>50 &mgr;mol/L), may act as a source for superoxide via redox cycling. Lower lucigenin concentrations (5 &mgr;mol/L) do not participate in redox cycling to an important extent in intact tissues and, therefore, provide an accurate assessment of the rate of superoxide production in such samples. Other useful assays for superoxide include those using the fluorescent dye dihydroethidine, 2-methyl-6-phenyl-3,7-dihydroimidazo(1,2-&agr;)pyrazin-3-one (CLA), and 2-(p-hydroxybenzyl)-6-(p-hydroxyphenyl) 8-benzylimidazo[1,2-&agr;]pyrazin-3-one (coelenterazine). The chemiluminescent compound 5-amino-2,3-dihydroxy-1,4-phthalayineidone (luminol) may also be used to detect various reactive oxygen species and may be made specific for various oxidants, such as hydrogen peroxide, superoxide, and peroxynitrite, by altering the experimental conditions. Although each of these methods may be associated with potential artifacts, the use of ≥2 different techniques that yield similar results provides a reliable approach for the study of reactive oxygen species in intact vascular tissues.
Discrete R\'enyi Classifiers

Consider the binary classification problem of predicting a target variable $Y$ from a discrete feature vector $X = (X_1,.,X_d)$. When the probability distribution $\mathbb{P}(X,Y)$ is known, the optimal classifier, leading to the minimum misclassification rate, is given by the Maximum A-posteriori Probability decision rule. However, estimating the complete joint distribution $\mathbb{P}(X,Y)$ is computationally and statistically impossible for large values of $d$. An alternative approach is to first estimate some low order marginals of $\mathbb{P}(X,Y)$ and then design the classifier based on the estimated low order marginals. This approach is also helpful when the complete training data instances are not available due to privacy concerns. In this work, we consider the problem of finding the optimum classifier based on some estimated low order marginals of $(X,Y)$. We prove that for a given set of marginals, the minimum Hirschfeld-Gebelein-Renyi (HGR) correlation principle introduced in [1] leads to a randomized classification rule which is shown to have a misclassification rate no larger than twice the misclassification rate of the optimal classifier. Then, under a separability condition, we show that the proposed algorithm is equivalent to a randomized linear regression approach. In addition, this method naturally results in a robust feature selection method selecting a subset of features having the maximum worst case HGR correlation with the target variable. Our theoretical upper-bound is similar to the recent Discrete Chebyshev Classifier (DCC) approach [2], while the proposed algorithm has significant computational advantages since it only requires solving a least square optimization problem. Finally, we numerically compare our proposed algorithm with the DCC classifier and show that the proposed algorithm results in better misclassification rate over various datasets.
Saliva-Derived Commensal and Pathogenic Biofilms in a Human Gingiva Model

In vitro models that closely mimic human host-microbiome interactions can be a powerful screening tool for antimicrobials and will hold great potential for drug validation and discovery. The aim of this study was to develop an organotypic oral mucosa model that could be exposed to in vitro cultured commensal and pathogenic biofilms in a standardized and scalable manner. The oral mucosa model consisted of a tissue-engineered human gingiva equivalent containing a multilayered differentiated gingiva epithelium (keratinocytes) grown on a collagen hydrogel, containing gingiva fibroblasts, which represented the lamina propria. Keratinocyte and fibroblast telomerase reverse transcriptase–immortalized cell lines were used to overcome the limitations of isolating cells from small biopsies when scalable culture experiments were required. The oral biofilms were grown under defined conditions from human saliva to represent 3 distinct phenotypes: commensal, gingivitis, and cariogenic. The in vitro grown biofilms contained physiologic numbers of bacterial species, averaging >70 operational taxonomic units, including 20 differentiating operational taxonomic units. When the biofilms were applied topically to the gingiva equivalents for 24 h, the gingiva epithelium increased its expression of elafin, a protease inhibitor and antimicrobial protein. This increased elafin expression was observed as a response to all 3 biofilm types, commensal as well as pathogenic (gingivitis and cariogenic). Biofilm exposure also increased secretion of the antimicrobial cytokine CCL20 and inflammatory cytokines IL-6, CXCL8, and CCL2 from gingiva equivalents. This inflammatory response was far greater after commensal biofilm exposure than after pathogenic biofilm exposure. These results show that pathogenic oral biofilms have early immune evasion properties as compared with commensal oral biofilms. The novel host-microbiome model provides an ideal tool for future investigations of gingiva responses to commensal and pathogenic biofilms and for testing novel therapeutics.
Functional Relevance of the Stretch-Dependent Slow Force Response in Failing Human Myocardium

Stretch induces immediate and delayed inotropic effects in mammalian myocardium via distinct mechanosensitive pathways, but these effects are poorly characterized in human cardiac muscle. We tested the effects of stretch on immediate and delayed force response in failing human myocardium. Experiments were performed in muscle strips from 52 failing human hearts (37°C, 1 Hz, bicarbonate buffer). Muscles were stretched from 88% of optimal length to 98% of optimal length. The resulting immediate and delayed (ie, slow force response [SFR]) increases in twitch force were assessed without and after blockade of the sarcoplasmic reticulum (SR; cyclopiazonic acid and ryanodine), stretch-activated ion channels (SACs; gadolinium, streptomycin), L-type Ca2+-channels (diltiazem), angiotensin II type-1 (AT1) receptors (candesartan), endothelin (ET) receptors (PD145065 or BQ123), Na+/H+ exchange (NHE1; HOE642), or reverse-mode Na+/Ca+ exchange (NCX; KB-R7493). We also tested the effects of stretch on SR Ca2+ load (rapid cooling contractures [RCCs]) and intracellular pH (in BCECF-loaded trabeculae). Stretch induced an immediate (<10 beats), followed by a slow (5 to 10 minutes), force response. Twitch force increased to 232±6% of prestretch value during the immediate phase, followed by a further increase to 279±8% during the SFR. RCC amplitude significantly increased, but pHi did not change during SFR. Inhibition of SACs, L-type Ca2+ channels, AT1 receptors, or ET receptors did not affect the stretch-dependent immediate or SFR. In contrast, the SFR was reduced by NHE1 inhibition and almost completely abolished by reverse-mode NCX inhibition or blockade of sarcoplasmic reticulum function. The data demonstrate the existence of a functionally relevant, SR-Ca2+–dependent SFR in failing human myocardium, which partly depends on NHE1 and reverse-mode NCX activation.
PROPRIOCEPTION, BODY BALANCE AND FUNCTIONALITY IN INDIVIDUALS WITH ACL RECONSTRUCTION

Objective : To evaluate and compare proprioception, body balance and knee functionality of individuals with or without unilateral anterior cruciate ligament (ACL) reconstruction. Methods : Forty individuals were divided in two groups: Experimental group, 20 individuals with ACL reconstruction at six months postoperative, and control group, 20 individuals with no history of lower limb pathologies. In the experimental group, we assessed lower limbs with reconstructed ACL and contralateral limb; in the control group the dominant and the non-dominant lower limbs were assessed. All subjects were submitted to joint position sense test to evaluate proprioception, postural control measure in single-limb, and step up and down (SUD) test for functional assessment. Results : There were no deficits in proprioception and postural control. In the SUD test, a 5% decrease in lift up force was found in reconstructed ACL lower limbs, however, a statistically not significant difference. The impact and step down force during the course of test were 30% greater in anatomic ACL than in control lower limbs. Conclusion : The individuals with ACL reconstruction at six months postoperative did not show changes in proprioception and postural control, but showed motor control changes, influencing knee functionality. Level of Evidence IV, Prognostic Studies.
Bronchial Epithelial Cells Elastase-Induced Inflammatory Responses in Viral Inhibition of IL-1- and Neutrophil

Previously, we elucidated the intracellular mechanisms by which neutrophil elastase (NE) up-regulates inﬂammatory gene expression in bronchial epithelial cells. In this study, we examine the effects of both IL-1 and NE on inﬂammatory gene expression in 16HBE14o (cid:1) bronchial epithelial cells and investigate approaches to abrogate these inﬂammatory responses. IL-1 induced IL-8 protein production in time- and dose-dependent fashions, an important observation given that IL-8 is a potent neutrophil chemoattractant and a key inﬂammatory mediator. IL-1 and NE were shown to activate the p38 MAPK pathway in 16HBE14o (cid:1) cells. Western blot analysis demonstrated IL-1R-associated kinase 1 (IRAK-1) degradation in response to stimulation with both IL-1 and NE. In addition, the expression of dominant negative IRAK-1 (IRAK-1 (cid:2) ), IRAK-2 (cid:2) , or IRAK-4 (cid:2) inhibited IL-1- and NE-induced NF- (cid:3) B-linked reporter gene expression. Dominant negative versions of the intracellular adaptor proteins MyD88 (MyD88 (cid:2) ) and MyD88 adaptor-like (Mal P/H) abrogated NE-induced NF- (cid:3) B reporter gene expression. In contrast, only MyD88 (cid:2) was found to inhibit IL-1-induced NF- (cid:3) B reporter activity. We also investigated the vaccinia virus proteins, A46R and A52R, which have been shown to antagonize IL-1 signaling. Transfection with A46R or A52R cDNA inhibited IL-1- and NE-induced NF- (cid:3) B and IL-8R gene expression and IL-8 protein production in primary and transformed bronchial epithelial cells. Further-more, cytokine array studies demonstrated that IL-1 and NE can up-regulate the expression of IL-6, oncostatin M, epithelial cell-derived neutrophil activating peptide-78, growth-related oncogene family members, vascular endothelial growth factor, and GM-CSF, with induction of these proteins inhibited by the viral proteins. These ﬁndings identify vaccinia virus proteins as possible therapeutic agents for the manifestations of several inﬂammatory lung diseases. The Journal of Immunology, 2005, 175: 7594– 7601.