Miracle-dz/UniFAR-FTUs huggingface dataset:
Dental caries vaccine: are we there yet?

Dental caries, caused by Streptococcus mutans, is a common infection. Caries vaccine has been under investigation for the last 40 years. Many in vitro and in vivo studies and some human clinical trials have determined many pertinent aspects regarding vaccine development. The virulence determinants of Strep. mutans, such as Ag I/II, responsible for adherence to surfaces, glucosyltransferase, responsible for the production of glucan, and the glucan‐binding protein, responsible for the attachment of glucan to surfaces, have been known to elicit an antigen‐specific immune response. It is also known that more than one antigen or a functional part of the genome responsible for these virulence determinants provide a better host response compared with the monogenic vaccine or complete genome of a specific antigen. To enhance the host response, the use of adjuvants has been studied and the routes of antigen administration have been investigated. In recent years, some promising vaccines such as pGJA‐P/VAX, LT derivative/Pi39‐512, KFD2‐rPAc and SBR/GBR‐CMV‐nirB have been developed and tested in animals. New virulence targets need to be explored. Multicentre collaborative studies and human clinical trials are required and some interest from funders and public health experts should be generated to overcome this hurdle.
Predicting impact of a biocontrol agent: Integrating distribution modeling with climate-dependent vital rates.

Species distribution models can predict the suitable climatic range of a potential biological control agent (BCA), but they provide little information on the BCA's potential impact. To predict high population build-up, a pre-requisite of biocontrol impact, studies are needed which assess the effect of environmental factors on vital rates of a BCA across the environmental gradient of the BCA's suitable habitats, especially for the region where the BCA is considered for field release. We extended a published species distribution model with climate-dependent vital rates of Ophraella communa, a recently and accidentally introduced potential BCA of common ragweed, Ambrosia artemisiifolia in Europe. In field and laboratory experiments, we collected data on climate-dependent parameters assumed to be the most relevant for the population build-up of O. communa, i.e., temperature driving the number of generations per year and relative humidity (RH) determining egg hatching success. We found that O. communa concluded one generation in 334 cumulative degree days, and that egg hatching success strongly decreased from >80% to <20% when RH drops from 55% to 45% during the day. We used these values to spatially explicitly project population densities across the European range suitable for both A. artemisiifolia and the beetle and found that the present distribution of the beetle in Europe is within the range with the highest projected population growth. The highest population density of O. communa was predicted for northern Italy and parts of western Russia and western Georgia. Field observations of high impact on A. artemisiifolia with records of 80% aerial pollen reduction in the Milano area since the establishment of O. communa are in line with these predictions. The relative importance of temperature and RH on the population density of O. communa varies considerably across its suitable range in Europe. We propose that the combined statistical and mechanistic approach outlined in this paper helps to more accurately predict the potential impact of a weed BCA than a species distribution model alone. Identifying the factors limiting the population build-up of a BCA across the suitable range allows implementation of more targeted release and management strategies to optimize biocontrol efficacy.
Multisensory Integration as a Window into Orderly and Disrupted Cognition and Communication.

During our everyday lives, we are confronted with a vast amount of information from several sensory modalities. This multisensory information needs to be appropriately integrated to effectively engage with and learn from our world. Research carried out over the last half century has provided new insights into the way such multisensory processing improves human performance and perception; the neurophysiological foundations of multisensory function; the time course for its development; how multisensory abilities differ in clinical populations; and, most recently, the links between multisensory processing and cognitive abilities. This review summarizes the extant literature on multisensory function in typical and atypical circumstances, discusses the implications of the work carried out to date for theory and research, and points toward next steps for advancing the field. Expected final online publication date for the Annual Review of Psychology, Volume 71 is January 4, 2020. Please see http://www.annualreviews. org/page/journal/pubdates for revised estimates.
Neoadjuvant chemotherapy improves survival compared with concurrent chemoradiation alone in nasopharyngeal carcinoma patients with N3 disease

Neoadjuvant chemotherapy (NAC) trials in endemic regions of nasopharyngeal carcinoma (NPC) found improved survival, but studies are lacking in nonendemic regions. We assessed whether adding NAC to concurrent chemoradiation (CRT) improves overall survival (OS), especially in high‐risk nonendemic patients.
Abstract inference of unchosen option values

Reinforcement learning research has pursued a persistent question: Does reward feedback prompt inferences that transcend simple associations? Reversal learning data suggest an affirmative answer: When the positive stimulus (S+) becomes the negative stimulus (S−), trained humans rapidly switch to choosing the former S−. The operations supporting such inferences remain ambiguous. Do participants identify transitions between stimulus‐specific contexts (i.e., A+B− and A−B+), or deduce values by learning the abstract contingency structure? Across two experiments, we probed humans’ use of abstract rules to infer the values of unchosen alternatives. In Experiment 1, 37 participants attempted a task that originally demonstrated monkeys’ difficulty with this form of inference. We presented modified discrimination problems in which the initially chosen stimulus (abstract inference group) or unchosen stimulus (control group) was replaced with a novel stimulus of identical status on Trial 2. In the abstract inference condition, accurate performance can be achieved by applying the consistent contingency structure (but not memory of stimulus‐specific reward associations) to infer to the unchosen stimulus’ value. The abstract inference group learned to make accurate choices, but only after committing substantially more errors than were observed among control participants—suggesting that unchosen value inferences are infrequently drawn in standard discrimination scenarios. In Experiment 2, 17 participants completed abstract inference problems that had been modified to be suitable for fMRI investigations. Behavioral results both corroborated the Experiment 1 trends and further revealed marked individual differences in explicit awareness of the novel stimulus values.
Observational pain assessment in older persons with dementia in four countries: Observer agreement of items and factor structure of the Pain Assessment in Impaired Cognition

Recognition of pain in people with dementia is challenging. Observational scales have been developed, but there is a need to harmonize and improve the assessment process. In EU initiative COST‐Action TD1005, 36 promising items were selected from existing scales to be tested further. We aimed to study the observer agreement of each item, and to analyse the factor structure of the complete set.
Knowing who knows: Metacognitive and causal learning abilities guide infants' selective social learning.

Given the widespread interest in the development of children's selective social learning, there is mounting evidence suggesting that infants prefer to learn from competent informants (Poulin-Dubois & Brosseau-Liard, 2016). However, little research has been dedicated to understanding how this selectivity develops. The present study investigated whether causal learning and precursor metacognitive abilities govern discriminant learning in a classic word-learning paradigm. Infants were exposed to a speaker who accurately (reliable condition) or inaccurately (unreliable condition) labeled familiar objects and were subsequently tested on their ability to learn a novel word from the informant. The predictive power of causal learning skills and precursor metacognition (as measured through decision confidence) on infants' word learning was examined across both reliable and unreliable conditions. Results suggest that infants are more inclined to accept an unreliable speaker's testimony on a word learning task when they also lack confidence in their own knowledge on a task measuring their metacognitive ability. Additionally, when uncertain, infants draw on causal learning abilities to better learn the association between a label and a novel toy. This study is the first to shed light on the role of causal learning and precursor metacognitive judgments in infants' abilities to engage in selective trust.
A study of cortical and brainstem mechanisms of diffuse noxious inhibitory controls in anaesthetised normal and neuropathic rats

Diffuse noxious inhibitory controls (DNIC) are a mechanism of endogenous descending pain modulation and are deficient in a large proportion of chronic pain patients. However, the pathways involved remain only partially determined with several cortical and brainstem structures implicated. This study examined the role of the dorsal reticular nucleus (DRt) and infralimbic (ILC) region of the medial prefrontal cortex in DNIC. In vivo electrophysiology was performed to record from dorsal horn lamina V/VI wide dynamic range neurones with left hind paw receptive fields in anaesthetised sham‐operated and L5/L6 spinal nerve‐ligated (SNL) rats. Evoked neuronal responses were quantified in the presence and absence of a conditioning stimulus (left ear clamp). In sham rats, DNIC were reproducibly recruited by a heterotopically applied conditioning stimulus, an effect that was absent in neuropathic rats. Intra‐DRt naloxone had no effect on spinal neuronal responses to dynamic brush, punctate mechanical, evaporative cooling and heat stimuli in sham and SNL rats. In addition, intra‐DRt naloxone blocked DNIC in sham rats, but had no effect in SNL rats. Intra‐ILC lidocaine had no effect on spinal neuronal responses to dynamic brush, punctate mechanical, evaporative cooling and heat stimuli in sham and SNL rats. However, differential effects were observed in relation to the expression of DNIC; intra‐ILC lidocaine blocked activation of DNIC in sham rats but restored DNIC in SNL rats. These data suggest that the ILC is not directly involved in mediating DNIC but can modulate its activation and that DRt involvement in DNIC requires opioidergic signalling.
Improving the modelling of susceptibility-induced spatial distortions in MRI-guided extra-cranial radiotherapy

Magnetic-resonance linear-accelerator (MR-LINAC) systems integrating in-room magnetic-resonance-imaging (MRI) guidance are a currently emerging technology. Such systems address the need to provide frequent imaging at optimal soft-tissue contrast for treatment guidance. However, the use of MRI-guidance in radiotherapy should address imaging-related spatial distortions, which may hinder accurate geometrical characterization of the treatment site. Since spatial encoding relies on well-defined magnetic fields, accurate modeling of the magnetic field alterations due to -inhomogeneities, gradient nonlinearities, and susceptibilities is needed. In this work, the modeling of susceptibility induced distortions is considered. Dedicated susceptibility measurements are reported, aiming at extending the characterization of different tissues for MRI-guided extra-cranial radiotherapy applications. A digital 4D anthropomorphic phantom, providing time-resolved anatomical changes due to breathing, is exploited as reference anatomy to quantify spatial distortions due to variations in tissue susceptibility. Sub-millimeter values can be attributed to susceptibility-induced distortions, with maximum values up to 2.3 mm at a gradient strength of 5 mT m−1. Improvements in susceptibility simulation for extra-cranial sites are shown when including specifically the contributions from lung, liver and muscular tissues.
Quantum Confinement Effects on Solvatochromic Shifts of Molecular Solutes.

We demonstrate the pivotal role of QM density confinement effects on solvatochromic shifts. In particular, by resorting to a QM/MM approach capable of accounting for confinement effects we successfully reproduce vacuo-to-water solvatochromic shifts for dark nπ* and bright ππ* transitions of acrolein and dark nπ* transitions of pyridine and pyrimidine without the need of including explicit water molecules in the QM portion. Remarkably, our approach is also able to dissect the effects of the single forces acting on the solute-solvent couple, and allows for a rationalization of the experimental findings in terms of physico-chemical quantities.
The effects of sympathetic activity induced by ice water on blood flow and brachial artery flow-mediated dilatation response in healthy volunteers

Objective To investigate the association between sympathetic activity, reactive hyperemia and brachial artery flow-mediated dilation (FMD). Background It is claimed that major surgery has an impact on endothelial function, as observed by post-operative reduced brachial artery FMD response. However, another explanation for the observed reduced FMD response post-operatively may be sympathetic stress-induced reduction in blood flow. Methods Seventeen healthy volunteers with a median age (25th-75th percentiles) of 23.5 (23–24.8) years were recruited. Participants’ brachial blood flow and FMD response were measured (i) during normal non-stress conditions (Normal1); (ii) during exposure to ice water; and (iii) afterwards, under normal non-stress conditions (Normal2). We continuously measured arterial blood pressure (Finometer), heart rate (ECG), skin blood flow of the index finger (laser Doppler), and brachial artery blood flow and diameter (Ultrasound Doppler). Measurements were taken at baseline; before a 5-min suprasystolic forearm occlusion; and following a 3-min post-occlusion, to measure reactive hyperemia and FMD. Results Median (25th-75th percentiles) FMD response after exposure to ice water was reduced compared to non-stress conditions [4.9 (2.9–8.4) % during ice water vs. 9.7 (7.6–12.2) % Normal1 and 9.7 (6.4–10.3) % Normal2, P < 0.001]. Blood flow 60 s after cuff-deflation during ice water exposure was significantly reduced to 328 (289–421) mL compared to non-stress conditions (both P < 0.05). No differences were observed between Normal1 [446 (359–506) mL] and Normal2 [455 (365–515) mL] (both P > 0.05). Heart rate significantly increased during ice water exposure [67 (59–69) beats/min)] compared to 55 (49–60) beats/min during Normal1 and 54 (47–60) beats/min during Normal2 (both P < 0.05). MAP did not change during Normal1 [72 (64–84)] or during Normal2 [71 (65–81) mm Hg] (both P > 0.05), but increased to 86 (75–98) mm Hg during ice water exposure (P < 0.05). Conclusions Increased sympathetic activity resulted in decreased blood flow and brachial artery FMD response in healthy volunteers, independent of endothelial dysfunction. Future studies should adjust for blood flow when interpreting the FMD response.
Partial LPL deletions: rare copy-number variants contributing towards severe hypertriglyceridemia[S]

Severe hypertriglyceridemia (HTG) is a relatively common form of dyslipidemia with a complex pathophysiology and serious health complications. HTG can develop in the presence of rare genetic factors disrupting genes involved in the triglyceride (TG) metabolic pathway, including large-scale copy-number variants (CNVs). Improvements in next-generation sequencing technologies and bioinformatic analyses have better allowed assessment of CNVs as possible causes of or contributors to severe HTG. We screened targeted sequencing data of 632 patients with severe HTG and identified partial deletions of the LPL gene, encoding the central enzyme involved in the metabolism of TG-rich lipoproteins, in four individuals (0.63%). We confirmed the genomic breakpoints in each patient with Sanger sequencing. Three patients carried an identical heterozygous deletion spanning the 5′ untranslated region (UTR) to LPL exon 2, and one patient carried a heterozygous deletion spanning the 5′UTR to LPL exon 1. All four heterozygous CNV carriers were determined to have multifactorial severe HTG. The predicted null nature of our identified LPL deletions may contribute to relatively higher TG levels and a more severe clinical phenotype than other forms of genetic variation associated with the disease, particularly in the polygenic state. The identification of novel CNVs in patients with severe HTG suggests that methods for CNV detection should be included in the diagnostic workup and molecular genetic evaluation of patients with high TG levels.
Introduction to the Sixth Global Summit on the Health Effects of Yogurt: Yogurt, More than the Sum of Its Parts

ABSTRACT Foods are not only a collection of individual components but are complex matrices. The food matrix is defined by the USDA as “the nutrient and nonnutrient components of foods and their molecular relations. ” The matrix of a food is an important factor in evaluating its nutritional and health contributions to the consumer. Dairy foods are a complex mix of various nutrients and other components, which together form the food matrix. There are three main types of dairy food matrices: liquid (milk, some fermented milks), semi-solid (yogurt, some fresh cheeses), and solid (most cheeses). The nutritional value of dairy foods is determined by their nutrient composition and matrix structure, which can affect digestibility and the bioavailability of nutrients. Additionally, a number of studies have shown that the health effects of dairy products, of similar nutrient content, vary by their matrix.
Bacteria isolated from Bengal cat (Felis catus × Prionailurus bengalensis) anal sac secretions produce volatile compounds potentially associated with animal signaling

In social animals, scent secretions and marking behaviors play critical roles in communication, including intraspecific signals, such as identifying individuals and group membership, as well as interspecific signaling. Anal sacs are an important odor producing organ found across the carnivorans (species in the mammalian Order Carnivora). Secretions from the anal sac may be used as chemical signals by animals for behaviors ranging from defense to species recognition to signaling reproductive status. In addition, a recent study suggests that domestic cats utilize short-chain free fatty acids in anal sac secretions for individual recognition. The fermentation hypothesis is the idea that symbiotic microorganisms living in association with animals contribute to odor profiles used in chemical communication and that variation in these chemical signals reflects variation in the microbial community. Here we examine the fermentation hypothesis by characterizing volatile organic compounds (VOC) and bacteria isolated from anal sac secretions collected from a male Bengal cat (Felis catus × Prionailurus bengalensis), a cross between the domestic cat and the leopard cat. Both left and right anal sacs of a male Bengal cat were manually expressed (emptied) and collected. Half of the material was used to culture bacteria or to extract bacterial DNA and the other half was used for VOC analysis. DNA was extracted from the anal sac secretions and used for a 16S rRNA gene PCR amplification and sequencing based characterization of the microbial community. Additionally, some of the material was plated out in order to isolate bacterial colonies. Three taxa (Bacteroides fragilis, Tessaracoccus, and Finegoldia magna) were relatively abundant in the 16S rRNA gene sequence data and also isolated by culturing. Using Solid Phase Microextraction (SPME) gas chromatography-mass spectrometry (GC-MS), we tentatively identified 52 compounds from the Bengal cat anal sac secretions and 67 compounds from cultures of the three bacterial isolates chosen for further analysis. Among 67 compounds tentatively identified from bacterial isolates, 51 were also found in the anal sac secretion. We show that the bacterial community in the anal sac consists primarily of only a few abundant taxa and that isolates of these taxa produce numerous volatiles that are found in the combined anal sac volatile profile. Several of these volatiles are found in anal sac secretions from other carnivorans, and are also associated with known bacterial biosynthesis pathways. This is consistent with the fermentation hypothesis and the possibility that the anal sac is maintained at least in part to house bacteria that produce volatiles for the host.
Racial Differences in Sepsis Recognition in the Emergency Department

We aimed to evaluate racial differences in pediatric sepsis recognition in a pediatric ED with an established electronic sepsis alert system. OBJECTIVES: We assessed racial differences in sepsis recognition in a pediatric emergency department (ED) with an established electronic sepsis alert system. METHODS: Quality-improvement data from June 1, 2016 to May 31, 2017 was used in this retrospective cohort study. All ED visits were included for non-Hispanic black (NHB) and non-Hispanic white (NHW) patients. The sepsis pathway was activated through the alert, 2 stages and a huddle, or outside of the alert using clinician judgment alone. We evaluated racial differences in the frequency of alerts and sepsis pathway activation within and outside of the alert. Multivariable regression adjusted for high-risk condition, sex, age, and insurance. RESULTS: There were 97 338 ED visits: 56 863 (58.4%) and 23 008 (23.6%) from NHBs and NHWs, respectively. NHWs were more likely than NHBs to have a positive second alert (adjusted odds ratio [aOR] 2.4; 95% confidence interval [CI] 2.1–2.8). NHWs were more likely than NHBs to have the sepsis pathway activated (aOR 1.4; 95% CI 1.02–2.1). Of those treated within the alert, there was no difference in pathway activation (aOR 0.93; 95% CI 0.62–1.4). Of those recognized by clinicians when the alert did not fire, NHWs were more likely than NHBs to be treated (aOR 3.4; 95% CI 1.8–6.4). CONCLUSIONS: NHWs were more likely than NHBs to be treated for sepsis, although this difference was specifically identified in the subset of patients treated for sepsis outside of the alert. This suggests that an electronic alert reduces racial differences compared with clinician judgment alone.
Uncertainty versus prediction error in Pavlovian fear conditioning: Commentary on Walker et al. (2019)

Prediction error, or a mismatch between what is expected and what occurs, is a fundamental feedback mechanism across modalities including sensory, attention, motivation, and associative learning. Identifying what has changed in our environment allows us to appropriately direct attention toward new information. In learning tasks, "surprise" - or the unexpected occurrence or omission of a biologically relevant event - is thought to act as a teaching signal that drives new learning.