Miracle-dz/UniFAR-FTUs huggingface dataset:
Human milk composition and infant growth

Purpose of review This review highlights relevant studies published between 2015 and 2017 on human milk composition and the association with infant growth. Recent findings High-quality studies investigating how human milk composition is related to infant growth are sparse. Recent observational studies show that human milk concentrations of protein, fat, and carbohydrate likely have important influence on infant growth and body composition. Furthermore, some observational studies examining human milk oligosaccharides and hormone concentrations suggest functional relevance to infant growth. For human milk micronutrient concentrations and microbiota content, and other bioactive components in human milk, the association with infant growth is still speculative and needs further investigation. The included studies in this review are all limited in their methodological design and methods but have interesting potential in understanding infant growth. Summary Available evidence on human milk composition in relation to infant growth is sparse. This review summarizes recent publications investigating human milk composition; including micro- and macronutrients, human milk oligosaccharides, hormones and other bioactive components, and the association with infant weight, length, body mass index, and body composition.
Early Sites of Virus Replication After Oral SIVmac251 Infection of Infant Macaques: Implications for Pathogenesis.

Despite optimization of preventative measures for vertical HIV-1 transmission, daily, roughly 400 infants become HIV infected, most of them through breastfeeding. Viral entry has been presumed to occur in the gastrointestinal tract; however, the exact entry site(s) have not been defined. Therefore, we quantified simian immunodeficiency virus (SIV) RNA and DNA in oral, intestinal, and systemic tissues of 15 infant macaques within 48-96 h after oral SIVmac251 exposure. SIV DNA was detected as early as 48 h, whereas SIV RNA was typically detected at later time points (72-96 h). Transmitted founder viruses were identical or very similar to a single genotype in the SIVmac251 challenge stock. SIV RNA and DNA were most frequently found in lymph nodes (LNs) draining the oral cavity and in the ileum. Using in situ hybridization, SIV-infected cells in LNs were exclusively represented by CD3+ T cells. SIV RNA and DNA were also detected in the lungs of 20% of the animals, and 60% of the animals had detectable SIV DNA in the cerebrum. The early detection of viral RNA or DNA in lung and brain tissues emphasizes the need for early treatment of pediatric HIV infection to prevent damage not only to the immune system but also to the respiratory tract and central nervous system.
Glycosylation of MUC1 influences the binding of a therapeutic antibody by altering the conformational equilibrium of the antigen

In cancer cells, the glycoprotein Mucin 1 (MUC1) undergoes abnormal, truncated glycosylation. The truncated glycosylation exposes cryptic peptide epitopes that can be recognized by antibodies. Since these immunogenic regions are cancer specific, they represent ideal targets for therapeutic antibodies. We investigated the role of tumor-specific glycosylation on antigen recognition by the therapeutic antibody AR20.5. We explored the affinity of AR20.5 to a synthetic cancer-specific MUC1 glycopeptide and peptide. The antibody bound to the glycopeptide with an order of magnitude stronger affinity than the naked peptide. Given these results, we postulated that AR20.5 must specifically bind the carbohydrate as well as the peptide. Using X-ray crystallography, we examined this hypothesis by determining the structure of AR20.5 in complex with both peptide and glycopeptide. Surprisingly, the structure revealed that the carbohydrate did not form any specific polar contacts with the antibody. The high affinity of AR20.5 for the glycopeptide and the lack of specific binding contacts support a hypothesis that glycosylation of MUC1 stabilizes an extended bioactive conformation of the peptide recognized by the antibody. Since high affinity binding of AR20.5 to the MUC1 glycopeptide may not driven by specific antibody-antigen contacts, but rather evidence suggests that glycosylation alters the conformational equilibrium of the antigen, which allows the antibody to select the correct conformation. This study suggests a novel mechanism of antibody-antigen interaction and also suggests that glycosylation of MUC1 is important for the generation of high affinity therapeutic antibodies.
Altered Functional Connectivity of Striatal Subregions in Patients with Multiple Sclerosis

Abnormal corticostriatal resting-state functional connectivity (rsFC) has been implicated in the neuropathology of multiple sclerosis. The striatum, a component of the basal ganglia, is involved in diverse functions including movement, cognition, emotion, and limbic information processing. However, the brain circuits of the striatal subregions contributing to the changes in rsFC in relapsing–remitting multiple sclerosis (RRMS) patients remain unknown. We used six subdivisions of the striatum in each hemisphere as seeds to investigate the rsFC of striatal subregions between RRMS patients and matched healthy controls (HCs). In addition, we also scanned a subcohort of RRMS patients after an average of 7 months to test the reliability of our findings. Compared to HCs, we found significantly increased dorsal caudal putamen (DCP) connectivity with the premotor area, dorsal lateral prefrontal cortex (DLPFC), insula, precuneus, and superior parietal lobule, and significantly increased connectivity between the superior ventral striatum and posterior cingulate cortex (PCC) in RRMS patients following both scans. Furthermore, we found significant associations between the Expanded Disability Status Scale and the rsFC of the left DCP with the DLPFC and parietal areas in RRMS patients. Our results suggest that the DCP may be a critical striatal subregion in the pathophysiology of RRMS.
Statistical analysis of relation between plasma methotrexate concentration and toxicity in high‐dose methotrexate therapy of childhood nonHodgkin lymphoma

Plasma monitoring of Methotrexate (MTX) levels is a standard approach to predict MTX‐related toxicities in a high‐dose (HD) MTX monotherapy for childhood acute lymphoblastic leukemia. However, it is uncertain whether plasma MTX levels can predict MTX‐related toxicity in the HDMTX plus additional chemotherapy for childhood B‐cell nonHodgkin lymphoma (B‐NHL).
Effect of Religious Practices of Ramadan on Sleep and Perceived Sleepiness of Medical Students

Background: Observant Muslims substantially alter their normal routines, including daytime fasting and day-night activity patterns during the month of Ramadan. Purpose: It is unknown whether observing the religious practices of Ramadan impacts negatively on daytime somnolence, a factor known to impair learning. Methods: A cross-sectional survey measuring self-reported sleep time and the Epworth Sleepiness Scale of observant Muslim medical students before, during, and after Ramadan. Results: There was no significant variation in sleep score pre-Ramadan (10.04 ± 3.47), during Ramadan (10.46 ± 3.57), and post Ramadan (9.73 ± 3.33), F(2, 355) = 1.278, p =. 280. Night sleep hours were significantly longer both before (6.22 ± 1.45) and after (6.22 ± 1.59) than during Ramadan (5.22 ± 1.85), F(2, 366) = 15.289, p <. 001. Daytime sleep hours pre-Ramadan (1.05 ± 1.36) and post Ramadan (0.70 ± 1.21) were significantly shorter than during Ramadan (1.48 ± 1.46; pre: z = 2.654, p =. 08; post: z = -4.940, p <. 001). Conclusion: Students successfully adapt and avoid a rise in daytime somnolence by increasing daytime sleep hours during Ramadan.
Maternal serum bisphenol A levels and risk of pre-eclampsia: a nested case–control study

Abstract Background Although recent studies have indicated the potential adverse effects of maternal bisphenol A (BPA) exposure on pregnancy such as increasing the risk of pre-eclampsia, epidemiological evidence is limited. We aimed to evaluate the relationship between maternal BPA exposure and the risk of pre-eclampsia. Methods We conducted a nested case–control study among 173 women (74 cases of pre-eclampsia and 99 controls). BPA concentrations were measured using liquid chromatography-mass spectrometry in the maternal serum samples collected during 16–20 gestational weeks. Multivariate logistic models were used to examine the relationship between maternal serum BPA concentrations and the risk of pre-eclampsia. Results BPA was detectable (>0.1 µg/l) in 78.6% of the maternal serum samples at three levels: low (<2.24 µg/l), medium (2.24-4.44 µg/l), and high (>4.44 µg/l). BPA concentrations were significantly higher in the serum samples collected from the pre-eclampsia cases than those from controls (median: 3.40 vs. 1.50 µg/l, P < 0.01). With adjustment for maternal age, primiparous and BMI, the odds of developing pre-eclampsia were significantly elevated in subjects with high serum BPA levels compared with those with low levels (adjusted OR = 16.46, 95%CI = 5.42–49.85) regardless of subcategories of pre-eclampsia including severity and onset time. Among the pre-eclampsia subjects, the maternal serum concentration of BPA was not different between the early- and late-onset subjects (median: 3.09 vs. 3.50 µg/l, P = 0.57), but surprisingly higher in mild pre-eclampsia subjects compared with severe pre-eclampsia subjects (median: 5.20 vs. 1.80 µg/l, P < 0.01). Conclusions These results demonstrated that maternal exposure to high level of BPA could be associated with an increased risk of pre-eclampsia.
Identification of a signaling cascade that maintains constitutive δ-opioid receptor incompetence in peripheral sensory neurons

μ-Opioid receptor (MOR) agonists are often used to treat severe pain but can result in adverse side effects. To circumvent systemic side effects, targeting peripheral opioid receptors is an attractive alternative treatment for severe pain. Activation of the δ-opioid receptor (DOR) produces similar analgesia with reduced side effects. However, until primed by inflammation, peripheral DOR is analgesically incompetent, raising interest in the mechanism. We recently identified a novel role for G-protein-coupled receptor kinase 2 (GRK2) that renders DOR analgesically incompetent at the plasma membrane. However, the mechanism that maintains constitutive GRK2 association with DOR is unknown. Protein kinase A (PKA) phosphorylation of GRK2 at Ser-685 targets it to the plasma membrane. Protein kinase A-anchoring protein 79/150 (AKAP), residing at the plasma membrane in neurons, scaffolds PKA to target proteins to mediate downstream signal. Therefore, we sought to determine whether GRK2-mediated DOR desensitization is directed by PKA via AKAP scaffolding. Membrane fractions from cultured rat sensory neurons following AKAP siRNA transfection and from AKAP-knock-out mice had less PKA activity, GRK2 Ser-685 phosphorylation, and GRK2 plasma membrane targeting than controls. Site-directed mutagenesis revealed that GRK2 Ser-685 phosphorylation drives the association of GRK2 with plasma membrane-associated DOR. Moreover, overexpression studies with AKAP mutants indicated that impaired AKAP-mediated PKA scaffolding significantly reduces DOR-GRK2 association at the plasma membrane and consequently increases DOR activity in sensory neurons without a priming event. These findings suggest that AKAP scaffolds PKA to increase plasma membrane targeting and phosphorylation of GRK2 to maintain DOR analgesic incompetence in peripheral sensory neurons.
First evaluation of QuantiFERON-TB Gold Plus performance in contact screening

Identifying latently infected individuals is crucial for the elimination of tuberculosis (TB). We evaluated for the first time the performance of a new type of interferon-γ release assay, QuantiFERON-TB Plus (QFT-Plus), which includes an additional antigen tube (TB2), stimulating both CD4+ and CD8+ T-cells in contacts of TB patients. Contacts were screened for latent TB infection by tuberculin skin test, QFT-Plus and QuantiFERON-TB Gold in Tube (QFT-GIT). In 119 TB contacts, the overall agreement between QFT-Plus and QFT-GIT was high, with a Cohen's κ of 0.8. Discordant results were found in 12 subjects with negative QFT-GIT and positive QFT-Plus results. In analyses of markers of TB exposure and test results, the average time spent with the index case was the strongest risk factor for positivity in each of these tests. The difference in interferon-γ production between the two antigen tubes (TB2−TB1) was used as an estimate of CD8+ stimulation provided by the TB2. TB2−TB1 values >0.6 IU·mL−1 were significantly associated with proximity to the index case and European origin. QFT-Plus has a stronger association with surrogate measures of TB exposure than QFT-GIT in adults screened for latent TB infection. Interferon-γ response in the new antigen tube used an indirect estimate of specific CD8+ response correlates with increased Mycobacterium tuberculosis exposure, suggesting a possible role in identifying individuals with recent infection. QuantiFERON-TB Plus improved the diagnostic accuracy for latent TB infection in the setting of contact screening http://ow.ly/2Az0300SDg3
Numerical Relations and Skill Level Constrain Co-Adaptive Behaviors of Agents in Sports Teams

Similar to other complex systems in nature (e.g., a hunting pack, flocks of birds), sports teams have been modeled as social neurobiological systems in which interpersonal coordination tendencies of agents underpin team swarming behaviors. Swarming is seen as the result of agent co-adaptation to ecological constraints of performance environments by collectively perceiving specific possibilities for action (affordances for self and shared affordances). A major principle of invasion team sports assumed to promote effective performance is to outnumber the opposition (creation of numerical overloads) during different performance phases (attack and defense) in spatial regions adjacent to the ball. Such performance principles are assimilated by system agents through manipulation of numerical relations between teams during training in order to create artificially asymmetrical performance contexts to simulate overloaded and underloaded situations. Here we evaluated effects of different numerical relations differentiated by agent skill level, examining emergent inter-individual, intra- and inter-team coordination. Groups of association football players (national – NLP and regional-level – RLP) participated in small-sided and conditioned games in which numerical relations between system agents were manipulated (5v5, 5v4 and 5v3). Typical grouping tendencies in sports teams (major ranges, stretch indices, distances of team centers to goals and distances between the teams' opposing line-forces in specific team sectors) were recorded by plotting positional coordinates of individual agents through continuous GPS tracking. Results showed that creation of numerical asymmetries during training constrained agents' individual dominant regions, the underloaded teams' compactness and each team's relative position on-field, as well as distances between specific team sectors. We also observed how skill level impacted individual and team coordination tendencies. Data revealed emergence of co-adaptive behaviors between interacting neurobiological social system agents in the context of sport performance. Such observations have broader implications for training design involving manipulations of numerical relations between interacting members of social collectives.
Resource Supply Overrides Temperature as a Controlling Factor of Marine Phytoplankton Growth

The universal temperature dependence of metabolic rates has been used to predict how ocean biology will respond to ocean warming. Determining the temperature sensitivity of phytoplankton metabolism and growth is of special importance because this group of organisms is responsible for nearly half of global primary production, sustains most marine food webs, and contributes to regulate the exchange of CO2 between the ocean and the atmosphere. Phytoplankton growth rates increase with temperature under optimal growth conditions in the laboratory, but it is unclear whether the same degree of temperature dependence exists in nature, where resources are often limiting. Here we use concurrent measurements of phytoplankton biomass and carbon fixation rates in polar, temperate and tropical regions to determine the role of temperature and resource supply in controlling the large-scale variability of in situ metabolic rates. We identify a biogeographic pattern in phytoplankton metabolic rates, which increase from the oligotrophic subtropical gyres to temperate regions and then coastal waters. Variability in phytoplankton growth is driven by changes in resource supply and appears to be independent of seawater temperature. The lack of temperature sensitivity of realized phytoplankton growth is consistent with the limited applicability of Arrhenius enzymatic kinetics when substrate concentrations are low. Our results suggest that, due to widespread resource limitation in the ocean, the direct effect of sea surface warming upon phytoplankton growth and productivity may be smaller than anticipated.
Genetic evidence that β-arrestins are dispensable for the initiation of β2-adrenergic receptor signaling to ERK

Ligand activation of β2-adrenergic receptors induces the phosphorylation of the kinase ERK in a β-arrestin–independent manner. β-Arrestins not necessary The β2-adrenergic receptor is thought to activate signaling mediated by the kinase ERK through a pathway that does not require G proteins but rather the β-arrestin family of scaffolding proteins. Biased agonists for the β2-adrenergic receptor are being developed to selectively activate this pathway. O’Hayre et al. took advantage of improved technologies for knocking out proteins in cells and unexpectedly found that β-arrestins were not required for ERK activation downstream of the β2-adrenergic receptor, although β-arrestin 2 was required for receptor internalization. Instead, the pathway depended on Gαs, Gβγ, and various other signaling molecules. These results suggest that biased agonists for the β2-adrenergic receptor may exert their effects in a β-arrestin–independent manner. The β2-adrenergic receptor (β2AR) has provided a paradigm to elucidate how G protein–coupled receptors (GPCRs) control intracellular signaling, including the discovery that β-arrestins, which bind to ligand-activated GPCRs, are central for GPCR function. We used genome editing, conditional gene deletion, and small interfering RNAs (siRNAs) to determine the roles of β-arrestin 1 (β-arr1) and β-arr2 in β2AR internalization, trafficking, and signaling to ERK. We found that only β-arr2 was essential for β2AR internalization. Unexpectedly, β-arr1 and β-arr2 and receptor internalization were dispensable for ERK activation. Instead, β2AR signaled through Gαs and Gβγ subunits through a pathway that involved the tyrosine kinase SRC, the adaptor protein SHC, the guanine nucleotide exchange factor SOS, the small GTPase RAS, and the kinases RAF and MEK, which led to ERK activation. These findings provide a molecular framework for β2AR signaling through β-arrestin–independent pathways in key physiological functions and under pathological conditions.
Pressure thresholds and stiffness on the plantar surface of the human foot

Abstract A methodology to assess Pressure Discomfort Thresholds (PDT), Pressure Pain Thresholds (PPT) and tissue stiffness on the plantar surface of the foot was developed. Ten male and 10 female participants volunteered for the study. Foot landmarks were used to create a standardised grid-type template of 95 points. For each test point, PPT and PDT values were obtained, and stiffness was calculated for each of the 20 participants. Cluster analyses were performed to determine the regions of similarity for the three dependent variables, PPT, PDT and stiffness. Moran’s-I-index was used to determine the spatial auto correlations. The use of k-means clustering showed five distinct clusters while the three dependent variables showed strong correlations to each other. Morisita’s similarity index was used to check the similarity of the grid among all participants. Both male and female participants showed a Morisita’s index greater than 0.7 confirming the reliability of the foot template. Practitioner Summary: Pressure Discomfort thresholds (PPT), Pressure pain thresholds (PPT) and tissue stiffness were evaluated at 95 points on the plantar surface of the foot. The PPT and related PDT map are useful to design the footbeds of shoes. Based on the data collected, five distinct clusters of locations were identified.
Walking Back to the Future: The Impact of Walking Backward and Forward on Spatial and Temporal Concepts

Embodied cognition frameworks suggest a direct link between sensorimotor experience and cognitive representations of concepts (Shapiro, 2011). We examined whether this holds also true for concepts that cannot be directly perceived with the sensorimotor system (i.e., temporal concepts). To test this, participants learned object-space (Exp. 1) or object-time (Exp. 2) associations. Afterwards, participants were asked to assign the objects to their location in space/time meanwhile they walked backward, forward, or stood on a treadmill. We hypothesized that walking backward should facilitate the online processing of “behind”/“past”-related stimuli, but hinder the processing of “ahead”/“future”-related stimuli, and a reversed effect for forward walking. Indeed, “ahead”- and “future”-related stimuli were processed slower during backward walking. During forward walking and standing, stimuli were processed equally fast. The results provide partial evidence for the activation of specific spatial and temporal concepts by whole-body movements and are discussed in the context of movement familiarity.
Portrayal of Alcohol Brands Popular Among Underage Youth on YouTube: A Content Analysis.

OBJECTIVE We characterized leading YouTube videos featuring alcohol brand references and examined video characteristics associated with each brand and video category. METHOD We systematically captured the 137 most relevant and popular videos on YouTube portraying alcohol brands that are popular among underage youth. We used an iterative process to codebook development. We coded variables within domains of video type, character sociodemographics, production quality, and negative and positive associations with alcohol use. All variables were double coded, and Cohen's kappa was greater than . 80 for all variables except age, which was eliminated. RESULTS There were 96,860,936 combined views for all videos. The most common video type was "traditional advertisements," which comprised 40% of videos. Of the videos, 20% were "guides" and 10% focused on chugging a bottle of distilled spirits. While 95% of videos featured males, 40% featured females. Alcohol intoxication was present in 19% of videos. Aggression, addiction, and injuries were uncommonly identified (2%, 3%, and 4%, respectively), but 47% of videos contained humor. Traditional advertisements represented the majority of videos related to Bud Light (83%) but only 18% of Grey Goose and 8% of Hennessy videos. Intoxication was most present in chugging demonstrations (77%), whereas addiction was only portrayed in music videos (22%). Videos containing humor ranged from 11% for music-related videos to 77% for traditional advertisements. CONCLUSIONS YouTube videos depicting the alcohol brands favored by underage youth are heavily viewed, and the majority are traditional or narrative advertisements. Understanding characteristics associated with different brands and video categories may aid in intervention development.