Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of the lipopolysaccharide O‐antigen biosynthesis priming enzyme and the O‐antigen ligase in Myxococcus xanthus: critical role of LPS O‐antigen in motility and development

Myxococcus xanthus is a model bacterium to study social behavior. At the cellular level, the different social behaviors of M. xanthus involve extensive cell–cell contacts. Here, we used bioinformatics, genetics, heterologous expression and biochemical experiments to identify and characterize the key enzymes in M. xanthus implicated in O‐antigen and lipopolysaccharide (LPS) biosynthesis and examined the role of LPS O‐antigen in M. xanthus social behaviors. We identified WbaPMx (MXAN_2922) as the polyisoprenyl‐phosphate hexose‐1‐phosphate transferase responsible for priming O‐antigen synthesis. In heterologous expression experiments, WbaPMx complemented a Salmonella enterica mutant lacking the endogenous WbaP that primes O‐antigen synthesis, indicating that WbaPMx transfers galactose‐1‐P to undecaprenyl‐phosphate. We also identified WaaLMx (MXAN_2919), as the O‐antigen ligase that joins O‐antigen to lipid A‐core. Our data also support the previous suggestion that WzmMx (MXAN_4622) and WztMx (MXAN_4623) form the Wzm/Wzt ABC transporter. We show that mutations that block different steps in LPS O‐antigen synthesis can cause pleiotropic phenotypes. Also, using a wbaPMx deletion mutant, we revisited the role of LPS O‐antigen and demonstrate that it is important for gliding motility, conditionally important for type IV pili‐dependent motility and required to complete the developmental program leading to the formation of spore‐filled fruiting bodies.
Long-term autobiographical memory across middle childhood: patterns, predictors, and implications for conceptualizations of childhood amnesia

ABSTRACT We examined recall of events by children 4–11 years to inform patterns of retention of autobiographical memories as well as factors that predict their survival. 101 children participated in a 4-year prospective study. At study inception, children were 4, 6, and 8 years. They were tested annually for three more years for a total of four waves of data collection. At each wave, we obtained narrative reports of recent (all waves) and distant (Waves 2–4) events, resulting in virtually continuous sampling of memories formed by 4- to 11-year-olds and recalled after 1–3-year delays. We also measured children's language, and domain-general and memory-specific cognitive skills. Multi-level modelling revealed age-related increases in the likelihood of survival of memories over the delays. Critically, the rate of increase in retention of individual memories was the same across the cohorts. In addition to age, thematic coherence of original memory reports predicted memory survivability. Other factors were not predictive. The dense sampling and prospective tracking of memories across the 4–11-year age period permitted an especially strong test for continuity versus discontinuity in autobiographical memory across the second half of the first decade of life. The data are strongly indicative of continuity and gradual change.
Acute and late effects of combined internal and external radiation exposures on the hematopoietic system

Abstract Purpose: Incidents, such as nuclear facility accidents and the release of a ‘dirty bomb’, might result in not only external irradiation of personnel, but additional internal exposures through concomitant inhalation and/or ingestion of radioactive particulates. The purpose of this study was to define the impact of such a combination of radiation injuries on the hematopoietic niche. Material and methods: To assess changes in the murine hematopoietic system, we used a combined exposure of total body irradiation (TBI, 6 Gy) followed immediately by an internal (intraperitoneal) administration of 100 µCi of soluble 137Cs. We then evaluated acute survival in combined versus single modality exposure groups, as well as assessing hematopoietic function at 12 and 26 week time points. Results: Acutely, the combination of external and internal exposures led to an unexpected delay in excretion of 137Cs, increasing the absorbed dose in the combined exposure group and leading to mortality from an acute hematopoietic syndrome. At 12 weeks, all exposure paradigms resulted in decreased numbers of phenotypic hematopoietic stem cells (HSCs), particularly the short-term HSCs (ST-HSC); long-term HSCs (LT-HSC) were depleted only in the internal and combined exposure groups. At 26 weeks, there was significant anemia in both the TBI alone and combined exposure groups. There were decreased numbers in both the LT- and ST-HSCs and decreased functionality, as measured by competitive repopulation, was seen in all radiation groups, with the greatest effects seen in the internal and combined exposure groups. Conclusions: Our data indicate that a combined injury of sublethal external irradiation with internal contamination induces significant and persistent changes in the hematopoietic system, as may have been predicted from the literature and our own group’s findings. However, a novel observation was that the combined exposure led to an alteration in the excretion kinetics of the internal contamination, increasing the acute effects beyond those anticipated. As a result, we believe that a combined exposure poses a unique challenge to the medical community during both the acute and, possibly, delayed recovery stages.
Early Pregnancy Cardiovascular Health and Subclinical Atherosclerosis

Background Assessing and optimizing cardiovascular health (CVH) early in life, such as in pregnancy, could lead to a longer lifetime spent in better CVH and reduce the risk of cardiovascular disease. This might especially benefit women with a hypertensive disorder of pregnancy (HDP) who are more likely to develop atherosclerosis and cardiovascular disease. We hypothesized that CVH in pregnancy is related to later life CVH and carotid intima‐media thickness (CIMT), and that these associations differ between women with a normotensive pregnancy and women with an HDP. Methods and Results This study was conducted within the prospective population‐based Generation R Study. CVH in pregnancy was based on 5 metrics (blood pressure, total‐cholesterol, glucose, smoking, and body mass index). Postpartum CVH additionally included physical activity and diet scores, according to the American Heart Association classification. Postpartum CVH and CIMT were measured 10 years after pregnancy. Results were analyzed for women with a normotensive pregnancy and those with an HDP. Women with a normotensive pregnancy (n=1786) and women with an HDP (n=138) were evaluated from early pregnancy until 10 years postpartum. Better CVH in early pregnancy was associated with a smaller CIMT and better postpartum CVH in all women, especially in those with an HDP (CIMT: −9.82 μm [95% CI: −17.98, −1.67]). Conclusions Already in pregnancy, better CVH is associated with a smaller CIMT and better CVH 10 years postpartum, especially in women with an HDP. As pregnancy is an incentive for women to improve lifestyle, assessing CVH in pregnancy might help improve postpartum CVH and reduce cardiovascular disease risk.
Association between Lipoprotein (a) Levels and Metabolic Syndrome in a Middle-aged and Elderly Chinese Cohort.

OBJECTIVE The association between lipoprotein (a) [Lp(a)] levels and metabolic syndrome (MetS) remains uncertain, especially in the Asian population. The purpose of this study was to demonstrate the association between Lp(a) levels and MetS in a middle-aged and elderly Chinese cohort. METHODS A cross-sectional study of 10,336 Chinese adults aged 40 years or older was conducted in Jiading District, Shanghai, China. Logistic regression analysis was used to evaluate the association between serum Lp(a) levels and MetS. RESULTS In the overall population, 37.5% of participants had MetS. Compared with individuals in the lowest quartile of serum Lp(a) levels, those in the highest quartile had a lower prevalence of MetS (30.9% vs. 46.9%, P for trend < 0.0001). Multivariate logistic regression analyses showed that compared with participants in the bottom quartile of serum Lp(a) levels, those in the top quartile had decreased odds ratio (OR) for prevalent MetS [multivariate-adjusted OR 0.45 (95% confidence interval 0.39-0.51); P < 0.0001]. Additionally, Lp(a) level was conversely associated with the risk of central obesity, high fasting glucose, high triglycerides, and low HDL cholesterol, but not with hypertension. Stratified analyses suggested that increasing levels of Lp(a) was associated with decreased risk of MetS in all the subgroups. CONCLUSION Serum Lp(a) level was inversely associated with the risk of prevalent MetS in a middle-aged and elderly Chinese cohort.
S100-EPISPOT: A New Tool to Detect Viable Circulating Melanoma Cells

Metastatic melanoma is one of the most aggressive and drug-resistant cancers with very poor overall survival. Circulating melanoma cells (CMCs) were first described in 1991. However, there is no general consensus on the clinical utility of CMC detection, largely due to conflicting results linked to the use of heterogeneous patient populations and different detection methods. Here, we developed a new EPithelial ImmunoSPOT (EPISPOT) assay to detect viable CMCs based on their secretion of the S100 protein (S100-EPISPOT). Then, we compared the results obtained with the S100-EPISPOT assay and the CellSearch® CMC kit using blood samples from a homogeneous population of patients with metastatic melanoma. We found that S100-EPISPOT sensitivity was significantly higher than that of CellSearch®. Specifically, the percentage of patients with ≥2 CMCs was significantly higher using S100-EPISPOT than CellSearch® (48% and 21%, respectively; p = 0.0114). Concerning CMC prognostic value, only the CellSearch® results showed a significant association with overall survival (p = 0.006). However, due to the higher sensitivity of the new S100-EPISPOT assay, it would be interesting to determine whether this functional test could be used in patients with non-metastatic melanoma for the early detection of tumor relapse and for monitoring the treatment response.
Common and Distinct Functional Brain Networks for Intuitive and Deliberate Decision Making

Reinforcement learning studies in rodents and primates demonstrate that goal-directed and habitual choice behaviors are mediated through different fronto-striatal systems, but the evidence is less clear in humans. In this study, functional magnetic resonance imaging (fMRI) data were collected whilst participants (n = 20) performed a conditional associative learning task in which blocks of novel conditional stimuli (CS) required a deliberate choice, and blocks of familiar CS required an intuitive choice. Using standard subtraction analysis for fMRI event-related designs, activation shifted from the dorso-fronto-parietal network, which involves dorsolateral prefrontal cortex (DLPFC) for deliberate choice of novel CS, to ventro-medial frontal (VMPFC) and anterior cingulate cortex for intuitive choice of familiar CS. Supporting this finding, psycho-physiological interaction (PPI) analysis, using the peak active areas within the PFC for novel and familiar CS as seed regions, showed functional coupling between caudate and DLPFC when processing novel CS and VMPFC when processing familiar CS. These findings demonstrate separable systems for deliberate and intuitive processing, which is in keeping with rodent and primate reinforcement learning studies, although in humans they operate in a dynamic, possibly synergistic, manner particularly at the level of the striatum.
Provider-perceived barriers to diagnosis and treatment of acute coronary syndrome in Tanzania: a qualitative study

Abstract Background The incidence of acute coronary syndrome (ACS) is growing across sub-Saharan Africa and many healthcare systems are ill-equipped for this growing burden. Evidence suggests that healthcare providers may be underdiagnosing and undertreating ACS, leading to poor health outcomes. The goal of this study was to examine provider perspectives on barriers to ACS care in Tanzania in order to identify opportunities for interventions to improve care. Methods Semistructured in-depth interviews were conducted with physicians and clinical officers from emergency departments and outpatient departments in northern Tanzania. Thematic analysis was conducted using an iterative cycle of coding and consensus building. Results The 11 participants included six physicians and five clinical officers from health centers, community hospitals and one referral hospital. Providers identified barriers related to providers, systems and patients. Provider-related barriers included inadequate training regarding ACS and poor application of textbook-based knowledge. System-related barriers included lack of diagnostic equipment, unavailability of treatments, referral system delays, lack of data regarding disease burden, absence of locally relevant guidelines and cost of care. Patient-related barriers included inadequate ACS knowledge, inappropriate healthcare-seeking behavior and non-adherence. Conclusions This study identified actionable barriers to ACS care in northern Tanzania. Multifaceted interventions are urgently needed to improve care.
Is There a Correlation Between Nasolabial Appearance and Dentoalveolar Relationships in Patients With Repaired Unilateral Cleft Lip and Palate?

Objective: To determine whether a relationship exists between the aesthetic scores given to photographic records of the nasolabial region of patients with repaired unilateral cleft lip and palate (UCLP) and the 5-Year Olds’ Index scores of study models for the same participants. Design: Retrospective study. Setting: University of Bristol Dental Hospital, United Kingdom. Participants: Patients with nonsyndromic UCLP previously enrolled in the Cleft Care UK (CCUK) Study. Methods: The CCUK participants, who had both study models and photographs (frontal and worm’s eye view), were identified and their records retrieved. These were rated by 2 consultants and 2 senior registrars in orthodontics. The 5-Year Olds’ Index was used to score the study models, and at a separate sitting, a 5-point Likert scale was used to score the cropped frontal and worm’s eye view photographs of the same children. The results were analyzed using intraclass correlation coefficients and Cohen κ. Main Outcome Measures: Correlation between the aesthetic scores of the photographic views and the concordant 5-Year Olds’ Index scores of the study models. Results: The intraclass correlation coefficient scores showed very poor agreement between the photographic views and their concordant study models. The level of inter- and intra-rater reliability was strongest when scoring the study models. Conclusions: There was no agreement between the scores given to various photographic views and their corresponding study models. Scoring the study models using the 5-Year Olds’ Index was the most reliable outcome measure for this age-group.
Effect of Parent–Child Attachment on College Students’ Social Anxiety: A Moderated Mediation Model

This study investigated the relationship between parent–child attachment and social anxiety in college students, as well as the mediating role of psychological resilience and the moderating role of online social support. In total, 614 college students were recruited by the cluster sampling method. The results showed that (1) parent–child attachment was negatively correlated with college students’ social anxiety and positively correlated with their psychological resilience, (2) psychological resilience played a mediating role between parent–child attachment and college students’ social anxiety, and (3) online social support regulated the first half and second half of the mediation process in which parent–child attachment affected college students’ social anxiety through psychological resilience. These findings revealed the mechanism of parent–child attachment affecting social anxiety, which had important theoretical and empirical value for enhancing the strength of college students’ psychological resilience and alleviating social anxiety.
Hospital-related, maternal, and fetal risk factors for neonatal asphyxia and moderate or severe hypoxic-ischemic encephalopathy: a retrospective cohort study

Abstract Aim A previous large US study had documented an increased risk of asphyxia in small volume and rural hospitals. Our objective was to evaluate this in all hospitals in Alberta, a Canadian province. Methods Retrospective cohort study of all singleton births ≥ 35-week gestation, in Alberta, from 2002–16 recorded in a perinatal database. Asphyxia was defined as intrapartum stillbirth or neonatal death from asphyxia or Neonatal Intensive Care Unit admission and at least two of the following: a. Apgar score of ≤ 5 at 10 minutes; b. mechanical ventilation or chest compressions for resuscitation within 10 minutes; c. cord pH < 7.00 (venous or arterial), or arterial base excess ≥ 12 at birth. Urban hospitals were defined as those serving a population of ≥ 50 000. Hospital volume was categorized by the following: urban: < 1200, 1200–2399, 2400–3600, > 3600 annual births and Rural: < 50, 50–599, 600–1699 annual births. Data on moderate–severe neonatal hypoxic-ischemic encephalopathy was also obtained from two provincial asphyxia databases for 2010–2016. Results The overall rate of neonatal asphyxia was 2.28 per 1000 births for the study period and was 2.5/1000 in the urban hospitals and 1.35/1000 in the rural hospitals, OR: 1.86 95% CI (1.58, 2.19). The rate of moderate or severe neonatal hypoxic-ischemic encephalopathy was 0.9/1000 and was not associated with urban hospital birth; OR: 1.12 95%CI (0.82, 1.53) hospital volume was also not associated with asphyxia or moderate or severe neonatal hypoxic-ischemic encephalopathy. Conclusions This study observed similar rates of asphyxia and moderate or severe neonatal hypoxic-ischemic encephalopathy for rural and urban hospitals in Alberta and no association with hospital volume.
Telomere attrition predicts reduced survival in a wild social bird, but short telomeres do not

Attempts to understand the causes of variation in senescence trajectories would benefit greatly from biomarkers that reflect the progressive declines in somatic integrity (SI) that lead to senescence. While telomere length has attracted considerable interest in this regard, sources of variation in telomere length potentially unrelated to declines in SI could, in some contexts, leave telomere attrition rates a more effective biomarker than telomere length alone. Here, we investigate whether telomere length and telomere attrition rates predict the survival of wild white‐browed sparrow‐weaver nestlings (Plocepasser mahali). Our analyses of telomere length reveal counterintuitive patterns: telomere length soon after hatching negatively predicted nestling survival to fledging, a pattern that appears to be driven by differentially high in‐nest predation of broods with longer telomeres. Telomere length did not predict survival outside this period: neither hatchling telomere length nor telomere length in the mid‐nestling period predicted survival from fledging to adulthood. Our analyses using within‐individual telomere attrition rates, by contrast, revealed the expected relationships: nestlings that experienced a higher rate of telomere attrition were less likely to survive to adulthood, regardless of their initial telomere length and independent of effects of body mass. Our findings support the growing use of telomeric traits as biomarkers of SI, but lend strength to the view that longitudinal assessments of within‐individual telomere attrition since early life may be a more effective biomarker in some contexts than telomere length alone.
Comparative Transcriptome Analysis of Streptomyces Clavuligerus in Response to Favorable and Restrictive Nutritional Conditions

Background: Clavulanic acid (CA), a β-lactamase inhibitor, is industrially produced by the fermentation of Streptomyces clavuligerus. The efficiency of CA production is associated with media composition, culture conditions and physiological and genetic strain characteristics. However, the molecular pathways that govern CA regulation in S. clavuligerus remain unknown. Methods and Results: Here we used RNA-seq to perform a comparative transcriptome analysis of S. clavuligerus ATCC 27064 wild-type strain grown in both a favorable soybean-based medium and in limited media conditions to further contribute to the understanding of S. clavuligerus metabolism and its regulation. A total of 350 genes were found to be differentially expressed between conditions; 245 genes were up-regulated in favorable conditions compared to unfavorable. Conclusion: The up-regulated expression of many regulatory and biosynthetic CA genes was positively associated with the favorable complex media condition along with pleiotropic regulators, including proteases and some genes whose biological function have not been previously reported. Knowledge from differences between transcriptomes from complex/defined media represents an advance in the understanding of regulatory paths involved in S. clavuligerus’ metabolic response, enabling the rational design of future experiments.
Understanding the Female Hispanic and Latino American Facial Aesthetic Patient

Background: Among the growing aesthetic patient population, Hispanic/Latinos represent the largest proportion of non-Caucasians patients. While treatment of Caucasian facial aging patterns are well documented, far less information describes the aesthetic needs of the Hispanic/Latino patient. Objective: An online study was designed to survey facial aesthetic concerns, treatment priorities, and future treatment considerations among a US-based population of Hispanic/Latino American women. Materials and Methods: A total of 401 participants ages 30 to 65 years reported their attitudes toward facial aging, current facial conditions, most bothersome facial areas, areas most/least likely to be treated first, awareness of treatment options and their consideration rates, and motives and barriers that factor into consideration of injectable treatments. Results: Most participants wanted to look good for their age and treatment interests reflected predominant conditions: facial wrinkles, periorbital signs of aging, and uneven skin tone. Most bothersome facial areas included the submental area, periorbital area, and forehead, which were also among the areas most-likely to treat first. The majority of participants would consider injectables. Cost and safety/side effects were cited as frequent concerns. Conclusion: An understanding of the facial aesthetic concerns and treatment priorities specific to Hispanic/Latino women will enhance the practitioner’s patient-centric treatment approach. J Drugs Dermatol. 2019;18(7):623-632.