Miracle-dz/UniFAR-FTUs huggingface dataset:
Measurement Invariance and Convergent Validity of Anger and Sadness Self-Regulation Among Youth From Six Cultural Groups

The present study examined measurement invariance and convergent validity of a novel vignette-based measure of emotion-specific self-regulation that simultaneously assesses attributional bias, emotion-regulation, and self-efficacy beliefs about emotion regulation. Participants included 541 youth–mother dyads from three countries (Italy, the United States, and Colombia) and six ethnic/cultural groups. Participants were 12.62 years old (SD = 0.69). In response to vignettes involving ambiguous peer interactions, children reported their hostile/depressive attribution bias, self-efficacy beliefs about anger and sadness regulation, and anger/sadness regulation strategies (i.e., dysregulated expression and rumination). Across the six cultural groups, anger and sadness self-regulation subscales had full metric and partial scalar invariance for a one-factor model, with some exceptions. We found support for both a four- and three-factor oblique model (dysregulated expression and rumination loaded on a second-order factor) for both anger and sadness. Anger subscales were related to externalizing problems, while sadness subscales were related to internalizing symptoms.
In Utero Oxcarbazepine Exposure and Neonatal Abstinence Syndrome: Case Report and Brief Review of the Literature

Oxcarbazepine is a second‐generation antiepileptic drug that is used to treat partial seizures. Although it has been increasingly used in pregnant women, its fetal safety has not been fully validated. We describe a 12‐hour‐old neonate who developed neonatal abstinence syndrome (NAS) after intrauterine exposure to oxcarbazepine. The neonate was born via cesarean section to a mother who took oxcarbazepine 300 mg/day for treatment of seizures throughout her pregnancy. Approximately 12 hours after birth, the infant developed paroxysmal jitter, which mainly presented as increased excitability, irritability, limb shaking, and increased muscle tone. These symptoms resolved by day 9 of life. Although NAS occurs most often after in utero exposure to opioids, exposure to other drugs during pregnancy may contribute to a small proportion of NAS cases. To our knowledge, this is the second case report of oxcarbazepine‐induced NAS. Pregnant women with epilepsy should weigh the pros and cons of continuing oxcarbazepine during their pregnancy when they are prescribed this drug. For infants with in utero oxcarbazepine exposure, comprehensive assessments and examinations are necessary for screening oxcarbazepine‐induced NAS.
Maintenance of mixed mating after the loss of self-incompatibility in a long-lived perennial herb

Background and Aims Many hermaphroditic plants avoid self-fertilization by means of a molecular self-incompatibility (SI) system, a complex trait that is difficult to evolve but relatively easy to lose. Loss of SI is a prerequisite for an evolutionary transition from obligate outcrossing to self-fertilization, which may bring about rapid changes in the genetic diversity and structure of populations. Loss of SI is also often followed by the evolution of a ‘selfing syndrome’, with plants having small flowers, little nectar and few pollen grains per ovule. Here, we document the loss of SI in the long-lived Spanish toadflax Linaria cavanillesii, which has led to mixed mating rather than a transition to a high rate of selfing and in which an outcrossing syndrome has been maintained. Methods We performed crosses within and among six populations of L. cavanillesii in the glasshouse, measured floral traits in a common-garden experiment, performed a pollen-limitation experiment in the field and conducted population genetic analyses using microsatellites markers. Key Results Controlled crosses revealed variation in SI from fully SI through intermediate SI to fully self-compatible (SC). Flowers of SC individuals showed no evidence of a selfing syndrome. Although the SC population of L. cavanillesii had lower within-population genetic diversity than SI populations, as expected, population differentiation among all populations was extreme and represents an FST outlier in the distribution for both selfing and outcrossing species of flowering plants. Conclusions Together, our results suggest that the transition to SC in L. cavanillesii has probably been very recent, and may have been aided by selection during or following a colonization bottleneck rather than in the absence of pollinators. We find little indication that the transition to SC has been driven by selection for reproductive assurance under conditions currently prevailing in natural populations.
Cost analyses of peer health worker and mHealth support interventions for improving AIDS care in Rakai, Uganda

Abstract A cost analysis study calculates resources needed to deliver an intervention and can provide useful information on affordability for service providers and policy-makers. We conducted cost analyses of both a peer health worker (PHW) and a mHealth (mobile phone) support intervention. Excluding supervisory staffing costs, total yearly costs for the PHW intervention was $8475, resulting in a yearly cost per patient of $8.74, per virologic failure averted cost of $189, and per patient lost to follow-up averted cost of $1025. Including supervisory staffing costs increased total yearly costs to $14,991. Yearly costs of the mHealth intervention were an additional $1046, resulting in a yearly cost per patient of $2.35. In a threshold analysis, the PHW intervention was found to be cost saving if it was able to avert 1.50 patients per year from switching to second-line antiretroviral therapy. Other AIDS care programs may find these intervention costs affordable.
A Label-Free, Quantitative Assay of Amyloid Fibril Growth Based on Intrinsic Fluorescence

Kinetic assay of seeded growth: The graph shows the variation in intrinsic fluorescence intensity of amyloid fibrils. Fluorescence increases during the seeded aggregation of α-synuclein seeds with α-synuclein monomeric protein (blue curve) but not when α-synuclein seeds are incubated with β-synuclein monomeric protein (black curve), thus showing that no seeded growth occurred in this case.
Audiovisual integration supports face–name associative memory formation

ABSTRACT Prior multisensory experience influences how we perceive our environment, and hence how memories are encoded for subsequent retrieval. This study investigated if audiovisual (AV) integration and associative memory formation rely on overlapping or distinct processes. Our functional magnetic resonance imaging results demonstrate that the neural mechanisms underlying AV integration and associative memory overlap substantially. In particular, activity in anterior superior temporal sulcus (STS) is increased during AV integration and also determines the success of novel AV face–name association formation. Dynamic causal modeling results further demonstrate how the anterior STS interacts with the associative memory system to facilitate successful memory formation for AV face–name associations. Specifically, the connection of fusiform gyrus to anterior STS is enhanced while the reverse connection is reduced when participants subsequently remembered both face and name. Collectively, our results demonstrate how multisensory associative memories can be formed for subsequent retrieval.
HLA type and immune response to Borrelia burgdorferi outer surface protein a in people in whom arthritis developed after Lyme disease vaccination.

OBJECTIVE To investigate whether persons with treatment-resistant Lyme arthritis-associated HLA alleles might develop arthritis as a result of an autoimmune reaction triggered by Borrelia burgdorferi outer surface protein A (OspA), the Lyme disease vaccine antigen. METHODS Persons in whom inflammatory arthritis had developed after Lyme disease vaccine (cases) were compared with 3 control groups: 1) inflammatory arthritis but not Lyme disease vaccine (arthritis controls), 2) Lyme disease vaccine but not inflammatory arthritis (vaccine controls), and 3) neither Lyme disease vaccine nor inflammatory arthritis (normal controls). HLA-DRB1 allele typing, Western blotting for Lyme antigen, and T cell reactivity testing were performed. RESULTS Twenty-seven cases were matched with 162 controls (54 in each control group). Odds ratios (ORs) for the presence of 1 or 2 treatment-resistant Lyme arthritis alleles were 0.8 (95% confidence interval [95% CI] 0.3-2.1), 1.6 (95% CI 0.5-4.4), and 1.75 (95% CI 0.6-5.3) in cases versus arthritis controls, vaccine controls, and normal controls, respectively. There were no significant differences in the frequency of DRB1 alleles. T cell response to OspA was similar between cases and vaccine controls, as measured using the stimulation index (OR 1.6 [95% CI 0.5-5.1]) or change in uptake of tritiated thymidine (counts per minute) (OR 0.7 [95% CI 0.2-2.3]), but cases were less likely to have IgG antibodies to OspA (OR 0.3 [95% CI 0.1-0.8]). Cases were sampled closer to the time of vaccination (median 3.59 years versus 5.48 years), and fewer cases had received 3 doses of vaccine (37% versus 93%). CONCLUSION Treatment-resistant Lyme arthritis alleles were not found more commonly in persons who developed arthritis after Lyme disease vaccination, and immune responses to OspA were not significantly more common in arthritis cases. These results suggest that Lyme disease vaccine is not a major factor in the development of arthritis in these cases.
Clinical Evaluation of a Blood Assay to Diagnose Paucibacillary Tuberculosis via Bacterial Antigens.

BACKGROUND The diagnosis of active tuberculosis (TB) cases primarily relies on methods that detect Mycobacterium tuberculosis (Mtb) bacilli or their DNA in patient samples (e.g., mycobacterial culture and Xpert MTB/RIF assays), but these tests have low clinical sensitivity for patients with paucibacillary TB disease. Our goal was to evaluate the clinical performance of a newly developed assay that can rapidly diagnose active TB cases by direct detection of Mtb-derived antigens in patients' blood samples. METHODS Nanoparticle (NanoDisk)-enriched peptides derived from the Mtb virulence factors CFP-10 (10-kDa culture factor protein) and ESAT-6 (6-kDa early secretory antigenic target) were analyzed by high-throughput mass spectrometry (MS). Serum from 294 prospectively enrolled Chinese adults were analyzed with this NanoDisk-MS method to evaluate the performance of direct serum Mtb antigen measurement as a means for rapid diagnosis of active TB cases. RESULTS NanoDisk-MS diagnosed 174 (88.3%) of the study's TB cases, with 95.8% clinical specificity, and with 91.6% and 85.3% clinical sensitivity for culture-positive and culture-negative TB cases, respectively. NanoDisk-MS also exhibited 88% clinical sensitivity for pulmonary and 90% for extrapulmonary TB, exceeding the diagnostic performance of mycobacterial culture for these cases. CONCLUSIONS Direct detection and quantification of serum Mtb antigens by NanoDisk-MS can rapidly and accurately diagnose active TB in adults, independent of disease site or culture status, and outperform Mycobacterium-based TB diagnostics.
Poxviral vectors for cancer immunotherapy

Introduction: Poxviral vaccines have been given to over 1 billion people in the successful global eradication of smallpox. Recombinant poxviruses have been investigated extensively as a novel immunotherapy for cancer, undergoing several iterations to optimize their immunogenicity and efficacy. The current platform expressing multiple costimulatory molecules plus a tumor-associated antigen such as PSA, that is, PSA-TRICOM (PROSTVAC-V/F), is promising and is currently in a Phase III randomized, placebo-controlled clinical trial in metastatic castration-resistant prostate cancer. Areas covered: This review discusses the clinical development of poxviral-based cancer vaccines, with a particular focus on the rationale for combining vaccines with other treatment modalities, including radiotherapy, chemotherapy, hormonal therapy, other immune-based therapies and molecularly targeted therapy. We also discuss the importance of appropriate patient selection in clinical trial design. Expert opinion: Preclinical and early clinical studies employing poxviral-vector vaccines have shown promising results with this novel immunologic approach, both alone and combined with other therapies. The challenges of translating the science of immunotherapy to clinical practice include clinical trial design that includes appropriate patient selection, appropriate end points and identification of meaningful surrogate biomarkers.
Understanding the Links between Positive Wellbeing and Health

People with higher levels of positive wellbeing may enjoy better health and live longer, but it is not clear why. This thesis explores the notion that links between positive wellbeing and health-relevant biological correlates could provide some explanation for the relationship between positive wellbeing and health. Two complementary approaches were used. First, associations between the positive personality trait of resilience (the ability to withstand chronic stress or adversity) and various biological and psychological factors were explored using secondary data. Second, an intervention study was used to test causal mechanisms between changes in positive wellbeing and changes in biology. Resilience (from the Resilience Scale), psychosocial stressors and affect and wellbeing outcomes were assessed in around 200 healthy working women as part of the Daytracker study. Measures of cortisol and heart rate variability (HRV) were also collected across a work and leisure day. Results of regression analyses suggested that higher resilience was associated with greater HRV across the work period, but there was no association with cortisol. Resilience mediated the relationship between particular stressors and affect and wellbeing outcomes. A two week gratitude-based intervention in 119 healthy women was used to try to increase positive wellbeing. Psychological and biological factors (cortisol, blood pressure and heart rate) were assessed before and after the intervention. The gratitude condition was associated with increased optimism, reduced depressive symptoms and lower diastolic blood pressure. However, associations with measures of positive wellbeing were not robust. It was therefore not possible to demonstrate causal links between changes in positive wellbeing and changes in biology. Future studies could focus on strengthening positive wellbeing intervention tasks. Overall the results provided modest evidence for links between positive wellbeing and biological correlates of health. Resilience may provide cardiac health protective effects, since reduced HRV has previously been associated with increased cardiovascular disease incidence.
An Exploratory Study on University Students’ Perceptions of Posthumous Organ Donation Base on the Theory of Reasoned Action

In view of the general support for organ donation but low registration rate in Hong Kong, the present research attempted to understand the attitude-behavior inconsistency by identifying the underlying beliefs for organ donation through employing the theory of reasoned action. A qualitative approach using semi-structured focus groups was adopted and 19 students from three universities in Hong Kong participated; 10 constructs were identified: attitude, subjective norm, helping, continuation, contribution, body intact, distrust to the medical system, indifference to organ donation, negative affect, and family burden. Findings suggested that their attitudes toward organ donation were of both the cognitive and affective nature; subjective norm of family, friends, and people they respect were identified as influential to students’ views on organ donation. The study provided insight in promoting organ donation, that the cognitive concerns about keeping the body intact, and the negative affects introduced should also be addressed.
Porphyromonas gingivalis Stimulates TLR2-PI3K Signaling to Escape Immune Clearance and Induce Bone Resorption Independently of MyD88

Porphyromonas gingivalis is a gram-negative anaerobic periodontal pathogen that persists in dysbiotic mixed-species biofilms alongside a dense inflammatory infiltrate of neutrophils and other leukocytes in the subgingival areas of the periodontium. Toll-like receptor 2 (TLR2) mediates the inflammatory response to P. gingivalis and TLR2-deficient mice resist alveolar bone resorption following oral challenge with this organism. Although, MyD88 is an adaptor protein considered necessary for TLR2-induced inflammation, we now report for the first time that oral challenge with P. gingivalis leads to alveolar bone resorption in the absence of MyD88. Indeed, in contrast to prototypical TLR2 agonists, such as the lipopeptide Pam3CSK4 that activates TLR2 in a strictly MyD88-dependent manner, P. gingivalis strikingly induced TLR2 signaling in neutrophils and macrophages regardless of the presence or absence of MyD88. Moreover, genetic or antibody-mediated inactivation of TLR2 completely reduced cytokine production in P. gingivalis-stimulated neutrophils or macrophages, suggesting that TLR2 plays a non-redundant role in the host response to P. gingivalis. In the absence of MyD88, inflammatory TLR2 signaling in P. gingivalis-stimulated neutrophils or macrophages depended upon PI3K. Intriguingly, TLR2-PI3K signaling was also critical to P. gingivalis evasion of killing by macrophages, since their ability to phagocytose this pathogen was reduced in a TLR2 and PI3K-dependent manner. Moreover, within those cells that did phagocytose bacteria, TLR2-PI3K signaling blocked phago-lysosomal maturation, thereby revealing a novel mechanism whereby P. gingivalis can enhance its intracellular survival. Therefore, P. gingivalis uncouples inflammation from bactericidal activity by substituting TLR2-PI3K in place of TLR2-MyD88 signaling. These findings further support the role of P. gingivalis as a keystone pathogen, which manipulates the host inflammatory response in a way that promotes bone loss but not bacterial clearance. Modulation of these host response factors may lead to novel therapeutic approaches to improve outcomes in disease conditions associated with P. gingivalis.
The Adaptor 3BP2 Is Required for KIT Receptor Expression and Human Mast Cell Survival

SH3-binding protein 2 (3BP2) is a cytoplasmic adaptor protein that acts as a positive regulator in mast cell FcεRI–dependent signaling. The KIT receptor whose ligand is the stem cell factor is necessary for mast cell development, proliferation, and survival as well as for optimal IgE-dependent signal. Activating mutations in KIT have been associated with several diseases including mastocytosis. In the present work, we found that 3BP2 silencing impairs KIT signaling pathways, thus affecting phosphoinositide 3-kinase and MAPK pathways in human mast cells (huMCs) from HMC-1, LAD2 (huMC lines), and CD34+-derived mast cells. Unexpectedly, silencing of 3BP2 reduces KIT expression in normal huMCs as well as in HMC-1 cells where KIT is mutated, thus increasing cellular apoptosis and caspase-3/7 activity. 3BP2 silencing reduces KIT transcription expression levels. Interestingly, 3BP2 silencing decreased microphthalmia-associated transcription factor (MITF) expression, a transcription factor involved in KIT expression. Reconstitution of 3BP2 in knockdown cells leads to reversal of KIT expression as well as survival phenotype. Accordingly MITF reconstitution enhances KIT expression levels in 3BP2-silenced cells. Moreover, downregulation of KIT expression by miRNA-221 overexpression or the proteasome inhibitor bortezomib also reduced 3BP2 and MITF expression. Furthermore, KIT tyrosine activity inhibition reduced 3BP2 and MITF expression, demonstrating again a tight and reciprocal relationship between these molecules. Taken together, our results show that 3BP2 regulates huMC survival and participates in KIT-mediated signal transduction by directly controlling KIT receptor expression, suggesting its potential as a therapeutic target in mast cell–mediated inflammatory diseases and deregulated KIT disorders.
Forebrain GABAergic projections to locus coeruleus in mouse

The noradrenergic locus coeruleus (LC) regulates arousal, memory, sympathetic nervous system activity, and pain. Forebrain projections to LC have been characterized in rat, cat, and primates, but not systematically in mouse. We surveyed mouse forebrain LC‐projecting neurons by examining retrogradely labeled cells following LC iontophoresis of Fluoro‐Gold and anterograde LC labeling after forebrain injection of biotinylated dextran amine or viral tracer. Similar to other species, the central amygdalar nucleus (CAmy), anterior hypothalamus, paraventricular nucleus, and posterior lateral hypothalamic area (PLH) provide major LC inputs. By using mice expressing green fluorescent protein in γ‐aminobutyric acid (GABA)ergic neurons, we found that more than one‐third of LC‐projecting CAmy and PLH neurons are GABAergic. LC colocalization of biotinylated dextran amine, following CAmy or PLH injection, with either green fluorescent protein or glutamic acid decarboxylase (GAD)65/67 immunoreactivity confirmed these GABAergic projections. CAmy injection of adeno‐associated virus encoding channelrhodopsin‐2‐Venus showed similar fiber labeling and association with GAD65/67‐immunoreactive (ir) and tyrosine hydroxylase (TH)‐ir neurons. CAmy and PLH projections were densest in a pericoerulear zone, but many fibers entered the LC proper. Close apposition between CAmy GABAergic projections and TH‐ir processes suggests that CAmy GABAergic neurons may directly inhibit noradrenergic principal neurons. Direct LC neuron targeting was confirmed by anterograde transneuronal labeling of LC TH‐ir neurons following CAmy or PLH injection of a herpes virus that expresses red fluorescent protein following activation by Cre recombinase in mice that express Cre recombinase in GABAergic neurons. This description of GABAergic projections from the CAmy and PLH to the LC clarifies important forebrain sources of inhibitory control of central nervous system noradrenergic activity. J. Comp. Neurol. 521:2373–2397, 2013. © 2012 Wiley Periodicals, Inc.
Enhanced Cell Growth of Adipocyte-Derived Mesenchymal Stem Cells Using Chemically-Defined Serum-Free Media

The multipotency and anti-inflammatory effects of mesenchymal stem cells (MSCs) make them attractive for cell therapy in regenerative medicine. A large number of MSCs is required for efficient therapy owing to the low homing efficiency of MSCs to target sites. Furthermore, owing to limitations in obtaining sufficient amounts of MSCs, in vitro expansion of MSCs that preserves their differentiation and proliferative potential is essential. The animal factor included in culture media also limits clinical application. In this study, adipose-derived MSCs showed a significantly higher proliferation rate in STK2, a chemically-defined medium, than in DMEM/FBS. The expression of MSC surface markers was increased in the culture using STK2 compared to that using DMEM/FBS. Tri-lineage differentiation analyses showed that MSCs cultured in STK2 were superior to those cultured in DMEM/FBS. In addition, MSCs cultured in STK2 showed a reduced senescence rate, small and homogenous cell size, and were more genetically stable compared to those cultured in DMEM/FBS. Furthermore, secretome analysis showed that the expression of factors related to proliferation/migration, anti-inflammation, and differentiation were increased in STK2 culture medium compared to DMEM/FBS. Taken together, these results suggest that culture using STK2 medium offers many advantages through which it is possible to obtain safer, superior, and larger numbers of MSCs.