Miracle-dz/UniFAR-FTUs huggingface dataset:
HIV stigma and its metaphors: Photos, symbols, and solutions

Abstract The objective of this study was to explore how PLWH use visual metaphors to describe and make sense of stigma. This study solicited PLWH’s experiences with stigma via photovoice—a participatory research method in which participants use images to identify, share, and advocate for their needs and experiences. Photographs and discussions centered on stigma as two-parted, including both challenge and resilience. Participants used eight different categories of visual metaphors to describe their experiences of stigma (e.g., how it felt, what it was like) and four different categories of visual metaphors to describe their resilience or resistance to stigma. Participant photography and photo-elicitation is an accessible method to combine arts and health, especially for discovering ways patients understand and explain their perceptions of difference. Creative photography can help patients express themselves, practitioners understand illness, and frame health promotion and prevention programs.
The nematic-isotropic transition of the Lebwohl–Lasher model revisited

We revisited the nematic-isotropic (NI) transition of the Lebwohl–Lasher lattice model with a detailed investigation of samples containing 200 × 200 × 200 particles. The large-scale Monte Carlo (MC) simulations involved were carried out following the standard Metropolis, as well as the cluster MC Wolff algorithms. A notable free-energy barrier was observed between the isotropic and nematic phase, leading to long-lived metastable states and hysteresis. We provide an improved estimate of the nematic-isotropic transition temperature TNI, of the supercooling and superheating temperatures, of the temperature of divergence of pretransitional effects TC∗ as well as an analysis of the size distribution of the ordered domains above TNI, contributing to a better understanding of this transition of key importance for liquid crystals. This article is part of the theme issue ‘Topics in mathematical design of complex materials’.
Reactions of lignin and lignin model compounds with ozone

An investigation was made of the reactions resulting from treatment of Kraft lignin and lignin model compounds with ozone. Ozonolysis of aromatic compounds usually results in ring opening and formation of carboxyl groups. While destruction of lignin chromophores occurs during oxidation, because of the specificity of the reaction of lignin with ozone, the conclusion is drawn that less damage occurs to the lignin macrostructure during ozonolysis than during oxygen bleaching processes. -- AATA
Short-term elevations in glucocorticoids do not alter telomere lengths: A systematic review and meta-analysis of non-primate vertebrate studies

Background The neuroendocrine stress response allows vertebrates to cope with stressors via the activation of the Hypothalamic-Pituitary-Adrenal (HPA) axis, which ultimately results in the secretion of glucocorticoids (CORT). Glucocorticoids have pleiotropic effects on behavior and physiology, and might influence telomere length dynamics. During a stress event, CORT mobilizes energy towards survival mechanisms rather than to telomere maintenance. Additionally, reactive oxidative species produced in response to increased CORT levels can damage telomeres, also leading to telomere shortening. In our systematic review and meta-analysis, we tested whether CORT levels impact telomere length and if this relationship differs among time frame, life history stage, or stressor type. We hypothesized that elevated CORT levels are linked to a decrease in telomere length. Methods To test this hypothesis, we conducted a literature search for studies investigating the relationship between telomere length and CORT levels in non-human vertebrates using four search engines: Web of Science, Google Scholar, Pubmed and Scopus, last searched on September 27th, 2020. This review identified 31 studies examining the relationship between CORT and telomere length. We pooled the data using Fisher’s Z for 15 of these studies. All quantitative studies underwent a risk of bias assessment. This systematic review study was registered in the Open Science Framework Registry (https://osf.io/rqve6). Results The pooled effect size from fifteen studies and 1066 study organisms shows no relationship between CORT and telomere length ((Fisher’s Z= 0.1042, 95% CI = 0.0235; 0.1836). While these results support some previous findings, other studies have found a direct relationship between CORT and telomere dynamics, suggesting underlying mechanisms or concepts that are not currently taken into account in our analysis. The risk of bias assessment revealed an overall low risk of bias with occasional instances of bias from missing outcome data or bias in the reported result. Conclusion We highlight the need for more targeted experiments to understand how conditions, such as experimental timeframes, stressor(s), and stressor magnitudes can drive a relationship between the neuroendocrine stress response and telomere length.
Genetic inhibition of serum glucocorticoid kinase 1 prevents obesity-related atrial fibrillation

Rationale Given its rising prevalence in both the adult and pediatric populations, obesity has become an increasingly important risk factor in the development of atrial fibrillation. However, a better mechanistic understanding of obesity-related atrial fibrillation is required. Serum glucocorticoid kinase 1 (SGK1) is a kinase positioned downstream of multiple obesity-related pathways, and prior work has shown a pathologic role for SGK1 signaling in ventricular remodeling and arrhythmias. Objective To determine the mechanistic basis of obesity associated atrial fibrillation and explore the therapeutic potential of targeting SGK1 in this context. Methods and Results We utilized a mouse model of diet induced obesity to determine the atrial electrophysiologic effects of obesity using electrophysiologic studies, optical mapping, and biochemical analyses. In C57BL/6J mice fed a high fat diet, there was upregulation of SGK1 signaling along with an increase in AF inducibility determined at electrophysiology (EP) study. These changes were associated with an increase in fibrotic and inflammatory signaling. Transgenic mice expressing a cardiac specific dominant negative SGK1 (SGK1 DN) were protected from obesity-related AF as well as the fibrotic and inflammatory consequences of AF. Finally, optical mapping demonstrated a shorter action potential duration and patch clamp revealed effects on INa, with a decreased peak current as well as a depolarizing shift in activation/inactivation properties in atrial myocytes. Conclusions Diet induced obesity leads to increased cardiac SGK1 signaling as well as an increase in AF inducibility in obese mice. Genetic SGK1 inhibition reduced AF inducibility, and this effect may be mediated by effects on inflammation, fibrosis, and cellular electrophysiology.
A Dynamic Affective Core to bind the Contents, Context, and Value of Conscious Experience

The private and dynamic nature of conscious subjective experience poses an empirical challenge that has led neuroscience-based theories about consciousness to note the importance of ‘the hard problem’ of explaining how subjective phenomenal experience can arise from neural activity but set it aside and focus on the ‘easier’ problems associated with information representation and behavior. This approach leaves a major gap in our understanding of the neural mechanisms underlying conscious subjective experience and its dynamic nature. However, computational methods integrated with a variety of tools for measuring human brain activity are beginning to link dynamic changes in subjective affect with reproducible neurobehavioral signals in humans. In particular, research applying computational reinforcement learning theory has shown tremendous utility in investigating human choice behavior and the role the dopaminergic system plays in dynamic behavioral control. This research is beginning to reveal an explicit connection between the dynamics of dopaminergic signals and dynamic changes in subjective affect. However, it should be obvious that the dopaminergic system alone is not sufficient to explain all of the complexities of affective dynamics. We review foundational work, highlight current problems and open questions, and propose a Dynamic Affective Core Hypothesis that integrates advances in our understanding of the representation of the content and context of conscious experiences with our nascent understanding about how these representations acquire and retain affective subjective value.
Urinary Metabolomics from a Dose-Fractionated Polymyxin B Rat Model of Acute Kidney Injury

Background Polymyxin B remains an important antimicrobial against multi-drug resistant bacteria; however, kidney injury is often a treatment limiting event with kidney failure rates that range from 5-13%. Methods Samples were obtained from a previously conducted study of male Sprague-Dawley rats that received dose fractionated polymyxin B (12 mg/kg/day subcutaneously) once daily (QD), twice daily (BID), and thrice daily (TID) for three days. In the original study, urinary biomarkers and kidney histopathology scores were determined. Urine was sampled daily and analyzed for urinary metabolites via 1H NMR analysis. Unsupervised Principal Components Analysis was applied for exploratory data analysis to identify trends and outliers in the spectral data. Then, supervised Orthogonal Partial Least Square Discriminant Analysis was applied to classify the samples collected in different days and identify metabolic differences during the treatment. Metabolomes were compared across study groups (i.e. those receiving QD, BID, TID, and control) using a mixed-effects models. Spearman correlation was performed for injury biomarkers and the metabolome. Results A total of 27 rats contributed 77 urinary samples; n=25 rats were included that were treated with Polymyxin B and n=2 received saline. Pre-dosing samples clustered well and were characterized by higher amounts of citrate, 2-oxoglutarate, and Hippurate. On day 1 post treatment, day 1 samples showed higher taurine; day 3 samples had higher lactate, acetate and creatine. Taurine was the only metabolite significantly increased in both BID and TID compared to QD group. Taurine on day 1 correlated with increasing histopathology scores (Spearman’s rho = 0.4167, P=0.038) and KIM-1 (Spearman’s rho =0.4052, P=0.036); whereas KIM-1 on day one and day 3 did not reach significance with histopathology (Spearman’s rho = 0.3248, P=0.11 and Spearman’s rho = 0.3739, P=0.066). Conclusion Polymyxin B causes increased amounts of urinary taurine on day 1 which then normalizes to baseline concentrations. Taurine may provide one of the earlier signals of acute kidney damage caused by polymyxin B.
Diel light cycles affect phytoplankton competition in the global ocean

Light, essential for photosynthesis, is present in two periodic cycles in nature: seasonal and diel. Although seasonality of light is typically resolved in ocean ecosystem and biogeochemistry models because of its significance for seasonal succession and biogeography of phytoplankton, the diel light cycle is generally not resolved. Here we use a three-dimensional global ocean model and compare high temporal resolution simulations with and without diel light cycles. The model simulates 15 phytoplankton types of different cell size, encompassing two broad ecological strategies: small cells with high nutrient affinity (gleaners) and larger cells with high maximal growth rate (opportunists). Both are grazed by zooplankton and limited by nitrogen, phosphorus and iron. Simulations show that diel cycles of light induce diel cycles in phytoplankton populations and limiting nutrients in the global ocean. Diel nutrient cycles are associated with higher concentration of limiting nutrients by up to 200% at low latitudes (-40° to 40°), a process that increases opportunists’ biomass by up to 50%. Size classes with the highest maximal growth rates from both gleaner and opportunist groups are favored the most by diel light cycles. This mechanism weakens as latitude increases because the effects of the seasonal cycle dominate over those of the diel cycle. The present work shows that resource competition under diel light cycles has a significant impact on phytoplankton biogeography, indicating the necessity of resolving diel processes in global ocean models.
PRDM proteins control Wnt/β-catenin activity to regulate craniofacial chondrocyte differentiation

Cranial neural crest (NCC)-derived chondrocyte precursors undergo a dynamic differentiation and maturation process to establish a scaffold for subsequent bone formation, alterations in which contribute to congenital birth defects. Here, we demonstrate that transcription factor and histone methyltransferase proteins Prdm3 and Prdm16 control the differentiation switch of cranial NCCs to craniofacial cartilage. Loss of either results in hypoplastic and unorganized chondrocytes due to impaired cellular orientation and polarity. We show that PRDMs regulate cartilage differentiation by controlling the timing of Wnt/β-catenin activity in strikingly different ways: prdm3 represses while prdm16 activates global gene expression, though both by regulating Wnt enhanceosome activity and chromatin accessibility. Finally, we show that manipulating Wnt/β-catenin signaling pharmacologically or generating prdm3-/-;prdm16-/- double mutants rescues craniofacial cartilage defects. Our findings reveal upstream regulatory roles for Prdm3 and Prdm16 in cranial NCCs to control Wnt/β-catenin transcriptional activity during chondrocyte differentiation to ensure proper development of the craniofacial skeleton. Highlights Prdm3 and Prdm16 are required for chondrocyte organization in vertebrate craniofacial cartilage Loss of Prdm3 and Prdm16 alters expression of Wnt/β-catenin signaling components Prdm3 and Prdm16 oppositely control global chromatin accessibility Prdm3 and Prdm16 cartilage defects can be rescued pharmacologically or genetically
Taxon‐specific or universal? Using target capture to study the evolutionary history of rapid radiations

Target capture has emerged as an important tool for phylogenetics and population genetics in non-model taxa. Whereas developing taxon-specific capture probes requires sustained efforts, available universal kits may have a lower power to reconstruct relationships at shallow phylogenetic scales and within rapidly radiating clades. We present here a newly-developed target capture set for Bromeliaceae, a large and ecologically-diverse plant family with highly variable diversification rates. The set targets 1,776 coding regions, including genes putatively involved in key innovations, with the aim to empower testing of a wide range of evolutionary hypotheses. We compare the relative power of this taxon-specific set, Bromeliad1776, to the universal Angiosperms353 kit. The taxon-specific set results in higher enrichment success across the entire family, however, the overall performance of both kits to reconstruct phylogenetic trees is relatively comparable, highlighting the vast potential of universal kits for resolving evolutionary relationships. For more detailed phylogenetic or population genetic analyses, e.g. the exploration of gene tree concordance, nucleotide diversity or population structure, the taxon-specific capture set presents clear benefits. We discuss the potential lessons that this comparative study provides for future phylogenetic and population genetic investigations, in particular for the study of evolutionary radiations.
The Neural Determinants of Beauty

What are the conditions that determine whether the medial orbito-frontal cortex (mOFC), in which activity correlates with the experience of beauty derived from different sources, becomes co-active with sensory areas of the brain during the experience of sensory beauty? We addressed this question by studying the neural determinants of facial beauty. The perception of faces correlates with activity in a number of brain areas, but only when a face is perceived as beautiful is the mOFC also engaged. The enquiry thus revolved around the question of whether a particular pattern of activity, within or between areas implicated in face perception, emerges when a face is perceived as beautiful, and which determines that there is, as a correlate, activity in mOFC. 17 subjects of both genders viewed and rated facial stimuli according to how beautiful they perceived them to be while the activity in their brains was imaged with functional magnetic resonance imaging (fMRI). A univariate analysis revealed parametrically scaled activity within several areas in which the strength of activity correlated with the declared intensity of the aesthetic experience of faces; the list included the mOFC and two core areas strongly implicated in the perception of faces - the occipital face area (OFA), fusiform face area (FFA)- and, additionally, the cuneus. Multivariate analyses, which reveal the more fine-grained distribution of activity in brain areas, revealed strong and distinctive patterns of activation in the FFA and the cuneus and weaker ones in the OFA and posterior superior temporal sulcus (pSTS). It is only when distinctive patterns emerged in these areas that there was co-activation of the mOFC, in which a strong pattern of activity also emerged during the experience of facial beauty. A psychophysiological interaction analysis with mOFC as the seed area revealed the involvement of the right FFA and the right OFA, but only when faces were experienced as beautiful. We conjecture that these collective patterns of activity constitute the neural basis for the experience of facial beauty, bringing us a step closer to understanding the neural determinants of aesthetic experience.
Fides: Reliable trust-region optimization for parameter estimation of ordinary differential equation models

Ordinary differential equation (ODE) models are widely used to describe biochemical processes, since they effectively represent mass action kinetics. Optimization-based calibration of ODE models on experimental data can be challenging, even for low-dimensional problems. However, reliable model calibration is a prerequisite for uncertainty analysis, model comparison, and biological interpretation. Multiple hypotheses have been advanced to explain why optimization based calibration of biochemical models is challenging, but there are few comprehensive studies that test these hypotheses, likely because tools for performing such studies are also lacking. We implemented an established trust-region method as a modular Python framework (fides) to enable systematic comparison of different approaches to ODE model calibration involving various Hessian approximation schemes. We evaluated fides on a set of benchmark problems for which real experimental data are available. Unexpectedly, we observed high variability in optimizer performance among different implementations of the same algorithm. Overall, fides performed most reliably and efficiently. Our investigation of possible sources of poor optimizer performance identified drawbacks in the widely used Gauss-Newton, BFGS and SR1 Hessian approximations. We address these drawbacks by proposing a novel hybrid Hessian approximation scheme that enhances optimizer performance and outperforms existing hybrid approaches. We expect fides to be broadly useful for ODE constrained optimization problems and to enable future methods development. Availability fides is published under the permissive BSD-3-Clause license with source code publicly available at https://github.com/fides-dev/fides. Citeable releases are archived on Zenodo. Code to reproduce results presented in this manuscript is available at https://github.com/fides-dev/fides-benchmark.
Challenges of γ9δ2TCR affinity maturation when using phage display

Background Over the past years we showed that the efficacy of αβT cells engineered to express a defined γδTCR (TEG) depends on the functional avidity of the γ9δ2TCR. We hypothesized that functional avidity mediated through γ9δ2TCR in the TEG format could be further enhanced by increasing affinity of the γ9δ2TCR. Methods We attempted to overcome limited affinity of natural occurring γ9δ2TCRs through affinity maturation by phage display using a library containing mutations in CDR1 and CDR2 of both TCR chains. Conclusion Affinity maturation of γ9δ2TCR by using phage display was not successful. The largest hurdle was the periplasmic expression of γ9δ2TCR constructs in E.coli which is a prerequisite for successful phage display. The underlying reason for this lack of expression was the instability of the single chain (sc)TCR format. Expression of scTCR formats in HEK293F cells yielded only 15-20% correctly folded scTCR.
Measurement of the B ! D ðÞ D ðÞ K branching fractions

The authors present a measurement of the branching fractions of the 22 decay channels of the B{sup 0} and B{sup +} mesons to {bar D}{sup (*)}D{sup (*)}K, where the D{sup (*)} and {bar D}{sup (*)} mesons are fully reconstructed. Summing the 10 neutral modes and the 12 charged modes, the branching fractions are found to be {Beta}(B{sup 0} {yields} {bar D}{sup (*)}D{sup (*)}K) = (3.68 {+-} 0.10 {+-} 0.24)% and {Beta}(B{sup +} {yields} {bar D}{sup (*)}D{sup (*)}K) = (4.05 {+-} 0.11 {+-} 0.28)%, where the first uncertainties are statistical and the second systematic. The results are based on 429 fb{sup -1} of data containing 471 x 10{sup 6} B{bar B} pairs collected at the {Upsilon}(4S) resonance with the BABAR detector at the SLAC National Accelerator Laboratory.
New-Onset Atrial Fibrillation in Patients With Primary Aldosteronism Receiving Different Treatment Strategies: Systematic Review and Pooled Analysis of Three Studies

Background Primary aldosteronism (PA) is a common cause of secondary hypertension and associated with higher incidence of new-onset atrial fibrillation (NOAF). However, the effects of surgical or medical therapies on preventing NOAF in PA patents remain unclear. The aim of this meta-analysis study was to assess the risk of NOAF among PA patients receiving mineralocorticoid receptor antagonist (MRA) treatment, PA patients receiving adrenalectomy, and patients with essential hypertension. Methods We performed the meta-analysis of the randomized or observational studies that investigated the incidence rate of NOAF in PA patients receiving MRA treatment versus PA patients receiving adrenalectomy from database inception until December 01, 2020 which were identified from PubMed, Embase, and Cochrane Library. Results A total of 172 related studies were reviewed, of which three fulfilled the inclusion criteria, including a total of 2,705 PA patients. The results of meta-analysis demonstrated a higher incidence of NOAF among the PA patients receiving MRA treatment compared to the PA patients receiving adrenalectomy (pooled odds ratio [OR]: 2.83, 95% confidence interval [CI]: 1.76–4.57 in the random effects model, I 2 = 0%). The pooled OR for the PA patients receiving MRA treatment compared to the patients with essential hypertension was 1.91 (95% CI: 1.11–3.28). The pooled OR for the PA patients receiving adrenalectomy compared to the patients with essential hypertension was 0.70 (95% CI: 0.28–1.79). Conclusion Compared to the essential hypertension patients and the PA patients receiving adrenalectomy, the patients with PA receiving MRA treatment had a higher risk of NOAF. Systematic Review Registration https://www.crd. york.ac. uk/prospero/, identifier CRD42021222022.