Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetics, Epigenetics, and Gender Impact in Axial-Spondyloarthritis Susceptibility: An Update on Genetic Polymorphisms and Their Sex Related Associations

Spondyloarthritis (SpA) is a group of chronic inflammatory rheumatic disease that can be divided into predominantly axial or predominantly peripheral involvement, with or without associated psoriasis, inflammatory bowel disease or previous infection. Axial SpA (axSpA) encompasses ankylosing spondylitis (AS) with radiological sacroiliitis, and a type without radiographic sacroiliitis, called “non-radiographic axial SpA” (nr-axSpA). Males and females show large differences in their susceptibility to SpA, such as distinctions in clinical patterns, phenotypes and in therapeutical response, particularly to TNF inhibitors (TNFi). Several studies indicate that AS women have doubled risk to failure TNFi compared with males. This diversity in drugs’ efficacy among women and men may be caused by differences in the balance of sex hormones and in gene-specific expression likely triggered by X-chromosome instability and gene-specific epigenetic modifications. Evidence reported that polymorphisms in microRNAs on X- and other chromosomes, such as miR-146a, miR-155, miR-125a-5p, miR-151a-3p and miR-22-3p, miR-199a-5p could be involved in the different clinical presentation of SpA, as well as disease activity. In addition, association with non−response to TNFi treatment and presence of IRAK3 and CHUCK genes in SpA patients was recently detected. Finally, polymorphisms in genes involved in IL-23/IL-17 pathway, such as in drug pharmacodynamics and pharmacokinetics may have a role in response to TNFi, IL17i, and IL23i. A major understanding of genomic variability could help in the development of new therapeutic targets or in taking advantages of different mechanisms of action of biological drugs. Moving from the multifactorial etiology of disease, the present review aims at evaluating genetic and epigenetic factors and their relationship with sex and bDMARDs response, helping to investigate the different expression among males and females of genes on X- and other chromosomes, as well as mi-RNA, to highlight relationships between sex and occurrence of specific phenotypes and symptoms of the disease. Moreover, the role of the epigenetic modification in relation to immune-regulatory mechanisms will be evaluated.
On the Vernacular Language Games of an Antagonistic Online Subculture

In this paper we develop an empirical, big data approach to analyze how alt-right vernacular concepts (such as kek and beta) were used on the notorious anonymous and ephemeral imageboard 4chan/pol/and the fan wiki Encyclopedia Dramatica. While 4chan/pol/is broadly regarded as an influential source of many of the web’s most successful memes such as Pepe the Frog, Encyclopedia Dramatica functions as a kind of satirical Wikipedia for this meme subculture, written in high concept and highly offensive vernacular style. While the site’s affordances make them distinct, they are connected by a subcultural style and politics that has recently become increasingly connected with violent right-wing activism, forming a loose subcultural language community. Contrary to “memetic” theories of cultural evolution in media studies, our analysis draws on theoretical frameworks from poststructuralist and pragmatist philosophies of language and deploys empirical techniques from corpus linguistics to consider the role of online platforms in shaping these vernacular modes of expression. This approach helps us to identify instances of vernacular innovation within these corpora from 2012-2020—a period during which the white supremacist “alt-right” movement arose online. Through these analyses we contribute both to ongoing interdisciplinary attempts to bridge the gap between cultural-theoretical and computational-linguistic approaches to studying online subcultures, and to the empirical study of the vernacular roots of the “toxic memes” that appear to be an increasingly common feature on social media.
Improvement of the LbCas12a-crRNA System for Efficient Gene Targeting in Tomato

Plant gene targeting (GT) can be utilized to precisely replace up to several kilobases of a plant genome. Recent studies using the powerful clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) nucleases significantly improved plant GT efficiency. However, GT for loci without associated selection markers is still inefficient. We previously utilized Lachnospiraceae bacterium Cas12a (LbCas12a) in combination with a replicon for tomato GT and obtained high GT efficiency with some selection markers. In this study, we advance our GT system by inhibiting the cNHEJ pathway with small chemical molecules such as NU7441. Further optimization of the GT is also possible with the treatment of silver nitrate possibly via its pronounced actions in ethylene inhibition and polyamine production. Importantly, the GT efficiency is significantly enhanced with the use of a temperature-tolerant LbCas12a (ttLbCas12a) that is capable of performing target cleavage even at low temperatures. Targeted deep sequencing, as well as conventional methods, are used for the assessment of the editing efficiency at both cell and plant levels. Our work demonstrates the significance of the selection of gene scissors, the appropriate design and number of LbCas12a crRNAs, the use of chemical treatments, and the establishment of favorable experimental conditions for further enhancement of plant HDR to enable efficient GT in tomato.
The Relationship Between Elevated Serum Uric Acid and Risk of Stroke in Adult: An Updated and Dose–Response Meta-Analysis

Background: Uric acid (UA) is proposed as a potential risk factor for stroke in adult, yet the results from published studies are not generally accordant. Method: We included prospective studies that explored the relationship between serum UA (SUA) and strokes. In this study, strokes include ischemic stroke and hemorrhagic stroke, which consists of intracerebral hemorrhage and subarachnoid hemorrhage. The effect-size estimates were expressed as hazard ratio (HR) and 95% confidence interval (CI). Sensitivity and subgroup analyses were performed to assess the robustness of the pooled estimation and potential sources of heterogeneity between studies. Results: We meta-analyzed 19 prospective cohort articles, which involve 37,386 males and 31,163 females. Overall analyses results showed a significant association between a 1 mg/dl increase in high levels of SUA and the risk of total stroke (HR = 1.13; 95% CI: 1.09–1.18; P < 0.001), ischemic stroke (HR = 1.15; 95% CI: 1.10–1.21; P < 0.001), and hemorrhagic stroke (HR = 1.07; 95% CI: 1.00 to 1.15; P = 0.046). No significant difference was found between ischemic stroke and hemorrhagic stroke. In the subgroup analyses, the association of high SUA levels and the risk of total stroke was statistically significant in females (HR = 1.19; 95% CI: 1.12–1.26; P < 0.001) and males (HR = 1.11; 95% CI: 1.05–1.17; P < 0.001). Coincidentally, the association was also statistically significant for ischemic stroke, both in females (HR = 1.26; 95% CI: 1.17–1.36; P < 0.001) and in males (HR = 1.12; 95% CI: 1.06–1.19; P < 0.001). However, for hemorrhagic stroke, it was only statistically significant in females (HR = 1.19; 95% CI: 1.04–1.35; P = 0.01). Our dose–response research indicated the J-shaped trend between the ascending SUA levels and the higher risk of suffering from a stroke. Conclusions: Our findings indicate that elevated SUA is a significant risk factor for adult stroke, both for ischemic stroke and hemorrhagic stroke, and especially in females.
The Predictive Value of Carotid Ultrasonography With Cardiovascular Risk Factors—A “SPIDER” Promoting Atherosclerosis

Insufficient recommendations do not support the clinical use of carotid ultrasonography for further risk stratification in moderate-to-high risk patients with cardiovascular disease (CVD). A literature review was performed to assess six aspects of the research progress and limitations of carotid ultrasonography and carotid atherosclerosis-related risk factors: (1) structures of the carotid intima and media; (2) plaques; (3) inflammation; (4) dynamics of carotid blood flow; (5) early detection and intervention; and (6) risk factors for CVD. Although carotid intima-media thickness and carotid plaques are well-acknowledged independent predictors of CVD risk, normative and cut-off values are difficult to define due to the heterogeneous measurements reported in previous studies. Plaque properties, including location, number, density, and size, become more important risk predictors for cardiovascular disease, but a better approach for clinical use needs to be further established. Three-dimensional ultrasound and contrast-enhanced ultrasound are promising for promoting risk stratification with more details on plaque morphology. Moreover, inflammatory diseases and biomarkers should be evaluated for a full assessment of the inflammatory burden for atherosclerosis. Carotid flow velocity is not only an indicator for stenosis but also a potential risk predictor. Carotid atherosclerosis should be detected and treated early, and additional clinical trials are needed to determine the efficacy of these measures in reducing CVD risk. Cardiovascular risk factors tend to affect carotid plaques, and early treat-to-target therapy might yield clinical benefits. Based on the aforementioned six aspects, we consider that these six important factors act like a “SPIDER” spinning the web of atherosclerosis; a timely comprehensive assessment and intervention may halt the progression to CVD. Carotid ultrasound results should be combined with other atherosclerotic factors, and a comprehensive risk assessment may help to guide cardiovascular prevention decisions.
Fetal Brain Biometric Measurements on 3D Super-Resolution Reconstructed T2-Weighted MRI: An Intra- and Inter-observer Agreement Study

We present the comparison of two-dimensional (2D) fetal brain biometry on magnetic resonance (MR) images using orthogonal 2D T2-weighted sequences (T2WSs) vs. one 3D super-resolution (SR) reconstructed volume and evaluation of the level of confidence and concordance between an experienced pediatric radiologist (obs1) and a junior radiologist (obs2). Twenty-five normal fetal brain MRI scans (18–34 weeks of gestation) including orthogonal 3-mm-thick T2WSs were analyzed retrospectively. One 3D SR volume was reconstructed per subject based on multiple series of T2WSs. The two observers performed 11 2D biometric measurements (specifying their level of confidence) on T2WS and SR volumes. Measurements were compared using the paired Wilcoxon rank sum test between observers for each dataset (T2WS and SR) and between T2WS and SR for each observer. Bland–Altman plots were used to assess the agreement between each pair of measurements. Measurements were made with low confidence in three subjects by obs1 and in 11 subjects by obs2 (mostly concerning the length of the corpus callosum on T2WS). Inter-rater intra-dataset comparisons showed no significant difference (p > 0.05), except for brain axial biparietal diameter (BIP) on T2WS and for brain and skull coronal BIP and coronal transverse cerebellar diameter (DTC) on SR. None of them remained significant after correction for multiple comparisons. Inter-dataset intra-rater comparisons showed statistical differences in brain axial and coronal BIP for both observers, skull coronal BIP for obs1, and axial and coronal DTC for obs2. After correction for multiple comparisons, only axial brain BIP remained significantly different, but differences were small (2.95 ± 1.73 mm). SR allows similar fetal brain biometry as compared to using the conventional T2WS while improving the level of confidence in the measurements and using a single reconstructed volume.
The Impact of Action Effects on Infants’ Predictive Gaze Shifts for a Non-Human Grasping Action at 7, 11, and 18 Months

During the observation of goal-directed actions, infants usually predict the goal at an earlier age when the agent is familiar (e.g., human hand) compared to unfamiliar (e.g., mechanical claw). These findings implicate a crucial role of the developing agentive self for infants’ processing of others’ action goals. Recent theoretical accounts suggest that predictive gaze behavior relies on an interplay between infants’ agentive experience (top-down processes) and perceptual information about the agent and the action-event (bottom-up information; e.g., agency cues). The present study examined 7-, 11-, and 18-month-old infants’ predictive gaze behavior for a grasping action performed by an unfamiliar tool, depending on infants’ age-related action knowledge about tool-use and the display of the agency cue of producing a salient action effect. The results are in line with the notion of a systematic interplay between experience-based top-down processes and cue-based bottom-up information: Regardless of the salient action effect, predictive gaze shifts did not occur in the 7-month-olds (least experienced age group), but did occur in the 18-month-olds (most experienced age group). In the 11-month-olds, however, predictive gaze shifts occurred only when a salient action effect was presented. This sheds new light on how the developing agentive self, in interplay with available agency cues, supports infants’ action-goal prediction also for observed tool-use actions.
Dynamic Changes of the Bone Marrow Niche: Mesenchymal Stromal Cells and Their Progeny During Aging and Leukemia

Mesenchymal stromal cells (MSCs) are a heterogenous cell population found in a wide range of tissues in the body, known for their nutrient-producing and immunomodulatory functions. In the bone marrow (BM), these MSCs are critical for the regulation of hematopoietic stem cells (HSC) that are responsible for daily blood production and functional immunity throughout an entire organism’s lifespan. Alongside other stromal cells, MSCs form a specialized microenvironment BM tissue called “niche” that tightly controls HSC self-renewal and differentiation. In addition, MSCs are crucial players in maintaining bone integrity and supply of hormonal nutrients due to their capacity to differentiate into osteoblasts and adipocytes which also contribute to cellular composition of the BM niche. However, MSCs are known to encompass a large heterogenous cell population that remains elusive and poorly defined. In this review, we focus on deciphering the BM-MSC biology through recent advances in single-cell identification of hierarchical subsets with distinct functionalities and transcriptional profiles. We also discuss the contribution of MSCs and their osteo-adipo progeny in modulating the complex direct cell-to-cell or indirect soluble factors-mediated interactions of the BM HSC niche during homeostasis, aging and myeloid malignancies. Lastly, we examine the therapeutic potential of MSCs for rejuvenation and anti-tumor remedy in clinical settings.
Surface and Size Effects on the Behaviors of Point Defects in Irradiated Crystalline Solids

We present an elaborate study of the surface and size effects on the transient and steady-state behaviors of point defects in irradiated solids. In this investigation, both pure Ni and binary Ni-Cr were utilized as model systems. We utilize the spatially-resolved rate-theory (SRRT) modeling approach, and directly account for the effects of dose rate, production bias, and defects recombination, reactions with volumetric sinks, and diffusion to surface sinks. Several simulations were conducted to investigate the effects of these parameters in both coupled and decoupled manners. In the presence of production bias, the effects of surface and size persist even as the surface to volume ratio decreases. This was associated with a surface-induced and size-regulated instability. This instability is only triggered above a critical size between 100 and 500 nm. The critical size decreases with increasing dose rate, increasing production bias, or lowering the temperature. Moreover, this instability results in a pattern that favors the separation of vacancies and interstitials. Once this pattern develops, anomalies in the dependence on size for the transient and steady-state concentrations of point defects and the surface/boundary sink strength are observed. These anomalies tend to render irradiation damage more severe. For pure Ni, it was shown that vacancy supersaturation increases with size, and the rate of increase also rises with size. For the binary Ni-Cr system, it was shown that the magnitude of enrichment/depletion of Ni/Cr at the boundary increases with size, and the width of the enrichment/depletion layer also increases with size. The results obtained here agree well with experimental observations in irradiated materials such as the formation of void denuded zones adjacent to grain boundaries and the size and temperature dependence of the radiation resistance of nanomaterials. The size-dependent behaviors reported here also shed new light on the radiation tolerance of nanomaterials, i.e., the irradiation-induced instabilities are suppressed in such materials. Lastly, the implications of the results obtained here on the development of efficient reduced order models or the utilization of ion irradiation as a surrogate to neutron irradiation are discussed.
Evaluation of the Dietary Black Soldier Fly Larvae Meal (Hermetia illucens) on Growth Performance, Intestinal Health, and Disease Resistance to Vibrio parahaemolyticus of the Pacific White Shrimp (Litopenaeus vannamei)

The present study evaluated the effects of the dietary black soldier fly larvae meal (BSF) on growth performance, intestinal health, and susceptibility to Vibrio parahaemolyticus in the Pacific white shrimp Litopenaeus vannamei. The basal diet was formulated to contain 25% fish meal (FM), and then the FM was replaced with BSF for 10, 20, and 30% of the FM protein in the experimental diets, which are referred to as FM, BSF10, BSF20, and BSF30, respectively. Four hundred and eighty healthy and uniform-sized shrimp (~0.88 g) were distributed among four groups of three replicates, each with 40 shrimp in a 300-L tank and they were fed four times daily for 7 weeks. The results showed that the growth performance did not change significantly in shrimp fed with BSF10 and BSF20 diets, but significantly decreased in those fed with BSF30 diet compared to the ones fed with FM diet. After feeding trial and sampling, a V. parahaemolyticus infection challenge trial was conducted on shrimp. The results showed that the survival rate of shrimp fed with BSF10 was significantly higher than those fed with FM. The results of the midgut histology showed that the width and height of intestinal mucosal folds decreased significantly in shrimp fed with BSF20 and BSF30, and the early signs of apoptosis in the intestinal cells were found in shrimp fed with BSF30. The mRNA levels of non-specific immune-related genes dorsal and relish were downregulated in shrimp fed with BSF20 and BSF30 diets. The mRNA levels of antimicrobial peptides–related genes alf (anti-lipopolysaccharide factor) were upregulated in shrimp fed with BSF10 but downregulated in shrimp fed with BSF30. The mRNA level pen3 (penaeidins 3) was upregulated in shrimp fed with BSF10 and BSF20 diets. The intestinal bacterial communities on operational taxonomic unit levels among groups were not significantly differentiated according to the beta diversity analysis. At the genus levels, a decrease in Vibrio, Photobacterium, and Candidatus_Bacilloplasma, as well as the increase in Bacillus and Pseudoalteromonas abundance, indicated the improvement of intestinal microbiota in shrimp fed with dietary BSF. Therefore, the use of BSF in shrimp diet should be controlled at a dosage of 20% of the FM, which can improve the intestinal microbiota without causing any negative effects.
Domain Shifts in Reinforcement Learning: Identifying Disturbances in Environments

A signiﬁcant drawback of End-to-End Deep Rein-forcement Learning (RL) systems is that they return an action no matter what situation they are confronted with. This is true even for situations that differ entirely from those an agent has been trained for. Although crucial in safety-critical applications, dealing with such situations is inherently difﬁcult. Various approaches have been proposed in this direction, such as robustness, domain adaption, domain generalization, and out-of-distribution detection. In this work, we provide an overview of approaches towards the more general problem of dealing with disturbances to the environment of RL agents and show how they struggle to provide clear boundaries when mapped to safety-critical problems. To mitigate this, we propose to formalize the changes in the environment in terms of the Markov Decision Process (MDP), resulting in a more formal framework when dealing with such problems. We apply this framework to an example real-world scenario and show how it helps to isolate safety concerns.
Coordinated Control for Frequency Regulation in a Stand-Alone Microgrid Bolstering Demand Side Management Capability

Abstract The growing needs of distributed generation (DG) units in electrical power systems have a significant impact on stand-alone microgrid operation, which is increasingly faced with problems owing to low inertia. Residential, commercial, and industrial loads comprise a substantial portion of thermostatic devices (viz. air-conditioner), which leads to difficulty in managing the Demand Response (DR). Thus, in today’s microgrid scenario, the analytical study of the dynamics of such loads, along with its control, is gaining significance regarding providing ancillary services to the power network. This article presents a coordinated frequency control strategy for an impeccable demand-side management solution in a stand-alone microgrid, where, a large number of thermostatic devices are scheduled to reduce the overall energy usage during long-term operation, thus controlling the frequency in conjunction with IEC 60929 without hindering the quality of service (QoS) of the customer under various circumstances. The test system taken under consideration comprises a solar photovoltaic (PV) system with V-f control mechanism along with a battery management system (BMS), a slow responding diesel generator, and thermostatically controlled loads (TCL) of the cooling type which was simulated in Matlab/Simulink. Extensive simulation results indicate that the proposed approach can effectively manage a large number of thermostatically controlled loads to facilitate optimum demand-side management through frequency regulation under realistic conditions.
The Benefits of Living on Campus for Low-Income, First-Generation Students’ Belonging, Perceptions of Campus Climate, and Resilience

ABSTRACT The purpose of this study was to examine the effects of living on campus for first-year, first-generation students from low-income backgrounds. Using propensity score matching techniques with Multi-Institutional Study of Leadership survey data (n = 642) drawn from four-year colleges and universities, we found that first-year, first-generation students from low-income backgrounds who lived on campus had a significantly higher sense of belonging, a more welcoming perception of campus climate, and higher resilience compared to a group of matched peers who did not live on campus.
Preparers and the financial reporting system

We review the accounting and related literature on the preparation of public company financial reports. We highlight numerous impediments to producing high quality financial reports, focusing on the roles of management, the board of directors, and internal audit. Key incentives of the CEO do not encourage investments in financial reporting quality, despite evidence that these investments provide net benefits to the firm, instead, key incentives appear to elicit myopia. We also demonstrate that although theoretically the board of directors and internal audit are integral components of firms’ internal controls, in practice there are numerous obstacles to effective oversight, including a lack of independence from management. Recent regulations have lessened but not fully mitigated these concerns.