Miracle-dz/UniFAR-FTUs huggingface dataset:
Updated Evidence of the Association Between Elevated Serum Uric Acid Level and Psoriasis

Background: Our earlier meta-analysis showed that the correlation between psoriasis and hyperuricemia might be region-dependent and that hyperuricemia was more common in patients with psoriasis in Western Europe. However, no further analysis could be conducted owing to the scarcity of data. Objective: Our study aimed to further explore the association between psoriasis and hyperuricemia. Methods: Six databases (PubMed, Embase, the Cochrane Central Register of Controlled Trials, the China National Knowledge Infrastructure database, the Chinese Scientific Journals Full Text Database, and the Wanfang Data Knowledge Service Platform) were searched for studies published between January 1980 and February 2021. Results: The search strategy yielded 291 relevant studies, of which 27 observational studies were included in this analysis. Serum uric acid (SUA) levels (mean difference [MD] 0.99, 95% confidence interval [CI] 0.48–1.49, P = 0.0001) and hyperuricemia frequency (odds ratio [OR] 5.39, 95% CI 1.88–15.40, P = 0.002) were higher in the psoriasis group than in the control group, and the subgroup differences were significant. In addition, SUA levels were significantly higher in patients with moderate to severe psoriasis from European and American countries (MD 0.89, 95% CI 0.18–1.60, P = 0.01) and Southeast Asia (MD 1.79, 95% CI 0.55–3.02, P = 0.004), while no significant differences were found between the Middle East subgroup (MD 0.63, 95% CI −0.33 to 1.59, P = 0.20). Similar results were obtained from the meta-analysis of SUA levels in patients with metabolic syndrome, obesity, or a special type of psoriasis (such as arthritic or erythrodermic psoriasis). Conclusions: Our meta-analysis study provides extended data regarding the correlation between psoriasis and hyperuricemia and the differences in SUA levels between psoriasis patients and controls in Southeast Asia, the Middle East, and European and American countries. Patients with moderate to severe psoriasis in European and American countries and Southeast Asia or those with metabolic syndrome and obesity were more likely to have higher uric acid levels. Systematic Review Registration: PROSPERO, identifier: CRD42014015091.
An Exploratory Analysis of the Association Between Catechol-O-Methyltransferase and Response to a Randomized Open-Label Placebo Treatment for Cancer-Related Fatigue

Previous studies have identified catechol-O-methyltransferase (COMT), as a key enzyme influencing sympathetic function. Although the COMT SNP rs4680 and rs4818, are well-studied, little is known about their influence on cancer-related fatigue (CrF) and placebo response. In this study, we examined whether genetic variation in COMT, at the functional SNP rs4680 and linked rs4818, influenced open-label placebo (OLP) responses found in cancer survivors reporting moderate to severe CrF. We randomized cancer survivors (N = 74) reporting moderate-to-severe CrF to receive OLP or to treatment-as-usual (TAU) and assessed if rs4680 and rs4818 were associated with changes in fatigue severity and fatigue-distressed quality of life. At the end of the initial 21 days, the treatments were crossed over and both groups were re-assessed. Participants with the rs4680 high-activity G-allele (G/G or G/A) or rs4818 C/G genotypes reported significant decreases in fatigue severity and improvements in fatigue-distressed quality of life. The COMT rs4818 findings replicated findings in a similar study of OLP in cancer fatigue. Clinical Trial Registration: www.ClinicalTrials. gov, identifier: NCT02522988.
How and to What Extent Immunological Responses to SARS-CoV-2 Shape Pulmonary Function in COVID-19 Patients

COVID-19 is a disease caused by a new coronavirus SARS-CoV-2, primarily impacting the respiratory system. COVID-19 can result in mild illness or serious disease leading to critical illness and requires admission to ICU due to respiratory failure. There is intense discussion around potential factors predisposing to and protecting from COVID-19. The immune response and the abnormal respiratory function with a focus on respiratory function testing in COVID-19 patients will be at the center of this Perspective article of the Frontiers in Physiology Series on “The Tribute of Physiology for the Understanding of COVID-19 Disease. ” We will discuss current advances and provide future directions and present also our perspective in this field.
Widespread Parenchymal Abnormalities and Pulmonary Embolism on Contrast-Enhanced CT Predict Disease Severity and Mortality in Hospitalized COVID-19 Patients

Purpose: Severe COVID-19 is associated with inflammation, thromboembolic disease, and high mortality. We studied factors associated with fatal outcomes in consecutive COVID-19 patients examined by computed tomography pulmonary angiogram (CTPA). Methods: This retrospective, single-center cohort analysis included 130 PCR-positive patients hospitalized for COVID-19 [35 women and 95 men, median age 57 years (interquartile range 51–64)] with suspected pulmonary embolism based on clinical suspicion. The presence and extent of embolism and parenchymal abnormalities on CTPA were recorded. The severity of pulmonary parenchymal involvement was stratified by two experienced radiologists into two groups: lesions affecting ≤50% or >50% of the parenchyma. Patient characteristics, radiological aspects, laboratory parameters, and 60-day mortality data were collected. Results: Pulmonary embolism was present in 26% of the patients. Most emboli were small and peripheral. Patients with widespread parenchymal abnormalities, with or without pulmonary embolism, had increased main pulmonary artery diameter (p < 0.05) and higher C-reactive protein (p < 0.01), D-dimer (p < 0.01), and troponin T (p < 0.001) and lower hemoglobin (p < 0.001). A wider main pulmonary artery diameter correlated positively with C-reactive protein (r = 0.28, p = 0.001, and n = 130) and procalcitonin. In a multivariant analysis, D-dimer >7.2 mg/L [odds ratio (±95% confidence interval) 4.1 (1.4–12.0)] and ICU stay were significantly associated with embolism (p < 0.001). The highest 60-day mortality was found in patients with widespread parenchymal abnormalities combined with pulmonary embolism (36%), followed by patients with widespread parenchymal abnormalities without pulmonary embolism (26%). In multivariate analysis, high troponin T, D-dimer, and plasma creatinine and widespread parenchymal abnormalities on CT were associated with 60-day mortality. Conclusions: Pulmonary embolism combined with widespread parenchymal abnormalities contributed to mortality risk in COVID-19. Elevated C-reactive protein, D-dimer, troponin-T, P-creatinine, and enlarged pulmonary artery were associated with a worse outcome and may mirror a more severe systemic disease. A liberal approach to radiological investigation should be recommended at clinical deterioration, when the situation allows it. Computed tomography imaging, even without intravenous contrast to assess the severity of pulmonary infiltrates, are of value to predict outcome in COVID-19. Better radiological techniques with higher resolution could potentially improve the detection of microthromboses. This could influence anticoagulant treatment strategies, preventing clinical detoriation.
Effectiveness of Nutritional Advice for Community-Dwelling Obese Older Adults With Frailty: A Systematic Review and Meta-Analysis

Objectives: This systematic review was aimed to examine the effectiveness of nutritional advise interventions compared with usual care, or exercise, or exercise combined with nutritional advice as a means of improving the body weight, body composition, physical function, and psychosocial well-being of frail, obese older adults. Methods: CINAHL, Cochrane Library, Embase, MEDLINE, PsycINFO, and Scopus databases were searched to identify relevant studies. The quality of the included studies was assessed using Cochrane's risk of bias tool 2. Meta-analysis was performed with respect to body weight and fat mass. Other outcomes were synthesized narratively. Results: Eight articles (from two studies) with a total of 137 participants were included in the review. The results revealed that nutritional advice was more effective than exercise in reducing body weight and fat mass. The nutritional advice was also beneficial in enhancing physical function and psychosocial well-being. However, it was less effective than exercise or combined interventions in increasing muscle strength and preventing lean mass loss. Conclusions: Nutritional advice is an essential intervention for reducing body weight and fat mass, for enhancing physical function, and for improving the psychosocial well-being of obese older adults experiencing frailty. The limited number of studies included in this review suggests that there is a need for more well-designed interventional studies in order to confirm these findings.
Social Class and Changes in Australian Women's Affect and Alcohol Consumption During COVID-19

Introduction: Before the pandemic, mid-life women in Australia were among the “heaviest” female alcohol consumers, giving rise to myriad preventable health risks. This paper uses an innovative model of social class within a sample of Australian women to describe changes in affective states and alcohol consumption patterns across two time points during COVID-19. Methods: Survey data were collected from Australian mid-life women (45–64 years) at two time points during COVID-19—May 2020 (N = 1,218) and July 2020 (N = 799). We used a multi-dimensional model for measuring social class across three domains—economic capital (income, property and assets), social capital (social contacts and occupational prestige of those known socially), and cultural capital (level of participation in various cultural activities). Latent class analysis allowed comparisons across social classes to changes in affective states and alcohol consumption patterns reported at the two time points using alcohol consumption patterns as measured by the Alcohol Use Disorders Identification Test—Consumption (AUDIT-C) and its component items. Results: Seven social classes were constructed, characterized by variations in access to capital. Affective states during COVID-19 differed according to social class. Comparing between the survey time points, feeling fearful/anxious was higher in those with high economic and cultural capital and moderate social capital (“emerging affluent”). Increased depression was most prominent in the class characterized by the highest volumes of all forms of capital (“established affluent”). The social class characterized by the least capital (“working class”) reported increased prevalence of uncertainty, but less so for feeling fearful or anxious, or depressed. Women's alcohol consumption patterns changed across time during the pandemic. The “new middle” class—a group characterized by high social capital (but contacts with low prestige) and minimal economic capital—had increased AUDIT-C scores. Conclusion: Our data shows the pandemic impacted women's negative affective states, but not in uniform ways according to class. It may explain increases in alcohol consumption among women in the emerging affluent group who experienced increased feelings or fear and anxiety during the pandemic. This nuanced understanding of the vulnerabilities of sub-groups of women, in respect to negative affect and alcohol consumption can inform future pandemic policy responses designed to improve mental health and reduce the problematic use of alcohol. Designing pandemic responses segmented for specific audiences is also aided by our multi-dimensional analysis of social class, which uncovers intricate differences in affective states amongst sub-groups of mid-life women.
How Self-Appraisal Is Mediated by the Brain

Self-appraisal is a process that leads to the formation of self-esteem, which contributes to subjective well-being and mental health. Neuroimaging studies link self-esteem with the activity of the medial prefrontal cortex (MPFC), right temporoparietal junction (rTPJ), posterior cingulate cortex (PCC), anterior insula (AIns), and dorsolateral prefrontal cortex. It is not known, however, how the process of self-appraisal itself is mediated by the brain and how different nodes of the self-appraisal network interact with each other. In this study, we used multilevel mediation analysis of functional MRI data recorded during the trait adjective judgment task, treating the emotional valence of adjectives as the predictor, behavioral response as the dependent variable, and brain activity as the mediator. The mediation effect was revealed in the rTPJ. Dynamic causal modeling showed that positive self-descriptions trigger communication within the network, with the rTPJ exerting the strongest excitatory output and MPFC receiving the strongest excitatory input. rAIns receives the strongest inhibitory input and sends exclusively inhibitory connections to other regions pointing out to its role in the processing of negative self-descriptions. Analysis of individual differences showed that in some individuals, self-appraisal is mostly driven by the endorsement of positive self-descriptions and is accompanied by increased activation and communication between rTPJ, MPFC, and PCC. In others, self-appraisal is driven by the rejection of negative self-descriptions and is accompanied by increased activation of rAIns and inhibition of PCC and MPFC. Membership of these groups was predicted by different personality variables. This evidence uncovers different mechanisms of positive self-bias, which may contribute to different facets of self-esteem and are associated with different personality profiles.
Therapeutic and Prognostic Implications of Immune-Related Adverse Events in Advanced Non-Small-Cell Lung Cancer

Introduction PD-(L)1 inhibitors have improved prognosis of non-small-cell lung cancer (NSCLC), but can also cause immune-related adverse events (irAEs) that complicate management. Methods We analyzed NSCLC patients receiving PD-(L)1 inhibitors from 2012 to 2020 in a German academic center. Results IrAE showed comparable frequencies in stage IV (198/894 or 22%) vs. III (14/45 or 31%, p = 0.15), after anti-PD-(L)1 monotherapy vs. chemoimmunotherapy (139/483 vs. 58/213, p = 0.75), and across treatment lines. In stage IV, irAE occurred after 3.1 months in median, affected multiple organs (median 2) in 27/894 patients and were associated with PD-L1 positivity (25 vs. 14%, p = 0.003), lower neutrophil-to-lymphocyte ratios (29 vs. 17%, p < 0.001 for NLR dichotomized at 5), better ECOG status (26 vs. 18% for 0 vs. 1, p = 0.004), but not related to age, sex, smoking and palliative radiotherapy. Two hundred thirty two irAEs occurred mostly in endocrine glands (4.9%), lungs (4.4%), the musculoskeletal system (4.2%), colon (4.1%), liver (3.7%), and skin (2.6%), while pneumonitis was most frequent with durvalumab following definitive chemoradiation (16% or 7/45, p < 0.01). IrAE severity was grade 1 in 11%, 2 in 41%, 3 in 36%, and 4 in 11% events, while two were lethal (<1%, myocarditis and pneumonitis). Therapy was suspended in 72%, while steroids were initiated in 66% and complemented by other immunosuppressants in 6%, with longest treatment duration for rheumatic events (mean >3 months), and average cumulative prednisone doses >700 mg for all organs, except for skin. Patients developing irAE had longer progression-free (PFS) and overall survival (OS) in multivariable 12/14-week landmark analyses including ECOG status, treatment line, treatment type, PD-L1 TPS, and NLR (median PFS 17 vs. 10 months, HR = 0.68, p = 0.009; median OS 37 vs. 15 months, HR = 0.40, p < 0.001), regardless of grade. OS was longest with skin (95% at 2 years) and shortest with pneumonitis, hepatitis, neurologic, and cardiologic irAE (38, 37, 28, and 0% at 2 years, p < 0.001). Conclusions Approximately one-fourth of immunotherapy-treated NSCLC patients develop irAEs, most of which necessitate treatment suspension and steroids. Despite more frequent occurrence with PD-L1 positive tumors, lower NLR, and better ECOG PS, irAEs are independently associated with longer survival, especially when affecting the skin. Lethality is below 1%.
Spheres of Influence: Host Tree Proximity and Soil Chemistry Shape rRNA, but Not DNA, Communities of Symbiotic and Free-Living Soil Fungi in a Mixed Hardwood-Conifer Forest

Host and symbiont diversity are inextricably linked across partnerships and ecosystems, with degree of partner reliance governing the strength of this correlation. In many forest soils, symbiotic ectomycorrhizal fungi coexist and compete with free-living saprotrophic fungi, with the outcomes of these interactions shaping resource availability and competitive outcomes for the trees aboveground. Traditional approaches to characterizing these communities rely on DNA sequencing of a ribosomal precursor RNA gene (the internal transcribed spacer region), but directly sequencing the precursor rRNA may provide a more functionally relevant perspective on the potentially active fungal communities. Here, we map ectomycorrhizal and saprotrophic soil fungal communities through a mixed hardwood-conifer forest to assess how above- and belowground diversity linkages compare across these differently adapted guilds. Using highly spatially resolved transects (sampled every 2 m) and well-mapped stands of varying host tree diversity, we sought to understand the relative influence of symbiosis versus environment in predicting fungal diversity measures. Canopy species in this forest included two oaks (Quercus agrifolia and Quercus douglasii) and one pine (Pinus sabiniana). At the scale of our study, spatial turnover in rRNA-based communities was much more predictable from measurable environmental attributes than DNA-based communities. And while turnover of ectomycorrhizal fungi and saprotrophs were predictable by the presence and abundance of different canopy species, they both responded strongly to soil nutrient characteristics, namely pH and nitrogen availability, highlighting the niche overlap of these coexisting guilds and the strong influence of aboveground plants on belowground fungal communities.
Improved Understanding of the Role of Gene and Genome Duplications in Chordate Evolution With New Genome and Transcriptome Sequences

Comparative approaches to understanding chordate genomes have uncovered a significant role for gene duplications, including whole genome duplications (WGDs), giving rise to and expanding gene families. In developmental biology, gene families created and expanded by both tandem and WGDs are paramount. These genes, often involved in transcription and signalling, are candidates for underpinning major evolutionary transitions because they are particularly prone to retention and subfunctionalisation, neofunctionalisation, or specialisation following duplication. Under the subfunctionalisation model, duplication lays the foundation for the diversification of paralogues, especially in the context of gene regulation. Tandemly duplicated paralogues reside in the same regulatory environment, which may constrain them and result in a gene cluster with closely linked but subtly different expression patterns and functions. Ohnologues (WGD paralogues) often diversify by partitioning their expression domains between retained paralogues, amidst the many changes in the genome during rediploidisation, including chromosomal rearrangements and extensive gene losses. The patterns of these retentions and losses are still not fully understood, nor is the full extent of the impact of gene duplication on chordate evolution. The growing number of sequencing projects, genomic resources, transcriptomics, and improvements to genome assemblies for diverse chordates from non-model and under-sampled lineages like the coelacanth, as well as key lineages, such as amphioxus and lamprey, has allowed more informative comparisons within developmental gene families as well as revealing the extent of conserved synteny across whole genomes. This influx of data provides the tools necessary for phylogenetically informed comparative genomics, which will bring us closer to understanding the evolution of chordate body plan diversity and the changes underpinning the origin and diversification of vertebrates.
The Ability of AhR Ligands to Attenuate Delayed Type Hypersensitivity Reaction Is Associated With Alterations in the Gut Microbiota

Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that regulates T cell function. The aim of this study was to investigate the effects of AhR ligands, 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), and 6-Formylindolo[3,2-b]carbazole (FICZ), on gut-associated microbiota and T cell responses during delayed-type hypersensitivity (DTH) reaction induced by methylated bovine serum albumin (mBSA) in a mouse model. Mice with DTH showed significant changes in gut microbiota including an increased abundance of Bacteroidetes and decreased Firmicutes at the phylum level. Also, there was a decrease in Clostridium cluster XIV and IV, which promote anti-inflammatory responses, and an increase in Prevotella copri that facilitates pro-inflammatory responses. Interestingly, treatment of mice with TCDD attenuated the DTH response, induced Tregs, suppressed Th17 cells in the mesenteric lymph nodes (MLNs), and reversed the gut microbiota composition toward normalcy. In contrast, FICZ exacerbated the DTH response, induced heightened Th17 cells, and failed to cause a major shift in gut microbiota. Furthermore, TCDD but not FICZ caused an increase in the levels of short-chain fatty acids (SCFA), n-butyric acid, and acetic acid. Administration of sodium butyrate into mice with DTH suppressed the response, increased Tregs, and reduced Th17 cells IL17. Butyrate also caused an increase in the abundance of Clostridium and a decrease in Prevotella. Lastly, TCDD, as well as butyrate but not FICZ, were able to inhibit proinflammatory Histone deacetylases (HDACs) class I and II. Together, our data suggest that AhR ligands, such as TCDD that suppress DTH response, may mediate this effect by reversing the gut dysbiosis induced during this inflammatory response, while FICZ may fail to suppress the DTH response because of its inability to overturn the dysbiosis.
Fluid Overload

Fluid overload (FO) is characterized by hypervolemia, edema, or both. In clinical practice it is usually suspected when a patient shows evidence of pulmonary edema, peripheral edema, or body cavity effusion. FO may be a consequence of spontaneous disease, or may be a complication of intravenous fluid therapy. Most clinical studies of the association of FO with fluid therapy and risk of harm define it in terms of an increase in body weight of at least 5–10%, or a positive fluid balance of the same magnitude when fluid intake and urine output are measured. Numerous observational clinical studies in humans have demonstrated an association between FO, adverse events, and mortality, as have two retrospective observational studies in dogs and cats. The risk of FO may be minimized by limiting resuscitation fluid to the smallest amount needed to optimize cardiac output and then limiting maintenance fluid to the amount needed to replace ongoing normal and pathological losses of water and sodium.