Miracle-dz/UniFAR-FTUs huggingface dataset:
Research progress of metabolomics in psoriasis

Abstract Psoriasis is a chronic inflammatory skin disease with significant physical and psychological burdens. The interplay between the innate and adaptive immune systems is thought to contribute to the pathogenesis; however, the details of the pathogenesis remain unclear. In addition, reliable biomarkers for diagnosis, assessment of disease activity, and monitoring of therapeutic response are limited. Metabolomics is an emerging science that can be used to identify and analyze low molecular weight molecules in biological systems. During the past decade, metabolomics has been widely used in psoriasis research, and substantial progress has been made. This review summarizes and discusses studies that applied metabolomics to psoriatic disease. These studies have identified dysregulation of amino acids, carnitines, fatty acids, lipids, and carbohydrates in psoriasis. The results from these studies have advanced our understanding of: (1) the molecular mechanisms of psoriasis pathogenesis; (2) diagnosis of psoriasis and assessment of disease activity; (3) the mechanism of treatment and how to monitor treatment response; and (4) the link between psoriasis and comorbid diseases. We discuss common research strategies and progress in the application of metabolomics to psoriasis, as well as emerging trends and future directions.
iGen or shyGen? Generational Differences in Shyness

Generation Z (1997–2012) has been characterized in the popular media as more socially inhibited, cautious, and risk averse than prior generations, but are these differences found between generations on an empirical level? And, if so, are these differences observable within generations in response to acute events such as the COVID-19 pandemic? Using a simplified time-lagged design to control for age effects, we examined between-group differences in self-reported shyness in young adult participants (N = 806, age: 17–25 years) at the same developmental age and university from the millennial generation (tested: 1999–2001; n = 266, Mage = 19.67 years, 72.9% female) and Generation Z (tested: 2018–2020), the latter generation stratified into prepandemic (n = 263, M = 18.86 years, 82.4% female) and midpandemic (n = 277, Mage = 18.67 years, 79.6% female) groups. After first establishing measurement invariance to ensure trustworthy group comparisons, we found significantly higher mean levels of shyness across each successive cohort, starting with millennials, through Generation Z before the pandemic, to Generation Z during the pandemic.
Alterations and Co-Occurrence of C-MYC, N-MYC, and L-MYC Expression are Related to Clinical Outcomes in Various Cancers

Background and Objectives MYC, also known as an oncogenic reprogramming factor, is a multifunctional transcription factor that maintains induced pluripotent stem cells (iPSCs). Although MYC is frequently upregulated in various cancers and is correlated with a poor prognosis, MYC is downregulated and correlated with a good prognosis in lung adenocarcinoma. MYC and two other MYC family genes, MYCN and MYCL, have similar structures and could contribute to tumorigenic conversion both in vitro and in vivo. Methods and Results We systematically investigated whether MYC family genes act as prognostic factors in various human cancers. We first evaluated alterations in the expression of MYC family genes in various cancers using the Oncomine and The Cancer Genome Atlas (TCGA) database and their mutation and copy number alterations using the TCGA database with cBioPortal. Then, we investigated the association between the expression of MYC family genes and the prognosis of cancer patients using various prognosis databases. Multivariate analysis also confirmed that co-expression of MYC/MYCL/MYCN was significantly associated with the prognosis of lung, gastric, liver, and breast cancers. Conclusions Taken together, our results demonstrate that the MYC family can function not only as an oncogene but also as a tumor suppressor gene in various cancers, which could be used to develop a novel approach to cancer treatment.
Effects of chronic dichlorodiphenyldichloroethylene exposure on testosterone secretion and steroidogenic pathway in the male gonad

Abstract Endocrine disrupting chemicals are present in the environment and/or in consumer products. These agents have the capacity to mimic and/or antagonize endogenous hormones and thus perturb the endocrine axis. The male reproductive tract expresses steroid hormone (androgen and estrogen) receptors at high levels and is a major target for endocrine disrupting chemicals. In this study, Long–Evans male rats were exposed to dichlorodiphenyldichloroethylene, a metabolite of dichlorodiphenyltrichloroethane and a chemical present in the environment, in drinking water at 0.1 and 10 µg/L for 4 weeks. At the end of exposure, we measured steroid hormone secretion and analyzed steroidogenic proteins, including 17β-hydroxysteroid dehydrogenase, 3β-hydroxysteroid dehydrogenase, steroidogenic acute regulatory protein, aromatase, and the LH receptor. We also analyzed Leydig cell apoptosis (poly-(ADP-ribose) polymerase) and caspase-3 in the testes. Testicular testosterone (T) and 17β-estradiol (E2) were both affected by exposure to dichlorodiphenyldichloroethylene by displaying altered steroidogenic enzyme expression. Dichlorodiphenyldichloroethylene exposure also increased the expression of enzymes mediating the pathway for programmed cell death, including caspase 3, pro-caspase 3, PARP, and cleaved PARP. Altogether, the present results demonstrate that dichlorodiphenyldichloroethylene directly and/or indirectly can target specific proteins involved in steroid hormone production in the male gonad and suggest that exposure to environmentally relevant dichlorodiphenyldichloroethylene levels has implications for male reproductive development and function. Summary Sentence Exposure to environmentally relevant DDE levels has implications for male reproductive development and activity due to disruption of testicular T and E2 secretion.
Dissection of Cellular Communication between Human Primary Osteoblasts and Bone Marrow Mesenchymal Stem Cells in Osteoarthritis at Single-Cell Resolution

Background and Objectives Osteoblasts are derived from bone marrow mesenchymal stem cells (BMMSCs) and play important role in bone remodeling. While our previous studies have investigated the cell subtypes and heterogeneity in osteoblasts and BMMSCs separately, cell-to-cell communications between osteoblasts and BMMSCs in vivo in humans have not been characterized. The aim of this study was to investigate the cellular communication between human primary osteoblasts and bone marrow mesenchymal stem cells. Methods and Results To investigate the cell-to-cell communications between osteoblasts and BMMSCs and identify new cell subtypes, we performed a systematic integration analysis with our single-cell RNA sequencing (scRNA-seq) transcriptomes data from BMMSCs and osteoblasts. We successfully identified a novel preosteoblasts subtype which highly expressed ATF3, CCL2, CXCL2 and IRF1. Biological functional annotations of the transcriptomes suggested that the novel preosteoblasts subtype may inhibit osteoblasts differentiation, maintain cells to a less differentiated status and recruit osteoclasts. Ligand-receptor interaction analysis showed strong interaction between mature osteoblasts and BMMSCs. Meanwhile, we found FZD1 was highly expressed in BMMSCs of osteogenic differentiation direction. WIF1 and SFRP4, which were highly expressed in mature osteoblasts were reported to inhibit osteogenic differentiation. We speculated that WIF1 and sFRP4 expressed in mature osteoblasts inhibited the binding of FZD1 to Wnt ligand in BMMSCs, thereby further inhibiting osteogenic differentiation of BMMSCs. Conclusions Our study provided a more systematic and comprehensive understanding of the heterogeneity of osteogenic cells. At the single cell level, this study provided insights into the cell-to-cell communications between BMMSCs and osteoblasts and mature osteoblasts may mediate negative feedback regulation of osteogenesis process.
Myc controls NK cell development, IL-15-driven expansion, and translational machinery

Myc ablation in vivo impacts immature NK cells’ ribosomagenesis and development. Accordingly, mice with NK cells lacking Myc exhibit impaired anticancer immunity. MYC is a pleiotropic transcription factor involved in cancer, cell proliferation, and metabolism. Its regulation and function in NK cells, which are innate cytotoxic lymphocytes important to control viral infections and cancer, remain poorly defined. Here, we show that mice deficient for Myc in NK cells presented a severe reduction in these lymphocytes. Myc was required for NK cell development and expansion in response to the key cytokine IL-15, which induced Myc through transcriptional and posttranslational mechanisms. Mechanistically, Myc ablation in vivo largely impacted NK cells’ ribosomagenesis, reducing their translation and expansion capacities. Similar results were obtained by inhibiting MYC in human NK cells. Impairing translation by pharmacological intervention phenocopied the consequences of deleting or blocking MYC in vitro. Notably, mice lacking Myc in NK cells exhibited defective anticancer immunity, which reflected their decreased numbers of mature NK cells exerting suboptimal cytotoxic functions. These results indicate that MYC is a central node in NK cells, connecting IL-15 to translational fitness, expansion, and anticancer immunity. Graphical Abstract
Molecular and clinicopathologic characterization of pediatric histiocytoses

The spectrum of somatic mutations in pediatric histiocytoses and their clinical implications are not fully characterized, especially for non‐Langerhans cell histiocytosis (‐LCH) subtypes. A cohort of 415 children with histiocytosis from the French histiocytosis registry was reviewed and analyzed for BRAFV600E. Most BRAFWT samples were analyzed by next‐generation sequencing (NGS) with a custom panel of genes for histiocytosis and myeloid neoplasia. Of 415 case samples, there were 366 LCH, 1 Erdheim‐Chester disease, 21 Rosai‐Dorfman disease (RDD), 21 juvenile xanthogranuloma (JXG, mostly with severe presentation), and 6 malignant histiocytosis (MH). BRAFV600E was the most common mutation found in LCH (50.3%, n = 184). Among 105 non‐BRAFV600E‐mutated LCH case samples, NGS revealed mutations as follows: MAP2K1 (n = 44), BRAF exon 12 deletions (n = 26), and duplications (n = 8), other BRAF V600 codon mutation (n = 4), and non‐MAP‐kinase pathway genes (n = 5). Wild‐type sequences were identified in 17.1% of samples. BRAFV600E was the only variant significantly correlated with critical presentations: organ‐risk involvement and neurodegeneration. MAP‐kinase pathway mutations were identified in seven RDD (mostly MAP2K1) and three JXG samples, but most samples were wild‐type on NGS. Finally, two MH samples had KRAS mutations, and one had a novel BRAFG469R mutation. Rarely, we identified mutations unrelated to MAP‐kinase pathway genes. In conclusion, we characterized the mutational spectrum of childhood LCH and clinical correlations of variants and subtypes. Variants responsible for JXG and RDD were not elucidated in more than half of the cases, calling for other sequencing approaches.
Experiences with recruitment and retention of adolescents and emerging adults in a weight loss intervention trial

Background/Aims: Efficient and effective participant recruitment is key for successful clinical research. Adolescent and emerging adult recruitment into clinical trials can be particularly challenging, especially when targeting underrepresented groups. This study aimed to determine the most successful recruitment strategies from those employed during a pediatric trial testing the efficacy of a behavioral intervention on adiposity and cardiovascular disease risk. Methods: We determined the effectiveness, cost, and diversity of the final research population by each recruitment method utilized in the EMPower trial, a randomized clinical trial designed to test the effect of a technology-delivered behavioral Healthy Lifestyle intervention on adiposity, blood pressure, and left ventricular mass among adolescents and emerging adults with overweight or obesity. Effectiveness was determined by respondent yield (RY; number of respondents/number contacted), scheduled yield (SY; number scheduled for a baseline visit/number of respondents), enrollment yield (EY; number enrolled/number of respondents), and retention (number completed/number enrolled). Cost-effectiveness of each recruitment method was calculated and demographics of participants recruited via each method was determined. Results: A minimum of 109,314 adolescents and emerging adults were contacted by at least one recruitment method (clinic, web-based, postal mailing, electronic medical record (EMR) messaging) leading to 429 respondents. The most successful strategies in terms of RY were clinic-based recruitment (n = 47, 61% RY), community web-postings (n = 109, 5.33% RY), and EMR messaging (n = 163, 0.99% RY); however, website, postal mailings, and EMR recruitment led to more successful SY and EY. Postal mailings were the most costly strategy to employ (US$3261/completed participant) with EMR messaging the second most costly (US$69/completed participant). Community web-postings were free of charge. Clinic-based recruitment did not add additional costs, per se, but did require a substantial amount of personnel time (63.6 h/completed participant). Final cohort diversity primarily came from postal mailings (57% Black) and EMR messages (50% female). Conclusion: Electronic medical record messaging and web-based recruitment were highly successful and cost-effective strategies in a pediatric clinical trial targeting adolescents and emerging adults, but was less successful in recruiting a diverse cohort. Clinic recruitment and postal mailings, despite being costly and time-consuming, were the strategies that enrolled a greater proportion of underrepresented groups. While online forms of trial recruitment are growing in popularity, clinic-based recruitment and non-web-based strategies may be required to ensure participant diversity and representation.
Global trajectories of liver cancer burden from 1990 to 2019 and projection to 2035

Abstract Background: Large disparities exist in liver cancer burden trends across countries but are poorly understood. We aimed to investigate the global trajectories of liver cancer burden, explore the driving forces, and predict future trends. Methods: Data on the liver cancer burden in 204 countries and territories from 1990 to 2019 were extracted from the Global Burden of Disease Study. The age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR) trajectories were defined using growth mixture models. Five major risk factors contributing to changes in the ASIR or ASMR and socioeconomic determinants were explored using the identified trajectories. A Bayesian age–period–cohort model was used to predict future trends through 2035. Results: Three trajectories of liver cancer burden were identified: increasing, stable, and decreasing groups. Almost half of the American countries were classified in the decreasing group (48.6% for ASIR and ASMR), and the increasing group was the most common in the European region (ASIR, 49.1%; ASMR, 37.7%). In the decreasing group, the decrease of liver cancer due to hepatitis B contributed 63.4% and 60.4% of the total decreases in ASIR and ASMR, respectively. The increase of liver cancer due to alcohol use, hepatitis C, and hepatitis B contributed the most to the increase in the increasing group (30.8%, 31.1%, and 24.2% for ASIR; 33.7%, 30.2%, and 22.2% for ASMR, respectively). The increasing group was associated with a higher sociodemographic index, gross domestic product per capita, health expenditure per capita, and universal health coverage (all P <0.05). Significant variations in disease burden are predicted to continue through 2035, with a disproportionate burden in the decreasing group. Conclusion: Global disparities were observed in liver cancer burden trajectories. Hepatitis B, alcohol use, and hepatitis C were identified as driving forces in different regions.
Relationships between contract status and player performance in the Australian Football League

ABSTRACT This study analysed the extent to which player performance differs within the Australian Football League (AFL) with respect to the status of a player’s contract. AFL Player Ratings (AFLPR) and contract data were obtained during the 2013–2020 AFL seasons for all 827 players listed by an AFL club at the beginning of the 2020 season. A model of “expected performance” was created allowing for an exploration into the differential with actual performance as a function of contract status. Paired t-tests indicated that there was a difference in performance pre- and post-signing their contract for players who signed mid-season (mean change and 95% confidence interval of −1.48 ± 0.93 and −0.49 ± 0.48 AFLPR, at ten match intervals for those in- and out-of-contract at the conclusion of that year’s season, respectively). Further differences existed between the groups of players who signed mid-season, as compared to those who signed during the off-season. Correlation analyses indicated that more consistent performers are somewhat less likely to see a reduction in performance post signing as compared to less consistent performers. The applications of these findings have the potential to support organisational decisions relating to the timing and nature of player contracting.
Change in CT-measured acetabular bone density following total hip arthroplasty: a systematic review and meta-analysis

Background and purpose Assessing peri-acetabular bone quality is valuable for optimizing the outcomes of primary total hip arthroplasty (THA) as preservation of good quality bone stock likely affects implant stability. The aim of this study was to perform a meta-analysis of peri-acetabular bone mineral density (BMD) changes over time measured using quantitative computer tomography (CT) and, second, to investigate the influence of age, sex, and fixation on the change in BMD over time. Methods A systematic search of Embase, Scopus, Web of Science, and PubMed databases identified 19 studies that measured BMD using CT following THA. The regions of interest (ROI), reporting of BMD results, and scan protocols were extracted. A meta-analysis of BMD was performed on 12 studies that reported measurements immediately postoperatively and at follow-up. Results The meta-analysis determined that periacetabular BMD around both cemented and uncemented components decreases over time. The amount of BMD loss increased relative to proximity of the acetabular component. There was a greater decrease in cortical BMD over time in females and cancellous BMD for young patients of any sex. Conclusion Peri-acetabular BMD decreases at different rates relative to its proximity to the acetabular component. Cancellous BMD decreases more in young patients and cortical bone decreases more in females. Standardized reporting parameters and suggested ROI to measure peri-acetabular BMD are proposed, to enable comparison between implant and patient variables in the future.
Assessing the economic impacts of a perfect storm of extreme weather, pandemic control, and export restrictions: A methodological construct

This article investigates the economic impacts of a multi‐disaster mix comprising extreme weather, such as flooding, pandemic control, and export restrictions, dubbed a “perfect storm. ” We develop a compound‐hazard impact model that improves on the ARIO model by considering the economic interplay between different types of hazardous events. The model considers simultaneously cross‐regional substitution and production specialization, which can influence the resilience of the economy to multiple shocks. We build scenarios to investigate economic impacts when a flood and a pandemic lockdown collide and how these are affected by the timing, duration, and intensity/strictness of each shock. In addition, we examine how export restrictions during a pandemic impact the economic losses and recovery, especially when there is the specialization of production of key sectors. The results suggest that an immediate, stricter but shorter pandemic control policy would help to reduce the economic costs inflicted by a perfect storm, and regional or global cooperation is needed to address the spillover effects of such compound events, especially in the context of the risks from deglobalization.
Bcl11b sustains multipotency and restricts effector programs of intestinal-resident memory CD8+ T cells

The networks of transcription factors (TFs) that control intestinal-resident memory CD8+ T (TRM) cells, including multipotency and effector programs, are poorly understood. In this work, we investigated the role of the TF Bcl11b in TRM cells during infection with Listeria monocytogenes using mice with post-activation, conditional deletion of Bcl11b in CD8+ T cells. Conditional deletion of Bcl11b resulted in increased numbers of intestinal TRM cells and their precursors as well as decreased splenic effector and circulating memory cells and precursors. Loss of circulating memory cells was in part due to increased intestinal homing of Bcl11b−/− circulating precursors, with no major alterations in their programs. Bcl11b−/− TRM cells had altered transcriptional programs, with diminished expression of multipotent/multifunctional (MP/MF) program genes, including Tcf7, and up-regulation of the effector program genes, including Prdm1. Bcl11b also limits the expression of Ahr, another TF with a role in intestinal CD8+ TRM cell differentiation. Deregulation of TRM programs translated into a poor recall response despite TRM cell accumulation in the intestine. Reduced expression of MP/MF program genes in Bcl11b−/− TRM cells was linked to decreased chromatin accessibility and a reduction in activating histone marks at these loci. In contrast, the effector program genes displayed increased activating epigenetic status. These findings demonstrate that Bcl11b is a frontrunner in the tissue residency program of intestinal memory cells upstream of Tcf1 and Blimp1, promoting multipotency and restricting the effector program. Description Bcl11b has a dual role in intestinal resident memory CD8+ T cells, driving multipotency and limiting the effector program. Fate in the hands of Bcl11b During infection, antigen-specific CD8+ T cells undergo clonal expansion and differentiate into effector or memory cells. Whether memory cells become tissue resident (TRM) or circulatory is a fate decision governed by multiple transcription factors. In this work, Helm et al. investigate how Bcl11b influences TRM differentiation in the context of foodborne pathogen infection. They identify that deletion of Bcl11b in CD8+ T cells after their activation causes accumulation of TRM cells in the gut and a reduction of circulating memory cells. The authors show that Bcl11b regulates multipotency of TRM through recruitment to and activation of essential genes involved in the multipotent/multifunctional program and repression of genes involved in effector function. Bcl11b therefore determines the lineage fate of gut CD8+ resident memory cells. —HMI