bluuebunny/crossref_metadata_2025_split huggingface dataset:
Retinoic acid signaling modulates smooth muscle cell phenotypic switching in atherosclerosis through epigenetic regulation of gene expression
Authors: Pan Huize , Ho Sebastian E. , Xue Chenyi , Cui Jian , Ross Leila S. , Reilly Muredach P. 
Published: November 2022

ABSTRACTBACKGROUNDSmooth muscle cells (SMCs) substantially contribute to the development of atherosclerosis through a process called “phenotypic switching.” Our previous work identified an SMC-derived intermediate cell type, termed “SEM” cells, which plays a crucial role in SMC transition to other cell types and in lesion development. Activation of retinoic acid (RA) signaling by all-trans retinoic acid (ATRA) attenuates atherosclerosis in mice coincident with suppression of SEM cell formation. However, the effect of RA signaling on advanced disease and the underlying molecular mechanisms by which RA modulates SMC transition to SEM cells are largely unknown.METHODSWe applied SMC lineage tracing atheroprone mice and biochemistry and cell and molecular biology techniques (e.g., RNA sequencing, quantitative reverse transcription PCR, co-immunoprecipitation, and chromatin immunoprecipitation-quantitative PCR) to reveal the regulatory mechanisms of RA signaling in SMC transition to SEM cells.RESULTSActivation of RA signaling with ATRA in established atherosclerosis significantly reduced SEM cells and lesion size while increasing fibrous cap thickness. Mechanistically, retinoic acid receptor alpha (RARα) directly targets the promoters ofLy6aandLy6c1in mouse SMCs, and activation of RA signaling recruits EZH2 to the regulatory elements triggering local H3K27me3. Distinct from a molecular model that reported for RA recruitment of HDAC1 during embryogenesis, RARα/EZH2 complex recruits SIRT1 and SIRT6, rather than classical HDACs, to the regulatory regions of key SEM cell marker genes. This subsequently reduces multiple acetylated histone modifications (e.g., H3K27ac, H3K4ac, H3K9ac, H3K14ac, H3K56ac) with recruitment of the transcription corepressor, NCOR1, to repress downstream SEM cell marker genes.CONCLUSIONSOur findings provide novel mechanistic insights into RA modulating SMC phenotypic switching in atherosclerosis, suggesting molecular targets for preventive and therapeutic interventions for atherosclerosis and its clinical complications.
Correcting for volunteer bias in GWAS uncovers novel genetic variants and increases heritability estimates
Authors: van Alten Sjoerd , Domingue Benjamin W. , Faul Jessica , Galama Titus , Marees Andries T. 
Published: November 2022

AbstractThe implications of selection bias due to volunteering (volunteer bias) for genetic association studies are poorly understood. Because of its large sample size and extensive phenotyping, the UK Biobank (UKB) is included in almost all large genomewide association studies (GWAS) to date, as it is one of the largest cohorts. Yet, it is known to be highly selected. We develop inverse probability weighted GWAS (WGWAS) to estimate GWAS summary statistics in the UKB that are corrected for volunteer bias. WGWAS decreases the effective sample size substantially compared to GWAS by an average of 61% (from 337,543 to 130,684) depending on the phenotype. The extent to which volunteer bias affects GWAS associations and downstream results is phenotype-specific. Through WGWAS we find 11 novel genomewide significant loci for type 1 diabetes and 3 for breast cancer. These loci were not identified previously in any prior GWAS. Further, genetic variant’s effect sizes and heritability estimates become more predictive in WGWAS for certain phenotypes (e.g., educational attainment, drinks per week, breast cancer and type 1 diabetes). WGWAS also alters biological annotation relations in gene-set analyses. This suggests that not accounting for volunteer-based selection can result in GWASs that suffer from bias, which in turn may drive spurious associations. GWAS consortia may therefore wish to provide population weights for their data sets or rely more on population-representative samples.
The role of cholesterol metabolism in predicting clinical outcome of patients with severe COVID-19
Authors: Usenko T.S. , Miroshnikova V.V. , Bezrukova A.I. , Basharova K.S. , Landa S.B. , Korobova Z.R. , Liubimova N.E. , Vlasov I.N. , Nikolaev M.A. , Izyumchenko A.D. , Gavrilova E.G. , Shlyk I.V. , Chernitskaya E.L. , Kovalchuk Y.P. , Slominsky P.A. , Totolian A.A. , Polushin Yu.S. , Pchelina S.N. 
Published: November 2022

AbstractTranscriptomic analysis conducted by us previously revealed upregulation of genes involved in low-density lipoprotein particle receptor (LDLR) activity pathway in lethal COVID-19. Last data suggested the possible role of extracellular vesicles and exomeres in COVID-19 pathogenesis. The aim of the present study was to retrospectively evaluate parameters of cholesterol metabolism as possible predictors of fatal outcome of COVID-19. Blood from 39 patients with severe COVID-19 (the main cohort) were collected at the time of admission to the intensive care unit (ICU) (T1) and 7 days after admission to the ICU (T2). After 30 days patients were divided into two subgroups according to outcome-21 non-survivors and 18 survivors. 28 patients (13 non-survivors and 15 survivors) with severe COVID-19 were included as the replication cohort. The study demonstrated that plasma low-and high-density lipoprotein cholesterol levels (LDL-C and HDL-C) were decreased and CCL20/MIP3ɑ, IL-10, IL-15, IL-27 concentrations were increased in non-survivors compared to controls in T1.STAB1gene expression was higher in non-survivors than in survivors (p=0.017) in T2. The conjoint fraction of exomeres and LDL particles measured by dynamic light scattering (DLS) was decreased in non-survivors com-pared to survivors in both the main and replication cohorts. We first showed that change of exomeres fraction may be critical in fatal outcome of COVID-19.
How detritivores, plant traits and time modulate coupling of leaf versus woody litter decomposition rates across species
Authors: Guo Chao , Tuo Bin , Ci Hang , Sai Bi‐Le , Zhang Yu , Yan En‐Rong , Cornelissen Johannes H. C. 
Published: November 2022

Abstract

Plant functional traits are increasingly used to understand ecological relationships and (changing) ecosystem functions. For understanding ecosystem‐level biogeochemistry, we need to understand how (much) traits co‐vary between different plant organs across species and its implications for litter decomposition. However, we do not know how the degree of synchronous variation in decomposition rates between organs across species could be influenced by different keystone invertebrates decomposing different senesced plant organs, especially in warm‐climate forests. Here we asked whether interspecific patterns in wood and leaf decomposition rates and in the spectra of resource economics traits underpinning them, co‐vary across woody species; and how (much) the keystone invertebrate decomposers of the litter of these organs enhance or lower such co‐variation of decomposition rates through time.

We addressed these questions through an 18‐month ‘common‐garden’ decomposition experiment using leaf, twig and branch litter of 41 woody species in two distant subtropical forest sites in east China. We quantified the effects of leaf, twig and branch functional traits and their respective key invertebrates (moth larvae, termites) on the decomposition rates of those organs.

Interspecific variation in wood traits was partly decoupled from that in leaf traits across species, while strong coupling was found between twigs and branches. The co‐variation between leaf and woody organ decomposition rates was altered dynamically through the shifting activities of the key decomposers, which created nonlinear relationships of invertebrate litter consumption as a function of species rankings along the resource economic trait spectra of leaves and branches.

The deviations from coupling of decomposition rates between organs were likely caused by combinations of three mechanisms: (1) (de‐)coupling between organs of other traits, not commonly considered in resource economics spectra (e.g. resins) (2) leaf and wood decomposers having specific diet requirements and (3) temporal patterns of the decomposers' activity.

Synthesis. Our study highlights the importance of considering the different ways by which invertebrate detritivores drive decomposition processes through time. Under the ongoing biodiversity decline, future research would benefit from a better understanding of the role of the dynamic interactions between detritivore activities and plant functional traits on the carbon turnover in ecosystems.
“Because we all love K‐Pop”: How young adults reshape symbolic boundaries in Paris, Manchester, and Philadelphia
Authors: Cicchelli Vincenzo , Octobre Sylvie , Katz‐Gerro Tally , Yodovich Neta , Handy Femida , Ruiz Stefanie 
Published: November 2022

AbstractIn this paper, we examine how young adults who are consumers of K‐Pop in three culturally diverse cities (Paris, Philadelphia, and Manchester) reshape their symbolic boundaries to face social challenges. Analyzing data from 132 interviews, we show how young adults mainly confront social exclusion in Paris, fight racism in Philadelphia and deal with xenophobia in Manchester. Although K‐Pop adds to the dynamics of exclusion due to being perceived as culturally foreign, our participants use K‐Pop as a resource to reshape social boundaries towards new forms of inclusion. They do this by relying on K‐Pop as a cultural product that promotes inclusion, and on their affiliation with the K‐Pop community on a local and global level.
Composition, formation mechanism, and removal method of off‐odor in soymilk products
Authors: Ji Guo‐Zhi , Li Xiao‐Min , Dong Yang , Shi Yu‐Dong 
Published: November 2022

AbstractSoybean is a protein‐rich material for plant‐based products, and its application in soymilk products is limited due to its off‐odor such as beany. In order to explore a solution to address this issue, composition, formation mechanism, and removal methods of the off‐odor produced in the processing of soymilk products are comprehensively described in this paper. The main off‐odor compounds in soymilk products include hexanal, hexanol, 1‐octene‐3‐ol, (E,E)‐2, 4‐decadienal, 2‐pentylfuran, (E,E)‐2,4‐nonadienal, (E)‐2‐nonenal, (E) ‐2‐hexenal, and so on. These odor compounds are mainly produced by the enzymatic and nonenzymatic oxidation of unsaturated fatty acids. At present, physical methods are used to remove off‐odor in the industrial production of soymilk products, of which heat treatment is still the most effective. With the development of no beany soybean breeding technology, the combination of multiple methods will become a technical trend for removing off‐odor. Some new research directions are also explored about removal methods, which can provide a theoretical reference for the production and technical research of soymilk products.
Long‐term fasting glucose variability and risk of cancer in patients with type 2 diabetes mellitus: A retrospective population‐based cohort study in Shanghai
Authors: Cui Xiao‐rui , Li Jun , Yang Ya‐ting , Wu Jing‐yi , Xu Hui‐lin , Yu Yong‐fu , Qin Guo‐you 
Published: November 2022

AbstractBackgroundsFasting blood glucose (FBG) variability may make an impact on adverse events in patients with diabetes mellitus. However, the association between long‐term changes in FBG and cancer remains unclear. We aimed to investigate this association in a large‐scale longitudinal study.MethodsData were collected from 46 761 patients with type 2 diabetes mellitus aged 20–80 years who participated in the Diabetes Standardized Management Program in Shanghai, China. We adopted four indicators, including standard deviation (SD), coefficient of variation (CV), variation independent of the mean (VIM), and average real variability (ARV) to describe FBG variability. Adjusted multivariable Cox regression analyses and restricted cubic splines were used to investigate the association between long‐term FBG variability and cancer risk. We also determined the interactive effect of FBG variability with hypertension and FBG‐mean with hypertension on cancer risk, respectively.ResultsIn this study, we confirmed 2218 cancer cases (51.1% male) over a median follow‐up of 2.86 years. In the multivariable‐adjusted models, participants in the highest quartile of FBG variability had an increased risk of cancer compared with those in the lowest quartile. The nonlinear association was found when using FBG‐VIM, FBG‐ARV, and FBG‐SD in restricted cubic spline plots. There was a significant interaction effect of FBG variability with hypertension on cancer, whereas the effect of FBG‐mean with hypertension did not attain significance.ConclusionsOur retrospective cohort study demonstrated a positive association between the long‐term changes in FBG and cancer risk in patients with type 2 diabetes mellitus. FBG variability may independently predict cancer incidence.
Combined modality therapy for patients with esophageal squamous cell carcinoma: Radiation dose and survival analyses
Authors: Shueng Pei‐Wei , Huang Chun‐Chieh , Liu Yu‐Ming , Wu Yuan‐Hong , Huang Pin‐I , Yen Sang‐Hue , Lin Kuan‐Heng , Hsu Chen‐Xiong 
Published: November 2022

AbstractBackgroundWe aimed to analyze the radiation dose and compare survival among combined modality therapy using modern radiation techniques for patients with esophageal squamous cell carcinoma (ESCC).MethodsThis retrospective study included patients with clinically staged T1‐4N0‐3M0 ESCC from 2014 to 2018. Patients who received combined modality therapies with curative intent were enrolled. The overall survival (OS) rates among combined modality therapy were compared. The clinical variables and impacts of radiation dose on survival were analyzed by the Kaplan–Meier method and Cox regression model.ResultsOf the 259 patients, 141 (54.4%) received definitive concurrent chemoradiotherapy (DCCRT); 67 (25.9%) underwent neoadjuvant chemoradiotherapy followed by surgery (NCRT+S); 51 (19.7%) obtained surgery followed by adjuvant chemoradiotherapy (S+ACRT). Two‐year OS rates of the DCCRT, NCRT+S and S+ACRT group were 48.9, 61.5 and 51.2%. In the subgroup analysis of DCCRT group, the 2‐year OS of patients receiving radiation dose 55–60 Gy was 57.1%. Multivariate analyses showed that clinical stage (p = 0.004), DCCRT with 55–60 Gy (p = 0.043) and NCRT+S with pathological complete response (pCR) (p = 0.014) were significant prognostic factors for better OS. The radiation dose–survival curve demonstrated a highly positive correlation between higher radiation dose and better survival.ConclusionOur results suggest that NCRT+S can provide a favorable survival for patients with ESCC, especially in patients who achieved pCR. The optimal radiation dose might be 55–60 Gy for patients receiving DCCRT via modern radiation techniques. Further randomized clinical studies are required to confirm the survival benefits between NCRT+S and DCCRT with escalated dose.
Peripheral nerve‐blocks and associations with length of stay and readmissions in fast‐track total hip and knee arthroplasty
Authors: Jørgensen Christoffer C. , Petersen Pelle B. , Daugberg Louise O. , Jakobsen Thomas , Gromov Kirill , Varnum Claus , Andersen Mikkel R. , Palm Henrik , Kehlet Henrik 
Published: November 2022

AbstractBackgroundPeripheral nerve blocks (PNB) have recently been recommended in total hip (THA) and knee (TKA) arthroplasty as they may reduce pain, morphine consumption, length of stay (LOS) and complications. However, whether PNBs are associated with early discharge within an enhanced recovery protocol including multimodal analgesia is uncertain.MethodsAn observational multicenter study from January to August 2017 in six Danish Arthroplasty Centers with established fast‐track protocols. Prospective recording of preoperative characteristics and information on PNB, LOS and readmissions through the Danish National Patient Registry and medical records. Multiple logistic regression was used to investigate associations between PNB and a LOS >1 day, LOS >4 days, and 30‐days readmissions. We also reported on mobilization, pain, opioid and fall‐related complications leading to LOS >4 days or readmissions.ResultsA total of 2027 (58.6%) THA and 1432 (41.4%) TKAs with a median LOS of 1 day (IQR 1–2) and 5.3% (CI:4.6–6.1) 30‐days readmission rate were identified. PNB was used in 40.7% (CI:38.2–43.3) of TKA and 2.7% (CI:2.0–3.5) of THA, but with considerable interdepartmental variation (0.0–89.0% for TKA). There was no association between PNB and LOS >1 day (OR:1.19 CI:0.82–1.72; p = .354), LOS >4 days (OR:1.4 CI:0.68–2.89; p = .359) or 30‐days readmissions (OR:1.02 CI:0.63–1.65; p = .935) in TKA. Logistic regression in THA was not possible due to limited use of PNB. In TKA there were 12 (2.1% CI:1.2–3.6) with and 1 (0.1% CI:0.02–0.7) without a PNB, who had mobilization, pain or opioid‐related complications, and 5 (0.9% CI:0.4–2.0) versus 4 (0.5% CI:0.2–1.2) who fell. Correspondingly, 2 (3.7% CI:1.0–12.6) and 11 (0.6% CI:0.3–1.0) of THA patients had these complications, while 0 (0.0% CI:0.0–6.6) and 17 (0.8% CI:0.5–1.3) fell.ConclusionRoutine use of peripheral nerve blocks was not associated with early discharge or 30‐days readmissions in fast‐track THA and TKA. Future studies should focus on benefits of PNB in high‐risk patients.
Outcome of intentional replantation of endodontically treated teeth with periapical pathosis: A systematic review and meta‐analysis
Authors: Javed Faizan , Zafar Kamil , Khan Farhan R. 
Published: November 2022

AbstractThe purpose of the present review was to examine success, survival and failure following intentional replantation of endodontically treated teeth with existing periapical pathosis and to determine the factors that might affect the outcome of replantation. Clinical trials, longitudinal studies, case series with >10 cases and at least 1‐year follow‐up were included. The average rate of success following intentional replantation was 77.23%. Meta‐analysis revealed the mean weighted survival to be 85.9% (95% CI: 79.6–91.2) Common complications include inflammatory root resorption (0%–27%) and ankylosis (0%–25%). Variables influencing successful outcome include extra alveolar dry time <15 min; root‐end resection (2–3 mm) and cavity preparation (3 mm); manipulation of the tooth using the crown only; and use of an appropriate storage media. The review concludes that intentional replantation is a viable treatment option with acceptable survival rates for endodontically treated teeth with periapical pathosis.
Preoperative serum CA125 level and age at diagnosis: An effective prognosis prediction tool for patients with early‐stage endometrial cancer
Authors: Sun Shuai , Wei Lichun , Zou Lijuan , Wang Tiejun , Liu Zi , He Jianli , Sun Xiaoge , Zhong Wei , Zhao Fengju , Li Xiaomei , Li Sha , Zhu Hong , Ma Zhanshu , Wang Wenhui , Zhang Fuquan , Hou Xiaorong , Hu Ke 
Published: November 2022

AbstractObjectiveTo investigate the combined predictive value of the preoperative serum cancer antigen 125 (CA125) level and age at diagnosis among patients with early‐stage endometrial cancer (EC) after initial treatment.MethodsWe retrospectively analyzed data from patients with early‐stage EC from 1999 to 2015 in multiple institutions in China. All 447 patients received postoperative adjuvant radiotherapy for FIGO 2009 stage I and II EC with complete data on preoperative serum CA125 levels. All patients were divided into four groups according to the ESMO‐ESGO‐ESTRO risk classification. The predictive probability of 5‐year overall survival (OS) and the sensitivity and specificity of CA125 and age were calculated.ResultsThe median follow‐up time was 59 months (3–201 months). The 5‐year OS and disease‐free survival rates were 94.4% and 89.1%. Multivariate analysis showed that the preoperative CA125 level and age at diagnosis were independent prognostic factors for 5‐year OS. The area under the curve for CA125 combined with age at diagnosis for 5‐year OS was .692, and the corresponding sensitivity and specificity were 68.2% and 68.2% (p < .002), which were significantly better than the corresponding values for CA125 or age alone. After all 447 patients were divided into four groups according to CA125 combined with age, the 5‐year OS of the elderly and higher CA125 group was only 73.7%.ConclusionsAlthough preoperative CA125 had limited sensitivity in predicting the prognosis for early‐stage EC after initial treatment, it remains a useful serum marker for risk assessment of early‐stage EC. Combining CA125 with age may increase its predictive sensitivity.
Editorial: gluten‐free but not pain‐free in IBS—authors' reply
Authors: Algera Joost P. , Magnusson Maria K. , Öhman Lena , Störsrud Stine , Simrén Magnus , Törnblom Hans 
Published: November 2022

LINKED CONTENTThis article is linked to Algera et al papers. To view these articles, visit https://doi.org/10.1111/apt.17239 and https://doi.org/10.1111/apt.17253
Sleep duration and daytime napping in relation to incident inflammatory bowel disease: a prospective cohort study
Authors: Yuan Shuai , Sun Yuhao , Tan Xiao , Geng Jiawei , Sun Jing , Chen Xuejie , Yu Lili , Wang Jiayi , Zhou Xuan , Hesketh Therese , Larsson Susanna C. , Chen Jie , Wang Xiaoyan , Li Xue , Liu Zhanju 
Published: November 2022

SummaryBackgroundSleep dysregulation has been linked to gastrointestinal dysfunction and inflammation.AimsTo explore the associations between sleep duration, daytime napping and inflammatory bowel disease (IBD), Crohn's disease (CD) and ulcerative colitis (UC).MethodsExposure information was obtained from the baseline questionnaire. Sleep duration was coded as continuous and categorical (≤5, 6, 7, 8, ≥9 h/day) variables. Daytime napping was defined as yes (sometimes/usually) and no (never/rarely). Incident IBD cases were defined from primary care and hospital inpatient records. Polygenic risk scores (PRS) for the outcomes were constructed and categorised into low, intermediate and high risk. Hazard ratio (HR) and confidence interval (CI) were estimated using Cox proportional hazard regression.ResultsThe analysis included 2604 incident IBD cases (806 CD and 1798 UC) with a median follow‐up of 12.0 years. Comparing sleep duration ≤5 with 7 h/day, the HR of IBD, CD and UC was 1.36 (95% CI, 1.17–1.59), 1.53 (95% CI, 1.17–2.00) and 1.29 (95% CI, 1.07–1.56), respectively. Comparing participants with and without daytime napping, the HR of IBD, CD and UC was 1.13 (95% CI, 1.05–1.23), 1.25 (95% CI, 1.08–1.44) and 1.09 (95% CI, 0.90–1.20), respectively. No interaction of sleep duration and daytime napping with PRS was detected. However, the associations appeared stronger in individuals with high rather than low PRS.ConclusionsThis study reveals positive associations between short sleep duration and daytime napping and IBD risk.