bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intra-cluster correlations from the CLustered OUtcome Dataset bank to inform the design of longitudinal cluster trials
Authors: Korevaar Elizabeth , Kasza Jessica , Taljaard Monica , Hemming Karla , Haines Terry , Turner Elizabeth L , Thompson Jennifer A , Hughes James P , Forbes Andrew B 
Published: June 2021

Background: Sample size calculations for longitudinal cluster randomised trials, such as crossover and stepped-wedge trials, require estimates of the assumed correlation structure. This includes both within-period intra-cluster correlations, which importantly differ from conventional intra-cluster correlations by their dependence on period, and also cluster autocorrelation coefficients to model correlation decay. There are limited resources to inform these estimates. In this article, we provide a repository of correlation estimates from a bank of real-world clustered datasets. These are provided under several assumed correlation structures, namely exchangeable, block-exchangeable and discrete-time decay correlation structures. Methods: Longitudinal studies with clustered outcomes were collected to form the CLustered OUtcome Dataset bank. Forty-four available continuous outcomes from 29 datasets were obtained and analysed using each correlation structure. Patterns of within-period intra-cluster correlation coefficient and cluster autocorrelation coefficients were explored by study characteristics. Results: The median within-period intra-cluster correlation coefficient for the discrete-time decay model was 0.05 (interquartile range: 0.02–0.09) with a median cluster autocorrelation of 0.73 (interquartile range: 0.19–0.91). The within-period intra-cluster correlation coefficients were similar for the exchangeable, block-exchangeable and discrete-time decay correlation structures. Within-period intra-cluster correlation coefficients and cluster autocorrelations were found to vary with the number of participants per cluster-period, the period-length, type of cluster (primary care, secondary care, community or school) and country income status (high-income country or low- and middle-income country). The within-period intra-cluster correlation coefficients tended to decrease with increasing period-length and slightly decrease with increasing cluster-period sizes, while the cluster autocorrelations tended to move closer to 1 with increasing cluster-period size. Using the CLustered OUtcome Dataset bank, an RShiny app has been developed for determining plausible values of correlation coefficients for use in sample size calculations. Discussion: This study provides a repository of intra-cluster correlations and cluster autocorrelations for longitudinal cluster trials. This can help inform sample size calculations for future longitudinal cluster randomised trials.
CD36 deficiency ameliorates drug-induced acute liver injury in mice
Authors: Zhang Chen , Shi Xiao , Su Zhongping , Hu Chao , Mu Xianmin , Pan Jinshun , Li Mengjing , Teng Fengmeng , Ling Tao , Zhao Ting , Xu Che , Ji Guozhong , You Qiang 
Published: June 2021

Abstract
Background
Acetaminophen (APAP) overdose causes hepatotoxicity and even acute liver failure. Recent studies indicate that sterile inflammation and innate immune cells may play important roles in damage-induced hepatocytes regeneration and liver repair. The scavenger receptor CD36 has its crucial functions in sterile inflammation. However, the roles of CD36 in APAP induced acute liver injury remain unclear and warrant further investigation.

Methods
WT C57BL/6 J and CD36−/− mice were intraperitoneally injected with APAP (300 mg/kg) after fasting for 16 h. Liver injury was evaluated by serum alanine aminotransferase (ALT) level and liver tissue hematoxylin and eosin (H&E) staining. Liver inflammatory factor expression was determined by real-time polymerase chain reaction (PCR). The protein adducts forming from the metabolite of APAP and the metabolism enzyme cytochrome P450 2E1 (CYP2E1) levels were measured by Western blot. Liver infiltrating macrophages and neutrophils were characterized by flow cytometry. RNA sequencing and Western blot were used to evaluate the effect of damage-associated molecular patterns (DAMP) molecule high mobility group B1 (HMGB1) on WT and CD36−/− macrophages. Moreover, PP2, a Src kinase inhibitor, blocking CD36 signaling, was applied in APAP model.

Results
The expression of CD36 was increased in the liver of mice after APAP treatment. Compared with WT mice, APAP treated CD36−/− mice show less liver injury. There was no significant difference in APAP protein adducts and CYP2E1 expression between these two strains. However, reduced pro-inflammatory factor mRNA expression and serum IL-1β level were observed in APAP treated CD36−/− mice as well as infiltrating macrophages and neutrophils. Moreover, CD36 deficiency impaired the activation of c-Jun N-terminal kinase (JNK) caused by APAP. Interestingly, the lack of CD36 reduced the activation of extracellular regulated protein kinases (Erk) and v-akt murine thymoma viral oncogene homolog (Akt) induced by HMGB1. RNA transcription sequencing data indicated that HMGB1 has a different effect on WT and CD36−/− macrophages. Furthermore, treatment with PP2 attenuated APAP induced mouse liver injury.

Conclusion
Our data demonstrated that CD36 deficiency ameliorated APAP-induced acute liver injury and inflammatory responses by decreasing JNK activation. CD36 might serve as a new target to reduce acute liver injury.
Perfluoroalkyl and polyfluoroalkyl substance exposure and association with sex hormone concentrations: results from the NHANES 2015–2016
Authors: Xie Xin , Weng Xueqiong , Liu Shan , Chen Jingmin , Guo Xinrong , Gao Xinyu , Fei Qiaoyuan , Hao Guang , Jing Chunxia , Feng Liping 
Published: June 2021

Abstract
Background
There is increasing global concern regarding the health impacts of perfluoroalkyl and polyfluoroalkyl substances (PFAS), which are emerging environmental endocrine disruptors. Results from previous epidemiological studies on the associations between PFAS exposure and sex hormone levels are inconsistent.

Objective
We examined the associations between serum PFAS compounds (PFDeA, PFHxS, PFNA, PFOA, PFOS) and sex hormones, including total testosterone (TT), free testosterone (FT), estradiol (E), and serum hormone binding globulin (SHBG).

Results
After adjusting for potential confounders, PFDeA, PFOS, and PFHxS exposures were significantly associated with increased serum testosterone concentrations in males. PFDeA, PFOA, and PFOS exposures were positively correlated with FT levels in 20–49-year-old women, while PFOS exposure was negatively associated with TT levels in 12–19-year-old girls. PFAS exposure was negatively associated with estradiol levels including: PFDeA in all females, PFHxS, PFNA, PFOS, and PFOA in 12–19-year-old girls, PFNA in women above 50 years, and PFOA in 12–19-year-old boys, while PFDeA and PFOS exposures were positively associated with estradiol levels in these boys. n-PFOS exposure was positively associated with SHBG levels in men older than 20 and in all females.

Conclusions
Using a large cohort of males and females aged from 12 to 80, we found that PFAS exposure appears to disrupt sex hormones in a sex-, age-, and compound-specific manner. Future work is warranted to clarify the causality and mechanisms involved.
Evolution of dominance in gene expression pattern associated with phenotypic robustness
Authors: Okubo Kenji , Kaneko Kunihiko 
Published: June 2021

Abstract
Background
Mendelian inheritance is a fundamental law of genetics. When we consider two genomes in a diploid cell, a heterozygote’s phenotype is dominated by a particular homozygote according to the law of dominance. Classical Mendelian dominance is concerned with which proteins are dominant, and is usually based on simple genotype–phenotype relationship in which one gene regulates one phenotype. However, in reality, some interactions between genes can exist, resulting in deviations from Mendelian dominance. Whether and how Mendelian dominance is generalized to the phenotypes of gene expression determined by gene regulatory networks (GRNs) remains elusive.

Results
Here, by using the numerical evolution of diploid GRNs, we discuss whether the dominance of phenotype evolves beyond the classical Mendelian case of one-to-one genotype–phenotype relationship. We examine whether complex genotype–phenotype relationship can achieve Mendelian dominance at the expression level by a pair of haplotypes through the evolution of the GRN with interacting genes. This dominance is defined via a pair of haplotypes that differ from each other but have a common phenotype given by the expression of target genes. We numerically evolve the GRN model for a diploid case, in which two GRN matrices are added to give gene expression dynamics and simulate evolution with meiosis and recombination. Our results reveal that group Mendelian dominance evolves even under complex genotype–phenotype relationship. Calculating the degree of dominance shows that it increases through the evolution, correlating closely with the decrease in phenotypic fluctuations and the increase in robustness to initial noise. We also demonstrate that the dominance of gene expression patterns evolves concurrently. This evolution of group Mendelian dominance and pattern dominance is associated with phenotypic robustness against meiosis-induced genome mixing, whereas sexual recombination arising from the mixing of genomes from the parents further enhances dominance and robustness. Due to this dominance, the robustness to genetic differences increases, while optimal fitness is sustained to a significant difference between the two genomes.

Conclusion
Group Mendelian dominance and gene-expression pattern dominance are achieved associated with the increase in phenotypic robustness to noise.
Consequences of mutation accumulation for growth performance are more likely to be resource-dependent at higher temperatures
Authors: Chu Xiao-Lin , Zhang Quan-Guo 
Published: June 2021

AbstractBackgroundMutation accumulation (MA) has profound ecological and evolutionary consequences. One example is that accumulation of conditionally neutral mutations leads to fitness trade-offs among heterogenous habitats which cause population divergence. Here we suggest that temperature, which controls the rates of all biochemical and biophysical processes, should play a crucial role for determining mutational effects. Particularly, warmer temperatures may mitigate the effects of some, not all, deleterious mutations and cause stronger environmental dependence in MA effects.ResultsWe experimentally tested the above hypothesis by measuring the growth performance of tenEscherichia coligenotypes on six carbon resources across ten temperatures, where the ten genotypes were derived from a single ancestral strain and accumulated spontaneous mutations. We analyzed resource dependence of MA consequences for growth yields. The MA genotypes typically showed reduced growth yields relative to the ancestral type; and the magnitude of reduction was smaller at intermediate temperatures. Stronger resource dependence in MA consequences for growth performance was observed at higher temperatures. Specifically, the MA genotypes were more likely to show impaired growth performance on all the six carbon resources when grown at lower temperatures; but suffered growth performance loss only on some, not all the six, carbon substrates at higher temperatures.ConclusionsHigher temperatures increase the chance that MA causes conditionally neutral fitness effects while MA is more likely to cause fitness loss regardless of available resources at lower temperatures. This finding has implications for understanding how geographic patterns in population divergence may emerge, and how conservation practices, particularly protection of diverse microhabitats, may mitigate the impacts of global warming.
Patterns of yeast diversity distribution and its drivers in rhizosphere soil of Hami melon orchards in different regions of Xinjiang
Authors: Zhu ShanShan , Lei YongHui , Wang Chong , Wei YuMei , Wang ChunCheng , Sun YanFei 
Published: June 2021

Abstract
Background
The unique climatic conditions of the Xinjiang region nurture rich melon and fruit resources, the melon and fruit sugar sources provide sufficient nutrients for the survival of yeast, and the diverse habitats accompanied by extreme climatic conditions promote the production of yeast diversity and strain resources. However, the relationship between yeast species and their relationship with environmental factors in the soil of Xinjiang specialty cash crop Hami melon is not clear. Here, we aimed to characterize the diversity, community structure, and relationship between yeast species and environmental factors in Hami melon orchards soils in different regions of Xinjiang, China.

Results
Based on Illumina MiSeq high-throughput sequencing analysis of the D1 domain of the LSU rRNA genes, the community richness of yeast in the soil of Northern Xinjiang was higher than in the Southern and Eastern Xinjiang, but the community diversity was significantly lower in the Northern Xinjiang than in the Southern and Eastern Xinjiang. A total of 86 OTUs were classified into 59 genera and 86 species. Most OTUs (90.4%) belonged to the Basidiomycota; only a few (9.6%) belonged to Ascomycota. The most dominant species in the Southern, Eastern and Northern Xinjiang were Filobasidium magnum (17.90%), Solicoccozyma aeria (35.83%) and Filobasidium magnum (75.36%), respectively. Principal coordinates analysis (PCoA) showed that the yeast community composition in the soils of the three regions were obviously different, with the Southern and Eastern Xinjiang having more similar yeast community. Redundancy analysis (RDA) showed that soil factors such as conductivity (CO), total phosphorus (TP) and Total potassium (TK) and climate factors such as average annual precipitation (PRCP), relative humidity (RH) and net solar radiation intensity (SWGNT) were significantly correlated with yeast communities (P < 0.05).

Conclusion
There are abundant yeast resources in the rhizosphere soil of Hami melon orchard in Xinjiang, and there are obvious differences in the diversity and community structure of yeast in the three regions of Xinjiang. Differences in climatic factors related to precipitation, humidity and solar radiation intensity and soil factors related to conductivity, total phosphorus and total potassium are key factors driving yeast diversity and community structure.
Low nitrogen availability inhibits the phosphorus starvation response in maize (Zea mays ssp. mays L.)
Authors: Torres-Rodríguez J. Vladimir , Salazar-Vidal M. Nancy , Chávez Montes Ricardo A. , Massange-Sánchez Julio A. , Gillmor C. Stewart , Sawers Ruairidh J. H. 
Published: June 2021

Abstract
Background
Nitrogen (N) and phosphorus (P) are macronutrients essential for crop growth and productivity. In cultivated fields, N and P levels are rarely sufficient, contributing to the gap between realized and potential production. Fertilizer application increases nutrient availability, but is not available to all farmers, nor are current rates of application sustainable or environmentally desirable. Transcriptomic studies of cereal crops have revealed dramatic responses to either low N or low P single stress treatments. In the field, however, levels of both N and P may be suboptimal. The interaction between N and P starvation responses remains to be fully characterized.

Results
We characterized growth and root and leaf transcriptomes of young maize plants under nutrient replete, low N, low P or combined low NP conditions. We identified 1555 genes to respond to our nutrient treatments, in one or both tissues. A large group of genes, including many classical P starvation response genes, were regulated antagonistically between low N and P conditions. An additional experiment over a range of N availability indicated that a mild reduction in N levels was sufficient to repress the low P induction of P starvation genes. Although expression of P transporter genes was repressed under low N or low NP, we confirmed earlier reports of P hyper accumulation under N limitation.

Conclusions
Transcriptional responses to low N or P were distinct, with few genes responding in a similar way to the two single stress treatments. In combined NP stress, the low N response dominated, and the P starvation response was largely suppressed. A mild reduction in N availability was sufficient to repress the induction of P starvation associated genes. We conclude that activation of the transcriptional response to P starvation in maize is contingent on N availability.
Prognostic value of D-dimer for adverse outcomes in patients with infective endocarditis: an observational study
Authors: Lin Ying-Wen , Jiang Mei , Wei Xue-biao , Huang Jie-leng , Su Zedazhong , Wang Yu , Chen Ji-yan , Yu Dan-qing 
Published: June 2021

Abstract
Background
Increased D-dimer levels have been shown to correlate with adverse outcomes in various clinical conditions. However, few studies with a large sample size have been performed thus far to evaluate the prognostic value of D-dimer in patients with infective endocarditis (IE).

Methods
613 patients with IE were included in the study and categorized into two groups according to the cut-off of D-dimer determined by receiver operating characteristic (ROC) curve analysis for in-hospital death: > 3.5 mg/L (n = 89) and ≤ 3.5 mg/L (n = 524). Multivariable regression analysis was used to determine the association of D-dimer with in-hospital adverse events and six-month death.

Results
In-hospital death (22.5% vs. 7.3%), embolism (33.7% vs 18.2%), and stroke (29.2% vs 15.8%) were significantly higher in patients with D-dimer > 3.5 mg/L than in those with D-dimer ≤ 3.5 mg/L. Multivariable analysis showed that D-dimer was an independent risk factor for in-hospital adverse events (odds ratio = 1.11, 95% CI 1.03–1.19, P = 0.005). In addition, the Kaplan–Meier curve showed that the cumulative 6-month mortality was significantly higher in patients with D-dimer > 3.5 mg/L than in those with D-dimer ≤ 3.5 mg/L (log-rank test = 39.19, P < 0.0001). Multivariable Cox regression analysis showed that D-dimer remained a significant predictor for six-month death (HR 1.11, 95% CI 1.05–1.18, P < 0.001).

Conclusions
D-dimer is a reliable prognostic biomarker that independently associated with in-hospital adverse events and six-month mortality in patients with IE.
Open science saves lives: lessons from the COVID-19 pandemic
Authors: Besançon Lonni , Peiffer-Smadja Nathan , Segalas Corentin , Jiang Haiting , Masuzzo Paola , Smout Cooper , Billy Eric , Deforet Maxime , Leyrat Clémence 
Published: June 2021

AbstractIn the last decade Open Science principles have been successfully advocated for and are being slowly adopted in different research communities. In response to the COVID-19 pandemic many publishers and researchers have sped up their adoption of Open Science practices, sometimes embracing them fully and sometimes partially or in a sub-optimal manner. In this article, we express concerns about the violation of some of the Open Science principles and its potential impact on the quality of research output. We provide evidence of the misuses of these principles at different stages of the scientific process. We call for a wider adoption of Open Science practices in the hope that this work will encourage a broader endorsement of Open Science principles and serve as a reminder that science should always be a rigorous process, reliable and transparent, especially in the context of a pandemic where research findings are being translated into practice even more rapidly. We provide all data and scripts at https://osf.io/renxy/.
Clinicopathological characteristics and prognosis of signet ring cell carcinoma of the gallbladder
Authors: Wang Shijie , Li Jiayi , You Jun , Zhou Yanming 
Published: June 2021

Abstract
Background
Signet ring cell carcinoma (SRC) is a rare histological subtype of gallbladder adenocarcinoma. The current study evaluates the clinicopathologic features and prognosis of SRC.

Methods
Patients with adenocarcinoma of the gallbladder were identified in the Surveillance, Epidemiology, and End Results database from 1973 to 2016. Overall survival (OS) and cancer-specific survival (CSS) of patients who had SRC were compared with those of patients who had non-SRC using Cox regression and propensity score methods.

Results
Of 22,781 gallbladder adenocarcinomas retrieved, 377 (1.7%) were SRC and the other 22,404 were non-SRC. SRC was more significantly associated with older age, female gender, poor differentiation, advanced tumor stage, lymph node metastasis, distant metastasis, and advanced AJCC stage. The 5-year OS and CSS in the SRC group were 7.2 and 6.5%, respectively, both of which were significantly worse than the 13.2 and 13.3% seen in the SRC group (P = 0.002 and P = 0.012, respectively). This survival disadvantage persisted in multivariable analyses [hazard ratio (HR) = 1.256, P = 0.021 and HR = 1.211, P = 0.036] and after propensity score matching (OS: HR = 1.341, P = 0.012 and CSS: HR = 1.625, P = 0.005). Surgery in combination with chemotherapy improved OS of gallbladder SRC patients compared with surgery alone (HR = 0.726, P = 0.036) or chemotherapy alone (HR = 0.433, P < 0.001).

Conclusion
Patients with SRC of the gallbladder have distinct clinicopathological features with poor prognosis. Surgery in combination with chemotherapy can improve survival.
Multiple thrombosis associated with Cytomegalovirus enterocolitis in an immunocompetent patient: a case report
Authors: Kamatani Kaisei , Kenzaka Tsuneaki , Sugimoto Ryu , Kumabe Ayako , Kitao Akihito , Akita Hozuka 
Published: June 2021

Abstract
Background
Cytomegalovirus (CMV) is reported to have thrombogenic characteristics that activate factor X in vitro and stimulate the production of factor VIII and von Willebrand factor (vWF). Thrombosis associated with CMV infection is prevalent among immunocompromised patients and predominantly presents as a solitary large thrombus in the deep vein, pulmonary artery, splanchnic arteriovenous ducts, or other similar sites. Multiple thrombi, however, are rarely observed in such cases. Here, we report about an immunocompetent man with multiple microthrombi associated with CMV infection.

Case presentation
A 72-year-old Japanese man who complained of abdominal pain was hospitalized with multiple colonic stenosis. He was later diagnosed with CMV enterocolitis and treated with ganciclover from Day 27 post-admission. During hospitalization, the patient developed thrombi in his fingers. He was initially treated with anticoagulant therapy (rivaroxaban); however, the therapy was discontinued owing to a prolonged activated thromboplastin time and an elevated international normalized ratio of prothrombin time. Instead, vitamin K and fresh-frozen plasma were administered. Nevertheless, his coagulation profile remained abnormal. Eventually, he developed colonic perforation and had to undergo emergency surgery. An intraoperative specimen showed several microthrombi in the middle and small arteriovenous ducts of his small and large intestines. The patient’s coagulopathy improved preoperatively, and his overall condition improved postoperatively. Since the activation of ADAMTS13 was reduced remarkably, the thrombotic tendency was determined to be a thrombotic microangiopathy-like condition owing to increased vWF. We could not attribute the coagulopathy to any other cause except CMV infection; therefore, we concluded that this was a case of multiple thrombosis associated with CMV.

Conclusions
We present an extremely rare case of a patient with multiple thrombotic microangiopathy-like microthrombosis caused by CMV infection. Our findings suggest that CMV infection may be considered as a differential diagnosis for immunocompetent individuals who present with thrombosis of unspecified cause.