bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dietary carbon loaded with nano-ZnO alters the gut microbiota community to mediate bile acid metabolism and potentiate intestinal immune function in fattening beef cattle
Authors: Zhang Haibo , Guan Weikun , Li Lizhi , Guo Dongsheng , Zhang Xiangfei , Guan Jiuqiang , Luo Runxiao , Zheng Siying , Fu Jiangwen , Cheng Yingying , He Qin 
Published: December 2022

Abstract
Background
To our knowledge, carbon loaded with nano-ZnO (NZnOC) represents a new nutritional additive for the animal husbandry industry. However, the mechanism by which NZnOC mediates beef cattle growth and intestinal health is not fully understood. This study aimed to investigate the effects of carbon loaded with nano-ZnO (NZnOC) supplementation on growth performance, gut microbiota, bile acid (BAs) metabolism and intestinal immunity in fattening cattle. Twenty cattle (16 ± 0.95 months) were randomly assigned to two dietary groups: CON (control, without feed additive) and NZnOC (diet supplemented with 80 mg NZnOC/kg diet dry matter basic) for 60 d. The colon digesta microbiota composition and BAs concentration were determined by microbiota metagenomics and gas chromatography methods, respectively.

Results
The results showed that the NZnOC-supplemented cattle had greater final weight, average daily gain and gain-to-feed ratio than those in the CON group. Cattle fed the NZnOC diet had a higher relative abundance of the secondary BAs synthesizing phyla Firmicutes, Tenericutes and Actinobacteria than those fed the CON diet. Dietary supplementation with NZnOC increased the relative abundance of the secondary BAs synthesis microbiota genera Clostridium, Ruminococcus, Eubacterium, and Brevibacillus in colon digesta. Cattle fed the NZnOC diet had increased activities of 3α-hydroxysteroid dehydrogenase (EC: 1.1.1.52) and bile acid-CoA ligase BaiB (EC: 6.2.1.7) in the colon digesta compared with those fed the CON diet. The primary BAs taurocholic acid, taurochenodeoxycholic acid and taurodeoxycholate acid were significantly decreased by dietary NZnOC supplementation, while the secondary BAs deoxycholic acid, taurolithocholic acid, beta-muricholic acid, 12-ketolithocholic acid and ursodeoxycholic acid were significantly increased. Dietary supplementation with NZnOC increased the mRNA abundance of G protein-coupled bile acid receptor 1, protein kinase cAMP-activated catalytic subunit alpha, cyclic-AMP response element binding protein 1 and interleukin (IL)-10 in the colon mucosa of cattle, while the mRNA abundance of tumor necrosis factor and IL-1β were significantly decreased.

Conclusions
In summary, dietary supplementation with NZnOC can facilitate the growth performance and intestinal immune function of cattle by improving BAs metabolism. NZnOC can be supplemented in the diet as a safe regulator of gut microbiota and as a feed additive in the ruminants industry.
Prevalence and detection of Tropheryma whipplei in the stools of Korean patients with diarrhea using real-time PCRs
Authors: Yoon Sumi , Choi Yoo Jeong , Lim Yong Kwan , Kweon Oh Joo , Kim Hye Ryoun , Kim Tae-Hyoung , Lee Mi-Kyung 
Published: December 2022

Abstract
Background
The prevalence of Tropheryma whipplei varies depending on age, region, and underlying disease. We estimated the prevalence of T. whipplei in the stools of Korean patients with diarrhea using real-time PCR (RT-PCR) and compared three RT-PCR targets, rpoB, hsp65, and Dig15.

Methods
A total of 1404 nucleic acid samples extracted from the stools of Korean patients with diarrhea were tested using an initial RT-PCR targeting T. whipplei-specific regions of 16S–23S rRNA intergenic spacer. Subsequently, the samples positive for the initial RT-PCR were tested using the follow-up RT-PCRs targeting rpoB, hsp65, and Dig15 and analyzed by sequencing to confirm the presence of T. whipplei. We estimated the prevalence of T. whipplei and compared them according to gender and age. We also compared the performance of three targets in the follow-up RT-PCRs.

Results
T. whipplei was detected in 1.4% of all samples (20 of 1404), and there were no differences according to gender and age. In pediatric samples (≤ 19 years), T. whipplei was detected higher in children aged 6–19 than in those aged 1–5 (2.7% vs. 0.7%, P = 0.01). Sensitivities of the rpoB, hsp65, and Dig15 RT-PCR were 50.0%, 85.0%, and 95.0%, respectively; specificities were 100.0%, 100.0%, and 84.6%, respectively.

Conclusions
This is the first study that estimated the prevalence of T. whipplei in the stools of Korean patients with diarrhea. This study demonstrated the presence of T. whipplei in stools of Koreans, even though the bacterium was detected low. The RT-PCRs targeting hsp65 and Dig15 showed reliable performance, and a multiplex PCR including these targets is expected to be useful for T. whipplei detection.
Evaluation of asthma–chronic obstructive pulmonary disease overlap using a mouse model of pulmonary disease
Authors: Jo Yong Suk , Rhee Chin Kook , Yoon Hyoung Kyu , Park Chan Kwon , Lim Jeong Uk , An Tai Joon , Hur Jung 
Published: December 2022

Abstract
Background
Features of asthma and chronic obstructive pulmonary disease (COPD) can coexist in the same patient, in a condition termed asthma– chronic obstructive pulmonary disease overlap (ACO). ACO is heterogeneous condition exhibiting various combinations of asthma and COPD features. No clinically acceptable experimental model of ACO has been established. We aimed to establish an animal model of ACO.

Methods
We generated two phenotypes of ACO by administering ovalbumin and porcine pancreatic elastase in combination, and papain. The proinflammatory cytokines and cell types in bronchoalveolar lavage fluid (BALF) were investigated, and lung function parameters were measured using the FlexiVent system.

Results
Greater airway inflammation was observed in the asthma and both ACO models, and emphysema was found in the COPD and both ACO models. The proportion of eosinophils in BALF was elevated in the asthma and ACO-a model. Type 2 inflammatory cytokine levels were highest in the ACO-a model, and the neutrophil gelatinase–associated lipocalin level was elevated in the asthma and ACO-a model. Of lung function parameters, compliance was greater in the COPD and ACO-b model, in which elastance was lower than in the asthma model. Airway resistance increased with the methacholine concentration in the asthma and both ACO models, but not in the control or COPD model.

Conclusion
We established two murine models of ACO that exhibit features of asthma and COPD. We validated the clinical relevance of the ACO models based on changes in cytokine profiles and lung function. These models will be useful in further studies of the pathogenesis of, and therapeutic targets for ACO.
Smooth muscle cell fate decisions decipher a high-resolution heterogeneity within atherosclerosis molecular subtypes
Authors: Zhang Ge , Liu Zaoqu , Deng Jinhai , Liu Long , Li Yu , Weng Siyuan , Guo Chunguang , Zhou Zhaokai , Zhang Li , Wang Xiaofang , Liu Gangqiong , Guo Jiacheng , Bai Jing , Wang Yunzhe , Du Youyou , Li Tao-Sheng , Tang Junnan , Zhang Jinying 
Published: December 2022

Abstract
Background
Mounting evidence has revealed the dynamic variations in the cellular status and phenotype of the smooth muscle cell (SMC) are vital for shaping the atherosclerotic plaque microenvironment and ultimately mapping onto heterogeneous clinical outcomes in coronary artery disease. Currently, the underlying clinical significance of SMC evolutions remains unexplored in atherosclerosis.

Methods
The dissociated cells from diseased segments within the right coronary artery of four cardiac transplant recipients and 1070 bulk samples with atherosclerosis from six bulk cohorts were retrieved. Following the SMC fate trajectory reconstruction, the MOVICS algorithm integrating the nearest template prediction was used to develop a stable and robust molecular classification. Subsequently, multi-dimensional potential biological implications, molecular features, and cell landscape heterogeneity among distinct clusters were decoded.

Results
We proposed an SMC cell fate decision signature (SCFDS)-based atherosclerosis stratification system and identified three SCFDS subtypes (C1–C3) with distinguishing features: (i) C1 (DNA-damage repair type), elevated base excision repair (BER), DNA replication, as well as oxidative phosphorylation status. (ii) C2 (immune-activated type), stronger immune activation, hyper-inflammatory state, the complex as well as varied lesion microenvironment, advanced stage, the most severe degree of coronary stenosis severity. (iii) C3 (stromal-rich type), abundant fibrous content, stronger ECM metabolism, immune-suppressed microenvironment.

Conclusions
This study uncovered atherosclerosis complex cellular heterogeneity and a differentiated hierarchy of cell populations underlying SMC. The novel high-resolution stratification system could improve clinical outcomes and facilitate individualized management.
A functional loop between YTH domain family protein YTHDF3 mediated m6A modification and phosphofructokinase PFKL in glycolysis of hepatocellular carcinoma
Authors: Zhou Rong , Ni Wen , Qin Chao , Zhou Yunxia , Li Yuqing , Huo Jianping , Bian Lijuan , Zhou Aijun , Li Jianming 
Published: December 2022

Abstract
Background & aims
N6-methyladenosine (m6A) modification plays a critical role in progression of hepatocellular carcinoma (HCC), and aerobic glycolysis is a hallmark of cancer including HCC. However, the role of YTHDF3, one member of the core readers of the m6A pathway, in aerobic glycolysis and progression of HCC is still unclear.

Methods
Expression levels of YTHDF3 in carcinoma and surrounding tissues of HCC patients were evaluated by immunohistochemistry. Loss and gain-of-function experiments in vitro and in vivo were used to assess the effects of YTHDF3 on HCC cell proliferation, migration and invasion. The role of YTHDF3 in hepatocarcinogenesis was observed in a chemically induced HCC model with Ythdf3−/− mice. Untargeted metabolomics and glucose metabolism phenotype assays were performed to evaluate relationship between YTHDF3 and glucose metabolism. The effect of YTHDF3 on PFKL was assessed by methylated RNA immunoprecipitation assays (MeRIP). Co-immunoprecipitation and immunofluorescence assays were performed to investigate the connection between YTHDF3 and PFKL.

Results
We found YTHDF3 expression was greatly upregulated in carcinoma tissues and it was correlated with poor prognosis of HCC patients. Gain-of-function and loss-of-function assays demonstrated YTHDF3 promoted proliferation, migration and invasion of HCC cells in vitro, and YTHDF3 knockdown inhibited xenograft tumor growth and lung metastasis of HCC cells in vivo. YTHDF3 knockout significantly suppressed hepatocarcinogenesis in chemically induced mice model. Mechanistically, YTHDF3 promoted aerobic glycolysis by promoting phosphofructokinase PFKL expression at both mRNA and protein levels. MeRIP assays showed YTHDF3 suppressed PFKL mRNA degradation via m6A modification. Surprisingly, PFKL positively regulated YTHDF3 protein expression, not as a glycolysis rate-limited enzyme, and PFKL knockdown effectively rescued the effects of YTHDF3 overexpression on proliferation, migration and invasion ability of Sk-Hep-1 and HepG2 cells. Notably, co-immunoprecipitation assays demonstrated PFKL interacted with YTHDF3 via EFTUD2, a core subunit of spliceosome involved in pre-mRNA splicing process, and ubiquitination assays showed PFKL could positively regulate YTHDF3 protein expression via inhibiting ubiquitination of YTHDF3 protein by EFTUD2.

Conclusions
our study uncovers the key role of YTHDF3 in HCC, characterizes a positive functional loop between YTHDF3 and phosphofructokinase PFKL in glucose metabolism of HCC, and suggests the connection between pre-mRNA splicing process and m6A modification.
Association between cholinesterase activity and critical illness brain dysfunction
Authors: Hughes Christopher G. , Boncyk Christina S. , Fedeles Benjamin , Pandharipande Pratik P. , Chen Wencong , Patel Mayur B. , Brummel Nathan E. , Jackson James C. , Raman Rameela , Ely E. Wesley , Girard Timothy D. 
Published: December 2022

Abstract
Background
Delirium is a frequent manifestation of acute brain dysfunction and is associated with cognitive impairment. The hypothesized mechanism of brain dysfunction during critical illness is centered on neuroinflammation, regulated in part by the cholinergic system. Point-of-care serum cholinesterase enzyme activity measurements serve as a real-time index of cholinergic activity. We hypothesized that cholinesterase activity during critical illness would be associated with delirium in the intensive care unit (ICU) and cognitive impairment after discharge.

Methods
We enrolled adults with respiratory failure and/or shock and measured plasma acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activity on days 1, 3, 5, and 7 after enrollment. AChE values were also normalized per gram of hemoglobin (AChE/Hgb). We assessed for coma and delirium twice daily using the Richmond Agitation Sedation Scale and the Confusion Assessment Method for the ICU to evaluate daily mental status (delirium, coma, normal) and days alive without delirium or coma. Cognitive impairment, disability, and health-related quality of life were assessed at up to 6 months post-discharge. We used multivariable regression to determine whether AChE, AChE/Hgb, and BChE activity were associated with outcomes after adjusting for relevant covariates.

Results
We included 272 critically ill patients who were a median (IQR) age 56 (39–67) years and had a median Sequential Organ Failure Assessment score at enrollment of 8 (5–11). Higher daily AChE levels were associated with increased odds of being delirious versus normal mental status on the same day (Odds Ratio [95% Confidence Interval] 1.64 [1.11, 2.43]; P = 0.045). AChE/Hgb and BChE activity levels were not associated with delirious mental status. Lower enrollment BChE was associated with fewer days alive without delirium or coma (P = 0.048). AChE, AChE/Hgb, and BChE levels were not significantly associated with cognitive impairment, disability, or quality of life after discharge.

Conclusion
Cholinesterase activity during critical illness is associated with delirium but not with outcomes after discharge, findings that may reflect mechanisms of acute brain organ dysfunction.
Trial Registration: NCT03098472. Registered 31 March 2017.
Activation of primary hepatic stellate cells and liver fibrosis induced by targeting TGF-β1/Smad signaling in schistosomiasis in mice
Authors: Huang Ping , Ma Huihui , Cao Yun , Zhan Tingzheng , Zhang Tingting , Wang Xinyi , Zhang Yanan , Xu Jing , Xia Chaoming 
Published: December 2022

Abstract
Background
In mice, liver fibrosis is the most serious pathologic change during Schistosoma japonicum (S. japonicum) infection. Schistosomiasis is mainly characterized by schistosome egg-induced granulomatous fibrosis. Hepatic stellate cells (HSCs) are mainly responsible for the net accumulation of collagens and fibrosis formation in the liver. Activated HSCs regulated by transforming growth factor-β1 (TGF-β1)/Smad signaling have emerged as the critical regulatory pathway in hepatitis virus or carbon tetrachloride-induced liver fibrosis. However, the detailed mechanism of HSC activation in schistosome-induced liver fibrosis is poorly understood.

Methods
Schistosoma japonicum-induced murine models and a control group were generated by abdominal infection with 15 (± 1) cercariae. The purity of cultured primary HSCs was evaluated by immunocytochemistry. The histopathological changes in the livers of infected mice were estimated by hematoxylin–eosin and Masson staining. Dynamic expression of pro-fibrotic molecules and microRNAs was detected by real-time quantitative PCR (RT-qPCR). Mainly members involved in the TGF-β1/Smad signaling pathway were examined via RT-qPCR and Western blot.

Results
The egg-induced granulomatous inflammation formed at 4 weeks post-infection (wpi) and developed progressively. Alpha-smooth muscle actin (α-SMA), collagen I, collagen III, TGF-β1, Smad2, Smad3, and Smad4 showed a significant increase in mitochondrial RNA (mRNA) and protein expression compared with the control group at 7 and 9 weeks post-infection (wpi), while an opposite effect on Smad7 was observed. In addition, the mRNA expression of microRNA-21 (miRNA-21) was significantly increased at 7 wpi, and the mRNA expression of miRNA-454 was decreased starting from 4 wpi.

Conclusion
Our present findings revealed that HSCs regulated by the TGF-β1/Smad signaling pathway play an important role in liver fibrosis in S. japonicum-infected mice, which may provide proof of concept for liver fibrosis in schistosomiasis.

Graphical Abstract
Cerebrovascular accident in a child with precursor B-cell acute lymphoblastic leukemia and coronavirus disease 2019: a case report
Authors: Karimi Hanie , Sarmadian Roham , Gilani Abolfazl , salajegheh Poorya , Nejad Biglari Habibe , Gholizadeh Mahsa 
Published: December 2022

Abstract
Background
Coronavirus disease 2019 can lead to rare but severe and life-threatening diseases in susceptible high-risk populations, including patients with immunodeficiency. A rare event in this report is stroke following COVID-19 disease in a patient with an immunocompromised background due to leukemia and anti-cancer treatments.

Case presentation
A 6-year-old iranian girl with precursor B-cell leukemia receiving vincristine therapy presented with fever and absolute neutrophil count < 500. Her severe acute respiratory syndrome coronavirus 2 polymerase chain reaction test was positive. During hospitalization, she had abrupt onset tachypnea, reduced O2 saturation, and generalized tonic–clonic seizures treated with phenytoin and levetiracetam. Right parietal lobe ischemia was found on a brain computed tomography scan, and the cerebrospinal fluid polymerase chain reaction test was positive for severe acute respiratory syndrome coronavirus 2. Several days later, she developed lower extremity paralysis and speech impairment, so speech therapy and physiotherapy were initiated. The patient also received dexamethasone, mannitol, heparin, and remdesivir. She was discharged with enoxaparin and levetiracetam. Chemotherapy resumed 2 weeks following discharge. Her speech and walking improved after 10 months of follow-up, and bone marrow aspiration showed total remission.

Conclusion
Owing to the link between coronavirus disease 2019 and hematologic cancers with hypercoagulopathy and the tendency of patients with leukemia to have coronavirus disease 2019 complications, children with leukemia as well as suspected coronavirus disease 2019 must be hospitalized to prevent blood clot formation.
Efficacy and Safety of Osilodrostat in Paraneoplastic Cushing Syndrome: A Real-World Multicenter Study in France
Authors: Dormoy Alexandre , Haissaguerre Magalie , Vitellius Géraldine , Do Cao Christine , Geslot Aurore , Drui Delphine , Lasolle Hélène , Vieira-Pinto Oceana , Salenave Sylvie , François Maud , Puerto Marie , Boullay Hélène Du , Mayer Anne , Rod Anne , Laurent Claire , Chanson Philippe , Reznik Yves , Castinetti Frédéric , Chabre Olivier , Baudin Eric , Raverot Gérald , Tabarin Antoine , Young Jacques 
Published: December 2022

Abstract

Context
Prospective studies have demonstrated the efficacy of osilodrostat in Cushing disease. No study has evaluated osilodrostat in a series of patients with paraneoplastic Cushing syndrome/ectopic adrenocorticotropin syndrome (PNCS/EAS).

Objective
This work aimed to evaluate in France the real-world efficacy and safety of osilodrostat in patients with PNCS/EAS.

Methods
A total of 33 patients with PNCS/EAS with intense/severe hypercortisolism were involved in this retrospective, multicenter, real-world study. Patients received osilodrostat between May 2019 and March 2022 at a median initial dose (range) of 4 mg/day (1-60) and maximum dose, 20 mg/day (4-100), first under patient then cohort temporary authorizations and after marketing authorization. Regimens used titration (n = 6), block and replace (n = 16), or titration followed by block and replace (n = 11).

Results
In 11 patients receiving osilodrostat as first-line monotherapy, median 24-hour urinary free cortisol (24h-UFC) decreased dramatically (from 26 × upper limit of normal [ULN; 2.9-659] to 0.11 × ULN [0.08-14.9]; P &lt; .001). In 9 of them, 24h-UFC normalization was achieved in 2 weeks (median). Thirteen additional patients were previously treated with classic steroidogenesis inhibitors but 10 of these 13 were not controlled. In these patients, osilodrostat monotherapy, used as second line, induced a significantly decreased of 24h-UFC (from 2.6 × ULN [1.1-144] to 0.22 × ULN [0.12-0.66]; P &lt; .01). Nine additional patients received osilodrostat in combination with another anticortisolic drug, decreasing 24h-UFC from 11.8 × ULN (0.3-247) to 0.43 × ULN (0.33-2.4) (P &lt; .01). In parallel, major clinical symptoms/comorbidities improved dramatically with improvement in blood pressure, hyperglycemia, and hypokalemia, allowing the discontinuation or dose reduction of patient treatments. Adrenal insufficiency (grade 3-4) was reported in 8 of 33 patients.

Conclusion
Osilodrostat is a rapidly efficient therapy for PNCS/EAS with severe/intense hypercortisolism. Osilodrostat was generally well tolerated; adrenal insufficiency was the main side effect.
Bayesian and MLE of R=P(Y>X) for Exponential Distribution Based on Varied L Ranked Set Sampling
Authors: Abdallah Mohamed S. 
Published: December 2022

The ranked set sampling (RSS) is an effective scheme popularly used to produce more precisely estimators. Despite its popularity, RSS suffers from some drawbacks which includes high sensitivity to outliers and it cannot sometimes be applicable when the population is relatively small. To overcome these limitations, varied L ranked set sampling (VLRSS) is recently introduced. It is shown that VLRSS scheme enjoys with many interesting properties over RSS and also encompasses several existing RSS schemes. In addition, it is also helpful for providing precise estimates of several population parameters. To fill this gap, this article extends the work and address the estimation of based ℛ on VLRSS when the strength and stress both follow exponential distribution. Maximum likelihood approach as well as Bayesian method are considered for estimating ℛ. The Bayes estimators are obtained by using gamma distribution under general entropy loss function and LINEX loss function. The performance of the estimators based on VLRSS are investigated by a simulation study as well as a real dataset relevant to industrial field. The results reveal that the proposed estimators are more efficient relative to their analogues estimators under L ranked set sampling given that the quality of ranking is fairly good.