bluuebunny/crossref_metadata_2025_split huggingface dataset:
CCL3 secreted by hepatocytes promotes the metastasis of intrahepatic cholangiocarcinoma by VIRMA-mediated N6-methyladenosine (m6A) modification
Authors: Zhou Shurui , Yang Kege , Chen Shaojie , Lian Guoda , Huang Yuzhou , Yao Hanming , Zhao Yue , Huang Kaihong , Yin Dong , Lin Haoming , Li Yaqing 
Published: January 2023

Abstract
Background
Intrahepatic cholangiocarcinoma (ICC) is a malignant disease characterized by onset occult, rapid progression, high relapse rate, and high mortality. However, data on how the tumor microenvironment (TME) regulates ICC metastasis at the transcriptomic level remains unclear. This study aimed to explore the mechanisms and interactions between hepatocytes and ICC cells.

Methods
We analyzed the interplay between ICC and liver microenvironment through cytokine antibody array analysis. Then we investigated the role of N6-methyladenosine (m6A) modification and the downstream target in vitro, in vivo experiments, and in clinical specimens.

Results
Our study demonstrated that cytokine CCL3, which is secreted by hepatocytes, promotes tumor metastasis by regulating m6A modification via vir-like m6A methyltransferase associated (VIRMA) in ICC cells. Moreover, immunohistochemical analyses showed that VIRMA correlated with poor outcomes in ICC patients. Finally, we confirmed both in vitro and in vivo that CCL3 could activate VIRMA and its critical downstream target SIRT1, which fuels tumor metastasis in ICC.

Conclusions
In conclusion, our results enhanced our understanding of the interaction between hepatocytes and ICC cells, and revealed the molecular mechanism of the CCL3/VIRMA/SIRT1 pathway via m6A-mediated regulation in ICC metastasis. These studies highlight potential targets for the diagnosis, treatment, and prognosis of ICC.
Early peripheral blood gene expression associated with good and poor 90-day ischemic stroke outcomes
Authors: Amini Hajar , Knepp Bodie , Rodriguez Fernando , Jickling Glen C. , Hull Heather , Carmona-Mora Paulina , Bushnell Cheryl , Ander Bradley P. , Sharp Frank R. , Stamova Boryana 
Published: January 2023

Abstract
Background
This study identified early immune gene responses in peripheral blood associated with 90-day ischemic stroke (IS) outcomes.

Methods
Peripheral blood samples from the CLEAR trial IS patients at ≤ 3 h, 5 h, and 24 h after stroke were compared to vascular risk factor matched controls. Whole-transcriptome analyses identified genes and networks associated with 90-day IS outcome assessed using the modified Rankin Scale (mRS) and the NIH Stroke Scale (NIHSS).

Results
The expression of 467, 526, and 571 genes measured at ≤ 3, 5 and 24 h after IS, respectively, were associated with poor 90-day mRS outcome (mRS ≥ 3), while 49, 100 and 35 genes at ≤ 3, 5 and 24 h after IS were associated with good mRS 90-day outcome (mRS ≤ 2). Poor outcomes were associated with up-regulated genes or pathways such as IL-6, IL-7, IL-1, STAT3, S100A12, acute phase response, P38/MAPK, FGF, TGFA, MMP9, NF-kB, Toll-like receptor, iNOS, and PI3K/AKT. There were 94 probe sets shared for poor outcomes vs. controls at all three time-points that correlated with 90-day mRS; 13 probe sets were shared for good outcomes vs. controls at all three time-points; and 46 probe sets were shared for poor vs. good outcomes at all three time-points that correlated with 90-day mRS. Weighted Gene Co-Expression Network Analysis (WGCNA) revealed modules significantly associated with 90-day outcome for mRS and NIHSS. Poor outcome modules were enriched with up-regulated neutrophil genes and with down-regulated T cell, B cell and monocyte-specific genes; and good outcome modules were associated with erythroblasts and megakaryocytes. Finally, genes identified by genome-wide association studies (GWAS) to contain significant stroke risk loci or loci associated with stroke outcome including ATP2B, GRK5, SH3PXD2A, CENPQ, HOXC4, HDAC9, BNC2, PTPN11, PIK3CG, CDK6, and PDE4DIP were significantly differentially expressed as a function of stroke outcome in the current study.

Conclusions
This study suggests the immune response after stroke may impact functional outcomes and that some of the early post-stroke gene expression markers associated with outcome could be useful for predicting outcomes and could be targets for improving outcomes.
A two-year follow-up: Twitter activity regarding misinformation about spinal manipulation, chiropractic care and boosting immunity during the COVID-19 pandemic
Authors: Kawchuk Gregory Neil , Harsted Steen , Hartvigsen Jan , Nyirö Luana , Nim Casper Glissmann 
Published: January 2023

Abstract
Background
Spinal manipulative therapy (SMT) is offered by many health professions, most often by chiropractors. While SMT can be effective for some musculoskeletal disorders, there is no evidence that SMT improves human immunity in a clinically meaningful way. Despite this, we showed previously that Twitter misinformation about chiropractic/SMT improving immunity increased sharply at the start of the COVID-19 pandemic. Here, we perform a two-year follow-up.

Methods
We previously employed specialized software (i.e. Talkwalker) to search the entirety of Twitter activity in the months before and after the COVID-19 pandemic was declared (March 11, 2020). In this paper, we conducted follow-up searches over two successive 12 month periods using terms related to SMT, immunity and chiropractic. The resulting tweets were then coded into those promoting/refuting a relation between SMT and immunity (tone) and messaging about chiropractic/interventions (content). Further analyses were performed to subcategorize tweet content, tally likes, retweets and followers, and evaluate refuting tweets and the country of origin. Finally, we created a chronology of Twitter activity superimposed with dates of promoting or refuting activities undertaken by chiropractic organizations.

Results
Over the 27 month study period, Twitter activity peaked on March 31, 2020 then declined continuously. As in our first paper, our follow-up data showed that (1) the ratio of refuting/promoting tweets remained constant and (2) tweets that refuted a relationship between SMT and immunity were substantially more liked, retweeted and followed than those promoting. We also observed that promoting tweets suggesting that SMT improves immunity decreased more rapidly. Overwhelmingly, promoting tweets originated in the USA while refuting tweets originated in Canada, Europe and Australia. The timing of the decline in peak Twitter activity, together with a parallel decline in tweets claiming that SMT improves immunity, was coincident with initiatives by chiropractic organizations and regulators targeting misinformation.

Conclusion
Overwhelmingly, Twitter activity during the COVID-19 pandemic focussed on refuting a relation between chiropractic/SMT and immunity. A decline in Twitter activity promoting a relation between SMT and immunity was observed to coincide with initiatives from chiropractic organizations and regulators to refute these claims. The majority of misinformation about this topic is generated in the United States.
Comparison of the effectiveness of different machine learning algorithms in predicting new fractures after PKP for osteoporotic vertebral compression fractures
Authors: Ma Yiming , Lu Qi , Yuan Feng , Chen Hongliang 
Published: January 2023

Abstract
Background
The use of machine learning has the potential to estimate the probability of a second classification event more accurately than traditional statistical methods, and few previous studies on predicting new fractures after osteoporotic vertebral compression fractures (OVCFs) have focussed on this point. The aim of this study was to explore whether several different machine learning models could produce better predictions than logistic regression models and to select an optimal model.

Methods
A retrospective analysis of 529 patients who underwent percutaneous kyphoplasty (PKP) for OVCFs at our institution between June 2017 and June 2020 was performed. The patient data were used to create machine learning (including decision trees (DT), random forests (RF), support vector machines (SVM), gradient boosting machines (GBM), neural networks (NNET), and regularized discriminant analysis (RDA)) and logistic regression models (LR) to estimate the probability of new fractures occurring after surgery. The dataset was divided into a training set (75%) and a test set (25%), and machine learning models were built in the training set after ten cross-validations, after which each model was evaluated in the test set, and model performance was assessed by comparing the area under the curve (AUC) of each model.

Results
Among the six machine learning algorithms, except that the AUC of DT [0.775 (95% CI 0.728–0.822)] was lower than that of LR [0.831 (95% CI 0.783–0.878)], RA [0.953 (95% CI 0.927–0.980)], GBM [0.941 (95% CI 0.911–0.971)], SVM [0.869 (95% CI 0.827–0.910), NNET [0.869 (95% CI 0.826–0.912)], and RDA [0.890 (95% CI 0.851–0.929)] were all better than LR.

Conclusions
For prediction of the probability of new fracture after PKP, machine learning algorithms outperformed logistic regression, with random forest having the strongest predictive power.

Graphical Abstract
Assessing welfare risks in unowned unsocialised domestic cats in Denmark based on associations with low body condition score
Authors: Nielsen Søren Saxmose , Thuesen Ida Sofie , Mejer Helena , Agerholm Jørgen Steen , Nielsen Stine Thorsø , Jokelainen Pikka , Thamsborg Stig Milan , Sandøe Peter 
Published: January 2023

Abstract
Background
Populations of unowned unsocialised cats are present worldwide. Generally, there is concern about their welfare. Low body condition score (BCS) is a potentially relevant indicator that is relatively easy to assess: emaciated cats are likely to have welfare problems while thin cats may be at risk of becoming emaciated. The objective of this study was to assess the association of low BSC with a selection of factors relating to the host, disease, and infection in unowned unsocialised domestic cats. We necropsied 598 euthanised unowned unsocialised cats from Denmark. We recorded each cat’s age-group, sex, and neuter status, together with its pregnancy status, the season and location of trapping, as well as gross lesions at necropsy. We also tested for feline immunodeficiency virus and feline leukaemia virus, recorded presence of ectoparasites, and a subsample of the cats were also tested for endoparasites. Cats with no or sparse adipose deposits were categorised as having low BCS, and logistic regression was used to determine the factors associated with low BCS.

Results
Of the cats, 11.4% had low BCS. Season, age-group and sex were associated with low BCS and confounded potential associations with other variables. Intact adult males and females in spring and early summer were at highest risk of low BCS. When these factors were taken into account, cats with biting lice had 2.8 (95% confidence interval (CI) 1.4–5.4) times higher odds of low BCS, and cats with gastro-intestinal findings (i.e., enlarged mesenteric lymph nodes, abdominal hernia, diarrhoea, obstructive foreign bodies, or diaphragmatic hernia) had 50 (95% CI 10–417) times higher odds of low BCS, than cats with no such findings. Cats with low BCS were primarily adult intact cats with tooth lesions and skin lesions, ear mite infection, and positive test result for feline immunodeficiency virus.

Conclusions
The results highlight associations that can be used to define a risk profile: low BCS, notably in summer-autumn, in an unowned unsocialised cat was associated with underlying, less visible problems. Thus, low BCS can be more than a step towards being emaciated; it can also be an indicator of other underlying welfare problems.
The Weimberg pathway: an alternative for Myceliophthora thermophila to utilize d-xylose
Authors: Liu Defei , Zhang Yongli , Li Jingen , Sun Wenliang , Yao Yonghong , Tian Chaoguang 
Published: January 2023

Abstract
Background
With d-xylose being the second most abundant sugar in nature, its conversion into products could significantly improve biomass-based process economy. There are two well-studied phosphorylative pathways for d-xylose metabolism. One is isomerase pathway mainly found in bacteria, and the other one is oxo-reductive pathway that always exists in fungi. Except for these two pathways, there are also non-phosphorylative pathways named xylose oxidative pathways and they have several advantages over traditional phosphorylative pathways. In Myceliophthora thermophila, d-xylose can be metabolized through oxo-reductive pathway after plant biomass degradation. The survey of non-phosphorylative pathways in this filamentous fungus will offer a potential way for carbon-efficient production of fuels and chemicals using d-xylose.

Results
In this study, an alternative for utilization of d-xylose, the non-phosphorylative Weimberg pathway was established in M. thermophila. Growth on d-xylose of strains whose d-xylose reductase gene was disrupted, was restored after overexpression of the entire Weimberg pathway. During the construction, a native d-xylose dehydrogenase with highest activity in M. thermophila was discovered. Here, M. thermophila was also engineered to produce 1,2,4‐butanetriol using d-xylose through non-phosphorylative pathway. Afterwards, transcriptome analysis revealed that the d-xylose dehydrogenase gene was obviously upregulated after deletion of d-xylose reductase gene when cultured in a d-xylose medium. Besides, genes involved in growth were enriched in strains containing the Weimberg pathway.

Conclusions
The Weimberg pathway was established in M. thermophila to support its growth with d-xylose being the sole carbon source. Besides, M. thermophila was engineered to produce 1,2,4‐butanetriol using d-xylose through non-phosphorylative pathway. To our knowledge, this is the first report of non-phosphorylative pathway recombinant in filamentous fungi, which shows great potential to convert d-xylose to valuable chemicals.
Comparative genomic and transcriptome analysis of Bacillus velezensis CL-4 fermented corn germ meal
Authors: Chen Long , Qu Zihui , Yu Wei , Zheng Lin , Qiao Haixin , Wang Dan , Wei Bingdong , Zhao Zijian 
Published: January 2023

AbstractBacillus, an excellent organic-degrading agent, can degrade lignocellulose. Notably, some B. velezensis strains encode lignocellulases. However, their ability to degrade lignocellulose in fermented feed is not much appreciated. This study performed a comparative genomic analysis of twenty-three B. velezensis strains to find common carbohydrate-active enzymes (CAZymes) encoding genes and evaluated their potential to degrade lignocellulose. The comparative genomic and CAZyme database-based analyses identified several potential CAZymes genes that degrade cellulose (GH1, GH4, GH5, GH13, GH16, GH32, PL1, and PL9), hemicellulose (GH11, GH26, GH43, GH51, and CE3) and lignin (AA4, AA6, AA7, and AA10). Furthermore, Illumina RNA-seq transcriptome analysis revealed the expression of more than 1794 genes in B. velezensis CL-4 fermented corn germ meal at 48 h (FCGM 48 h). Gene ontology analysis of expressed genes revealed their enrichment in hydrolase activity (breaking the glycosyl bonds during carbohydrate metabolism), indicating the upregulation of CAZymes. In total, 58 differentially upregulated CAZymes-encoding genes were identified in FCGM 48 h compared to FCGM 0 h. The upregulated CAZymes-encoding genes were related to cellulose (6-phospho-β-galactosidase and 6-phospho-α-glucosidase), starch (α-glucosidase and α-amylase), pectin (pectin lyase), and hemicellulose (arabinan endo-1,5-α-L-arabinosidase, xylan 1,4-beta-xylosidase, α-N-arabinofuranosidase, and acetyl xylan esterase). Importantly, arabinoxylan degradation mainly occurred in FCGM 48 h, followed by partial degradation of cellulose, pectin, and starch. This study can support the development of enzymatic cocktails for the solid-state fermented feed (SFF).
Carbon pool dynamics after variable retention harvesting in Nothofagus pumilio forests of Tierra del Fuego
Authors: Chaves Jimena E. , Aravena Acuña Marie-Claire , Rodríguez-Souilla Julián , Cellini Juan M. , Rappa Nolan J. , Lencinas María V. , Peri Pablo L. , Martínez Pastur Guillermo J. 
Published: January 2023

Abstract
Background
It is necessary to determine the implications for managing forest stands using variable retention harvesting for maintaining carbon and for calculating the effects of different harvesting practices on above- and below-ground carbon balance in forest ecosystems. In this context, forest carbon management has gained more attention among managers and policy-makers during recent years. The aim of this study was to determine carbon pool dynamics in different forest ecosystem components after variable retention harvesting (VRH) to characterize the ecological stability and quantify the recovery rate through the years-after-harvesting (YAH).

Methods
Carbon pool compartmentalization of 14 different components was determined in 60 harvested and primary unmanaged forests during the first 18 YAH in Tierra del Fuego (Argentina). We compared them using uni- and multi-variate methods, relativizing the outputs with primary unmanaged forests.

Results
We determined the effectiveness to retain carbon components in post-harvested stands under different retention strategies (aggregated vs. dispersed). The balance among carbon pool components changed between managed and unmanaged stands across the YAH, and was directly related to the impact magnitude. Aggregated retention improved the ecological stability of the harvested areas, where the below-ground components were more stable than the above-ground components. The recovery rate was directly related to the post-harvesting natural dynamics of the stands. The studied period was not enough to fully recover the C levels of primary unmanaged forests, but VRH showed advantages to increase the C pools in the managed stands.

Conclusions
Promoting VRH can improve sustainable forestry at the landscape level and in the long term, generating positive synergies with biodiversity and the provision of ecosystem services. This study provides important new insights into forest carbon management, in particular to setting standards in carbon projects and sets the groundwork for analysing the economics of the mentioned harvesting systems.
Assessing rheometry for measuring the viscosity-average degree of polymerisation of cellulose in paper degradation studies
Authors: Maraghechi Siavash , Dupont Anne-Laurence , Cardinaels Ruth , Paris-Lacombe Sabrina , Hoefnagels Johan P. M. , Suiker Akke S. J. , Bosco Emanuela 
Published: January 2023

Abstract
In paper degradation studies, the viscosity-average degree of polymerisation (DPv) is often used as a key indicator of the extent of degradation of cellulosic paper. DPv can be deduced from the viscosity of dilute paper solutions, as typically measured through glass capillary viscometry. The current study proposes an efficient, alternative method to evaluate DPv of cellulosic paper, which is based on rotational rheometry. The proposed methodology relies on the application of a shear flow in a thin film of cellulose solution to measure its dynamic viscosity, from which DPv can be subsequently derived in a straightforward fashion. Rheometry allows to measure the viscosity for a range of shear rates, which results in multiple DPv evaluations per sample, and thus in statistically representative data from an individual test. Further, rheometry typically requires considerably less paper mass per test than glass capillary viscometry, which makes the method attractive for paper degradation studies with limited sample availability. Also, rheometry measurements are less work-intensive than glass capillary viscometry measurements. The rheometry method has been applied to 4 hygrothermally aged cellulose paper samples and the unaged counterpart. The measurement results regarding the age-dependency of DPv and the number of cellulose chain scissions are compared to those obtained by glass capillary viscometry, showing a very good agreement. At a longer ageing time, both experimental methods reveal a non-linear decrease in time of DPv, and a non-linear increase in time of the number of cellulose chain scissions, which indicate that the cellulose ageing process is realistically captured. The agreement in measurement results further demonstrates that rheometry is an easy-to-use, accurate and efficient alternative for DPv measurements by glass capillary viscometry.
Arbuscular mycorrhizal fungi inoculation impacts expression of aquaporins and salt overly sensitive genes and enhances tolerance of salt stress in tomato
Authors: Liu Ming-Yang , Li Qiu-Shuang , Ding Wan-Yu , Dong Li-Wei , Deng Min , Chen Jia-Hui , Tian Xiao , Hashem Abeer , Al-Arjani Al-Bandari Fahad , Alenazi Mekhled M. , Abd-Allah Elsayed Fathi , Wu Qiang-Sheng 
Published: January 2023

AbstractArbuscular mycorrhizal fungi (AMF) that establish reciprocal symbiosis with plant roots can enhance resistance to various stresses, including salt stress, but relevant mechanisms, especially at the molecular level, are scarce. The objective of this study was to analyze the effect of an arbuscular mycorrhizal fungus Paraglomus occultum on plant growth, leaf gas exchange, and expression of plasma membrane intrinsic proteins (PIPs), tonoplast intrinsic proteins (TIPs) and salt overly sensitive (SOS) genes in tomato under salt (150 mmol/L NaCl) and non-salt stress. Salt stress for 4 weeks inhibited root colonization rate of P. occultum and soil hyphal length by 0.21- and 0.57-fold, respectively. Salt stress also inhibited plant growth performance and leaf gas exchange, while inoculation with P. occultum significantly enhanced them under salt and non-salt stress conditions. AMF showed diverse regulation of root SlPIPs and SlTIPs expression, among which under salt stress, SlPIP1;2, SlPIP1;5, SlPIP2;1, SlPIP2;6, SlPIP2;9, SlPIP2;10, SlTIP2;2, SlTIP3;2, and SlTIP5;1 were up-regulated by AMF colonization, and SlPIP1;7, SlPIP2;5, SlPIP2;8, SlPIP2;11, SlPIP2;12, SlTIP2;3, and SlTIP3;1 were down-regulated, accompanied by no change in SlPIP1;1, SlPIP1;3, SlPIP2;4, SlTIP1;1, SlTIP1;2, SlTIP1;3, SlTIP2;1, and SlTIP2;5. Interestingly, salt stress inhibited the expression of SlSOS1 and SlSOS2 in non-mycorrhizal plants, while it increased the expression of SlSOS1 and SlSOS2 in mycorrhizal plants. AMF colonization down-regulated expression of SlSOS1 and SlSOS2 under non-salt stress while up-regulated expression of SlSOS1 and SlSOS2 under salt stress. It was concluded that AMF inoculation impacted the expression of stress-responsive genes, especially SOS1 and SOS2, and enhanced salt resistance of tomato.
Graphical Abstract