bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elesclomol: a copper ionophore targeting mitochondrial metabolism for cancer therapy
Authors: Zheng Peijie , Zhou Chuntao , Lu Liuyi , Liu Bin , Ding Yuemin 
Published: September 2022

AbstractElesclomol is an anticancer drug that targets mitochondrial metabolism. In the past, elesclomol was recognized as an inducer of oxidative stress, but now it has also been found to suppress cancer by inducing cuproptosis. Elesclomol’s anticancer activity is determined by the dependence of cancer on mitochondrial metabolism. The mitochondrial metabolism of cancer stem cells, cancer cells resistant to platinum drugs, proteasome inhibitors, molecularly targeted drugs, and cancer cells with inhibited glycolysis was significantly enhanced. Elesclomol exhibited tremendous toxicity to all three kinds of cells. Elesclomol's toxicity to cells is highly dependent on its transport of extracellular copper ions, a process involved in cuproptosis. The discovery of cuproptosis has perfected the specific cancer suppressor mechanism of elesclomol. For some time, elesclomol failed to yield favorable results in oncology clinical trials, but its safety in clinical application was confirmed. Research progress on the relationship between elesclomol, mitochondrial metabolism and cuproptosis provides a possibility to explore the reapplication of elesclomol in the clinic. New clinical trials should selectively target cancer types with high mitochondrial metabolism and attempt to combine elesclomol with platinum, proteasome inhibitors, molecularly targeted drugs, or glycolysis inhibitors. Herein, the particular anticancer mechanism of elesclomol and its relationship with mitochondrial metabolism and cuproptosis will be presented, which may shed light on the better application of elesclomol in clinical tumor treatment.
Clinical nutrition issues in 2022: What is missing to trust supplemental parenteral nutrition (SPN) in ICU patients?
Authors: Berger Mette M. , Burgos Rosa , Casaer Michael P. , De Robertis Edoardo , Delgado Juan Carlos Lopez , Fraipont Vincent , Gonçalves-Pereira João , Pichard Claude , Stoppe Christian 
Published: September 2022

AbstractA multidisciplinary group of international physicians involved in the medical nutrition therapy (MNT) of adult critically ill patients met to discuss the value, role, and open questions regarding supplemental parenteral nutrition (SPN) along with oral or enteral nutrition (EN), particularly in the intensive care unit (ICU) setting. This manuscript summarizes the discussions and results to highlight the importance of SPN as part of a comprehensive approach to MNT in critically ill adults and for researchers to generate new evidence based on well-powered randomized controlled trials (RCTs). The experts agreed on several key points: SPN has shown clinical benefits, resulting in this strategy being included in American and European guidelines. Nevertheless, its use is heterogeneous across European countries, due to the persistence of uncertainties, such as the optimal timing and the risk of overfeeding in absence of indirect calorimetry (IC), which results in divergent opinions and barriers to SPN implementation. Education is also insufficient. The experts agreed on actions needed to increase evidence quality on SPN use in specific patients at a given time point during acute critical illness or recovery.
Exosomal Wnt7a from a low metastatic subclone promotes lung metastasis of a highly metastatic subclone in the murine 4t1 breast cancer
Authors: Li Chunning , Yoshimura Teizo , Tian Miao , Wang Yuze , Kondo Takamasa , Yamamoto Ken-Ichi , Fujisawa Masayoshi , Ohara Toshiaki , Sakaguchi Masakiyo , Matsukawa Akihiro 
Published: September 2022

Abstract
Background
Patients with triple-negative breast cancer (TNBC) often have poorer prognosis than those with other subtypes because of its aggressive behaviors. Cancer cells are heterogeneous, and only a few highly metastatic subclones metastasize. Although the majority of subclones may not metastasize, they could contribute by releasing factors that increase the capacity of highly metastatic cells and/or provide a favorable tumor microenvironment (TME). Here, we analyzed the interclonal communication in TNBC which leads to efficient cancer progression, particularly lung metastasis, using the polyclonal murine 4T1 BC model.

Methods
We isolated two 4T1 subclones, LM.4T1 and HM.4T1 cells with a low and a high metastatic potential, respectively, and examined the effects of LM.4T1 cells on the behaviors of HM.4T1 cells using the cell scratch assay, sphere-forming assay, sphere invasion assay, RT-qPCR, and western blotting in vitro. We also examined the contribution of LM.4T1 cells to the lung metastasis of HM.4T1 cells and TME in vivo. To identify a critical factor which may be responsible for the effects by LM.4T1 cells, we analyzed the data obtained from the GEO database.

Results
Co-injection of LM.4T1 cells significantly augmented lung metastases by HM.4T1 cells. LM.4T1-derived exosomes promoted the migration and invasion of HM.4T1 cells in vitro, and blocking the secretion of exosome abrogated their effects on HM.4T1 cells. Analyses of data obtained from the GEO database suggested that Wnt7a might be a critical factor responsible for the enhancing effects. In fact, a higher level of Wnt7a was detected in LM.4T1 cells, especially in exosomes, than in HM.4T1 cells, and deletion of Wnt7a in LM.4T1 cells significantly decreased the lung metastasis of HM.4T1 cells. Further, treatment with Wnt7a increased the spheroid formation by HM.4T1 cells via activation of the PI3K/Akt/mTOR signaling pathway. Finally, infiltration of αSMA-positive fibroblasts and angiogenesis was more prominent in tumors of LM.4T1 cells and deletion of Wnt7a in LM.4T1 cells markedly reduced angiogenesis.

Conclusions
We demonstrated, for the first time, that a low metastatic subclone can enhance lung metastasis of highly metastatic subclone via exosomal Wnt7a and propose Wnt7a as a molecular target to treat TNBC patients.
Reversal Of Arterial Disease by modulating Magnesium and Phosphate (ROADMAP-study): rationale and design of a randomized controlled trial assessing the effects of magnesium citrate supplementation and phosphate-binding therapy on arterial stiffness in moderate chronic kidney disease
Authors: Vermeulen Emma A. , Eelderink Coby , Hoekstra Tiny , van Ballegooijen Adriana J. , Raijmakers Pieter , Beulens Joline W. , de Borst Martin H. , Vervloet Marc G. 
Published: September 2022

Abstract
Background
Arterial stiffness and calcification propensity are associated with high cardiovascular risk and increased mortality in chronic kidney disease (CKD). Both magnesium and phosphate are recognized as modulators of vascular calcification and chronic inflammation, both features of CKD that contribute to arterial stiffness. In this paper, we outline the rationale and design of a randomized controlled trial (RCT) investigating whether 24 weeks of oral magnesium supplementation with or without additional phosphate-binding therapy can improve arterial stiffness and calcification propensity in patients with stage 3–4 CKD.

Methods
In this multi-center, placebo-controlled RCT, a total of 180 participants with an estimated glomerular filtration rate of 15 to 50 ml/min/1.73 m2 without phosphate binder therapy will be recruited. During the 24 weeks intervention, participants will be randomized to one of four intervention groups to receive either magnesium citrate (350 mg elemental magnesium/day) or placebo, with or without the addition of the phosphate binder sucroferric oxyhydroxide (1000 mg/day). Primary outcome of the study is the change of arterial stiffness measured by the carotid-femoral pulse wave velocity over 24 weeks. Secondary outcomes include markers of calcification and inflammation, among others calcification propensity (T50) and high-sensitivity C-reactive protein. As explorative endpoints, repeated 18F-FDG and 18F-NaF PET-scans will be performed in a subset of participants (n = 40). Measurements of primary and secondary endpoints are performed at baseline, 12 and 24 weeks.

Discussion
The combined intervention of magnesium citrate supplementation and phosphate-lowering therapy with sucroferric oxyhydroxide, in stage 3–4 CKD patients without overt hyperphosphatemia, aims to modulate the complex and deregulated mineral metabolism leading to vascular calcification and arterial stiffness and to establish to what extent this is mediated by T50 changes. The results of this combined intervention may contribute to future early interventions for CKD patients to reduce the risk of CVD and mortality.

Trial registration
Netherlands Trial Register, NL8252 (registered December 2019), EU clinical Trial Register 2019-001306-23 (registered November 2019).
Sperm DNA methylation alterations from cannabis extract exposure are evident in offspring
Authors: Schrott Rose , Modliszewski Jennifer L. , Hawkey Andrew B. , Grenier Carole , Holloway Zade , Evans Janequia , Pippen Erica , Corcoran David L. , Levin Edward D. , Murphy Susan K. 
Published: September 2022

Abstract
Background
Cannabis legalization is expanding and men are the predominant users. We have limited knowledge about how cannabis impacts sperm and whether the effects are heritable.

Results
Whole genome bisulfite sequencing (WGBS) data were generated for sperm of rats exposed to: (1) cannabis extract (CE) for 28 days, then 56 days of vehicle only (~ one spermatogenic cycle); (2) vehicle for 56 days, then 28 days of CE; or (3) vehicle only. Males were then mated with drug-naïve females to produce F1 offspring from which heart, brain, and sperm tissues underwent analyses. There were 3321 nominally significant differentially methylated CpGs in F0 sperm identified via WGBS with select methylation changes validated via bisulfite pyrosequencing. Significant methylation changes validated in F0 sperm of the exposed males at the gene 2-Phosphoxylose Phosphatase 1 (Pxylp1) were also detectable in their F1 sperm but not in controls. Changes validated in exposed F0 sperm at Metastasis Suppressor 1-Like Protein (Mtss1l) were also present in F1 hippocampal and nucleus accumbens (NAc) of the exposed group compared to controls. For Mtss1l, a significant sex-specific relationship between DNA methylation and gene expression was demonstrated in the F1 NAc. Phenotypically, rats born to CSE-exposed fathers exhibited significant cardiomegaly relative to those born to control fathers.

Conclusions
This is the first characterization of the effect of cannabis exposure on the entirety of the rat sperm methylome. We identified CE-associated methylation changes across the sperm methylome, some of which persisted despite a “washout” period. Select methylation changes validated via bisulfite pyrosequencing, and genes associated with methylation changes were involved in early developmental processes. Preconception CE exposure is associated with detectable changes in offspring DNA methylation that are functionally related to changes in gene expression and cardiomegaly.
These results support that paternal preconception exposure to cannabis can influence offspring outcomes.
Insights into the deriving of rhizosphere microenvironments and its effects on the growth of authentic Angelica sinensis seedlings under continuous monoculture
Authors: Gong Xiaofang , Zhu Ying , Peng Yinan , Guo Zengxiang , Zhou Jianping , Yang Hui , Wang Zhiye 
Published: September 2022

Abstract
Purpose
Continuous monoculture leads to deterioration of soil microenvironment, which can severely threat the quality and efficiency of Angelica sinensis (A. sinensis), especially for seedlings production. However, little attention has been paid to investigate how continuous monocropping affects the growth of A. sinensis seedling, rhizosphere microbial populations, and nutrient status.

Methods
A field experiment consisting of two different planting patterns — raising A. sinensis seedlings in reclamation alpine uncultivated meadow (RW) and 1-year continuous monoculture (CC), was carried out at Min County, Gansu province, China.

Result
The results showed that compared with RW, the growth rate and valid quantity of A. sinensis seedlings were significantly reduced by 195.4% and 36.7% in CC, respectively. Continuous monocropping significantly increased the rhizosphere soil pH value during the growing season, ranging from 6.18 to 7.10, while reducing the content of SOM, total N, and available P and K. Glomalin, AMF spore densities, and the number of actinomycetes, ammonifiers, and azotobacter were also decreased by CC. The CC treatment significantly increased the abundance of fungi. The diversity and richness of bacteria in CC were lower than RW. Furthermore, the composition and structure of bacterial and fungal flora also changed and that the abundance of beneficial bacteria decreased, while the abundance of pathogens increased in CC. Thus, CC appeared to completely upend the relationship between soil nutrient availability and microbial activity.

Conclusion
The results illustrated that continuous monoculture led the flora of bacteria and fungi to changed dramatically, with the abundance of beneficial bacteria decreased and the abundance of harmful microbes, such as Lasiosphaeriaceae, Vishniacozyma, Myrmecridium, and Hypocreales, increased. The function of microbial population has changed from “beneficial bacteria dominated” to “harmful microbes dominant.” We concluded that continuous monoculture significantly reduced the growth and the efficiency of A. sinensis seedlings and deteriorated the rhizosphere soil microenvironment by increasing pH and decreasing nutrient availability, as well as altering the function of interactions between soil nutrients and microbial populations, thereby resulting in an unsuitable microenvironment for A. sinensis seedlings growth.
Review on camel production and marketing status in Ethiopia
Authors: Kena Doyo 
Published: September 2022

Abstract
Pastoralism has been the most productive livelihood option in the dryland of the Horn of Africa although recently its sustainability is becoming challenging. Camel is a livestock species uniquely adapted to the arid and semi-arid areas of the region. Camels are predominantly reared in the drier areas of Ethiopia such as Afar, Ethiopian Somali and the eastern and southern parts of Oromia region. This review is aimed at reviewing the camel population, marketing status, challenges and opportunities related to camel production and marketing in Ethiopia. Official reports on the camel population (1.42 million) underestimate the number of camel populations in Ethiopia while different research reports a higher figure of the camel population up to 4.8 million. However, each report indicated an increasing trend in the camel population. Camel is being adopted by different pastoral groups, in which camel rearing was less customary. The economic importance of the camel over other livestock species is immense, particularly during the harsh seasons due to less decline in its prices and the camel is the most expensive in both pastoral and agro-pastoral areas when compared to other livestock. Camel plays an important role in revenue generation, contributing to the earnings from export. Formal camel export status has shown a flat trend and informal export outweighed the formal one. Despite its ecological and economic importance, the camel has been neglected by researchers and the Ethiopian government. Poor market infrastructure, lack of market information, lack of market-oriented production system, the export ban by many countries and the inconvenience of an export regulatory institutional setting are among the major constraints of camel marketing in Ethiopia. Therefore, policy and development interventions are demanded that recognize the social, economic and ecological importance of camels for pastoral communities and the national economy.
Profile of chimeric RNAs and TMPRSS2-ERG e2e4 isoform in neuroendocrine prostate cancer
Authors: Wang Qiong , Chen Junxiu , Singh Sandeep , Xie Zhongqiu , Qin Fujun , Shi Xinrui , Cornelison Robert , Li Hui , Huang Hai 
Published: September 2022

Abstract
Purpose
Specific gene fusions and their fusion products (chimeric RNA and protein) have served as ideal diagnostic markers and therapeutic targets for cancer. However, few systematic studies for chimeric RNAs have been conducted in neuroendocrine prostate cancer (NEPC). In this study, we explored the landscape of chimeric RNAs in different types of prostate cancer (PCa) cell lines and aimed to identify chimeric RNAs specifically expressed in NEPC.

Methods
To do so, we employed the RNA-seq data of eight prostate related cell lines from Cancer Cell Line Encyclopedia (CCLE) for chimeric RNA identification. Multiple filtering criteria were used and the candidate chimeric RNAs were characterized at multiple levels and from various angles. We then performed experimental validation on all 80 candidates, and focused on the ones that are specific to NEPC. Lastly, we studied the clinical relevance and effect of one chimera in neuroendocrine process.

Results
Out of 80 candidates, 15 were confirmed to be expressed preferentially in NEPC lines. Among them, 13 of the 15 were found to be specifically expressed in NEPC, and four were further validated in another NEPC cell line. Importantly, in silico analysis showed that tumor malignancy may be correlated to the level of these chimeric RNAs. Clinically, the expression of TMPRSS2-ERG (e2e4) was elevated in tumor tissues and indicated poor clinical prognosis, whereas the parental wild type transcripts had no such association. Furthermore, compared to the most frequently detected TMPRSS2-ERG form (e1e4), e2e4 encodes 31 more amino acids and accelerated neuroendocrine process of prostate cancer.

Conclusions
In summary, these findings painted the landscape of chimeric RNA in NEPC and supported the idea that some chimeric RNAs may represent additional biomarkers and/or treatment targets independent of parental gene transcripts.
AMP-activated protein kinase α2 contributes to acute and chronic hyperuricemic nephropathy via renal urate deposition in a mouse model
Authors: Yang Chen , Su Hong-yong , An Ning , Wu Hong-luan , Guo Xiao-yan , Li Zhi-hang , Chen Xiao-cui , Zhu Shao-ping , Wu Dan , Li Hui-yuan , Pan Qing-jun , Liang Dong , Liu Hua-feng 
Published: September 2022

AbstractHyperuricemia can induce acute and chronic kidney damage, but the pathological mechanism remains unclear. The potential role of AMP-activated protein kinase (AMPK) α2 in hyperuricemia-induced renal injury was investigated in this study. Acute and chronic hyperuricemic nephropathy was induced by administering intraperitoneal injections of uric acid and oxonic acid to AMPK α2 knockout and wild-type mice. Changes in renal function, histopathology, inflammatory cell infiltration, renal interstitial fibrosis, and urate deposition were analyzed. In both acute and chronic hyperuricemic nephropathy mouse models, knockout of AMPK α2 significantly reduced serum creatinine levels and renal pathological changes. The tubular expression of kidney injury molecule-1 was also reduced in hyperuricemic nephropathy mice deficient in AMPK α2. In addition, knockout of AMPK α2 significantly suppressed the infiltration of renal macrophages and progression of renal interstitial fibrosis in mice with chronic hyperuricemic nephropathy. Knockout of AMPK α2 reduced renal urate crystal deposition, probably through increasing the expression of the uric acid transporter, multidrug resistance protein 4. In summary, AMPK α2 is involved in acute and chronic hyperuricemia-induced kidney injury and may be associated with increased urate crystal deposition in the kidney.
Comparison of malignancy and spatial distribution between latent and clinical prostate cancer: an 8-year biopsy study
Authors: Zhen Liang , Zhien Zhou , Hanzi Huang , Xingcheng Wu , Yu Xiao , Wenze Wang , Yuzhi Zuo , Yuliang Chen , Yi Zhou , Weigang Yan 
Published: September 2022

Abstract
Background
Current prostate cancer (PCa) screening may detect nonprogressive lesion, leading to overdiagnosis and overtreatment. The purpose of the present study is to investigate whether the tumor pathological origin of latent prostate cancer (lPCa) and clinical prostate cancer (cPCa) are consistent, and to verify the current clinically significant prostate cancer criteria.

Methods
Prostate specimens were obtained from postmortem autopsy between 2014 and 2021 and patients who went through radical prostatectomy from 2013 to 2021. The pathological characteristics and spatial distribution of the lPCa group and cPCa group were compared and analyzed through SPSS software with P < 0.05 representing statistical significant.

Results
In lPCa group, a total of 45 tumor lesions from 24 lPCa cases were included, 54.2% of lPCa patients were ISUP ≥ 2, 12.5% had tumor volume ≥ 0.5 ml, and 16.7% had extraprostatic extension (EPE). In cPCa group, there were a total of 429 tumor lesions in 126 cases, 92.1% of cPCa patients were ISUP ≥ 2, and 82.5% had tumor volume of ≥ 0.5 ml. 36.3% had EPE. LPCa and cPCa have the same spatial distribution characteristics, and no significant difference was detected between the anterior and posterior zone. Peripheral zone tumors were significantly more common than transitional zone tumors. Tumors in apical 1/3 and middle 1/3 were significantly more common than basal 1/3.

Conclusion
The malignancy of cPCa is significantly higher than that of lPCa, and the spatial distribution of cPCa and lPCa is consistent. ISUP grade 2 is not sufficient to determine clinical significance of tumor.
Need to go further: using INLA to discover limits and chances of burglaries’ spatiotemporal prediction in heterogeneous environments
Authors: Boqué Pere , Saez Marc , Serra Laura 
Published: September 2022

AbstractNear-repeat victimization patterns have made predictive models for burglaries possible. While the models have been implemented in different countries, the results obtained have not always been in line with initial expectations; to the point where their real effectiveness has been called into question. The ability to predict crime to improve preventive policing strategies is still under study. This study aims to discover the limitations to and the success of the models that attempt to predict burglaries based on spatiotemporal patterns of the risk of break-ins spreading in geographic proximity to the initial break-ins. A spatiotemporal log-Gaussian Cox process is contemplated to model the generic near-repeat victimization scenario and adjusted using the Integrated Nested Laplace Approximation (INLA) methodology. This approach is highly suitable for studying and describing the near-repeat phenomenon. However, predictions obtained with INLA are quite monotonous, of low variability and do not reproduce well the local and short-term dynamics of burglaries for predictive purposes. The conclusion is that predictive models cannot be restricted exclusively to distance decay risk, but they must be designed to detect other types of spatiotemporal patterns which, among other possibilities, open up the possibility of correlating distant events and clusters. Although other studies have already highlighted this problem, the proposal here is to go one step further and clearly extend the near-repeat spatial patterns to achieve better prediction results.