bluuebunny/crossref_metadata_2025_split huggingface dataset:
CRNDE acts as an epigenetic modulator of the p300/YY1 complex to promote HCC progression and therapeutic resistance
Authors: Liu Yu-Chin , Lin Yang-Hsiang , Chi Hsiang-Cheng , Huang Po-Shuan , Liao Chia-Jung , Liou Yu-Syuan , Lin Chiao-Chun , Yu Chia-Jung , Yeh Chau-Ting , Huang Ya-Hui , Lin Kwang-Huei 
Published: August 2022

Abstract
Background
Hepatocellular carcinoma (HCC) is one of the most common primary liver malignancies worldwide. The long-term prognosis for HCC remains extremely poor, with drug resistance being the major underlying cause of recurrence and mortality. The lncRNA colorectal neoplasia differentially expressed (CRNDE) is an epigenetic mediator and plays an important role to drive proliferation and drug resistance in HCC. However, CRNDE as an epigenetic regulator with influences sorafenib resistance in HCC is unclear. Thus, we explore the potential of targeting the CRNDE/p300/YY1 axis as a novel therapeutic strategy to overcome sorafenib resistance of HCC.

Method
Detection of the expression level of CRNDE and EGFR in clinical specimens of HCC. CRNDE, EGFR, p300, and YY1expression were altered in HCC cells through transfection with different plasmids, and cell proliferation, migration, invasion, and sorafenib resistance were subsequently observed. Immunoprecipitation, chromatin immunoprecipitation, re-chromatin immunoprecipitation, site-directed mutagenesis, RNA Immunoprecipitation, immune fluorescence, qRT-PCR, and western blotting were performed to uncover the mechanisms of CRNDE regulation. The xenograft nude mice model was used to investigate the tumor growth and sorafenib resistance.

Results
In this study, we showed that CRNDE expression is significantly positively correlated with that of epidermal growth factor receptor (EGFR) in clinical specimens of HCC and induces proliferation and sorafenib resistance of HCC via EGFR-mediated signaling. Mechanistically, CRNDE stabilized the p300/YY1 complex at the EGFR promoter and simultaneously enhanced histone H3K9 and H3K27 acetylation, which serve as markers of relaxed chromatin. EGFR was positively upregulated by the epigenetic complex, p300/YY1, in a manner dependent on CRNDE expression, leading to enhanced tumor cell proliferation and sorafenib resistance. Furthermore, C646, a p300 inhibitor, suppressed EGFR transcriptional activity by decreasing chromatin relaxation and YY1 binding, which effectively reduced proliferation/sorafenib resistance and prolonged overall survival.

Conclusion
Our collective findings support the potential of targeting the CRNDE/p300/YY1 axis as a novel therapeutic strategy to overcome sorafenib resistance of HCC.
Integrated single-cell RNA-seq and DNA methylation reveal the effects of air pollution in patients with recurrent spontaneous abortion
Authors: Zhu Weiqiang , Gu Yan , Li Min , Zhang Zhaofeng , Liu Junwei , Mao Yanyan , Zhu Qianxi , Zhao Lin , Shen Yupei , Chen Fujia , Xia Lingjin , He Lin , Du Jing 
Published: August 2022

Abstract
Background
Maternal air pollutants exposure is associated with a number of adverse pregnancy outcomes, including recurrent spontaneous abortion (RSA). However, the underlying mechanisms are still unknown. The present study aimed to understand the mechanism of RSA and its relationship with air pollution exposure. We compared data of decidual tissue from individuals with induced abortions and those with RSA by bulk RNA sequencing (RNA-seq), reduced representation bisulfite sequencing (RRBS), and single-cell RNA sequencing (scRNA-seq). Differentially expressed genes (DEGs) were verified using RT-qPCR and pyrosequencing. A logistic regression model was used to investigate the association between air pollutants exposure and RSA.

Results
We identified 98 DEGs with aberrant methylation by overlapping the RRBS and RNA-seq data. Nineteen immune cell subsets were identified. Compared with normal controls, NK cells and macrophages accounted for different proportions in the decidua of patients with RSA. We observed that the methylation and expression of IGF2BP1 were different between patients with RSA and controls. Furthermore, we observed significant positive associations between maternal air pollutants exposure during the year prior to pregnancy and in early pregnancy and the risk of RSA. Mediation analyses suggested that 24.5% of the effects of air pollution on the risk of RSA were mediated through IGF2BP1 methylation.

Conclusion
These findings reveal a comprehensive cellular and molecular mechanism of RSA and suggest that air pollution might cause pregnancy loss by affecting the methylation level of the IGF2BP1 promoter.
CircTRRAP (hsa_circ_0081234) participates in prostate cancer progression and glycolysis by HOXA1 via functioning as a miR-515-5p sponge
Authors: Li Zhihui , Guan Yawei , Teng Jingfei , Jia Zhuomin , Zhang Guohui , Ai Xing 
Published: August 2022

AbstractDysregulated circular RNAs (circRNAs) are implicated in prostate cancer (PCa) progression. Hsa_circ_0081234 (circTRRAP) has been revealed as a facilitator in PCa, but the mechanisms associated with circTRRAP in PCa progression are largely unclear. The present study was to explore the regulatory mechanism of circTRRAP-mediated PCa progression. A total of 50 PCa tissues and normal tissues were collected. RNA levels of circTRRAP, microRNA (miR)-515-5p and homeobox A1 (HOXA1) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. Cell viability, proliferation, migration, and invasion were estimated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide, 5-ethynyl-2ʹ-deoxyuridine (EdU) and transwell assays, respectively. Cell glycolysis was assessed by measuring glucose uptake and lactate production. The target interaction between circTRRAP or HOXA1 and miR-515-5p was investigated by the dual-luciferase reporter assay. We observed the overt upregulaiton of circTRRAP in PCa samples and cells. Silencing of circTRRAP lowered tumor growth in vivo and restrained PCa cell viability, proliferation, migration, invasion, and glycolysis in vitro. miR-515-5p was negatively regulated by circTRRAP and its deficiency reversed the inhibiting effects of circTRRAP knockdown on PCa cell malignancy and glycolysis. HOXA1 was confirmed as a miR-515-5p target and miR-515-5p overexpression lessened PCa cell malignancy and glycolysis by decreasing HOXA1 expression. Importantly, circTRRAP mediated HOXA1 expression by functioning as a miR-515-5p sponge. In conclusion, circTRRAP took part in PCa progression and glycolysis through mediating the miR-515-5p/HOXA1 axis, suggesting that circTRRAP can serve as a potential therapeutic target for PCa patients.
Biogeographical survey of soil microbiomes across sub-Saharan Africa: structure, drivers, and predicted climate-driven changes
Authors: Cowan DA , Lebre PH , Amon CER , Becker RW , Boga HI , Boulangé A , Chiyaka TL , Coetzee T , de Jager PC , Dikinya O , Eckardt F , Greve M , Harris MA , Hopkins DW , Houngnandan HB , Houngnandan P , Jordaan K , Kaimoyo E , Kambura AK , Kamgan-Nkuekam G , Makhalanyane TP , Maggs-Kölling G , Marais E , Mondlane H , Nghalipo E , Olivier BW , Ortiz M , Pertierra LR , Ramond J-B , Seely M , Sithole-Niang I , Valverde A , Varliero G , Vikram S , Wall DH , Zeze A 
Published: August 2022

AbstractBackgroundTop-soil microbiomes make a vital contribution to the Earth’s ecology and harbor an extraordinarily high biodiversity. They are also key players in many ecosystem services, particularly in arid regions of the globe such as the African continent. While several recent studies have documented patterns in global soil microbial ecology, these are largely biased towards widely studied regions and rely on models to interpolate the microbial diversity of other regions where there is low data coverage. This is the case for sub-Saharan Africa, where the number of regional microbial studies is very low in comparison to other continents.ResultsThe aim of this study was to conduct an extensive biogeographical survey of sub-Saharan Africa’s top-soil microbiomes, with a specific focus on investigating the environmental drivers of microbial ecology across the region. In this study, we sampled 810 sample sites across 9 sub-Saharan African countries and used taxonomic barcoding to profile the microbial ecology of these regions. Our results showed that the sub-Saharan nations included in the study harbor qualitatively distinguishable soil microbiomes. In addition, using soil chemistry and climatic data extracted from the same sites, we demonstrated that the top-soil microbiome is shaped by a broad range of environmental factors, most notably pH, precipitation, and temperature. Through the use of structural equation modeling, we also developed a model to predict how soil microbial biodiversity in sub-Saharan Africa might be affected by future climate change scenarios. This model predicted that the soil microbial biodiversity of countries such as Kenya will be negatively affected by increased temperatures and decreased precipitation, while the fungal biodiversity of Benin will benefit from the increase in annual precipitation.ConclusionThis study represents the most extensive biogeographical survey of sub-Saharan top-soil microbiomes to date. Importantly, this study has allowed us to identify countries in sub-Saharan Africa that might be particularly vulnerable to losses in soil microbial ecology and productivity due to climate change. Considering the reliance of many economies in the region on rain-fed agriculture, this study provides crucial information to support conservation efforts in the countries that will be most heavily impacted by climate change.
Preventing frailty with the support of a home-monitoring and communication platform among older adults—a study protocol for a randomised-controlled pilot study in Sweden
Authors: Teriö Minna , Pérez-Rodríguez Rodrigo , Guevara Guevara Tania , Valdes-Aragonés Myriam , Kornevs Maksims , Bjälevik-Chronan Sanna , Taloyan Marina , Meijer Sebastiaan , Guidetti Susanne 
Published: August 2022

Abstract
Background
POSITIVE (i.e. maintaining and imPrOving the intrinSIc capaciTy Involving primary care and caregiVErs) is a new intervention program consisting of home-monitoring equipment and a communication platform to support treatment of frailty symptoms initially in primary care and prevent disability in older adults.

Methods
The primary objectives are to estimate the potential efficacy of the POSITIVE system on improving frailty in at least one point in Fried’s criteria and five points in Frailty Trait Scale. The secondary objectives are to (A) assess the recruitment, retention, drop-out rates, compliance with the intervention and the intervention mechanisms of impact; (B) evaluate the usability and acceptance of the POSITIVE system, and to get estimations on; (C) the potential efficacy of the intervention on improving the participants’ physical performance, cognitive functions, mood, independency level in activities in daily living, the impact on quality of life and number of falls during the follow-up period; (D) the impact on the caregiver quality of life and caregiver burden; and (E) on the consumption of health care resources, participants’ perception of health and level of care received, and healthcare professionals’ workload and satisfaction.
A randomised controlled, assessor-blinded pilot study design recruiting from a primary care centre in Stockholm Region will be conducted. Fifty older adults identified as pre-frail or frail will be randomised into a control or an intervention group. Both groups will receive a medical review, nutritional recommendations and Vivifrail physical exercise program. The intervention group will receive the POSITIVE-system including a tablet, the POSITIVE application and portable measurement devices. The participants receiving the POSITIVE program will be monitored remotely by a primary care nurse during a 6-month follow-up. Data will be collected at baseline, 3 and 6 months into the intervention though the platform, standardised assessments and surveys. A process evaluation as per Medical Research Council guidance will be conducted after the 6-month follow-up period.

Discussion
The implications of the study are to provide estimations on the potential efficacy of the POSITIVE system in improving frailty among older adults and to provide relevant data to inform powered studies of potential efficacy and effectiveness, as well as to inform about the feasibility of the current study design.

Trial registration
ClinicalTrials.gov. Registration number: NCT04592146. October 19, 2020.
Competition vs cooperation: renewable energy investment under cap-and-trade mechanisms
Authors: Chen Wei , Chen Jing , Ma Yongkai 
Published: August 2022

AbstractThis paper explores the incentives of investment in renewable energy of two utility firms who compete or cooperate under either a cap-and-trade grandfathering mechanism (GM) or benchmarking mechanism (BM). We find that utility firms will invest in renewable energy more under BM than under GM, in both competitive and cooperative markets, and they will invest more in a competitive market than in a cooperative market, under either GM or BM. Furthermore, utility firms will produce more electricity and generate more total carbon emissions under BM than under GM. The profits of two firms, however, are higher in cooperative market than in competitive market. The government will benefit from implementing a BM to encourage utility firms to invest in renewable energy in a competing market.
Long-Term Efficacy and Safety of Luspatercept for Anemia Treatment in Patients With Lower-Risk Myelodysplastic Syndromes: The Phase II PACE-MDS Study
Authors: Platzbecker Uwe , Götze Katharina S. , Kiewe Philipp , Germing Ulrich , Mayer Karin , Radsak Markus , Wolff Thomas , Chromik Joerg , Sockel Katja , Oelschlägel Uta , Haase Detlef , Illmer Thomas , Al-Ali Haifa Kathrin , Silling Gerda , Reynolds Joseph G. , Zhang Xiaosha , Attie Kenneth M. , Shetty Jeevan K. , Giagounidis Aristoteles 
Published: August 2022

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co‐primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. Luspatercept has high clinical activity in patients with transfusion-dependent lower-risk myelodysplastic syndromes (LR-MDS) and ring sideroblasts (RS) relapsed or refractory to erythropoietin. We report long-term luspatercept safety and efficacy in 108 patients with LR-MDS in the PACE-MDS study, including 44 non-RS and 34 non–transfusion-dependent or previously untreated patients. The primary end point was safety. Secondary end points included rates of hematologic improvement (HI) erythroid (HI-E), HI neutrophil, and HI platelet. Exploratory end points included erythropoiesis biomarker quantitation and mutation data. Median duration of luspatercept exposure was 315 days (range, 21-1,934 days). No new safety signals emerged. HI-E was observed in 53.7% of patients, including 36.4% of non-RS and 70.6% of non–transfusion-dependent patients. HI neutrophil and HI platelet were observed in 33.3% and 9.5% of patients, respectively. An almost three-fold increase in bone marrow late to early progenitor cell ratio accompanied HI-E response, irrespective of RS status. Lower baseline erythropoietin levels in non-RS patients (69.6 v 623.3 IU/L; P = .0077) and higher late to early erythroid progenitor cell ratio (10.44 v 4.48; P = .0106) in RS patients were associated with HI-E. This study highlights luspatercept's effects across LR-MDS subtypes, including untreated MDS-RS, serving as a platform for future trials.
The Terrible We
Authors: Awkward-Rich Cameron 
Published: August 2022

In The Terrible We Cameron Awkward-Rich thinks with the bad feelings and mad habits of thought that persist in both transphobic discourse and trans cultural production. Observing that trans studies was founded on a split from and disavowal of madness, illness, and disability, Awkward-Rich argues for and models a trans criticism that works against this disavowal. By tracing the coproduction of the categories of disabled and transgender in the United States at the turn of the twentieth century and analyzing transmasculine literature and theory by Eli Clare, Elliott DeLine, Dylan Scholinski, and others, Awkward-Rich suggests that thinking with maladjustment might provide new perspectives on the impasses arising from the conflicted relationships among trans, feminist, and queer. In so doing, he demonstrates that rather than only impeding or confining trans life, thought, and creativity, forms of maladjustment have also been and will continue to be central to their development.
Duke University Press Scholars of Color First Book Award recipient
Advanced practice providers versus medical residents as leaders of rapid response teams: A 12-month retrospective analysis
Authors: Kreeftenberg Herman G. , De Bie Ashley J. R. , Mestrom Eveline H. J. , Bindels Alexander J. G. H. , van der Voort Peter H. J. 
Published: August 2022

Purpose
In a time of worldwide physician shortages, the advanced practice providers (APPs) might be a good alternative for physicians as the leaders of a rapid response team. This retrospective analysis aimed to establish whether the performance of APP-led rapid response teams is comparable to the performance of rapid response teams led by a medical resident of the ICU.

Material and methods
In a retrospective single-center cohort study, the electronic medical record of a tertiary hospital was queried during a 12-months period to identify patients who had been visited by our rapid response team. Patient- and process-related outcomes of interventions of rapid response teams led by an APP were compared with those of teams led by a medical resident using various parameters, including the MAELOR tool, which measures the performance of a rapid response team.

Results
In total, 179 responses of the APP-led teams were analyzed, versus 275 responses of the teams led by a resident. Per APP, twice as many calls were handled than per resident. Interventions of teams led by APPs, and residents did not differ in number of admissions (p = 0.87), mortality (p = 0.8), early warning scores (p = 0.2) or MAELOR tool triggering (p = 0.19). Both groups scored equally on time to admission (p = 0.67) or time until any performed intervention.

Conclusion
This retrospective analysis showed that the quality of APP-led rapid response teams was similar to the quality of teams led by a resident. These findings need to be confirmed by prospective studies with balanced outcome parameters.
Measuring socioeconomic inequalities in prenatal HIV test service uptake for prevention of mother to child transmission of HIV in East Africa: A decomposition analysis
Authors: Astawesegn Feleke Hailemichael , Conroy Elizabeth , Mannan Haider , Stulz Virginia 
Published: August 2022

Background
Despite efforts made towards the elimination of mother-to-child HIV transmission, socioeconomic inequality in prenatal HIV test uptake in East Africa is not well understood. Therefore, this study aimed at measuring socioeconomic inequalities in prenatal HIV test uptake and explaining its main determinants in East Africa

Method
We analysed a total weighted sample of 45,476 women aged 15–49 years who birthed in the two years preceding the survey. The study used the most recent DHS data from ten East African countries (Burundi, Comoros, Ethiopia, Kenya, Malawi, Mozambique, Rwanda, Uganda, Zambia, and Zimbabwe). The socioeconomic inequality in prenatal HIV test uptake was measured by the concentration index and illustrated by the concentration curve. Then, regression based Erreygers decomposition method was applied to quantify the contribution of socioeconomic factors to inequalities of prenatal HIV test uptake in East Africa.

Results
The concentration index for prenatal HIV test uptake indicates that utilization of this service was concentrated in higher socio-economic groups with it being 15.94% higher among these groups in entire East Africa (p <0.001), 40.33% higher in Ethiopia (p <0.001) which was the highest and only 1.87% higher in Rwanda (p <0.01) which was the lowest. The decomposition analysis revealed that household wealth index (38.99%) followed by maternal education (13.69%), place of residence (11.78%), partner education (8.24%), watching television (7.32%), listening to the radio (7.11%) and reading newsletters (2.90%) made the largest contribution to socioeconomic inequality in prenatal HIV test in East Africa.

Conclusion
In this study, pro-rich inequality in the utilization of prenatal HIV tests was evident. The decomposition analysis findings suggest that policymakers should focus on improving household wealth, educational attainment, and awareness of mother-to-child transmission of HIV (MTCT) through various media outlets targeting disadvantaged sub-groups.
The comparative study of antimicrobial activities of the composite mixture of

Gongronema

latifolium and

Pterocarpus

Soyauxii on

Bacillus

cereusand

Escherichia

coli
Authors: Michael Victor 
Published: August 2022

The antimicrobial activity of the composite mixture of crude, cold water, hot water, and hot ethanolic extracts of the leaves of
Gongronem

latifolium and
Pterocarpus

soyauxii on
Bacillus

cereus and
Escherichia

coli were comparatively studied.
Extract of the two plants show no activity against the test organisms except for the hot ethanolic extracts which were active against the organisms with mean maximum inhibitory zone of 4.67mm and 2mm at 80% concentration of
Pterocarpus

soyauxii on
Bacillus

cereus sand
Echerichia

coli respectively while 1.8mm and 2mm at 100% concentration of
Gongrenema

latifoium on both
Bacillus

cereus and
Escherichia

coli. The activities of the composite mixture of the plants at these concentrations were 3.17mm for
bacillus

cereus and 1.83mm for
Escherichia

coli. The results obtained indicated that the composite mixture of the plants were antagonistic on
Bacillus

cereus while showing indifference on
Escherichia

coli.