bluuebunny/crossref_metadata_2025_split huggingface dataset:
β-Arrestin2-biased Drd2 agonist UNC9995 alleviates astrocyte inflammatory injury via interaction between β-arrestin2 and STAT3 in mouse model of depression
Authors: Liu Yang , Song Nanshan , Yao Hang , Jiang Siyuan , Wang Yueping , Zheng Ying , Zhou Yuanzhang , Ding Jianhua , Hu Gang , Lu Ming 
Published: October 2022

Abstract
Background
Major depressive disorder (MDD) is a prevalent and devastating psychiatric illness. Unfortunately, the current therapeutic practice, generally depending on the serotonergic system for drug treatment is unsatisfactory and shows intractable side effects. Multiple evidence suggests that dopamine (DA) and dopaminergic signals associated with neuroinflammation are highly involved in the pathophysiology of depression as well as in the mechanism of antidepressant drugs, which is still in the early stage of study and well worthy of investigation.

Methods
We established two chronic stress models, including chronic unpredictable mild stress (CUMS), and chronic social defeat stress (CSDS), to complementarily recapitulate depression-like behaviors. Then, hippocampal tissues were used to detect inflammation-related molecules and signaling pathways. Pathological changes in depressive mouse hippocampal astrocytes were examined by RNA sequencing. After confirming the dopamine receptor 2 (Drd2)/β-arrestin2 signaling changes in the depressive mice brain, we then established the depressive mouse model using the β-arrestin2 knockout mice or administrating the β-arrestin2-biased Drd2 agonist to investigate the roles. Label-free mass spectrometry was used to identify the β-arrestin2-binding proteins as the underlying mechanisms. We modeled neuroinflammation with interleukin-6 (IL-6) and corticosterone treatment and characterized astrocytes using multiple methods including cell viability assay, flow cytometry, and confocal immunofluorescence.

Results
Drd2-biased β-arrestin2 pathway is significantly changed in the progression of depression, and genetic deletion of β-arrestin2 aggravates neuroinflammation and depressive-like phenotypes. Mechanistically, astrocytic β-arrestin2 retains STAT3 in the cytoplasm by structural combination with STAT3, therefore, inhibiting the JAK–STAT3 pathway-mediated inflammatory activation. Furtherly, pharmacological activation of Drd2/β-arrestin2 pathway by UNC9995 abolishes the inflammation-induced loss of astrocytes and ameliorates depressive-like behaviors in mouse model for depression.

Conclusions
Drd2/β-arrestin2 pathway is a potential therapeutic target for depression and β-arrestin2-biased Drd2 agonist UNC9995 is identified as a potential anti-depressant strategy for preventing astrocytic dysfunctions and relieving neuropathological manifestations in mouse model for depression, which provides insights for the therapy of depression.
Combination of long-term 13CO2 labeling and isotopolog profiling allows turnover analysis of photosynthetic pigments in Arabidopsis leaves
Authors: Banh Anh Thi-Mai , Thiele Björn , Chlubek Antonia , Hombach Thomas , Kleist Einhard , Matsubara Shizue 
Published: October 2022

Abstract
Background
Living cells maintain and adjust structural and functional integrity by continual synthesis and degradation of metabolites and macromolecules. The maintenance and adjustment of thylakoid membrane involve turnover of photosynthetic pigments along with subunits of protein complexes. Quantifying their turnover is essential to understand the mechanisms of homeostasis and long-term acclimation of photosynthetic apparatus. Here we report methods combining whole-plant long-term 13CO2 labeling and liquid chromatography - mass spectrometry (LC–MS) analysis to determine the size of non-labeled population (NLP) of carotenoids and chlorophylls (Chl) in leaf pigment extracts of partially 13C-labeled plants.

Results
The labeling chamber enabled parallel 13CO2 labeling of up to 15 plants of Arabidopsis thaliana with real-time environmental monitoring ([CO2], light intensity, temperature, relative air humidity and pressure) and recording. No significant difference in growth or photosynthetic pigment composition was found in leaves after 7-d exposure to normal CO2 (~ 400 ppm) or 13CO2 in the labeling chamber, or in ambient air outside the labeling chamber (control). Following chromatographic separation of the pigments and mass peak assignment by high-resolution Fourier-transform ion cyclotron resonance MS, mass spectra of photosynthetic pigments were analyzed by triple quadrupole MS to calculate NLP. The size of NLP remaining after the 7-d 13CO2 labeling was ~ 10.3% and ~ 11.5% for all-trans- and 9-cis-β-carotene, ~ 21.9% for lutein, ~ 18.8% for Chl a and 33.6% for Chl b, highlighting non-uniform turnover of these pigments in thylakoids. Comparable results were obtained in all replicate plants of the 13CO2 labeling experiment except for three that were showing anthocyanin accumulation and growth impairment due to insufficient water supply (leading to stomatal closure and less 13C incorporation).

Conclusions
Our methods allow 13CO2 labeling and estimation of NLP for photosynthetic pigments with high reproducibility despite potential variations in [13CO2] between the experiments. The results indicate distinct turnover rates of carotenoids and Chls in thylakoid membrane, which can be investigated in the future by time course experiments. Since 13C enrichment can be measured in a range of compounds, long-term 13CO2 labeling chamber, in combination with appropriate MS methods, facilitates turnover analysis of various metabolites and macromolecules in plants on a time scale of hours to days.
Randomized controlled trials in de-implementation research: a systematic scoping review
Authors: Raudasoja Aleksi J. , Falkenbach Petra , Vernooij Robin W. M. , Mustonen Jussi M. J. , Agarwal Arnav , Aoki Yoshitaka , Blanker Marco H. , Cartwright Rufus , Garcia-Perdomo Herney A. , Kilpeläinen Tuomas P. , Lainiala Olli , Lamberg Tiina , Nevalainen Olli P. O. , Raittio Eero , Richard Patrick O. , Violette Philippe D. , Komulainen Jorma , Sipilä Raija , Tikkinen Kari A. O. 
Published: October 2022

Abstract
Background
Healthcare costs are rising, and a substantial proportion of medical care is of little value. De-implementation of low-value practices is important for improving overall health outcomes and reducing costs. We aimed to identify and synthesize randomized controlled trials (RCTs) on de-implementation interventions and to provide guidance to improve future research.

Methods
MEDLINE and Scopus up to May 24, 2021, for individual and cluster RCTs comparing de-implementation interventions to usual care, another intervention, or placebo. We applied independent duplicate assessment of eligibility, study characteristics, outcomes, intervention categories, implementation theories, and risk of bias.

Results
Of the 227 eligible trials, 145 (64%) were cluster randomized trials (median 24 clusters; median follow-up time 305 days), and 82 (36%) were individually randomized trials (median follow-up time 274 days). Of the trials, 118 (52%) were published after 2010, 149 (66%) were conducted in a primary care setting, 163 (72%) aimed to reduce the use of drug treatment, 194 (85%) measured the total volume of care, and 64 (28%) low-value care use as outcomes. Of the trials, 48 (21%) described a theoretical basis for the intervention, and 40 (18%) had the study tailored by context-specific factors. Of the de-implementation interventions, 193 (85%) were targeted at physicians, 115 (51%) tested educational sessions, and 152 (67%) multicomponent interventions. Missing data led to high risk of bias in 137 (60%) trials, followed by baseline imbalances in 99 (44%), and deficiencies in allocation concealment in 56 (25%).

Conclusions
De-implementation trials were mainly conducted in primary care and typically aimed to reduce low-value drug treatments. Limitations of current de-implementation research may have led to unreliable effect estimates and decreased clinical applicability of studied de-implementation strategies. We identified potential research gaps, including de-implementation in secondary and tertiary care settings, and interventions targeted at other than physicians. Future trials could be improved by favoring simpler intervention designs, better control of potential confounders, larger number of clusters in cluster trials, considering context-specific factors when planning the intervention (tailoring), and using a theoretical basis in intervention design.

Registration
OSF Open Science Framework hk4b2
Prediction model for delirium in patients with cardiovascular surgery: development and validation
Authors: Xu Yanghui , Meng Yunjiao , Qian Xuan , Wu Honglei , Liu Yanmei , Ji Peipei , Chen Honglin 
Published: October 2022

Abstract
Background
The aim of this study was to construct a nomogram model for discriminating the risk of delirium in patients undergoing cardiovascular surgery.

Methods
From January 2017 to June 2020, we collected data from 838 patients who underwent cardiovascular surgery at the Affiliated Hospital of Nantong University. Patients were randomly divided into a training set and a validation set at a 5:5 ratio. A nomogram model was established based on logistic regression. Discrimination and calibration were used to evaluate the predictive performance of the model.

Results
The incidence of delirium was 48.3%. A total of 389 patients were in the modelling group, and 449 patients were in the verification group. Logistic regression analysis showed that CPB duration (OR $$=$$
=
1.004, 95% CI: 1.001–1.008, $$P=$$

P
=

0.018), postoperative serum sodium (OR $$=$$
=
1.112, 95% CI: 1.049–1.178, $$P<$$

P
<

0.001), age (OR $$=$$
=
1.027, 95% CI: 1.006–1.048, $$P=$$

P
=

0.011), and postoperative MV (OR $$=$$
=
1.019, 95% CI: 1.008–1.030, $$P<$$

P
<

0.001) were independent risk factors. The results showed that AUC$$^\text {ROC}$$

ROC

was 0.712 and that the 95% CI was 0.661–0.762. The Hosmer-Lemeshow goodness of fit test showed that the predicted results of the model were in good agreement with the actual situation ($$\chi ^{2}=$$

χ
2

=

6.200, $$P=$$

P
=

0.625). The results of verification showed that the AUC$$^\text {ROC}$$

ROC

was 0.705, and the 95% CI was 0.657–0.752. The Hosmer-Lemeshow goodness of fit test results were $$\chi ^{2}=$$

χ
2

=

8.653 and $$P=$$

P
=

0.372, indicating that the predictive effect of the model is good.

Conclusions
The establishment of the model provides accurate and objective assessment tools for medical staff to start preventing postoperative delirium in a purposeful and focused manner when a patient enters the CSICU after surgery.
Inflammatory aneurysm of ascending aorta and left anterior descending artery
Authors: Stella Amanda , Tuluca Alexandra , Arce Anastasia , Samuels Louis 
Published: October 2022

Abstract
Background
Inflammatory aortic aneurysms represent less than 5% of ascending aortic aneurysms and are mostly diagnosed intraoperatively. Furthermore, to our knowledge, a case of an accompanying inflammatory LAD aneurysm has not been previously reported.

Case presentation
We report an unusual case of a 42-year-old female with a symptomatic inflammatory aneurysm of the ascending aorta and the LAD. The patient underwent successful resection and replacement of the aneurysm as well as bypass of the LAD.

Conclusions
The underlying etiology of severe inflammatory ascending aortic aneurysms in a previously healthy individual remains unknown. The pre-operative diagnosis is difficult to obtain as it does not have a characteristic appearance on currently available imaging modalities.
Stents versus bypass surgery: 3-year mortality risk of patients with coronary interventions aged 50+ in Germany
Authors: Nestler Sophia , Kreft Daniel , Donndorf Peter , Ince Hüseyin , Doblhammer Gabriele 
Published: October 2022

Abstract
Objectives
Due to demographic aging, the prevalence of coronary artery disease (CAD) is expected to increase in the future, resulting in a growing demand for stent and bypass interventions. This study aims to investigate the mortality risk of patients following conventional coronary artery bypass grafting (CABG) or endovascular procedure by the implantation of bare-metal stents (BMS) or drug-eluting stents (DES).

Methods
Based on a random sample of 250,000 members of Germany’s largest health insurance ‘Allgemeine Ortskrankenkassen’ (AOK) from 2004 to 2015, incident CAD patients were analyzed by Cox Proportional-Hazard models. Risk adjustment was made for sex, age, other cardiac diseases, non-cardiovascular comorbidities and years since intervention. Due to later admission of DES and thus a shorter observation time, mortality was examined for 3 years since the intervention.

Results
BMS represented the most frequent procedure (48%). We found similar proportions of CABG (19%) and DES interventions (23%). After risk adjustment, the models showed a 21% (p = 0.004) lower mortality risk of patients with DES and also a 21% (p = 0.002) lower mortality risk of CABG patients compared to persons with BMS.

Conclusion
Based on a large-scale dataset, our study demonstrated survival advantages of CABG and DES interventions over BMS, with no differences between the DES and CABG groups. The results help to assess the risks of coronary interventions. Aspects of quality of life, severity of postoperative physical limitations, duration of rehabilitation, patients’ preferences, and aspects of cost-effectiveness for hospitals and society should be further considered.

Graphical abstract
Required displacement factors for evaluating and comparing climate impacts of intensive and extensive forestry in Germany
Authors: Christian Buschbeck , Stefan Pauliuk 
Published: October 2022

Abstract
Background
Forestry plays a major role in climate change mitigation. However, which intensity of logging is best suited for that task remains controversial. We contribute to the debate by quantitatively analyzing three different forest management scenarios in Germany—a baseline scenario which represents a continuation of current forest management practice as well as an intensive and an extensive logging scenario. We assess whether increased carbon storage in wood products and substitution of other emission-intensive materials can offset reduced carbon stocks in the forest due to increased harvesting. For that, we calculate annual required displacement factors (RDF)—a dimensionless quantity that indicates the minimal displacement factor (DF) so that intensive forestry outperforms extensive forestry from a climate perspective.

Results
If the intensive forest management scenario is included in the comparison, the RDF starts off with relatively high values (1 to 1.5) but declines over time and eventually even reaches negative values. Comparing the extensive scenario to a baseline yields RDF values between 0.1 and 0.9 with a slightly increasing trend. Compared to RDFs, expected future DFs are too low to favour the intensive forestry scenario and too high to favour the extensive forestry scenario, during the first 25 years of the modeling period. However, towards the end of the modeling period, the relationship between DFs and RDF is turned around in both comparisons. In the comparison between intensive and extensive forest management RDF values are very similar to future DF trajectories.

Conclusion
RDFs are a useful tool for comparing annual climate impacts of forest growth scenarios and can be used to benchmark material and energy substitution effects of wood. Our results indicate that the baseline scenario reflects an effective compromise between carbon stocks in the forest and carbon displacement by wood use. For a longer modeling period, however, this might not be the case. Which of the alternative scenarios would be best suited for climate change mitigation is heavily dependent on future DF trajectory. Hence, our findings highlight the necessity of robust projections of forest dynamics and industry decarbonization pathways.
EZCancerTarget: an open-access drug repurposing and data-collection tool to enhance target validation and optimize international research efforts against highly progressive cancers
Authors: Dora David , Dora Timea , Szegvari Gabor , Gerdán Csongor , Lohinai Zoltan 
Published: October 2022

AbstractThe expanding body of potential therapeutic targets requires easily accessible, structured, and transparent real-time interpretation of molecular data. Open-access genomic, proteomic and drug-repurposing databases transformed the landscape of cancer research, but most of them are difficult and time-consuming for casual users. Furthermore, to conduct systematic searches and data retrieval on multiple targets, researchers need the help of an expert bioinformatician, who is not always readily available for smaller research teams. We invite research teams to join and aim to enhance the cooperative work of more experienced groups to harmonize international efforts to overcome devastating malignancies. Here, we integrate available fundamental data and present a novel, open access, data-aggregating, drug repurposing platform, deriving our searches from the entries of Clue.io. We show how we integrated our previous expertise in small-cell lung cancer (SCLC) to initiate a new platform to overcome highly progressive cancers such as triple-negative breast and pancreatic cancer with data-aggregating approaches. Through the front end, the current content of the platform can be further expanded or replaced and users can create their drug-target list to select the clinically most relevant targets for further functional validation assays or drug trials. EZCancerTarget integrates searches from publicly available databases, such as PubChem, DrugBank, PubMed, and EMA, citing up-to-date and relevant literature of every target. Moreover, information on compounds is complemented with biological background information on eligible targets using entities like UniProt, String, and GeneCards, presenting relevant pathways, molecular- and biological function and subcellular localizations of these molecules. Cancer drug discovery requires a convergence of complex, often disparate fields. We present a simple, transparent, and user-friendly drug repurposing software to facilitate the efforts of research groups in the field of cancer research.
Circulating tumor DNA integrating tissue clonality detects minimal residual disease in resectable non-small-cell lung cancer
Authors: Wang Siwei , Li Ming , Zhang Jingyuan , Xing Peng , Wu Min , Meng Fancheng , Jiang Feng , Wang Jie , Bao Hua , Huang Jianfeng , Ren Binhui , Yu Mingfeng , Qiu Ninglei , Li Houhuai , Yuan Fangliang , Zhang Zhi , Jia Hui , Lu Xinxin , Zhang Shuai , Wang Xiaojun , Xu Youtao , Xia Wenjia , Liu Tongyan , Xu Weizhang , Xu Xinyu , Sun Mengting , Wu Xue , Shao Yang , Wang Qianghu , Dai Juncheng , Qiu Mantang , Wang Jinke , Zhang Qin , Xu Lin , Shen Hongbing , Yin Rong 
Published: October 2022

Abstract
Background
Circulating tumor DNA (ctDNA) has been proven as a marker for detecting minimal residual diseases following systemic therapies in mid-to-late-stage non-small-cell lung cancers (NSCLCs) by multiple studies. However, fewer studies cast light on ctDNA-based MRD monitoring in early-to-mid-stage NSCLCs that received surgical resection as the standard of care.

Methods
We prospectively recruited 128 patients with stage I–III NSCLCs who received curative surgical resections in our Lung Cancer Tempo-spatial Heterogeneity prospective cohort. Plasma samples were collected before the surgery, 7 days after the surgery, and every 3 months thereafter. Targeted sequencing was performed on a total of 628 plasma samples and 645 matched tumor samples using a panel covering 425 cancer-associated genes. Tissue clonal phylogeny of each patient was reconstructed and used to guide ctDNA detection.

Results
The results demonstrated that ctDNA was more frequently detected in patients with higher stage diseases pre- and postsurgery. Positive ctDNA detection at as early as 7 days postsurgery identified high-risk patients with recurrence (HR = 3.90, P < 0.001). Our results also show that longitudinal ctDNA monitoring of at least two postsurgical time points indicated a significantly higher risk (HR = 7.59, P < 0.001), preceding radiographic relapse in 73.5% of patients by a median of 145 days. Further, clonal ctDNA mutations indicated a high-level specificity, and subclonal mutations informed the origin of tumor recurrence.

Conclusions
Longitudinal ctDNA surveillance integrating clonality information may stratify high-risk patients with disease recurrence and infer the evolutionary origin of ctDNA mutations.
Long non-coding RNAs affecting cell metabolism in cancer
Authors: Agostini Massimiliano , Mancini Mara , Candi Eleonora 
Published: October 2022

AbstractMetabolic reprogramming is commonly recognized as one important hallmark of cancers. Cancer cells present significant alteration of glucose metabolism, oxidative phosphorylation, and lipid metabolism. Recent findings demonstrated that long non-coding RNAs control cancer development and progression by modulating cell metabolism. Here, we give an overview of breast cancer metabolic reprogramming and the role of long non-coding RNAs in driving cancer-specific metabolic alteration.
Effect of electrical impedance-guided PEEP in reducing pulmonary complications after craniotomy: study protocol for a randomized controlled trial
Authors: Zhang Zihao , Zhang Lianqin , Zhu Jiang , Dong Jun , Liu Hairui 
Published: October 2022

Abstract
Objective
The purpose of this study is to explore whether electrical impedance tomography (EIT)-guided individualized positive end-expiratory pressure (PEEP) can reduce the incidence of pulmonary complications within 1 week following a craniotomy compared with a single PEEP (PEEP = 6 cmH2O) from dura suturing to extubation.

Methods
A randomized controlled trial will be conducted at the Second Affiliated Hospital of Soochou University. Five hundred forty patients undergoing a craniotomy in the supine position will be randomly allocated into the P6 (PEEP = 6 cmH2O) or Pi (individualized PEEP) group. Both groups of patients will receive a lung recruitment maneuver before suturing the dura. Then, the P6 group will receive 6 cmH2O PEEP, and the Pi group will receive EIT-guided individualized PEEP. The incidence and severity score of pulmonary complications within 1 week following surgery, the lung ultrasound score (LUS), regional cerebral oxygen saturation (rScO2), and PaO2/FiO2 before anesthesia (T0), 10 min after extubation (T1), 24 h after extubation (T2), and 72 h after extubation (T3) will be compared between the two groups. The duration of surgery and anesthesia, the level and duration of PEEP during surgery, the volume of liquid intake and output during surgery, and the postoperative ICU and hospital stays will be recorded. The main outcome of this study will be the incidence of pulmonary complications within 1 week after surgery.

Discussion
The purposes of this study are to determine whether EIT-guided individualized PEEP from the beginning of dura suturing to extubation reduces the incidence of pulmonary complications within 1 week after a craniotomy compared with a single constant PEEP and to evaluate the length of ICU and hospital stays. If our results are positive, this study will show that EIT-guided individualized PEEP is better than a single constant PEEP and can further improve the prognosis of neurosurgical patients and reduce hospitalization costs, which will promote the wide application of individualized PEEP in clinical anesthesia.

Trial registration
Chinese Clinical Trial Registry CHiCTR2100051200. Registered on 15 September 2021.