bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neural ensembles in the murine medial prefrontal cortex process distinct information during visual perceptual learning
Authors: Wang Zhenni , Lou Shihao , Ma Xiao , Guo Hui , Liu Yan , Chen Wenjing , Lin Dating , Yang Yupeng 
Published: February 2023

Abstract
Background
Perceptual learning refers to an augmentation of an organism’s ability to respond to external stimuli, which has been described in most sensory modalities. Visual perceptual learning (VPL) is a manifestation of plasticity in visual information processing that occurs in the adult brain, and can be used to ameliorate the ability of patients with visual defects mainly based on an improvement of detection or discrimination of features in visual tasks. While some brain regions such as the primary visual cortex have been described to participate in VPL, the way more general high-level cognitive brain areas are involved in this process remains unclear. Here, we showed that the medial prefrontal cortex (mPFC) was essential for both the training and maintenance processes of VPL in mouse models.

Results
We built a new VPL model in a custom-designed training chamber to enable the utilization of miniScopes when mice freely executed the VPL task. We found that pyramidal neurons in the mPFC participate in both the training process and maintenance of VPL. By recording the calcium activity of mPFC pyramidal neurons while mice freely executed the task, distinct ON and OFF neural ensembles tuned to different behaviors were identified, which might encode different cognitive information. Decoding analysis showed that mouse behaviors could be well predicted using the activity of each ON ensemble. Furthermore, VPL recruited more reward-related components in the mPFC.

Conclusion
We revealed the neural mechanism underlying vision improvement following VPL and identify distinct ON and OFF neural ensembles in the mPFC that tuned to different information during visual perceptual training. These results uncover an important role of the mPFC in VPL, with more reward-related components being also involved, and pave the way for future clarification of the reward signal coding rules in VPL.
Efficient prioritization of CRISPR screen hits by accounting for targeting efficiency of guide RNA
Authors: Park Byung-Sun , Jeon Heeju , Chi Sung-Gil , Kim Tackhoon 
Published: February 2023

Abstract
Background
CRISPR-based screens are revolutionizing drug discovery as tools to identify genes whose ablation induces a phenotype of interest. For instance, CRISPR-Cas9 screening has been successfully used to identify novel therapeutic targets in cancer where disruption of genes leads to decreased viability of malignant cells. However, low-activity guide RNAs may give rise to variable changes in phenotype, preventing easy identification of hits and leading to false negative results. Therefore, correcting the effects of bias due to differences in guide RNA efficiency in CRISPR screening data can improve the efficiency of prioritizing hits for further validation. Here, we developed an approach to identify hits from negative CRISPR screens by correcting the fold changes (FC) in gRNA frequency by the actual, observed frequency of indel mutations generated by gRNA.

Results
Each gRNA was coupled with the “reporter sequence” that can be targeted by the same gRNA so that the frequency of mutations in the reporter sequence can be used as a proxy for the endogenous target gene. The measured gRNA activity was used to correct the FC. We identified indel generation efficiency as the dominant factor contributing significant bias to screening results, and our method significantly removed such bias and was better at identifying essential genes when compared to conventional fold change analysis. We successfully applied our gRNA activity data to previously published gRNA screening data, and identified novel genes whose ablation could synergize with vemurafenib in the A375 melanoma cell line. Our method identified nicotinamide N-methyltransferase, lactate dehydrogenase B, and polypyrimidine tract-binding protein 1 as synergistic targets whose ablation sensitized A375 cells to vemurafenib.

Conclusions
We identified the variations in target cleavage efficiency, even in optimized sgRNA libraries, that pose a strong bias in phenotype and developed an analysis method that corrects phenotype score by the measured differences in the targeting efficiency among sgRNAs. Collectively, we expect that our new analysis method will more accurately identify genes that confer the phenotype of interest.
Current status of hand-foot-and-mouth disease
Authors: Zhu Peiyu , Ji Wangquan , Li Dong , Li Zijie , Chen Yu , Dai Bowen , Han Shujie , Chen Shuaiyin , Jin Yuefei , Duan Guangcai 
Published: February 2023

AbstractHand-foot-and-mouth disease (HFMD) is a viral illness commonly seen in young children under 5 years of age, characterized by typical manifestations such as oral herpes and rashes on the hands and feet. These symptoms typically resolve spontaneously within a few days without complications. Over the past two decades, our understanding of HFMD has greatly improved and it has received significant attention. A variety of research studies, including epidemiological, animal, and invitrostudies, suggest that the disease may be associated with potentially fatal neurological complications. These findings reveal clinical, epidemiological, pathological, and etiological characteristics that are quite different from initial understandings of the illness. It is important to note that HFMD has been linked to severe cardiopulmonary complications, as well as severe neurological sequelae that can be observed during follow-up. At present, there is no specific pharmaceutical intervention for HFMD. An inactivated Enterovirus A71 (EV-A71) vaccine that has been approved by the China Food and Drug Administration (CFDA) has been shown to provide a high level of protection against EV-A71-related HFMD. However, the simultaneous circulation of multiple pathogens and the evolution of the molecular epidemiology of infectious agents make interventions based solely on a single agent comparatively inadequate. Enteroviruses are highly contagious and have a predilection for the nervous system, particularly in child populations, which contributes to the ongoing outbreak. Given the substantial impact of HFMD around the world, this Review synthesizes the current knowledge of the virology, epidemiology, pathogenesis, therapy, sequelae, and vaccine development of HFMD to improve clinical practices and public health efforts.
Study of the growth and biochemical composition of 20 species of cyanobacteria cultured in cylindrical photobioreactors
Authors: Baracho Douglas Henrique , Lombardi Ana Teresa 
Published: February 2023

Abstract
Background
Cyanobacteria are prokaryotic organisms with wide morphological and metabolic diversity. By means of photosynthesis, they convert inorganic compounds into biomolecules, which may have commercial interest. In this work, we evaluated 20 cyanobacterial strains regarding their physiological aspects such as growth, photosynthesis and biochemical composition, some of which are revealed here for the first time. The organisms were cultivated in cylindrical photobioreactors (CPBR) for 144 h and the biomass was obtained. The light inside cultures was constant throughout experimental time and maintained at the saturation irradiance (Ik) of each species. Culture pH was maintained within 7.8 and 8.4 by automatic CO2 bubbling. Growth rate, dry biomass, chlorophyll a, carotenoids, phycocyanin, proteins, carbohydrates, lipids, polyhydroxyalkanoate (PHA) and antioxidant activity were determined.

Results
The proportionality of the biochemical composition varied among species, as well as the growth rates. Leptolyngbya sp. and Nostoc sp. (CCIBt3249) showed growth rates in the range of 0.7–0.8 d−1, followed by Rhabdorderma sp. (~ 0.6 d−1), and Phormidium sp. (~ 0.5 d−1). High carotenoid content was obtained in Rhabdoderma sp. (4.0 μg mL−1) and phycocyanin in Leptolyngbya sp. (60 μg mL−1). Higher total proteins were found in the genus Geitlerinema (75% DW), carbohydrates in Microcystis navacekii (30% DW) and lipids in Phormidium sp. (15% DW). Furthermore, Aphanocapsa holsatica showed the highest antioxidant activity (65%) and Sphaerocavum brasiliense, Microcystis aeruginosa, Nostoc sp. (CCIBt3249) and A. holsatica higher levels of PHA (~ 2% DW).

Conclusions
This study reports on the biochemical composition of cyanobacteria that can impact the biotechnology of their production, highlighting potential strains with high productivity of specific biomolecules.
Applications of radiomics-based analysis pipeline for predicting epidermal growth factor receptor mutation status
Authors: Liu Zefeng , Zhang Tianyou , Lin Liying , Long Fenghua , Guo Hongyu , Han Li 
Published: February 2023

AbstractBackgroundThis study aimed to develop a pipeline for selecting the best feature engineering-based radiomic path to predict epidermal growth factor receptor (EGFR) mutant lung adenocarcinoma in18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT).MethodsThe study enrolled 115 lung adenocarcinoma patients with EGFR mutation status from June 2016 and September 2017. We extracted radiomics features by delineating regions-of-interest around the entire tumor in18F-FDG PET/CT images. The feature engineering-based radiomic paths were built by combining various methods of data scaling, feature selection, and many methods for predictive model-building. Next, a pipeline was developed to select the best path.ResultsIn the paths from CT images, the highest accuracy was 0.907 (95% confidence interval [CI]: 0.849, 0.966), the highest area under curve (AUC) was 0.917 (95% CI: 0.853, 0.981), and the highest F1 score was 0.908 (95% CI: 0.842, 0.974). In the paths based on PET images, the highest accuracy was 0.913 (95% CI: 0.863, 0.963), the highest AUC was 0.960 (95% CI: 0.926, 0.995), and the highest F1 score was 0.878 (95% CI: 0.815, 0.941). Additionally, a novel evaluation metric was developed to evaluate the comprehensive level of the models. Some feature engineering-based radiomic paths obtained promising results.ConclusionsThe pipeline is capable of selecting the best feature engineering-based radiomic path. Combining various feature engineering-based radiomic paths could compare their performances and identify paths built with the most appropriate methods to predict EGFR-mutant lung adenocarcinoma in18FDG PET/CT. The pipeline proposed in this work can select the best feature engineering-based radiomic path.
Biodegradable polymeric nanoparticles increase risk of cardiovascular diseases by inducing endothelium dysfunction and inflammation
Authors: Shi Wen , Fuad Atik Rohmana Maftuhatul , Li Yanhong , Wang Yang , Huang Junyang , Du Ruolin , Wang Guixue , Wang Yazhou , Yin Tieying 
Published: February 2023

AbstractBiodegradable polymers are expected to be an alternative to plastics. Because of its high biocompatibility, poly (lactic-co-glycolic acid) (PLGA) is widely used in medicine. It has been reported that micro-nano plastics can be accumulated in the circulatory system and cause tissue injury. With the increasing environmental exposure of degradable polymer nanoparticles (NPs), the impact of this risk factor on cardiovascular disease deserves attention. Thus, we aim to study the harmful effect of PLGA NPs on the process of vascular stenosis which is a typical pathological feature of cardiovascular diseases. We establish a mouse vascular stenosis model with intravenously injecting of PLGA NPs for 2 weeks. This model leads to a significant narrowing of the left common carotid artery which is characterized by the increasing intima area and focal stenosis. We observe that PLGA NPs accelerate stenosis progression by inducing inflammation and impairing vascular function. It promotes the proliferation of smooth muscle cells and causes abnormal collagen distribution. The combination of wall shear stress and PLGA NPs uptake speed up endothelial cell damage, decrease endothelial permeability and cell migration capacity. Our results suggest that PLGA NPs may pose a risk in cardiovascular stenosis which inspire us to concern the biodegradable polymeric materials in our living especially the clinic applications.
Graphical Abstract
Socio-economic, governance and health indicators shaping antimicrobial resistance: an ecological analysis of 30 european countries
Authors: Maugeri Andrea , Barchitta Martina , Puglisi Federico , Agodi Antonella 
Published: February 2023

Abstract
Background
Previous evidence shows that antibiotic use and antimicrobial resistance (AMR) spread are not always perfectly correlated within and between countries. We conducted an ecological analysis to evaluate how demographic, economic, governance, health, and freedom characteristics of 30 European countries contribute to antibiotic consumption and AMR.

Methods
Using three sources of data (World Bank DataBank, ECDC atlas, and the ESAC-Net database), we created a dataset of: 22 indicators of demographics, health, economic, governance, and freedom; AMR proportions for 25 combinations of pathogens and antibiotics; consumption of antibiotics in the community. We also computed five indexes of demographic, health, economic, governance, and freedom, and an aggregate AMR measure. Relationships between indexes, antibiotic consumption, and AMR proportions were explored using bivariate, multivariable, multivariate, and mediation analyses.

Results
Multivariate analysis identified three clusters of countries that mainly differed for demographic, health, governance, and freedom indexes. AMR proportion was lower in countries with better indexes (p < 0.001), but not necessarily with lower antibiotic consumption. In multivariable models including all five indexes, an increase in the governance index resulted in significant decreases of overall antibiotic consumption (p < 0.001) and AMR proportion (p = 0.006). Mediation analysis showed that the governance index had an indirect effect on AMR via reducing antibiotic consumption, which accounted only for 31.5% of the total effect.

Conclusions
These findings could be – at least partially – explained by the contagion theory, for which other factors contribute to high levels of AMR in countries with poor governance. As a result of this evidence, reducing antibiotic use alone is unlikely to solve the AMR problem, and more interventions are needed to increase governance efficiency at global level.
The ratio of cervical lordosis to C7 slope represents the reciprocal change between cervical sagittal alignment and global spinal alignment
Authors: Wang Dong-Fan , Lu Shi-Bao , Li Xiang-Yu , Shi Bin , Liu Cheng-Xin , Kong Chao 
Published: February 2023

Abstract
Purpose
This retrospective cross-sectional study investigated variations in the ratio of cervical lordosis to C7 slope (CL/C7S) at different stages of global sagittal balance to better understand how global sagittal alignment affects cervical alignment.

Methods
A total of 255 patients with the degenerative lumbar disease were retrospectively studied within a single medical center. Whole spine radiographs were used to evaluate sagittal parameters, mainly including occiput-C2 lordosis (OC2), cervical lordosis (CL), C7 slope (C7S), the ratio of cervical lordosis to C7 slope (CL/C7S), cervical sagittal vertical axis (CSVA), thoracic kyphosis (TK), lumbar lordosis (LL), pelvic tilt (PT), pelvic incidence (PI), PI minus LL mismatch (PI–LL), and sagittal vertical axis (SVA). Patients were divided into the balance group (SVA < 50 mm, PI–LL ≤ 10°), hidden imbalance group (SVA < 50 mm, PI–LL > 10°), and imbalance group (SVA > 50 mm).

Results
Significant correlations were found between CL/C7S and OC2 (r = − 0.334), CSVA (r = − 0.504), PI–LL (r = 0.189), and SVA (r = 0.309). Multivariable linear regression analysis indicated that patients in the hidden imbalance group had lower CL/C7S than those in the balance group (B = − 0.234, P < 0.001), whereas the value of CL/C7S in patients with imbalanced sagittal alignment was higher than those with balanced alignment (B = 0.164, P = 0.011). The mean value of CL/C7S was 0.71, 0.51, and 0.97 in the balance, hidden imbalance, and imbalance groups, respectively. The global spine tended to tilt forward as the LL decreased, while TK, PT, PI–LL, and SVA increased (all, P < 0.001) from the balance stage to the imbalance stage.

Conclusions
CL/C7S tended to be lower when the thoracic extension increased to maintain global sagittal balance at the hidden imbalance stage. Inversely, CL/C7S increased significantly when the global spine showed severe anterior malalignment.
The total polyphenolic glycoside extract of Lamiophlomis rotata ameliorates hepatic fibrosis through apoptosis by TGF-β/Smad signaling pathway
Authors: Wan Guoguo , Chen Zhiwei , Lei Lei , Geng Xiaoyu , Zhang Yi , Yang Congwen , Cao Wenfu , Pan Zheng 
Published: February 2023

Abstract
Background
Hepatic fibrosis is characterized by the excessive deposition of extracellular matrix (ECM) which is mainly secreted by activated hepatic stellate cells (HSCs). Lamiophlomis rotata (L. rotata) was recorded to treat jaundice in the traditional Tibetan medical system with the potential of hepatoprotection. However, the bioactivities and the possible mechanism of L. rotata on hepatic fibrosis is still largely unknown.

Aim of the study
To investigate the anti-hepatic fibrosis effects of bioactivities in L. rotata and the probable mechanism of action.

Materials and methods
Herein, total polyphenolic glycosides of L. rotata (TPLR) was purified with the selectivity adsorption resin and was analyzed by ultrahigh-performance liquid chromatography coupled with time-of-flight mass spectrometry (UPLC-Q/TOF/MSn). The anti-hepatic fibrosis effect of TPLR was evaluated by carbon tetrachloride (CCl4)-induced liver fibrosis, and was evaluated with the apoptosis of activated HSCs.

Results
In total, sixteen compounds, including nine phenylpropanoids and six flavonoids, were identified in the UPLC-TOF-MSn profile of the extracts. TPLR significantly ameliorated hepatic fibrosis in CCl4-induced mice and inhibited HSCs proliferation, Moreover, TPLR notably increased the apoptosis of activated HSCs along with up-regulated caspase-3, -8, -9, and -10. Furthermore, TPLR inhibited TGF-β/Smad pathway ameliorating hepatic fibrosis though downregulation the expression of Smad2/3, Smad4, and upregulation the expression of Smad7 in vivo and in vitro. Simultaneously, the expression of fibronectin (FN), α-smooth muscle actin (α-SMA), and Collagen I (Col1α1) were decreased in tissues and in cells with TPLR administration.

Conclusion
These results initially demonstrated that TPLR has the potential to ameliorate hepatic fibrosis through an apoptosis mechanism via TGF-β/Smad signaling pathway.

Graphical Abstract
Electro-acupuncture reduced steatosis on MRI-PDFF in patients with non-alcoholic steatohepatitis: a randomized controlled pilot clinical trial
Authors: Zhao Jingjie , Wang Qianyi , Zhao Xinyu , Wu Lina , Li Juanjuan , Zhang Wen , Xu Shuai , Han Chaoru , Du Yi , Tong Xiaofei , Duan Weijia , Cao Di , Ren Hao , Zhao Xinyan , Ou Xiaojuan , Jia Jidong , You Hong 
Published: February 2023

Abstract
Background
Non-alcoholic steatohepatitis (NASH) had not yet been approved therapy. Electro-acupuncture (EA) has been reported to have potential efficacy. However, high-quality clinical evidence was still lacking.

Methods
NASH patients were randomized and allocated to either sham acupuncture (SA) or EA group in a 1:1 ratio, with the patient blinded. Each patient received 36 sessions of SA or EA treatment over 12 weeks, followed by additional 4 weeks. The primary outcome was the changes in relative liver fat content measured by magnetic resonance imaging proton density fat fraction (MRI-PDFF).

Results
A total of 60 patients were enrolled. From baseline to week 12, the reduction of relative liver fat content measured by MRI-PDFF in the EA group (− 33.6%, quantile range: − 52.9%, − 22.7%) was significantly more significant than that in the SA group (− 15.8%, quantile range: − 36.1%, − 2.7%) (p = 0.022). Furthermore, the EA group had more patients who achieved MRI-PDFF to 30% reduction at week 12 (53.3% vs. 25.9%, p = 0.035). EA treatment also significantly reduced body weight (− 3.0 vs. + 0.1 kg, p = 0.034) and BMI (− 1.5 vs. − 0.2 kg/m2, p = 0.013) at week 16. Except for AST (− 27.4 vs. − 16.2 U/L, p = 0.015), other biochemical varieties, including ALT, fasting-glucose, cholesterol, and triglyceride, showed no statistically significant difference. Both groups measured no significant changes in liver stiffness by magnetic resonance elastography (MRE). There were no serious adverse events in either group.

Conclusions
Twelve weeks of EA effectively and safely reduces relative liver fat content in NASH patients. Further multicenter randomized controlled studies are needed.
Trial registration Chinese Clinical Trial Registry, ChiCTR2100046617. Registered 23 May 2021, http://www.chictr.org.cn/edit.aspx?pid=127023&htm=4
Plasma neurofilament light is a predictor of neurological outcome 12 h after cardiac arrest
Authors: Levin Helena , Lybeck Anna , Frigyesi Attila , Arctaedius Isabelle , Thorgeirsdóttir Bergthóra , Annborn Martin , Moseby-Knappe Marion , Nielsen Niklas , Cronberg Tobias , Ashton Nicholas J. , Zetterberg Henrik , Blennow Kaj , Friberg Hans , Mattsson-Carlgren Niklas 
Published: February 2023

Abstract
Background
Previous studies have reported high prognostic accuracy of circulating neurofilament light (NfL) at 24–72 h after out-of-hospital cardiac arrest (OHCA), but performance at earlier time points and after in-hospital cardiac arrest (IHCA) is less investigated. We aimed to assess plasma NfL during the first 48 h after OHCA and IHCA to predict long-term outcomes.

Methods
Observational multicentre cohort study in adults admitted to intensive care after cardiac arrest. NfL was retrospectively analysed in plasma collected on admission to intensive care, 12 and 48 h after cardiac arrest. The outcome was assessed at two to six months using the Cerebral Performance Category (CPC) scale, where CPC 1–2 was considered a good outcome and CPC 3–5 a poor outcome. Predictive performance was measured with the area under the receiver operating characteristic curve (AUROC).

Results
Of 428 patients, 328 (77%) suffered OHCA and 100 (23%) IHCA. Poor outcome was found in 68% of OHCA and 55% of IHCA patients. The overall prognostic performance of NfL was excellent at 12 and 48 h after OHCA, with AUROCs of 0.93 and 0.97, respectively. The predictive ability was lower after IHCA than OHCA at 12 and 48 h, with AUROCs of 0.81 and 0.86 (p ≤ 0.03). AUROCs on admission were 0.77 and 0.67 after OHCA and IHCA, respectively. At 12 and 48 h after OHCA, high NfL levels predicted poor outcome at 95% specificity with 70 and 89% sensitivity, while low NfL levels predicted good outcome at 95% sensitivity with 71 and 74% specificity and negative predictive values of 86 and 88%.

Conclusions
The prognostic accuracy of NfL for predicting good and poor outcomes is excellent as early as 12 h after OHCA. NfL is less reliable for the prediction of outcome after IHCA.