bluuebunny/crossref_metadata_2025_split huggingface dataset:
A quantitative metric of pioneer activity reveals that HNF4A has stronger in vivo pioneer activity than FOXA1
Authors: Hansen Jeffrey L. , Cohen Barak A. 
Published: October 2022

Abstract
Background
We and others have suggested that pioneer activity — a transcription factor’s (TF’s) ability to bind and open inaccessible loci — is not a qualitative trait limited to a select class of pioneer TFs. We hypothesize that most TFs display pioneering activity that depends on the TF concentration and the motif content at their target loci.

Results
Here, we present a quantitative in vivo measure of pioneer activity that captures the relative difference in a TF’s ability to bind accessible versus inaccessible DNA. The metric is based on experiments that use CUT&Tag to measure the binding of doxycycline-inducible TFs. For each location across the genome, we determine the concentration of doxycycline required for a TF to reach half-maximal occupancy; lower concentrations reflect higher affinity. We propose that the relative difference in a TF’s affinity between ATAC-seq labeled accessible and inaccessible binding sites is a measure of its pioneer activity. We estimate binding affinities at tens of thousands of genomic loci for the endodermal TFs FOXA1 and HNF4A and show that HNF4A has stronger pioneer activity than FOXA1. We show that both FOXA1 and HNF4A display higher binding affinity at inaccessible sites with more copies of their respective motifs. The quantitative analysis of binding suggests different modes of binding for FOXA1, including an anti-cooperative mode of binding at certain accessible loci.

Conclusions
Our results suggest that relative binding affinities are reasonable measures of pioneer activity and support the model wherein most TFs have some degree of context-dependent pioneer activity.
Genetic diversity in the transmission-blocking vaccine candidate Plasmodium vivax gametocyte protein Pvs230 from the China–Myanmar border area and central Myanmar
Authors: Zhao Xin , Hu Yubing , Zhao Yan , Wang Lin , Wu Zifang , Soe Myat Thu , Kyaw Myat Phone , Cui Liwang , Zhu Xiaotong , Cao Yaming 
Published: October 2022

AbstractBackgroundSexual stage surface antigens are potential targets of transmission-blocking vaccines (TBVs). The gametocyte and gamete surface antigen P230, a leading TBV candidate, is critical for red blood cell binding during exflagellation and subsequent oocyst development. Here, the genetic diversity ofPvs230was studied inPlasmodium vivaxparasite isolates from the China–Myanmar border (CMB) and central Myanmar.MethodsPlasmodium vivaxisolates were collected in clinics from malaria-endemic areas of the CMB (143 samples) and Myanmar (23 samples). The interspecies variable part (IVP, nucleotides 1–807) and interspecies conserved part (ICP, 808–2862) ofPvs230were amplified by PCR and sequenced. Molecular evolution studies were conducted to evaluate the genetic diversity, signature of selection, population differentiation, haplotype network, and population structure of the study parasite populations and publicly availablePvs230sequences from six globalP. vivaxpopulations.ResultsLimited genetic diversity was observed for the CMB (π = 0.002) and Myanmar (π = 0.001) isolates. Most amino acid substitutions were located in the IVP and cysteine-rich domain ofPvs230. Evidence of positive selection was observed for IVP and purifying selection for ICP. Codon-based tests identified specific codons under natural selection in both IVP and ICP. The fixation index (FST) showed low genetic differentiation between East and Southeast Asian populations, withFSTranging from 0.018 to 0.119. The highestFSTvalue (FST = 0.503) was detected between the Turkey and Papua New Guinea populations. A total of 92 haplotypes were identified in global isolates, with the major haplotypes 2 and 9 being the most abundant and circulating in East and Southeast Asia populations. Several detected non-synonymous substitutions were mapped in the predicted structure and B-cell epitopes of Pvs230.ConclusionsWe detected low levels of genetic diversity ofPvs230in globalP. vivaxpopulations. Geographically specific haplotypes were identified forPvs230. Some mutations are located within a potential B-cell epitope region and need to be considered in future TBV designs.Graphical Abstract
Cationic amino acid transporter-1 (CAT-1) promotes fibroblast-like synoviocyte proliferation and cytokine secretion by taking up L-arginine in rheumatoid arthritis
Authors: Lu Ying , Hao Chongbo , Yu Shanshan , Ma Zuan , Fu Xuelian , Qin Mingqing , Ding Menglei , Xu Zengguang , Fan Lieying 
Published: October 2022

Abstract

Background

Abnormal proliferation of fibroblast-like synoviocytes (FLSs) in the synovial lining layer is the primary cause of synovial hyperplasia and joint destruction in rheumatoid arthritis (RA). Currently, the relationship between metabolic abnormalities and FLS proliferation is a new focus of investigation. However, little is known regarding the relationship between amino acid metabolism and RA.

Methods
The concentrations of amino acids and cytokines in the synovial fluid of RA (n = 9) and osteoarthritis (OA, n = 9) were detected by LC–MS/MS and CBA assay, respectively. The mRNA and protein expression of cationic amino acid transporter-1 (CAT-1) were determined in FLSs isolated from RA and OA patients by real-time PCR and western blotting. MTT assay, cell cycle, apoptosis, invasion, and cytokine secretion were determined in FLSs knocked down of CAT-1 using siRNA or treated with D-arginine under normoxic and hypoxic culture conditions. A mouse collagen-induced arthritis (CIA) model was applied to test the therapeutic potential of blocking the uptake of L-arginine in vivo.

Results
L-rginine was upregulated in the synovial fluid of RA patients and was positively correlated with the elevation of the cytokines IL-1β, IL-6, and IL-8. Further examination demonstrated that CAT-1 was the primary transporter for L-arginine and was overexpressed on RA FLSs compared to OA FLSs. Moreover, knockdown of CAT-1 using siRNA or inhibition of L-arginine uptake using D-arginine significantly suppressed L-arginine metabolism, cell proliferation, migration, and cytokine secretion in RA FLSs under normoxic and hypoxic culture conditions in vitro but increased cell apoptosis in a dose-dependent manner. Meanwhile, in vivo assays revealed that an L-arginine-free diet or blocking the uptake of L-arginine using D-arginine suppressed arthritis progression in CIA mice.

Conclusion
CAT-1 is upregulated and promotes FLS proliferation by taking up L-arginine, thereby promoting RA progression.
Resuscitative endovascular balloon occlusion of the aorta in civilian pre-hospital care: a systematic review of the literature
Authors: Caicedo Yaset , Gallego Linda M. , Clavijo Hugo JC. , Padilla-Londoño Natalia , Gallego Cindy-Natalia , Caicedo-Holguín Isabella , Guzmán-Rodríguez Mónica , Meléndez-Lugo Juan J. , García Alberto F. , Salcedo Alexander E. , Parra Michael W. , Rodríguez-Holguín Fernando , Ordoñez Carlos A. 
Published: October 2022

AbstractBackgroundResuscitative endovascular balloon occlusion of the aorta (REBOA) is a damage control tool with a potential role in the hemodynamic resuscitation of severely ill patients in the civilian pre-hospital setting. REBOA ensures blood flow to vital organs by early proximal control of the source of bleeding. However, there is no consensus on the use of REBOA in the pre-hospital setting. This article aims to perform a systematic review of the literature about the feasibility, survival, indications, complications, and potential candidates for civilian pre-hospital REBOA.MethodsA literature search was conducted using Medline, EMBASE, LILACS and Web of Science databases. Primary outcome variables included overall survival and feasibility. Secondary outcome variables included complications and potential candidates for endovascular occlusion.ResultsThe search identified 8 articles. Five studies described the use of REBOA in pre-hospital settings, reporting a total of 47 patients in whom the procedure was attempted. Pre-hospital REBOA was feasible in 68–100% of trauma patients and 100% of non-traumatic patients with cardiac arrest. Survival rates and complications varied widely. Pre-hospital REBOA requires a coordinated and integrated emergency health care system with a well-trained and equipped team. The remaining three studies performed a retrospective analysis identifying 784 potential REBOA candidates.ConclusionsPre-hospital REBOA could be a feasible intervention for a significant portion of severely ill patients in the civilian setting. However, the evidence is limited. The impact of pre-hospital REBOA should be assessed in future studies.
Intestine-derived α-synuclein initiates and aggravates pathogenesis of Parkinson’s disease in Drosophila
Authors: Liu Wei , Lim Kah-Leong , Tan Eng-King 
Published: October 2022

Abstract
Background
Aberrant aggregation of α-synuclein (α-syn) is a key pathological feature of Parkinson’s disease (PD), but the precise role of intestinal α-syn in the progression of PD is unclear. In a number of genetic Drosophila models of PD, α-syn was frequently ectopically expressed in the neural system to investigate the pathobiology.

Method
We investigated the potential role of intestinal α-syn in PD pathogenesis using a Drosophila model. Human α-syn was overexpressed in Drosophila guts, and life span, survival, immunofluorescence and climbing were evaluated. Immunofluorescence, Western blotting and reactive oxygen species (ROS) staining were performed to assess the effects of intestinal α-syn on intestinal dysplasia. High‐throughput RNA and 16S rRNA gene sequencing, quantitative RT‐PCR, immunofluorescence, and ROS staining were performed to determine the underlying molecular mechanism.

Results
We found that the intestinal α-syn alone recapitulated many phenotypic and pathological features of PD, including impaired life span, loss of dopaminergic neurons, and progressive motor defects. The intestine-derived α-syn disrupted intestinal homeostasis and accelerated the onset of intestinal ageing. Moreover, intestinal expression of α-syn induced dysbiosis, while microbiome depletion was efficient to restore intestinal homeostasis and ameliorate the progression of PD. Intestinal α-syn triggered ROS, and eventually led to the activation of the dual oxidase (DUOX)–ROS–Jun N-terminal Kinase (JNK) pathway. In addition, α-syn from both the gut and the brain synergized to accelerate the progression of PD.

Conclusions
The intestinal expression of α-syn recapitulates many phenotypic and pathologic features of PD, and induces dysbiosis that aggravates the pathology through the DUOX–ROS–JNK pathway in Drosophila. Our findings provide new insights into the role of intestinal α-syn in PD pathophysiology.
Production of pyruvic acid with Candida glabrata using self-fermenting spent yeast cell dry powder as a seed nitrogen source
Authors: Lu Qiyuan , Shan Xiaoyu , Zeng Weizhu , Zhou Jingwen 
Published: October 2022

AbstractPyruvic acid is an important organic acid and a key industrial raw material. It is widely used in the chemical, agricultural, and food fields. Candida glabrata is the preferred strain for pyruvic acid production. The waste yeast cell for pyruvic acid fermentation with C. glabrata are rich in protein, amino acid, nucleic acid, and vitamins, as potential and cost-effective nitrogen source raw material. In this study, the potential of C. glabrata to produce pyruvic acid using spent yeast cell dry powder was evaluated. When 30 g/L of spray-dried spent yeast cell powder was used as the seed nitrogen source, a high titer of pyruvic acid was obtained. The pyruvic acid production reached 63.4 g/L with a yield of 0.59 g/g in a 5 L bioreactor. After scale-up to a 50 L bioreactor using the fermented spent yeast cell dry powder as a seed nitrogen source, 65.1 g/L of pyruvic acid was harvested, with a yield of 0.61 g/g. This study proposes a promisingapproach for increasing the pyruvic acid titer and reducing the costs.
Graphical Abstract
Power system transient stability assessment based on the multiple paralleled convolutional neural network and gated recurrent unit
Authors: Cheng Shan , Yu Zihao , Liu Ye , Zuo Xianwang 
Published: October 2022

AbstractIn order to accurately evaluate power system stability in a timely manner after faults, and further improve the feature extraction ability of the model, this paper presents an improved transient stability assessment (TSA) method of CNN + GRU. This comprises a convolutional neural network (CNN) and gated recurrent unit (GRU). CNN has the feature extraction capability for a micro short-term time sequence, while GRU can extract characteristics contained in a macro long-term time sequence. The two are integrated to comprehensively extract the high-order features that are contained in a transient process. To overcome the difficulty of sample misclassification, a multiple parallel (MP) CNN + GRU, with multiple CNN + GRU connected in parallel, is created. Additionally, an improved focal loss (FL) function which can implement self-adaptive adjustment according to the neural network training is introduced to guide model training. Finally, the proposed methods are verified on the IEEE 39 and 145-bus systems. The simulation results indicate that the proposed methods have better TSA performance than other existing methods.
Race-related differences in the economic, healthcare-access, and psychological impact of COVID-19: personal resources associated with resilience
Authors: Schwartz Carolyn E. , Borowiec Katrina , Biletch Elijah , Rapkin Bruce D. 
Published: October 2022

Abstract
Background
The impact of the coronavirus disease 2019 (COVID) is worse among those with fewer financial resources, in jobs not amenable to remote work, and in denser living conditions. People of color are more likely to be among these vulnerable groups. Although race itself is a social construction and not based on underlying genetic/biological differences, this study investigated race/ethnicity differences in the negative repercussions of COVID and in the benefits of psychological and social resources.

Methods
This cross-sectional, web-based study (n = 4817) was administered to a heterogeneous United States sample in Spring/Summer 2020. Information was gathered on the following COVID-specific variables: Infection Status, Coping with Lockdown, Social Support, Post-traumatic Growth, Interpersonal Conflict, Worry about Self, Financial Impact on Family, Lack of Money, Inadequate Access to Healthcare, and Housing Instability. Resilience was operationalized as the ability to maintain a sense of wellness in the face of the pandemic, using the DeltaQuest Wellness measure. Multivariate linear regression (adjusting for demographics) and propensity-matched cohort analysis (matched on demographics) evaluated the impact of COVID-specific variables on Wellness in separate models for Whites and Non-Whites.

Findings
Both sets of models retained the same COVID-specific variables and explained about half of the variance in wellness. Coping with Lockdown, Social Support, and Post-traumatic Growth were associated with higher levels of Wellness in both Whites and Non-Whites, while Interpersonal Conflict and Worry about Self were associated with lower levels of Wellness. While these associations are similar, Non-Whites reported worse levels of some positive resources (e.g., social support) and more challenging levels of negative stressors (e.g., interpersonal, worry, financial). Non-Whites also reported much higher levels of post-traumatic growth.

Conclusion
COVID was a source of worry and even conflict, but also unlocked people’s resources in use of health-enhancing behavioral strategies, social support, and renewed gratitude for sources of personal meaning and value. The similar relationships between Whites and Non-Whites on wellness and COVID-specific stressors across racial groups underscore that race is a social construction, not a biological fact. Focusing on a renewed appreciation for sources of personal meaning, and particularly faith, seemed to buffer much of the COVID-related stress for Non-Whites.
Spectral CT in peritoneal carcinomatosis from ovarian cancer: a tool for differential diagnosis of small nodules?
Authors: Zorzetto Giada , Coppola Andrea , Molinelli Valeria , Angeretti Maria Gloria , Casarin Jvan , Fontana Federico , Piacentino Filippo , Carcano Giulio , Ghezzi Fabio , Venturini Massimo 
Published: October 2022

AbstractThe detection of peritoneal carcinomatosis in patients with ovarian cancer is crucial to establish the correct therapeutic planning (debulking surgery versus neoadjuvant chemotherapy).Often, however, the nodules of peritoneal carcinomatosis are very small in size or have a reticular appearance that can mimic the fat stranding that is typical of acute inflammation conditions. Our hypothesis is that the use of dual-layer spectral computed tomography with its applications, such as virtual monoenergetic imaging and Z-effective imaging, might improve the detection and the characterisation of peritoneal nodules, increasing sensitivity and diagnostic accuracy, as recently described for other oncological diseases.
Could surgical transepicondylar axis be identified accurately in preoperative 3D planning for total knee arthroplasty? A reproducibility study based on 3D-CT
Authors: Lei Kai , Liu Li Ming , Luo Jiang Ming , Ma Chao , Feng Qing , Yang Liu , Guo Lin 
Published: October 2022

Abstract
Background
Surgical transepicondylar axis (sTEA) is frequently used for positioning of femoral component rotation in total knee arthroplasty (TKA). Previous studies showed that intraoperative identification of sTEA was not reliable. While surgeons or engineers need to identify sTEA with three-dimensional (3D) computer-aid techniques pre- or intraoperatively, the reproducibility of sTEA identification on preoperative 3D images has not been explored yet. This study aimed to investigate the reproducibility of identifying sTEA in preoperative planning based on computed tomography (CT).

Methods
Fifty-nine consecutive patients (60 knees involved) who received TKA in our center from April 2019 to June 2019 were included in this study. Six experienced TKA surgeons identified sTEA three times on 3D model established on the basis of knee CT data. The projection angle of each sTEA and the posterior condyle axis on the transverse plane were measured and analyzed.

Results
The overall intra-observer reproducibility was moderate. The median intra-observer variation was 1.27°, with a maximum being up to 14.07°. The median inter-observer variation was 1.24°, and the maximum was 11.47°. The overall intra-class correlation coefficient (ICC) for inter-observer was 0.528 (95% CI 0.417, 0.643).

Conclusion
The identification of sTEA on a 3D model established on the basis of knee CT data may not be reliable. Combined with the previous cadaveric and surgical studies, caution should be exercised in determining femoral component rotation by referencing sTEA both preoperatively and intraoperatively.

Level of evidence
III
Heritage tourism evolution in Guangfu Ancient City, Hebei Province, China: an analysis with the improved creative destruction model
Authors: Wang Menghan , Bai Xiaoran , Su Mingming 
Published: October 2022

AbstractAncient cities and towns are popular tourism destinations worldwide. In this paper, Guangfu Ancient City in Yongnian County, Hebei Province, China, is taken as the case study and the modified creative destruction model is applied as the analytical framework to evaluate the multiactor dynamics of heritage tourism development. A mixed method approach is adopted, including a local resident survey, in-depth interviews with staff of the Guangfu Ancient City tourism site and government officials responsible for the heritage conservation and tourism development of the site, and a review of online tourist reviews, relevant government documents and reports. Based on the modified creative destruction model, local residents’ attitudes towards tourism development, changes in tourist numbers, the level of business and government investments, and the motivations of different stakeholders in tourism development are assessed by synthesising on-site research, historical data and other materials. Then, the tourism development stages for Guangfu Ancient City are identified as the precommodification stage before 2006, the early commodification stage from 2006 to 2011 and the advanced commodification stage from 2012 to 2017. The findings indicate that with rapid increases in investments from both corporate and government sources and in the number of tourists, the attitude of local residents towards tourism development remained positive. The results show that instead of entering the initial destruction stage, Guangfu Ancient City is in the transition stage from advanced commodification to creative enhancement given the government’s dominant role in tourism development, the heritage conservation motives of tourism entrepreneurs, the benefits to residents from tourism development ensured by government policies, and the shift in tourist type to postmodern tourists with double demands. The applicability of the modified creative destruction model is further discussed, and policy and management recommendations are generated to support the sustainable development of Guangfu Ancient City after the COVID-19 pandemic.
Maternal Glycaemic and Insulinemic Status and Newborn DNA Methylation: Findings in Women With Overweight and Obesity
Authors: Lecorguillé Marion , McAuliffe Fionnuala M , Twomey Patrick J , Viljoen Karien , Mehegan John , Kelleher Cecily C , Suderman Matthew , Phillips Catherine M 
Published: October 2022

AbstractContextMaternal dysglycaemia and prepregnancy obesity are associated with adverse offspring outcomes. Epigenetic mechanisms such as DNA methylation (DNAm) could contribute.ObjectiveTo examine relationships between maternal glycaemia, insulinemic status, and dietary glycemic indices during pregnancy and an antenatal behavioral-lifestyle intervention with newborn DNAm.MethodsWe investigated 172 women from a randomized controlled trial of a lifestyle intervention in pregnant women who were overweight or obese. Fasting glucose and insulin concentrations and derived indices of insulin resistance (HOMA-IR), β-cell function (HOMA-%B), and insulin sensitivity were determined at baseline (15) and 28 weeks’ gestation. Dietary glycemic load (GL) and index (GI) were calculated from 3-day food diaries. Newborn cord blood DNAm levels of 850K CpG sites were measured using the Illumina Infinium HumanMethylationEPIC array. Associations of each biomarker, dietary index and intervention with DNAm were examined.ResultsEarly pregnancy HOMA-IR and HOMA-%B were associated with lower DNAm at CpG sites cg03158092 and cg05985988, respectively. Early pregnancy insulin sensitivity was associated with higher DNAm at cg04976151. Higher late pregnancy insulin concentrations and GL scores were positively associated with DNAm at CpGs cg12082129 and cg11955198 and changes in maternal GI with lower DNAm at CpG cg03403995 (Bonferroni corrected P &lt; 5.99 × 10−8). These later associations were located at genes previously implicated in growth or regulation of insulin processes. No effects of the intervention on cord blood DNAm were observed. None of our findings were replicated in previous studies.ConclusionAmong women who were overweight or obese, maternal pregnancy dietary glycemic indices, glucose, and insulin homeostasis were associated with modest changes in their newborn methylome.Trial registrationISRCTN29316280