bluuebunny/crossref_metadata_2025_split huggingface dataset:
Kernelized multiview signed graph learning for single-cell RNA sequencing data
Authors: Karaaslanli Abdullah , Saha Satabdi , Maiti Tapabrata , Aviyente Selin 
Published: April 2023

Abstract
Background
Characterizing the topology of gene regulatory networks (GRNs) is a fundamental problem in systems biology. The advent of single cell technologies has made it possible to construct GRNs at finer resolutions than bulk and microarray datasets. However, cellular heterogeneity and sparsity of the single cell datasets render void the application of regular Gaussian assumptions for constructing GRNs. Additionally, most GRN reconstruction approaches estimate a single network for the entire data. This could cause potential loss of information when single cell datasets are generated from multiple treatment conditions/disease states.

Results
To better characterize single cell GRNs under different but related conditions, we propose the joint estimation of multiple networks using multiple signed graph learning (scMSGL). The proposed method is based on recently developed graph signal processing (GSP) based graph learning, where GRNs and gene expressions are modeled as signed graphs and graph signals, respectively. scMSGL learns multiple GRNs by optimizing the total variation of gene expressions with respect to GRNs while ensuring that the learned GRNs are similar to each other through regularization with respect to a learned signed consensus graph. We further kernelize scMSGL with the kernel selected to suit the structure of single cell data.

Conclusions
scMSGL is shown to have superior performance over existing state of the art methods in GRN recovery on simulated datasets. Furthermore, scMSGL successfully identifies well-established regulators in a mouse embryonic stem cell differentiation study and a cancer clinical study of medulloblastoma.
Assessment of plasmids for relating the 2020 Salmonella enterica serovar Newport onion outbreak to farms implicated by the outbreak investigation
Authors: Commichaux Seth , Rand Hugh , Javkar Kiran , Molloy Erin K. , Pettengill James B. , Pightling Arthur , Hoffmann Maria , Pop Mihai , Jayeola Victor , Foley Steven , Luo Yan 
Published: April 2023

Abstract
Background
The Salmonella enterica serovar Newport red onion outbreak of 2020 was the largest foodborne outbreak of Salmonella in over a decade. The epidemiological investigation suggested two farms as the likely source of contamination. However, single nucleotide polymorphism (SNP) analysis of the whole genome sequencing data showed that none of the Salmonella isolates collected from the farm regions were linked to the clinical isolates—preventing the use of phylogenetics in source identification. Here, we explored an alternative method for analyzing the whole genome sequencing data driven by the hypothesis that if the outbreak strain had come from the farm regions, then the clinical isolates would disproportionately contain plasmids found in isolates from the farm regions due to horizontal transfer.

Results
SNP analysis confirmed that the clinical isolates formed a single, nearly-clonal clade with evidence for ancestry in California going back a decade. The clinical clade had a large core genome (4,399 genes) and a large and sparsely distributed accessory genome (2,577 genes, at least 64% on plasmids). At least 20 plasmid types occurred in the clinical clade, more than were found in the literature for Salmonella Newport. A small number of plasmids, 14 from 13 clinical isolates and 17 from 8 farm isolates, were found to be highly similar (> 95% identical)—indicating they might be related by horizontal transfer. Phylogenetic analysis was unable to determine the geographic origin, isolation source, or time of transfer of the plasmids, likely due to their promiscuous and transient nature. However, our resampling analysis suggested that observing a similar number and combination of highly similar plasmids in random samples of environmental Salmonella enterica within the NCBI Pathogen Detection database was unlikely, supporting a connection between the outbreak strain and the farms implicated by the epidemiological investigation.

Conclusion
Horizontally transferred plasmids provided evidence for a connection between clinical isolates and the farms implicated as the source of the outbreak. Our case study suggests that such analyses might add a new dimension to source tracking investigations, but highlights the need for detailed and accurate metadata, more extensive environmental sampling, and a better understanding of plasmid molecular evolution.
Titration-based normalization of antibody amount improves consistency of ChIP-seq experiments
Authors: Caride Ariel , Jang Jin Sung , Shi Geng-Xian , Lenz Sam , Zhong Jian , Kim Kwan Hyun , Allen Mariet , Robertson Keith D. , Farrugia Gianrico , Ordog Tamas , Ertekin-Taner Nilüfer , Lee Jeong-Heon 
Published: April 2023

AbstractChromatin immunoprecipitation (ChIP) is an antibody-based approach that is frequently utilized in chromatin biology and epigenetics. The challenge in experimental variability by unpredictable nature of usable input amounts from samples and undefined antibody titer in ChIP reaction still remains to be addressed. Here, we introduce a simple and quick method to quantify chromatin inputs and demonstrate its utility for normalizing antibody amounts to the optimal titer in individual ChIP reactions. For a proof of concept, we utilized ChIP-seq validated antibodies against the key enhancer mark, acetylation of histone H3 on lysine 27 (H3K27ac), in the experiments. The results indicate that the titration-based normalization of antibody amounts improves assay outcomes including the consistency among samples both within and across experiments for a broad range of input amounts.
Crystalline sirolimus-coated balloon (cSCB) angioplasty in an all-comers, patient population with stable and unstable coronary artery disease including chronic total occlusions: rationale, methodology and design of the SCORE trial
Authors: Otto Sylvia , Díaz Victor Alfonso Jiménez , Weilenmann Daniel , Cuculi Florim , Nuruddin Amin Ariff , Leibundgut Gregor , Alfonso Fernando , Wan Ahmad Wan Azman , Pyxaras Stylianos , Rittger Harald , Steen Philip , Gaede Luise , Schulze Christian , Wöhrle Jochen , Rosenberg Mark , Waliszewski Matthias W. 
Published: April 2023

Abstract
Background
A decade ago, the iopromide-paclitaxel coated balloon (iPCB) was added to the cardiologist‘s toolbox to initially treat in-stent restenosis followed by the treatment of de novo coronary lesions. In the meantime, DES technologies have been substantially improved to address in-stent restenosis and thrombosis, and shortened anti-platelet therapy. Recently, sirolimus-coated balloon catheters (SCB) have emerged to provide an alternative drug to combat restenosis.

Methods
The objective of this study is to determine the safety and efficacy of a novel crystalline sirolimus-coated balloon (cSCB) technology in an unselective, international, large-scale patient population. Percutaneous coronary interventions of native stenosis, in-stent stenosis, and chronic total occlusions with the SCB in patients with stable coronary artery disease or acute coronary syndrome were included. The primary outcome variable is the target lesion failure (TLF) rate at 12 months, defined as the composite rate of target vessel myocardial infarction (TV-MI), cardiac death or ischemia-driven target lesion revascularization (TLR). The secondary outcome variables include TLF at 24 months, ischemia driven TLR at 12 and 24 months and all-cause death, cardiac death at 12 and 24 months.

Discussion
Since there is a wealth of patient-based all-comers data for iPCB available for this study, a propensity-score matched analysis is planned to compare cSCB and iPCB for the treatment of de novo and different types of ISR. In addition, pre-specified analyses in challenging lesion subsets such as chronic total occlusions will provide evidence whether the two balloon coating technologies differ in their clinical benefit for the patient.

Trial registration number
ClinicalTrials.gov Identifier: NCT04470934.
Patients’ perspectives on, experience with and concerns about crohn's disease: insights from Chinese social media
Authors: Sun Shaopeng , Hu Yunhong , Li Heng , Chen Jiajia , Lou Yijie , Weng Chunyan , Chen Lixia , Lv Bin 
Published: April 2023

Abstract
Aim
The aim of this study was to explore the experience and perceptions of patients with Crohn’s disease in China.

Methods
Data mining was used to investigate posts in Crohn’s disease online medical communities. The data were collected through the crawler code, and latent Dirichlet allocation (LDA) and grounded theory were used to mine the theme features after data cleaning.

Results
In analyzing the topic characteristics of online posts, LDA divided 6757 posts into 15 topics on four aspects: seeking disease information, making decisions on medication use, psychological burden, and communicating about diet and nutrition.

Conclusion
Overall, social media is patient-centric and helps us better understand the experiences and perceptions of patients. This study can help medical staff predict the thoughts and concerns of Crohn's disease patients during the treatment process, facilitate doctor-patient communication, and assist in the formulation of medical policies.
Assessment of drug-related problems at the emergency department in older patients living with frailty: pharmacist-led medication reviews within a geriatric care team
Authors: van Nuland Merel , Butterhoff Madelon , Verwijmeren Karin , Berger Florine , Hogervorst Vera M. , de Jonghe Annemarieke , van der Linden Paul D 
Published: April 2023

Abstract
Background
Older patients are vulnerable to experiencing drug related problems (DRPs), which may result in emergency department (ED) visits. However, it is not standard practice to conduct medications reviews during ED visit. The aim of this study was to assess the number of DRPs in older patients living with frailty at the ED, identified through pharmacist-led medication reviews within a geriatric care team, and to determine the acceptance rate of pharmacists’ recommendations among hospital physicians and general practitioners or elderly care specialists.

Methods
A retrospective observational study was performed in patients ≥ 70 years living with frailty at the ED at Tergooi Medical Center. Pharmacist-led medication reviews were conducted to identify and classify DRPs as part of a larger geriatric assessment. The acceptance rate of given recommendations was determined during follow-up.

Results
A total of 356 ED visits were included. The mean (standard deviation, SD) age of patients was 83 (6.8) years. About 76% of patients had at least one DRP. In total, 548 DRPs were identified with a mean of 1.5 DRP (SD 1.3) per patient. The acceptance rate of medication recommendations in admitted patients was 55%, and 32% among general practitioners/elderly care specialists in discharged patients.

Conclusions
Pharmacist-led medication reviews as part of a geriatric care team identified DRPs in 76% of older patients living with frailty at the ED. The acceptance rate was substantially higher in admitted patients compared to discharged patients.
Association between any underlying health condition and COVID-19-associated hospitalization by age group, Washington State, 2020–2021: a retrospective cohort study
Authors: McConnell Kate H. , Hajat Anjum , Sack Coralynn , Mooney Stephen J. , Khosropour Christine M. 
Published: April 2023

Abstract
Background
Presence of at least one underlying health condition (UHC) is positively associated with severe COVID-19, but there is limited research examining this association by age group, particularly among young adults.

Methods
We examined age-stratified associations between any UHC and COVID-19-associated hospitalization using a retrospective cohort study of electronic health record data from the University of Washington Medicine healthcare system for adult patients with a positive SARS-CoV-2 test from February 29, 2020, to March 13, 2021. Any UHC was defined as documented diagnosis of at least one UHC identified by the CDC as a potential risk factor for severe COVID-19. Adjusting for sex, age, race and ethnicity, and health insurance, we estimated risk ratios (aRRs) and risk differences (aRDs), overall and by age group (18–39, 40–64, and 65 + years).

Results
Among patients aged 18–39 (N = 3,249), 40–64 (N = 2,840), 65 + years (N = 1,363), and overall (N = 7,452), 57.5%, 79.4%, 89.4%, and 71.7% had at least one UHC, respectively. Overall, 4.4% of patients experienced COVID-19-associated hospitalization. For all age groups, the risk of COVID-19-associated hospitalization was greater for patients with any UHC vs. those without (18–39: 2.2% vs. 0.4%; 40–64: 5.6% vs. 0.3%; 65 + : 12.2% vs. 2.8%; overall: 5.9% vs. 0.6%). The aRR comparing patients with vs. those without UHCs was notably higher for patients aged 40–64 years (aRR [95% CI] for 18–39: 4.3 [1.8, 10.0]; 40–64: 12.9 [3.2, 52.5]; 65 + : 3.1 [1.2, 8.2]; overall: 5.3 [3.0, 9.6]). The aRDs increased across age groups (aRD [95% CI] per 1,000 SARS-CoV-2-positive persons for 18–39: 10 [2, 18]; 40–64: 43 [33, 54]; 65 + : 84 [51, 116]; overall: 28 [21, 35]).

Conclusions
Individuals with UHCs are at significantly increased risk of COVID-19-associated hospitalization regardless of age. Our findings support the prevention of severe COVID-19 in adults with UHCs in all age groups and in older adults aged 65 + years as ongoing local public health priorities.
A potential link between fibroblast growth factor-23 and the progression of AKI to CKD
Authors: Lu Yinghui , Xu Shutian , Tang Rong , Han Cui , Zheng Chunxia 
Published: April 2023

Abstract
Background
Patients who recover from acute kidney injury (AKI) have a 25% increase in the risk of chronic kidney disease (CKD) and a 50% increase in mortality after a follow-up of approximately 10 years. Circulating FGF-23 increases significantly early in the development of AKI, is significantly elevated in patients with CKD and has become a major biomarker of poor clinical prognosis in CKD. However, the potential link between fibroblast growth factor-23 levels and the progression of AKI to CKD remains unclear.

Method
Serum FGF-23 levels in AKI patients and ischaemia‒reperfusion injury (IRI) mice were detected with ELISA. Cultured HK2 cells were incubated with FGF-23 and PD173074, a blocker of FGFR, and then TGFβ/Smad and Wnt/β-catenin were examined with immunofluorescence and immunoblotting. Quantitative real-time polymerase chain reaction was used to detect the expression of COL1A1 and COL4A1. Histologic staining confirmed renal fibrosis.

Results
The level of serum FGF-23 was significantly different between AKI patients and healthy controls (P < 0.01). Moreover, serum FGF-23 levels in the CKD progression group were significantly higher than those in the non-CKD progression group of AKI patients (P < 0.01). In the AKI-CKD mouse model, serum FGF-23 levels were increased, and renal fibrosis occurred; moreover, the protein expression of β-catenin and p-Smad3 was upregulated. PD173074 downregulated the expression of β-catenin and p-Smad3 and reduced fibrosis in both mice and HK2 cells.

Conclusion
The increase in FGF-23 may be associated with the progression of AKI to CKD and may mediate renal fibrosis via TGF-β and Wnt/β-catenin activation.
The relationship between psychological conditions and recurrence of benign paroxysmal positional vertigo: a retrospective cohort study
Authors: Shu Yuexin , Liao Nannan , Fang Fang , Shi Qiuling , Yan Ning , Hu Yaoyue 
Published: April 2023

Abstract
Background
Psychological conditions have been found to be associated with an increased risk of incident benign paroxysmal positional vertigo (BPPV). However, much less is known on whether and how psychological conditions such as anxiety, insomnia and obsessive–compulsive disorder (OCD) affect the recurrence of BPPV.

Methods
A retrospective cohort study of 2,612 outpatients and inpatients diagnosed with BPPV between September 2012 and August 2020. BPPV recurrence was followed up until February 2021. The Cox proportional hazard regression was used to analyze the association between psychological conditions and the risk of the first recurrence. Poisson regression was applied to analyze the association between psychological conditions and the number of recurrences in patients with at least one relapse.

Results
During the follow-up, 391 patients had at least one BPPV recurrence. Female BPPV patients were more likely than male patients to experience relapses than male patients, but the characteristics of BPPV recurrence (number of recurrences and duration between recurrences) did not differ between men and women. After adjustment for sex, age and comorbidities, a heightened risk of first BPPV recurrence was found to be associated with anxiety (hazard ratio [HR]: 1.30, 95% confidence interval [CI]: 1.01, 1.68) and OCD (HR: 2.15, 95% CI: 1.31, 3.52). An increased risk of first BPPV recurrence associated with insomnia was only observed in male patients (HR: 2.22, 95% CI: 1.24, 3.98) but not in female patients (HR: 0.91, 95% CI: 0.63, 1.31). None of these psychological conditions were associated with the number of recurrences in patients who experienced recurrence.

Conclusions
The presence of anxiety and OCD increased the risk of first BPPV recurrence, as well as insomnia for male patients. These psychological conditions were not associated with the number of BPPV recurrences. Diagnosis and treatment of these psychological conditions could be a useful strategy to prevent the recurrence of BPPV.
A prospective, double-blinded cohort study using quantitative fetal fibronectin testing in symptomatic women for the prediction of spontaneous preterm delivery
Authors: Ng Vivian Wai Yan , Seto Mimi Tin Yan , Lewis Holly , Cheung Ka Wang 
Published: April 2023

Abstract
Background
Spontaneous preterm birth (PTB) affects 6.5% of deliveries in Hong Kong. Quantitative fetal fibronectin (fFN) is under-utilised as a test for PTB prediction in Hong Kong. Our objective was to evaluate the effectiveness of quantitative fFN in predicting spontaneous PTB in women with symptoms of threatened preterm labour (TPTL) in our population.

Methods
A prospective, double-blinded cohort study of women with a singleton gestation and TPTL symptoms presenting to a tertiary hospital in Hong Kong between 24 + 0 to 33 + 6 weeks was performed from 1st October 2020 and 31st October 2021. Women with vaginal bleeding, ruptured membranes, and cervical dilation > 3 cm were excluded. The primary outcome was to test the characteristics of quantitative fFN in predicting spontaneous PTB < 37 weeks. Secondary outcome was to investigate the relationship between fFN value and time to PTB. Test characteristics of quantitative fFN at different thresholds were evaluated.

Results
48 women with TPTL were recruited. All had fFN testing at admission with the results being concealed from the obstetrician managing the patient. 10 mothers had PTB (< 37 weeks’ gestation). 7/48 (15%) had a subsequent PTB within 14 days from testing and 5 (10%) delivered within 48 h. The negative predictive value (NPV) of predicting delivery within 14 days was 97.3% and 100% when using a cut-off of < 50ng/ml and < 10ng/ml respectively. Using > 200 ng/ml as cut-off can also reliably predict delivery within 48 h – 7 days with positive predictive value PPV of 100%; as well as PTB before 37 weeks.

Conclusions
Quantitative fFN has predictive value for spontaneous PTB prediction in symptomatic women in a Hong Kong population. fFN concentration could help clinicians rule out PTB and avoid unnecessary interventions and hospitalisation.
Lovastatin inhibits erythroleukemia progression through KLF2-mediated suppression of MAPK/ERK signaling
Authors: Gao Jian , Hu Jifen , Yu Fang , Wang Chunlin , Sheng Danmei , Liu Wuling , Hu Anling , Yu Kunling , Xiao Xiao , Kuang Yi , Zacksenhaus Eldad , Gajendran Babu , Ben-David Yaacov 
Published: April 2023

Abstract
Background
Lovastatin, an HMG-CoA inhibitor and an effective cholesterol lowering drug, exhibits anti-neoplastic activity towards several types of cancer, although the underlying mechanism is still not fully understood. Herein, we investigated mechanism of growth inhibition of leukemic cells by lovastatin.

Methods
RNAseq analysis was used to explore the effect of lovastatin on gene expression in leukemic cells. An animal model of leukemia was used to test the effect of this statin in vivo. FAM83A and DDIT4 expression was knocked-downed in leukemia cells via lentivirus-shRNA. Western blotting, RT-qPCR, cell cycle analysis and apoptosis assays were used to determine the effect of lovastatin-induced growth suppression in leukemic cells in vitro.

Results
Lovastatin treatment strongly inhibited cancer progression in a mouse model of erythroleukemia induced by Friend virus. In tissue culture, lovastatin inhibited cell proliferation through induction of G1 phase cell cycle arrest and apoptosis. Interestingly, lovastatin induced most known genes associated with cholesterol biosynthesis in leukemic cells. Moreover, it suppressed ERK1/2 phosphorylation by downregulating FAM83A and DDIT4, two mediators of MAP-Kinase signaling. RNAseq analysis of lovastatin treated leukemic cells revealed a strong induction of the tumor suppressor gene KLF2. Accordingly, lentivirus-mediated knockdown of KLF2 antagonized leukemia cell suppression induced by lovastatin, associated with higher ERK1/2 phosphorylation compared to control. We further show that KLF2 induction by lovastatin is responsible for lower expression of the FAM83A and DDIT4 oncogenes, involved in the activation of ERK1/2. KLF2 activation by lovastatin also activated a subset of cholesterol biosynthesis genes that may further contribute to leukemia suppression.

Conclusions
These results implicate KLF2-mediated FAM83A/DDIT4/MAPK suppression and activation of cholesterol biosynthesis as the mechanism of leukemia cell growth inhibition by lovastatin.
Known risk factors of the developmental dysplasia of the hip predicting more severe clinical presentation and failure of Pavlik harness treatment
Authors: Lankinen Vilma , Helminen Mika , Bakti Karim , Välipakka Jarmo , Laivuori Hannele , Hyvärinen Anna 
Published: April 2023

Abstract
Purpose
Developmental dysplasia of the hip (DDH) varies from mild instability of the hip to subluxation or total dislocation of the joint. Well-known risk factors of DDH include pre-natal breech position, female sex, positive family history, hip side, primiparity and the mode of delivery. Aim of the present study was to further evaluate known risk-factors of DDH, find associations with more severe dysplasia (characterized with Ortolani positivity) and find risk factors of failure of the Pavlik harness treatment.

Material and methods
All children with the diagnosis of DDH treated in Tampere University hospital in the years 1998–2018 were retrospectively identified for the study and the data was collected from the medical records. Teratological dislocations (n = 3) were excluded from the analysis. Total of 945 patients were included.

Results
Breech presentation was strongly associated with Ortolani positivity (p < 0.001). Breech presentation was not associated with ending up for spica casting and/or operative treatment (p = 0.291) despite the association with Ortolani positivity. Ortolani positivity (p = 0.002), positive family history (p = 0.013) and girl sex (p = 0.029) were associated with ending up for spica casting and/or operative treatment.

Conclusion
Breech presentation seems to increase the risk of Ortolani positive DDH. However, these infants are likely to recover with initially started Pavlik harness treatment, as it was not associated with elevated risk for undergoing more robust treatments. Positive family history and girl sex are associated with the most severe cases of developmental dysplasia of the hip, and it may predispose to the failure of the Pavlik harness treatment.