bluuebunny/crossref_metadata_2025_split huggingface dataset:
SPECK: an unsupervised learning approach for cell surface receptor abundance estimation for single-cell RNA-sequencing data
Authors: Javaid Azka , Frost H Robert 
Published: June 2023

Abstract

Summary
The rapid development of single-cell transcriptomics has revolutionized the study of complex tissues. Single-cell RNA-sequencing (scRNA-seq) can profile tens-of-thousands of dissociated cells from a tissue sample, enabling researchers to identify cell types, phenotypes and interactions that control tissue structure and function. A key requirement of these applications is the accurate estimation of cell surface protein abundance. Although technologies to directly quantify surface proteins are available, these data are uncommon and limited to proteins with available antibodies. While supervised methods that are trained on Cellular Indexing of Transcriptomes and Epitopes by Sequencing data can provide the best performance, these training data are limited by available antibodies and may not exist for the tissue under investigation. In the absence of protein measurements, researchers must estimate receptor abundance from scRNA-seq data. Therefore, we developed a new unsupervised method for receptor abundance estimation using scRNA-seq data called SPECK (Surface Protein abundance Estimation using CKmeans-based clustered thresholding) and primarily evaluated its performance against unsupervised approaches for at least 25 human receptors and multiple tissue types. This analysis reveals that techniques based on a thresholded reduced rank reconstruction of scRNA-seq data are effective for receptor abundance estimation, with SPECK providing the best overall performance.

Availability and implementation
SPECK is freely available at https://CRAN.R-project.org/package=SPECK.

Supplementary information
Supplementary data are available at Bioinformatics Advances online.
A New Synthesis among IR Theories? Moral Leadership in International Relations
Authors: Fang Yuanyuan 
Published: June 2023

Abstract
There is currently not only a retrogression of the global economy and governance in progress but also one of international morality, which the growth of populism has destructed. Moral retrogression has yet to arouse the same level of awareness among policymakers and the public as has economic retrogression. Scholars like Yan Xuetong, Joseph Nye, and Richard Ned Lebow, however, have discerned this problem and its significance. This article compares Yan and Nye, with respect to the gradual convergence of their views on leadership, along with that of Lebow’s perceptions of morality. But how can the research agendas of a moral realist, a neoliberalist, and a constructivist converge? It is argued that deep underlying similarities exist between their views on the nature of world politics and the perceptions of the current international order that may facilitate a much broader account of the international system. The relevance of this theoretical movement to real-world events is clear. Such convergence on moral leadership both reflects the reality of a moral leadership deficit and constitutes an antidote to the current global chaos.
Nanopore Third-Generation Sequencing for Comprehensive Analysis of Hemoglobinopathy Variants
Authors: Huang Weilun , Qu Shoufang , Qin Qiongzhen , Yang Xu , Han Wanqing , Lai Yongli , Chen Jiaqi , Zhou Shihao , Yang Xuexi , Zhou Wanjun 
Published: June 2023

Abstract

Background
Oxford Nanopore Technology (ONT) third-generation sequencing (TGS) is a versatile genetic diagnostic platform. However, it is nonetheless challenging to prepare long-template libraries for long-read TGS, particularly the ONT method for analysis of hemoglobinopathy variants involving complex structures and occurring in GC-rich and/or homologous regions.

Methods
A multiplex long PCR was designed to prepare library templates, including the whole-gene amplicons for HBA2/1, HBG2/1, HBD, and HBB, as well as the allelic amplicons for targeted deletions and special structural variations. Library construction was performed using long-PCR products, and sequencing was conducted on an Oxford Nanopore MinION instrument. Genotypes were identified based on integrative genomics viewer (IGV) plots.

Results
This novel long-read TGS method distinguished all single nucleotide variants and structural variants within HBA2/1, HBG2/1, HBD, and HBB based on the whole-gene sequence reads. Targeted deletions and special structural variations were also identified according to the specific allelic reads. The result of 158 α-/β-thalassemia samples showed 100% concordance with previously known genotypes.

Conclusions
This ONT TGS method is high-throughput, which can be used for molecular screening and genetic diagnosis of hemoglobinopathies. The strategy of multiplex long PCR is an efficient strategy for library preparation, providing a practical reference for TGS assay development.
Pre-emptive iron supplementation prevents myocardial iron deficiency and attenuates adverse remodelling after myocardial infarction
Authors: Chung Bomee , Wang Yong , Thiel Marleen , Rostami Fatemeh , Rogoll Anika , Hirsch Valentin G , Malik Zulaikha , Bührke Anne , Bär Christian , Klintschar Michael , Schmitto Jan D , Vogt Carla , Werlein Christopher , Jonigk Danny , Bauersachs Johann , Wollert Kai C , Kempf Tibor 
Published: June 2023

Abstract

Aims
Heart failure (HF) after myocardial infarction (MI) is a major cause of morbidity and mortality. We sought to investigate the functional importance of cardiac iron status after MI and the potential of pre-emptive iron supplementation in preventing cardiac iron deficiency (ID) and attenuating left ventricular (LV) remodelling.

Methods and results
MI was induced in C57BL/6J male mice by left anterior descending coronary artery ligation. Cardiac iron status in the non-infarcted LV myocardium was dynamically regulated after MI: non-haem iron and ferritin increased at 4 weeks but decreased at 24 weeks after MI. Cardiac ID at 24 weeks was associated with reduced expression of iron-dependent electron transport chain (ETC) Complex I compared with sham-operated mice. Hepcidin expression in the non-infarcted LV myocardium was elevated at 4 weeks and suppressed at 24 weeks. Hepcidin suppression at 24 weeks was accompanied by more abundant expression of membrane-localized ferroportin, the iron exporter, in the non-infarcted LV myocardium. Notably, similarly dysregulated iron homeostasis was observed in LV myocardium from failing human hearts, which displayed lower iron content, reduced hepcidin expression, and increased membrane-bound ferroportin. Injecting ferric carboxymaltose (15 µg/g body weight) intravenously at 12, 16, and 20 weeks after MI preserved cardiac iron content and attenuated LV remodelling and dysfunction at 24 weeks compared with saline-injected mice.

Conclusion
We demonstrate, for the first time, that dynamic changes in cardiac iron status after MI are associated with local hepcidin suppression, leading to cardiac ID long term after MI. Pre-emptive iron supplementation maintained cardiac iron content and attenuated adverse remodelling after MI. Our results identify the spontaneous development of cardiac ID as a novel disease mechanism and therapeutic target in post-infarction LV remodelling and HF.
Neodb: a comprehensive neoantigen database and discovery platform for cancer immunotherapy
Authors: Wu Tao , Chen Jing , Diao Kaixuan , Wang Guangshuai , Wang Jinyu , Yao Huizi , Liu Xue-Song 
Published: June 2023

Abstract
Neoantigens derived from somatic deoxyribonucleic acid alterations are ideal cancer-specific targets. However, integrated platform for neoantigen discovery is urgently needed. Recently, many scattered experimental evidences suggest that some neoantigens are immunogenic, and comprehensive collection of these experimentally validated neoantigens is still lacking. Here, we have integrated the commonly used tools in the current neoantigen discovery process to form a comprehensive web-based analysis platform. To identify experimental evidences supporting the immunogenicity of neoantigens, we performed comprehensive literature search and constructed the database. The collection of public neoantigens was obtained by using comprehensive features to filter the potential neoantigens from recurrent driver mutations. Importantly, we constructed a graph neural network (GNN) model (Immuno-GNN) using an attention mechanism to consider the spatial interactions between human leukocyte antigen and antigenic peptides for neoantigen immunogenicity prediction. The new easy-to-use R/Shiny web–based neoantigen database and discovery platform, Neodb, contains currently the largest number of experimentally validated neoantigens. In addition to validated neoantigen, Neodb also includes three additional modules for facilitating neoantigen prediction and analysis, including ‘Tools’ module (comprehensive neoantigen prediction tools); ‘Driver-Neo’ module (collection of public neoantigens derived from recurrent mutations) and ‘Immuno-GNN’ module (a novel immunogenicity prediction tool based on a GNN). Immuno-GNN shows improved performance compared with known methods and also represents the first application of GNN model in neoantigen immunogenicity prediction. The construction of Neodb will facilitate the study of neoantigen immunogenicity and the clinical application of neoantigen-based cancer immunotherapy.
Database URL https://liuxslab.com/Neodb/
Tumor size and presence of metastases in differentiated thyroid cancer: comparing cohorts from two countries
Authors: van Velsen Evert F S , Peeters Robin P , Stegenga Merel T , Mäder Uwe , Reiners Christoph , van Kemenade Folkert J , van Ginhoven Tessa M , Visser W Edward , Verburg Frederik A 
Published: June 2023

Abstract

Objective
Incidence of thyroid cancer varies widely, even across neighboring countries. Data on this phenomenon are largely lacking but are likely related to differences in health care systems. Therefore, we explored whether there are differences between populations from these 2 countries with respect to the relationship between tumor size and advanced disease.

Methods
We retrospectively studied 2 cohorts of adult differentiated thyroid cancer (DTC) patients from a Dutch and a German university hospital. We analyzed the presence of lymph node metastases with respect to tumor size for papillary thyroid cancer (PTC), and the presence of distant metastases for DTC, and PTC and follicular thyroid cancer (FTC) separately.

Results
We included 1771 DTC patients (80% PTC, 20% FTC; 24% lymph node and 8% distant metastases). For PTC, the proportion of patients with lymph node metastases was significantly higher in the Dutch than in the German population for tumors ≤ 1 cm (45% vs. 14%; P &lt; .001). For DTC, distant metastases occurred particularly significantly more frequently in the Dutch than in the German population for tumors ≤ 2 cm (7% vs. 2%; P = .004).

Conclusion
The presence of lymph node and distant metastases is significantly higher in pT1 DTC cases in the Dutch compared to the German cohort, which might be caused by differences in the indication for and application of diagnostic procedures eventually leading to DTC diagnosis. Our results implicate that one should be cautious when extrapolating results and guidelines from 1 country to another.
Small regulatory RNAs in Vibrio cholerae
Authors: Ghandour Rabea , Papenfort Kai 
Published: June 2023

Abstract
Vibrio cholerae is a major human pathogen causing the diarrheal disease, cholera. Regulation of virulence in V. cholerae is a multifaceted process involving gene expression changes at the transcriptional and post-transcriptional level. Whereas various transcription factors have been reported to modulate virulence in V. cholerae, small regulatory RNAs (sRNAs) have now been established to also participate in virulence control and the regulation of virulence-associated processes, such as biofilm formation, quorum sensing, stress response, and metabolism. In most cases, these sRNAs act by base-pairing with multiple target transcripts and this process typically requires the aid of an RNA-binding protein, such as the widely conserved Hfq protein. This review article summarizes the functional roles of sRNAs in V. cholerae, their underlying mechanisms of gene expression control, and how sRNAs partner with transcription factors to modulate complex regulatory programs. In addition, we will discuss regulatory principles discovered in V. cholerae that not only apply to other Vibrio species, but further extend into the large field of RNA-mediated gene expression control in bacteria.
The molecular pathogenesis of achalasia: a paired lower esophageal sphincter muscle and serum 4D label-free proteomic study
Authors: Chen Songfeng , Xing Xiangbin , Hou Xun , Zhuang Qianjun , Tan Niandi , Cui Yi , Wang Jinhui , Zhang Mengyu , Hu Shixian , Xiao Yinglian 
Published: June 2023

Abstract

Background
Achalasia is a primary esophageal motility disorder with potential molecular pathogenesis remaining uncertain. This study aimed to identify the differentially expressed proteins and potential pathways among achalasia subtypes and controls to further reveal the molecular pathogenesis of achalasia.

Methods
Paired lower esophageal sphincter (LES) muscle and serum samples from 24 achalasia patients were collected. We also collected 10 normal serum samples from healthy controls and 10 normal LES muscle samples from esophageal cancer patients. The 4D label-free proteomic analysis was performed to identify the potential proteins and pathways involved in achalasia.

Results
Analysis of Similarities showed distinct proteomic patterns of serum and muscle samples between achalasia patients and controls (both P &lt; 0.05). Functional enrichment analysis suggested that these differentially expressed proteins were immunity-, infection-, inflammation-, and neurodegeneration-associated. The mfuzz analysis in LES specimens showed that proteins involved in the extracellular matrix–receptor interaction increased sequentially between the control group, type III, type II, and type I achalasia. Only 26 proteins altered in the same directions in serum and muscle samples.

Conclusions
This first 4D label-free proteomic study of achalasia indicated that there were specific protein alterations in both the serum and muscle of achalasia, involving immunity, inflammation, infection, and neurodegeneration pathways. Distinct protein clusters between types I, II, and III revealed the potential molecular pathways associated with different disease stages. Analysis of proteins changed in both muscle and serum samples highlighted the importance of further studies on LES muscle and revealed potential autoantibodies.
The Role of a Composite Fitness Score in the Association Between Low-Density Cholesterol and All-Cause Mortality in Older Adults: An Individual Patient Data Meta-Analysis
Authors: van der Ploeg Milly A , Poortvliet Rosalinde K E , Bogaerts Jonathan M K , van der Klei Veerle M G T H , Kerse Ngaire , Rolleston Anna , Teh Ruth , Robinson Louise , Jagger Carol , Arai Yasumichi , Shikimoto Ryo , Abe Yukiko , Blom Jeanet W , Drewes Yvonne M , Gussekloo Jacobijn 
Published: June 2023

Abstract

Background
In the general population, an increase in low-density lipoprotein cholesterol (LDL-C) predicts higher cardiovascular disease risk, and lowering LDL-C can prevent cardiovascular disease and reduces mortality risk. Interestingly, in cohort studies that include very old populations, no or inverse associations between LDL-C and mortality have been observed. This study aims to investigate whether the association between LDL-C and mortality in the very old is modified by a composite fitness score.

Methods
A 2-stage meta-analysis of individual participant data from the 5 observational cohort studies. The composite fitness score was operationalized by performance on a combination of 4 markers: functional ability, cognitive function, grip strength, and morbidity. We pooled hazard ratios (HR) from Cox proportional-hazards models for 5-year mortality risk for a 1 mmol/L increase in LDL-C. Models were stratified by high/low composite fitness score.

Results
Composite fitness scores were calculated for 2 317 participants (median 85 years, 60% females participants), of which 994 (42.9%) had a high composite fitness score, and 694 (30.0%) had a low-composite fitness score. There was an inverse association between LDL-C and 5-year mortality risk (HR 0.87 [95% CI: 0.80–0.94]; p &lt; .01), most pronounced in participants with a low-composite fitness score (HR 0.85 [95% CI: 0.75–0.96]; p = .01), compared to those with a high composite fitness score (HR = 0.98 [95% CI: 0.83–1.15]; p = .78), the test for subgroups differences was not significant.

Conclusions
In this very old population, there was an inverse association between LDL-C and all-cause mortality, which was most pronounced in participants with a low-composite fitness scores.
Use of Caregiving Support Services Among Diverse Dementia Caregivers by Geographic Context
Authors: Yoshikawa Aya , Bouldin Erin D , López-Anuarbe Mónika , Kindratt Tiffany B , Sylvers Dominique L , Webster Noah J 
Published: June 2023

Abstract

Background and Objectives
Little is known about how race/ethnicity and geographic context relate to support service use among dementia caregivers. Our objectives were to investigate (a) whether the use of at least one formal caregiving service—support groups, respite care, and training—differed by race/ethnicity and across metro and nonmetro areas; and (b) whether predisposing, enabling, and need characteristics influenced support service use by race/ethnicity.

Research Design and Methods
Data were analyzed from a sample of primary caregivers of care recipients aged 65 years or older with probable dementia (n = 482) in the 2017 National Health and Aging Trends Study and National Study of Caregiving. We calculated weighted prevalence estimates and then used the Hosmer–Lemeshow goodness of fit statistic to find the best-fitting logistic regression models.

Results
Among minority dementia caregivers, support service use was higher in metro than nonmetro areas (35% and 15%); the trend was reversed for non-Hispanic White caregivers (47% nonmetro and 29% metro). The best-fitting regression models included predisposing, enabling, and need factors for both minority and non-Hispanic White caregivers. Younger age and more disagreement within the family were consistently associated with more service use in both groups. Among minority caregivers, better caregiver and care recipient health were associated with using support services. Among non-Hispanic White caregivers, nonmetro geographic context and caregiving interfering with valued activities were associated with using support services.

Discussion and Implications
Geographic context differently affected support service use and the influence of predisposing, enabling, and need factors varied by race/ethnicity.
Effect of Temperature on Mosquito Olfaction
Authors: Lahondère Chloé , Vinauger Clément , Liaw Jessica E , Tobin Kennedy K S , Joiner Jillian M , Riffell Jeffrey A 
Published: June 2023

Synopsis
Mosquitoes use a wide range of cues to find a host to feed on, eventually leading to the transmission of pathogens. Among them, olfactory cues (e.g., host-emitted odors, including CO2, and skin volatiles) play a central role in mediating host-seeking behaviors. While mosquito olfaction can be impacted by many factors, such as the physiological state of the insect (e.g., age, reproductive state), the impact of environmental temperature on the olfactory system remains unknown. In this study, we quantified the behavioral responses of Aedes aegypti mosquitoes, vectors of dengue, yellow fever, and Zika viruses, among other pathogens, to host and plant-related odors under different environmental temperatures.
A fatal mono-intoxication with 4-fluoroisobutyrylfentanyl: Case report with postmortem concentrations
Authors: Roosendaal Jeroen , Oosting Roelof , Kloos Dick-Paul , de Boer Hans H , van den Berg Jorrit D.J , Oldenhof Sander , Bosman Ingrid J 
Published: June 2023

Abstract
We report on a case of a 35-year-old man who died suddenly and unexpectedly due to a 4-fluoroisobutyrylfentanyl (4-FIBF) mono-intoxication. Pathological, toxicological and chemical investigations were conducted at the Netherlands Forensic Institute. A full three-cavity forensic pathological examination was performed according to international guidelines. Biological samples obtained during autopsy were comprehensively investigated for the presence of toxic substances using headspace gas chromatography (GC) with flame ionization detection, liquid chromatography–time-of-flight mass spectrometry (LC–TOF-MS), GC–MS, high-performance LC with diode array detection and LC–tandem MS (LC–MS-MS). The seized crystalline substance found next to the body was investigated using a presumptive color test, GC–MS, Fourier-transform infrared spectroscopy and nuclear magnetic resonance. Pathological investigation identified minor lymphocytic infiltrates in the heart, considered irrelevant for the cause of death. Toxicological analysis of the victims’ blood indicated the presence of a fluorobutyrylfentanyl (FBF) isomer, with no other compounds detected. The FBF isomer was identified in the seized crystalline substance as 4-FIBF. 4-FIBF concentrations were quantified in femoral blood (0.030 mg/L), heart blood (0.12 mg/L), vitreous humor (0.067 mg/L), brain tissue (&gt;0.081 mg/kg), liver tissue (0.44 mg/kg) and urine (approximately 0.01 mg/L). Based on the outcomes of the pathological, toxicological and chemical investigations, the cause of death of the deceased was attributed to a fatal 4-FIBF mono-intoxication. The presented case underlines the added value of a combined bioanalytical and chemical investigative approach to identify and subsequently quantify fentanyl isomers in postmortem cases. Furthermore, it demonstrates the importance of investigating the postmortem redistribution of novel fentanyl analogs to establish reference values and to subsequently allow for correct interpretation of cause of death analysis in future casework.
Screening for resistance alleles to Cry1 proteins through targeted sequencing in the native and invasive range of Spodoptera frugiperda (Lepidoptera: Noctuidae)
Authors: Tandy Peter , Lamour Kurt , Placidi de Bortoli Caroline , Nagoshi Rodney , Emrich Scott J , Jurat-Fuentes Juan Luis 
Published: June 2023

Abstract
The fall armyworm, Spodoptera frugiperda (J. E. Smith), is a highly polyphagous pest native to the tropical Americas that has recently spread to become a global super-pest threatening food and fiber production. Transgenic crops producing insecticidal Cry and Vip3Aa proteins from Bacillus thuringiensis (Bt) are used for control of this pest in its native range. The evolution of practical resistance represents the greatest threat to sustainability of this technology and its potential efficacy in the S. frugiperda invasive range. Monitoring for resistance is vital to management approaches delaying S. frugiperda resistance to Bt crops. DNA-based resistance screening provides higher sensitivity and cost-effectiveness than currently used bioassay-based monitoring. So far, practical S. frugiperda resistance to Bt corn-producing Cry1F has been genetically linked to mutations in the SfABCC2 gene, providing a model to develop and test monitoring tools. In this study, we performed targeted SfABCC2 sequencing followed by Sanger sequencing to confirm the detection of known and candidate resistance alleles to Cry1F corn in field-collected S. frugiperda from continental USA, Puerto Rico, Africa (Ghana, Togo, and South Africa), and Southeast Asia (Myanmar). Results confirm that the distribution of a previously characterized resistance allele (SfABCC2mut) is limited to Puerto Rico and identify 2 new candidate SfABCC2 alleles for resistance to Cry1F, one of them potentially spreading along the S. frugiperda migratory route in North America. No candidate resistance alleles were found in samples from the invasive S. frugiperda range. These results provide support for the potential use of targeted sequencing in Bt resistance monitoring programs.