bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prediction of methylation status using WGS data of plasma cfDNA for multi-cancer early detection (MCED)
Authors: Cui Pin , Zhou Xiaozhou , Xu Shu , He Weihuang , Huang Guozeng , Xiong Yong , Zhang Chuxin , Chang Tingmin , Feng Mingji , Lai Hanming , Pan Yi 
Published: February 2024

Abstract
Background
Cell-free DNA (cfDNA) contains a large amount of molecular information that can be used for multi-cancer early detection (MCED), including changes in epigenetic status of cfDNA, such as cfDNA fragmentation profile. The fragmentation of cfDNA is non-random and may be related to cfDNA methylation. This study provides clinical evidence for the feasibility of inferring cfDNA methylation levels based on cfDNA fragmentation patterns. We performed whole-genome bisulfite sequencing and whole-genome sequencing (WGS) on both healthy individuals and cancer patients. Using the information of whole-genome methylation levels, we investigated cytosine–phosphate–guanine (CpG) cleavage profile and validated the method of predicting the methylation level of individual CpG sites using WGS data.

Results
We conducted CpG cleavage profile biomarker analysis on data from both healthy individuals and cancer patients. We obtained unique or shared potential biomarkers for each group and built models accordingly. The modeling results proved the feasibility to predict the methylation status of single CpG sites in cfDNA using cleavage profile model from WGS data.

Conclusion
By combining cfDNA cleavage profile of CpG sites with machine learning algorithms, we have identified specific CpG cleavage profile as biomarkers to predict the methylation status of individual CpG sites. Therefore, methylation profile, a widely used epigenetic biomarker, can be obtained from a single WGS assay for MCED.
Coronary chronic total occlusion on coronary CT angiography: what radiologists should know?
Authors: Xu Wei , Ma Junfeng , Chen Yiwen , Zhou Fan , Zhou Changsheng , Zhang Long Jiang 
Published: February 2024

AbstractCoronary chronic total occlusion (CTO) often occurs in patients with obstructive coronary artery disease, which remains one of the greatest challenges for interventional cardiologists. Coronary computed tomography angiography (CCTA) with its emerging post-processing techniques can provide a detailed assessment of CTO lesions before percutaneous coronary intervention (PCI), playing an important role in the clinical management of CTO PCI, from early diagnosis, pre-procedural outcome prediction, the crossing algorithm planning, intraprocedural guidance, and finally post-procedural assessment and follow-up. In addition, the feasibility of CT perfusion (CTP) in patients with CTO has been validated. Combined CCTA and CTP have the great potential to be the one-stop-shop imaging modality for assessing both anatomy and function of CTO lesions. This review aims to make radiologists understand the role of CCTA in the diagnosis and assessment of CTO lesions, thus assisting interventionalists in optimizing CTO PCI crossing strategies with the expertise of radiologists.Critical relevance statementThe anatomical features of CTO on CCTA can reveal the complexity of CTO lesions and are associated with CTO PCI outcome, thus helping interventionalists optimize CTO PCI crossing strategies.Key points• CTO is the common lesion in invasive coronary angiography, and CTO PCI is technically difficult and its success rate is relatively low.• Length, collaterals, and attenuation-related signs can help distinguish CTO from subtotal occlusion.• The anatomical features of CTO lesions can help grade the difficulty of CTO PCI and predict procedural outcomes and long-term outcomes of CTO PCI.• The real-time fusion of CCTA with fluoroscopic angiography can be applied in highly complicated CTO lesions.• After CTO PCI, CCTA can help guide a second CTO PCI re-entry or follow up stent patency.Graphical Abstract
Timing of preventive behavior in the case of a new and evolving health risk: the case of COVID-19 vaccination
Authors: Gupta Deeksha , Rudisill Caroline 
Published: February 2024

Abstract
Background
Time preferences for preventive behavior under novel risks and uncertain contexts may differ from timing preferences related to familiar risks. Therefore, it is crucial to examine drivers of preventative health behavior timing in light of new health risks. Using the case of COVID-19, we examine factors affecting vaccination timing plans when vaccines were widely available in the European Union (EU).

Methods
We use data from the Flash Eurobarometer 494 survey (May 21–26, 2021), which collected information on EU residents’ attitudes towards COVID-19 vaccinations. We also use the ‘Our World in Data’ vaccination database for country-level COVID-19 vaccination rates. Probit regressions were conducted to determine how local vaccination rates, trust in information sources, social norms, vaccine safety beliefs, and risk understanding affected the probability of COVID-19 vaccination delay.

Results
Of total participants (n = 26,106), 9,063 (34.7%) were vaccinated, 7,114 (27.3%) wanted to get vaccinated as soon as possible, 5,168 (19.8%) wanted to delay vaccination and 2,962 (11.4%) resisted vaccination. Participants were more likely to delay COVID-19 vaccination if they lived in a country with lower vaccination prevalence, trusted online social networks, family, friends, and colleagues for vaccination information, were eager to follow vaccination-related social norms, expressed vaccine safety concerns, and understood the risk of catching COVID-19 without a vaccine to be lower.

Conclusions
Results from the study contribute to understanding important factors that predict timing of vaccination plans. These findings can also contribute to the wider knowledge base about timing of preventive behavior uptake in novel risk contexts.
Impact and policy supporting Thailand innovation driven enterprise: orchestrating university innovation and entrepreneurship ecosystem with public and private stakeholders
Authors: Thawesaengskulthai Natcha , Chatmarathong Awirut , Koiwanit Jarotwan 
Published: February 2024

AbstractThis research paper aims to investigate the impediments faced by innovation-driven enterprises in Thailand and to explore the current measures, policies, and mechanisms related to innovation-driven enterprises (IDEs)’ development both domestically and internationally. The study encompasses a comprehensive approach, including an analysis of an innovation entrepreneur database comprising 320 investors and 883 IDEs. Moreover, semi-structure in-depth interviews were conducted with three investors, twenty-two IDEs’ founders, eight executives, and experts from various sectors, including government, university incubators, and the private sector in Thailand. Through this multifaceted investigation, this paper sheds light on the key factors that hinder the success of IDEs in Thailand, which primarily revolve around the quality of entrepreneurs (Team), Product and Market Fit, and Support. These factors collectively impact the depth of knowledge, business incubation, acceleration programs, and the effectiveness of laws, measures, and policies in supporting innovation capability development within IDEs. In addition, this paper presents a framework for Thailand’s IDEs hub, facilitating the connection between the university's innovation and entrepreneurship ecosystem with public and private stakeholders. This framework serves as a mechanism to address the identified hindrances and foster a conducive environment for IDEs development. To address the obstacles, this paper proposes three crucial strategies, namely, (1) talent management, (2) ease of doing scaleup, and (3) availability of funding. These strategies are envisioned to counteract the identified challenges and can be effectively implemented through an operating model and practical working procedures tailored to suit the specific context of Thailand.
Sustainability of European agri-food supply chain using MRP-PCI multicriteria analysis method
Authors: Ricciolini Elena , Rocchi Lucia , Paolotti Luisa , Gennari Nicola , Ottaviani Alessandro , de la Rúa Francisco Ruiz , Boggia Antonio 
Published: February 2024

AbstractThe need for a more sustainable agri-food system is a topic that has attracted growing interest in recent years. Several international and European policies such as Agenda 2030 and the European Green Deal have been defined with the aim of making agri-food systems more sustainable at all stages of the supply chain, from production to consumption. Particularly, the European Union concentrates several policies on it. Therefore, the assessment of the level of sustainability among the states of the European Union is a key aspect to properly address and evaluate the implementation of these policies. The objective of this paper is to measure the sustainability of the global agri-food supply chain (AFSC) of the European Union countries through the application of a multi-criteria analysis. In particular, the method used is the Multiple Reference Point Partially Compensatory Indicator, which allows the creation of composite indicators using different levels of compensation across them. A set of 50 indicators, referred to 2011 and 2019, were built and then divided into the three basic dimensions of sustainability (economic, social and environmental), aggregated into the four main AFSC sectors (agriculture, food industry, distribution, and consumption) in order to obtain an overall sustainability index. Through such an index we provided a sustainability ranking for the EU countries, while the analysis of dimensions of each sector contributed to increase the knowledge about the supply chain that can be used by decision-makers. According to the results, Italy achieved the best level of sustainability of the AFSC with a value of 48.53, followed by Sweden, Austria, Spain, France, Germany, the Czech Republic, Portugal and Slovakia. In relation to the different sectors, the biggest problems were observed in the consumption sector, where most countries did not perform well, especially for the social dimension (e.g. excess of overweight and obese persons). In contrast, the performance of the agricultural sector was good, with few exceptions, showing a fair state of sustainability.
Dual-targeted CAR T-cell immunotherapies for hematological malignancies: latest updates from the 2023 ASH annual meeting
Authors: Yang Jingyi , Guo Hao , Han Lu , Song Yongping , Zhou Keshu 
Published: February 2024

AbstractOver the past few years, dual-targeted chimeric antigen receptor (CAR) T-cell therapy has been employed in the management of hematological malignancies to mitigate treatment failure, particularly in cases of antigen escape. The most widely used approaches include CD19/CD20, CD20/CD22, and BCMA/CD19 CAR T-cells. Alternative immune cells, including natural killer T cells and invariant natural killer T cells, exhibit innate anti-tumor activity and reduced toxicity. This review summarizes several recent clinical trial reports and preclinical studies from the 2023 American Society of Hematology (ASH) annual meeting on dual-targeted CAR T-cell immunotherapy for hematological malignancies.
Combining full-length gene assay and SpliceAI to interpret the splicing impact of all possible SPINK1 coding variants
Authors: Wu Hao , Lin Jin-Huan , Tang Xin-Ying , Marenne Gaëlle , Zou Wen-Bin , Schutz Sacha , Masson Emmanuelle , Génin Emmanuelle , Fichou Yann , Le Gac Gerald , Férec Claude , Liao Zhuan , Chen Jian-Min 
Published: February 2024

Abstract
Background
Single-nucleotide variants (SNVs) within gene coding sequences can significantly impact pre-mRNA splicing, bearing profound implications for pathogenic mechanisms and precision medicine. In this study, we aim to harness the well-established full-length gene splicing assay (FLGSA) in conjunction with SpliceAI to prospectively interpret the splicing effects of all potential coding SNVs within the four-exon SPINK1 gene, a gene associated with chronic pancreatitis.

Results
Our study began with a retrospective analysis of 27 SPINK1 coding SNVs previously assessed using FLGSA, proceeded with a prospective analysis of 35 new FLGSA-tested SPINK1 coding SNVs, followed by data extrapolation, and ended with further validation. In total, we analyzed 67 SPINK1 coding SNVs, which account for 9.3% of the 720 possible coding SNVs. Among these 67 FLGSA-analyzed SNVs, 12 were found to impact splicing. Through detailed comparison of FLGSA results and SpliceAI predictions, we inferred that the remaining 653 untested coding SNVs in the SPINK1 gene are unlikely to significantly affect splicing. Of the 12 splice-altering events, nine produced both normally spliced and aberrantly spliced transcripts, while the remaining three only generated aberrantly spliced transcripts. These splice-impacting SNVs were found solely in exons 1 and 2, notably at the first and/or last coding nucleotides of these exons. Among the 12 splice-altering events, 11 were missense variants (2.17% of 506 potential missense variants), and one was synonymous (0.61% of 164 potential synonymous variants). Notably, adjusting the SpliceAI cut-off to 0.30 instead of the conventional 0.20 would improve specificity without reducing sensitivity.

Conclusions
By integrating FLGSA with SpliceAI, we have determined that less than 2% (1.67%) of all possible coding SNVs in SPINK1 significantly influence splicing outcomes. Our findings emphasize the critical importance of conducting splicing analysis within the broader genomic sequence context of the study gene and highlight the inherent uncertainties associated with intermediate SpliceAI scores (0.20 to 0.80). This study contributes to the field by being the first to prospectively interpret all potential coding SNVs in a disease-associated gene with a high degree of accuracy, representing a meaningful attempt at shifting from retrospective to prospective variant analysis in the era of exome and genome sequencing.
Chromosome-level genome assembly of Oncomelania hupensis: the intermediate snail host of Schistosoma japonicum
Authors: Liu Qin , Duan Lei , Guo Yun-Hai , Yang Li-Min , Zhang Yi , Li Shi-Zhu , Lv Shan , Hu Wei , Chen Nan-Sheng , Zhou Xiao-Nong 
Published: February 2024

Abstract
Background
Schistosoma japonicum is a parasitic flatworm that causes human schistosomiasis, which is a significant cause of morbidity in China, the Philippines and Indonesia. Oncomelania hupensis (Gastropoda: Pomatiopsidae) is the unique intermediate host of S. japonicum. A complete genome sequence of O. hupensis will enable the fundamental understanding of snail biology as well as its co-evolution with the S. japonicum parasite. Assembling a high-quality reference genome of O. hupehensis will provide data for further research on the snail biology and controlling the spread of S. japonicum.

Methods
The draft genome was de novo assembly using the long-read sequencing technology (PacBio Sequel II) and corrected with Illumina sequencing data. Then, using Hi-C sequencing data, the genome was assembled at the chromosomal level. CAFE was used to do analysis of contraction and expansion of the gene family and CodeML module in PAML was used for positive selection analysis in protein coding sequences.

Results
A total length of 1.46 Gb high-quality O. hupensis genome with 17 unique full-length chromosomes (2n = 34) of the individual including a contig N50 of 1.35 Mb and a scaffold N50 of 75.08 Mb. Additionally, 95.03% of these contig sequences were anchored in 17 chromosomes. After scanning the assembled genome, a total of 30,604 protein-coding genes were predicted. Among them, 86.67% were functionally annotated. Further phylogenetic analysis revealed that O. hupensis was separated from a common ancestor of Pomacea canaliculata and Bellamya purificata approximately 170 million years ago. Comparing the genome of O. hupensis with its most recent common ancestor, it showed 266 significantly expanded and 58 significantly contracted gene families (P < 0.05). Functional enrichment of the expanded gene families indicated that they were mainly involved with intracellular, DNA-mediated transposition, DNA integration and transposase activity.

Conclusions
Integrated use of multiple sequencing technologies, we have successfully constructed the genome at the chromosomal-level of O. hupensis. These data will not only provide the compressive genomic information, but also benefit future work on population genetics of this snail as well as evolutional studies between S. japonicum and the snail host.

Graphical Abstract
Deaths among adults under supervision of the England and Wales’ probation services: variation in individual and criminal justice-related factors by cause of death
Authors: Slade Karen , Justice Lucy , Martijn Frederica , Borschmann Rohan , Baguley Thom 
Published: February 2024

Abstract
Background
The mortality rate among people under probation supervision in the community is greater than that among incarcerated people and that among the general population. However, there is limited research on the distinct vulnerabilities and risks underlying the causes of death in this population. In this retrospective cohort study, we examined the individual and criminal justice-related factors associated with different causes of death. Factors were assessed in relation to the type of supervision, distinguishing between those under post-custodial release and those serving a community sentence.

Results
The study utilised the official data held by His Majesty’s Prison and Probation Service in England and Wales on the deaths of men and women under probation supervision between 01 April 2019 and 31 March 2021 where the cause of death had been definitively recorded (n = 1770). The high risk of deaths primarily caused by external factors (i.e., suspected suicide (10%), homicide (5%), and drug-related death (26%)) in this population was confirmed. A Gaussian Graphical Model (GGM) demonstrated unique relationships with suspected suicide and drug-related deaths for known suicide risk, history of drug use and recent (< 28 days of death) enforcement action due to a breach of probation conditions. Our findings suggest that that familial violence and abuse may be relevant in suicide and drug-related deaths and that minority groups may experience disproportional risk to certain types of death.

Conclusions
This study identified unique risk indicators and modifiable factors for deaths primarily caused by external factors in this population within the health and justice spheres. It emphasised the importance of addressing health inequalities in this population and improved joint-working across health and justice. This involves ensuring that research, policies, training, and services are responsive to the complex needs of those under probation supervision, including those serving community sentences. Only then can we hope to see lower rates of death within this population.
Iron overload induced submandibular glands toxicity in gamma irradiated rats with possible mitigation by hesperidin and rutin
Authors: Ahmed Salwa Farid , El-Maghraby Eman M. F. , Rashad Maha M. , Bashir Dina W. 
Published: February 2024

Abstract
Background
Radiation triggers salivary gland damage and excess iron accumulates in tissues induces cell injury. Flavonoids are found in some fruits and are utilized as potent antioxidants and radioprotective agents. This study aimed to evaluate the antioxidant and anti-inflammatory effects of hesperidin and rutin on gamma radiation and iron overload induced submandibular gland (SMG) damage and to evaluate their possible impact on mitigating the alteration in mTOR signaling pathway and angiogenesis.

Methods
Forty-eight adult male Wistar albino rats were randomly assigned to six groups: group C received a standard diet and distilled water; group H received hesperidin at a dose of 100 mg/kg; four times a week for four weeks; group U received rutin at a dose of 50 mg/kg; three times a week for three weeks; group RF received a single dose (5 Gy) of gamma radiation followed by iron at a dose of 100 mg/kg; five times a week for four weeks; group RFH received radiation and iron as group RF and hesperidin as group H; group RFU received radiation and iron as group RF and rutin as group U. SMG specimens from all groups were removed at the end of the experiment; and some were used for biochemical analysis, while others were fixed for histological and immunohistochemical examination.

Results
In the RF group, several genes related to antioxidants (Nrf-2 and SOD) and DNA damage (BRCA1) were significantly downregulated, while several genes related to inflammation and angiogenesis (TNFα, IL-1β and VEGF) and the mTOR signaling pathway (PIK3ca, AKT and mTOR) were significantly upregulated. Acinar cytoplasmic vacuolation, nuclear pyknosis, and interacinar hemorrhage with distinct interacinar spaces were observed as histopathological changes in SMGs. The duct system suffered significant damage, eventually degenerating entirely as the cells were shed into the lumina. VEGF and NF-κB were also significantly overexpressed. Hesperidin and rutin cotreatment generated partial recovery as indicated by significant upregulation of Nrf-2, SOD and BRCA1 and considerable downregulation of TNF-α, IL-1β, VEGF, PIK3ca, AKT, and mTOR. Although some acini and ducts continued to deteriorate, most of them had a normal appearance. There was a notable decrease in the expression of VEGF and NF-κB.

Conclusions
In γ-irradiated rats with iron overload, the administration of hesperidin and rutin may mitigate salivary gland damage.
Decoding of the surfaceome and endocytome in primary glioblastoma cells identifies potential target antigens in the hypoxic tumor niche
Authors: de Oliveira Kelin Gonçalves , Bång-Rudenstam Anna , Beyer Sarah , Boukredine Axel , Talbot Hugo , Governa Valeria , Johansson Maria C. , Månsson Ann-Sofie , Forsberg-Nilsson Karin , Bengzon Johan , Malmström Johan , Welinder Charlotte , Belting Mattias 
Published: February 2024

AbstractImmunotherapies with antibody–drug-conjugates (ADC) and CAR-T cells, targeted at tumor surface antigens (surfaceome), currently revolutionize clinical oncology. However, target identification warrants a better understanding of the surfaceome and how it is modulated by the tumor microenvironment. Here, we decode the surfaceome and endocytome and its remodeling by hypoxic stress in glioblastoma (GBM), the most common and aggressive brain tumor in adults. We employed a comprehensive approach for global and dynamic profiling of the surfaceome and endocytosed (endocytome) proteins and their regulation by hypoxia in patient-derived GBM cultures. We found a heterogeneous surface-endocytome profile and a divergent response to hypoxia across GBM cultures. We provide a quantitative ranking of more than 600 surface resident and endocytosed proteins, and their regulation by hypoxia, serving as a resource to the cancer research community. As proof-of-concept, the established target antigen CD44 was identified as a commonly and abundantly expressed surface protein with high endocytic activity. Among hypoxia induced proteins, we reveal CXADR, CD47, CD81, BSG, and FXYD6 as potential targets of the stressed GBM niche. We could validate these findings by immunofluorescence analyses in patient tumors and by increased expression in the hypoxic core of GBM spheroids. Selected candidates were finally confronted by treatment studies, showing their high capacity for internalization and ADC delivery. Importantly, we highlight the limited correlation between transcriptomics and proteomics, emphasizing the critical role of membrane protein enrichment strategies and quantitative mass spectrometry. Our findings provide a comprehensive understanding of the surface-endocytome and its remodeling by hypoxia in GBM as a resource for exploration of targets for immunotherapeutic approaches in GBM.