bluuebunny/crossref_metadata_2025_split huggingface dataset:
ORI-Explorer: a unified cell-specific tool for origin of replication sites prediction by feature fusion
Authors: Abbas Zeeshan , Rehman Mobeen Ur , Tayara Hilal , Chong Kil To 
Published: November 2023

Abstract

Motivation
The origins of replication sites (ORIs) are precise regions inside the DNA sequence where the replication process begins. These locations are critical for preserving the genome’s integrity during cell division and guaranteeing the faithful transfer of genetic data from generation to generation. The advent of experimental techniques has aided in the discovery of ORIs in many species. Experimentation, on the other hand, is often more time-consuming and pricey than computational approaches, and it necessitates specific equipment and knowledge. Recently, ORI sites have been predicted using computational techniques like motif-based searches and artificial intelligence algorithms based on sequence characteristics and chromatin states.

Results
In this article, we developed ORI-Explorer, a unique artificial intelligence-based technique that combines multiple feature engineering techniques to train CatBoost Classifier for recognizing ORIs from four distinct eukaryotic species. ORI-Explorer was created by utilizing a unique combination of three traditional feature-encoding techniques and a feature set obtained from a deep-learning neural network model. The ORI-Explorer has significantly outperformed current predictors on the testing dataset. Furthermore, by employing the sophisticated SHapley Additive exPlanation method, we give crucial insights that aid in comprehending model success, highlighting the most relevant features vital for forecasting cell-specific ORIs. ORI-Explorer is also intended to aid community-wide attempts in discovering potential ORIs and developing innovative verifiable biological hypotheses.

Availability and implementation
The used datasets along with the source code are made available through https://github.com/Z-Abbas/ORI-Explorer and https://zenodo.org/record/8358679.
Open MoA: revealing the mechanism of action (MoA) based on network topology and hierarchy
Authors: Liao Xinmeng , Ozcan Mehmet , Shi Mengnan , Kim Woonghee , Jin Han , Li Xiangyu , Turkez Hasan , Achour Adnane , Uhlén Mathias , Mardinoglu Adil , Zhang Cheng 
Published: November 2023

Abstract

Motivation
Many approaches in systems biology have been applied in drug repositioning due to the increased availability of the omics data and computational biology tools. Using a multi-omics integrated network, which contains information of various biological interactions, could offer a more comprehensive inspective and interpretation for the drug mechanism of action (MoA).

Results
We developed a computational pipeline for dissecting the hidden MoAs of drugs (Open MoA). Our pipeline computes confidence scores to edges that represent connections between genes/proteins in the integrated network. The interactions showing the highest confidence score could indicate potential drug targets and infer the underlying molecular MoAs. Open MoA was also validated by testing some well-established targets. Additionally, we applied Open MoA to reveal the MoA of a repositioned drug (JNK-IN-5A) that modulates the PKLR expression in HepG2 cells and found STAT1 is the key transcription factor. Overall, Open MoA represents a first-generation tool that could be utilized for predicting the potential MoA of repurposed drugs and dissecting de novo targets for developing effective treatments.

Availability and implementation
Source code is available at https://github.com/XinmengLiao/Open_MoA.
An integrative pipeline for circular RNA quantitative trait locus discovery with application in human T cells
Authors: Nguyen Dat Thanh 
Published: November 2023

Abstract

Motivation
Molecular quantitative trait locus (QTL) mapping has proven to be a powerful approach for prioritizing genetic regulatory variants and causal genes identified by genome-wide association studies. Recently, this success has been extended to circular RNA (circRNA), a potential group of RNAs that can serve as markers for the diagnosis, prognosis, or therapeutic targets of various human diseases. However, a well-developed computational pipeline for circRNA QTL (circQTL) discovery is still lacking.

Results
We introduce an integrative method for circQTL mapping and implement it as an automated pipeline based on Nextflow, named cscQTL. The proposed method has two main advantages. Firstly, cscQTL improves the specificity by systematically combining outputs of multiple circRNA calling algorithms to obtain highly confident circRNA annotations. Secondly, cscQTL improves the sensitivity by accurately quantifying circRNA expression with the help of pseudo references. Compared to the single method approach, cscQTL effectively identifies circQTLs with an increase of 20%–100% circQTLs detected and recovered all circQTLs that are highly supported by the single method approach. We apply cscQTL to a dataset of human T cells and discover genetic variants that control the expression of 55 circRNAs. By colocalization tests, we further identify circBACH2 and circYY1AP1 as potential candidates for immune disease regulation.

Availability and implementation
cscQTL is freely available at: https://github.com/datngu/cscQTL and https://doi.org/10.5281/zenodo.7851982.
A cetacean limb from the Middle Eocene of Ukraine sheds light on mammalian adaptations to life in water
Authors: Davydenko Svitozar , Solyanik Eugene , Tretiakov Roman , Kovalchuk Oleksandr , Gol’din Pavel 
Published: November 2023

Abstract
There are a few mammalian lineages secondarily adapted to life in water throughout their evolutionary history. Of them, only sirenians and cetaceans evolved as fully aquatic organisms. This transition was accompanied by changes in swimming mode, from foot paddling to tail-powered propulsion, with the forelimbs acting as efficient hydrofoils and the gradual loss of external hindlimbs. Here, we describe an isolated limb from the Middle Eocene of Ukraine, 43–42 Mya, identified as a hindlimb of a fully aquatic cetacean and being the earliest cetacean reported from Europe. It is represented by flattened, jointly articulated bones, identified as the tibia and fibula with a partly reduced knee joint and loose connection to the pes, and by flattened phalanges. This anatomy reveals a hitherto only presumed cetacean morphotype, showing that some of the early fully aquatic cetaceans were four-legged animals with functional hindlimbs that could be involved in advanced styles of swimming. They used either body undulation or lift-based propulsion powered by the tail or feet and could also use a transitional swimming style combining these modes.
Shear stress in the intervillous space promotes syncytial formation of iPS cells-derived trophoblasts
Authors: Inohaya Asako , Chigusa Yoshitsugu , Takakura Masahito , Io Shingo , Kim Min-A , Matsuzaka Yu , Yasuda Eriko , Ueda Yusuke , Kawamura Yosuke , Takamatsu Shiro , Mogami Haruta , Takashima Yasuhiro , Mandai Masaki , Kondoh Eiji 
Published: November 2023

Abstract
The intervillous space of human placenta is filled with maternal blood, and villous trophoblasts are constantly exposed to the shear stress generated by maternal blood pressure and flow throughout the entire gestation period. However, the effects of shear stress on villous trophoblasts and their biological significance remain unknown. Here, using our recently established naïve human pluripotent stem cells-derived cytotrophoblast stem cells (nCTs) and a device that can apply arbitrary shear stress to cells, we investigated the impact of shear stress on early-stage trophoblasts. After 72 h of exposure to 10 dyn/cm2 shear stress, nCTs became fused and multinuclear, and mRNA expression of the syncytiotrophoblast (ST) markers, such as glial cell missing 1, endogenous retrovirus group W member 1 envelope, chorionic gonadotropin subunit beta 3, syndecan 1, pregnancy specific beta-1-glycoprotein 3, placental growth factor, and solute carrier family 2 member 1 were significantly upregulated compared to static conditions. Immunohistochemistry showed that shear stress increased fusion index, human chorionic gonadotropin secretion, and human placental lactogen secretion. Increased microvilli formation on the surface of nCTs under flow conditions was detected using scanning electron microscopy. Intracellular cyclic adenosine monophosphate significantly increased under flow conditions. Moreover, transcriptome analysis of nCTs subjected to shear stress revealed that shear stress upregulated ST-specific genes and downregulated CT-specific genes. Collectively, these findings indicate that shear stress promotes the differentiation of nCTs into ST.
Protocol for transcriptome assembly by the TransBorrow algorithm
Authors: Zhao Dengyi , Liu Juntao , Yu Ting 
Published: November 2023

Abstract
High-throughput RNA-seq enables comprehensive analysis of the transcriptome for various purposes. However, this technology generally generates massive amounts of sequencing reads with a shorter read length. Consequently, fast, accurate, and flexible tools are needed for assembling raw RNA-seq data into full-length transcripts and quantifying their expression levels. In this protocol, we report TransBorrow, a novel transcriptome assembly software specifically designed for short RNA-seq reads. TransBorrow is employed in conjunction with a splice-aware alignment tool (e.g. Hisat2 and Star) and some other transcriptome assembly tools (e.g. StringTie, Cufflinks, and Scallop). The protocol encompasses all necessary steps, starting from downloading and processing raw sequencing data to assembling the full-length transcripts and quantifying their expressed abundances. The execution time of the protocol may vary depending on the sizes of processed datasets and computational platforms.
Future-proofing environmental DNA and trait-based predictions of food webs
Authors: Pereira Cátia Lúcio , Ersoy Zeynep , Gilbert M Thomas P , Gravel Dominique , Araújo Miguel B , Matias Miguel G 
Published: November 2023

Abstract
Food webs represent trophic interactions within ecosystems. Matching traits of consumers and resources helps infer trophic interactions and food-web properties. Environmental (e)DNA, commonly used for detecting species occurrences, is rarely used in trait-matching studies because abundance estimates and descriptions of relevant traits are generally missing. We synthesized recent literature on inferences of trophic interactions with eDNA and trait matching to identify challenges and opportunities for coupled eDNA–trait recording schemes. Our case study shows how coupling eDNA and trait data collection improves the ability to characterize greater numbers of food webs across multiple scales ranging from spatiotemporal to trait variation. Future-proofing eDNA data sets requires the collection of new traits or the compilation of existing trait data at spatiotemporal scales that are relevant to detect current and future changes in food webs and ecosystems.
Long noncoding RNA plasmacytoma variant translocation 1 is overexpressed in cutaneous squamous cell carcinoma and exon 2 is critical for its oncogenicity
Authors: Li Chen , Sun Chengxi , Mahapatra Kunal Das , Riihilä Pilvi , Knuutila Jaakko , Nissinen Liisa , Lapins Jan , Kähäri Veli-Matti , Homey Bernhard , Sonkoly Enikö , Pivarcsi Andor 
Published: November 2023

Abstract

Background
Cutaneous squamous cell carcinoma (cSCC) is one of the most common and fastest increasing forms of cancer worldwide with metastatic potential. Long noncoding RNAs (lncRNAs) are a group of RNA molecules with essential regulatory functions in both physiological and pathological processes.

Objectives
To investigate the function and mode of action of lncRNA plasmacytoma variant translocation 1 (PVT1) in cSCC.

Methods
Quantitative reverse transcriptase polymerase chain reaction and single-molecule in situ hybridization were used to quantify the expression level of PVT1 in normal skin, premalignant skin lesions, actinic keratosis (AK) and primary and metastatic cSCCs. The function of PVT1 in cSCC was investigated both in vivo (tumour xenografts) and in vitro (competitive cell growth assay, 5-ethynyl-2′-deoxyuridine incorporation assay, colony formation assay and tumour spheroid formation assay) upon CRISPR-Cas9-mediated knockout of the entire PVT1 locus, the knockout of exon 2 of PVT1, and locked nucleic acid (LNA) gapmer-mediated PVT1 knockdown. RNA sequencing analysis was conducted to identify genes and processes regulated by PVT1.

Results
We identified PVT1 as a lncRNA upregulated in cSCC in situ and cSCC, associated with the malignant phenotype of cSCC. We showed that the expression of PVT1 in cSCC was regulated by MYC. Both CRISPR-Cas9 deletion of the entire PVT1 locus and LNA gapmer-mediated knockdown of PVT1 transcript impaired the malignant behaviour of cSCC cells, suggesting that PVT1 is an oncogenic transcript in cSCC. Furthermore, knockout of PVT1 exon 2 inhibited cSCC tumour growth both in vivo and in vitro, demonstrating that exon 2 is a critical element for the oncogenic role of PVT1. Mechanistically, we showed that PVT1 was localized in the cell nucleus and its deletion resulted in cellular senescence, increased cyclin-dependent kinase inhibitor 1 (p21/CDKN1A) expression and cell cycle arrest.

Conclusions
Our study revealed a previously unrecognized role for exon 2 of PVT1 in its oncogenic role and that PVT1 suppresses cellular senescence in cSCC. PVT1 may be a potential biomarker and therapeutic target in cSCC.
S100 calcium-binding protein A9 promotes skin regeneration through toll-like receptor 4 during tissue expansion
Authors: Zhang Yu , Song Yajuan , Du Jing , Liu Wei , Dong Chen , Huang Zhaosong , Zhang Zhe , Yang Liu , Wang Tong , Xiong Shaoheng , Dong Liwei , Guo Yaotao , Dang Juanli , He Qiang , Yu Zhou , Ma Xianjie 
Published: November 2023

Abstract

Background
In plastic surgery, tissue expansion is widely used for repairing skin defects. However, low expansion efficiency and skin rupture caused by thin, expanded skin remain significant challenges in promoting skin regeneration during expansion. S100 calcium-binding protein A9 (S100A9) is essential in promoting wound healing; however, its effects on skin regeneration during tissue expansion remain unclear. The aim of the present study was to explore the role of S100A9 in skin regeneration, particularly collagen production to investigate its importance in skin regeneration during tissue expansion.

Methods
The expression and distribution of S100A9 and its receptors—toll-like receptor 4 (TLR-4) and receptor for advanced glycation end products were studied in expanded skin. These characteristics were investigated in skin samples of rats and patients. Moreover, the expression of S100A9 was investigated in stretched keratinocytes in vitro. The effects of S100A9 on the proliferation and migration of skin fibroblasts were also observed. TAK-242 was used to inhibit the binding of S100A9 to TLR-4; the levels of collagen I (COL I), transforming growth factor beta (TGF-β), TLR-4 and phospho-extracellular signal-related kinase 1/2 (p-ERK1/2) in fibroblasts were determined. Furthermore, fibroblasts were co-cultured with stretched S100A9-knockout keratinocytes by siRNA transfection and the levels of COL I, TGF-β, TLR-4 and p-ERK1/2 in fibroblasts were investigated. Additionally, the area of expanded skin, thickness of the dermis, and synthesis of COL I, TGF-β, TLR-4 and p-ERK1/2 were analysed to determine the effects of S100A9 on expanded skin.

Results
Increased expression of S100A9 and TLR-4 was associated with decreased extracellular matrix (ECM) in the expanded dermis. Furthermore, S100A9 facilitated the proliferation and migration of human skin fibroblasts as well as the expression of COL I and TGF-β in fibroblasts via the TLR-4/ERK1/2 pathway. We found that mechanical stretch-induced S100A9 expression and secretion of keratinocytes stimulated COL I, TGF-β, TLR-4 and p-ERK1/2 expression in skin fibroblasts. Recombined S100A9 protein aided expanded skin regeneration and rescued dermal thinning in rats in vivo as well as increasing ECM deposition during expansion.

Conclusions
These findings demonstrate that mechanical stretch promoted expanded skin regeneration by upregulating S100A9 expression. Our study laid the foundation for clinically improving tissue expansion using S100A9.
Tuning the potency and selectivity of ImmTAC molecules by affinity modulation
Authors: Robertson Ian B , Mulvaney Rachel , Dieckmann Nele , Vantellini Alessio , Canestraro Martina , Amicarella Francesca , O’Dwyer Ronan , Cole David K , Harper Stephen , Dushek Omer , Kirk Peter 
Published: November 2023

Abstract
T-cell-engaging bispecifics have great clinical potential for the treatment of cancer and infectious diseases. The binding affinity and kinetics of a bispecific molecule for both target and T-cell CD3 have substantial effects on potency and specificity, but the rules governing these relationships are not fully understood. Using immune mobilizing monoclonal TCRs against cancer (ImmTAC) molecules as a model, we explored the impact of altering affinity for target and CD3 on the potency and specificity of the redirected T-cell response. This class of bispecifics binds specific target peptides presented by human leukocyte antigen on the cell surface via an affinity-enhanced T-cell receptor and can redirect T-cell activation with an anti-CD3 effector moiety. The data reveal that combining a strong affinity TCR with an intermediate affinity anti-CD3 results in optimal T-cell activation, while strong affinity of both targeting and effector domains significantly reduces maximum cytokine release. Moreover, by optimizing the affinity of both parts of the molecule, it is possible to improve the selectivity. These results could be effectively modelled based on kinetic proofreading with limited signalling. This model explained the experimental observation that strong binding at both ends of the molecules leads to reduced activity, through very stable target-bispecific-effector complexes leading to CD3 entering a non-signalling dark state. These findings have important implications for the design of anti-CD3-based bispecifics with optimal biophysical parameters for both activity and specificity.
Serum sclerostin is associated with recurrent kidney stone formation independent of hypercalciuria
Authors: Rodríguez Daniel , Gurevich Ekaterina , Mohammadi Jouabadi Soroush , Pastor Arroyo Eva Maria , Ritter Alexander , Estoppey Younes Sandrine , Wagner Carsten A , Imenez Silva Pedro Henrique , Seeger Harald , Mohebbi Nilufar 
Published: November 2023

ABSTRACT

Background
Kidney stones are frequent in industrialized countries with a lifetime risk of 10 to 15%. A high percentage of individuals experience recurrence. Calcium-containing stones account for more than 80% of kidney stones. Diet, environmental factors, behavior, and genetic variants contribute to the development of kidney stones. Osteocytes excrete the 21 kDa glycoprotein sclerostin, which inhibits bone formation by osteoblasts. Animal data suggests that sclerostin might directly or indirectly regulate calcium excretion via the kidney. As hypercalciuria is one of the most relevant risk factors for kidney stones, sclerostin might possess pathogenic relevance in nephrolithiasis.

Methods
We performed a prospective cross-sectional observational controlled study in 150 recurrent kidney stone formers (rKSF) to analyse the association of sclerostin with known stone risk factors and important modulators of calcium-phosphate metabolism. Serum sclerostin levels were determined at the first visit. As controls, we used 388 non-stone formers from a large Swiss epidemiological cohort.

Results
Sclerostin was mildly increased in rKSF in comparison to controls. This finding was more pronounced in women compared to men. Logistic regression indicated an association of serum sclerostin with rKSF status. In hypercalciuric individuals, sclerostin levels were not different from normocalciuric patients. In Spearman correlation analysis we found a positive correlation between sclerostin, age, and BMI and a negative correlation with eGFR. There was a weak correlation with iPTH and intact FGF 23. In contrast, serum sclerostin levels were not associated with 25-OH Vitamin D3, 1,25-dihydroxy-Vitamin D3, urinary calcium and phosphate or other urinary lithogenic risk factors.

Conclusion
This is the first prospective controlled study investigating serum sclerostin in rKSF. Sclerostin levels were increased in rKSF independent of hypercalciuria and significantly associated with the status as rKSF. It appears that mechanisms other than hypercalciuria may be involved and thus further studies are required to elucidate underlying pathways.
Preproject ‘Swiss Virtual Natural History Collection’
Authors: Petrus Ana , Wildi Tobias , Müller Stefanie 
Published: November 2023

Abstract
The initiative ‘Swiss Natural History Collection Network’ (SwissCollNet) aims to improve the accessibility of the Swiss natural history collections for research, education and the wider public. In the 2021–24 funding period, SwissCollNet is identifying, prioritizing and digitizing as many collections as possible and building an online portal called the ‘Swiss Virtual Natural History Collection’ (hereafter SVNHC) to provide open access to harmonized sample data from Swiss collections. The University of Applied Sciences of the Grisons developed scenarios for the technical implementation of the SVNHC portal in a preliminary study on behalf of SwissCollNet and based on the requirements of collections and data centres.
Sex-specific presentation, care, and clinical events in individuals admitted with NSTEMI: the ACVC-EAPCI EORP NSTEMI registry of the European Society of Cardiology
Authors: Nadarajah Ramesh , Ludman Peter , Laroche Cécile , Appelman Yolande , Brugaletta Salvatore , Budaj Andrzej , Bueno Hector , Huber Kurt , Kunadian Vijay , Leonardi Sergio , Lettino Maddalena , Milasinovic Dejan , Gale Chris P 
Published: November 2023

Abstract

Aims
Women have historically been disadvantaged in terms of care and outcomes for non-ST-segment elevation myocardial infarction (NSTEMI). We describe patterns of presentation, care, and outcomes for NSTEMI by sex in a contemporary and geographically diverse cohort.

Methods and results
Prospective cohort study including 2947 patients (907 women, 2040 men) with Type I NSTEMI from 287 centres in 59 countries, stratified by sex. Quality of care was evaluated based on 12 guideline-recommended care interventions. The all-or-none scoring composite performance measure was used to define receipt of optimal care. Outcomes included acute heart failure, cardiogenic shock, repeat myocardial infarction, stroke/transient ischaemic attack, BARC Type ≥3 bleeding, or death in-hospital, as well as 30-day mortality. Women admitted with NSTEMI were older, more comorbid, and more frequently categorized as at higher ischaemic (GRACE &gt;140, 54.0% vs. 41.7%, P &lt; 0.001) and bleeding (CRUSADE &gt;40, 51.7% vs. 17.6%, P &lt; 0.001) risk than men. Women less frequently received invasive coronary angiography (ICA; 83.0% vs. 89.5%, P &lt; 0.001), smoking cessation advice (46.4% vs. 69.5%, P &lt; 0.001), and P2Y12 inhibitor prescription at discharge (81.9% vs. 90.0%, P &lt; 0.001). Non-receipt of ICA was more often due to frailty for women than men (16.7% vs. 7.8%, P = 0.010). At ICA, more women than men had non-obstructive coronary artery disease or angiographically normal arteries (15.8% vs. 6.3%, P &lt; 0.001). Rates of in-hospital adverse outcomes and 30-day mortality were low and did not differ by sex.

Conclusion
In contemporary practice, women presenting with NSTEMI, compared with men, less frequently receive antiplatelet prescription, smoking cessation advice, or are considered eligible for ICA.