bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of Wilms’ tumor protein 1 specific TCR repertoire in AML patients uncovers higher diversity in patients in remission than in relapsed
Authors: Gielis Sofie , Flumens Donovan , van der Heijden Sanne , Versteven Maarten , Reu Hans De , Bartholomeus Esther , Schippers Jolien , Campillo-Davo Diana , Berneman Zwi N. , Anguille Sébastien , Smits Evelien , Ogunjimi Benson , Lion Eva , Laukens Kris , Meysman Pieter 
Published: November 2023

AbstractThe Wilms’ tumor protein 1 (WT1) is a well-known and prioritized tumor-associated antigen expressed in numerous solid and blood tumors. Its abundance and immunogenicity have led to the development of different WT1-specific immune therapies. The driving player in these therapies, the WT1-specific T-cell receptor (TCR) repertoire, has received much less attention. Importantly, T cells with high affinity against the WT1 self-antigen are normally eliminated after negative selection in the thymus and are thus rare in peripheral blood. Here, we developed computational models for the robust and fast identification of WT1-specific TCRs from TCR repertoire data. To this end, WT137-45(WT1-37) and WT1126-134(WT1-126)-specific T cells were isolated from WT1 peptide-stimulated blood of healthy individuals. The TCR repertoire from these WT1-specific T cells was sequenced and used to train a pattern recognition model for the identification of WT1-specific TCR patterns for the WT1-37 or WT1-126 epitopes. The resulting computational models were applied on an independent published dataset from acute myeloid leukemia (AML) patients, treated with hematopoietic stem cell transplantation, to track WT1-specific TCRsin silico. Several WT1-specific TCRs were found in AML patients. Subsequent clustering analysis of all repertoires indicated the presence of more diverse TCR patterns within the WT1-specific TCR repertoires of AML patients in complete remission in contrast to relapsing patients. We demonstrate the possibility of tracking WT1-37 and WT1-126-specific TCRs directly from TCR repertoire data using computational methods, eliminating the need for additional blood samples and experiments for the two studied WT1 epitopes.
Phosphatase-independent activity of smooth-muscle calcineurin orchestrates a gene expression program leading to hypertension
Authors: Yunes-Leites Paula Sofía , Sun Yilin , Martínez-Martínez Sara , Alfayate Álvaro , Toral Marta , Colmenar Ángel , Torralbo Ana Isabel , López-Maderuelo Dolores , Mateos-García Sergio , Cornfield David N. , Vázquez Jesús , Redondo Juan Miguel , Campanero Miguel R. 
Published: November 2023

STRUCTURED ABSTRACTObjective:Angiotensin-II (Ang-II) drives pathological vascular wall remodeling in hypertension and abdominal aortic aneurysm (AAA). Previous studies showed that the phosphatase activity of calcineurin (Cn) mediates Ang-II-induced AAA, but the cell type involved in the action of Cn in AAA formation remained unknown.Methods:Smooth muscle cell (SMC)-specific and endothelial cell (EC)-specific Cn-deficient mice (SM-Cn-/-andEC-Cn-/-mice, respectively) were created and assessed for Ang-II-induced AAA formation and hypertension vs controls. Osmotic minipumps were used to administer Ang-II and cyclosporine A (CsA), a pharmaceutical Cn inhibitor. AAA formation and hypertension were monitored by ultrasonography, arterial blood pressure monitoring, and histological analysis. Deep RNA sequencing was used to identify the Ang-II-regulated transcriptome sensitive to Cn deletion or pharmacological inhibition. Arterial and SMC contractility were also assessed.Results:Cn expressed in SMCs, but not ECs, was required for Ang-II-induced AAA. Unexpectedly, SMC Cn played a structural role in the early onset and maintenance of Ang-II-induced hypertension independently of Cn phosphatase activity. Nearly 90% of the genes regulated by Ang-II in the aorta required Cn expression in SMCs. Cn orchestrated, independently of its enzymatic activity, the induction by Ang-II of a gene expression program closely related to SMC contractility and hypertension. Cn deletion in SMCs, but not its pharmacological inhibition, impaired the regulation of arterial contractility. Among the genes whose regulation by Ang-II required Cn expression but not its phosphatase activity, we discovered thatSerpine1was critical for Ang-II-induced hypertension. Indeed, pharmacological inhibition of PAI-1, the protein encoded bySerpine1, impaired SMCs contractility and readily regressed hypertension.Conclusions:Whereas the phosphatase activity of Cn mediates Ang-II-induced AAA, a phosphatase-independent action of SMC Cn mediates hypertension by orchestrating a gene expression program closely related to contractility and blood pressure regulation. Our results urge the evaluation of PAI-1 as a candidate therapeutic target for hypertension.
Proliferation history and transcription factor levels drive direct conversion
Authors: Wang Nathan B. , Lende-Dorn Brittany A. , Adewumi Honour O. , Beitz Adam M. , Han Patrick , O’Shea Timothy M. , Galloway Kate E. 
Published: November 2023

AbstractThe sparse and stochastic nature of reprogramming has obscured our understanding of how transcription factors drive cells to new identities. To overcome this limit, we developed a compact, portable reprogramming system that increases direct conversion of fibroblasts to motor neurons by two orders of magnitude. We show that subpopulations with different reprogramming potentials are distinguishable by proliferation history. By controlling for proliferation history and titrating each transcription factor, we find that conversion correlates with levels of the pioneer transcription factor Ngn2, whereas conversion shows a biphasic response to Lhx3. Increasing the proliferation rate of adult human fibroblasts generates morphologically mature, induced motor neurons at high rates. Using compact, optimized, polycistronic cassettes, we generate motor neurons that graft with the murine central nervous system, demonstrating the potential forin vivotherapies.One Sentence SummaryUsing a systems and synthetic biology approach to study the molecular determinants of reprogramming, we find that proliferation history and transcription factor levels drive cell fate in direct conversion to motor neurons.Highlightsminimal high-efficiency cocktail allows systematic interrogation of the reprogramming processhistory provides a principal axis to distinguish transcription factors’ influenceof the transcription factor cocktail impacts reprogramming efficiency and dynamicsof individual transcription factors differentially influence the rate of reprogrammingearly hyperproliferation increases direct conversion of adult human fibroblastsptimal cocktail allows neurotrophic factor-free reprogramming andin vivografting
Mycobacterium smegmatisNucS-promoted DNA mismatch repair involves limited resection by a 5’-3’ exonuclease and is independent of homologous recombination and NHEJ
Authors: Rivera-Flores Iris V. , Wang Emily X. , Murphy Kenan C. 
Published: November 2023

AbstractThe MutSL mismatch repair (MMR) system in bacteria and eukaryotes correct mismatches made at the replication fork to maintain genome stability. A novel MMR system is represented by the EndoMS/NucS endonuclease from actinobacteriumCorynebacterium glutamicum, which recognizes mismatched substrates in vitro and creates dsDNA breaks at the mismatch. In this report, a genetic analysis shows that anM. smegmatisΔnucSstrain could be complemented by expression of wild type NucS protein, but not by one deleted of its last five amino acids, a region predicted to be critical for binding to the β-clamp at the replication fork. Oligo-recombineering was then leveraged to deliver defined mismatches to a defective hygromycin resistance gene on theM. smegmatischromosome. We find that NucS recognizes and repairs G-G, G-T, and T-T mismatches in vivo, consistent with the recognition of these same mismatches in C.glutamicumin vitro, as well as mutation accumulation studies done inM. smegmatis. Finally, an assay that employs an oligo that promotes the generation of two mismatches in close proximity on the chromosome shows that a NucS-promoted cut is processed by a 5’–3’ exonuclease and that NucS-promoted MMR is independent of both homologous recombination and non-homologous end-joining.
Polygenic risk scores as a marker for epilepsy risk across lifetime and after unspecified seizure events
Authors: Heyne Henrike O. , Pajuste Fanny-Dhelia , Wanner Julian , Onwuchekwa Jennifer I. Daniel , Mägi Reedik , Palotie Aarno ,   FinnGen, Estonian Biobank research team, Kälviainen Reetta , Daly Mark J. 
Published: November 2023

AbstractA diagnosis of epilepsy has significant consequences for an individual but is often challenging in clinical practice. Novel biomarkers are thus greatly needed. Here, we investigated how common genetic factors (epilepsy polygenic risk scores, [PRSs]) influence epilepsy risk in detailed longitudinal electronic health records (EHRs) of > 360k Finns spanning up to 50 years of individuals’ lifetimes. Individuals with a high genetic generalized epilepsy PRS (PRSGGE) in FinnGen had an increased risk for genetic generalized epilepsy (GGE) (hazard ratio [HR] 1.55 per PRSGGEstandard deviation [SD]) across their lifetime and after unspecified seizure events. Effect sizes of epilepsy PRSs were comparable to effect sizes in clinically curated data supporting our EHR-derived epilepsy diagnoses. Within 10 years after an unspecified seizure, the GGE rate was 37% when PRSGGE> 2 SD compared to 5.6% when PRSGGE< –2 SD. The effect of PRSGGEwas even larger on GGE subtypes of idiopathic generalized epilepsy (IGE) (HR 2.1 per SD PRSGGE). We further report significantly larger effects of PRSGGEon epilepsy in females and in younger age groups. Analogously, we found significant but more modest focal epilepsy PRS burden associated with non-acquired focal epilepsy (NAFE). We found PRSGGEspecifically associated with GGE in comparison with >2000 independent diseases while PRSNAFEwas also associated with other diseases than NAFE such as back pain. Here, we show that epilepsy specific PRSs have good discriminative ability after a first seizure event i.e. in circumstances where the prior probability of epilepsy is high outlining a potential to serve as biomarkers for an epilepsy diagnosis.
Pro-ictal EEG scheduling improves the yield of epilepsy monitoring: Validating the use of multiday seizure cycles to optimize video-EEG timing
Authors: Naim-Feil Jodie , Stirling Rachel E. , Karoly Philippa J. , Payne Daniel , Winterling Nicholas , Eden Dominique , Cook Mark J. , Grayden David B. , Maturana Matias , Freestone Dean R. , Nurse Ewan S. 
Published: November 2023

AbstractA significant challenge of video-electroencephalography (vEEG) in epilepsy diagnosis is timing monitoring sessions to capture epileptiform activity. Given the significant consequences of misdiagnosis or delayed diagnosis, new techniques to improve diagnostic yield of vEEG are needed. In this study, we introduce and validate “pro-ictal EEG scheduling”, a method to schedule vEEG monitoring to coincide with periods of heightened seizure probability as a low-risk approach to enhance the diagnostic yield. A database of long-term ambulatory vEEG monitoring sessions (n=5038) of adults and children was examined. Data from linked electronic seizure diaries were extracted (minimum 10 self-reported events over 12-months) to generate cycle-based estimates of seizure risk. VEEG monitoring sessions coinciding with periods of estimated high-risk were allocated to the high-risk group (adultsn=305, childrenn=82) and compared to remaining studies (baseline: adultsn=3586, childrenn=1065). Test of Proportions and Risk-Ratios (RR) were used to index differences in proportions and likelihood of capturing outcome measures (abnormal report, confirmed seizure and diary event) during monitoring. The impact of clinical and demographic factors (sex, epilepsy-type, medication) was also explored. During vEEG monitoring, the high-risk group was 25% more likely to have an abnormal vEEG report (190/305:62.3% vs 1790/3586:49.9%, RR=1.25, 95% CI[1.137:1.370],p<0.001), 63% more likely to present with a confirmed seizure (56/305:18.4% vs 424/3586:11.3%, RR=1.63, 95% CI[1.265:2.101],p<0.001) and 42% more likely to report an event (153/305:50.2% vs 1267/3586:35.3%, RR=1.420, 95% CI[1.259:1.602],p<0.001). In children, the high-risk group was 93% more likely to have a confirmed seizure (21/82:25.6% vs 141/1065:13.2%, RR=1.93, 95% CI[1.297:2.885],p=0.002). Similar effects were observed across clinical and demographic features. This study provides the first large-scale validation of pro-ictal EEG scheduling in improving the yield of vEEG. This innovative approach offers a pragmatic and low-risk strategy to enhance the diagnostic capabilities of vEEG monitoring, significantly impacting epilepsy management.
An easy-to-produce HIS-based MIMO radio altimeter antenna design for aircraft
Authors: Kiriş Serap , Karaaslan Muharrem 
Published: November 2023

Purpose
The purpose of this study is to design a radio altimeter antenna whose production process is facilitated and can work with multiple-input multiple-output (MIMO) properties to provide space gain on the aircraft.

Design/methodology/approach
To create an easy-to-produce MIMO, a two-storied structure consisting of a reflector and a top antenna was designed. The dimensions of the reflector were prevented to get smaller to supply easy production. The unit cell nearly with the same dimensions of a lower frequency was protected through the original cell design. The co-planar structure with the use of a via connection was modified and a structure was achieved with no need to via for easy production, too. Finally, the antennas were placed side by side and the distance between them was optimized to achieve a MIMO operation.

Findings
As a result, an easy-to-produce, compact and successful radio altimeter antenna was obtained with high antenna parameters such as 10.14 dBi gain and 10.55 dBi directivity, and the conical pattern along with proper MIMO features, through original reflector surface and top antenna system.

Originality/value
Since radio altimeter antennas require high radiation properties, the microstrip antenna structure is generally used in literature. This paper contributes by presenting the radio altimeter application with antenna-reflective structure participation. The technical solutions were developed during the design, focusing on an easy manufacturing process for both the reflective surface and the upper antenna. Also, the combination of International Telecommunication Union’s recommended features that require high antenna properties was achieved, which is challenging to reach. In addition, by operating the antenna as a successful MIMO, two goals of easy production and space gain on aircraft have been attained at the same time.
Forecasting Right-of-Way (ROW) acquisition timeline of transportation projects
Authors: Zeng Shiqin , Chung Frederick , Ashuri Baabak 
Published: November 2023

PurposeCompleting Right-of-Way (ROW) acquisition process on schedule is critical to avoid delays and cost overruns on transportation projects. However, transportation agencies face challenges in accurately forecasting ROW acquisition timelines in the early stage of projects due to complex nature of acquisition process and limited design information. There is a need of improving accuracy of estimating ROW acquisition duration during the early phase of project development and quantitatively identifying risk factors affecting the duration.Design/methodology/approachThe quantitative research methodology used to develop the forecasting model includes an ensemble algorithm based on decision tree and adaptive boosting techniques. A dataset of Georgia Department of Transportation projects held from 2010 to 2019 is utilized to demonstrate building the forecasting model. Furthermore, sensitivity analysis is performed to identify critical drivers of ROW acquisition durations.FindingsThe forecasting model developed in this research achieves a high accuracy to predict ROW durations by explaining 74% of the variance in ROW acquisition durations using project features, which is outperforming single regression tree, multiple linear regression and support vector machine. Moreover, number of parcels, average cost estimation per parcel, length of projects, number of condemnations, number of relocations and type of work are found to be influential factors as drivers of ROW acquisition duration.Originality/value This research contributes to the state of knowledge in estimating ROW acquisition timeline through (1) developing a novel machine learning model to accurately estimate ROW acquisition timelines, and (2) identifying drivers (i.e. risk factors) of ROW acquisition durations. The findings of this research will provide transportation agencies with insights on how to improve practices in scheduling ROW acquisition process.
A machine learning-driven support vector regression model for enhanced generation system reliability prediction
Authors: Bolourchi Pouya , Gholami Mohammadreza 
Published: November 2023

Purpose
The purpose of this paper is to achieve high accuracy in forecasting generation reliability by accurately evaluating the reliability of power systems. This study uses the RTS-79 reliability test system to measure the method’s effectiveness, using mean absolute percentage error as the performance metrics. Accurate reliability predictions can inform critical decisions related to system design, expansion and maintenance, making this study relevant to power system planning and management.

Design/methodology/approach
This paper proposes a novel approach that uses a radial basis kernel function-based support vector regression method to accurately evaluate the reliability of power systems. The approach selects relevant system features and computes loss of load expectation (LOLE) and expected energy not supplied (EENS) using the analytical unit additional algorithm. The proposed method is evaluated under two scenarios, with changes applied to the load demand side or both the generation system and load profile.

Findings
The proposed method predicts LOLE and EENS with high accuracy, especially in the first scenario. The results demonstrate the method’s effectiveness in forecasting generation reliability. Accurate reliability predictions can inform critical decisions related to system design, expansion and maintenance. Therefore, the findings of this study have significant implications for power system planning and management.

Originality/value
What sets this approach apart is the extraction of several features from both the generation and load sides of the power system, representing a unique contribution to the field.
Assessing equity in disaster risk governance in Brazil and Colombia
Authors: Ulbrich Philipp , Leal Sobral André Vinicius , Rivera-Flórez Luis Alejandro , Rodríguez-Gaviria Edna Margarita , Coaffee Jon , Marchezini Victor , Porto de Albuquerque João 
Published: November 2023

PurposeDisasters continue to be most prevalent and severe for marginalised communities. To reach those furthest behind first, as the global community pledges in the 2030 Agenda, a critical assessment of equity in disaster risk governance is necessary. Yet, the understanding of factors that mediate the capacity of the governance processes to achieve equity ambitions is limited. This paper addresses this gap by proposing and testing a conceptual framework to assess equity in disaster risk governance.Design/methodology/approachThe framework analyses the extent to which institutional relationships and data in risk governance support inclusion and diversity of voice and enable the equitable engagement of communities. The study applied the framework to key risk policies across governance levels in Brazil and Colombia.FindingsThe study finds that institutional awareness of cross-sectoral and -scalar coordination clearly exists. Yet, the engagement of actors further down the governance scale is framed reactively at all scales in both countries. The analysis of the risk data practices indicates that although data integration and sharing are key policy priorities, the policies frame the relations of disaster risk data actors as hierarchical, with data needs determined from the top down.Originality/valueA key contribution of this framework is that its equity view results in a nuanced analysis, thus pointing to the differences between the two countries concerning the factors that mediate these challenges and providing specific entry points for strengthening equity in risk governance policies.
Dual solutions for the two-dimension copper oxide with silver (CuO–Αg) and zinc oxide with silver (ΖnO–Αg) hybrid nanofluid flow past a permeable shrinking sheet in a dusty fluid with velocity slip
Authors: Usafzai Waqar Khan , Pop Ioan , Revnic Cornelia 
Published: November 2023

Purpose
This paper aims to present dual solutions for the two-dimension copper oxide with silver (CuO–Ag) and zinc oxide with silver (ZnO–Ag) hybrid nanofluid flow past a permeable shrinking sheet in a dusty fluid with velocity slip.

Design/methodology/approach
The governing partial differential equations for the two dust particle phases are reduced to the pertinent ordinary differential equations using a similarity transformation. Closed-form analytical solutions for the reduced skin friction and reduced Nusselt number, as well as for the velocity and temperature profiles, were presented, both graphically and in tables, under specific non-dimensional physical parameters such as the suction parameter, Prandtl number, slip parameter and shrinking parameter, which are also presented in both figures and tables.

Findings
The results indicate that for the shrinking flow, the wall skin friction is higher in the dusty fluid when compared with the clear (viscous) fluid. In addition, the effect of the fluid–particle interaction parameter to the fluid phase can be seen more clearly in the shrinking flow. Furthermore, multiple (dual, upper and lower branch solutions) are found for the governing similarity equations and the upper branch solution expanded with higher values of the suction parameter. It can be confirmed that the lower branch solution is unstable.

Practical implications
In practice, the study of the stretching/shrinking flow is crucially important and useful. Both the problems of steady and unsteady flow of a dusty fluid have a wide range of possible applications in practice, such as in the centrifugal separation of particles, sedimentation and underground disposal of radioactive waste materials.

Originality/value
Even though the problem of dusty fluid has been broadly investigated, very limited results can be found for a shrinking sheet. Indeed, this paper has succeeded to obtain analytically dual solutions. The stability analysis can be performed by following many published papers on stretching/shrinking sheets. Finally, the critical values and plotting curves for obtaining single or dual solution are successfully presented.