bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synth4bench: a framework for generating synthetic genomics data for the evaluation of tumor-only somatic variant calling algorithms
Authors: Fragkouli Styliani-Christina , Pechlivanis Nikos , Anastasiadou Anastasia , Karakatsoulis Georgios , Orfanou Aspasia , Kollia Panagoula , Agathangelidis Andreas , Psomopoulos Fotis 
Published: March 2024

AbstractMotivationSomatic variant calling algorithms are widely used to detect genomic alterations associated with cancer. Evaluating their performance, even though being crucial, can be challenging due to the lack of high-quality ground truth datasets. To address this issue, we developed a synthetic data generation framework for benchmarking these algorithms, focusing on the TP53 gene, utilizing the NEATv3.3 simulator. We thoroughly evaluated the performance of Mutect2, Freebayes, VarDict, VarScan2 and LoFreq and compared their results with our synthetic ground truth, while observing their behavior. Synth4bench attempts to shed light on the underlying principles of each variant caller by presenting them with data from a given range across the genomics data feature space and inspecting their response.ResultsUsing synthetic dataset as ground truth provides an excellent approach for evaluating the performance of tumor-only somatic variant calling algorithms. Our findings are supported by an independent statistical analysis that was performed on the same data and output from all callers. Overall, synth4bench leverages the effort of benchmarking algorithms by offering the opportunity to utilize a generated ground truth dataset. This kind of framework is essential in the field of cancer genomics, where precision is an ultimate necessity, especially for variants of low frequency. In this context, our approach makes comparison of various algorithms transparent, straightforward and also enhances their comparability.Availabilitysynth4bench is available athttps://github.com/BiodataAnalysisGroup/synth4benchand all data available athttps://zenodo.org/records/10683211.
Highly multiplexed design of an allosteric transcription factor to sense novel ligands
Authors: Nishikawa Kyle K. , Chen Jackie , Acheson Justin F. , Harbaugh Svetlana V. , Huss Phil , Frenkel Max , Novy Nathan , Sieren Hailey R. , Lodewyk Ella C. , Lee Daniel H. , Chávez Jorge L. , Fox Brian G. , Raman Srivatsan 
Published: March 2024

AbstractAllosteric transcription factors (aTF), widely used as biosensors, have proven challenging to design for detecting novel molecules because mutation of ligand-binding residues often disrupts allostery. We developed Sensor-seq, a high-throughput platform to design and identify aTF biosensors that bind to non-native ligands. We screened a library of 17,737 variants of the aTF TtgR, a regulator of a multidrug exporter, against six non-native ligands of diverse chemical structures – four derivatives of the cancer therapeutic tamoxifen, the antimalarial drug quinine, and the opiate analog naltrexone – as well as two native flavonoid ligands, naringenin and phloretin. Sensor-seq identified novel biosensors for each of these ligands with high dynamic range and diverse specificity profiles. The structure of a naltrexone-bound design showed shape-complementary methionine-aromatic interactions driving ligand specificity. To demonstrate practical utility, we developed cell-free detection systems for naltrexone and quinine. Sensor-seq enables rapid, scalable design of new biosensors, overcoming constraints of natural biosensors.
A tale of two fusion proteins: understanding the metastability of human respiratory syncytial virus and metapneumovirus and implications for rational design of uncleaved prefusion-closed trimers
Authors: Lee Yi-Zong , Han Jerome , Zhang Yi-Nan , Ward Garrett , Gomes Keegan Braz , Auclair Sarah , Stanfield Robyn L. , He Linling , Wilson Ian A. , Zhu Jiang 
Published: March 2024

ABSTRACTRespiratory syncytial virus (RSV) and human metapneumovirus (hMPV) cause human respiratory diseases and are major targets for vaccine development. In this study, we designed uncleaved prefusion-closed (UFC) trimers for the fusion (F) proteins of both viruses by examining mutations critical to F metastability. For RSV, we assessed four previous prefusion F designs, including the first and second generations of DS-Cav1, SC-TM, and 847A. We then identified key mutations that can maintain prefusion F in a native-like, closed trimeric form (up to 76%) without introducing any interprotomer disulfide bond. For hMPV, we developed a stable UFC trimer with a truncated F2-F1linkage and an interprotomer disulfide bond. Tens of UFC constructs were characterized by negative-stain electron microscopy (nsEM), x-ray crystallography (11 RSV-F and one hMPV-F structures), and antigenic profiling. Using an optimized RSV-F UFC trimer as bait, we identified three potent RSV neutralizing antibodies (NAbs) from a phage-displayed human antibody library, with a public NAb lineage targeting sites Ø and V and two cross-pneumovirus NAbs recognizing site III. In mouse immunization, rationally designed RSV-F and hMPV-F UFC trimers induced robust antibody responses with high neutralizing titers. Our study provides a foundation for future prefusion F-based RSV and hMPV vaccine development.ONE-SENTENCE SUMMARYThe metastability analysis of fusion proteins has informed rational design of uncleaved prefusion-closed trimers for RSV and hMPV vaccine development.
Immune Signatures of SARS-CoV-2 Infection Resolution in Human Lung Tissues
Authors: Kenney Devin , O’Connell Aoife K. , Tseng Anna E. , Turcinovic Jacquelyn , Sheehan Maegan L. , Nitido Adam D. , Montanaro Paige , Gertje Hans P. , Ericsson Maria , Connor John H. , Vrbanac Vladimir , Crossland Nicholas A. , Harly Christelle , Balazs Alejandro B. , Douam Florian 
Published: March 2024

ABSTRACTWhile human autopsy samples have provided insights into pulmonary immune mechanisms associated with severe viral respiratory diseases, the mechanisms that contribute to a clinically favorable resolution of viral respiratory infections remain unclear due to the lack of proper experimental systems. Using mice co-engrafted with a genetically matched human immune system and fetal lung xenograft (fLX), we mapped the immunological events defining successful resolution of SARS-CoV-2 infection in human lung tissues. Viral infection is rapidly cleared from fLX following a peak of viral replication, histopathological manifestations of lung disease and loss of AT2 program, as reported in human COVID-19 patients. Infection resolution is associated with the activation of a limited number of hematopoietic subsets, including inflammatory monocytes and non-canonical double-negative T-cells with cytotoxic functions, which are highly enriched in viral RNA and dissipate upon infection resolution. Activation of specific human fibroblast and endothelial subsets also elicit robust antiviral and monocyte chemotaxis signatures, respectively. Notably, systemic depletion of human CD4+ cells, but not CD3+ cells, abrogates infection resolution in fLX and induces persistent infection, supporting evidence that peripheral CD4+ monocytes are important contributors to SARS-CoV-2 infection resolution in lung tissues. Collectively, our findings unravel a comprehensive picture of the immunological events defining effective resolution of SARS-CoV-2 infection in human lung tissues, revealing markedly divergent immunological trajectories between resolving and fatal COVID-19 cases.
Cryo-EM inspired NMR analysis reveals a pH-induced conformational switching mechanism for imparting dynamics to Betanodavirus protrusions
Authors: Štěrbová Petra , Wang Chun-Hsiung , Carillo Kathleen J.D. , Lou Yuan-Chao , Kato Takayuki , Namba Keiichi , Tzou Der-Lii M. , Chang Wei-Hau 
Published: March 2024

AbstractNervous necrosis virus (NNV), a non-enveloped betanodavirus, causes neuropathies and retinopathies in farmed fish, damaging aquaculture worldwide. NNV has 60 conspicuous surface protrusions comprising the protrusion domain (P-domain) of its capsid protein. Although NNV protrusions play critical roles in infectivity, the underlying dynamics remain unclear. Our cryogenic electron microscopy (cryo-EM)-derived structures of Dragon grouper (Epinephelus lanceolatus) NNV reveal that the protrusions undergo low-pH-induced compaction and movement. We show that the P-domain is monomeric in solution at a pH germane to infection (7.0). Moreover, nuclear magnetic resonance (NMR) structures reveal a peptide (amino acids 311-330) that adopts a flexible loop to form an open pocket. NMR spectral analysis at pH 5.0 aided by molecular dynamics (MD) simulations show that this loop switches to a β-strand under acidic conditions, eliciting pocket closure and P-domain trimerization, highlighting a unique pH-sensing feature. Our docking analysis revealed the N-terminal moiety of sialic acid inserted into and interacting with conserved residues in the pocket. Additionally, a low-pH-induced conformational change in the linker region via peptide bond isomerization conferred malleability on the protrusions. Our work uncovers the protrusion dynamics of a betanodavirus governing its infectivity through a pH-dependent conformational switching mechanism, providing insights into complex virus-host interactions.
A comparison between full-length 16S rRNA Oxford Nanopore sequencing and Illumina V3-V4 16S rRNA sequencing in head and neck cancer tissues
Authors: Yeo Kenny , Connell James , Bouras George , Smith Eric , Murphy William , Hodge John-Charles , Krishnan Suren , Wormald Peter-John , Valentine Rowan , Psaltis Alkis James , Vreugde Sarah , Fenix Kevin Aaron 
Published: March 2024

AbstractIntroductionDescribing the microbial community within the tumour has been a key aspect in understanding the pathophysiology of the tumour microenvironment. In head and neck cancer (HNC), most studies on tissue samples have only performed 16S ribosomal RNA (rRNA) short-read sequencing (SRS) on V3-V5 region. SRS is mostly limited to genus level identification. In this study, we compared full-length 16S rRNA long-read sequencing (FL-ONT) from Oxford Nanopore Technology (ONT) to V3-V4 Illumina SRS (V3V4-Illumina). To date, this is the largest study using HNC tissues samples to perform FL-ONT of the 16S rRNA using ONT.MethodsSequencing of the full-length and the V3-V4 16S rRNA region was conducted on tumour samples from 26 HNC patients, using ONT and Illumina technologies respectively. Paired sample analysis was applied to compare differences in diversities and abundance of microbial communities. Further validation was also performed using culture-based methods in 16 bacterial isolates obtained from 4 patients using MALDI-TOF MS.ResultsWe observed similar alpha diversity indexes between FL-ONT and V3V4-Illumina technologies. However, beta-diversity was significantly different between techniques (PERMANOVA - R2= 0.083, p < 0.0001). At higher taxonomic levels (Phylum to Family), all metrics were more similar among sequencing techniques, while lower taxonomy displayed more discrepancies. At higher taxonomic levels, correlation in microbial abundance from FL-ONT and V3V4-Illumina were higher, while this correlation decreased at lower levels. Finally, FL-ONT was able to identify more isolates at the species level that were identified using MALDI-TOF MS (81.3% v.s. 62.5%).ConclusionsFL-ONT was able to identify lower taxonomic levels at a better resolution as compared to V3V4-Illumina 16S rRNA sequencing. Depending on application purposes, both methods are suitable for identification of microbial communities, with FL-ONT being more superior at species level.
Exo70 promotes herpesvirus secretory vesicle tethering and virion release in an exocyst complex-dependent manner
Authors: Ma Wenqing , Xu Yanan , Xie Jialin , He Luteng , Wang Lin , Yu Jie , Sun Fachao , He Daniel Chang , Wang Hongmei , He Hongbin 
Published: March 2024

AbstractThe exocyst complex, a multisubunit protein complex, mediates secretory vesicles fusion with the plasma membrane (PM) to deliver materials to the cell surface or to release cargoes to the extracellular space, but whether it is related to viral secretory vesicles tethering and virion release is unknown. Here, we identified that the exocyst complex subunit Exo70 promotes the trafficking of herpesvirus secretory vesicles and the release of mature virions in an exocyst complex-dependent manner. Mechanistically, mutation of Exo70 Lys632 and Lys635 diminishes viral secretory vesicles anchoring to PM. Moreover, the small GTPase Rab11a is necessary for the transport of viral secretory vesicles, and the Snapin-Exo70-SNAP23 axis is involved in fusion of viral secretory vesicles to the PM and release of virions. Most significantly, we discovered that Endosidin2 (ES2), an inhibitor of exocytosis via the exocyst complex, provides protection against herpesvirus infection in cells and mice. Overall, these findings unveil a previously uncharacterized role and mechanism of the exocyst complex in viral replication, highlighting its potential as an effective strategy against herpesvirus infection.Author summaryHerpesviruses, such as herpes simplex virus 1 (HSV-1) and bovine herpes virus type 1 (BoHV-1), are highly prevalent pathogens that establish lifelong infections and cause various diseases in humans and animals. While the mechanisms underlying the transport of herpesvirus secretory vesicles from the Golgi to the PM and the subsequent viral release are still poorly understood. In our study, we have discovered that Exo70 promotes the trafficking of HSV-1 and BoHV-1 secretory vesicles and facilitates the release of mature virions in an exocyst complex-dependent manner. Mechanistically, both knockdown of Exo70 and a phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2)-binding-deficient mutant of Exo70 caused virions to be trapped in the cytoplasm and unable to tether to PM, indicating that the binding of Exo70 to PI(4,5)P2 is critical for the docking virus secretory vesicles with PM. Additionally, the Snapin-Exo70-SNAP23 axis plays a pivotal role in the fusion between viral secretory vesicles and the PM, ultimately facilitating the release of virions. We found that Rab11a is necessary for viral secretory vesicle trafficking mediated by Exo70. Most importantly, we discovered that ES2, a transport inhibitor that combines with Exo70 to terminate the final stage of exocytosis via the exocyst complex, can protect cells and mice from α-herpesvirus infection.
RegionalPlasmodium falciparumsubpopulations and malaria transmission connectivity in Africa detected with an enlarged panel of genome-wide microsatellite loci
Authors: Demba Martha Anita , Kamau Edwin , Raman Jaishree , Mane Karim , Emenga-Etego Lucas , Apinjo Tobias , Isheghoma Deus , Golassa Lemu , Maiga Oumou , Ghansah Anita , Bouyou-Akotet Marielle , Yavo William , Randrianarivelojosia Milijoana , Diop Fadel Muhammadou , Oriero Eniyou , Jeffries David , D’Alessandro Umberto , Djimde Abdoulaye , Amambua-Ngwa Alfred 
Published: March 2024

AbstractUnravelling the genetic diversity ofPlasmodium falciparummalaria parasite provides critical information on how populations are affected by interventions and the environment, especially the evolution of molecular markers associated with parasite fitness and adaptation to drugs and vaccines. This study expands previous studies based on small sets of microsatellite loci, which often showed limited substructure in African populations ofP. falciparum. Combining several short tandem repeat detection algorithms, we genotyped and analysed 2329 polymorphic microsatellite loci from next-generation sequences of 992 low-complexity P. falciparumisolates from 15 sub-Saharan African countries. Based on pairwise relatedness, we identified seven subpopulations and gene flow between the Central and Eastern African populations. The most divergent subpopulation was from Ethiopia, while unexpected unique subpopulations from Gabon and Malawi were resolved. Isolates from the Democratic Republic of Congo shared ancestry with multiple regional populations, suggesting a possible founder population of P. falciparum from the Congo basin, where there was stronger geneflow eastwards to Tanzania, and Kenya. and Malawi. The most differentiated microsatellite loci were those around theP. falciparumdihydropteroate synthase (Pfdhps) gene associated with sulphadoxine resistance. Haplotypes around thePfdhpsgene separated the West, Central, and East Africa parasite populations into distinct clusters, suggesting independent local evolution ofPfdhps-associated sulphadoxine resistance alleles in each African region. Overall, this study presents genome-wide microsatellites as markers for resolving P. falciparum population diversity, structure, and evolution in populations like Africa, where there is high gene flow.
Digital taxation, artificial intelligence and Tax Administration 3.0: improving tax compliance behavior – a systematic literature review using textometry (2016–2023)
Authors: Belahouaoui Rida , Attak El Houssain 
Published: March 2024

PurposeThis paper aims to analyze the impact of tax digitalization, focusing on artificial intelligence (AI), machine learning and blockchain technologies, on enhancing tax compliance behavior in various contexts. It seeks to understand how these emerging digital tools influence taxpayer behaviors and compliance levels and to assess their effectiveness in reducing tax evasion and avoidance practices.Design/methodology/approachUsing a systematic review technique with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses method, this study evaluates 62 papers collected from the Scopus database. The papers were analyzed through textometry of titles, abstracts and keywords to identify prevailing trends and insights.FindingsThe review reveals that digitalization, particularly through AI and blockchain, significantly enhances tax compliance and operational efficiency. However, challenges persist, especially in emerging economies, regarding the adoption and integration of these technologies in tax systems. The findings indicate a global trend toward digital Tax Administration 3.0, emphasizing the importance of regulatory frameworks, capacity building and simplification for small and medium enterprises (SMEs).Practical implicationsThe findings provide guidance for policymakers and tax administrations, underscoring the necessity of strategic planning, regulatory backing and global cooperation to effectively use digital technologies in tax compliance. Emphasizing the need for tailored support for SMEs, the study also calls for expanded research in less represented areas and specific sectors, such as SMEs and developing economies, to deepen global insights into digital tax compliance.Originality/valueThis study has attempted to fill the gap in the literature on the comprehensive impact of fiscal digitalization, particularly AI-based, on tax compliance across different global contexts, adding to the discourse on digital taxation.
The impacts of multiple privacy regulations and national security infrastructure on health information exchange: a study of hospitals across Europe
Authors: Shrivastava Utkarsh , Han Bernard , Zhou Ying , Razi Muhammad 
Published: March 2024

Purpose
Sharing patient health information (PHI) among hospitals has been much slower than the adoption of health record systems. This paper aims to investigate if privacy regulation (PR) or security measures (SMs) influence hospitals’ use of health information exchange (HIE) to share PHI with other providers (e.g. physicians, labs, hospitals). The study specifically focuses on how multiple PRs can impede and a strong national security infrastructure (NSI) can support HIE.

Design/methodology/approach
The study uses secondary data from a multi-national and multi-hospital survey administered by the European Union. The multi-level structure of the cross-sectional panel data is used to test the influence of both hospital-level (e.g. PR) and national-level variables (e.g. NSI) on HIE. A total of nine types of HIE, three types of PRs, nine SMs and other relevant control variables are considered. This study uses a two-level random intercept generalized linear model to test the hypothesis proposed in the study.

Findings
The study finds that national-level PRs (NLPR) have the strongest positive influence on HIE in comparison to regional (RLPR) and hospital-level (HLPR) PRs. Moreover, the study finds evidence that the presence of RLPR and HLPR, on average, decreases the positive impact of NLPR by 264%. The SMs also have a significant and positive impact on HIE. Adoption of an additional SM can increase the odds of engaging in a certain type of HIE between 21% and 61%. On the other hand, a strong NSI can also amplify the positive impact of SM on certain types of HIE.

Originality/value
This study extends prior research on the role of PRs in enabling HIE by considering the complexities brought up by adopting multiple PRs. NLPRs have the strongest impact on HIE in comparison to RLPRs or HLPRs. Moreover, public infrastructure initiatives such as those related to secure communications can also complement SMs adopted by the providers by encouraging HIE.
Attention Autism™ training for occupational therapists: a pilot study
Authors: Ruttledge Aideen 
Published: March 2024

Purpose
At present, there is no reference to Attention Autism (AA) as a framework and therapeutic tool with autistic children in occupational therapy (OT) literature. By way of introducing AA as a potential intervention to the OT community, this study aims to investigate the extent to which participation in a two-day AA training could contribute to increasing confidence and inspire changes in practice for Irish occupational therapists (OTs) supporting autistic children.

Design/methodology/approach
A pilot study design with mixed qualitative and quantitative methods was used to evaluate the impact of a two-day AA training on six OTs. The OTs support autistic children throughout Ireland across public, private and voluntary sectors. They completed brief, non-standardised questionnaires 2 weeks before the training (Time 1) and again 12 weeks post (Time 2) training session. At Time 2, additional exploratory questions were answered by OTs regarding their use of AA in practice.

Findings
This explorative study’s quantitative findings presented percentage change increases within three areas of confidence for all OTs. These include establishing attention, motivating and developing functional skill goals with autistic children. One of the participants did not score any change in confidence in a fourth area, building rapport, however, the five other participants scored percentage change increases. Qualitative data provided by participants showed that they were implementing AA in practice since attending the training. Five of the participants reported positive experiences of using AA and one participant reported the programme was not suitable for her caseload because of their level of understanding and need.

Research limitations/implications
This was a small, exploratory, practice-based study. As this is the first study exploring this area of practice for OTs, to the best of the authors’ knowledge, there were no standardised methods of assessment available, therefore a self-designed survey was used by the author which had a limited number of open-ended questions and four Likert scale questions. This study was also limited in that there was one main researcher who also delivered the two-day AA training. The sample data set was small which resulted in the limitation of the choice of methods used to analyse the quantitative data. Percentage changes were used as the only available and reliable method for a small data set.

Originality/value
Findings of this study, despite their preliminary nature, indicate that AA training may be a useful professional development consideration for OTs who provide a service for autistic children. Further AA research in OT is required including larger and more rigorous studies. An alternative training option of The Curiosity Programme may be considered for OTs supporting children who may not yet be ready to participate in AA.