bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tacrolimus After rATG and Infliximab Induction Immunosuppression—RIMINI Trial
Authors: Viklicky Ondrej , Zahradka Ivan , Bold Gantuja , Bestard Oriol , Hruba Petra , Otto Natalie M. , Stein Maik , Sefrin Anett , Modos Istvan , Meneghini Maria , Crespo Elena , Grinyo Josep , Volk Hans-Dieter , Christakoudi Sofia , Reinke Petra 
Published: August 2023

Background.
Infliximab selectively targets recently activated effector cells and, as an induction agent, might enable the safe elimination of mycophenolate from maintenance immunosuppression in kidney transplantation.

Methods.
This is a phase II international multicenter open-label single-arm confidence interval (CI)–based clinical trial of the BIO-DrIM EU consortium aimed at assessing the efficacy and safety of rabbit antithymocyte globulin and infliximab induction in kidney transplantation. Sixty-seven primary kidney transplant recipients at low risk (panel-reactive antibodies <20%, no donor-specific antibodies [DSA]) received rabbit antithymocyte globulin (2 × 1.5 mg/kg, postoperative days 0 and 1) and infliximab (5 mg/kg, postoperative day 2), followed by mycophenolate-free tacrolimus-based immunosuppression for 12 mo. The primary endpoint was efficacy failure, defined as a composite of acute rejection, graft loss, or poor graft function (estimated glomerular filtration rate <40 mL/min) at 12 mo and was based on the endpoint of the comparator study. Additionally, a historical propensity-matched control cohort was established.

Results.
Primary endpoint occurred in 22 of 67 patients (32.84%), with upper bound of an exact 1-sided 95% CI of 43.47%, which met the predefined criteria (efficacy failure of <40% and upper-bound 95% CI of <50%) and was similar in the historical matched cohort. By 12 mo, 79.1% of patients remained on the study protocol. Lower rates of BK replication (6% versus 22.4%; P = 0.013) but higher rates of de novo DSAs (11.9% versus 1.5%; P = 0.039) were observed in the study cohort.

Conclusions.
A similar efficacy of the study immunosuppression regimen to the comparator study and the historical matched cohort was found. However, a higher de novo DSA emergence points to an increased risk of antibody-mediated rejection (NCT04114188).
SalmonellaInfantis, the emerging human multidrug resistant pathogen – a One Health perspective
Authors: Mattock Jennifer , Chattaway Marie Anne , Hartman Hassan , Dallman Timothy J. , Smith Anthony M. , Keddy Karen , Petrovska Liljana , Manners Emma J. , Duze Sanelisiwe T. , Smouse Shannon , Tau Nomsa , Timme Ruth , Baker Dave J. , Mather Alison E. , Wain John , Langridge Gemma C. 
Published: August 2023

AbstractSalmonella Infantis presents an ever-increasing threat to public health due to its spread throughout many countries and association with high levels of antimicrobial resistance (AMR). Whole genome sequences of 5,284S. Infantis strains from 74 countries, isolated between 1989 and 2020 from a wide variety of sources including humans, animals, and food, were analysed to compare genetic phylogeny, AMR determinants and plasmid presence.The globalS. Infantis population structure diverged into three clusters: a North American cluster, European cluster and a global cluster. The levels of AMR varied between theS. Infantis clusters and by isolation source; 73% of poultry isolates had multidrug resistance (MDR) compared to 35% of human isolates. This correlated with plasmid of emergingS. Infantis (pESI) presence; 71% of poultry isolates contained pESI versus 32% of human isolates. This provides important information for public health teams engaged in reducing the spread of this pathogen.
ATML1 Regulates the Differentiation of ER Body-containing Large Pavement Cells in Rosette Leaves of Brassicaceae Plants
Authors: Wilkens Alwine , Czerniawski Paweł , Bednarek Paweł , Libik-Konieczny Marta , Yamada Kenji 
Published: August 2023

AbstractEndoplasmic reticulum (ER)-derived organelles, ER bodies, participate in the defense against herbivores in Brassicaceae plants. ER bodies accumulate β-glucosidases, which hydrolyse specialized thioglucosides known as glucosinolates to generate bioactive substances. InArabidopsis thaliana, the leaf ER (LER) bodies are formed in large pavement cells, which are found in the petioles, margins, and blades of rosette leaves. However, the regulatory mechanisms involved in establishing large pavement cells are unknown. Here, we show that the ARABIDOPSIS THALIANA MERISTEM L1 LAYER (ATML1) transcription factor regulates the formation of LER bodies in large pavement cells of rosette leaves. Overexpression ofATML1enhanced the expression of LER body-related genes and the number of LER body-containing large pavement cells, whereas its knockout resulted in opposite effects. ATML1 enhances endoreduplication and cell size through LOSS OF GIANT CELLS FROM ORGANS (LGO). Although the overexpression and knockout ofLGOaffected the appearance of large pavement cells in Arabidopsis, the effect on LER body-related gene expression and LER body formation was weak. LER body-containing large pavement cells were also found inEutrema salsugineum, another Brassicaceae species. Our results demonstrate that ATML1 establishes large pavement cells to induce LER body formation in Brassicaceae plants, contributing to the defense against herbivores.
Potential to Enhance Large Scale Molecular Assessments of Skin Photoaging through Virtual Inference of Spatial Transcriptomics from Routine Staining
Authors: Srinivasan Gokul , Davis Matthew , LeBoeuf Matthew , Fatemi Michael , Azher Zarif , Lu Yunrui , Diallo Alos , Montivero Marietta Saldias , Kolling Fred , Perrard Laurent , Salas Lucas , Christensen Brock , Palisoul Scott , Tsongalis Gregory , Vaickus Louis , Preum Sarah , Levy Joshua 
Published: August 2023

AbstractThe advent of spatial transcriptomics technologies has heralded a renaissance in research to advance our understanding of the spatial cellular and transcriptional heterogeneity within tissues. Spatial transcriptomics allows investigation of the interplay between cells, molecular pathways and the surrounding tissue architecture and can help elucidate developmental trajectories, disease pathogenesis, and various niches in the tumor microenvironment. Photoaging is the histological and molecular skin damage resulting from chronic/acute sun exposure and is a major risk factor for skin cancer. Spatial transcriptomics technologies hold promise for improving the reliability of evaluating photoaging and developing new therapeutics. Current challenges, including limited focus on dermal elastosis variations and reliance on self-reported measures, can introduce subjectivity and inconsistency. Spatial transcriptomics offer an opportunity to assess photoaging objectively and reproducibly in studies of carcinogenesis and discern the effectiveness of therapies that intervene on photoaging and prevent cancer. Evaluation of distinct histological architectures using highly-multiplexed spatial technologies can identify specific cell lineages that have been understudied due to their location beyond the depth of UV penetration. However, the cost and inter-patient variability using state-of-the-art assays such as the 10x Genomics Spatial Transcriptomics assays limits the scope and scale of large-scale molecular epidemiologic studies. Here, we investigate the inference of spatial transcriptomics information from routine hematoxylin and eosin-stained (H&E) tissue slides. We employed the Visium CytAssist spatial transcriptomics assay to analyze over 18,000 genes at a 50-micron resolution for four patients from a cohort of 261 skin specimens collected adjacent to surgical resection sites for basal and squamous keratinocyte tumors. The spatial transcriptomics data was co-registered with 40x resolution whole slide imaging (WSI) information. We developed machine learning models that achieved a macro-averaged median AUC and F1 score of 0.80 and 0.61 and Spearman coefficient of 0.60 in inferring transcriptomic profiles across the slides, and accurately captured biological pathways across various tissue architectures.
EstablishingAc/DsStarter Lines for Large-Scale Transposon-Tagged Mutagenesis in Tomato
Authors: Kumari Alka , Ponukumatla Rachana , Pandey Arun Kumar , Sreelakshmi Yellamaraju , Sharma Rameshwar 
Published: August 2023

AbstractTomato (Solanum lycopersicum), a model system for ripening of fleshy fruits, has ∼40,000 genes predicted byin silicohomology-based annotation. However, functional validation is lacking for most annotated tomato genes. Among the strategies for functional annotations, transposon-tagged mutagenesis is the most powerful approach. Transposon- tagged genes can be functionally validated by phenotyping and activation tagging. However, the lack of a robustin plantatransformation system precludes large-scale transposon- mutagenesis of tomato. To overcome this limitation, we developed two sets of starter lines in tomato, each carrying maize transposon element (Ds) and transposase (Ac), respectively. TheDsandAclines were crossed to allow theAc-mediated transposition of theDsin the F1generation. In the F2generation, the location of excisedDsat new sites in the tomato genome was monitored. TheDstransposition was interspersed on different chromosomes of the tomato, indicating unlinked transposition of theDs. The analysis of DNA sequences flankingDsshowed random integration ofDsin intergenic, genes, and the promoter region of the genome. Our study paves the way for the generation of large-scale transposon-tagged tomato lines usingAc/Dsstarter lines and provides a potential tool for the functional validation of genes in tomato.Short summaryWe developed two sets of starter lines in tomato, carrying maize transposon element (Ds) and transposase (Ac), to enable large-scale transposon-mutagenesis, facilitating functional validation of tomato genes and for generating an insertional mutant resource in tomato.
Protein kinase PfPK2 mediated signalling is critical for host erythrocyte invasion by malaria parasite
Authors: Rawat Rahul Singh , Gupta Ankit , Antil Neelam , Bhatnagar Sonika , Prasad T.S. Keshava , Sharma Pushkar 
Published: August 2023

AbstractSignalling pathways in malaria parasite remain poorly defined and major reason for this is the lack of understanding of the function of majority of parasite protein kinases and phosphatases in parasite signalling and its biology. In the present study, we have elucidated the function of Protein Kinase 2 (PfPK2), which is known to be indispensable for the survival of human malaria parasitePlasmodium falciparum. We demonstrate that it is involved in the invasion of host erythrocytes, which is critical for establishing infection. In addition, PfPK2 may also be involved in the maturation of the parasite post-invasion. PfPK2 regulates the release of microneme proteins like Apical Membrane Antigen 1 (AMA1), which facilitates the formation of Tight Junction between the merozoite and host erythrocyte-a key step in the process of invasion. Comparative phosphoproteomics studies revealed that PfPK2 may be involved in regulation of several key proteins involved in invasion and signalling. Furthermore, PfPK2 regulates the generation of cGMP and the release of calcium in the parasite, which are key second messengers for the process of invasion. These and other studies have shed light on a novel signalling pathway in which PfPK2 acts as an upstream regulator of important cGMP-calcium signalling, which is plays an important role in parasite invasion.
Pleiotropic effects of trisomy and pharmacologic modulation on structural, functional, molecular, and genetic systems in a Down syndrome mouse model
Authors: Llambrich Sergi , Tielemans Birger , Saliën Ellen , Atzori Marta , Wouters Kaat , Van Bulck Vicky , Platt Mark , Vanherp Laure , Gallego Fernandez Nuria , Grau de la Fuente Laura , Poptani Harish , Verlinden Lieve , Himmelreich Uwe , Croitor Anca , Attanasio Catia , Callaerts-Vegh Zsuzsanna , Gsell Willy , Martínez-Abadías Neus , Vande Velde Greetje 
Published: August 2023

ABSTRACTDown syndrome (DS) is characterized by skeletal and brain structural malformations, cognitive impairment, altered hippocampal metabolite concentration and gene expression imbalance. These alterations were usually investigated separately, and the potential rescuing effects of green tea extracts enriched in epigallocatechin-3-gallate (GTE-EGCG) provided disparate results due to different experimental conditions. We overcame these limitations by conducting the first longitudinal controlled experiment evaluating genotype and GTE-EGCG prenatal chronic treatment effects before and after treatment discontinuation. Our findings revealed that the Ts65Dn mouse model reflected the pleiotropic nature of DS, exhibiting brachycephalic skull, ventriculomegaly, neurodevelopmental delay, hyperactivity, and impaired memory robustness with altered hippocampal metabolite concentration and gene expression. GTE-EGCG treatment modulated most systems simultaneously but did not rescue DS phenotypes. On the contrary, the treatment exacerbated trisomic phenotypes including body weight, tibia microarchitecture, neurodevelopment, adult cognition, and metabolite concentration, not supporting the therapeutic use of GTE-EGCG as a prenatal chronic treatment. Our results highlight the importance of longitudinal experiments assessing the co-modulation of multiple systems throughout development when characterizing preclinical models in complex disorders and evaluating the pleiotropic effects and general safety of pharmacological treatments.
Multiple host targets ofPseudomonaseffector protein HopM1 form a protein complex regulating apoplastic immunity and water homeostasis
Authors: Nomura Kinya , Imboden Lori Alice , Tanaka Hirokazu , He Sheng Yang 
Published: August 2023

AbstractBacterial type III effector proteins injected into the host cell play a critical role in mediating bacterial interactions with plant and animal hosts. Notably, some bacterial effectors are reported to target sequence-unrelated host proteins with unknown functional relationships. ThePseudomonas syringaeeffector HopM1 is such an example; it interacts with and/or degrades several HopM1-interacting (MIN) Arabidopsis proteins, including HopM1-interacting protein 2 (MIN2/RAD23), HopM1-interacting protein 7 (MIN7/BIG5), HopM1-interacting protein 10 (MIN10/14-3-3ĸ), and HopM1-interacting protein 13 (MIN13/BIG2). In this study, we purified the MIN7 complex formedin plantaand found that it contains MIN7, MIN10, MIN13, as well as a tetratricopeptide repeat protein named HLB1. Mutational analysis showed that, like MIN7, HLB1 is required for pathogen-associated molecular pattern (PAMP)-, effector-, and benzothiadiazole (BTH)-triggered immunity. HLB1 is recruited to the trans-Golgi network (TGN)/early endosome (EE) in a MIN7-dependent manner. Bothmin7andhlb1mutant leaves contained elevated water content in the leaf apoplast and artificial water infiltration into the leaf apoplast was sufficient to phenocopy immune-suppressing phenotype of HopM1. These results suggest that multiple HopM1-targeted MIN proteins form a protein complex with a dual role in modulating water level and immunity in the apoplast, which provides an explanation for the dual phenotypes of HopM1 during bacterial pathogenesis.
Probing Bioactive Chemical Space to Discover RNA-Targeted Small Molecules
Authors: Wicks Sarah L. , Morgan Brittany S. , Wilson Alexander W. , Hargrove Amanda E. 
Published: August 2023

ABSTRACTSmall molecules have become increasingly recognized as invaluable tools to study RNA structure and function and to develop RNA-targeted therapeutics. To rationally design RNA-targeting ligands, a comprehensive understanding and explicit testing of small molecule properties that govern molecular recognition is crucial. To date, most studies have primarily evaluated properties of small molecules that bind RNAin vitro, with little to no assessment of properties that are distinct to selective and bioactive RNA-targeted ligands. Therefore, we curated an RNA-focused library, termed theDukeRNA-TargetedLibrary (DRTL), that was biased towards the physicochemical and structural properties of biologically active and non-ribosomal RNA-targeted small molecules. The DRTL represents one of the largest academic RNA-focused small molecule libraries curated to date with more than 800 small molecules. These ligands were selected using computational approaches that measure similarity to known bioactive RNA ligands and that diversify the molecules within this space. We evaluated DRTL bindingin vitroto a panel of four RNAs using two optimized fluorescent indicator displacement assays, and we successfully identified multiple small molecule hits, including several novel scaffolds for RNA. The DRTL has and will continue to provide insights into biologically relevant RNA chemical space, such as the identification of additional RNA-privileged scaffolds and validation of RNA-privileged molecular features. Future DRTL screening will focus on expanding both the targets and assays used, and we welcome collaboration from the scientific community. We envision that the DRTL will be a valuable resource for the discovery of RNA-targeted chemical probes and therapeutic leads.
Determinants of blockchain adoption and organizational performance in the healthcare sector in India
Authors: Kabra Gaurav 
Published: August 2023

PurposeBlockchain technology (BCT) has multiple benefits across industries in varied contexts, but limited organizations have adopted such disruptive innovative technologies in the healthcare industry in India. The research on advancing the understanding of blockchain adoption (BCA) determinants in India's healthcare industry is limited. Thus, the study aims to identify the BCA determinants in the healthcare sector in India. Further, the impact of BCA was examined on organizational performance (OP).Design/methodology/approachThe study utilizes Technology, Organization, and Environment (TOE) framework to investigate the determinants of BCA in the healthcare sector in India. The data were gathered using a seven-point Likert seven-point ranging from “strongly agree” to “strongly disagree” from 272 respondents working in the healthcare industry in India. The relationship within the framework was investigated using structural equation modeling.FindingsThe results demonstrate the positive impact of top management support, organizational size, organizational readiness, competitive pressure and government support on BCA in the healthcare sector. On the other hand, compatibility, security and privacy issues do not affect BCA. The results emphasize and validate blockchain’s importance in improving OP in the healthcare sector. Further, the results indicate that non-technological factors are paramount to improving BCA within the healthcare sector. Organizations should invest in employee training and development to ensure their staff have the necessary knowledge and skills to effectively manage BCT.Research limitations/implicationsThe model was developed for BCA in the healthcare sector in the Indian context; however, the model applies to other countries with the same business environment. Hence, the model can be further examined in diverse countries to generalize the findings.Practical implicationsThe study offers valuable insights into the factors that influence BCA and OP in the healthcare sector. The results of this research can be used to inform policy decisions and guide practitioners toward promoting and facilitating the use of BCT in healthcare organizations.Originality/valueTo the best of the author’s knowledge, the present study is the first of its kind to examine the TOE framework in BCA within the healthcare sector and its implications on OP.
Roles of clients in buildability improvement in Nigeria: an exploratory factor analysis
Authors: Osuizugbo Innocent Chigozie , Aina Omotayo Olugbenga , Onokwai Anthony Ogochukwu 
Published: August 2023

PurposeConstruction industry is a vital sector for national and economic development of any country. Past studies reveal that the Nigerian construction industry is suffering from buildability problems. Buildability improvement is the duty of every key stakeholder, including designers, builders and clients. This study sets out to determine the principal roles of clients in buildability improvement in Nigerian construction projects.Design/methodology/approachA questionnaire survey was adopted to evaluate construction industry professionals’ views on the roles of clients in buildability improvement in Nigeria. Eighty-one questionnaires were sufficiently filled and returned, representing a return percentage of 76% which formed the basis of this study. Data elicited were analysed using descriptive and inferential statistics.FindingsThe results from factors analysis show that the roles of clients in buildability improvement can be categorised into two constructs: commitment to buildability assessment and other related practices, and adequate planning of project objectives.Originality/valueThis study contributed to more effective buildability studies by highlighting the roles of clients in buildability improvement in the construction industry. An understanding of these roles is very significant for minimising buildability problems as well as for improving and embedding buildability as a practice in the construction industry.
Antecedents of big data analytics (BDA) adoption in private firms: a sequential explanatory approach
Authors: Waqar Javaria , Paracha Osman Sadiq 
Published: August 2023

Purpose
This study aims to examine the key antecedents influencing the private firm’s intention to adopt big data analytics (BDA) in developing economies. To do so, the study follows the sequential explanatory approach.

Design/methodology/approach
To test the hypothesized model that draws on the technology–organization–environment (TOE) framework paired with the diffusion of innovation (DOI) theory, a purposive sampling technique was applied to gather data from 156 IT and management domain experts from the private firms that intend to adopt BDA and operate in Pakistan’s service industry, including telecommunication, information technology, agriculture, and e-commerce. The data were analysed using the partial least squares structural equations modelling (PLS-SEM) technique and complemented with qualitative analysis of 10 semi-structured interviews in NVIVO 12 based on grounded theory.

Findings
The empirical findings revealed that the two constructs – perceived benefits and top management support – are the powerful drivers of a firm’s intention to adopt BDA in the private sector, whereas IT infrastructure, data quality, technological complexity and financial readiness, along with the moderators, BDA adoption of competitors and government policy and regulation, do not significantly influence the intention. In addition, the qualitative analysis validates and further complements the SEM findings.

Originality/value
Unlike the previous studies on technology adoption, this study proposed a unique research model with contextualized indicators to measure the constructs relevant to private firms, based on the TOE framework and DOI theory, to investigate the causal relationship between drivers and intention. Furthermore, the findings of PLS-SEM were complemented by qualitative analysis to validate the causation. The findings of this study have both theoretical and practical implications.