bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic value of plasma IgG N-glycome traits in patients with pulmonary arterial hypertension: an observational cohort study
Authors: Zhang Ze-Jian , Liu Chao , Ma Jie-Ling , Ma Jing-Si , Wang Jia , Li Ruo-Nan , Lu Dan , Zhou Yu-Ping , Lian Tian-Yu , Zhang Si-Jin , Li Jing-Hui , Wang Lan , Sun Kai , Cheng Chun-Yan , Wu Wen-Hui , Jing Zhi-Cheng 
Published: December 2023

AbstractBackgroundBNP (brain natriuretic peptide) or NT-proBNP (N-terminal proBNP) is the only blood biomarker in the established risk calculators for pulmonary arterial hypertension (PAH). New plasma biomarkers of systemic origin may improve the risk assessment in PAH.MethodsWe utilized a robust mass spectrometry-based method to identify prognostic plasma IgG N-glycome traits in PAH patients from two national referral centers in China (Beijing [discovery] cohort, n = 273; Shanghai cohort [validation], n = 349). Then the candidate IgG N-glycan traits were evaluated in combined cohorts adjusted for potential confounders and subgroup analyses. At last, the candidate IgG N-glycan traits were further evaluated against the established prognostic risk equation (three-strata model from the SPAHR and COMPERA analyses) for PAH. The primary endpoint was all-cause mortality.ResultsIgG Fucosylation was found to predict survival independent of age and sex in the discovery cohort (HR: 0.377, 95% CI: 0.168-0.845,P= 0.018) with confirmation in the validation cohort (HR: 0.264, 95% CI: 0.445-0.751,P= 0.005). IgG Fucosylation remained a robust predictor of mortality in PAH patients in the combined cohorts adjusting for potential confounders and in subgroup analyses based on sex and treatment strategies. Moreover, the addition of the IgG Fucosylation to the established three-strata model significantly improved the predictive accuracy from AUC of 0.67 to AUC of 0.70 (P= 0.043) and IgG Fucosylation was useful in further stratifying the intermediate risk PAH patients classified by the three-strata model into intermediate-low and intermediate-high risk subgroups.ConclusionsThe plasma IgG Fucosylation informs prognosis independent of the existing clinical assessments in PAH and may be useful in the clinical management of patients with PAH.Clinical Perspective What is new?The plasma IgG Fucosylation, which is in different pathophysiological pathways from other established risk factors of pulmonary arterial hypertension (PAH), can inform prognosis independent of the existing clinical assessments in patients with PAH.The addition of the IgG Fucosylation to the established three-strata model for PAH prognosis significantly improved the predictive accuracy.IgG Fucosylation was useful in further stratifying the intermediate risk PAH patients classified by the three-strata model into intermediate-high and intermediate-low risk subgroups.What are the clinical implications?Plasma IgG N-glycan biomarkers may provide a refined risk stratification in PAH used in combination with the established risk factors.IgG Fucosylation involved in inflammatory pathways may not only be a promising prognostic biomarker but also a potential novel therapeutic target, distinct from existing targets, for patients with PAH.
Inflammatory bowel disease burden in Asia from 1990 to 2019 and predictions to 2040
Authors: Wang Xingchen , Xiong Jiannan , Ding Zhao , Liu Yueting , Yang Chongguang , Xu Pengfei 
Published: December 2023

AbstractBackgroundWhile the incidence of inflammatory bowel disease (IBD) has stabilized in Western countries since 1990, it is experiencing an upward trend in newly industrializing countries. The Asian region encompasses a multitude of developing countries at varying stages of IBD progression. Therefore, comprehending the current epidemiological characteristics of the disease in this region becomes imperative, enabling countries and locales in Asia to proactively address the evolving IBD burden in the upcoming several decades.MethodsWe analyze variation trends in the burden of IBD in Asia from 1990 to 2019, employing data and methods from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD), and provide projections for future changes in IBD incidence in Asia over the next 20 years.ResultsIn 2019, the number of incidence cases of IBD in Asia was 145,561 (95% UI 124,960-170,895), the total number of prevalence cases reached nearly 2 million (95% UI 1.71-2.32), and 13,957 (95% UI 11,898-16,021) patients died of IBD. Meanwhile, the total years lived with disability (YLDs) attributed to IBD amounted to 299,663 (95% UI 198,365-418,635), while the total disability-adjusted life-years (DALYs) rose to 649,760 (95% UI 530,395-783,181). The total number of incidence cases in Asia is projected to reach 179,756 in 2040, with an age-standardized incidence rate of 2.92 per 100,000 population.ConclusionsThe increase in the overall burden of IBD in Asia is primarily driven by population growth and aging, with both incidence and DALYs continuing to rise in most countries. It is imperative for each country to adapt its measures to local conditions, improve prevailing healthcare service patterns, and draw insights from the frontier countries to respond to the evolving epidemic characteristics of IBD.
Predicting the dynamic interaction of intrinsically disordered proteins
Authors: Zheng Yuchuan , Li Qixiu , Freiberger Maria I. , Song Haoyu , Hu Guorong , Zhang Moxin , Gu Ruoxu , Li Jingyuan 
Published: December 2023

AbstractIntrinsically disordered proteins (IDPs) participate in various biological processes. Interactions involving IDPs are usually dynamic and affected by their inherent conformation fluctuations. Comprehensive characterization of these interactions based on current techniques is challenging. Here, we present GSALIDP, a GraphSAGE-LSTM Network to capture the dynamic nature of IDP-involved interactions and predict their behaviors. This framework models multiple conformations of IDP as a dynamic graph which can effectively describe the fluctuation of its flexible conformation. The dynamic interaction between IDPs is studied and the datasets of IDP conformations and their interactions are obtained through atomistic molecular dynamic (MD) simulations. Residues of IDP are encoded through a series of features, including their frustration. GSALIDP can effectively predict the interaction sites of IDP and the contact residue pairs between IDPs. Its performance in predicting IDP interaction is on par with or even better than the conventional models in predicting the interaction of structural proteins. To the best of our knowledge, this is the first model to extend the protein interaction prediction to IDP-involved interactions.
High-Throughput Screening of the Effects of 90 Xenobiotics on the Simplified Human Gut Microbiota Model (SIHUMIx): A Metaproteomic and Metabolomic Study
Authors: Castañeda-Monsalve Victor , Fröhlich Laura-Fabienne , Haange Sven-Bastiaan , Homsi Masun Nabhan , Rolle-Kampczyk Ulrike , Fu Qiuguo , von Bergen Martin , Jehmlich Nico 
Published: December 2023

AbstractThe human gut microbiota is a complex microbial community with critical functions for the host, including the transformation of various chemicals. While effects on microorganisms has been evaluated using single-species models, their functional effects within more complex microbial communities remain unclear. In this study, we investigated the response of a simplified human gut microbiota model (SIHUMIx) cultivated in an in vitro bioreactor system in combination with 96 deep-well plates after exposure to 90 different xenobiotics, comprising 54 plant protection products and 36 food additives and dyes, at environmentally relevant concentrations. We employed metaproteomics and metabolomics to evaluate changes in bacterial abundances, the production of Short Chain Fatty Acids (SCFAs), and the regulation of metabolic pathways.Our findings unveiled significant changes induced by 23 out of 54 plant protection products and 28 out of 36 food additives across all three categories assessed. Notable highlights include azoxystrobin, fluroxypyr, and ethoxyquin causing a substantial reduction (log2FC <-0.5) in the concentrations of the primary SCFAs: acetate, butyrate, and propionate. Several food additives had significant effects on the relative abundances of bacterial species; for example, acid orange 7 and saccharin led to a 75% decrease inClostridium butyricum, with saccharin causing an additional 2.5-fold increase inE. colicompared to the control. Furthermore, both groups exhibited up- and down-regulation of various pathways, including those related to the metabolism of amino acids such as histidine, valine, leucine, and isoleucine, as well as bacterial secretion systems and energy pathways like starch, sucrose, butanoate, and pyruvate metabolism.This research introduces an efficient in vitro technique that enables high-throughput screening of the structure and function of a simplified and well-defined human gut microbiota model against 90 chemicals using metaproteomics and metabolomics. We believe this approach will be instrumental in characterizing chemical-microbiota interactions especially important for regulatory chemical risk assessments.
Cdc13 exhibits dynamic DNA strand exchange in the presence of telomeric DNA
Authors: Nickens David G. , Feng Zhitong , Shen Jiangchuan , Gray Spencer J. , Simmons Robert H. , Niu Hengyao , Bochman Matthew L. 
Published: December 2023

ABSTRACTTelomerase is the enzyme that lengthens telomeres and is tightly regulated by a variety of means to maintain genome integrity. Several DNA helicases function at telomeres, and we previously found that theSaccharomyces cerevisiaehelicases Hrq1 and Pif1 directly regulate telomerase. To extend these findings, we are investigating the interplay between helicases, single-stranded DNA (ssDNA) binding proteins (ssBPs), and telomerase. The yeast ssBPs Cdc13 and RPA differentially affect Hrq1 and Pif1 helicase activity, and experiments to measure helicase disruption of Cdc13/ssDNA complexes instead revealed that Cdc13 can exchange between substrates. Although other ssBPs display dynamic binding, this was unexpected with Cdc13 due to the reportedin vitrostability of the Cdc13/telomeric ssDNA complex. We found that the DNA exchange by Cdc13 occurs rapidly at physiological temperatures, requires telomeric repeat sequence DNA, and is affected by ssDNA length. Cdc13 truncations revealed that the low-affinity binding site (OB1), which is distal from the high-affinity binding site (OB3), is required for this intermolecular dynamic DNA exchange (DDE). We hypothesize that DDE by Cdc13 is the basis for how Cdc13 “moves” at telomeres to alternate between modes where it regulates telomerase activity and assists in telomere replication.
Un1Cas12f1 and Cas9 gene drive in HSV1: viruses that ‘infect’ viruses
Authors: Yao Qiaorui , Lin Zhuangjie , Lai Keyuan , Zeng Xianying , Lei Guangxiong , Zhang Tongwen , Dai Hongsheng 
Published: December 2023

AbstractCas9-based synthetic gene drives have been used for pest control, however, they face high resistance rates, and mitigation strategies developed thus far are difficult to implement. Here, we engineered herpes simplex virus type 1 (HSV1) as a vector for gene drive, generated viruses harboring either the Cas9 or Un1Cas12f1 gene drive, and evaluated these viruses for spreading gene drive and causing resistance. HSV1 supported fast and effective transmission of gene drives, and the Un1Cas12f1 gene drives yielded greater conversion and lower resistance than did the Cas9 gene drives. This positions the Un1Cas12f1 gene drive as a promising alternative, and HSV1 emerges as a dependable and swift platform for gene drive assessment. The gene drive viruses function like pathogens that specifically infect viruses, offering potential applications in attenuating viral infections.
Membrane fusion activity of herpes simplex virus 1 glycoproteins from a hyperfusogenic virus
Authors: Gianopulos Katrina A. , Makio Albina O. , Pritchard Suzanne M. , Cunha Cristina W. , Hull McKenna A. , Nicola Anthony V. 
Published: December 2023

AbstractHerpes simplex virus 1 (HSV-1) causes significant morbidity and death in humans worldwide. Herpes simplex virus 1 has a complex fusion mechanism that is incompletely understood. The HSV-1 strain ANG has notable fusion and entry activities that distinguish it from wild type. HSV-1 ANG virions fused with the Vero cell surface at 4°C and also entered cells more efficiently at 15°C relative to wild type virions, consistent with a hyperfusogenic phenotype. Understanding the molecular basis for the unique entry and fusion activities of HSV-1 strain ANG will help decipher the HSV fusion reaction and entry process. Sequencing of HSV-1 ANG genes revealed multiple changes in gB, gC, gD, gH, and gL proteins relative to wild type HSV-1 strains. The ANG UL45 gene sequence, which codes for a non-essential envelope protein, was identical to wild type. HSV-1 ANG gB, gD, and gH/gL were necessary and sufficient to mediate cell-cell fusion in a virus-free reporter assay. ANG gB, when expressed with wild type gD and gH/gL, increased membrane fusion, suggesting that ANG gB has hyperfusogenic cell-cell fusion activity. Replacing the wild type gD, gH, or gL with the corresponding ANG alleles did not enhance cell-cell fusion. Wild type gC is proposed to facilitate fusion and entry into epithelial cells by optimizing conformational changes in the fusion protein gB. ANG gC substitution or addition also had no effect on cell-cell fusion. The novel mutations in the ANG fusion and entry glycoproteins provide a platform for dissecting the cascade of interactions that culminate in HSV fusion and entry.
A genome-wide association study suggests new susceptibility loci for primary antiphospholipid syndrome
Authors: Casares-Marfil Desiré , Martínez-Bueno Manuel , Borghi Maria Orietta , Pons-Estel Guillermo ,   PRECISESADS Clinical Consortium, Reales Guillermo , Zuo Yu , Espinosa Gerard , Radstake Timothy , van den Hoogen Lucas L. , Wallace Chris , Guthridge Joel , James Judith A , Cervera Ricard , Meroni Pier Luigi , Martin Javier , Knight Jason S. , Alarcón-Riquelme Marta E. , Sawalha Amr H. 
Published: December 2023

ABSTRACTObjectivesPrimary antiphospholipid syndrome (PAPS) is a rare autoimmune disease characterized by the presence of antiphospholipid antibodies and the occurrence of thrombotic events and pregnancy complications. Our study aimed to identify novel genetic susceptibility loci associated with PAPS.MethodsWe performed a genome-wide association study comprising 5,485 individuals (482 affected individuals) of European ancestry. Significant and suggestive independent variants from a meta-analysis of approximately 7 million variants were evaluated for functional and biological process enrichment. The genetic risk variability for PAPS in different populations was also assessed. Hierarchical clustering, Mahalanobis distance, and Dirichlet Process Mixtures with uncertainty clustering methods were used to assess genetic similarities between PAPS and other immune-mediated diseases.ResultsWe revealed genetic associations with PAPS in a regulatory locus within the HLA class II region nearHLA-DRAand inSTAT4with a genome-wide level of significance. 34 additional suggestive genetic susceptibility loci for PAPS were also identified. The disease risk allele in the HLA class II locus is associated with overexpression ofHLA-DRB6,HLA-DRB9,HLA-DPB2,HLA-DQA2andHLA-DQB2, and is independent of the association between PAPS andHLA-DRB1*1302. Functional analyses highlighted immune and nervous system related pathways in PAPS-associated loci. The comparison with other immune-mediated diseases revealed a close genetic relatedness to neuromyelitis optica, systemic sclerosis, and Sjögren’s syndrome, suggesting colocalized causal variations close toSTAT4,TNPO3, andBLK.ConclusionsThis study represents a comprehensive large-scale genetic analysis for PAPS and provides new insights into the genetic basis and pathophysiology of this rare disease.
Organizational digital transformation: from evolution to future trends
Authors: Omol Edwin Juma 
Published: December 2023

PurposeThis article explores the emergence of organizational digital transformation in the rapidly advancing technological era. It discusses the origins, driving forces, strategies, challenges and broader implications.Design/methodology/approachThe article employs a scoping review methodology that synthesizes knowledge from the existing literature, research, case studies and other relevant sources.FindingsThe findings underscore the pivotal role that organizational digital transformation plays in an era of relentless technological advancement. Leadership, organizational culture and technological enablers are identified as crucial drivers of innovation and competitiveness within organizations. The article also emphasizes ethics as a crucial element of digital transformation, focusing in particular on concerns about data privacy and the morality of artificial intelligence. Additionally, the author talks about anticipated future trends that are anticipated to influence the future of digital transformation, such as the growing influence of artificial intelligence, the trend toward hyper-personalization and the emergence of quantum computing.Research limitations/implicationsThe assessment has failed to provide recommendations for the actual implementation because it has mainly concentrated on conceptual and strategic aspects. Furthermore, it does not clearly define the criteria for choosing real-world examples, which limits the representation of the different industries, size ranges of organizations and outcomes associated with digital transformation.Practical implicationsThe article stresses the significance of paying attention to the forces driving digital transformation while navigating ethical and societal concerns. In addition to highlighting the importance of anticipating future trends for strategic planning in the rapidly changing digital landscape, it emphasizes the advantages as incentives for organizations to invest in digital initiatives.Social implicationsThe investigation demonstrates how technology contributes to progress while posing complex ethical and change management issues. In light of increased connectivity, data analytics and artificial intelligence, it highlights the crucial need for societal adaptability and highlights the crucial role that cooperative human–machine coexistence plays in responsible development and transformative societal evolution.Originality/valueThe article stands out because it examines organizational digital transformation in-depth while considering its historical roots, ethical implications and future prospects. It is a priceless contribution to the field because real-world case studies and a scoping review provide a distinctive viewpoint and a comprehensive view of the effects of digital transformation on organizations and society.
Gattani Industries: growth strategy for India
Authors: Mehdi Mokhalles Mohammad , Nafees Lubna , Sarma Tridib Ranjan , Sultana Farnaz 
Published: December 2023

Learning outcomes
After completion of the case study, students will be able to understand general and specific challenges associated with carrying on a family business that faces market challenges including stiff competition from existing and newer players, understand the plywood manufacturing process and its supply chain management, understand the businesses operating in an organized versus the unorganized market, comprehend the marketing strategies adopted and identify a reasonable solution to address the challenges associated with the operations of a business.

Case overview/synopsis
This case study focuses on Gattani Industries (a plywood manufacturing company) located in the northeastern region of the Indian state of Assam. Headquartered at Cinnamara industrial zone of Jorhat district, Assam, the company began its operation in 1992 under the leadership of Makhan Gattani (Director). Gattani Industries catered to both residential and commercial demand. Its clients included the departments of central and state governments in India, public sector undertakings and civil contractors. The company had a wider distribution network across the country and adopted the one- and two-level marketing channels to reach consumers. It aimed to sell its products through dealers across the cities in India. However, in December 2019, Gattani faced the challenge of developing a growth strategy to overcome competition and use the upcoming market opportunities for business growth in the diverse and complex environment that existed in the country.

Complexity academic level
This case study is designed for use in graduate or undergraduate programs. This case study can be used in strategy, supply chain and marketing courses at Bachelor of Business Administration and Master of Business Administration levels.

Supplementary material
Teaching notes are available for educators only.

Subject code
CSS11: Strategy.
Transitioning beyond single-use plastic drinks cups: an emergent social marketing case study in Scotland
Authors: Carrigan Marylyn , Wells Victoria , Mackay Kerry 
Published: December 2023

Purpose
This study aims to investigate whether consumers and small businesses can transition from disposable to reusable coffee cups, using a community social marketing intervention, led by a Social Purpose Organisation.

Design/methodology/approach
An emergent case study approach using multiple sources of data developed an in-depth, multifaceted, real-world context evaluation of the intervention. The methodology draws on citizen science “messy” data collection involving multiple, fragmented sources.

Findings
Moving from single-use cups to reusables requires collective commitment by retailers, consumers and policymakers, despite the many incentives and penalties applied to incentivise behaviour change. Difficult post-COVID economics, austerity and infrastructure gaps are undermining both reusable acceptance and interim solutions to our dependence upon disposables.

Research limitations/implications
Although the non-traditional methodology rendered gaps and omissions in the data, the citizen science was democratising and inclusive for the community.

Practical implications
Our practical contribution evaluates a whole community intervention setting to encourage reusable cups, integrating multiple stakeholders, in a non-controllable, non-experimental environment in contrast to previous research. This paper demonstrates how small community grants can foster impactful collaborative partnerships between an SPO and researchers, facilitate knowledge-exchange beyond the initial remit and provide a catalyst for possible future impact and outcomes.

Originality/value
To assess the impact at both the outcome and the process level of the intervention, we use Pawson and Tilley’s realist evaluation theory – the Context Mechanism Outcome framework. The methodological contribution demonstrates the process of citizen science “messy” data collection, likely to feature more frequently in future social science research addressing climate change and sustainability challenges.