bluuebunny/crossref_metadata_2025_split huggingface dataset:
A putative hepatitis B virus sequence motif associated with hepatocellular carcinoma in South African adults
Authors: Maponga Tongai G , McNaughton Anna L , Campbell Cori , de Cesare Mariateresa , Mokaya Jolynne , Lumley Sheila F , Bonsall David , Ip Camilla LC , Chai Haiting , Van Rensburg Christo , Glashoff Richard H , Waddilove Elizabeth , Preiser Wolfgang , Blackard Jason T , Ansari M Azim , Kramvis Anna , Andersson Monique I , Matthews Philippa C 
Published: January 2024

ABSTRACTAimChronic hepatitis B virus (HBV) infection is a major risk factor for hepatocellular carcinoma (HCC) particularly in African populations, in whom malignancy frequently presents at an advanced stage with poor outcomes. We derived HBV whole genome sequences (WGS) from individuals with HCC and compared them to sequences from individuals without HCC.Methods:We identified adults with HBV infection, with and without complicating HCC, in Cape Town, South Africa and utilized pan-genotypic probe-based enrichment followed by Illumina sequencing to derive HBV WGS.ResultsCompared to the non-HCC group, HCC patients were more likely to be male (p < 0.0001), older (p = 0.01), HIV-negative (p = 0.006), and to have higher HBV viral loads (p < 0.0001). Among 19 HCC and 12 non-HCC patients, genotype A dominated (74%), of which 96% were subtype A1. PreS2 deletions (Δ38–55) were enriched in HBV sequences from HCC patients (n = 7). The sequence motif most strongly associated with HCC comprised either deletion or polymorphism at site T53 in PreS2 – collectively coined ‘non-T53’ – together with a basal core promoter (BCP) mutation G1764A (AUROC 0.79).ConclusionsIn this setting, HBV sequence polymorphisms and deletions are associated with HCC, and ‘non-T53 + G1764A’ represents a putative signature motif for HCC. Additional investigations are needed to disaggregate the impact of age, sex and HIV status, to ascertain the extent to which viral polymorphisms contribute to oncogenesis, and to determine whether HBV sequence is a useful biomarker for risk stratification.
Enhancing marine resilience in temperate coastal systems requires the implementation of multiple management strategies
Authors: Sanabria-Fernandez Jose A. , Lazzari Natali 
Published: January 2024

AbstractResilience is a critical property in the current Anthropocene era responsible for keeping temperate coastal systems healthy and preventing their collapse. The cumulative effect of unsustainable practices, however, leads to pollution, physical impacts, or overfishing, which threaten the resilience of these coastal systems. This situation, coupled with a lack of studies on resilience in temperate coastal systems, hampers management toward building more resilient systems. To contribute to this knowledge gap, we assessed the resilience of temperate coastal systems in five marine ecoregions, taking into account three dimensions: biological, environmental, and anthropogenic. Our study identified sixteen top resilient areas to be conserved and thirteen bottom resilient areas with the potential for improved management of anthropogenic factors. In a simulated management scenario within bottom resilient areas, our findings demonstrate that although the management potential of anthropogenic factors varies significantly from 76% for anthropogenic pollution to 27.4% for proximity to the nearest city, the strict management of these factors can enhance resilience by up to 27.97%. Therefore, this research not only contributes to advancing our understanding of resilience in temperate coastal areas but also provides valuable insights into the strategic management of temperate coastal systems, offering a promising pathway towards their sustainability.
ArborSim: Articulated, branching, OpenSim routing for constructing models of multi-jointed appendages with complex muscle-tendon architecture
Authors: Fu Xun , Withers Jack , Miyamae Juri A. , Moore Talia Y. 
Published: January 2024

AbstractComputational models of musculoskeletal systems are essential tools for understanding how muscles, tendons, bones, and actuation signals generate motion. In particular, the OpenSim family of models has facilitated a wide range of studies on diverse human motions, clinical studies of gait, and even non-human locomotion. However, biological structures with many joints, such as fingers, necks, tails, and spines, have been a longstanding challenge to the OpenSim modeling community, especially because these structures comprise numerous bones and are frequently actuated by extrinsic muscles that span multiple joints—often more than three—and act through a complex network of branching tendons. Existing model building software, typically optimized for limb structures, makes it difficult to build OpenSim models that accurately reflect these intricacies. Here, we introduceArborSim, customized software that efficiently creates musculoskeletal models of highly jointed structures and can build branched muscle-tendon architectures. We usedArborSimto construct toy models of articulated structures to determine which morphological features make a structure most sensitive to branching. By comparing the joint kinematics of models constructed with branched and parallel muscle-tendon units, we found that the number of tendon branches and the number of joints between branches are most sensitive to branching modeling method—notably, the differences between these models showed no predictable pattern with increased complexity. As the proportion of muscle increased, the kinematic differences between branched and parallel models units also increased. Our findings suggest that stress and strain interactions between distal tendon branches and proximal tendon and muscle greatly affect the overall kinematics of a musculoskeletal system. By incorporating complex muscle-tendon branching into OpenSim models usingArborSim, we can gain deeper insight into the interactions between the axial and appendicular skeleton, model the evolution and function of diverse animal tails, and understand the mechanics of more complex motions and tasks.
Examining the relationships between psychological distress and financial hardship and uncertainty during the COVID-19 pandemic and the subsequent cost-of-living crisis in the United Kingdom
Authors: Wels Jacques , Hamarat Natasia 
Published: January 2024

AbstractBackgroundThe study tests whether financial hardship and uncertainty have increased during the COVID-19 pandemic and the early stage of the subsequent cost-of-living crisis and whether these might explain increased psychological distress among the UK population.MethodsWe derive two cohorts from Understanding Society, a study representative of the UK population. Cohort 1 (C1) starts in 2016 and includes a 3-year follow-up until 2019. Cohort 2 (C2) starts in 2019 and ends in 2022. We provide descriptive statistics on financial hardship and uncertainty and apply parallel Latent Growth Modelling (LGM) on each cohort to explain variations in psychological distress (GHQ-36) based on baseline and follow-up financial trajectories. The sample is adjusted using cross-sectional weights and inverse probability weights for attrition.ResultsFinancial hardship rates do not differ across cohorts but a marginal increase of 10 percent in financial uncertainty is observed in 2022 for C2. No significant difference in associations is observed across cohorts in the LGM with constant financial hardship increasing the GHQ-36 slope by 0.89 (95%CI=0.76;1.02) and 0.89 (95%CI=0.73;1.05) units in C1 and C2 and constant financial uncertainty increasing it respectively by 0.95 (95%CI=0.74;1.17) and 1.04 (95%CI=0.82;1.25). Baseline hardship and uncertainty increase the intercept by 2.39 (95%CI=2.11;2.67) and 1.74 (195%CI=1.38;2.10) in C1 and 2.97 (95%CI=2.65;3.29) and 2.12 (95%CI=1.75;2.49) in C2.DiscussionThe uncertainty caused by the 2022 cost-of-living crisis might have contributed to increase psychological distress within the UK population. Stronger detrimental effects might be expected if financial hardship were to increase.
Nasopharyngeal Carcinoma and Head and Neck Cancer in Patients with Type-2 Diabetes Mellitus receiving SGLT2I, DPP4I or GLP1a: A population-based cohort study
Authors: Li Lifang , Chou Oscar Hou In , Mak Kar Kei , Yang Yifan , Chung Cheuk To , Li Guoliang , Chan Catherine , Wong Wing Tak , Liu Tong , Cheung Bernard Man Yung , Tse Gary , Zhou Jiandong 
Published: January 2024

AbstractIntroductionNasopharyngeal carcinoma (NPC) remains endemic in Asian regions, which risk factors were distinct from other head and neck (H&N) cancers. Anti-diabetic drugs has been proposed to reduce the risk of NPC. The associations between sodium glucose cotransporter 2 inhibitors (SGLT2I) versus dipeptidyl peptidase-4 inhibitors (DPP4I) and the risks of NPC and H&N cancer amongst type-2 diabetes mellitus (T2DM) patients remains unknown.MethodThis was a retrospective population-based cohort study including T2DM patients treated with either SGLT2I or DPP4I between 1stJanuary 2015 and 31stDecember 2019 in Hong Kong. The primary outcome was new-onset NPC and other H&N cancer. The secondary outcome was cancer-related mortality. Propensity score matching (1:1 ratio) was performed using the nearest neighbour search. Multivariable Cox regression was applied to identify significant predictors.ResultsThis cohort included 75,884 patients with T2DM, amongst whom 28,778 patients were on SGLT2I and 47,106 patients were on DPP4I. After matching (57556 patients), 106 patients developed NPC (0.18%), and 50 patients developed H&N cancer (0.08%). Compared to DPP4I, SGLT2I was associated with significantly lower risks of NPC (Hazard ratio [HR]: 0.41; 95% Confidence interval [CI]: 0.21-0.81) but not H&N cancer (HR: 1.00; 95% CI: 0.26-3.92) after adjustments. The result remained significant regardless of demographics and obesity. The association remained consistent in different risk models, matching approaches, and the sensitivity analysis.ConclusionThis study provides real-world evidence that SGLT2I was associated with lower risks of NPC, but not H&N cancer compared to DPP4I after adjustments amongst T2DM patients.
IL6 mediated cFLIP downregulation increases the migratory and invasive potential of triple negative breast cancer cell
Authors: Sinha Samraj , Roy Rajdeep , Barman Nilesh , Sarkar Purandar , Saha Abhik , Biswas Nabendu 
Published: January 2024

Abstractc-FLIP (cellular FLICE-Like Inhibitor of Apoptotic protein) which belongs to the negative regulators of the death receptor pathway, control apoptosis in a number of cancers. literatures suggest that its overexpression facilitate cancer progression and also helps in the drug resistance. However, there is a very few data available to show how it control metastasis. Moreover, how cFLIP is regulated during the progression of cancer into advanced stage and its mechanism of action on tumor cell migration and invasion is yet to be known. Our TCGA data analysis has shown that cFLIP is downregulated in many cancers, including breast cancer, especially at the later stages. when, we analysed and compared early-stage breast carcinoma cell line MCF7 (luminal) and advanced stage triple negative cell line MDAMB-231, which is highly metastatic, we found a negative correlation between cFLIP expression and metastasis. Our results indicated that Il6, one of the most prominent cytokines inside tumor microenvironment, activated p38 and the later helped in cFLIP downregulation in MDA-MB-231 cell line. Moreover, we have found that cFLIP negatively regulated autophagy and this autophagy downregulation resulted in decrease in metastasis. Thus, we have shown, for the first time, a complete interconnecting pathway in which IL6 mediated p38 activation directly influences metastasis by regulating autophagy via cFLIP downregulation.
Methyl substitutedβ–lactam framework based antibiotics andβ-lactamase inhibitors: Proof of concept by computations
Authors: Thakkur Vaishali , Das Chandan Kumar , Verma Shivani , Saha Suman , Nair Nisanth N. 
Published: January 2024

AbstractIncreasing the life-time of the acyl-enzyme complex formed between an inhibitor or drug molecule and theβ-lactamase through chemical modifications of existing drug molecules is an important strategy towards developing inhibitors. In this direction, our group proposed a methyl-substitutedβ-lactam framework for the design of inhibitors forβ-lactamases (J. Phys. Chem. B.2018, 122, 4299). This unconventional design was guided by the transition state structure of the deacylation reaction of the acyl-enzyme complex. Here, we present a proof of principle study of this concept through detailed molecular simulations and free energy calculations. In particular, we improve the antimicrobial activity of the first-generation cephalosporin antibiotic, cephalothin, through C6-methylation. The proposed molecule, (6R,7R)-3-(acetyloxymethyl)-6-methyl-8-oxo-7-[(2-thiophen-2-ylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate) slows down the deacylation of the acyl-enzyme complex 109-fold with no apparent effect on its binding to class-Cβ-lactamase and formation of the acyl-enzyme intermediate. The design strategy presented in this work can be further extended to allβ–lactam antibiotics, like monobactams, carbapenems, cephalosporins, and penicillins.
A novel human pluripotent stem cell-based gene activation system identifies IGFBP2 as a mediator in the production of hematopoietic progenitors in vitro
Authors: Petazzi Paolo , Ventura Telma , Luongo Francesca Paola , McClafferty Heather , May Alisha , Taylor Helen Alice , Shipston Micheal J , Romanò Nicola , Forrester Lesley M. , Menéndez Pablo , Fidanza Antonella 
Published: January 2024

AbstractA major challenge in the stem cell biology field is the ability to produce fully functional cells from induced pluripotent stem cells (iPSCs) that are a valuable resource for cell therapy, drug screening and disease modelling. Here we developed a novel inducible CRISPR-mediated activation strategy (iCRISPRa) to drive the expression of multiple endogenous transcription factors important forin vitrocell fate and differentiation of iPSCs to haematopoietic progenitor cells. This work has identified a key role for IGFBP2 in the development of hematopoietic progenitors. We first identified nine candidate transcription factors that we predicted to be involved in blood cell emergence during development, then generated tagged gRNAs directed to the transcriptional start site of these transcription factors that could also be detected during scRNAseq. iCRISPRa activation of these endogenous transcription factors resulted in a significant expansion of arterial-fated endothelial cells expressing high levels of IGFBP2 and our analysis indicated that IGFBP2 is involved in the remodeling of metabolic activity duringin vitroendothelial to hematopoietic transition. As well as providing fundamental new insights into the mechanisms of haematopoietic cell fate and differentiation, the broader applicability of iCRISPRa provides a valuable tool for studying dynamic processes controlling developmental events and for recapitulating abnormal phenotypes characterised by ectopic activation of specific endogenous gene expression in a wide range of systems.
Transposon-mediated genic rearrangements underlie variation in small RNA pathways
Authors: Zhang Gaotian , Félix Marie-Anne , Andersen Erik C. 
Published: January 2024

AbstractTransposable elements (TEs) are parasitic DNA sequences that insert into the host genome and can cause alterations in host gene structure and expression. Host organisms cope with the often detrimental consequences caused by recent transposition and develop mechanisms that repress TE activities. In the nematodeCaenorhabditis elegans, a small interfering RNA (siRNA) pathway dependent on the helicase ERI-6/7 primarily silences long terminal repeat retrotransposons and recent genes of likely viral origin. By studying gene expression variation among wildC. elegansstrains, we discovered that structural variants and transposon remnants at theeri-6/7locus alter its expression incisand underlie atrans-acting expression quantitative trait locus affecting non-conserved genes and pseudogenes. Multiple insertions of thePolintonDNA transposon (also known asMavericks) reshuffled theeri-6/7locus in different configurations, separating theeri-6anderi-7exons and causing the inversion oferi-6as seen in the reference N2 genome. In the inverted configuration, gene function was previously shown to be repaired by unusualtrans-splicing mediated by direct repeats flanking the inversion. We show that these direct repeats originated from terminal inverted repeats specific toC. elegans Polintons. Thistrans-splicing event occurs infrequently compared tocis-splicing to novel downstream exons, thus affecting the production of ERI-6/7. DiversePolinton-induced structural variations display regulatory effects within the locus and on targets of ERI-6/7-dependent siRNA pathways. Our findings highlight the role of host-transposon interactions in driving rapid host genome diversification among natural populations and shed light on evolutionary novelty in genes and splicing mechanisms.
Allyship in the university setting: supporting women's success
Authors: Silver Elisabeth R. , Bilotta Isabel , Stewart Dillon , Argueta-Rivera Jazmin , Spitzmueller Christiane , Brown Hayley , King Eden , Hebl Mikki 
Published: January 2024

PurposeThe lack of progress toward equity in the U.S. is evident across many spheres of society, academia notwithstanding. Women academicians, in particular, face many barriers that prevent them from advancing–including a continued unsupportive climate, competing work and family demands, and interpersonal discrimination. This paper reflects on a collaborative research effort in the United States to enhance allyship for women in academia.Design/methodology/approachThe authors partnered with a major university to hold ally training for department chairs during a university-wide department chair meeting. The authors developed a methodology for creating and implementing training content using a focus-group-based training needs analysis and a diversity science grounded approach to allyship training. The authors followed this up with surveys to assess impact.FindingsParticipants indicated that they learned from the training, but participation in follow-up data collection was limited, hampering the ability to conduct rigorous quantitative analyses around intervention impact.Research limitations/implicationsAlthough the sample size may have been too limited to detect effects, the current study provides an approach that furthers the way in which researchers and practitioners can better assess the impact of allyship to women academicians.Practical implicationsPublished research on allies is very limited. The current research examines allies in the context of helping women in academia.Originality/valueDespite widespread recognition of the importance of first-line supervisors in support of diversity, limited intervention designs are available. The authors add to the extant literature on diversity interventions, while highlighting barriers to rigorous intervention evaluation.
Creating a positive behavior intention using an online learning platform technology: the mediating role of perceived online learning enjoyment
Authors: Azman Ong Mohd Hanafi , Ibrahim Nur Syafikah 
Published: January 2024

Purpose Since there is lack of studies in determine factors that affecting enjoyment sentiment when using online learning system, this study aims to explore the antecedents of perceived online learning enjoyment by using extended technology acceptance model (TAM) and its effect on behavioral intentions (BIN) among higher education institutions students.Design/methodology/approach The research framework was empirically evaluated using a cross-sectional research design and the data was collected from 715 undergraduate students from public higher education institutions in Malaysia using an online survey method. A structural equation modeling using partial least square method was used to examine the hypothesized model.Findings The results of partial least squares structural equation modeling indicated that the main predictive variables of TAM along with the extended variables were significantly influence the perceived online learning enjoyment. Meanwhile, the analysis also identified that perceived online learning enjoyment can significantly generate positive BIN for using online learning platforms as well as it also plays as a significant mediator role.Practical implications This study has significant implications for higher education institutions that wish to develop online learning environment for their students by providing answers to higher education institutions on how to successfully use the learning management system to assist students' learning performance from the aspect of online learning enjoyment sentiment.Originality/value This study is remarkable because it is the first attempt to explore the effect of these five predictors on students' learning enjoyment toward online learning platforms and subsequently on BIN to use this learning platforms, especially in the context of Malaysian higher education system. It is also unique in the way to extend the use of TAM predictive variables with others variables to produce more informative results about the study. Hence, this study also has a new contribution in the literature in the domain of digital learning.
Effects and optimization of bionic texture parameters on the tribological behavior of line contacts under starved lubrication conditions
Authors: Zhang Longchang , Chen Qi , Yin Yanguo , Song Hui , Tang Jun 
Published: January 2024

Purpose
Gears are prone to instantaneous failure when operating under extreme conditions, affecting the machinery’s service life. With numerous types of gear meshing and complex operating conditions, this study focuses on the gear–rack mechanism. This study aims to analyze the effects and optimization of biomimetic texture parameters on the line contact tribological behavior of gear–rack mechanisms under starvation lubrication conditions.

Design/methodology/approach
Inspired by the microstructure of shark skin surface, a diamond-shaped biomimetic texture was designed to improve the tribological performance of gear–rack mechanism under starved lubrication conditions. The line contact meshing process of gear–rack mechanisms under lubrication-deficient conditions was simulated by using a block-on-ring test. Using the response surface method, this paper analyzed the effects of bionic texture parameters (width, depth and spacing) on the tribological performance (friction coefficient and wear amount) of tested samples under line contact and starved lubrication conditions.

Findings
The experimental results show an optimal proportional relationship between the texture parameters, which made the tribological performance of the tested samples the best. The texture parameters were optimized by using the main objective function method, and the preferred combination of parameters was a width of 69 µm, depth of 24 µm and spacing of 1,162 µm.

Originality/value
The research results have practical guiding significance for designing line contact motion pairs surface texture and provide a theoretical basis for optimizing line contact motion pairs tribological performance under extreme working conditions.