bluuebunny/crossref_metadata_2025_split huggingface dataset:
Machine learning predictions improve identification of real-world cancer driver mutations
Authors: Tran Thinh N. , Fong Chris , Pichotta Karl , Luthra Anisha , Shen Ronglai , Chen Yuan , Waters Michele , Kim Susie , Berger Michael F , Riely Gregory , Ladanyi Marc , Chakravarty Debyani , Schultz Nikolaus , Jee Justin 
Published: April 2024

AbstractCharacterizing and validating which mutations influence development of cancer is challenging. Machine learning has delivered significant advances in protein structure prediction, but its utility for identifying cancer drivers is less explored. We evaluated multiple computational methods for identifying cancer driver alterations. For identifying known drivers, methods incorporating protein structure or functional genomic data outperformed methods trained only on evolutionary data. We further validated VUSs annotated as pathogenic by testing their association with overall survival in two cohorts of patients with non-small cell lung cancer (N=7,965 and 977). “Pathogenic” VUSs inKEAP1andSMARCA4identified by several methods were associated with worse survival, unlike “benign” VUSs. “Pathogenic” VUSs exhibited mutual exclusivity with known oncogenic alterations at the pathway level, further suggesting biological validity. Despite training primarily on germline, rather than somatic, mutation data, computational predictions contribute to a more comprehensive understanding of tumor genetics as validated by real-world data.
Assessing Heterogeneity in the N-Telopeptides of Type I Collagen by Mass Spectrometry
Authors: Darula Zsuzsanna , McCabe Maxwell C. , Barrett Alex , Schmitt Lauren R. , Maslanka Mark D. , Saviola Anthony J , Orgel Joseph , Burlingame Alma , Staab-Weijnitz Claudia A. , Stenmark Kurt , Weaver Valerie , Chalkley Robert J. , Hansen Kirk C. 
Published: April 2024

AbstractCollagen cross-links created by the lysyl oxidase and lysyl hydroxylase families of enzymes are a significant contributing factor to the biomechanical strength and rigidity of tissues, which in turn influence cell signaling and ultimately cell phenotype. In the clinic, the proteolytically liberated N-terminal cross-linked peptide of collagen I (NTX) is used as a biomarker of bone and connective tissue turnover, which is altered in several disease processes. Despite the clinical utility of these collagen breakdown products, the majority of the cross-linked peptide species have not been identified in proteomic datasets. Here we evaluate several parameters for the preparation and identification of these peptides from the collagen I-rich Achilles tendon. Our refined approach involving chemical digestion for protein solubilization coupled with mass spectrometry allows for the identification of the NTX cross-links in a range of modification states. Based on the specificity of the enzymatic cross-linking reaction we utilized follow-up variable modification searches to facilitate identification with a wider range of analytical workflows. We then applied a spectral library approach to identify differences in collagen cross-links in bovine pulmonary hypertension. The presented method offers unique opportunities to understand extracellular matrix remodeling events in development, aging, wound healing, and fibrotic disease that modulate collagen architecture through lysyl-hydroxylase and lysyl-oxidase enzymes.
Essential genes forHaemophilus parainfluenzaesurvival and biofilm growth
Authors: de Palma Thais H. , Powers Chris , McPartland Morgan J. , Welch Jessica Mark , Ramsey Matthew 
Published: April 2024

AbstractHaemophilus parainfluenzae(Hp) is a Gram-negative, pleomorphic rod, highly prevalent and abundant as a commensal in the human oral cavity, and an infrequent extraoral opportunistic pathogen.Hpoccupies multiple niches in the oral cavity, including the tongue dorsum, keratinized gingiva, and the supragingival plaque biofilm. As a member of the HACEK group,Hpis also known to cause infective endocarditis. Additionally, case reports have identifiedHpas the causative agent of meningitis, septic arthritis, chronic osteomyelitis, septicemia, and a variety of other infectious diseases. Little is known about howHpinteracts with its neighbors in the healthy biofilm nor about its mechanisms of pathogenesis as an extraoral opportunistic pathogen. To address these unknowns, we identified the essential genomes of twoHpstrains and the conditionally essential genes for their growth inin vitrobiofilms aerobically and anaerobically. Using transposon insertion sequencing (TnSeq) with a highly saturatedmarinertransposon library in two strains, the ATCC33392 type-strain (Hp392) and a commensal oral isolate EL1 (HpEL1), we show that the essential genome ofHp392 andHpEL1 is composed of 395 and 384 genes, respectively. The core essential genome, consisting of 341 essential genes conserved between both strains, was composed of genes associated with genetic information processing, carbohydrate, protein, and energy metabolism. We also identified conditionally essential genes for aerobic and anaerobic biofilm growth, which were associated with carbohydrate and energy metabolism in both strains ofHp. Additionally, RNAseq analysis determined that most genes upregulated during anaerobic growth are not essential forHp392 anaerobic biofilm survival. The completion of this library and analysis under these conditions gives us a foundational insight into the basic biology ofH. parainfluenzaein differing oxygen conditions, similar to itsin vivooral habitat. Further, the creation of this library presents a valuable tool for further investigation into conditionally essential genes for an organism that lives in close contact with many microbial species in the human oral habitat.
Axonal organelle buildup from loss of AP-4 complex function causes exacerbation of amyloid plaque pathology and gliosis in Alzheimer’s disease mouse model
Authors: Orlowski Alex , Karippaparambil Joseph , Paumier Jean-Michel , Ghanta Shraddha , Pallares Eduardo , Chandran Rumamol , Edmison Daisy , Tandukar Jamuna , Gao Ruixuan , Gowrishankar Swetha 
Published: April 2024

AbstractLysosomes and related precursor organelles robustly build up in swollen axons that surround amyloid plaques and disrupted axonal lysosome transport has been implicated in worsening Alzheimer’s pathology. Our prior studies have revealed that loss of Adaptor protein-4 (AP-4) complex function, linked primarily to Spastic Paraplegia (HSP), leads to a similar build of lysosomes in structures we term “AP-4 dystrophies”. Surprisingly, these AP-4 dystrophies were also characterized by enrichment of components of APP processing machinery, β-site cleaving enzyme 1 (BACE1) and Presenilin 2. Our studies examining whether the abnormal axonal lysosome build up resulting from AP-4 loss could lead to amyloidogenesis revealed that the loss of AP-4 complex function in an Alzheimer’s disease model resulted in a strong increase in size and abundance of amyloid plaques in the hippocampus and corpus callosum as well as increased microglial association with the plaques. Interestingly, we found a further increase in enrichment of the secretase, BACE1, in the axonal swellings of the plaques of Alzheimer model mice lacking AP-4 complex compared to those having normal AP-4 complex function, suggestive of increased amyloidogenic processing under this condition. Additionally, the exacerbation of plaque pathology was region-specific as it did not increase in the cortex. The burden of the AP-4 linked axonal dystrophies/AP-4 dystrophies was higher in the corpus callosum and hippocampus compared to the cortex, establishing the critical role of AP-4 -dependent axonal lysosome transport and maturation in regulating amyloidogenic amyloid precursor protein processing.Significance StatementA major pathological feature of Alzheimer’s disease is the accumulation of axonal lysosomes near sites of amyloid plaques. Lysosome accumulation is thought to contribute to amyloid production. In fact, a genetic perturbation that arrests lysosomes in axons exacerbates amyloid plaque pathology. The mechanisms that control axonal lysosome abundance as well the molecular composition of axonal endolysosomes that produce Abeta, however, are not fully understood. Axonal lysosome build-up is emerging as a common pathology in other neurodegenerative disorders such as Hereditary Spastic Paraplegia (HSP), but its relevance to amyloid production is unknown. We find that a model of HSP caused by loss of AP-4 adaptor complex lead to axonal lysosome buildup that differs in some of its content, but still contributes to amyloidogenesis. This demonstrates that different perturbations leading to changes in heterogeneous pool of axonal lysosomes can converge on a common pathology.
Two distinct integrin binding sites on MMP9 drive cancer invasion by mediating integrin membrane trafficking & stabilization
Authors: Dutta Sarbajeet , Sarkar Soumili , Tolani Simran , Hazari Asrafuddoza , Sen Shamik 
Published: April 2024

AbstractMatrix stiffening has been established to drive cancer progression through increased activity of matrix metalloproteases (MMPs) which degrade the matrix creating paths for migration. However, the non-proteolytic functions of MMPs in cancer invasion remain relatively less understood. Here we have probed the importance of proteolytic and non-proteolytic functions of MMP9, which exhibits robust stiffness dependent expression and secretion in highly invasive cancer cells. We show that while MMP9 sustains spreading and 2D migration non-proteolytically by stabilizing focal adhesions, MMP9 proteolytic activity is essential for 3D invasion. We then establish the function of two distinct integrin β1 (ITG β1) binding sites on MMP9, with the hemopexin domain mediating co-packaging and co-transport of ITG β1/MMP9 to the cell periphery, and the RGD domain stabilizing ITG β1 on the cell membrane prior to matrix degradation. Together, our results illustrate how MMP9 optimizes cancer invasion by spatiotemporally integrating matrix remodeling with adhesion formation.
Fluctuation theorem on a Riemannian manifold
Authors: Cai Yifan , Wang Tao , Zhao Liu 
Published: April 2024

Based on the covariant underdamped and overdamped Langevin equations with Stratonovich coupling to multiplicative noises and the associated Fokker-Planck equations on a Riemannian manifold, we present the first law of stochastic thermodynamics on the trajectory level. The corresponding fluctuation theorems are also established, with the total entropy production of the Brownian particle and the heat reservoir playing the role of dissipation function.

Published by the American Physical Society
2024
The effect of organizational culture on territorial exclusivity in international marketing channels: a study of Japanese manufacturing exporters
Authors: Ishii Ryuta 
Published: April 2024

PurposeIt is important for an exporting manufacturer to motivate its foreign channel partners to sell and promote its products. An excellent way to motivate such foreign channel partners is to give them exclusive territories. Unfortunately, there is a lack of knowledge regarding the determinants of territorial exclusivity. This study aims to investigate the relationship between organizational culture and territorial exclusivity and the moderating role of firm size in this relationship.Design/methodology/approachSurvey data were collected from manufacturing small and medium-sized enterprises (SMEs) in Japan. To test the hypotheses, a regression analysis was conducted using the ordinary least squares technique.FindingsEmpirical evidence shows that the cultural values of collectivism and uncertainty avoidance influence territorial exclusivity; collectivist exporters are likely to use territorial exclusivity, whereas exporters with high uncertainty avoidance are not likely to use it. Furthermore, the larger the firm size, the smaller the impact of cultural values on territorial exclusivity; this suggests that large SMEs do not rely on their organizational culture to make decisions about exclusive territories.Originality/valueThe export marketing literature emphasizes the advantages of exclusive territories. By contrast, the channel management literature suggests that exclusive territories also have disadvantages. As exclusive territories have both advantages and disadvantages, it is crucial to answer the following question: What kinds of exporting manufacturers grant exclusive territories to their foreign channel partners? By addressing this question, this study contributes to a better understanding of export channel strategy.
Exploring the impact of green supply chain strategies and sustainable practices on circular supply chains
Authors: Singh Rohit Kumar 
Published: April 2024

Purpose The study attempts to explore the effectiveness of green supply chain strategies (GSCS) and sustainable practices (SP) in achieving a circular supply chain (CSC) within a business-to-business (B2B) context. The study further investigates the moderating role of green innovation (GIN) on the relationship between GSCS and SP.Design/methodology/approach The conceptual model was developed by adopting constructs from the existing studies. A self-administered tool was created, and data were gathered from supply chain (SC) specialists in the food, energy, tire, textile and paper industries. The structural equation model was employed to test the hypothesis, analyzing 243 responses obtained.Findings The findings indicate an affirmative association between GSCS, SP and the achievement of CSC, with SP acting as a partial mediator between GSCS and CSC. Results show that GSCS and SP are crucial for transitioning toward a circular model in the SC, emphasizing resource regeneration and sustainability. The data from our sample suggest that GIN significantly moderates the relationship between GSCS and CSC. These insights underline the importance of green strategies and sustainable practices (SP) in fostering CSCs in a B2B setting. The study’s implications are significant for SC management, suggesting that firms must integrate green and SP to achieve circularity and long-term viability.Originality/value This article brings forward a distinctive perspective on sustainability within the field of SC management emphasizing the crucial need for implementing CSC and GSCS in a B2B context.
Institutionalization and framing of Industry 4.0: a framework for understanding stakeholders and comparing countries
Authors: Fogaça Diego Rorato , Grijalvo Mercedes , Oliveros Iglesias Alberto , Sacomano Neto Mario 
Published: April 2024

Purpose
This paper aims to propose and assess a framework to analyse the institutionalization of Industry 4.0 (I4.0) through a framing analysis.

Design/methodology/approach
The framework was developed by combining the institutional approach with orders of worth, drawing insights from a comprehensive literature review. To assess it, the authors conducted a qualitative analysis of annual reports from companies with the largest market capitalization over a six-year period and interviewed union representatives in Spain and Sweden.

Findings
The framework comprises five dimensions (industrial, market, civic, green and connectionist). The empirical results reveal that companies consistently frame I4.0 with an emphasis on industrial and market perspectives. In contrast, unions place a stronger emphasis on civic issues, with Spanish unions holding a more negative view of I4.0, expressing concerns about working conditions and unemployment.

Research limitations/implications
The proposed framework brings interesting insights into the dispute over the meaning of I4.0. Although this empirical study was limited to companies and unions in Sweden and Spain, the framework can be expanded for broader investigations, involving additional stakeholders in one or more countries. The discussion outlined using the varieties of capitalism approach is relevant for understanding the connection between the meso and macro levels of this phenomenon.

Practical implications
In navigating the landscape of I4.0, managers should remain flexible, and ready to tailor their strategies and operations to align with the distinct demands and expectations of stakeholders and their specific institutional environments. Similarly, policymakers are urged to acknowledge these contextual intricacies when crafting strategies for implementing I4.0 initiatives across national settings.

Social implications
Based on the empirical findings, this study underscores the importance of fostering social dialogue and involving stakeholders in the implementation of I4.0. Policymakers and other stakeholders should take proactive measures, tailored to each country’s context, to mitigate potential adverse effects on labour and workers.

Originality/value
The study presents a novel framework that facilitates the systematic comparison of I4.0 framing by different actors. This contribution is significant because the way actors frame I4.0 affects its interpretation and implementation. Additionally, the aggregate analysis of results enables cross-country comparisons, enhancing our understanding of regional disparities.
A topology optimization of on-chip planar inductor based on evolutional on/off method and CMA-ES
Authors: Sato Takahiro , Watanabe Kota 
Published: April 2024

Purpose
There are few reports that evolutional topology optimization methods are applied to the conductor geometry design problems. This paper aims to propose an evolutional topology optimization method is applied to the conductor design problems of an on-chip inductor model.

Design/methodology/approach
This paper presents a topology optimization method for conductor shape designs. This method is based on the normalized Gaussian network-based evolutional on/off topology optimization method and the covariance matrix adaptation evolution strategy. As a target device, an on-chip planer inductor is used, and single- and multi-objective optimization problems are defined. These optimization problems are solved by the proposed method.

Findings
Through the single- and multi-objective optimizations of the on-chip inductor, it is shown that the conductor shapes of the inductor can be optimized based on the proposed methods.

Originality/value
The proposed topology optimization method is applicable to the conductor design problems in that the connectivity of the shapes is strongly required.
Shining a light on the unseen athletes: stories of exclusion and resistance among gay athletes in professional team sports
Authors: Voth Chris , Yi Kyoung June 
Published: April 2024

PurposeThis study uncovers the challenges and coping mechanisms related to stigma and discrimination experienced by gay professional team sport athletes.Design/methodology/approachUtilizing interpretive phenomenological analysis, this study recruited six gay athletes in professional team sports. Data were collected through virtual one-on-one semi-structured interviews, along with field notes and reflexive journaling, and were thematically analyzed.FindingsThe first theme highlights the discrimination and marginalization experienced by gay athletes in professional team sports, as well as the perceived differences between these athletes and their heterosexual counterparts. The second theme includes anecdotes illustrating their experiences of exclusion, along with counter-stories that resist marginalization. The last theme comprises stories that underscore the lack of acceptance and advocacy, emphasizing the awareness education aimed at making the sporting realm more inclusive.Research limitations/implicationsDespite the extensive recruiting efforts for this study, numerous sports and countries remain unexplored. Follow-up studies are required to fill this gap. As this study was initiated, additional research is needed to provide information on athletes who are still in the closet. Cross-comparisons between gay athletes and their heterosexual teammates can help bridge the gap in perspectives.Practical implicationsParticipants emphasized collective efforts in creating inclusive and welcoming environments for gay athletes, including anti-discrimination policies related to language use, showers and relocation adjustments.Social implicationsParticipants have put forth concrete recommendations for enhancing inclusivity within team sport environments and society at large, including proposals for early educational initiatives within the school systems.Originality/valueThis is the first empirical study that focuses on the experiences of gay professional team sport athletes.
Constraint-based analysis of heat transport and irreversibility in magnetic nanofluidic thermal systems
Authors: Manna Nirmal K. , Saha Abhinav , Biswas Nirmalendu , Ghosh Koushik 
Published: April 2024

Purpose
This paper aims to investigate the thermal performance of equivalent square and circular thermal systems and compare the heat transport and irreversibility of magnetohydrodynamic (MHD) nanofluid flow within these systems.

Design/methodology/approach
The research uses a constraint-based approach to analyze the impact of geometric shapes on heat transfer and irreversibility. Two equivalent systems, a square cavity and a circular cavity, are examined, considering identical heating/cooling lengths and fluid flow volume. The analysis includes parameters such as magnetic field strength, nanoparticle concentration and accompanying irreversibility.

Findings
This study reveals that circular geometry outperforms square geometry in terms of heat flow, fluid flow and heat transfer. The equivalent circular thermal system is more efficient, with heat transfer enhancements of approximately 17.7%. The corresponding irreversibility production rate is also higher, which is up to 17.6%. The total irreversibility production increases with Ra and decreases with a rise in Ha. However, the effect of magnetic field orientation (γ) on total EG is minor.

Research limitations/implications
Further research can explore additional geometric shapes, orientations and boundary conditions to expand the understanding of thermal performance in different configurations. Experimental validation can also complement the numerical analysis presented in this study.

Originality/value
This research introduces a constraint-based approach for evaluating heat transport and irreversibility in MHD nanofluid flow within square and circular thermal systems. The comparison of equivalent geometries and the consideration of constraint-based analysis contribute to the originality and value of this work. The findings provide insights for designing optimal thermal systems and advancing MHD nanofluid flow control mechanisms, offering potential for improved efficiency in various applications.

Graphical Abstract