bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of obesity on the acute response to SARS-CoV-2 infection and development of post-acute sequelae of COVID-19 (PASC) in nonhuman primates
Authors: Sauter Kristin A. , Webb Gabriela M. , Bader Lindsay , Kreklywich Craig N. , Takahashi Diana L. , Zaro Cicely , McGuire Casey M. , Lewis Anne D. , Colgin Lois M. A. , Kirigiti Melissa A. , Blomenkamp Hannah , Pessoa Cleiton , Humkey Matthew , Hulahan Jesse , Sleeman Madeleine , Zweig Robert C. , Thomas Sarah , Thomas Archana , Gao Lina , Hirsch Alec. J. , Levy Mayaan , Cherry Sara R. , Kahn Steven E. , Slifka Mark K. , Streblow Daniel N. , Sacha Jonah B. , Kievit Paul , Roberts Charles T. 
Published: February 2025

AbstractLong-term adverse consequences of SARS-CoV-2 infection, termed “long COVID” or post-acute sequelae of COVID (PASC), are a major component of overall COVID-19 disease burden. Prior obesity and metabolic disease increase the severity of acute disease, but SARS-CoV-2 infection also contributes to the development of new-onset metabolic disease. Since the COVID pandemic occurred in the context of the global obesity epidemic, an important question is the extent to which pre-existing obesity modifies long-term responses to SARS-CoV-2 infection. We utilized a nonhuman primate model to compare the effects of infection with the SARS-CoV-2 delta variant in lean and obese/insulin-resistant adult male rhesus macaques over a 6-month time course. While some longitudinal responses to SARS-CoV-2 infection, including overall viral dynamics, SARS-CoV-2-specific IgG induction, cytokine profiles, and tissue persistence of viral RNA, did not appreciably differ between lean and obese animals, other responses, including neutralizing Ab dynamics, lung pathology, body weight, degree of insulin sensitivity, adipocytokine profiles, body temperature, and nighttime activity levels were significantly different in lean versus obese animals. Furthermore, several parameters in lean animals were altered following SARS-CoV-2 infection to resemble those in obese animals. Notably, persistent changes in multiple parameters were present in most animals, suggesting that PASC may be more prevalent than estimated from self-reported symptoms in human studies.
Galleria mellonellamodel for studying Gram-positive bacterial implant biofilms
Authors: Mirza Kamran A. , Nietzsche Sandor , Tchatchiashvili Tinatini , Makarewicz Oliwia , Pletz Mathias W. , Thieme Lara 
Published: February 2025

AbstractImplant-associated biofilm infections, particularly those caused byStaphylococcus aureusandEnterococcus faecalis, present significant challenges in clinical settings, often necessitating surgical removal. This study investigates the potential of the invertebrate modelGalleria mellonellafor evaluating biofilm formation ofS. aureusandE. faecalisclinical isolates, the leading causes of implant-associated infections. Utilizing expanded polytetrafluoroethylene (ePTFE) sutures as a surrogate for cardiac implants, we employed two biofilm formation methodologies reflecting the two main routes of implant infections:in vivobiofilm development within larvae mimicking hematogenous spread and pre-formed biofilm transplantation mimicking contamination during surgery. Scanning electron microscopy revealed complex biofilm structures for the biofilm formed inside of the larvae on implant, closely mimicking clinical conditions. Antibiotic treatments with vancomycin and rifampicin demonstrated significant reductions in bacterial biofilms, proving highly effective. The study highlights theG. mellonellamodel’s potential for preclinical biofilm research, offering a cost-effective and ethical alternative to vertebrate models while providing valuable insights into biofilm-related infections and their treatment.
Membrane vesicles ofShewanella oneidensisMR-1 enhance denitrification growth in a species-specific manner
Authors: Takahashi Kohei , Takeda Riku , Savage Thomas Kouyou , Kataoka Masahito , Yamamoto Tatsuya , Okabe Satoshi , Nomura Nobuhiko , Oshiki Mamoru , Toyofuku Masanori , Tokunou Yoshihide 
Published: February 2025

AbstractDenitrification, a fundamental bacterial respiratory process that occurs in anoxic environments, plays a pivotal role in energy synthesis and the global nitrogen cycle. Although the significance of this process is well-recognized, its regulation within polymicrobial communities remains poorly understood, particularly concerning interspecies interactions. In this study, we investigated the role that bacterial membrane vesicles (MV) play in modulating denitrification across bacterial species. MV is known to carry specific biomolecules such as secondary metabolites, proteins, and nucleic acids, therefore considered to be a secretion pathway. We found that MV produced byShewanella oneidensisenhanced denitrification in a species-specific manner. Bacteria with highly hydrophobic surfaces tended to respond to denitrification enhancement, suggesting that the MV–bacteria attachment process is the key to generating species specificity. Transcriptome analysis and isotopic metabolite tracking indicated that the MV influenced denitrifying activities, rather than the transcription of denitrification-related genes. We further demonstrated thatc-type cytochromes in MV act as key components that enhance denitrification. These insights expand our understanding of bacterial ecology, highlighting the role of membrane vesicles in facilitating respiratory competition and cooperation in polymicrobial communities.
Cholesterol efflux protein, ABCA1, supports anti-cancer functions of myeloid immune cells
Authors: Bendre Shruti V. , Wang Yu , Hajyousif Basel , Rajendra K C , Bhogale Shounak G. , Pradeep Dhanya , Krawczynska Natalia , Schane Claire P. , Weisser Erin , Singh Avni , Han Simon , Kim Hannah , Kockaya Lara , Das Gupta Anasuya , Nelczyk Adam T. , Gamage Hashni Epa Vidana , Fei Yifan , Guo Xingyu , Deaton Ryan J. , Sverdlov Maria , Gann Peter H. , Sinha Saurabh , Wang Kun , Bortle Kevin Van , Tajkorshid Emad , Woodward Wendy A. , Cho Wonhwa , Nelson Erik R. 
Published: February 2025

ABSTRACTAlthough immune therapy has seen significant advances, the majority of breast and other solid tumors do not respond or quickly developde novoresistance. One factor driving resistance is highly immune suppressive myeloid cells (MCs) such as macrophages. Previous work has established clinical links between cholesterol and cancer outcome, and that MC function can be regulated through disruption in cholesterol metabolism. Thus, we screened for proteins that were expressed in MCs, involved in cholesterol homeostasis and whose expression was associated with survival; we identify the cholesterol efflux protein ABCA1. Preclinical studies revealed that ABCA1 activity resulted in increased anti-cancer functions of macrophages: enhanced tumor infiltration, decreased angiogenic potential, reduced efferocytosis, and improved support of CD8+ T cell activity. Mechanistically, different AKT isoforms are involved, through both PI3K dependent and independent mechanisms. Assessment of human blood and breast tumors revealed correlations between ABCA1 in macrophages and angiogenic potential,VEGFA, and CD8 T cell abundance and activity, highlighting the clinical relevance of our findings. The culmination of the effects of ABCA1 on MC function were demonstrated through increased tumor growth and metastasis in mice with MC specific knockout of ABCA1. Therefore, modulating ABCA1 activity within MCs may represent a novel approach to immune therapy.
Molecular interactome of HNRNPU reveals regulatory networks in neuronal differentiation and DNA methylation
Authors: Oksanen Marika , Mastropasqua Francesca , Mazan-Mamczarz Krystyna , Martindale Jennifer L. , Ye Xuan , Arora Abishek , Banskota Nirad , Gorospe Myriam , Tammimies Kristiina 
Published: February 2025

ABSTRACTHNRNPU is an RNA-binding protein with diverse roles in regulating gene expression. Pathogenic genetic variants of HNRNPU cause a severe neurodevelopmental disorder (NDD), but the underlying molecular mechanisms are unclear. Here, we investigated the protein-protein interaction (PPI) network and RNA targets of HNRNPU in neuroepithelial stem cells (NES) and differentiating neural cells derived from human induced pluripotent stem cells. Using high-throughput approaches, we found HNRNPU interacting with the mammalian SWI/SNF complex and highlight its putative role in multiple stages of mRNA regulation. Notably, both PPI partners and interacting mRNAs implicated HNRNPU in translation, a role that had not been recognized before. Also, we found that HNRNPU associated with mRNAs encoding proteins important for neuronal development. Based on our findings, we propose a regulatory model in which HNRNPU, in coordination with SWI/SNF, modulates the levels and accessibility of DNA methylation factors, leading to global methylation differences in HNRNPU deficiency states, as we validated in our cell model. This mechanism provides a molecular link to the distinct methylation signature seen in individuals with HNRNPU-related NDDs as well as to crucial epigenetic regulation during early brain development.
DdiA, an XRE family transcriptional regulator, regulates a LexA-independent DNA damage response inMyxococcus xanthus
Authors: Jung Jana , Glatter Timo , Herfurth Marco , Søgaard-Andersen Lotte 
Published: February 2025

AbstractRepair of DNA damage is essential for genome integrity. DNA damage elicits a DNA damage response (DDR) that includes error-free and error-prone, i.e. mutagenic, repair. The SOS response is a widely conserved system in bacteria that regulates the DDR and depends on the recombinase RecA and the transcriptional repressor LexA. However, RecA/LexA-independent DDRs have been identified in several bacterial species. Here, using a whole-cell, label-free quantitative proteomics approach, we map the proteomic response inMyxococcus xanthusto mitomycin C treatment and the lack of LexA. In doing so, we confirm a LexA-independent DDR inM. xanthus. Using a candidate approach, we identify DdiA, a transcriptional regulator of the XRE family, and demonstrate that it regulates a subset of the LexA-independent DDR genes.ddiAis expressed heterogeneously in a subpopulation of cells in the absence of exogenous genotoxic stress and reversibly induced population-wide in response to such stress. DdiA, indirectly or directly, activates the expression ofdnaE2, which encodes the DnaE2 error-prone DNA polymerase, and inhibits the expression ofrecX, which encodes RecX, a negative regulator of RecA. Accordingly, the ΔddiAmutant has a lower mutation frequency than the wild-type but also a fitness defect, suggesting that DdiA mediates a trade-off between fitness and mutagenesis. We speculate that the DdiA-dependent response is tailored to counter replication stress, thereby preventing the induction of the complete RecA/LexA-dependent DDR in the absence of exogenous genotoxic stress.ImportanceDNA damage repair is essential for genome integrity and depends on the DNA damage response (DDR). While the RecA/LexA-dependent SOS response is widely conserved in bacteria, there are also RecA/LexA-independent DDRs. Here, we identify the DNA damage-induced transcriptional regulator DdiA inMyxococcus xanthusand demonstrate that it regulates part of the RecA/LexA-independent DDR. DdiA activates the expression ofdnaE2, which encodes the DnaE2 error-prone DNA polymerase, and inhibits the expression ofrecX, which encodes RecX, a negative regulator of RecA. Because the ΔddiAmutant has a lower mutation frequency than the wild-type but also a fitness defect, we suggest that DdiA mediates a trade-off between fitness and mutagenesis and that the DdiA-dependent DDR is specifically tailored to counter replication stress.
Design, development, and evaluation of gene therapeutics specific to KSHV-associated diseases
Authors: Inagaki Tomoki , Espera Jonna , Wang Kang-Hsin , Komaki Somayeh , Nair Sonali , Davis Ryan R. , Kumar Ashish , Nakajima Ken-ichi , Izumiya Yoshihiro 
Published: February 2025

AbstractKaposi’s sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi’s sarcoma (KS) and two human lymphoproliferative diseases: primary effusion lymphoma and AIDS-related multicentric Castleman’s disease. KSHV-encoded latency-associated nuclear antigen (LANA) is expressed in KSHV-infected cancer cells and is responsible for maintaining viral genomes in infected cells. Thus, LANA is an attractive target for therapeutic intervention for KSHV-associated diseases.Here, we devised a cancer gene therapy vector using the adeno-associated virus (AAV), which capitalizes the LANA’s function to maintain terminal repeat (TR) containing circular genome in latently infected cells and the TR’s enhancer function for KSHV inducible gene promoters. By including two TR copies with a lytic inducible gene promoter (TR2-OriP), we prepared an AAV vector, which expresses an engineered thymidine kinase (TK) selectively in KSHV-infected cells. Ganciclovir (GCV), an anti-herpesvirus drug, effectively eradicated multiple KSHV-infected cells that include iPSC-derived epithelial colony-forming cells, but not non-KSHV-infected counterparts in the presence of AAV8-TR2-OriP-TK. In addition, AAV8-TR2-OriP-TK prevents KSHV virion production from reactivated cells, spreading KSHV infections from reactivated cells. Anti-cancer drugs, known to reactivate KSHV, stimulated TK expression from the vector and, therefore, synergized with AAV8 TR2-OriP-TK to induce KSHV-infected cancer cell death. Finally, the AAV8-TR2-OriP-TK with GCV completely diminished KSHV-infected cancer cells in the xenograft tumor model. The new cancer gene therapeutics should augment the current clinical protocol for KS.
Development of a Transcriptional Biosensor for Hydrogen Sulfide that Functions under Aerobic and Anaerobic Conditions
Authors: Fernez Matthew T. , Hegde Shanthi , Hayes Justin A. , Hoyt Kathryn O. , Carrier Rebecca L. , Woolston Benjamin M. 
Published: February 2025

AbstractHydrogen sulfide (H2S) is a gaseous gut metabolite with disputed effects on gastrointestinal health. Monitoring H2S concentration in the gut would provide insight into its role in disease, but is complicated by sulfide’s reactivity and volatility. Here we develop a transcriptional sulfide biosensor inE. coli. The sensor relies on enzymatic oxidation of sulfide catalyzed by a sulfide:quinone reductase (Sqr) to polysulfides, which bind to the repressor SqrR, triggering unbinding from the promoter and transcription of the reporter. Through promoter engineering and improving soluble SqrR expression, we optimized the system to provide an operational range of 50 µM - 750 µM and dynamic range of 18 aerobically. To enable sensing in anaerobic environments, we identified an Sqr fromWolinella succinogenesthat uses menaquinone, facilitating reoxidation through the anaerobic electron transport chain by fumarate or nitrate. Use of this homolog resulted in an anaerobic H2S response up to 750 µM. This sensor could ultimately enable spatially and temporally resolved measurements of H2S in the gastrointestinal tract to elucidate the role of this metabolite in disease, and potentially as a non-invasive diagnostic.
Role of social media dependency and online reputation in instituting stress among social media users
Authors: Karunarathne E.A.C.P. , Wijesundara W.M.T.H. , Athukorala A.S.T. , Chithrananda K.P.S.P. 
Published: February 2025

PurposeDespite the growing use of social media platforms, it’s important to acknowledge and understand the potential negative aspects associated with its usage. This paper aims to explore the impacts of social media stress development and understand the roles of self-esteem, social media dependency and online reputation.Design/methodology/approachA survey-based quantitative approach was followed for this study, targeting social media users over 18 years of age, and the data were gathered through an online questionnaire. Exploratory factor analysis (EFA) and structural equation modeling (SEM) were employed to evaluate the study model.FindingsStudy findings indicate that higher self-esteem reduces reliance on social media. Also, social media users’ concern about the digital image is caused by increasing social media dependency, which may lead to stress as individuals struggle to maintain a positive digital image on these platforms.Originality/valueThis study provides valuable insights into the negative aspects of social media use, emphasizing the need for strategies to mitigate the risks associated with excessive social media use and encourage the use of healthier digital habits to ensure user’s psychological well-being.
Integration of knowledge and technology in the co-production of AI-based solutions for the healthcare sector
Authors: Leszczyński Grzegorz , Zieliński Marek , Gaczek Piotr , Kociński Jędrzej 
Published: February 2025

PurposeThis article aims to explain how organizations create and integrate medical knowledge to develop AI-based medical solutions. The study resulted from a discussion on value co-production with digital technologies and the capabilities needed for it.Design/methodology/approachThe study explores the case of value co-production with the digitalization of traditional medical stethoscopes. It considers integrated resources to create AI-based medical solutions, actors engaged in co-production and activities related mainly to knowledge embodiment.FindingsThis article presents operand and operant resources integration when AI is implemented in innovative medical solutions. Furthermore, it shows which activities are undertaken for value co-production and what roles actors from various fields play in resource integration.Originality/valueOur article discusses the integration of knowledge and the role of knowledge embodiment among resource integration in value co-production when working on AI.
The late mover advantage: unveiling Bajaj Auto’s potential to lead in the two-wheeler EV space
Authors: Das Arindam , Ghosal Debraj 
Published: February 2025

Learning outcomes
On completion of the analysis of this case, students would be able to: analyze how external environmental factors impact the product market matrix; evaluate growth choices open to an incumbent business and how they create and capture value; and develop corporate strategies of a multi-business firm to respond to external dynamics.

Case overview/synopsis
The case presents an opportunity to examine the timing of entry of an incumbent firm in a new market segment. Bajaj Auto, a well-established Indian two-wheeler and three-wheeler manufacturer and exporter, chose to enter the electric vehicle space much later than technology start-ups and other incumbents. After three years, the company’s business in this segment might appear successful, but it is not in a position to dislodge the market leader, Ola Electric. The case focuses on the dilemma of market entry timing, positioning of a new product, managing an interlinked product portfolio, the need to develop a robust ecosystem of partners and dealing with unpredictable export markets.

Complexity academic level
The case can be discussed in a session of graduate-level business strategy/corporate strategy/international business course that deals with the growth strategies of an incumbent.

Supplementary material
Teaching notes are available for educators only.

Subject code
CSS 11: Strategy.
Making sustainable voices heard at the workplace
Authors: Nazeer Shakira , Naveed Shabana , Sair Shrafat Ali , Khan Kamran 
Published: February 2025

Purpose
This study aims to investigate employee motivation, enabling environmental factors and barriers to exercising green voice behavior (GVB) in Oil and Gas companies in Pakistan using the theoretical lens of the theory of planned behavior (TPB) and value–belief–norm (VBN) theory.

Design/methodology/approach
Thirty-five in-depth, semistructured interviews were conducted with middle-level employees of the three Oil and Gas exploration companies to explore the antecedents behind GVB of professionals.

Findings
Qualitative data show various antecedents of GVB (i.e. biospheric values, ecological worldview, awareness of adverse environmental consequences of irresponsible behavior, previous negative experiences with the environment, ascribed responsibility, personal norms, proenvironmental attitude, leaders’ related subjective norms, colleagues-related subjective norms, organizational-related subjective norms and perceived behavioral controls) and several contextual factors (employee’s previous eroded relationship with the management, inaction of management on green voice, organizational limited green capacity in terms of technical, financial or intellectual resources) as significant determinants to influence the exercise of GVB in the workplace. Out of the interviewees’ responses, a two-phase decision-making model has been developed showing the individual’s decision to engage in a proenvironmental voice.

Originality/value
This research integrates TPB and VBN theory to explain the GVB of industry professionals in Pakistan’s Oil and Gas sector. The study uniquely highlights how personal, organizational and environmental factors influence proenvironmental behavior.
Kyoto's Clean Development Mechanism for Emissions Reduction in Developing Economies
Authors: Fernando Lakmini , McWhinnie Stephanie 
Published: February 2025

ABSTRACTThis paper investigates the effectiveness of Kyoto's Clean Development Mechanism (CDM) on emissions reduction in developing countries. Whilst global responses are needed for global problems, global environmental policies are likely to have heterogeneous impacts. Understanding this heterogeneity allows for more nuanced policy evaluation and design. We use a quantile difference‐in‐differences approach to uncover where a significant early global mechanism for implementing climate policy, the CDM, does and does not have an impact. Evaluating a panel of 104 developing countries over the period 1996–2016, we find that the CDM had a strong impact only at lower quantiles of the distribution of greenhouse gas (GHG) emissions. In particular, countries in the 10th and 25th quantiles show a 9% reduction in emissions, whereas countries in the 90th quantile exhibit a 21% increase over the post‐policy period. Emissions intensity and emissions per capita also experience mixed results with strong reductions in the bottom half of the distribution but increases at the very top. Decomposition across GHG emissions types indicates mixed results across the distribution for each; with carbon dioxide results acting similarly to aggregate emissions but fluorinated gases reducing across the distribution. Heterogeneity of the policy effect is observed across regions, the CDM is associated with: reduced emissions in the Latin America and Caribbean region; weaker reductions in Asia–Pacific; and mixed results in Africa. Identification of heterogeneity across subgroups of countries can assist with effective policy design and implementation of future global environmental policies.