bluuebunny/crossref_metadata_2025_split huggingface dataset:
PTEN knockout using retrogradely transported AAVs restores locomotor abilities in both acute and chronic spinal cord injury
Authors: Stewart Andrew N. , Kumari Reena , Bailey William M. , Glaser Ethan P. , Hammers Gabrielle V. , Wireman Olivia H. , Gensel John C. 
Published: April 2023

AbstractRestoring function in chronic stages of spinal cord injury (SCI) has often been met with failure or reduced efficacy when regenerative strategies are delayed past the acute or sub-acute stages of injury. Restoring function in the chronically injured spinal cord remains a critical challenge. We found that a single injection of retrogradely transported adeno-associated viruses (AAVrg) to knockout the phosphatase and tensin homolog protein (PTEN) in chronic SCI can effectively target both damaged and spared axons and restore locomotor functions in near-complete injury models. AAVrg’s were injected to deliver cre recombinase and/or a red fluorescent protein (RFP) under the human Synapsin 1 promoter (hSyn1) into the spinal cords of C57BL/6 PTENFloxΔ/Δmice to knockout PTEN (PTEN-KO) in a severe thoracic SCI crush model at both acute and chronic time points. PTEN-KO improved locomotor abilities in both acute and chronic SCI conditions over a 9-week period. Regardless of whether treatment was initiated at the time of injury (acute), or three months after SCI (chronic), mice with limited hindlimb joint movement gained hindlimb weight support after treatment. Interestingly, functional improvements were not sustained beyond 9 weeks coincident with a loss of RFP reporter-gene expression and a near-complete loss of treatment-associated functional recovery by 6 months post-treatment. Treatment effects were also specific to severely injured mice; animals with weight support at the time of treatment lost function over a 6-month period. Retrograde tracing with Fluorogold revealed viable neurons throughout the motor cortex despite a loss of RFP expression at 9 weeks post-PTEN-KO. However, few Fluorogold labeled neurons were detected within the motor cortex at 6 months post-treatment. BDA labeling from the motor cortex revealed a dense corticospinal tract (CST) bundle in all groups except chronically treated PTEN-KO mice indicating a potential long-term toxic effect of PTEN-KO to neurons in the motor cortex. PTEN-KO mice had significantly more β-tubulin III labeled axons within the lesion when treatment was delivered acutely, but not chronically post-SCI. In conclusion, we have found that using AAVrg’s to knockout PTEN is an effective manipulation capable of restoring motor functions in chronic SCI and can enhance axon growth of currently unidentified axon populations when delivered acutely after injury. However, the long-term consequences of PTEN-KO may exert neurotoxic effects.
Resistance to abemaciclib is associated with increased metastatic potential and lysosomal protein deregulation in breast cancer cells
Authors: Scheidemann Erin R. , Demas Diane M. , Hou Chunyan , Ma Junfeng , He Wei , Weilbaecher Katherine N. , Shajahan-Haq Ayesha N. 
Published: April 2023

ABSTRACTCyclin dependent kinase 4 and 6 inhibitors (CDK4/6i) such as abemaciclib are routinely used to treat metastatic estrogen receptor positive (ER+)/HER2-negative breast cancer. However, adaptive mechanisms inhibit their effectiveness and allow for disease progression. Using murine metastatic ER+ breast cancer cells, we show that acquired resistance to abemaciclib is accompanied by increase in metastatic potential. Mass spectrometry-based proteomics from abemaciclib sensitive and resistant cells showed that lysosomal proteins including CTSD (cathepsin D), CTSA (cathepsin A) and CD68 were significantly increased in resistant cells. Combination of abemaciclib and a lysosomal destabilizer, such as hydroxychloroquine (HCQ) or bafilomycin A1, re-sensitized resistant cells to abemaciclib. Also, combination of abemaciclib and HCQ decreased migration and invasive potential and increased lysosomal membrane permeability (LMP) in resistant cells. Pro-survival BCL2 protein levels were elevated in resistant cells, and a triple treatment with abemaciclib, HCQ, and BCL2 inhibitor, venetoclax, significantly inhibited cell growth compared to treatment with abemaciclib and HCQ. Furthermore, resistant cells showed increased levels of TFEB (Transcription Factor EB), a master regulator of lysosomal-autophagy genes, and siRNA mediated knockdown ofTFEBdecreased invasion in resistant cells.TFEBgene was found to be mutated in a subset of invasive human breast cancer samples, and overall survival analysis in ER+, lymph node-positive breast cancer showed that increasedTFEBexpression correlated with decreased survival. Collectively, we show that prolonged exposure to abemaciclib in ER+ breast cancer cells leads to resistance accompanied by an aggressive phenotype that is partly supported by deregulated lysosomal function.Implications: Our data implicate that resistance to abemaciclib is associated with deregulation of lysosomes and augmented metastatic potential, and therefore, the lysosomal pathway could be a therapeutic target in advanced ER+ breast cancer.GRAPHICAL ABSTRACT
The patatin-like protein PlpD forms novel structurally dynamic homodimers in thePseudomonas aeruginosaouter membrane
Authors: Hanson Sarah E. , Doyle Matthew Thomas , Bernstein Harris D. 
Published: April 2023

ABSTRACTMembers of the Omp85 superfamily of outer membrane proteins (OMPs) found in Gram-negative bacteria, mitochondria and chloroplasts are characterized by a distinctive 16-stranded β-barrel transmembrane domain and at least one periplasmic POTRA domain. All previously studied Omp85 proteins promote critical OMP assembly and/or protein translocation reactions.Pseudomonas aeruginosaPlpD is the prototype of an Omp85 protein family that contains an N-terminal patatin-like (PL) domain that is thought to be translocated across the OM by a C-terminal β-barrel domain. Challenging the current dogma, we found that the PlpD PL-domain resides exclusively in the periplasm and, unlike previously studied Omp85 proteins, PlpD forms a homodimer. Remarkably, the PL-domain contains a segment that exhibits unprecedented dynamicity by undergoing transient strand-swapping with the neighboring β-barrel domain. Our results show that the Omp85 superfamily is more structurally diverse than currently believed and suggest that the Omp85 scaffold was utilized during evolution to generate novel functions.
Allogeneic Tumor Cell-Derived Extracellular Vesicles Stimulate CD8 T Cell Response in Colorectal Cancer
Authors: Gates Travis J , Wangmo Dechen , Zhao Xianda , Subramanian Subbaya 
Published: April 2023

ABSTRACTColorectal Cancer (CRC) is the second leading cause of cancer-related death in the United States. Most CRC patients present with a microsatellite stable (MSS) phenotype and are highly resistant to immunotherapies. Tumor extracellular vesicles (TEVs), secreted by tumor cells, can contribute to intrinsic resistance to immunotherapy in CRC. We previously showed that autologous TEVs without functional miR-424 induce anti-tumor immune responses. We hypothesized that allogeneic modified CRC-TEVs without miR-424 (mouse homolog miR-322) derived from an MC38 background would effectively stimulate CD8+T cell response and limit CT26 tumor growth. Here we show that prophylactic administration of MC38 TEVs without functional miR-424 significantly increased CD8+T cells in CT26 CRC tumors and limited tumor growth, not B16-F10 melanoma tumors. We further show that the depletion of CD4+and CD8+T cells abolished the protective effects of MC38 TEVs without functional miR-424. We further show that TEVs can be taken up by DCsin vitro,and subsequent prophylactic administration of autologous DCs exposed to MC38 TEVs without functional miR-424 suppressed tumor growth and increased CD8+T cells compared to MC38 wild-type TEVs exposed to DCs, in Balb/c mice bearing CT26 tumors. Notably, the modified EVs were well tolerated and did not increase cytokine expression in peripheral blood. These findings suggest that allogeneic-modified CRC-EVs without immune suppressive miR-424 can induce antitumor CD8+T cell responses and limit tumor growth in vivo.
PI3K/mTOR is a therapeutically targetable genetic dependency in diffuse intrinsic pontine glioma
Authors: Duchatel Ryan J. , Jackson Evangeline R. , Parackal Sarah G. , Sun Claire , Daniel Paul , Mannan Abdul , Findlay Izac J. , Staudt Dilana , Germon Zacary P. , Laternser Sandra , Kiltschewskij Dylan , Kearney Padraic S. , Fairuz M. , Jamaluddin B. , Douglas Alicia M. , Beitaki Tyrone , Persson Mika , Manning Elizabeth E. , Murray Heather C. , Verrills Nicole M. , Skerrett-Byrne David A. , Nixon Brett , Hua Susan , Fatima Valdes-Mora , Tsoli Maria , Ziegler David S. , Cairns Murray J. , Raabe Eric , Vitanza Nicholas A. , Koschmann Carl , Alvaro Frank , Dayas Christopher V. , Tinkle Christopher L. , Eisenstat David D. , Firestein Ron , Mueller Sabine , Nazarian Javad , Cain Jason E. , Dun Matthew D. 
Published: April 2023

AbstractDiffuse midline glioma (DMG), including tumors diagnosed in the brainstem (diffuse intrinsic pontine glioma – DIPG), are uniformly fatal brain tumors that lack effective pharmacological treatment. Analysis of pooled CRISPR-Cas9 loss-of-function gene deletion screen datasets, identifiedPIK3CAandMTORas targetable molecular dependencies across DIPG patient derived models, highlighting the therapeutic potential of the blood-brain barrier penetrant PI3K/Akt/mTOR inhibitor paxalisib. At the human equivalent maximum tolerated dose, mice treated with paxalisib experienced systemic feedback resulting in increased blood glucose and insulin levels, commensurate with DIPG patients in Phase 1b clinical trials who experienced hyperglycemia/hyperinsulinemia. To exploit genetic dependences, but maintain compliance and benefit, we optimized a paxalisib treatment regimen that employed reduced dosing more frequently, in combination with the anti-hyperglycemic drug, metformin. Combining optimized dosing with metformin restored glucose homeostasis and decreased phosphorylation of the insulin receptorin vivo, a common mechanism of PI3K-inhibitor resistance, extending the survival of DIPG xenograft models. RNA sequencing and phosphoproteomic profiling of DIPG models treated with paxalisib identified increased calcium-activated PKC signaling. Using the brain penetrant PKC inhibitor, enzastaurin in combination with paxalisib, we synergistically extended the survival of orthotopic xenograft models, benefits further promoted by metformin; thus, identifying a clinically relevant DIPG combinatorial approach.Brief SummaryDiffuse intrinsic pontine glioma is a lethal childhood brain tumor. Here we identifyPIK3CAas a genetic dependency targeted by the brain penetrant pan-PI3K-inhibitor paxalisib.
Interaction of marine organisms on localized corrosion of 316L stainless steel in Dalian seawater
Authors: Chen Wanbin , Wang Mingyu , Li Mingyu , Li Kaiqiang , Huang Yi , Xu Yunze 
Published: April 2023

Purpose
The purpose of this paper is to study the interaction of main marine organisms on localized corrosion of 316L stainless steel in the Dalian Sea area.

Design/methodology/approach
The steel plate was immersed in the Dalian Sea area for nine months to observe the biofouling and localized corrosion. The local potential distribution on the steel plate covered by marine organisms was measured. The local electrochemical measurements were performed to facilitate understanding the interfacial status under different biofouling conditions. The local surface morphologies and corrosion products were characterized.

Findings
The localized corrosion of stainless steel is mainly induced by the attachment of barnacles on the steel. The mussels have no influence on the localized corrosion. The cover of sea squirts could mitigate the localized corrosion induced by barnacles. Both crevice corrosion and pitting corrosion were found beneath the barnacle without the covering of sea squirts. The pitting damage was more serious than the crevice corrosion in the Dalian Sea area. The probing of sulfur element indicates that the potential growth of sulfate-reducing bacteria at barnacle center.

Originality/value
The above findings revealed that the interaction of marine organisms has significant influences on the localized corrosion of stainless steel. The influences of macro-fouling and micro-fouling on localized corrosion are discussed.
Firm’s exploration-exploitation capabilities. Do diversity and empowerment matter?
Authors: Singh Subodh , Sinha Sabyasachi 
Published: April 2023

Purpose
This paper aims to explore the effect of gender diversity and female empowerment on a firm’s exploration and exploitation capabilities.

Design/methodology/approach
This is an empirical paper. This study investigated the research question in this paper using data on UK Financial Times Stock Exchange 100 firms and OLS regression analysis.

Findings
This study found a positive association between senior management gender diversity in the workforce and exploitation and exploration capabilities. Also, female empowerment positively moderates senior management gender diversity’s impact on exploration capability.

Practical implications
This study advises firms aspiring ambidextrous to establish gender diversity – especially at the senior management level – and focus on female empowerment in their organisations.

Originality/value
This paper argued for the role of females in making the organisations ambidextrous by impacting both exploitation and exploration capabilities, which did not receive adequate research attention to date.
Understanding the psychological determinants of buy-now-pay-later (BNPL) in the UK: a user perspective
Authors: Relja Ruffin , Ward Philippa , Zhao Anita L. 
Published: April 2023

PurposeThis study explores the psychological determinants of buy-now-pay-later (BNPL) use in the UK and reviews the efficacy of existing payment constructs.Design/methodology/approachA total of 533 BNPL users engaged in story stem completion. Template analysis was used, supported by the identification of four BNPL sentiment groups to enable comparison.FindingsWhilst positive attitudes towards BNPL dominate, other psychological determinants are apparent to a varied extent. Psychological distance and ownership of borrowed money are redolent, while transparency and transaction convenience are less appreciable. BNPL users understand temporality beyond its current conceptualizations. Some users construe BNPL as a “savings” product, and hence payment format conceptualizations may be erroneous. Those with a positive sentiment foreground BNPL’s consumption and budget management benefits. However, the potential for unintended consequences is manifest across all users.Research limitations/implicationsThe potentially unwanted consequences, or dark side, of BNPL use in the UK are highlighted. The specified constructs, whilst helpful, do not particularize the complex interconnected nature of the psychological determinants of BNPL use. Improved conceptualization offering richness and clarity is needed – temporality specifically requires consideration.Practical implicationsUsers’ sophistication and misunderstanding are both evident, necessitating fuller conversations among various stakeholders, including, providers, policymakers, consumers and advocacy groups.Originality/valueThis research advances the scarce literature exploring consumers’ BNPL use determinants and challenges current conceptualizations surrounding payment format perceptions.
Toward a framework for perceived yuanfen in the accommodation service encounter: a grounded theory study
Authors: Tang Xiangjie , Fong Lawrence Hoc Nang , So Amy Siu-Ian 
Published: April 2023

Purpose
This study aims to conceptualize the potential stimuli and consequences of perceived yuanfen in the accommodation service encounter by interpreting how Chinese customers perceive yuanfen during their stay in accommodations.

Design/methodology/approach
Online accommodation reviews containing yuanfen perception were interpreted using a grounded theory approach. Group interviews were conducted to verify the interpretations.

Findings
Positive outcome-generated emotional accommodation experiences (e.g. happiness) can elicit perceived yuanfen, which then evokes customers’ feelings of gratitude, emotional attachment to an accommodation and memorable accommodation experiences. Also, perceived yuanfen facilitates customers’ tolerance of service failures and promotes customers’ intention to stay longer at, recommend and revisit the accommodation.

Research limitations/implications
This study contributes to the literature on accommodation experiences, loyalty, word-of-mouth and service recovery. Future research can explore the interventions that trigger Chinese customers’ perceived yuanfen during accommodation.

Practical implications
This study informs practitioners of the importance of perceived yuanfen in enhancing accommodation experiences and service recovery. Moreover, the conceptualized characteristics and stimuli of perceived yuanfen offer possible guidelines for practitioners on how to stimulate customers’ yuanfen perception.

Originality/value
This study fills the gap of how perceived yuanfen functions in the service encounters in accommodations.
A nexus between sustainability, energy utilisation and economic growth at aggregate and disaggregate level: a case of India
Authors: Dhillon Dilpreet Kaur , Kaur Kuldip 
Published: April 2023

Purpose
The growth of the Indian economy is accompanied by the rising trend of energy utilisation and its devastating effect on the environment. It is vital to understand the nexus between energy utilisation, climate and environment degradation and growth to devise a constructive policy framework for achieving the goal of sustainable growth. This study aims to analyse the long- and short-run association and direction of association between energy utilisation, carbon emission and growth of the Indian economy in the presence of structural break.

Design/methodology/approach
The study probes the association and direction of association between variables at both aggregate (total energy utilisation, total carbon emission and gross domestic product [GDP]) and disaggregates level (coal utilisation and coal emission, oil utilisation and oil emission, natural gas utilisation and natural gas emission along with GDP) over the time period of 50 years, i.e. 1971–2020. Autoregressive distributed lag model is used to examine the association between the variables and presence of structural break is confirmed with the help of Zivot–Andrews unit root test. To check the direction of association, vector error correction model Granger causality is performed.

Findings
Aggregate carbon emissions are affected positively by aggregate energy consumption and GDP in both short and long run. Bidirectional causality exists between total emissions and GDP, whereas a unidirectional causality runs from energy consumption towards carbon emission and GDP in the long run. At disaggregate level, consumption of coal energy impacts positively, whereas GDP influences coal emission negatively in the long run only. Furthermore, consumption of oil and GDP influences oil emissions positively in the long run. Lastly, natural gas is the energy source that has the fewest emissions in both short and long run.

Originality/value
There is a rapidly growing body of research on the connections and cause-and-effect relationships between energy use, economic growth and carbon emissions, but it has not conclusively proved how important the presence of structural breaks or changes within the economy is in shaping the outcomes of the aforementioned variables, especially when focusing on the Indian economy. By including the impact of structural break on the association between energy use, carbon emission and growth, where energy use and carbon emission are evaluated at both aggregate and disaggregate level, the current study aims to fill this gap in Indian literature.
Real estate investment decisions in underrepresented Southeast Asian countries: evidence from Cambodia, Myanmar, and Vietnam
Authors: Yeh Wilson Wai Kwan , Hao Gang , Ozer Muammer 
Published: April 2023

Purpose
Although real estate investment decisions are among the most important managerial decisions, such decisions are usually made in an ad hoc fashion in Southeast Asia. The purpose of this study is to present a two-tier multi-criteria decision-making model for real estate investment decisions across three rapidly growing but significantly understudied Southeast Asian countries: Cambodia, Myanmar and Vietnam.

Design/methodology/approach
Using three data sources (secondary data, two surveys and nearly 100 experts and senior executives), the authors applied a combination of the Analytic Hierarchy Process and the Simple Additive Weighting (or weighted sum) methods as two special cases of multi-criteria decision-making to assess nine real estate investment projects across Cambodia, Myanmar and Vietnam.

Findings
The results of this study indicated that Vietnam, Cambodia and Myanmar were the first, second and third most preferred countries for real estate investments, respectively. Moreover, the results clearly show a trade-off between perceived country risk and financial returns, indicating that a higher perceived country risk can be compensated for with higher financial returns.

Originality/value
Real estate investment decisions are usually made in an ad hoc manner in Southeast Asia. This study helps investors make more informed decisions when investing in real estate projects across three rapidly growing but significantly understudied Southeast Asian countries: Cambodia, Myanmar and Vietnam.
Measuring buying intention of generation Z on social networking sites: an application of social commerce adoption model
Authors: Azhar Mohd , Akhtar Mohd Junaid , Rahman Mohd Nayyer , Khan Fawaz Ahmad 
Published: April 2023

PurposeThe present study intends to measure buying intention of Generation Z (Gen Z) on social networking sites (SNSs) incorporating perceived risk with the social commerce adoption model (SCAM).Design/methodology/approachData were collected via an online questionnaire, and the study used a total of 349 accurate and useable responses. The population of the study includes Indian young consumers coming from the Gen Z cohort. Data were analyzed using SPSS 20 and AMOS 22.0. The proposed hypotheses were statistically tested.FindingsThe empirical results show that perceived risk is a significant and strong predictor of perceived usefulness that, in turn, negatively influences buying intention. Among all the constructs of SCAM, perceived usefulness is the most influential and strongest predictor of buying intention. The proposed model explained approximately 34% of the variance in the behavioral intention.Research limitations/implicationsBased on the findings of this study, many theoretical and practical implications may be inferred that can be used to make recommendations to social commerce companies and help them understand the buying intention of Gen Z.Originality/valueThere are many studies that have examined buying intention and a few have measured it on Gen Z. The present study is novel in itself as it has measured the buying intention of Gen Z using the SCAM in the Indian context. Hence, the present research attempts to comprehend the variables influencing buying intention and analyses the relationship between these factors in the social media setting.