bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pembrolizumab alters the tumor immune landscape in a patient with dMMR glioblastoma
Authors: Bartkowiak Todd , Brockman Asa A. , Mobley Bret C. , Harmsen Hannah , Moots Paul , Merrell Ryan , Johnson Douglas B. , Thompson Reid C. , Puduvalli Vinay K. , Ihrie Rebecca A. 
Published: December 2023

AbstractCongenital DNA mismatch repair defects (dMMR), such as Lynch Syndrome, predispose patients to a variety of cancers and account for approximately 1% of glioblastoma cases. While few therapeutic options exist for glioblastoma, checkpoint blockade therapy has proven effective in dMMR tumors. Here we present a case study of a male in their 30s diagnosed with dMMR glioblastoma treated with pembrolizumab who experienced a partial response to therapy. Using a multiplex IHC analysis pipeline on archived slide specimens from tumor resections at diagnosis and after therapeutic interventions, we quantified changes in the frequency and spatial distribution of key cell populations in the tumor tissue. Notably, proliferating (KI67+) macrophages and T cells increased in frequency as did other KI67+ cells within the tumor. Therapeutic intervention remodeled the cellular spatial distribution in the tumor leading to a greater frequency of macrophage/tumor cell interactions and T cell/T cell interactions, highlighting impacts of checkpoint blockade on tumor cytoarchitecture and revealing spatial patterns that may indicate advantageous immune interactions in glioma and other solid tumors treated with these agents.InsightThis work sheds light on the capacity of checkpoint blockade therapy to modulate the immune microenvironment in DNA mismatch repair deficient glioblastoma, highlights the utility of window-of-opportunity clinical trials in patient selection of immunomodulatory therapies, and demonstrates the feasibility and utility of mapping cellular interactions associated with therapeutic responses in gliomas and other solid tumors.Statement regarding non-clinical trial statusWe confirmed with a treating neurologist in this case that the treatment received by the individual whose samples are studied was part of routine clinical care and not a clinical trial, as the patient was previously diagnosed with Lynch syndrome (a mismatch repair deficiency). The use of pembrolizumab is recommended for treatment of tumors with high mutational burden due to mismatch repair deficiency and is currently considered standard of care for these tumors. Additionally, though the intervention and outcome are detailed in the manuscript, the focus of the manuscript is on reporting changes observed in the immune microenvironment at different points in the clinical trajectory - a retrospective analysis performed after clinical care was complete.
Utilization of Triglyceride Levels and Estimated Average Plasma Glucose Using Glycated Hemoglobin in Assessing Insulin Resistance: TyHBA1c index
Authors: de Oliveira Andrade Luís Jesuino , de Brito Luiz Felipe Moreno , de Oliveira Gabriela Correia Matos , de Oliveira Luisa Correia Matos , Vinhaes Bittencourt Alcina Maria , Baptista Gustavo Magno , Silva Catharina Peixoto , de Oliveira Luís Matos 
Published: December 2023

ABSTRACTIntroductionInsulin resistance (IR) is a metabolic disorder characterized by reduced sensitivity to the physiological effects of insulin, leading to an impaired ability of cells to take up glucose from the bloodstream. There are multiple indices available for assessing IR, however, they often rely on a single glycemic parameter at a specific moment, leaving a gap in the evaluation of IR over a certain period.ObjectiveTo develop a novel index for assessing IR by combining triglyceride levels and estimated glycemia through glycated hemoglobin (HBA1c).MethodWe used the fasting triglycerides and glucose levels (TyG) index formula by replacing fasting glucose with estimated average glucose calculated through HbA1c. The study included 200 laboratory samples, including fasting glucose, triglycerides, insulin, homeostasis model assessment for IR (HOMA-IR) index, TyG index, and estimated average glucose by HbA1c. The ideal cut-off value of the TyHBA1c index for estimating IR was established compared to the HOMA-IR index, and TyG index using a receiver operating characteristic (ROC) analysis. A weighted kappa test was used to estimate the diagnostic agreement between the TyHBA1c index and the HOMA-IR and Tyg index.ResultsThe TyHBA1c index showed a higher correlation with the HOMA-IR index (r = 0.273, p = 0.000) compared to the TyG index (r = -0.617, p < 0.000). An association between HBA1c and the HOMA-IR index was observed (r = 0.215, p = 0.002). The ROC curve showed that the cutoff value for the TyHBA1c index to best estimate IR is Ln 4.74 (sensitivity 85.0% and specificity 95.0%) compared to the TyG index. The weighted kappa test revealed moderate agreement between the TyHBA1c index and the HOMA-IR index (k = 0.45, p = 0.006), and satisfactory agreement between the TyHBA1c index and the TyG index (k = 0.71, p = 0.009).ConclusionOur results demonstrated a strong association between the TyHBA1c index and TyG index, and the HOMA-IR index, suggesting that the TyHBA1c index may be more a indicator of IR, and more a tool in clinical practice for assessing IR.
STAT3 regulates the generation of astroglia in human brain organoids with high mTORC1 activity
Authors: Deb Bipan K. , Li Thomas L. , Blair John D. , Hockemeyer Dirk , Bateup Helen S. 
Published: December 2023

AbstractDuring brain development, neural progenitor cells first produce neurons, then astrocytes and other glial cell types, which provide important trophic support and shape neuronal development and function. Intrinsic genetic programs interact with extracellular signals to control progenitor fate, resulting in temporally segregated periods of neurogenesis and gliogenesis. Animal models have implicated STAT3 as an important driver of astrogenesis; however, the signaling pathways that control glial differentiation during human brain development are less well understood. Prior work demonstrated that constitutive activation of mTORC1 signaling in human brain organoid models resulted in the precocious generation of glial-lineage cells. In this study, we tested whether mTORC1 acts via STAT3 to control astrogenesis in brain organoids. We show that knockdown of STAT3 reduces astrogenesis in wild-type organoids and in organoids with constitutively high mTORC1 signaling caused by deletion of the negative regulator TSC2. However, mTORC1 is not required for cytokine-induced activation of STAT3 and expression of the astrocytic protein GFAP. Together, these results show that mTORC1 acts through STAT3 to control astroglia production in human brain organoid models, but that mTOR signaling is dispensable for STAT3-driven astrogenesis.Summary statementDeb et al, use human brain organoid models to show a requirement for STAT3 downstream of mTORC1 in regulating astrogliogenesis during early human brain development.
A wearable, steerable, transcranial Low-Intensity Focused Ultrasound system
Authors: Bawiec Christopher R. , Hollender Peter J. , Ornellas Sarah B. , Schachtner Jessica N. , Dahill-Fuchel Jacob F. , Konecky Soren D. , Allen John J.B. 
Published: December 2023

AbstractObjectivesTranscranial Low-Intensity Focused Ultrasound (LIFU) offers unique opportunities for precisely neuromodulating small and/or deep targets within the human brain, which may be useful for treating psychiatric and neurological disorders. This paper presents a novel ultrasound system that delivers focused ultrasound through the forehead to anterior brain targets and evaluates its safety and usability in a volunteer study.MethodsThe ultrasound system and workflow are described, including neuronavigation, LIFU planning, and ultrasound delivery components. Its capabilities are analyzed through simulations and experiments to establish its safe steering range. A cohort of 20 healthy volunteers received a LIFU protocol aimed at the anterior medial prefrontal cortex (amPFC), using imaging and questionnaires to screen for adverse effects.ResultsSimulations and hydrophone readings agreed with less than 5% error, and the safe steering range was found to encompass a 1.8cm x 2.5cm x 2cm volume. There were no adverse effects evident on qualitative assessments, nor any signs of damage in susceptibility-weighted imaging scans. All participants tolerated the treatment well, and the users found the interface effective as the system was capable of accurately targeting the amPFC in all participants. A post hoc analysis showed that “virtual fitting” could aid in steering the beams around subjects’ sinuses.ConclusionsThe presented system was successfully used to safely deliver LIFU through the forehead to the amPFC in all volunteers, and was well-tolerated. With the capabilities validated here and positive results of the study, this technology appears well-suited to explore LIFU’s efficacy in clinical neuromodulation contexts.
“There is nothing that can prevent me from supporting her:” Men’s perspectives on their involvement and support of women’s use of topical therapy for cervical precancer treatment in Kenya
Authors: Mungo Chemtai , Adewumi Konyin , Adoyo Everlyn , Zulu Graham , Goraya Supreet Kaur , Ogollah Cirillus , Omoto Jackton , Ferrari Renée M. , Rahangdale Lisa 
Published: December 2023

AbstractPurposeCervical cancer disproportionately impacts women in low- and middle-income countries (LMICs). The World Health Organization’s (WHO) 90/70/90 strategy aims to eliminate cervical cancer by 2030 by increasing HPV vaccination coverage to 90%, screening 70% of eligible women, and effectively treating 90% of those with abnormal results by 2030, potentially preventing 62 million deaths in LMICs. LMICs, however, struggle with limited access to cervical precancer treatment, in part due to a lack of trained professionals and weak health systems. Effective non-surgical, self-administered, which have demonstrated efficacy in high-income countries, could bridge the treatment gap in LMICs and may be more scalable and cost-effective than provider-administered therapies. To inform feasibility studies in LMICs, data are needed on the role of male partners in influencing the acceptability and uptake of self-administered topical therapies, including their support of recommended abstinence and contraception guidelines associated with these therapies.MethodsBetween November 2022 and April 2023, we conducted five focus group discussions (FGDs) with men aged 25 to 65 years in Kenya to explore their perspective and perceived support regarding their female partners using topical self-administered therapies for cervical precancer treatment. The FGDs were moderated by local qualitative research assistants and conducted in local languages, transcribed, coded, and analyzed using qualitative description.ResultsMale participants in the FGDs strongly expressed acceptance and willingness to support their wives or partners in using topical therapies for cervical precancer treatment, if available. Reported supportive behavior included permitting the use of the therapies and support of maintaining abstinence during the recommended times. Additionally, participants desired male involvement in clinic and community-based education about topical therapies to facilitate widespread support.ConclusionThe use of self-administered topical therapies for cervical precancer treatment, if supported by efficacy studies in LMICs, may support achieving the WHO’s 2030 goal of 90% treatment access. We find that with adequate education, men express overwhelming support of their female partner’s use of topical therapies, including adherence to abstinence and contraception guidelines.
Role of behind-the-border factors in determining state-level differences in FDI inflows to India
Authors: Prabhakar Prerna , Aggarwal Muskan 
Published: December 2023

Purpose
Although India is seen as a key player in the global economy, it is still below its potential level of growth. In this age of globalism, integration with the global economy through trade and foreign investments fosters domestic growth. For India, although this integration has strengthened over the years, there are certain gaps that remain to be addressed. Though numerous studies in the literature have tried to find answers to these questions, an important aspect that has not been considered by these studies relates to India’s federal structure and the role of states in determining the aggregate economic outcome. As Foreign Direct Investment (FDI) inflows to India are concentrated in a few states, this paper aims to provide an assessment of the reasons behind this trend.

Design/methodology/approach
This paper aims to investigate the reasons behind the interstate differences with respect to FDI inflows in India. The analytical work undertaken for this paper is based on secondary data, collected and collated from various sources. The approach adopted for this paper includes a heat graph analysis to examine whether there is a clear pattern in terms of the state-specific factors for high FDI states versus the low FDI states. This data analysis is followed by an econometric estimation to gauge the impact of state-specific factors in determining the FDI inflows.

Findings
As per the secondary data–driven heat graph and econometric analysis, factors like industrial output, social sector expenditure, judicial quality, connectivity indicators, labor cost and availability of credit, act as differentiators between high and low FDI-receiving states. It then becomes imperative to bridge the gap between the two sets of states in terms of these specific factors. Implementation and success of policy interventions can only be derived at the state level and therefore needs more decentralized approach.

Originality/value
This paper tries to identify the reasons that are responsible for FDI inflows being concentrated in a few Indian states. This involves a comprehensive analysis of several variables to understand whether there is a clear pattern where high-FDI states are also in a better position with respect to these attributes. This effort to factor in the federal aspect of a macroeconomic indicator like FDI provides new dynamic to this area of work.
Artefacts as boundary objects for concept development: a configurational approach
Authors: Zasa Federico Paolo , Buganza Tommaso 
Published: December 2023

PurposeThis study aims to investigate how configurations of boundary objects (BOs) support innovation teams in developing innovative product concepts. Specifically, it explores the effectiveness of different artefact configurations in facilitating collaboration and bridging knowledge boundaries during the concept development process.Design/methodology/approachThe research is based on data from ten undergraduate innovation teams working with an industry partner in a creative industry. Six categories of BOs are identified, which serve as tools for collaboration. The study applies fsQCA (fuzzy-set qualitative comparative analysis) to analyse the configurations employed by the teams to bridge knowledge boundaries and support the development of innovative product concepts.FindingsThe findings of the study reveal two distinct groups of configurations: product envisioning and product design. The configurations within the “product envisioning” group support the activities of visioning and pivoting, enabling teams to innovate the product concept by altering the product vision. On the other hand, the configurations within the “product design” group facilitate experimenting, modelling and prototyping, allowing teams to design the attributes of the innovative product concept while maintaining the product vision.Originality/valueThis research contributes to the field of innovation by providing insights into the role of BOs and their configurations in supporting innovation teams during concept development. The results suggest that configurations of “product envisioning” support bridging semantic knowledge boundaries, while configurations within “product design” bridge pragmatic knowledge boundaries. This understanding contributes to the broader field of knowledge integration and innovation in design contexts.
Rethinking innovation through industry and society 5.0 paradigms: a multileveled approach for management and policy-making
Authors: Troisi Orlando , Visvizi Anna , Grimaldi Mara 
Published: December 2023

PurposeIndustry 4.0 defines the application of digital technologies on business infrastructure and processes. With the increasing need to take into account the social and environmental impact of technologies, the concept of Society 5.0 has been proposed to restore the centrality of humans in the proper utilization of technology for the exploitation of innovation opportunities. Despite the identification of humans, resilience and sustainability as the key dimensions of Society 5.0, the definition of the key factors that can enable Innovation in the light of 5.0 principles has not been yet assessed.Design/methodology/approach An SLR, followed by a content analysis of results and a clustering of the main topics, is performed to (1) identify the key domains and dimensions of the Industry 5.0 paradigm; (2) understand their impact on Innovation 5.0; (3) discuss and reflect on the resulting implications for research, managerial practices and the policy-making process.Findings The findings allow the elaboration of a multileveled framework to redefine Innovation through the 5.0 paradigm by advancing the need to integrate ICT and technology (Industry 5.0) with the human-centric, social and knowledge-based dimensions (Society 5.0).Originality/value The study detects guidelines for managers, entrepreneurs and policy-makers in the adoption of effective strategies to promote human resources and knowledge management for the attainment of multiple innovation outcomes (from technological to data-driven and societal innovation).
An electric vehicle routing model with charging stations consideration for sustainable logistics
Authors: Li Yan , Lim Ming K. , Xiong Weiqing , Huang Xingjun , Shi Yuhe , Wang Songyi 
Published: December 2023

PurposeRecently, electric vehicles have been widely used in the cold chain logistics sector to reduce the effects of excessive energy consumption and to support environmental friendliness. Considering the limited battery capacity of electric vehicles, it is vital to optimize battery charging during the distribution process.Design/methodology/approachThis study establishes an electric vehicle routing model for cold chain logistics with charging stations, which will integrate multiple distribution centers to achieve sustainable logistics. The suggested optimization model aimed at minimizing the overall cost of cold chain logistics, which incorporates fixed, damage, refrigeration, penalty, queuing, energy and carbon emission costs. In addition, the proposed model takes into accounts factors such as time-varying speed, time-varying electricity price, energy consumption and queuing at the charging station. In the proposed model, a hybrid crow search algorithm (CSA), which combines opposition-based learning (OBL) and taboo search (TS), is developed for optimization purposes. To evaluate the model, algorithms and model experiments are conducted based on a real case in Chongqing, China.FindingsThe result of algorithm experiments illustrate that hybrid CSA is effective in terms of both solution quality and speed compared to genetic algorithm (GA) and particle swarm optimization (PSO). In addition, the model experiments highlight the benefits of joint distribution over individual distribution in reducing costs and carbon emissions.Research limitations/implicationsThe optimization model of cold chain logistics routes based on electric vehicles provides a reference for managers to develop distribution plans, which contributes to the development of sustainable logistics.Originality/valueIn prior studies, many scholars have conducted related research on the subject of cold chain logistics vehicle routing problems and electric vehicle routing problems separately, but few have merged the above two subjects. In response, this study innovatively designs an electric vehicle routing model for cold chain logistics with consideration of time-varying speeds, time-varying electricity prices, energy consumption and queues at charging stations to make it consistent with the real world.
Exploring independent learning (IL) and its relationship to mindset, motivated strategies for learning and academic performance
Authors: Forbes-McKay Katrina E. , Bremner Pauline A.M. , Johnston Pamela , Air Carol 
Published: December 2023

PurposeThis study addresses gaps in the existing literature on students' understanding of Independent Learning (IL), whilst exploring the link between levels of IL, growth mindset, motivated strategies for learning and academic performance.Design/methodology/approachThree hundred and eighty-six university students recruited via opportunistic sampling completed an online survey to measure: understanding and level of IL, Motivated Strategies for Learning (MSL) (Duncan and McKeachie, 2005) and growth mindset (Dweck, 2000). Interaction with the university Virtual Learning Environment (VLE) and academic grades were also measured. A correlational design was implemented, and a Spearman Rho was calculated to explore the relationship between level of IL, MSL and growth mindset. A between-subjects design using independent measures t-test was employed to determine the significance of any difference in level of IL and VLE engagement according to academic grade.FindingsWhilst most students: considered themselves an IL and understood what IL was, the majority erroneously believed it meant learning alone or without help. Level of IL, however, was positively associated with motivational beliefs (self-efficacy and mindset), cognitive strategies (rehearsal, elaboration, organisation and critical thinking), and metacognitive strategies (time management and self-regulation). Further, those with grades A-C scored significantly higher than those with grades D and below on cognitive strategies (elaboration and organisation). Those attaining higher grades also interacted with the VLE significantly more frequently and regularly than those attaining lower grades.Originality/valueThis study adds to the existing literature by highlighting the positive relationship between level of IL, MSL, mindset and academic achievement. It also addresses the under-explored potential for VLE engagement in predicting grades amongst on-campus courses. Given that cognitive strategies and VLE engagement differentiate the high and low achievers, interventions to develop such skills may enhance academic achievement.