bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring prognostic and immunological characteristics of pancreatic ductal adenocarcinoma through comprehensive genomic analysis of tertiary lymphoid structures and CD8 + T-cells
Authors: Hu Hao , Xu Yang , Zhang Qiang , Ai Xiangnan , Wang Tengfei , Li Huixing , Jin Changguo , Ouyang Caiguo , Wu Zhenyu 
Published: June 2024

Abstract
Purpose
Tertiary lymphoid structures (TLSs) and CD8 + T-cells are potential prognostic indicators for pancreatic ductal adenocarcinoma (PDAC). We established a novel scoring system for evaluating the risk for PDAC based on TLS- and CD8 + T-cell-related genes.

Methods
We analyzed single-cell sequence data from PDAC patients in the Genome Sequence Archive. Bioinformatics and machine algorithms established and validated a scoring method (T-C score) based on PDAC survival-related genes highly expressed in TLSs and CD8 + T-cells. Patients were stratified into the low- and high-T-C score groups. Differences in survival, pathway enrichment, mutation status, immune cell infiltration, expression of immune checkpoint-associated genes, tumor stemness, and response to antitumor therapy were compared through computer simulation methods.

Results
Overall survival differed significantly between the training and validation cohorts’ low- and high-T-C score groups. The low-T-C score group correlated with lower tumor mutation burden and lower levels of tumor stemness compared with the high-T-C score group. Patients with lower T-C scores exhibited advantages in immunotherapeutic responses and might be more sensitive to the chemotherapeutic regimen and multi-kinase inhibitors.

Conclusion
The T-C score could serve as an effective model for predicting the survival and therapeutic responses of patients with PDAC.
Biomarker conversion from primary breast cancer to synchronous axillary lymph node metastasis and neoadjuvant therapy response: a single-center analysis
Authors: Ding Mao , Li Mengyuan , Liu Qian , Xu Ling 
Published: June 2024

Abstract
Purpose
The biomarker characteristics of breast cancer plays an important role in predicting treatment sensitivity. The aim of the present study was to compare immunohistochemical profiles (ER, PR, HER2, and Ki67) between the primary tumor and synchronous axillary lymph node metastasis and investigate the subsequent effects on neoadjuvant therapy response.

Methods
A total of 358 patients with pathologically confirmed synchronous axillary lymph node metastasis at first diagnosis and treated by neoadjuvant therapy at Peking University First Hospital from January 1, 2013 to December 31, 2022 were included in this retrospective study. Clinicopathologic data, especially receptor status in primary and metastatic foci, was collected for each case.

Results
Change of ER, PR, HER2, and Ki67 expression was observed in 5.9%, 8.7%, 12.6%, and 17.3% of patients, respectively. HR discordance was observed more frequently when the ER status (p = 0.023) or PR status (p = 0.010) of primary tumor was negative, while HER2 discordance seemed to be more frequent when the HER2 status of primary tumor was HER2-0 or HER2-low (p < 0.001). Patients with loss of HR-positivity (positive to negative) responded to neoadjuvant chemotherapy better compared to those with stable positive HR expression (50% vs. 11.1%, p = 0.0017). A significantly decrease in pCR rate was observed in patients with unstable HER2 status, but not in the HER2-0/HER2-low subgroup.

Conclusion
Receptor discordance between primary tumor and synchronous axillary LNM appears to already exist before any anti-tumor therapy. This instability has limited clinical impact on the choice of neoadjuvant therapy at current stage, but further investigation is warranted with the incremental application of endocrine drugs and ADCs in neoadjuvant therapy.
Comprehensive sensitivity analysis of repeated eigenvalues and eigenvectors for structures with viscoelastic elements
Authors: Łasecka-Plura Magdalena 
Published: June 2024

AbstractThe paper discusses systems with viscoelastic elements that exhibit repeated eigenvalues in the eigenvalue problem. The mechanical behavior of viscoelastic elements can be described using classical rheological models as well as models that involve fractional derivatives. Formulas have been derived to calculate first- and second-order sensitivities of repeated eigenvalues and their corresponding eigenvectors. A specific case was also examined, where the first derivatives of eigenvalues are repeated. Calculating derivatives of eigenvectors associated with repeated eigenvalues is complex because they are not unique. To compute their derivatives, it is necessary to identify appropriate adjacent eigenvectors to ensure stable control of eigenvector changes. The derivatives of eigenvectors are obtained by dividing them into particular and homogeneous solutions. Additionally, in the paper, a special factor in the coefficient matrix has been introduced to reduce its condition number. The provided examples validate the correctness of the derived formulas and offer a more detailed analysis of structural behavior for structures with viscoelastic elements when altering a single design parameter or simultaneously changing multiple parameters.
Combined assessment of lysine and N-acetyl cadaverine levels assist as a potential biomarker of the smoker periodontitis
Authors: Rashid Md Haroon , Yellarthi Sandhya Pavan Kumar , Yellarthi Pavan Kumar , Didugu Brinda Goda Lakshmi , Mamillapalli Anitha 
Published: June 2024

AbstractPeriodontitis is an inflammatory condition of supporting structures of teeth leading to attachment and bone loss. Cigarette smoking is the single most important and modifiable risk factor with 5 to 20-fold susceptibility for periodontal diseases. Reverse smoking is a peculiar habit of smoking where the lit end is kept inside the mouth, which is predominant in the northern coastal districts of Andhra Pradesh. Polyamines are biologically active amines involved in tissue regeneration and modulation of inflammation. The study aimed to evaluate polyamines and check their utility as a marker in detection of periodontitis among different groups. Total polyamine levels showed significant increase in reverse smokers with periodontitis when compared to the other groups. Qualitative analysis by thin layer chromatography showed three polyamine bands with varying intensity among the different groups. Mass spectrometric and NMR analyses of the three bands identified them as N1, N8-diacetyl spermidine, N-acetyl cadaverine and lysine. Most significantly elevated levels of lysine was observed in the smoker and reverse smoker periodontitis groups when compared to healthy and non-smoker periodontitis groups. The significantly elevated levels of N-acetyl cadaverine could be responsible for the more destruction of periodontium in the reverse smoker group. Antioxidant potential decreased significantly in different smoker periodontitis groups. The present study suggests that the quantitative analysis of salivary polyamines, lysine and N-acetyl cadaverine can aid as an easy noninvasive diagnostic method for assessing the periodontal status, especially in smokers.
TMEM205 induces TAM/M2 polarization to promote cisplatin resistance in gastric cancer
Authors: Fu Qiang , Wu Xuwei , Lu Zhongqi , Chang Ying , Jin Quanxin , Jin Tiefeng , Zhang Meihua 
Published: June 2024

AbstractCisplatin (DDP) is a basic chemotherapy drug for gastric cancer (GC). With the increase of DDP drug concentration in clinical treatment, cancer cells gradually became resistant. Therefore, it is necessary to find effective therapeutic targets to enhance the sensitivity of GC to DDP. Studies have shown that Transmembrane protein 205 (TMEM205) is overexpressed in DDP-resistant human epidermoid carcinoma cells and correlates with drug resistance, and database analyses show that TMEM 205 is also overexpressed in GC, but its role in cisplatin-resistant gastric cancer remains unclear. In this study, we chose a variety of experiments in vivo and vitro, aiming to investigate the role of TMEM 205 in cisplatin resistance in gastric cancer. The results showed that TMEM 205 promoted proliferation, stemness, epithelial–mesenchymal transition (EMT), migration and angiogenesis of gastric cancer cells through activation of the Wnt/β-catenin signaling pathway. In addition, TMEM205 promotes GC progression by inducing M2 polarization of tumor-associated macrophages (TAMs). These results suggest that TMEM205 may be an effective target to regulate the sensitivity of GC to DDP, providing a new therapeutic direction for clinical treatment.
Age, preoperative tumor volume and widening of the internal acoustic meatus are independent factors associated with poor preoperative hearing in vestibular schwannoma patients – results of a single-center retrospective analysis
Authors: Dörner Lorenz , Suhm Elisa-Maria , Ries Vanessa , Goncalves Vitor , Skardelly Marco , Schittenhelm Jens , Tatagiba Marcos , Behling Felix 
Published: June 2024

AbstractPreoperative hearing function shows wide variations among patients diagnosed with vestibular schwannoma. Besides the preoperative tumor size there are other factors that influence the preoperative hearing function that are frequently discussed. A comprehensive analysis of a large cohort of vestibular schwannomas has the potential to describe new insights and influence the preoperative management. We analyzed clinical factors, imaging data and the expression of the proliferation marker MIB1 as potential influencing factors on the preoperative hearing function in a retrospective cohort of 523 primary sporadic vestibular schwannomas. The results of the preoperative audiometry were quantified using the Gardner-Robertson Score. Uni- and multivariate analyses were performed. Serviceable hearing (Gardner-Robertson class 1 or 2) was documented in 391 patients (74.8%). Factors associated with non-serviceable hearing (Gardner-Robertson class 3–5) were patients of older age (p < 0.0001), larger preoperative tumor volume (p = 0.0013) and widening of the internal acoustic meatus compared to the healthy side (p = 0.0353). Gender and differences in the expression of the proliferation marker MIB1 had no influence on preoperative hearing. In the multivariate nominal logistic regression older age (OR 27.60 (CI 9.17–87.18), p < 0.0001), larger preoperative tumor volume (OR 20.20 (CI 3.43–128.58), p = 0.0011) and widening of the internal acoustic canal (OR 7.86 (CI 1.77–35.46), p = 0.0079) remained independent factors associated with non-serviceable hearing. Widening of the internal acoustic canal is an independent factor for non-serviceable preoperative hearing in vestibular schwannoma patients together with older age and larger preoperative tumor volume.
Identifying higher education students’ profiles of academic engagement and burnout and analysing their predictors and outcomes
Authors: Cano Francisco , Pichardo C. , Justicia-Arráez A. , Romero-López M. , Berbén A.B.G. 
Published: June 2024

AbstractA review of research on the relationship between academic engagement and burnout reveals three research gaps as most of the research was conducted: i) without analysing all its multiple dimensions; ii) from a variable-centred perspective; and iii) in educational contexts other than higher education. We seek to address these gaps and thus enhance our understanding of the nature of the mentioned relationship. Adopting a person-centred perspective, a latent profile analysis (LPA) was used to identify how all the dimensions of academic engagement and burnout combine in different profiles of higher education students (n=430). Additional analyses were used to validate these LPA profiles by relating them to a set of auxiliary variables (i.e., predictors and outcomes), grounded on theoretical models relevant to higher education. LPA revealed three ordered profiles (burned-out, moderately engaged and engaged) and the additional analyses detected statistically significant associations between predictors (e.g., perceptions of academic quality, perceptions of stress) and profile membership; and between these and outcomes. The latter tended to be ordered from the least to the most desirable in learning strategies (e.g., self-regulation, deep processing) and learning outcomes (e.g., generic skills, satisfaction), with the most desirable generally being associated more with the two engaged profiles than with the burned-out profile.Taken together, the findings i) expand our understanding of the nature of academic engagement and burnout in higher education, suggesting that they are related but independent constructs at different levels (high/low and weaker levels), and ii) hold implications for theory, methodology and educational practice (adjusted to the distinctiveness of the detected profiles).
Selective depletion of tumor-infiltrating regulatory T cells with BAY 3375968, a novel Fc-optimized anti-CCR8 antibody
Authors: Roider Helge G. , Hoff Sabine , Tseng Su-Yi , Berndt Sandra , Trautwein Mark , Filarsky Katharina , Gritzan Uwe , Camps Jordi , Nadler Wiebke Maria , Grudzinska-Goebel Joanna , Ellinger Philipp , Pesch Theresa , Soon Chai Fen , Geyer Marcel , Gluske Katja , Stelte-Ludwig Beatrix , Gorjánácz Mátyás 
Published: June 2024

AbstractRegulatory T cells (Tregs) are known to facilitate tumor progression by suppressing CD8+ T cells within the tumor microenvironment (TME), thereby also hampering the effectiveness of immune checkpoint inhibitors (ICIs). While systemic depletion of Tregs can enhance antitumor immunity, it also triggers undesirable autoimmune responses. Therefore, there is a need for therapeutic agents that selectively target Tregs within the TME without affecting systemic Tregs. In this study, as shown also by others, the chemokine (C–C motif) receptor 8 (CCR8) was found to be predominantly expressed on Tregs within the TME of both humans and mice, representing a unique target for selective depletion of tumor-residing Tregs. Based on this, we developed BAY 3375968, a novel anti-human CCR8 antibody, along with respective surrogate anti-mouse CCR8 antibodies, and demonstrated their in vitro mode-of-action through induction of potent antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis (ADCP) activities. In vivo, anti-mouse CCR8 antibodies effectively depleted Tregs within the TME primarily via ADCP, leading to increased CD8+ T cell infiltration and subsequent tumor growth inhibition across various cancer models. This monotherapeutic efficacy was significantly enhanced in combination with ICIs. Collectively, these findings suggest that CCR8 targeting represents a promising strategy for Treg depletion in cancer therapies. BAY 3375968 is currently under investigation in a Phase I clinical trial (NCT05537740).
Trichoderma metabolites 6-pentyl-α-pyrone and harzianic acid affect the reproduction and microbiome of Bactrocera oleae
Authors: Jesu Giovanni , Vinale Francesco , Lorito Matteo , Laudonia Stefania 
Published: June 2024

AbstractEndosymbiosis is very common between bacteria and insects, and it has been deeply studied for over a century on model insects such as Bactrocera oleae, the key pest of the olives. It was demonstrated that “Candidatus Erwinia dacicola” is the main component of its midgut bacterial communities, acting a fundamental role in the fly’s nutrition process and thus on its fitness. In this study, Trichoderma secondary metabolites have been used to treat olive fruit fly in order to alter the “Ca. Erwinia dacicola” titer and to assess the subsequent effects on its host. The selected metabolites, 6-pentyl-α-pyrone and harzianic acid, directly affect the insect’s fitness also on the subsequent generation, but not always in a concentration-dependent manner. Aside from the direct effects, the treatments also showed a modification of the bacterial titer. Therefore, real-time qPCRs were carried out on wild individual flies highlighting natural variations of the symbiont presence and activity during the seasons. The data obtained suggest that bioactive fungal metabolites can be formulated for direct or indirect control strategies of B. oleae in integrated pest management programs.
Evaluating the Risk Landscape of Hawaiian Monk Seal Exposure to Toxoplasma gondii
Authors: Robinson Stacie , Falinski Kim , Johnson Devin , VanWormer Elizabeth , Shapiro Karen , Amlin Angela , Barbieri Michelle 
Published: June 2024

AbstractToxoplasmosis is a disease of primary concern for Hawaiian monk seals (Neomonachus schauinslandi), due to its apparently acute lethality and especially heavy impacts on breeding female seals. The disease-causing parasite, Toxoplasma gondii, depends on cats to complete its life cycle; thus, in order to understand how this pathogen infects marine mammals, it is essential to understand aspects of the terrestrial ecosystem and land-to-sea transport. In this study, we constructed a three-tiered model to assess risk of Hawaiian monk seal exposure to T. gondii oocysts: (1) oocyst contamination as a function of cat population characteristics; (2) land-to-sea transport of oocysts as a function of island hydrology, and (3) seal exposure as a function of habitat and space use. We were able to generate risk maps highlighting watersheds contributing the most to oocyst contamination of Hawaiian monk seal habitat. Further, the model showed that free-roaming cats most associated with humans (pets or strays often supplementally fed by people) were able to achieve high densities leading to high levels of oocyst contamination and elevated risk of T. gondii exposure.
The Role of Anatomic Connectivity in Inhibitory Control Revealed by Combining Connectome-based Lesion-symptom Mapping with Event-related Potentials
Authors: Nono Alex S. T. , Anziano Marco , Mouthon Michael , Chabwine Joelle N. , Spierer Lucas 
Published: June 2024

AbstractInhibitory control refers to the ability to suppress cognitive or motor processes. Current neurocognitive models indicate that this function mainly involves the anterior cingulate cortex and the inferior frontal cortex. However, how the communication between these areas influence inhibitory control performance and their functional response remains unknown. We addressed this question by injecting behavioral and electrophysiological markers of inhibitory control recorded during a Go/NoGo task as the ‘symptoms’ in a connectome-based lesion-symptom mapping approach in a sample of 96 first unilateral stroke patients. This approach enables us to identify the white matter tracts whose disruption by the lesions causally influences brain functional activity during inhibitory control. We found a central role of left frontotemporal and frontobasal intrahemispheric connections, as well as of the connections between the left temporoparietal and right temporal areas in inhibitory control performance. We also found that connections between the left temporal and right superior parietal areas modulate the conflict-related N2 event-related potential component and between the left temporal parietal area and right temporal and occipital areas for the inhibition P3 component. Our study supports the role of a distributed bilateral network in inhibitory control and reveals that combining lesion-symptom mapping approaches with functional indices of cognitive processes could shed new light on post-stroke functional reorganization. It may further help to refine the interpretation of classical electrophysiological markers of executive control in stroke patients.
Sustainable Governance: Board Sustainability Experience and the Interplay with Board Age for Firm Sustainability
Authors: Collevecchio Francesca , Temperini Valerio , Barba-Sanchez Virginia , Meseguer-Martinez Angel 
Published: June 2024

AbstractThe growing emphasis on sustainability in the business landscape has prompted scholars and industry practitioners to explore the role of corporate governance, particularly the board of directors, in promoting corporate sustainability. Companies are called upon to operate ethically and to redefine their objectives beyond mere economic pursuits to create social impacts that contribute to sustainability challenges. Corporate governance plays a key role in this regard, as it defines the purpose and ethical orientation of the firm, thereby shaping its sustainability. While previous research has primarily focused on observable board characteristics, this study delves into a critical yet underexplored aspect of sustainable boards, i.e., the sustainability experience. Drawing on the upper echelon and resource dependency theories, our research examines how the sustainability experience of board members influences a firm’s sustainability performance, investigating the moderating effect of board age. We analyzed European listed companies from 2014 to 2020, and our findings show that the effect of board sustainability experience on firm performance is contingent on board age. Specifically, our results show that younger boards amplify the positive effect of sustainability experience, while for older boards, this effect diminishes, up to the point of being completely mitigated, highlighting a potential misalignment between sustainability efforts and ethical business conduct. This study is pioneering in investigating the joint effects of board sustainability experience and board age on a firm’s sustainability, thus, providing valuable contributions to theory and practical recommendations for firms in director recruitment, as well as recommendations for regulatory practices.
Models of sub-national U.S. quasi-governmental organizations: implications for climate adaptation governance
Authors: Nix Paul , Goldstein Adam , Oppenheimer Michael 
Published: June 2024

AbstractThe politicization of climate change and the difficulty of achieving multi-level or sectoral stakeholder coordination are common institutional barriers to effective climate change adaptation governance outcomes. In the U.S., quasi-government organizations (QGOs) were designed to overcome such barriers, albeit traditionally for non-climatic purposes. This study’s objective is to illustrate how the design characteristics of QGOs may be useful for overcoming the above climate adaptation barriers. Methodologically, this paper analyzes six case studies, selected to illustrate the major characteristics of QGOs, of climate-focused and non climate-focused QGOs at the sub-national level in the U.S. Non climate-focused examples are included for comparison with, and to supplement, the limited number of QGOs currently working on climate efforts. For each case, this study focuses on eight design characteristics: seven that represent measures of political and financial independence, and one focused on board composition, to illustrate the extent to which QGOs enable multi-level and multi-sectoral stakeholder coordination. This study finds that among the assortment of existing QGO designs some are particularly well suited to overcoming either the politicization of climate adaptation policy or obstacles to enhancing policy coordination, while some reduce both, albeit to a lesser extent. Broadly, this paper concludes that QGOs can strengthen effective action by depoliticizing informational sources and fostering cross scale coordination of planning and implementation.