bluuebunny/crossref_metadata_2025 huggingface dataset:
When the "Matchmaker" Does Not Have Your Interest at Heart: Perceived Algorithmic Harms, Folk Theories, and Users' Counter-Strategies on Tinder
Authors: Alizadeh Fatemeh , Lawo Dennis , Stevens Gunnar , Zytko Douglas , Eslami Motahhare
Published: November 2024

On online platforms, algorithms help us build and manage our relationships. However, their invisible interventions might also pose harm to these connections. Dating platforms offer a prime example where, despite extensive research on human-inflicted harm, the potential harm from the algorithms themselves, and user strategies for mitigating them, remains largely unexplored. In our analysis of 7,043 reviews and interviews with 30 Tinder users, we unveiled how users perceive algorithmic harm as damaging self-esteem, sabotaging potential relationships, encouraging antisocial behavior, and misrepresenting or marginalizing certain identities. We introduce a new algorithmic folk theory, the
"conflict of interest"
theory, perceived to perpetuate these harms. This theory encapsulates users' sense of a contradiction between the dating platform's promise of finding the perfect partner (leading to discontinued use of Tinder) and its commercial interest in retaining users to increase revenue. Users suspected various algorithmic processes pursuant to this theory, such as (a) throttling profile visibility, (b) manipulating users' matches, and (c) recommending large quantities of profiles that will not lead to matches. They also described various strategies in resistance or defense of these suspected algorithmic processes, such as engaging in counter-intuitive behaviour to disrupt the unfavorable algorithmic processes or leveraging location based filtering for match variety and safety. We conclude by discussing how the perceived algorithmic harms can inform the development of new algorithmic implementations that balance both user and company interests.
Simplifying Distributed Neural Network Training on Massive Graphs: Randomized Partitions Improve Model Aggregation
Authors: Zhu Jiong , Reganti Aishwarya , Huang Edward W. , Dickens Charles , Rao Nikhil , Subbian Karthik , Koutra Danai
Published: November 2024

Distributed graph neural network (GNN) training facilitates learning on massive graphs that surpass the storage and computational capabilities of a single machine. Traditional distributed frameworks strive for performance parity with centralized training by maximally recovering cross-instance node dependencies, relying either on inter-instance communication or periodic fallback to centralized training. However, these processes create overhead and constrain the scalability of the framework. In this work, we propose a streamlined framework for distributed GNN training that eliminates these costly operations, yielding improved scalability, convergence speed, and performance over state-of-the-art approaches. Our framework (1) comprises independent trainers that
asynchronously
learn local models from locally available parts of the training graph and (2) synchronizes these local models only through periodic (time-based) model aggregation. Contrary to prevailing belief, our theoretical analysis shows that it is not essential to maximize the recovery of cross-instance node dependencies to achieve performance parity with centralized training. Instead, our framework leverages randomized assignment of nodes or super-nodes (i.e., collections of original nodes) to partition the training graph in order to enhance data uniformity and minimize discrepancies in gradient and loss function across instances. Experiments on social and e-commerce networks with up to 1.3 billion edges show that our proposed framework achieves state-of-the-art performance and 2.31

\(\times\)

speedup compared to the fastest baseline despite using less training data.
DIRformer: A Novel Image Restoration Approach Based on U-shaped Transformer and Diffusion Models
Authors: Hu Cong , Wei Xiao-Zhong , Wu Xiao-Jun
Published: November 2024

Image restoration (IR) involves the retrieval of missing or damaged image information and represents a significant challenge in the field of visual reconstruction. Currently, U-Net based Diffusion Models (DMs) display favorable results when utilized for IR tasks. However, the DM based on U-Net demonstrates shortcomings in capturing the global context for IR. To address this issue, we propose a Novel Image Restoration Approach Based on U-shaped Transformer and DMs (DIRformer). DIRformer enhances the modeling capacity for long-range dependencies within DMs. In particular, DIRformer replaces the traditional U-Net downsampling with Patch merging, dedicated to improving detail preservation, and replaces upsampling with Dual up-sample, strategically designed to alleviate checkerboard artifacts. Besides, as a lightweight and versatile transformer-based solution for IR, DIRformer incorporates time and degradation mapping into the transformer design, all while preserving the fundamental U-shaped structural framework. We assess the efficacy of DIRformer in a multi-tasking IR setting across four datasets. The experimental performance illustrates that DIRformer achieves competitive performance on distortion metrics, including PSNR and SSIM. Remarkably, our proposed approach is almost 25

\(\times\)

smaller and 2

\(\times\)

faster than the existing methods while achieving comparable high performance.
Demonstrative Learning for Human-Agent Knowledge Transfer
Authors: Dongye Xiaonuo , Jiang Haiyan , Weng Dongdong , Zhang Zhenliang
Published: November 2024

Demonstrative learning in virtual reality (VR) is a pivotal learning strategy for knowledge transfer for embodied agents. While existing studies have extensively explored agents’ knowledge transfer through self-demonstrative learning (SDL) or teacher-demonstrative learning (TDL), there has been limited focus on a system that integrates both paradigms. This article proposes a comprehensive system that combines the SDL paradigm with the TDL paradigm in VR from a top-down perspective. The system involves using directed probabilistic graphs (DPGs) for knowledge representation, constructing detectors and actuators based on object fluents and atomic actions, representing knowledge acquired from both learning paradigms on the DPGs, and incorporating knowledge integration and visualization. Through system evaluation, we show the advantages of integrating two demonstrative learning paradigms, including increased learning efficiency, mitigating demonstrator’s deficiencies, and more logical task execution. The study also reveals that a dynamically decreasing fusion factor with the learning progresses, performs well across different correct percentages of teacher demonstrations. Additionally, we show a more decentralized demonstration in the middle of the agent’s learning progress maximizing learning efficiency when demonstrating only a few atomic actions. Finally, we assess the system’s generalizability and delineate its boundaries. With the ongoing development and the increasing availability of human data in VR, we anticipate that our system can be applied to future scenarios of efficient human-agent knowledge transfer in human-agent symbiosis.
Budget-aware Query Tuning: An AutoML Perspective
Authors: Wu Wentao , Wang Chi
Published: November 2024

Modern database systems rely on cost-based query optimizers to come up with good execution plans for input queries. Such query optimizers rely on cost models to estimate the costs of candidate query execution plans. A cost model represents a function from a set of cost units to query execution cost, where each cost unit specifies the unit cost of executing a certain type of query processing operation (such as table scan or join). These cost units are traditionally viewed as constants, whose values only depend on the platform configuration where the database system runs on top of but are invariant for queries processed by the database system. In this paper, we challenge this classic view by thinking of these cost units as variables instead. We show that, by varying the cost-unit values one can obtain query plans that significantly outperform the default query plans returned by the query optimizer when viewing the cost units as constants. We term this cost-unit tuning process 'query tuning' (QT) and show that it is similar to the well-known hyper-parameter optimization (HPO) problem in AutoML. As a result, any state-of-the-art HPO technologies can be applied to QT. We study the QT problem in the context of anytime tuning, which is desirable in practice by constraining the total time spent on QT within a given budget-we call this problem budgetaware query tuning. We further extend our study from tuning a single query to tuning a workload with multiple queries, and we call this generalized problem budgetaware workload tuning (WT), which aims for minimizing the execution time of the entire workload. WT is more challenging as one needs to further prioritize individual query tuning within the given time budget. We propose solutions to both QT and WT and experimental evaluation using both benchmark and real workloads demonstrates the efficacy of our proposed solutions.
Racial Disparities in Preoperative Breast MRI Use and Surgical Margin Outcomes among Patients with Recently Diagnosed Breast Cancer
Authors: Simmons Amber , Han Lynn K. , Reiner Jeffrey S. , Mango Victoria L. , Sevilimedu Varadan , Pinker Katja , Zhang Hong , Moo Tracy-Ann , Eskreis-Winkler Sarah
Published: November 2024

Black patients with recently diagnosed breast cancer were less likely to undergo preoperative breast MRI and more likely to have positive surgical margins when preoperative MRI was not performed, in comparison with White patients.
Review—Carbon Negative Technologies: Carbon Capture, Sequestration, and Conversion
Authors: Rangarajan Murali , Pillai Zeena Subramonia , Subramanian Vaidyanathan Ravi
Published: November 2024

Carbon dioxide (CO2) capture and storage are now an essential reality that we are required to adapt to address global climate change concerns. Adapting carbon neutrality or carbon negative processes in mainstream energy generation, manufacturing, and transportation is possible using current technologies, albeit with some limitations. Carbon neutral technologies (CNTs) can be seamlessly integrated with existing systems as well as green technologies to ensure that carbon capture gets a boost. On-land and undersea storage are realistic possibilities since there is immense potential to lock atmospheric CO2 using existing technologies. Thermocatalytic, electrochemical, photo(electro)catalytic, and biological—based approaches do offer promising options, but require optimization of different parameters to ensure commercial viability, scalability, and safety. The role of electrochemical process specifically is examined. New directions for further research in the area of electrochemical—driven applications are identified and opportunities in three areas, viz., electrocatalysts design, pilot scale integrated systems, and simultaneous CO2 capture and conversion, are discussed in detail. The global implementation of any CNTs requires dramatic policy shift, unequivocal support from the world governments, public acceptance, backing from industries, and unwavering financial backing from stakeholders to ensure that there is a real chance to address climate change issues.
Convergent and divergent immune aberrations in COVID-19, post-COVID-19-interstitial lung disease, and idiopathic pulmonary fibrosis
Authors: Tourki Bochra , Jia Minxue , Karampitsakos Theodoros , Vera Iset M. , Arsenault Alyssa , Fatima Zainab , Perrot Carole Y. , Allen Dylan , Farsaei Forouzandeh , Rutenberg David , Bandyopadhyay Debabrata , Restrepo-Jaramillo Ricardo , Qureshi Muhammad R. , Patel Kapilkumar , Tzouvelekis Argyris , Kapetanaki Maria G. , Juan-Guardela Brenda M. , Kim Kami , Benos Panayiotis V. , Herazo-Maya Jose D.
Published: November 2024

Changes in the 50-gene signature, reflective of increase in CD14+HLA-DRlowCD163+ monocytes and decrease in CD4 and CD8 T cells, are associated with increased mortality in COVID-19. A reversal of this pattern can be seen in post-COVID-19-ILD, whereas its persistence can be seen in IPF. Modulating the imbalance between HLA-DRlow monocytes and T cell subsets should be investigated as a potential strategy to treat pulmonary fibrosis associated with severe COVID-19 and progressive IPF.
Averaged oxygen desaturation improves the prognostic value of the six-minute walk test in elderly patients with heart failure
Authors: Sunayama Isamu , Min Kyung-Duk , Orihara Yoshiyuki , Ohno Junichi , Matsumoto Yuki , Daimon Aika , Soyama Yuko , Manabe Eri , Oboshi Makiko , Azuma Kohei , Sugahara Masataka , Eguchi Akiyo , Naito Yoshiro , Suna Shinichiro , Asakura Masanori , Ishihara Masaharu
Published: November 2024

This study evaluates the use of Δ[Formula: see text]-Ex, measured during the six-minute walk test (6MWT), as a complementary prognostic marker to the six-minute walk distance (6MWD) in elderly patients with heart failure. We hypothesize that combining Δ[Formula: see text]-Ex with 6MWD will improve the predictive accuracy for cardiovascular outcomes, offering a practical, noninvasive method for risk stratification and enhancing clinical decision-making for this patient population.
Enhancing the Quality of Research Synopsis of International Students Through Peer Feedback: A Case Study
Authors: Rehman Nadia , Huang Xiao , Mahmood Amir , Maqbool Samra , Javed Saima
Published: November 2024

The role of peer feedback in academic writing has garnered increasing attention from educators and research supervisors in recent years. Nevertheless, limited information exists about the perceptions and experiences of international doctoral students concerning the learning outcomes derived from giving and receiving feedback on research synopsis writing. This case study employs a variety of data sources, including research synopsis drafts, written peer evaluations, and semistructured interviews, to explore how 11 junior and seven senior doctoral candidates at Chinese universities benefit from receiving and providing feedback on their peers’ research synopses, respectively. Through the analysis of the interview data, four emergent themes related to student learning were generated through the exchange of peer feedback: (1) enhancing research synopsis writing awareness, (2) progressing in synopsis writing drafts, (3) improving research skills with peer feedback, and (4) fostering reflective and critical learning. These findings contribute to a deeper understanding of the potential educational opportunities that arise from exchanging peer evaluations in scholarly work.
A Kinetic and Thermodynamic Study of Cationic Thiazine Dye Removal From Aqueous Solution by Date Stones Variety Ghars
Authors: Gherbia Abdelali , Sahel Djamel , Bouabidi Abdallah , Chergui Abdelmalek
Published: November 2024

Date stones represent an unused resource that is often incinerated or disposed of directly as waste. Therefore, great attention has been paid to transforming it into useful products. This study was conducted to evaluate the ability of activated carbon prepared from the stones of one of the date varieties, called “Ghars,” as an agricultural waste to remove a basic dye, methylene blue (MB), from aqueous solutions. The surface characteristics of prepared activated carbon Ghars stones (ACGS) were characterized using scanning electron microscope (SEM) and Fourier transform infrared (FTIR) spectroscopy. Physical and chemical factors affecting MB adsorption, such as contact time, the mass of adsorbent, potential of hydrogen (pH) value, and initial concentration of the solution, were studied in a batch system. Isotherm equilibrium data are well described by the Freundlich model (R2 = 0.98), and the experimental adsorption capacity was found to be (qe.exp = 130.3 mg/g) at 298 K. The kinetic study indicates that the adsorption process of MB follows the pseudo‐second‐order (PSO) model. ΔH° (19.94 J/mol) and ΔG° (−1.101, −1.127, −1.430, and −1.546 kJ/mol) values revealed that the adsorption of MB on ACGS was endothermic nature, feasible, and spontaneous. The positive value of ∆S° (15.67 kJ/mol) confirmed the increased in the randomness at the solid‐solution interface during the adsorption process of MB on ACGS. MB adsorption/desorption experiments demonstrated the reusability of ACGS for five consecutive cycles. The results showed that ACGS developed from agricultural waste could be successfully used to remove cationic organic pollutants from wastewater.
Intramammary Tumor Location and Ipsilateral Lymphatic Spread in Early Breast Cancer Patients Using One‐Step Nucleic Acid Amplification (OSNA) Assay
Authors: Cordeiro Mariana Robalo , Gante Inês , David Daniela , Gomes Ana , Figueiredo-Dias Margarida
Published: November 2024

Establishing an accurate prognosis for women diagnosed with breast cancer (BC) is extremely challenging. Axillary lymph node (ALN) evaluation is considered of major prognostic value. The one‐step nucleic acid amplification (OSNA) assay is currently used for assessing axillary sentinel lymph node (SLN) status in BC. Additionally, total tumor load (TTL) may help predict further metastatic axillary involvement beyond the SLN. The prognostic value of primary BC location remains controversial due to lack of consensus on the biological differences among tumors at various sites. Evidence suggests that tumors in the internal quadrants (INLs) have worse prognosis compared to those in the external quadrants. Furthermore, ALN involvement is believed to be mainly associated with external quadrant tumors, mainly due to the lymphatic drainage system of the breast. This pilot observational study, despite lacking a control group and having a relatively small sample size, is the first to evaluate the potential relationship between primary BC location and ALN metastasis using the OSNA assay. A sample of consecutive BC patients undergoing axillary staging with the OSNA assay were included. Tumors were categorized into three groups based on primary location: external quadrants and axillary tail (EXL), INLs, and nipple and areola location (NAL). Although not statistically significant, the INL group exhibited a higher mean TTL. Additionally, no significant differences were observed between groups concerning SLN detection techniques, SLN status, number of metastatic SLN, or mean TTL. These findings support the use of the innovative tracer superparamagnetic iron oxide regardless of tumor site. This study underscores the importance of understanding the relationship between BC location and ALN status, which may improve prognostic stratification and targeted therapies based on tumor site. If these observations are confirmed in larger, multicentric studies, the potential conclusions may shift the paradigm of INL tumor treatment, significantly impacting clinical practice and research.
CSTF2 Supports Hypoxia Tolerance in Hepatocellular Carcinoma by Enabling m6A Modification Evasion of PGK1 to Enhance Glycolysis
Authors: Zhang Qiangnu , Zhang Yusen , Fu Chuli , He Xiaoyan , Huang Zuotian , Wu Geyan , Wei Teng , Jin Wen , Yan Lesen , Wu Meilong , Peng Gongze , Fan LinLan , Li Mingyue , Guo Yuehua , Bi Jiangang , Bai Yu , Roessler Stephanie , Yan Guang-Rong , Liu Liping
Published: November 2024

Cleavage stimulation factor subunit 2 (CSTF2) is a fundamental factor in the regulation of 3′-end cleavage and alternative polyadenylation of pre-mRNAs. Previous work has identified a tumor-promoting role of CSTF2, suggesting that it may represent a potential therapeutic target. In this study, we aimed to elucidate the mechanistic function of CSTF2 in hepatocellular carcinoma (HCC). CSTF2 upregulation was frequent in HCC, and elevated levels of CSTF2 correlated with poor patient prognosis. Although CSTF2 inhibition did not suppress HCC growth under nonstress conditions, it supported tolerance and survival of HCC cells under hypoxic conditions. Mechanistically, CSTF2 increased phosphoglycerate kinase 1 (PGK1) protein production to enhance glycolysis, thereby sustaining the energy supply under hypoxic conditions. CSTF2 shortened the 3′ untranslated region of PGK1 pre-mRNA by binding near the proximal polyadenylation site. This shortening led to a loss of N6-methyladenosine (m6A) modification sites that are bound by YTH m6A RNA-binding protein F2 and increase degradation of PGK1 mRNA. Concurrently, hypoxia increased m6A modification of PGK1 mRNA near the proximal polyadenylation site that was recognized by the YTH m6A RNA-binding protein C1, which recruited CSTF2 to enhance the shortening of the PGK1 3′ untranslated region. A small-molecule screen identified masitinib as an inhibitor of CSTF2. Masitinib counteracted PGK1 upregulation by CSTF2 and suppressed the growth of HCC xenograft and patient-derived organoid models. In conclusion, this study revealed a function of CSTF2 in supporting HCC survival under hypoxia conditions through m6A modification evasion and metabolic reprogramming, indicating that inhibiting CSTF2 may overcome hypoxia tolerance in HCC.

Significance: Targeting CSTF2 inhibits hepatocellular carcinoma survival in hypoxic microenvironments, which may be a promising therapeutic strategy for treating liver cancer.
Peritumoral Venous Vessels: Autobahn and Portal for T Cells to Melanoma Brain Metastasis
Authors: Izar Benjamin , Kim Minah
Published: November 2024

Melanoma brain metastasis is associated with high morbidity and mortality and remains a major clinical challenge. Despite recent successes with combination immune checkpoint inhibitors in the treatment of affected patients, the mechanistic underpinnings of T-cell entry and response to these drugs in brain metastasis are poorly understood. Using real-time intravital microscopy, Messmer and colleagues identified peritumoral venous vessels (PVV) as critical sites for T-cell entry into brain metastases, a process accelerated by immune checkpoint inhibitor treatment. The expression of intercellular adhesion molecule 1 on PVVs was found to be important for T-cell recruitment in preclinical models and associated with increased T-cell infiltration in human brain metastatic lesions. This study highlights PVVs as key vascular entry points for T cells into brain metastases, laying the foundation for enhancing the efficacy of cancer immunotherapies.
Genomic, Epigenomic, and Transcriptomic Inter- and Intratumor Heterogeneity in Desmoid Tumors
Authors: De Bellis Chelsea , Vennam Sujay , Eeles Christopher , Rahimizadeh Pegah , Cates Justin , Stricker Thomas , Hoffman Jenny , Ganjoo Kristen , Charville Gregory W. , Haibe-Kains Benjamin , van de Rijn Matt , Przybyl Joanna
Published: November 2024

Purpose:

Desmoid tumors are bland fibroblastic tumors that do not metastasize but have a high rate of local recurrence. Previously published studies proposed two different transcriptomic signatures to predict relapse. Molecular heterogeneity has been well established in high-grade sarcomas, but little is known about molecular variability within locally aggressive tumors such as desmoids.

Experimental Design:

We performed transcriptomic profiling of 31 specimens from 20 primary desmoid tumors to identify genes predictive of relapse. We also performed multiomic analysis including DNA methylation, copy-number alterations, point mutations, and gene expression on 24 specimens from different regions of primary and recurrent desmoid tumors from three patients (7–9 specimens per patient).

Results:

We observed highly variable expression of transcriptomic prognostic signatures both in patients who did and did not progress. Signatures associated with favorable and unfavorable outcomes were detected in different regions within the same tumor. Further multiomic studies showed remarkable intra- and intertumor heterogeneity of genomic, epigenomic, and transcriptomic patterns. The transcriptomic profiles showed the highest degree of variability within tumors and between primary and recurrent tumors from the same patient.

Conclusions:

This study shows an unexpected degree of intra- and intertumor heterogeneity in desmoid tumors. Our analysis indicates that molecular analysis of a single-tumor biopsy may underestimate the magnitude of molecular alterations in desmoid tumors. Our study also shows that recurrent desmoid tumors acquire multiple new molecular alterations. Thus, molecular heterogeneity is an important consideration in drug development and validation of prognostic and predictive biomarkers for desmoid tumors.
A Tumor-Naïve ctDNA Assay Detects Minimal Residual Disease in Resected Stage II or III Colorectal Cancer and Predicts Recurrence: Subset Analysis from the GALAXY Study in CIRCULATE-Japan
Authors: Nakamura Yoshiaki , Kaneva Kristiyana , Lo Christine , Neems Daniel , Freaney Jonathan E. , Boulos Hala , Hyun Seung Won , Islam Farahnaz , Yamada-Hanff Jason , Driessen Terri M. , Sonnenschein Anne , DeSantis Dana F. , Kotani Daisuke , Watanabe Jun , Kotaka Masahito , Mishima Saori , Bando Hideaki , Yamazaki Kentaro , Taniguchi Hiroya , Takemasa Ichiro , Kato Takeshi , Sangli Chithra , Tell Robert , Blidner Richard , Yoshino Takayuki , Sasser Kate , Oki Eiji , Nimeiri Halla
Published: November 2024

Purpose:

Analysis of ctDNA may enable early identification of patients likely to relapse, presenting an opportunity for early interventions and improved outcomes. Tumor-naïve plasma-only approaches for minimal residual disease (MRD) assessment accelerate turnaround time, enabling rapid treatment decisions and ongoing surveillance.

Experimental Design:

Plasma samples were obtained from 80 study participants with stage II or III colorectal cancer selected from CIRCULATE-Japan GALAXY. MRD status was assessed using a tumor-naïve ctDNA assay (xM) that integrates methylation and genomic variant data, delivering a binary call. MRD was assessed at 4 weeks postsurgery [landmark time point (LMT)] using methylation and genomic variant data and longitudinally (median, 22.1 months) using only methylation data.

Results:

At LMT, 69/80 study participants were evaluable (36 recurrent; 33 nonrecurrent). Of recurrent study participants, 22/36 had detectable ctDNA (MRD-positive) at LMT and 29/33 nonrecurrent study participants had undetectable ctDNA (MRD-negative), yielding a clinical sensitivity of 61.1% and specificity of 87.9%. Additionally, 74 study participants were evaluable for longitudinal performance with a clinical sensitivity of 83.3% and specificity of 89.5%. The median lead time from the first MRD-positive result to recurrence was 4.77 months overall, and 5.30 months for study participants with no adjuvant treatment. At 12 weeks postsurgery, MRD status strongly correlated with disease-free survival (adjusted HR, 9.69), outperforming carcinoembryonic antigen correlation (HR, 2.13).

Conclusions:

This tumor-naïve MRD assay demonstrated clinically meaningful performance at LMT and longitudinally, accurately predicting clinical recurrence. MRD status was a stronger prognostic biomarker for disease-free survival compared with standard-of-care carcinoembryonic antigen.
HPV and p53 Status as Precision Determinants of Head and Neck Cancer Response to DNA-PKcs Inhibition in Combination with Irradiation
Authors: Hayrapetyan Liana , Roth Selina M. , Quintin Aurélie , Hovhannisyan Lusine , Medo Matúš , Riedo Rahel , Ott Julien G. , Albers Joachim , Aebersold Daniel M. , Zimmer Yitzhak , Medová Michaela
Published: November 2024

Major risk factors of head and neck squamous cell carcinoma (HNSCC) are tobacco use and human papillomavirus (HPV). HPV E6 oncoprotein leads to p53 degradation, whereas HPV-negative cancers are frequently associated with TP53 mutations. Peposertib is a potent and selective, orally administered small-molecule inhibitor of the catalytic subunit of the DNA-dependent kinase (DNA-PKcs), a key regulator of nonhomologous end joining (NHEJ). NHEJ inhibition along with irradiation (IR)-induced DNA double-strand breaks has the potential to increase antitumor treatment efficacy. In this study, we investigated the responses of a panel of HNSCC models with distinct HPV and p53 status to treatments with IR, DNA-PKcs inhibition, and their combination in vitro and in vivo. IR-induced DNA damage combined with peposertib administration shortly before IR results in decreased cell viability and proliferation and causes DNA repair delay in all studied HNSCC cell lines. However, our data confirm that the actual cell fate upon this treatment is determined by cellular p53 and/or HPV status. Cells lacking functional p53 due to its degradation by HPV or due to a loss-of-function mutation are arrested in the G2/M phase of the cell cycle and eliminated by apoptosis, whereas p53-proficient HNSCC cell lines preferentially undergo senescence. This is also recapitulated in vivo, where HPV+ UD-SCC-2 xenografts display stronger and more durable responses to the combined treatment as compared with p53 wild-type UM-SCC-74A tumors. In conclusion, DNA-PKcs inhibitor peposertib should be further studied as a potential radiosensitizer for HNSCCs, taking into consideration the genetic background and the HPV status of a particular tumor.
Sympathetic Neurons Promote Small Cell Lung Cancer through the β2-Adrenergic Receptor
Authors: FNU Tala , Shi Peiguo , Zhang Wanwei , Chung Sanny S.W. , Damoci Christopher B. , Fang Yinshan , Chen Qi-Yue , Saqi Anjali , Huang Yuefeng , Wu Xuebing , Lu Chao , Yang Dian , Wang Timothy C. , Que Jianwen
Published: November 2024

The vagal nerve is linked to tumorigenesis in multiple tissues, including small cell lung cancer (SCLC). However, the role of sympathetic neurons in SCLC development remains unknown. In this study, we observed a significant reduction in tumor growth following chemical denervation of local sympathetic nerves in a mouse model of SCLC. Further study identified that β2-adrenergic receptor (ADRB2) expression on cancer cells mediated the cross-talk with nerve fibers. Genetic deletion or pharmacological inhibition of ADRB2 led to reduced tumor growth and improved survival. Moreover, blocking ADRB2 also reduced the growth of human SCLC organoids and xenografts. Further studies revealed that ADRB2 promoted cancer cell expansion through activating protein kinase A (PKA) signaling. Consistently, inhibition of PKA also reduced the growth of SCLC cells. These findings offer the initial insight into the role played by sympathetic neurons in the development of SCLC and may open a new therapeutic avenue to treat this deadly malignancy.

Significance:

SCLC is highly aggressive, with limited effective treatment options. We show that ablating sympathetic nerves or inhibiting the ADRB2 receptor slows SCLC progression and prolongs survival in mice. Additionally, ADRB2 inhibition reduces the growth of human SCLC organoids and xenografts by disrupting PKA signaling, identifying a new therapeutic target.
Supplementary Figure Legends 1-6 from Acetalax (Oxyphenisatin Acetate, NSC 59687) and Bisacodyl Cause Oncosis in Triple-Negative Breast Cancer Cell Lines by Poisoning the Ion Exchange Membrane Protein TRPM4
Authors: Mizunuma Makito , Redon Christophe E. , Saha Liton Kumar , Tran Andy D. , Dhall Anjali , Sebastian Robin , Taniyama Daiki , Kruhlak Michael J. , Reinhold William C. , Takebe Naoko , Pommier Yves
Published: November 2024

Legends for the Supplementary figures.
Supplementary Figure 6 from Acetalax (Oxyphenisatin Acetate, NSC 59687) and Bisacodyl Cause Oncosis in Triple-Negative Breast Cancer Cell Lines by Poisoning the Ion Exchange Membrane Protein TRPM4
Authors: Mizunuma Makito , Redon Christophe E. , Saha Liton Kumar , Tran Andy D. , Dhall Anjali , Sebastian Robin , Taniyama Daiki , Kruhlak Michael J. , Reinhold William C. , Takebe Naoko , Pommier Yves
Published: November 2024

Exogenous TRPM4 expression sensitizes TRPM4 negative and acetalax-resistant MDAMB231 and MDAMB436 cells to acetalax.
Leptolaimus petrelense n. sp. (Plectida: Leptolaimidae), a new nematode species from the Petrel lagoon, central Chile
Authors: Bastidas Brynelly , Morales-Montero Patricia , Holovochov Oleksandr , Sulbarán Yoelvis , San-Blas Ernesto
Published: November 2024

During a survey on the biodiversity of nematodes in the Petrel lagoon (central Chile), a population of Leptolaimus was found in sediment samples. Morphological, morphometric and molecular data indicated that the recovered nematode is a new species. This nematode belongs to the group in which the males only have four pre-cloacal tubular supplements present, and females have no supplements. The new species can be separated from the other species of the group by the length of both males and females (843-1060 μm), the tail length (118-208 μm), the shape of the gubernaculum, and the arrangement of the caudal setae in males (a pair of ventral precloacal setae at level of spicules, a pair of dorsal post-cloacal setae, two subventral and two subdorsal caudal pairs. The differences from closely related species L. gerlachi, L. praeclarus, L. octavus, L. hydrothermalis, L. vipriensis, and L. hadalis are discussed. The recovered population is described herein as Leptolaimus petrelense n. sp.
Nakba and the US-Israel Imperial Regime
Authors: Sussman Gerald
Published: November 2024

The US-Israeli genocide is best understood as the end game of empire, the culmination of failed Anglo-American and Zionist policies in the Middle East and, indeed, virtually the entire non-Western world. It is the outcome of a US-sponsored apartheid system in Israel, largely carried out by the IDF and other militarist forces in the West Bank, East Jerusalem, Gaza, and Israel itself and funded by American financial assistance and weapons transfers to the Israeli army. The threats of multipolarity to US/NATO hegemony, Britain being the major junior partner, pushed the Trump and Biden administrations, along with the British Tories and post-Corbyn Labour Party, to support de facto the “final solution” in Gaza and the rest of Palestine. This article puts the Israeli assault on the people of Gaza, the Hamas-led attack on October 7 being the main pretext, in historical perspective. It argues that it is a logical sequence of the pre-war Zionist idea of an exclusive Jewish state and US and UK post-war power politics in the Middle East and in two imperial states’ respective domestic electoral politics.
Marxism and Ukraine’s Struggle for Independence and Self-Determination
Authors: Harris Jerry
Published: November 2024

This article traces the historic development of socialist thought on the importance of upholding independence and self-determination for oppressed nations. The examination starts with Marx on independence for Ireland and Lenin’s political and theoretical principals on nations oppressed by the Tsarist dictatorship. It proceeds to Ho Chi Minh’s address to the Comintern, Chou En Lai at the Bandung Conference, and Mao’s writings on contradictions. This article then applies these principals to the Russian invasion of Ukraine, debates in the Left, and the need to support Ukraine.
The Ukrainian Crisis: a Game-Theoretic Analysis of the Complex Interplay between Ukraine, Russia, and the West
Authors: Alibeli Madalla Awad
Published: November 2024

This study gives a general overview of the Ukrainian crisis through the lens of game theory, examining the motivations and constraints of Ukraine, Russia, and the West. Game theory provides structural concepts that explore trust, cooperation, risk-taking, and coordination challenges within the crisis. The analysis considers the impact of power imbalances and external factors like alliances and historical ties, strategic behavior, and other factors. The article concludes by highlighting key takeaways from the game-theoretic approach that can provide a roadmap towards a deeper analysis, and a structural diplomatic approach to conflict resolution.
China’s Connectivity Politics vis-à-vis Global Challenges: a Roadmap to Strategic Development?
Authors: Chajdas Tymoteusz
Published: November 2024

This article examines the transformative role of connectivity politics amid global upheaval, focusing on China’s Belt and Road Initiative (BRI) and Western connectivity strategies. It explores how China’s strategic use of connectivity has enabled it to navigate crises and exert global influence, while also analyzing the strengths and weaknesses of both Chinese and Western approaches. The article highlights the importance of multilateral collaboration, environmental sustainability, local empowerment, and adaptive policies for future connectivity initiatives. By synthesizing lessons from both the BRI and Western models, the article proposes a balanced and sustainable framework for global development, offering insights into fostering a more interconnected, equitable, and resilient world.
The Value of Negotiation Research in Perilous Times
Authors: Druckman Daniel , Wagner Lynn
Published: November 2024

Over the past 30 years, articles in this journal and elsewhere have offered insights and advice about making our world more peaceful through negotiation. This time in history provides a moment for reflection about the contributions we have made. This article shows how research findings add value for solving practical problems. Examples include two contemporaneous conflicts, the Russian invasion of Ukraine and the war in Gaza. We also explore issues that could trigger tipping points and spur greater global unrest, as well as avenues that could help reduce growing tensions: the world of international diplomacy, global climate diplomacy, insights on summitry, and negotiation skills training. These contributions are evaluated for ease of application, attentiveness of practitioners, and impact. We conclude optimistically: While research will not save us from the horrors of war, it can enhance our understanding of how to make the world a little safer for peace.
Penguin Books
Authors: Graham Tim
Published: November 2024

This article is an edited version of a public lecture that addressed three main areas of the history of Penguin Books Ltd: the origin and initial history of the company and its books; some aspects of the development of the design of the books; and the impact the publisher had on 20th-century society, principally in the UK. The article argues that this impact was greater than that of any other publisher in the last century.
A Typology of Authorship
Authors: Span Madeleine
Published: November 2024

The growing share of self-publishing titles on the book market has sparked debates about their position within the literary sphere. Although some consider self-publishing to be a parallel universe in its own right, our understanding of self-publishing’s links to traditional structures is still evolving. This study showcases three distinct types of perspectives. The first type strategically utilizes self-publishing to build authorial renown and increase their likelihood of securing a contract with a royalty publisher. The second type makes use of self-publishing to measure the quality of authors’ work, assessing the work’s popularity with readers and comparing its quality with that of competing authors and titles. Finally, the third type sees self-publishing as a way to preserve creative autonomy and self-determined authorial work. Drawing further on the broader sociocultural context of these findings, the research contributes to our understanding of self-publishing’s diverse landscape as well as its implications for the contemporary literary sphere.
Amino acid requirements of yellow mealworm and black soldier fly larvae
Authors: Spranghers T. , Moradei A. , Vynckier K. , Boudrez M. , Pinotti L. , Ottoboni M.
Published: November 2024

In order to achieve optimal growth and health of farm animals, a different amount/ratio of essential amino acids in the feed is necessary in each phase of life. Knowledge about which amino acids are essential and in which quantities/proportions they are best administered has already greatly advanced the pig and poultry sector and is still being generated today. For the still young, rapidly developing insect sector, this knowledge could mean a major step forward towards breeding optimization. Therefore, in this research the needs of the 2 most commercially reared insect species, namely mealworms (Tenebrio molitor) (MW) and black soldier fly larvae (Hermetia illucens) (BSF), were investigated. The focus was on requirements for lysine, methionine, threonine, phenylalanine and tryptophan based on evidence from the literature and those of pigs. Semi-artificial diets based on at least 25% wheat bran (MW) and chicken feed/water (30/70) (BSF) (basic feed important for structure and certain micronutrients) supplemented with sugar and synthetic amino acids were tested. The diets were isoenergetic and isoproteinous. Of the amino acids studied, one was administered in different doses per experiment. The non-essential glutamic acid was used as a substitute at lower doses. Growth, as measured by weight gain, and survival were observed. The following results were for MW and BSF respectively. For lysine from a content of 0.35 g/100 g diet and 0.53 g/100 g diet no extra growth was noticeable. For methionine this was from 0.13 g/100 g and 0.16 g/100 g. Each time more threonine was given, a significant difference could be noticed and the minimum doses were around 0.42 g/100 g and 0.49 g/100 g. With tryptophan, for MW, there were no differences between the different concentrations. At the lowest dose of 0.06 g/100 g the maximum growth was already reached, whereas for BSF this was at 0.13 g/100 g.
Sex Robot Utopianism and the Transhumanist Vision: A Critical Reflection
Authors: Kwan Kai-man
Published: November 2024

The sex robots (or sexbots) are coming, and this has generated a lot of discussion. The scholarly debate on love & sex with sexbots has been ignited mostly by David Levy’s book in 2007, Love + Sex with Robots: The Evolution of Human-Robot Relationships. There exist many perspectives on sexbots, and one way to assess them is to view this as an embodiment of the transhumanist or posthumanist vision (see Michael Hauskeller’s book, Sex and the Posthuman Condition, in 2014). Some enthusiasts for sexbots such as David Levy espouse a kind of sex robot utopianism that largely mirrors the transhumanist vision of posthuman transformation. Thus, this essay will first introduce transhumanism as well as the major philosophical and theological criticisms of transhumanism. In a second step, it will introduce Levy’s sex robot utopianism and then critically assess his arguments. The critical discussions of both parts will prove to be mutually illuminating and reinforcing.
A Requiem for “Jadidism”? Debates on Islamic Education in Contemporary Tatarstan
Authors: Almazova Leila , Kemper Michael
Published: November 2024

Over the last two decades, the public discourse on Islam in Tatarstan has seen a shift from celebrating “Jadidism” to a new emphasis on “Qadimism”. This paper explores the Tatar national movement’s use of “Jadidism” in the 1990s and 2000s and then reconstructs the “Qadimist” countertrend which started to gain visibility with the works of DUM RT deputy mufti Valiulla Yakupov (d. 2012), and which became dominant in the religious establishment of DUM RT under Mufti Kamil’ Samigullin (in office since 2013). In the second part of the paper we trace the marginalization of “Jadid” literature in Tatarstan’s Islamic teaching institutions. We argue that also “Qadimism”, as the discursive counterpart of “Jadidism”, has undergone changes in scope and meaning over time, and eventually became a self-ascription of the current Islamic leadership. Furthermore, our paper compares the attack on “Jadidophilia” by religious leaders in Tatarstan with the ongoing critique of “Jadidophilia” by Western academic scholars.
Conflict and Context: Jadidism, Pan-Islamism, and the Muslims of Akmolinsk at the Beginning of the 20th Century
Authors: Shabley Pavel
Published: November 2024

This article analyzes a conflict between the imam of Akmolinsk’s Second Congregational Mosque Hujjat Mahmudov and the Tatar merchant Nur-Muhammad Zabirov. The conflict took place in 1912–1913, and attracted the attention of the public at large, editorial boards of Muslim newspapers, and the Russian colonial administration. The depictions of the conflict were contradictory and depended on who was telling the story: the immediate participants, residents of Akmolinsk, or external observers. When the imam accused the Tatar merchant of ignorance and a grossly over-extravagant lifestyle, the merchant’s defenders immediately accused the imam of spreading forbidden innovations and selling banned literature, i.e., the works by the Kazakh writer Mir-Zhaqïp Dulatov and the editor of the newspaper Waqït, Fatih Karimi. These works were regarded by imperial officials as politically dangerous on account of containing false information about the Romanov Dynasty, as well as Pan-Turkic and Pan-Islamic ideas. At first glance, the Akmolinsk story appears to illustrate how Muslims themselves made use of the imperial discourse about the threat of jadidism and Pan-Islamism to eliminate their enemies; but it also exhibits a series of distinct peculiarities. My aim is to show that it is not so much the conflict as such that is important, but rather the context in which it arose. A careful study of this context allows us to understand the principles by which the local society functioned. Focusing on specific representations of the conflict (newspaper accounts, the point of view of imperial bureaucrats, the petitions of the immediate participants), we ignore the epistemic value of other sources – for example, the opinions of local Muslims who do not necessarily describe what happened through the prism of fundamental contradictions and imply, among other things, the confrontation between so-called reformers and traditionalists. The Muslims of Akmolinsk, like those of other regions of the Russian Empire, were aware of the nature of external threats and challenges; however, they could also perceive them based on their own rationality as expressed in their prevailing cultural and everyday life. In some cases, that rationality was draped in pragmatism; in others, it stemmed from an attempt to protect cultural self-sufficiency – that is, a specific world of ideas and values; in yet others, it was justified by the need to carry out those small reforms and changes that could fit organically into the customary course of things.