bluuebunny/crossref_metadata_2025 huggingface dataset:
Symplectic quantization and general constraint structure of a prototypical second-class system
Authors: Gomez Ignacio S. , Pandey Vipul Kumar , Thibes Ronaldo
Published: December 2024

We discuss a general prototypical constrained Hamiltonian system with a broad application in quantum field theory and similar contexts where dynamics is defined through a functional action obeying a stationarity principle. The prototypical model amounts to a Dirac–Bergmann singular system, whose constraints restrict the actual dynamics to occur within a differential submanifold, as is the case in the major part of field theoretical models with gauge symmetry. We apply the Dirac–Bergmann algorithm in its full generality unraveling a total of 4m second-class constraints and obtain the corresponding Dirac brackets algebra in phase space. We follow with the Faddeev–Jackiw–Barcelos–Wotzasek approach in which the geometric character of the mentioned submanifold is emphasized by means of an internal metric function encoding its symplectic properties. We consider two straightforward examples, applying our general results to constrained motion along a toroidal geometry and to a Lorentz violating toy model in field theory. Since toroidal geometry has been recently used in cosmological models, we suggest how our results could lead to different proposals for the shape of the universe in cosmology.
Model Can Be Subtle: Two Important Mechanisms for Social Media Popularity Prediction
Authors: Xu Ning , Wang Xiaowen , Liu Jing , Wang Lanjun , Li Xuanya , Zhu Mengxiao , Zhang Yongdong , Liu An-An
Published: December 2024

Social media popularity prediction is an important channel to explore content sharing and communication on social networks. It aims to capture informative cues by analyzing multi-type data (such as user profile, image, and text) to decide the popularity of a specified post. In this article, we divide social network users into two categories (i.e., active and inactive users) and find a dilemma in existing models: If an active user publishes the low-popularity post, the model will habitually predict the high score. On the contrary, if an inactive user provides the high-popularity post, the model still gives the low score incorrectly. Therefore, how to make the model more subtle to users is important. Comparing to existing methods that directly leverage multi-modal features for regression training, this article stresses more on two novel mechanisms. The first method aims to prevent the over-fitting on user IDs. We propose the attribute-sensitive interactive mechanism (M1) by incorporating explicit user-attribute and post-attribute interaction. It can analyze which type of features a user cares the most and weaken the model’s dependence on user IDs. The second method aims to strengthen the influence of post content. We propose the knowledge embedding mechanism (M2) to revise the popularity scores in existing models by fusing the statistical frequency over multi-type data. Note that both mechanisms are model-agnostic, which can be applicable in any popularity prediction model. Extensive experiments conducted on the Social Media Prediction Dataset further validate the effectiveness.
Deepfake Detection Model Combining Texture Differences and Frequency Domain Information
Authors: Fang Shuaijv , Zhang Zhiyong , Song Bin
Published: December 2024

In recent years, public security incidents caused by deepfake technology have occurred frequently around the world, which makes an efficient and accurate deepfake detection model crucial. The existing advanced methods use the manipulation features in the image to realize the binary classification of real and fake images by training complex neural network models. However, these models rely on a single manipulation feature, and the detection accuracy of these methods will be greatly reduced when the forgery technology or image quality of the training dataset and the validation dataset are different. Inspired by the existing work, we propose a two-stream collaborative learning framework that combines spatial texture differences and frequency information. The average difference convolution (ADC) is designed to extract the spatial texture difference information of the image, and the gray image frequency-aware decomposition (GFAD) is used to extract the artifact information of the image in the frequency domain. At the same time, the ViT idea is combined with cross-attention mechanism for feature fusion to comprehensively mine forged features in forged images. Experimental results show that the proposed model has good detection effects on three benchmark datasets. In terms of cross-dataset evaluation, the AUC on Celeb-DF dataset reaches 82.86%, which is better than the existing advanced methods.
Enhancing Nutrition: A Review of Provitamin A Carotenoid Cassava Breeding Initiatives in East Africa
Authors: Abincha Wilfred , Dzidzienyo Daniel Kwadjo , Wesonga Lilian Noela , Mwimali Murenga , Ozimati Alfred , Kayondo Ismail Siraj , Ofori Kwadwo , Tongoona Pangirayi , Kivuva Benjamin Musembi
Published: December 2024

Biofortification of staple food stands as one of the most reliable methods of alleviating vitamin A deficiency (VAD). Evidence suggests that introducing provitamin A carotenoid (pVAC) cassava into the diets of preschool and primary school children in East Africa has led to improvements in their retinol levels. Notably, Kenya and Uganda have initiated cassava biofortification programs in the region. These efforts involve the assembly and characterization of pVAC cassava germplasm, alongside the development of essential tools such as genomic prediction (GP) models and molecular markers for accelerating genetic gains in the biofortification programs. However, several challenges have emerged, including a negative correlation between carotenoid content and dry matter content in cassava roots, diseases, the absence of affordable high‐throughput phenotyping methods, poor cassava flowering, poor pollen viability, low capacity in bioinformatics analyses, degradation of carotenoids during processing, and inadequate germplasm conservation facilities. To address these hurdles, cassava breeding programs in the region require enhanced infrastructure and human capacity to optimize efficiency in cassava biofortification with pVACs.
Optimizing Aquaponic Systems for Improved Food Production Efficiency in Climate‐Vulnerable Coastal Regions
Authors: Asadujjaman Md. , Salam Md. Abdus , Chowdhury Muhammad Tanvir Hossain , Alam Sarker Mohammed Rafiqul , Albeshr Mohammed Fahad , Arai Takaomi , Hossain M. Belal
Published: December 2024

Aquaponics, a sustainable agricultural approach, integrates aquaculture and hydroponics to optimize water consumption and enhance resource efficiency. The coastal region of Bangladesh, prone to frequent natural disasters, necessitates the development of resilient food production systems. In the present study, an adaptive aquaponic system was developed to evaluate the effectiveness of fish and vegetable production and assess the adoption process of this technology by the local communities to address climatic effects. The study design involved three treatment groups from the local communities, namely: local farmers (T1), school teachers (T2), and boat sailors (T3). The aquaponics system was stocked with monosex tilapia (Oreochromis niloticus) fry and various fast‐growing vegetable crops. The tilapia fry had an initial mean length of 7.1 ± 0.845 cm and weight of 10.02 ± 0.02 g and were introduced at a stocking density of 95 fry per 0.8 m³ in a 1000‐L capacity water tank. Seedlings of tomato, basil, turnip, cauliflower, and eggplant were planted in separate tubs and tank heads within the aquaponic systems. Results indicated that both fish and plant production in the treatment managed by local farmers surpassed that of other community groups. Treatment T1 demonstrated the highest fish production at 1542.69 ± 1.0 kg/ha/120 days, followed by T2 (1317.44 ± 0.37 kg/ha/120 days) and T3 (1278.204 ± 0.37 kg/ha/120 days). Similarly, turnip production mirrored this trend, with values of 8960 ± 672, 7440 ± 432, and 5120 ± 640 (kg/ha/120 days) for T1, T2, and T3, respectively. Tomato production ranked second highest production, with values of 5132.31 ± 361.85, 4520 ± 272, and 4349.6 ± 300.48 kg/ha/120 days in T1, T2, and T3, respectively. The measured water quality parameters were recorded as follows: temperature at 20.17 ± 0.23°C, dissolved oxygen (DO) at 5.80 ± 0.55 mg/L, pH at 8.04 ± 0.11, NH3─N at 0.26 ± 0.01 mg/L, NO2─N at 0.35 ± 0.01 mg/L, NO3─N at 0.03 ± 0.01 mg/L, and PO4─P at 0.43 ± 0.01 mg/L. A survey on the implementation of the technology revealed that participants had positive perceptions regarding the effectiveness of the aquaponic system, with 76.67% strongly agreeing to adopt the technology for future fish and vegetable production. Significantly, there were no opposing views, demonstrating a high level of acceptance. The study highlights the need to assess the technology’s effectiveness and community acceptance in other climatically vulnerable regions.
The Effect of User Behavior in Online Banking on Cybersecurity Knowledge
Authors: Alrababah Hamza , Iqbal Hena , Khan Muhammad Adnan
Published: December 2024

The expanding importance of technology, particularly mobile banking, in the financial industry, is examined in this literature review, as well as the crucial role that cybersecurity knowledge plays in protecting online transactions. Users now have the flexibility to conduct payments whenever and wherever they wish thanks to the advent of mobile banking. Further consumer behavior study is necessary due to difficulties with its acceptability. Given the hazards involved in online and mobile banking, cybersecurity is revealed as a critical component. Users’ actions might lead to financial losses since they represent security concerns. The evaluation places a strong emphasis on the necessity of increasing user cybersecurity knowledge and comprehension. Wireless banking is still in its early phases and needs more study on consumer acceptability and behavior despite the greater accessibility of technology. Furthermore, the research study emphasizes the socio‐technical difficulties governments encounter in tackling cybersecurity and emphasizes how urgently better readiness is needed in the face of cyberwarfare threats. It investigated how user behavior in mobile banking in particular geographic areas, such as Thailand, relates to cyberspace knowledge and consciousness. The assessment emphasizes the value of technology in banking, the difficulties associated with cybersecurity, and the demand for increased customer knowledge and comprehension to ensure safe digital transactions. To conduct this research activity, standardized questionnaires are used. The technique employed to get this data was convenience sampling. The statistics collection size stood at 500 and was gathered from males as well as females of all ages, belonging to diverse revenue groups, and numerous professional backgrounds. The survey finds that even while these services are becoming widespread in the UAE, customers’ awareness and understanding of cyber security are still insufficient. Users frequently underrate the security dangers involved with online transactions, which might create openings. Additionally, the study underlines the necessity of more effective training programs and efforts to raise mobile banking consumers’ knowledge of cybersecurity issues. It also emphasizes how crucial it is to build cybersecurity precautions into the structure and functioning of services for mobile banking. The purpose of this study was to examine the demographic characteristics of consumers and companies (online transactions) that use mobile banking apps to get special advantages. It was shown that people’s satisfaction with mobile banking applications was influenced by a number of criteria, including age, employment, income, marital status, and educational attainment. Younger consumers, such as students and recent graduates, are seen to be happy than customers of various ages and vocations, and males are thought to be happier than women.
Evaluation of Multiple Breast Cancer Polygenic Risk Score Panels in Women of Latin American Heritage
Authors: Huang Xiaosong , Lott Paul C. , Hu Donglei , Zavala Valentina A. , Jamal Zoeb N. , Vidaurre Tatiana , Casavilca-Zambrano Sandro , Navarro Vásquez Jeannie , Castañeda Carlos A. , Valencia Guillermo , Morante Zaida , Calderón Mónica , Abugattas Julio E. , Fuentes Hugo A. , Liendo-Picoaga Ruddy , Cotrina Jose M. , Neciosup Silvia P. , Rioja Viera Patricia , Salinas Luis A. , Galvez-Nino Marco , Huntsman Scott , Sanchez Sixto E. , Williams Michelle A. , Gelaye Bizu , Estrada-Florez Ana P. , Polanco-Echeverry Guadalupe , Echeverry Magdalena , Velez Alejandro , Carmona-Valencia Jenny A. , Bohorquez-Lozano Mabel E. , Torres Javier , Cruz Miguel , Ho Weang-Kee , Teo Soo Hwang , Tai Mei Chee , John Esther M. , Haiman Christopher A. , Conti David V. , Chen Fei , Torres-Mejía Gabriela , Kushi Lawrence H. , Neuhausen Susan L. , Ziv Elad , Carvajal-Carmona Luis G. ,   for the COLUMBUS Consortium, Fejerman Laura
Published: December 2024

Background:

A substantial portion of the genetic predisposition for breast cancer is explained by multiple common genetic variants of relatively small effect. A subset of these variants, which have been identified mostly in individuals of European (EUR) and Asian ancestries, have been combined to construct a polygenic risk score (PRS) to predict breast cancer risk, but the prediction accuracy of existing PRSs in Hispanic/Latinx individuals (H/L) remain relatively low. We assessed the performance of several existing PRS panels with and without addition of H/L-specific variants among self-reported H/L women.

Methods:

PRS performance was evaluated using multivariable logistic regression and the area under the ROC curve.

Results:

Both EUR and Asian PRSs performed worse in H/L samples compared with original reports. The best EUR PRS performed better than the best Asian PRS in pooled H/L samples. EUR PRSs had decreased performance with increasing Indigenous American (IA) ancestry, while Asian PRSs had increased performance with increasing IA ancestry. The addition of two H/L SNPs increased performance for all PRSs, most notably in the samples with high IA ancestry, and did not impact the performance of PRSs in individuals with lower IA ancestry.

Conclusions:

A single PRS that incorporates risk variants relevant to the multiple ancestral components of individuals from Latin America, instead of a set of ancestry-specific panels, could be used in clinical practice.

Impact:

The results highlight the importance of population-specific discovery and suggest a straightforward approach to integrate ancestry-specific variants into PRSs for clinical application.
The Society for Immunotherapy of Cancer Perspective on Tissue-Based Technologies for Immuno-Oncology Biomarker Discovery and Application
Authors: Monette Anne , Aguilar-Mahecha Adriana , Altinmakas Emre , Angelos Mathew G. , Assad Nima , Batist Gerald , Bommareddy Praveen K. , Bonilla Diana L. , Borchers Christoph H. , Church Sarah E. , Ciliberto Gennaro , Cogdill Alexandria P. , Fattore Luigi , Hacohen Nir , Haris Mohammad , Lacasse Vincent , Lie Wen-Rong , Mehta Arnav , Ruella Marco , Sater Houssein Abdul , Spatz Alan , Taouli Bachir , Tarhoni Imad , Gonzalez-Kozlova Edgar , Tirosh Itay , Wang Xiaodong , Gnjatic Sacha
Published: December 2024

With immuno-oncology becoming the standard of care for a variety of cancers, identifying biomarkers that reliably classify patient response, resistance, or toxicity becomes the next critical barrier toward improving care. Multiparametric, multi-omics, and computational platforms generating an unprecedented depth of data are poised to usher in the discovery of increasingly robust biomarkers for enhanced patient selection and personalized treatment approaches. Deciding which developing technologies to implement in clinical settings ultimately, applied either alone or in combination, relies on weighing pros and cons, from minimizing patient sampling to maximizing data outputs, and assessing the reproducibility and representativeness of findings, while lessening data fragmentation toward harmonization. These factors are all assessed while taking into consideration the shortest turnaround time. The Society for Immunotherapy of Cancer Biomarkers Committee convened to identify important advances in biomarker technologies and to address advances in biomarker discovery using multiplexed IHC and immunofluorescence, their coupling to single-cell transcriptomics, along with mass spectrometry–based quantitative and spatially resolved proteomics imaging technologies. We summarize key metrics obtained, ease of interpretation, limitations and dependencies, technical improvements, and outward comparisons of these technologies. By highlighting the most interesting recent data contributed by these technologies and by providing ways to improve their outputs, we hope to guide correlative research directions and assist in their evolution toward becoming clinically useful in immuno-oncology.
Table S6 from Discovery and Characterization of Brigimadlin, a Novel and Highly Potent MDM2–p53 Antagonist Suitable for Intermittent Dose Schedules
Authors: Gollner Andreas , Rudolph Dorothea , Weyer-Czernilofsky Ulrike , Baumgartinger Rosa , Jung Peter , Weinstabl Harald , Ramharter Jürgen , Grempler Rolf , Quant Jens , Rinnenthal Jörg , Pérez Pitarch Alejandro , Golubovic Bojana , Gerlach Daniel , Bader Gerd , Wetzel Kristiane , Otto Sebastian , Mandl Christian , Boehmelt Guido , McConnell Darryl B. , Kraut Norbert , Sini Patrizia
Published: December 2024

IC50 in mouse cell lines with different TP53 status.
Supplementary Figure S7 from TR-107, an Agonist of Caseinolytic Peptidase Proteolytic Subunit, Disrupts Mitochondrial Metabolism and Inhibits the Growth of Human Colorectal Cancer Cells
Authors: Giarrizzo Michael , LaComb Joseph F. , Patel Hetvi R. , Reddy Rohan G. , Haley John D. , Graves Lee M. , Iwanowicz Edwin J. , Bialkowska Agnieszka B.
Published: December 2024

Supplementary Figure S7. TR-107 reduces mitochondrial metabolic function in CRC cells. (A-D) Mitochondrial oxygen consumption rate (OCR) and (E-H) glycolytic proton efflux rate (PER) were evaluated in colorectal cancer cells LoVo, NCI-H508, LS 174T, and RKO treated with vehicle control (0.1% DMSO) or indicated concentrations of TR-107 for 12 hours. Quantification of OCR and PER was measured with the Seahorse XF Real-Time ATP Rate Assay. Baseline rates were captured for the first three time points, followed by injection of indicated compounds at concentrations described in Materials and Methods. Data are presented as mean ± SD values (N=6).
Supplementary Figure Legends from TR-107, an Agonist of Caseinolytic Peptidase Proteolytic Subunit, Disrupts Mitochondrial Metabolism and Inhibits the Growth of Human Colorectal Cancer Cells
Authors: Giarrizzo Michael , LaComb Joseph F. , Patel Hetvi R. , Reddy Rohan G. , Haley John D. , Graves Lee M. , Iwanowicz Edwin J. , Bialkowska Agnieszka B.
Published: December 2024

Supplementary Figure Legends
Supplementary Table 3 from Immunoproteasome Activation Expands the MHC Class I Immunopeptidome, Unmasks Neoantigens, and Enhances T-cell Anti-Myeloma Activity
Authors: Rana Priyanka S. , Ignatz-Hoover James J. , Guo Chunna , Mosley Amber L. , Malek Ehsan , Federov Yuriy , Adams Drew J. , Driscoll James J.
Published: December 2024

Supplementary Table 3
Supplemental Fig. S5 from Trametinib Potentiates Anti-PD-1 Efficacy in Tumors Established from Chemotherapy-Primed Pancreatic Cancer Cells
Authors: Pham Thao D. , Metropulos Anastasia E. , Mubin Nida , Becker Jeffrey H. , Shah Dhavan , Spaulding Christina , Shields Mario A. , Bentrem David J. , Munshi Hidayatullah G.
Published: December 2024

Supplemental Fig. S5. A-D. KPC-FIO cells display reduced sensitivity to oxaliplatin. The parental KPC and KPC-FIO cells were treated with increasing doses of oxaliplatin (0.5, 1, 2, 4 µM). After 72 hours, the effects of drug treatments on cell proliferation were evaluated by WST1 assay and analyzed by GraphPad. Error bars ± SEM from 3 biological replicates. One-way ANOVA, followed by Dunnett multiple comparison test. *, p<0.05 **, p<0.01 ****, p<0.0001 ns, non-significant.
Data from Targeting PDHK1 by DCA to Restore NK Cell Function in Hepatocellular Carcinoma
Authors: Yang Xinyi , Liu Yuanyuan , Wang Peng , Li Min , Xiang Tong , Xie Songzuo , Li Minxing , Wang Yan , Weng Desheng , Zhao Jingjing
Published: December 2024

Abstract
Pyruvate dehydrogenase complex is a crucial enzyme involved in the oxidation of glucose. It is regulated by pyruvate dehydrogenase kinase (PDHK) and pyruvate dehydrogenase phosphatase. Studies have demonstrated that PDHK1, a key enzyme in glucose metabolism, behaves like oncogenes. It is highly expressed in tumors and is associated with poor patient prognosis. However, there is limited research on how PDHK1 affects immune cell function. We have established a model of NK cell exhaustion to investigate the impact of dichloroacetate (DCA) on NK cell function. The production of granzyme B, IFNγ, TNFα, and CD107a by NK cells was explored by flow cytometry. The real-time live-cell imaging system was used to monitor the ability of NK cells against tumor cells. The Seahorse analyzer was utilized to measure the oxygen consumption rate and extracellular acidification rate of NK cells. A mouse model was used to investigate the potential of combining DCA with adjuvant NK cell infusion. Our study demonstrated that the hepatocellular carcinoma microenvironment mediated NK cellular exhaustion and high expression of PDHK1 and reduced cytokine secretion. We discovered that the PDHK1 inhibitor DCA enhances the activity and function of exhausted NK cells infiltrating the tumor microenvironment. Furthermore, in a s.c. hepatocellular carcinoma mouse model, DCA combined with NK cell treatment resulted in retarding cancer progression. This study indicates the potential of DCA in rescuing NK cell exhaustion and eliciting antitumor immunity.
Data from Immunoproteasome Activation Expands the MHC Class I Immunopeptidome, Unmasks Neoantigens, and Enhances T-cell Anti-Myeloma Activity
Authors: Rana Priyanka S. , Ignatz-Hoover James J. , Guo Chunna , Mosley Amber L. , Malek Ehsan , Federov Yuriy , Adams Drew J. , Driscoll James J.
Published: December 2024

Abstract
Proteasomes generate antigenic peptides that are presented on the tumor surface to cytotoxic T-lymphocytes. Immunoproteasomes are highly specialized proteasome variants that are expressed at higher levels in antigen-presenting cells and contain replacements of the three constitutive proteasome catalytic subunits to generate peptides with a hydrophobic C-terminus that fit within the groove of MHC class I (MHC-I) molecules. A hallmark of cancer is the ability to evade immunosurveillance by disrupting the antigen presentation machinery and downregulating MHC-I antigen presentation. High-throughput screening was performed to identify compound A, a novel molecule that selectively increased immunoproteasome activity and expanded the number and diversity of MHC-I–bound peptides presented on multiple myeloma cells. Compound A increased the presentation of individual MHC-I–bound peptides by >100-fold and unmasked tumor-specific neoantigens on myeloma cells. Global proteomic integral stability assays determined that compound A binds to the proteasome structural subunit PSMA1 and promotes association of the proteasome activator PA28α/β (PSME1/PSME2) with immunoproteasomes. CRISPR/Cas9 silencing of PSMA1, PSME1, or PSME2 as well as treatment with immunoproteasome-specific suicide inhibitors abolished the effects of compound A on antigen presentation. Treatment of multiple myeloma cell lines and patient bone marrow–derived CD138+ cells with compound A increased the anti-myeloma activity of allogenic and autologous T cells. Compound A was well-tolerated in vivo and co-treatment with allogeneic T cells reduced the growth of myeloma xenotransplants in NOD/SCID gamma mice. Taken together, our results demonstrate the paradigm shifting impact of immunoproteasome activators to diversify the antigenic landscape, expand the immunopeptidome, potentiate T-cell–directed therapy, and reveal actionable neoantigens for personalized T-cell immunotherapy.
Supplementary Figure-6 from TEAD2 Promotes Hepatocellular Carcinoma Development and Sorafenib Resistance via TAK1 Transcriptional Activation
Authors: Zhang Yahui , Ren Yidan , Dong Guoying , Jiao Qinlian , Guo Nan , Gao Ping , Li Ya , Wang Yunshan , Zhao Wei
Published: December 2024

Supplementary Figure-6
Table S4 from Ruthenium Drug BOLD-100 Regulates BRAFMT Colorectal Cancer Cell Apoptosis through AhR/ROS/ATR Signaling Axis Modulation
Authors: Griffin Daryl , Carson Robbie , Moss Debbie , Sessler Tamas , Lavin Deborah , Tiwari Vijay K. , Karelia Shivaali , Kennedy Richard , Savage Kienan I. , McDade Simon , Carie Adam , Pankovich Jim , Bazett Mark , Van Schaeybroeck Sandra
Published: December 2024

Table S4: Enrichr KEGG Pathways
Supplementary Table 15 from EHMT1/2 Inhibition Promotes Regression of Therapy-Resistant Ovarian Cancer Tumors in a CD8 T-cell–Dependent Manner
Authors: Nguyen Lily L. , Watson Zachary L. , Ortega Raquel , Woodruff Elizabeth R. , Jordan Kimberly R. , Iwanaga Ritsuko , Yamamoto Tomomi M. , Bailey Courtney A. , To Francis , Lin Shujian , Villagomez Fabian R. , Jeong Abigail D. , Guntupalli Saketh R. , Behbakht Kian , Gibaja Veronica , Arnoult Nausica , Chuong Edward B. , Bitler Benjamin G.
Published: December 2024

Hallmark pathways enriched in ID8-R cells treated with combinatory EZM8266/Olaparib compared to Olaparib alone.
Supplementary Table 13 from EHMT1/2 Inhibition Promotes Regression of Therapy-Resistant Ovarian Cancer Tumors in a CD8 T-cell–Dependent Manner
Authors: Nguyen Lily L. , Watson Zachary L. , Ortega Raquel , Woodruff Elizabeth R. , Jordan Kimberly R. , Iwanaga Ritsuko , Yamamoto Tomomi M. , Bailey Courtney A. , To Francis , Lin Shujian , Villagomez Fabian R. , Jeong Abigail D. , Guntupalli Saketh R. , Behbakht Kian , Gibaja Veronica , Arnoult Nausica , Chuong Edward B. , Bitler Benjamin G.
Published: December 2024

Hallmark pathways enriched in ID8-R cells treated with combinatory EZM8266/Olaparib compared to EZM8266 alone.
Supplementary Table 12 from EHMT1/2 Inhibition Promotes Regression of Therapy-Resistant Ovarian Cancer Tumors in a CD8 T-cell–Dependent Manner
Authors: Nguyen Lily L. , Watson Zachary L. , Ortega Raquel , Woodruff Elizabeth R. , Jordan Kimberly R. , Iwanaga Ritsuko , Yamamoto Tomomi M. , Bailey Courtney A. , To Francis , Lin Shujian , Villagomez Fabian R. , Jeong Abigail D. , Guntupalli Saketh R. , Behbakht Kian , Gibaja Veronica , Arnoult Nausica , Chuong Edward B. , Bitler Benjamin G.
Published: December 2024

Hallmark pathways negatively enriched in ID8-R cells treated with combinatory EZM8266/Olaparib compared to DMSO control.
Supplementary Figure 1 from EHMT1/2 Inhibition Promotes Regression of Therapy-Resistant Ovarian Cancer Tumors in a CD8 T-cell–Dependent Manner
Authors: Nguyen Lily L. , Watson Zachary L. , Ortega Raquel , Woodruff Elizabeth R. , Jordan Kimberly R. , Iwanaga Ritsuko , Yamamoto Tomomi M. , Bailey Courtney A. , To Francis , Lin Shujian , Villagomez Fabian R. , Jeong Abigail D. , Guntupalli Saketh R. , Behbakht Kian , Gibaja Veronica , Arnoult Nausica , Chuong Edward B. , Bitler Benjamin G.
Published: December 2024

GSEA of ID8 Olaparib-resistant (ID8-OR) and sensitive (ID8) ovarian cancer cells.
Data from LRRC75A-AS1 Drives the Epithelial–Mesenchymal Transition in Cervical Cancer by Binding IGF2BP1 and Inhibiting SYVN1-Mediated NLRP3 Ubiquitination
Authors: Sui Hongying , Shi Caixia , Yan Zhipeng , Chen Jinyang , Man Lin , Wang Fang
Published: December 2024

Abstract
Cervical cancer severely affects women’s health with increased incidence and poor survival for patients with metastasis. Our study aims to investigate the mechanism by which lncRNA LRRC75A-AS1 regulates the epithelial–mesenchymal transition (EMT) of cervical cancer through modulating m6A and ubiquitination modification. In this study, tumor tissues were collected from patients to analyze the expression of LRRC75A-AS1 and SYVN1. Migratory and invasive capacities of HeLa and CaSki cells were evaluated with wound healing and transwell assays. CCK-8 and EdU incor-poration assays were employed to examine cell proliferation. The interaction between LRRC75A-AS1, IGF2BP1, SYVN1, and NLRP3 was evaluated through RNA immunoprecipitation, RNA pull-down, FISH, and coimmunoprecipitation assays, respectively. MeRIP-qPCR was applied to analyze the m6A modification of SYVN1 mRNA. A subcutaneous tumor model of cervical cancer was established. We showed LRRC75A-AS1 was upregulated in tumor tissues, and LRRC75A-AS1 enhanced EMT through activating NLRP3/IL1β/Smad2/3 signaling in cervical cancer. Furthermore, LRRC75A-AS1 inhibited SYVN1-mediated NLRP3 ubiquitination by destabilizing SYVN1 mRNA. LRRC75A-AS1 competitively bound to IGF2BP1 protein and subsequently impaired the m6A modification of SYVN1 mRNA and its stability. Knockdown of LRRC75A-AS1 repressed EMT and tumor growth via inhibiting NLRP3/IL-1β/Smad2/3 signaling in mice. In conclusion, LRRC75A-AS1 competitively binds to IGF2BP1 protein to destabilize SYVN1 mRNA, subsequently suppresses SYVN1-mediated NLRP3 ubiquitination degradation and activates IL1β/Smad2/3 signaling, thus promoting EMT in cervical cancer.

Implication: LRRC75A-AS1 promotes cervical cancer progression, and this study suggests LRRC75A-AS1 as a new therapeutic target for cervical cancer.
METTL3-Mediated m6A Modification Regulates the Polycomb Repressive Complex 1 Components BMI1 and RNF2 in Hepatocellular Carcinoma Cells
Authors: Chen Weina , Zhang Jinqiang , Ma Wenbo , Liu Nianli , Wu Tong
Published: December 2024

Methyltransferase-like 3 (METTL3) is a primary RNA methyltransferase that catalyzes N6-methyladenosine (m6A) modification. The current study aims to further delineate the effect and mechanism of METTL3 in hepatocellular carcinoma (HCC). By using a murine model of hepatocellular cancer development induced via hydrodynamic tail vein injection, we showed that METTL3 enhanced HCC development. In cultured human HCC cell lines (Huh7 and PLC/PRF/5), we observed that stable knockdown of METTL3 by short hairpin RNA significantly decreased tumor cell proliferation, colony formation, and invasion, in vitro. When Huh7 and PLC/PRF/5 cells with short hairpin RNA knockdown of METTL3 were inoculated into the livers of SCID mice, we found that METTL3 knockdown significantly inhibited the growth of HCC xenograft tumors. These findings establish METTL3 as an important oncogene in HCC. Through m6A sequencing, RNA sequencing, and subsequent validation studies, we identified BMI1 and RNF2, two key components of the polycomb repressive complex 1, as direct downstream targets of METTL3-mediated m6A modification in HCC cells. Our data indicated that METTL3 catalyzed m6A modification of BMI1 and RNF2 mRNAs which led to increased mRNA stability via the m6A reader proteins IGF2BP1/2/3. Furthermore, we showed that the METTL3 inhibitor, STM2457, significantly inhibited HCC cell growth in vitro and in mice. Collectively, this study provides novel evidence that METTL3 promotes HCC development and progression through m6A modification of BMI1 and RNF2. Our findings suggest that the METTL3–m6A–BMI1/RNF2 signaling axis may represent a new therapeutic target for the treatment of HCC.

Implications: The METTL3–m6A–BMI1/RNF2 signaling axis promotes HCC development and progression.
Supplementary Figure 1 from Oncogenic HRAS Induces Metformin Resistance in Head and Neck Cancer by Promoting Glycolytic Metabolism
Authors: Wu Xingyu , Adame-Garcia Sendi Rafael , Koshizuka Keiichi , Vo Pham Thuy Tien , Hoang Thomas S. , Sato Kuniaki , Izumi Hiroki , Goto Yusuke , Allevato Michael M. , Wood Kris C. , Lippman Scott M. , Gutkind Jorge Silvio
Published: December 2024

Supplementary Figure 1: cancer-associated HRAS mutations in HNSCC using data from The Cancer Genome Atlas (TCGA) and Represetive images of the clonogenic assays.
Figure S11 from Integrated Germline and Somatic Features Reveal Divergent Immune Pathways Driving Response to Immune Checkpoint Blockade
Authors: Sears Timothy J. , Pagadala Meghana S. , Castro Andrea , Lee Ko-han , Kong JungHo , Tanaka Kairi , Lippman Scott M. , Zanetti Maurizio , Carter Hannah
Published: December 2024

Fig S11. A. Checkpoint expression and neoantigen levels by MHC Reliance category in discovery samples. B. Checkpoint expression and neoantigen levels by MHC Reliance category in validation samples. C. Pearson correlation between various checkpoint genes across discovery samples. D. Pearson correlation between various checkpoint genes across validation samples.
Table S3 from Inflammation Mediated by Gut Microbiome Alterations Promotes Lung Cancer Development and an Immunosuppressed Tumor Microenvironment
Authors: Rahal Zahraa , Liu Yuejiang , Peng Fuduan , Yang Sujuan , Jamal Mohamed A. , Sharma Manvi , Moreno Hannah , Damania Ashish V. , Wong Matthew C. , Ross Matthew C. , Sinjab Ansam , Zhou Tieling , Chen Minyue , Tarifa Reischle Inti , Feng Jiping , Chukwuocha Chidera , Tang Elizabeth , Abaya Camille , Lim Jamie K. , Leung Cheuk Hong , Lin Heather Y. , Deboever Nathaniel , Lee Jack J. , Sepesi Boris , Gibbons Don L. , Wargo Jennifer A. , Fujimoto Junya , Wang Linghua , Petrosino Joseph F. , Ajami Nadim J. , Jenq Robert R. , Moghaddam Seyed Javad , Cascone Tina , Hoffman Kristi , Kadara Humam
Published: December 2024

LEfSe analysis of differential abundance across groups.
Table S1 from CD91 and Its Ligand gp96 Confer Cross-Priming Capabilities to Multiple APCs during Immune Responses to Nascent, Emerging Tumors
Authors: Nayak Devanshi A. , Sedlacek Abigail L. , Cillo Anthony R. , Watkins Simon C. , Binder Robert J.
Published: December 2024

List of antibodies used.
Supplementary Figure S4 from Spatially Resolved Whole-Transcriptomic and Proteomic Profiling of Lung Cancer and Its Immune Microenvironment According to PD-L1 Expression
Authors: Koh Jaemoon , Lee Dongjoo , Kim Sehui , Song Seung Geun , Han Bogyeong , Jeong Hyein , Kim Young A , Keam Bhumsuk , Lee Se-Hoon , Kim Kwangsoo , Jeon Yoon Kyung , Chung Doo Hyun
Published: December 2024

The difference in immune factors across metabolic subtypes.
Supplementary Figure S2 from Spatially Resolved Whole-Transcriptomic and Proteomic Profiling of Lung Cancer and Its Immune Microenvironment According to PD-L1 Expression
Authors: Koh Jaemoon , Lee Dongjoo , Kim Sehui , Song Seung Geun , Han Bogyeong , Jeong Hyein , Kim Young A , Keam Bhumsuk , Lee Se-Hoon , Kim Kwangsoo , Jeon Yoon Kyung , Chung Doo Hyun
Published: December 2024

Principal Component Analysis (PCA) and the distribution of tumor PD-L1 expression in total or per group using DSP analysis.
Claudin-4 Stabilizes the Genome via Nuclear and Cell-Cycle Remodeling to Support Ovarian Cancer Cell Survival
Authors: Villagomez Fabian R. , Lang Julie , Nunez-Avellaneda Daniel , Behbakht Kian , Dimmick Hannah L. , Webb Patricia G. , Nephew Kenneth P. , Neville Margaret , Woodruff Elizabeth R. , Bitler Benjamin G.
Published: December 2024

Alterations in the interplay between the nucleus and the cell cycle during cancer development lead to a state of genomic instability, often accompanied by observable morphologic aberrations. Tumor cells can regulate these aberrations to evade cell death, either by preventing or eliminating genomic instability. In epithelial ovarian cancer, overexpression of claudin-4 significantly contributes to therapy resistance through mechanisms associated with genomic instability regulation. However, the molecular mechanisms underlying claudin-4 overexpression in epithelial ovarian cancer remain poorly understood. In this study, we modified claudin-4 expression and employed a unique claudin mimic peptide to investigate claudin-4’s function. Our findings show that claudin-4 supports ovarian cancer cell survival by stabilizing the genome through nuclear and cell-cycle remodeling. Specifically, claudin-4 induced nuclear constriction by excluding lamin B1 and promoting perinuclear F-actin accumulation, thereby altering nuclear structure and dynamics. Similarly, cell-cycle modifications due to claudin-4 overexpression resulted in fewer cells entering the S-phase and reduced genomic instability in tumors. Importantly, disrupting claudin-4’s biological effects using claudin mimic peptide and forskolin increased the efficacy of PARP inhibitor treatment, correlating with alterations in the oxidative stress response. Our data indicate that claudin-4 protects tumor genome integrity by modulating the crosstalk between the nucleus and the cell cycle, leading to resistance to genomic instability formation and the effects of genomic instability–inducing agents.

Significance:

High-grade serous ovarian carcinoma is marked by chromosomal instability, which can serve to promote disease progression and allow cancer to evade therapeutic insults. The report highlights the role of claudin-4 in regulating genomic instability and proposes a novel therapeutic approach to exploit claudin-4–mediated regulation.
Efficacy of Perfluorohexyloctane for the Treatment of Patients With Dry Eye Disease: A Meta-Analysis
Authors: Taloni Andrea , Coco Giulia , Pellegrini Marco , Scorcia Vincenzo , Giannaccare Giuseppe
Published: December 2024

Introduction: To systematically review the evidence from randomized controlled trials that evaluate the efficacy and safety of perfluorohexyloctane in the treatment of dry eye disease.
Methods: Literature search was conducted on PubMed and Scopus in April 2024 with the search strategy ("perfluorohexyloctane" or "NOV03" or "semifluorinated alkane") and "dry eye". Extension and paired-eyes study were excluded. The risk of bias was assessed using the Cochrane Risk of Bias Tool. Forest plots and a summary of findings were prepared for total corneal fluorescein staining (tCFS), tear film break-up time (TFBUT), eye dryness score (EDS), and Ocular Surface Disease Index (OSDI).
Results: The pooled standardized mean difference (SMD) for tCFS after 8 weeks of treatment was -0.53 (95% CI, -0.68 to -0.38; P<0.001), indicating a significant improvement in patients treated with perfluorohexyloctane. The between-study heterogeneity was moderately high (I2=52.0%). No significant differences in TFBUT were observed (SMD=0.05; 95% CI, -0.16 to 0.25; P=0.654). Regarding symptoms, patients treated with NOV03 had significantly lower EDS compared to controls (SMD=-0.49; 95% CI, -0.66 to -0.32; P<0.001), with moderately high heterogeneity (I2=71.1%). Conversely, the pooled SMD of OSDI was -0.13 (95% CI, -0.43 to 0.17; P=0.412), indicating no significant difference.
Conclusion: Perfluorohexyloctane is an effective and safe alternative for the treatment of evaporative dry eye disease due to MGD that can significantly reduce tCFS and eye dryness symptoms. More well-designed non-sponsored randomized clinical trials are required to investigate the impact on other ocular surface parameters.
Current Status and Future Directions of Research on Artificial Intelligence in Nasopharyngolaryngoscopy
Authors: Fan Cui , Miao Xiangwan , Sun Xingmei , Zhong Yiming , Liu Bin , Xiang Mingliang , Ye Bin
Published: December 2024

The nasopharyngolaryngoscopy (NPL) has emerged as a valuable tool for detecting early cases of head and neck cancers (HNCs). However, misdiagnoses and missed diagnoses are still common phenomena. The expertise of examining physicians often serves as the primary limiting factor, leading to issues such as incomplete visualization, imprecise identification, and unclear vision. Over recent years, the application of artificial intelligence (AI) in medical imaging, particularly in the realm of gastrointestinal endoscopy, has instigated revolutionary changes in site quality control, lesion identification, and report generation. However, there remains a lack of standardized guidelines for the proper application of NPL across various countries. While AI-related research in NPL is still in its nascent stages, it shows substantial potential for clinical application and endoscopic training. In this paper, we set our sights on reviewing the current clinical applications and summarizing the primary shortcomings of NPL. In addition, we encapsulate the progress of AI application within gastrointestinal endoscopy and NPL. Drawing from real-world clinical practice, we propose future directions and prospects for AI research in NPL. We firmly believe that the pace of clinical application of AI in NPL will accelerate significantly in the near future.
Pore-Forming Toxin-Like Proteins in the Anti-Parasitoid Immune Response of Drosophila
Authors: Magyar Lilla B. , Ábrahám Edit , Lipinszki Zoltán , Tarnopol Rebecca L. , Whiteman Noah K. , Varga Viktória , Hultmark Dan , Andó István , Cinege Gyöngyi
Published: December 2024

Introduction: Species of the ananassae subgroup of Drosophilidae are highly resistant to parasitoid wasp infections. We have previously shown that the genes encoding cytolethal distending toxin B (CdtB) and the apoptosis inducing protein of 56 kDa (AIP56) were horizontally transferred to these fly species from prokaryotes and are now instrumental in the anti-parasitoid immune defense of Drosophila ananassae. Here we describe a new family of genes, which encode proteins with hemolysin E domains, heretofore only identified in prokaryotes. Hemolysin E proteins are pore-forming toxins, important virulence factors of bacteria. Methods: Bioinformatical, transcriptional, and protein expressional studies were used. Results: The hemolysin E-like genes have a scattered distribution among the genomes of species belonging to several different monophyletic lineages in the family Drosophilidae. We detected structural homology with the bacterial Hemolysin E toxins and showed that the origin of the D. ananassae hemolysin E-like genes (hl1-38) is consistent with prokaryotic horizontal gene transfer. These genes encode humoral factors, secreted into the hemolymph by the fat body and hemocytes. Their expression is induced solely by parasitoid infection and the proteins bind to the developing parasitoids. Conclusions: Hemolysin E-like proteins acquired by horizontal gene transfer and expressed by the primary immune organs may contribute to the elimination of parasitoids, as novel humoral factors in Drosophila innate immunity.
Management of twin-reversed arterial perfusion (TRAP) sequence: a systematic review and meta-analysis
Authors: Stellon Michael A. , Joshi Devashish S. , Beninati Michael J. , Leverson Glen , Yang Qiuyu , Antony Kathleen M. , Christensen Leslie , Hinshaw J. Louis , Monroe Eric , Lobeck Inna N.
Published: December 2024

Introduction: Twin reversed arterial perfusion (TRAP) sequence is a rare complication of monochorionic twin pregnancies characterized by placental anastomoses between a normally developed twin and an acardiac mass. Though several treatment modalities exist, the optimal management strategy is unclear. This study aims to compare the various treatment strategies for TRAP sequence.

Methods: A systematic review of the literature was performed using PRISMA guidelines including PubMed, Scopus, Web of Science and the Cochrane Library. Studies were imported into Covidence, where they were independently screened by two authors. Studies included described interventions for TRAP sequence. Those excluded were unavailable in English and lacked differentiation between intervention strategies for TRAP and other monochorionic twin pregnancies. Fisher’s exact test and random effects modeling were used for statistical analysis.

Results: 2340 abstracts were screened, of which 218 articles progressed to full review and 120 qualified for data extraction. 757 twin pregnancies were described. Most were treated with radiofrequency ablation (RFA) (n=363, 47.95%) and laser ablation (n=220, 29.06%). Statistically significant differences amongst the modalities were seen in technical success (p = 0.005), gestational age at presentation (p < 0.01), intervention (p = 0.01), and delivery (p = 0.01), respectively, and time between treatment and delivery (p < 0.01). Notably, pump twin survival did not differ based on treatment modality used (p = 0.196). Overall, complication rates were low with no differences in preterm premature rupture of membranes (PPROM) (p = 0.66), preterm labor (p = 0.58) or maternal hemorrhage between modalities (p = 0.28). Suture cord ligation, however, had a greater hemorrhage rate than RFA (p = 0.03).

Conclusions: This embodies the first meta-analysis comparing treatment modalities for TRAP sequence with outcomes and complications. RFA is the most technically successful strategy. Prospective data is required to further understand the optimal modality and gestational age at treatment to ensure best overall outcomes.
De novo Light Chain Deposition Disease in a kidney allograft. A case report and literature review
Authors: Ali Ala A. , Maakaron Joseph , Karam Sabine
Published: December 2024

Light chain deposition disease (LCDD) is a rare entity that can occur with and without an associated hematological malignancy, involves the deposition of clonal light chains in the kidney, and can often progress to end-stage kidney disease. Managing LCDD involves treatment to eliminate the underlying clone, which can recur in the transplanted kidney. Very few cases of de novo LCDD have been described in a kidney allograft; and most of them have occurred with an associated malignancy. They have also had variable outcomes as their management can be extremely challenging to mitigate infection risk and avoid rejection. We report a de novo case of LCDD occurring in a renal allograft without an associated hematological malignancy that presented with rapidly progressive acute kidney injury and crescentic glomerulonephritis on the kidney biopsy. Early initiation of chemotherapy using bortezomib, cyclophosphamide and dexatmethasone with minimal adjustment of the immunosuppressive therapy mostly preserved kidney function. De novo LCDD disease after renal transplantation can be challenging to suspect, especially in the absence of signs of hematologic malignancy. An early kidney biopsy is beneficial for diagnosis with light chain restriction using fluorescent immunostaining, even if there is no M-protein present and the mode of presentation is crescentic glomerulonephritis, which is atypical LCDD.