bluuebunny/crossref_metadata_2025 huggingface dataset:
Towards Automated Accessibility Report Generation for Mobile Apps
Authors: Swearngin Amanda , Wu Jason , Zhang Xiaoyi , Gomez Esteban , Coughenour Jen , Stukenborg Rachel , Garg Bhavya , Hughes Greg , Hilliard Adriana , Bigham Jeffrey P. , Nichols Jeffrey
Published: July 2024

Many apps have basic accessibility issues, like missing labels or low contrast. To supplement manual testing, automated tools can help developers and QA testers find basic accessibility issues, but they can be laborious to use or require writing dedicated tests. To motivate our work, we interviewed eight accessibility QA professionals at a large technology company. From these interviews, we synthesized three design goals for accessibility report generation systems. Motivated by these goals, we developed a system to generate whole app accessibility reports by combining varied data collection methods (e.g., app crawling, manual recording) with an existing accessibility scanner. Many such scanners are based on single-screen scanning, and a key problem in whole app accessibility reporting is to effectively de-duplicate and summarize issues collected across an app. To this end, we developed a screen grouping model with 96.9% accuracy (88.8% F1-score) and UI element matching heuristics with 97% accuracy (98.2% F1-score). We combine these technologies in a system to report and summarize unique issues across an app, and enable a unique pixel-based ignore feature to help engineers and testers better manage reported issues across their app’s lifetime. We conducted a user study where 19 accessibility engineers and testers used multiple tools to create lists of prioritized issues in the context of an accessibility audit. Our system helped them create lists they were more satisfied with while addressing key limitations of current accessibility scanning tools.
Apoptotic and Nonapoptotic Cell Death in Caenorhabditis elegans Development
Authors: Horowitz Lauren Bayer , Shaham Shai
Published: July 2024

Programmed cell death (PCD) is an essential component of animal development, and aberrant cell death underlies many disorders. Understanding mechanisms that govern PCD during development can provide insight into cell death programs that are disrupted in disease. Key steps mediating apoptosis, a highly conserved cell death program employing caspase proteases, were first uncovered in the nematode Caenorhabditis elegans, a powerful model system for PCD research. Recent studies in C. elegans also unearthed conserved nonapoptotic caspase-independent cell death programs that function during development. Here, we discuss recent advances in understanding cell death during C. elegans development. We review insights expanding the molecular palette behind the execution of apoptotic and nonapoptotic cell death, as well as new discoveries revealing the mechanistic underpinnings of dying cell engulfment and clearance. A number of open questions are also discussed that will continue to propel the field over the coming years.
Circadian Rhythms in Anticancer Immunity: Mechanisms and Treatment Opportunities
Authors: Pick Robert , Wang Chen , Zeng Qun , Gül Zeynep Melis , Scheiermann Christoph
Published: July 2024

Circadian rhythms of approximately 24 h have emerged as important modulators of the immune system. These oscillations are important for mounting short-term, innate immune responses, but surprisingly also long-term, adaptive immune responses. Recent data indicate that they play a central role in antitumor immunity, in both mice and humans. In this review, we discuss the evolving literature on circadian antitumor immune responses and the underlying mechanisms that control them. We further provide an overview of circadian treatment regimens—chrono-immunotherapies—that harness time-of-day differences in immunity for optimal efficacy. Our aim is to provide an overview for researchers and clinicians alike, for a better understanding of the circadian immune system and how to best harness it for chronotherapeutic interventions. This knowledge is important for a better understanding of immune responses per se and could revolutionize the way we approach the treatment of cancer and a range of other diseases, ultimately improving clinical practice.
Searches for New High-Mass Resonances Decaying to Fermions at the LHC
Authors: Clerbaux Barbara , Gwilliam Carl
Published: July 2024

Accelerator searches for new resonances have a long-standing history of discoveries that have driven advances in our understanding of nature. Since 2010, the Large Hadron Collider (LHC) has probed previously inaccessible energy scales, enabling searches for new heavy resonances predicted by a wide range of theories beyond the Standard Model (BSM). In particular, resonance decays into fermionic final states are often seen as golden channels since they provide a clear signal—typically a peak in the invariant mass of the decay products over a smoothly falling background distribution. This review summarizes the key concepts of the experimental searches for new resonances decaying to fermions, in the context of the BSM theories that motivate them, and presents the latest results of the ATLAS and CMS experiments, focusing on the complete LHC Run 2 dataset. Future prospects at the High-Luminosity LHC and potential future colliders are also surveyed.
Rigorous Progress in Coarse-Graining
Authors: Noid W.G. , Szukalo Ryan J. , Kidder Katherine M. , Lesniewski Maria C.
Published: July 2024

Low-resolution coarse-grained (CG) models provide remarkable computational and conceptual advantages for simulating soft materials. In principle, bottom-up CG models can reproduce all structural and thermodynamic properties of atomically detailed models that can be observed at the resolution of the CG model. This review discusses recent progress in developing theory and computational methods for achieving this promise. We first briefly review variational approaches for parameterizing interaction potentials and their relationship to machine learning methods. We then discuss recent approaches for simultaneously improving both the transferability and thermodynamic properties of bottom-up models by rigorously addressing the density and temperature dependence of these potentials. We also briefly discuss exciting progress in modeling high-resolution observables with low-resolution CG models. More generally, we highlight the essential role of the bottom-up framework not only for fundamentally understanding the limitations of prior CG models but also for developing robust computational methods that resolve these limitations in practice.
Machine Learning of Reactive Potentials
Authors: Yang Yinuo , Zhang Shuhao , Ranasinghe Kavindri D. , Isayev Olexandr , Roitberg Adrian E.
Published: July 2024

In the past two decades, machine learning potentials (MLPs) have driven significant developments in chemical, biological, and material sciences. The construction and training of MLPs enable fast and accurate simulations and analysis of thermodynamic and kinetic properties. This review focuses on the application of MLPs to reaction systems with consideration of bond breaking and formation. We review the development of MLP models, primarily with neural network and kernel-based algorithms, and recent applications of reactive MLPs (RMLPs) to systems at different scales. We show how RMLPs are constructed, how they speed up the calculation of reactive dynamics, and how they facilitate the study of reaction trajectories, reaction rates, free energy calculations, and many other calculations. Different data sampling strategies applied in building RMLPs are also discussed with a focus on how to collect structures for rare events and how to further improve their performance with active learning.
The Absorption, Storage, and Transport of Ocular Carotenoids and Retinoids
Authors: von Lintig Johannes , Bandara Sepalika
Published: July 2024

Carotenoids, yellow and red pigments found abundantly in nature, play essential roles in various aspects of human physiology. They serve as critical molecules in vision by functioning as antioxidants and as filters for blue light within the retina. Furthermore, carotenoids are the natural precursors of vitamin A, which is indispensable for the synthesis of retinaldehyde, the visual chromophore, and retinoic acid, a small molecule that regulates gene expression. Insufficient levels of carotenoids and retinoids have been linked to age-related macular degeneration and xerophthalmia, respectively. Nevertheless, the mechanisms by which the eye maintains carotenoid and retinoid homeostasis have remained a mystery. Recent breakthroughs identified the molecular players involved in this process and provided valuable biochemical insights into their functioning. Mutations in the corresponding genes disrupt the homeostasis of carotenoids and retinoids, leading to visual system pathologies. This review aims to consolidate our current understanding of these pathways, including their regulatory principles.
Solar Light-Induced Photoelectrochemical H2 Generation Over Hierarchical TiO2 Nanotube Arrays Decorated with CdS Nanoparticles
Authors: Raza Waseem , Tesler Alexander B. , Mazare Anca , Schmuki Patrik
Published: July 2024

The process of converting solar energy into chemical energy through photoelectrochemical (PEC) water splitting holds significant promise for hydrogen and oxygen gas production. In the current study, we have demonstrated the feasibility of designing a high-performance heterojunction photoanode in a scalable manner. This photoanode sensitizes visible light active CdS onto hierarchical TiO2 nanotubes (TNTs), thereby enhancing H2 generation. To achieve this, we initially employed an electrochemical anodization technique to fabricate vertically aligned self-organized TNT on a titanium (Ti) substrate. Subsequently, we designed a hierarchical structure for TNT by uniformly decorating them with TiO2 nanoparticles (NPs), thus amplifying the available surface area. By employing the sequential ionic layer adsorption and reaction (SILAR) technique, we establish visible light sensitization. The resulting decorated hierarchical TNT photoanode demonstrates an enhanced photocurrent of 2.60 mA cm−2 under AM 1.5 G simulated solar light, surpassing the performance of hierarchical TNT, and most importantly classic CdS/TNT structures by 17-fold, and 1.6-fold, respectively. Moreover, the developed photoanodes achieved photoconversion efficiency with an applied bias (ABPE) of 2.48%. Thus, this work shows that a hierarchical scaffold can be exploited to achieve enhanced activity in photoelectrochemical H2 generation.
Unveiling the Thermal Stability of Sodium Ion Pouch Cells Using Accelerating Rate Calorimetry
Authors: Chak Chanmonirath (Michael) , Jayakumar Rishivandhiga , Shipitsyn Vadim , Bass Ean , McCloskey Reece , Zuo Wenhua , Le Phung M. L. , Xu Jun , Ma Lin
Published: July 2024

The thermal stability of ∼420 mAh Na0.97Ca0.03[Mn0.39Fe0.31Ni0.22Zn0.08]O2 (NCMFNZO)/hard carbon (HC) pouch cells was investigated using accelerating rate calorimetry (ARC) at elevated temperatures. 1 m NaPF6 in propylene carbonate (PC):ethyl methyl carbonate (EMC) (1:1 by volume) was used as a control electrolyte. Adding 2 wt% fluoroethylene carbonate to the electrolyte improves the cell’s thermal stability by decreasing the self-heating rate (SHR) across the whole testing temperature range. The selected states-of-charge (SoC), including 70%, 84%, and 100%, exhibit minimal impact on the exothermic behavior, except for a slight decrease in SHR after ∼275 °C at 70% SoC. When compared to traditional lithium-ion batteries operating at 100% SoC, NCMFNZO/HC pouch cells demonstrate inferior thermal stability compared to LiFePO4 (LFP)/graphite pouch cells, displaying a higher SHR from 220 to 300 °C. LiNi0.8Mn0.1Co0.1O2/graphite + SiOx pouch cells exhibit the worst safety performance, with an early onset temperature of ∼100 °C and the highest SHR across the entire temperature range. These results offer a direct comparison of the impact of SoC and electrolyte compositions on the thermal stability of SIBs at elevated temperatures, highlighting that there is still room for improvement in SIBs safety performance compared to LFP/graphite chemistry.
“You Go There and You are Welcomed and People do not Judge”: A Reflexive Thematic Analysis of Service Providers’ and Users’ Views of Brief Health and Wellbeing Conversations within the Third and Social Economy Sector
Authors: Nichol Beth , Rodrigues Angela M. , Wilson Rob , Haighton Catherine
Published: July 2024

Brief health and wellbeing conversations within the Third and Social Economy (TSE) sector (groups or organisations operating independently to family and government with social justice as the primary aim) could help to reduce health inequalities through increased access to disadvantaged populations. This study aimed to explore the acceptability of health and wellbeing conversations such as within the TSE, including their existence without specific training. A qualitative design was adopted, utilising semistructured, one‐to‐one interviews. Service providers (n = 15) and users (n = 5) across a variety of TSE settings including charities and religious settings were interviewed, most of whom had not received no specific training in initiating and engaging in health and wellbeing conversations. Reflexive thematic analysis was applied using Nvivo. Five themes were identified; TSE as an ecosystem of empowerment, an existing community‐initiated style of health and wellbeing conversations, readiness to engage in brief health and wellbeing conversations, capabilities of TSE as determined by external factors, and apprehension towards health and wellbeing conversations. Generally, the safe and empowering TSE environment naturally fostered health and wellbeing conversations, mostly initiated by service users. The TSE shows a readiness to conduct health and wellbeing conversations through existing infrastructure, partnerships, expertise, and an ambition for social justice. Barriers include fear of worsening the situation such as damaging strong and trusting relationships with service users, safeguarding concerns, and the instability and uncertainty of funding within the TSE. Relevant recommendations in light of these findings are made, including that the TSE is appropriate for the conduct of health and wellbeing conversations, and funding would provide cost efficiencies for its delivery at scale. Specific training within the TSE should focus on actively initiating health and wellbeing conversations and addressing fears of adverse consequences.
TableS3 from CD106 in Tumor-Specific Exhausted CD8+ T Cells Mediates Immunosuppression by Inhibiting TCR Signaling
Authors: Naoi Yuto , Morinaga Takao , Nagasaki Joji , Ariyasu Ryo , Ueda Youki , Yamashita Kazuo , Zhou Wenhao , Kawashima Shusuke , Kawase Katsushige , Honobe-Tabuchi Akiko , Ohnuma Takehiro , Kawamura Tatsuyoshi , Umeda Yoshiyasu , Kawahara Yu , Nakamura Yasuhiro , Kiniwa Yukiko , Yamasaki Osamu , Fukushima Satoshi , Kawazu Masahito , Suzuki Yutaka , Nishikawa Hiroyoshi , Hanazawa Toyoyuki , Ando Mizuo , Inozume Takashi , Togashi Yosuke
Published: July 2024

Summary of the antibodies used in flow cytometry analyses
PDXNet consortium members from A Pan-Cancer Patient-Derived Xenograft Histology Image Repository with Genomic and Pathologic Annotations Enables Deep Learning Analysis
Authors: White Brian S. , Woo Xing Yi , Koc Soner , Sheridan Todd , Neuhauser Steven B. , Wang Shidan , Evrard Yvonne A. , Chen Li , Foroughi pour Ali , Landua John D. , Mashl R. Jay , Davies Sherri R. , Fang Bingliang , Rosa Maria Gabriela , Evans Kurt W. , Bailey Matthew H. , Chen Yeqing , Xiao Min , Rubinstein Jill C. , Sanderson Brian J. , Lloyd Michael W. , Domanskyi Sergii , Dobrolecki Lacey E. , Fujita Maihi , Fujimoto Junya , Xiao Guanghua , Fields Ryan C. , Mudd Jacqueline L. , Xu Xiaowei , Hollingshead Melinda G. , Jiwani Shahanawaz , Acevedo Saul , Davis-Dusenbery Brandi N. , Robinson Peter N. , Moscow Jeffrey A. , Doroshow James H. , Mitsiades Nicholas , Kaochar Salma , Pan Chong-xian , Carvajal-Carmona Luis G. , Welm Alana L. , Welm Bryan E. , Govindan Ramaswamy , Li Shunqiang , Davies Michael A. , Roth Jack A. , Meric-Bernstam Funda , Xie Yang , Herlyn Meenhard , Ding Li , Lewis Michael T. , Bult Carol J. , Dean Dennis A. , Chuang Jeffrey H.
Published: July 2024

List of consortium members
Figure S6 from CD106 in Tumor-Specific Exhausted CD8+ T Cells Mediates Immunosuppression by Inhibiting TCR Signaling
Authors: Naoi Yuto , Morinaga Takao , Nagasaki Joji , Ariyasu Ryo , Ueda Youki , Yamashita Kazuo , Zhou Wenhao , Kawashima Shusuke , Kawase Katsushige , Honobe-Tabuchi Akiko , Ohnuma Takehiro , Kawamura Tatsuyoshi , Umeda Yoshiyasu , Kawahara Yu , Nakamura Yasuhiro , Kiniwa Yukiko , Yamasaki Osamu , Fukushima Satoshi , Kawazu Masahito , Suzuki Yutaka , Nishikawa Hiroyoshi , Hanazawa Toyoyuki , Ando Mizuo , Inozume Takashi , Togashi Yosuke
Published: July 2024

Influence of CD106 on various surface molecules
Figure S8 from A Pan-Cancer Patient-Derived Xenograft Histology Image Repository with Genomic and Pathologic Annotations Enables Deep Learning Analysis
Authors: White Brian S. , Woo Xing Yi , Koc Soner , Sheridan Todd , Neuhauser Steven B. , Wang Shidan , Evrard Yvonne A. , Chen Li , Foroughi pour Ali , Landua John D. , Mashl R. Jay , Davies Sherri R. , Fang Bingliang , Rosa Maria Gabriela , Evans Kurt W. , Bailey Matthew H. , Chen Yeqing , Xiao Min , Rubinstein Jill C. , Sanderson Brian J. , Lloyd Michael W. , Domanskyi Sergii , Dobrolecki Lacey E. , Fujita Maihi , Fujimoto Junya , Xiao Guanghua , Fields Ryan C. , Mudd Jacqueline L. , Xu Xiaowei , Hollingshead Melinda G. , Jiwani Shahanawaz , Acevedo Saul , Davis-Dusenbery Brandi N. , Robinson Peter N. , Moscow Jeffrey A. , Doroshow James H. , Mitsiades Nicholas , Kaochar Salma , Pan Chong-xian , Carvajal-Carmona Luis G. , Welm Alana L. , Welm Bryan E. , Govindan Ramaswamy , Li Shunqiang , Davies Michael A. , Roth Jack A. , Meric-Bernstam Funda , Xie Yang , Herlyn Meenhard , Ding Li , Lewis Michael T. , Bult Carol J. , Dean Dennis A. , Chuang Jeffrey H.
Published: July 2024

Figure S8
Table S5 from Single-Cell and Spatial Transcriptome Profiling Identifies the Transcription Factor BHLHE40 as a Driver of EMT in Metastatic Colorectal Cancer
Authors: Yang Sheng , Zhang Dongsheng , Sun Qingyang , Nie Hongxu , Zhang Yue , Wang Xiaowei , Huang Yuanjian , Sun Yueming
Published: July 2024

Supplementary Table S5: The top50 differentially expressed genes of each CAFs and Malignant EPCs subgroups are displayed.
Figure S1 from A Pan-Cancer Patient-Derived Xenograft Histology Image Repository with Genomic and Pathologic Annotations Enables Deep Learning Analysis
Authors: White Brian S. , Woo Xing Yi , Koc Soner , Sheridan Todd , Neuhauser Steven B. , Wang Shidan , Evrard Yvonne A. , Chen Li , Foroughi pour Ali , Landua John D. , Mashl R. Jay , Davies Sherri R. , Fang Bingliang , Rosa Maria Gabriela , Evans Kurt W. , Bailey Matthew H. , Chen Yeqing , Xiao Min , Rubinstein Jill C. , Sanderson Brian J. , Lloyd Michael W. , Domanskyi Sergii , Dobrolecki Lacey E. , Fujita Maihi , Fujimoto Junya , Xiao Guanghua , Fields Ryan C. , Mudd Jacqueline L. , Xu Xiaowei , Hollingshead Melinda G. , Jiwani Shahanawaz , Acevedo Saul , Davis-Dusenbery Brandi N. , Robinson Peter N. , Moscow Jeffrey A. , Doroshow James H. , Mitsiades Nicholas , Kaochar Salma , Pan Chong-xian , Carvajal-Carmona Luis G. , Welm Alana L. , Welm Bryan E. , Govindan Ramaswamy , Li Shunqiang , Davies Michael A. , Roth Jack A. , Meric-Bernstam Funda , Xie Yang , Herlyn Meenhard , Ding Li , Lewis Michael T. , Bult Carol J. , Dean Dennis A. , Chuang Jeffrey H.
Published: July 2024

Figure S1
Figure S7 from Single-Cell and Spatial Transcriptome Profiling Identifies the Transcription Factor BHLHE40 as a Driver of EMT in Metastatic Colorectal Cancer
Authors: Yang Sheng , Zhang Dongsheng , Sun Qingyang , Nie Hongxu , Zhang Yue , Wang Xiaowei , Huang Yuanjian , Sun Yueming
Published: July 2024

Figure S7. BHLHE40 promoted the proliferation, invasion, and migration of colorectal cancer in vitro. (A–D) CCK8 assays and colony formation assays were used to detect the cell proliferation ability of BHLHE40 knockdown or overexpression cells. (E–H) Transwell assays and wound healing assays were used to migration and invasion abilities of BHLHE40 knockdown or overexpression cells. Scale bar: 100 µm. All data were presented as the means ± SD of three independent experiments. *, P < 0.05, **, P < 0.01, and ***, P < 0.001, Student t test.
Data from A Pan-Cancer Patient-Derived Xenograft Histology Image Repository with Genomic and Pathologic Annotations Enables Deep Learning Analysis
Authors: White Brian S. , Woo Xing Yi , Koc Soner , Sheridan Todd , Neuhauser Steven B. , Wang Shidan , Evrard Yvonne A. , Chen Li , Foroughi pour Ali , Landua John D. , Mashl R. Jay , Davies Sherri R. , Fang Bingliang , Rosa Maria Gabriela , Evans Kurt W. , Bailey Matthew H. , Chen Yeqing , Xiao Min , Rubinstein Jill C. , Sanderson Brian J. , Lloyd Michael W. , Domanskyi Sergii , Dobrolecki Lacey E. , Fujita Maihi , Fujimoto Junya , Xiao Guanghua , Fields Ryan C. , Mudd Jacqueline L. , Xu Xiaowei , Hollingshead Melinda G. , Jiwani Shahanawaz , Acevedo Saul , Davis-Dusenbery Brandi N. , Robinson Peter N. , Moscow Jeffrey A. , Doroshow James H. , Mitsiades Nicholas , Kaochar Salma , Pan Chong-xian , Carvajal-Carmona Luis G. , Welm Alana L. , Welm Bryan E. , Govindan Ramaswamy , Li Shunqiang , Davies Michael A. , Roth Jack A. , Meric-Bernstam Funda , Xie Yang , Herlyn Meenhard , Ding Li , Lewis Michael T. , Bult Carol J. , Dean Dennis A. , Chuang Jeffrey H.
Published: July 2024

Abstract
Patient-derived xenografts (PDX) model human intra- and intertumoral heterogeneity in the context of the intact tissue of immunocompromised mice. Histologic imaging via hematoxylin and eosin (H&E) staining is routinely performed on PDX samples, which could be harnessed for computational analysis. Prior studies of large clinical H&E image repositories have shown that deep learning analysis can identify intercellular and morphologic signals correlated with disease phenotype and therapeutic response. In this study, we developed an extensive, pan-cancer repository of >1,000 PDX and paired parental tumor H&E images. These images, curated from the PDX Development and Trial Centers Research Network Consortium, had a range of associated genomic and transcriptomic data, clinical metadata, pathologic assessments of cell composition, and, in several cases, detailed pathologic annotations of neoplastic, stromal, and necrotic regions. The amenability of these images to deep learning was highlighted through three applications: (i) development of a classifier for neoplastic, stromal, and necrotic regions; (ii) development of a predictor of xenograft-transplant lymphoproliferative disorder; and (iii) application of a published predictor of microsatellite instability. Together, this PDX Development and Trial Centers Research Network image repository provides a valuable resource for controlled digital pathology analysis, both for the evaluation of technical issues and for the development of computational image–based methods that make clinical predictions based on PDX treatment studies.

Significance: A pan-cancer repository of >1,000 patient-derived xenograft hematoxylin and eosin–stained images will facilitate cancer biology investigations through histopathologic analysis and contributes important model system data that expand existing human histology repositories.
Figure S3 from Optimizing the Design and Geometry of T Cell–Engaging Bispecific Antibodies Targeting CEA in Colorectal Cancer
Authors: Elsayed Abdullah , Plüss Louis , Nideroest Larissa , Rotta Giulia , Thoma Marina , Zangger Nathan , Peissert Frederik , Pfister Stefanie K. , Pellegrino Christian , Dakhel Plaza Sheila , De Luca Roberto , Manz Markus G. , Oxenius Annette , Puca Emanuele , Halin Cornelia , Neri Dario
Published: July 2024

Supplementary Figure S3
Data from A Bispecific Antibody That Targets the Membrane-Proximal Region of Mesothelin and Retains High Anticancer Activity in the Presence of Shed Mesothelin
Authors: Chakraborty Anirban , Onda Masanori , O’Shea Tara , Wei Junxia , Liu Xiufen , Bera Tapan K. , Pastan Ira
Published: July 2024

Abstract
Mesothelin (MSLN) is a cell-surface protein that is expressed in many cancers, which makes it a popular target for Ab-based cancer therapy. However, MSLN is shed from cancer cells at high levels via proteases that cleave at its membrane-proximal C-terminal region. Shed MSLN accumulates in patients’ fluids and tumors and can block Ab-based MSLN-targeting drugs from killing cancer cells. A previously established mAb, 15B6, binds MSLN at its protease-sensitive C-terminal region and does not bind shed MSLN. Moreover, 15B6 variable fragment (Fv)–derived chimeric antigen receptor T cells are not inhibited by shed MSLN and kill tumors in mice more effectively than mAb SS1 Fv-derived chimeric antigen receptor T cells, which bind an epitope retained in shed MSLN. In this study, we have established 15B6 Fv-derived MSLN × CD3 bispecific antibodies (BsAb) that target MSLN-expressing cancers. We identified our lead candidate BsAb 5 after screening multiple 15B6-derived BsAb formats in vitro for cytotoxic activity. BsAb 5 activates T cells to kill various cancer cell lines in a MSLN-specific manner. MSLN 296-591 His, a recombinant protein mimicking shed MSLN, does not inhibit 15B6-derived BsAb 5 but completely inhibits humanized SS1-derived BsAb 7. Furthermore, BsAb 5 inhibits and delays tumor growth and is not inhibited by MSLN 296-585 His in mice. Our findings indicate that by targeting the protease-sensitive region of MSLN, BsAb 5 has high MSLN-specific anticancer activity that is not inhibited by shed MSLN. BsAb 5 may be a promising immunotherapy candidate for MSLN-expressing cancers.
Supplementary Table 3 from Hepatitis B Virus–Mediated m6A Demethylation Increases Hepatocellular Carcinoma Stemness and Immune Escape
Authors: Meng Yuting , Shu Zheyue , Wang Xueyao , Hong Liang , Wang Baohua , Jiang Jingjing , He Kangxin , Cao Qingyi , Shi Fan , Wang Hai , Gong Lan , Diao Hongyan
Published: July 2024

Supplementary Table 3 shows primer sequences
Supplementary Table S1 from Distinct Regulation of ASCL1 by the Cell Cycle and Chemotherapy in Small Cell Lung Cancer
Authors: Liu Yuning , Wu Qingzhe , Jiang Bin , Hou Tingting , Wu Chuanqiang , Wu Ming , Song Hai
Published: July 2024

Supplementary Table S1. Sequences for sgRNA, shRNA or siRNA.
Supplementary Table 2 from Hepatitis B Virus–Mediated m6A Demethylation Increases Hepatocellular Carcinoma Stemness and Immune Escape
Authors: Meng Yuting , Shu Zheyue , Wang Xueyao , Hong Liang , Wang Baohua , Jiang Jingjing , He Kangxin , Cao Qingyi , Shi Fan , Wang Hai , Gong Lan , Diao Hongyan
Published: July 2024

Supplementary Table 2 shows the Sequences of oligonucleotides for siRNA/shRNA
Figure S3 from Hepatitis B Virus–Mediated m6A Demethylation Increases Hepatocellular Carcinoma Stemness and Immune Escape
Authors: Meng Yuting , Shu Zheyue , Wang Xueyao , Hong Liang , Wang Baohua , Jiang Jingjing , He Kangxin , Cao Qingyi , Shi Fan , Wang Hai , Gong Lan , Diao Hongyan
Published: July 2024

Supplementary Figure S3 shows the extended data of "ALKBH5 is required for the maintenance of hepatoma cell self-renewal in HBV-positive HCC"
Supplementary Table S3 from Low- and High-Grade Glioma-Associated Vascular Cells Differentially Regulate Tumor Growth
Authors: Muthukrishnan Sree Deepthi , Qi Haocheng , Wang David , Elahi Lubayna , Pham Amy , Alvarado Alvaro G. , Li Tie , Gao Fuying , Kawaguchi Riki , Lai Albert , Kornblum Harley I.
Published: July 2024

Downregulated canonical pathways in LG-, PRI- and REC-GVC
Supplementary Table S3 from ETS1, a Target Gene of the EWSR1::FLI1 Fusion Oncoprotein, Regulates the Expression of the Focal Adhesion Protein TENSIN3
Authors: Ebegboni Vernon Justice , Jones Tamara L. , Brownmiller Tayvia , Zhao Patrick X. , Pehrsson Erica C. , Sundara Rajan Soumya , Caplen Natasha J.
Published: July 2024

EWSR1::FLI1-regulated transcription factor genes
Supplementary Figure S2 from Vasorin Exocytosed from Glioma Cells Facilitates Angiogenesis via VEGFR2/AKT Signaling Pathway
Authors: Zhong Ying , Kang Hui , Ma Ziqing , Li Jiayu , Qin Zixi , Zhang Zixuan , Li Peiwen , Zhong Ying , Wang Lihui
Published: July 2024

VASN knockdown inhibits HUVEC migration
Data from Distinct Regulation of ASCL1 by the Cell Cycle and Chemotherapy in Small Cell Lung Cancer
Authors: Liu Yuning , Wu Qingzhe , Jiang Bin , Hou Tingting , Wu Chuanqiang , Wu Ming , Song Hai
Published: July 2024

Abstract
Small cell lung cancer (SCLC) is an aggressive and lethal malignancy. Achaete-scute homolog 1 (ASCL1) is essential for the initiation of SCLC in mice and the development of pulmonary neuroendocrine cells (PNEC), which are the major cells of origin for SCLC. However, the regulatory mechanism of ASCL1 in SCLC remains elusive. Here, we found that ASCL1 expression gradually increases as the tumors grow in a mouse SCLC model, and is regulated by the cell cycle. Mechanistically, CDK2–CyclinA2 complex phosphorylates ASCL1, which results in increased proteasome-mediated ASCL1 protein degradation by E3 ubiquitin ligase HUWE1 during mitosis. TCF3 promotes the multisite phosphorylation of ASCL1 through the CDK2–CyclinA2 complex and the interaction between ASCL1 and TCF3 protects ASCL1 from degradation. The dissociation of TCF3 from ASCL1 during mitosis accelerates the degradation of ASCL1. In addition, chemotherapy drugs greatly reduce the transcription of ASCL1 in SCLC cells. Depletion of ASCL1 sensitizes SCLC cells to chemotherapy drugs. Together, our study demonstrates that ASCL1 is a cell-cycle–regulated protein and provides a theoretical basis for applying cell-cycle–related antitumor drugs in SCLC treatment.

Implications:Our study revealed a novel regulatory mechanism of ASCL1 by cell cycle and chemotherapy drugs in SCLC. Treating patients with SCLC with a combination of ASCL1-targeting therapy and chemotherapy drugs could potentially be beneficial.
Supplementary Figure 3 from Melanoma Clonal Heterogeneity Leads to Secondary Resistance after Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes
Authors: König David , Sandholzer Michael T. , Uzun Sarp , Zingg Andreas , Ritschard Reto , Thut Helen , Glatz Katharina , Kappos Elisabeth A. , Schaefer Dirk J. , Kettelhack Christoph , Passweg Jakob R. , Holbro Andreas , Baur Katharina , Medinger Michael , Buser Andreas , Lardinois Didier , Jeker Lukas T. , Khanna Nina , Stenner Frank , Kasenda Benjamin , Homicsko Krisztian , Matter Matthias , Rodrigues Mantuano Natalia , Zippelius Alfred , Läubli Heinz
Published: July 2024

Supplementary Figure 3. Regressing soft tissue metastasis (Biopsy 10 weeks after TIL transfer). No vital tumor is detectable.
Supplementary Figure S15 from The CD33xCD123xCD70 Multispecific CD3-Engaging DARPin MP0533 Induces Selective T Cell–Mediated Killing of AML Leukemic Stem Cells
Authors: Bianchi Matteo , Reichen Christian , Croset Amelie , Fischer Stefanie , Eggenschwiler Aline , Grübler Yvonne , Marpakwar Rajlakshmi , Looser Thamar , Spitzli Patricia , Herzog Christel , Villemagne Denis , Schiegg Dieter , Abduli Liridon , Iss Chloé , Neculcea Alexandra , Franchini Marco , Lekishvili Tamara , Ragusa Simone , Zitt Christof , Kaufmann Yvonne , Auge Alienor , Hänggi Martin , Ali Waleed , Frasconi Teresa M. , Wullschleger Stephan , Schlegel Iris , Matzner Mirela , Lüthi Ursina , Schlereth Bernd , Dawson Keith M. , Kirkin Vladimir , Ochsenbein Adrian F. , Grimm Sebastian , Reschke Nina , Riether Carsten , Steiner Daniel , Leupin Nicolas , Goubier Anne
Published: July 2024

Supplementary Fig. S15. TCE-induced CD70 upregulation on activated CD4 and CD8 T cells. Expression of CD70 on T cells in cocultures with MOLM-13 cells and 1 nmol/L MP0533 or CD123-CD3 DART.
Supplementary Figure 7 from SIRT3 Negatively Regulates TFH-Cell Differentiation in Cancer
Authors: Hou Yueru , Cao Yejin , He Ying , Dong Lin , Zhao Longhao , Dong Yingjie , Niu Ruiying , Bi Yujing , Liu Guangwei
Published: July 2024

Fig.S7. SIRT3 deficiency promotes TFH cell differentiation to inhibit tumor growth.
Supplementary Fig. S23 from Orchestrated Codelivery of Peptide Antigen and Adjuvant to Antigen-Presenting Cells by Using an Engineered Chimeric Peptide Enhances Antitumor T-Cell Immunity
Authors: Pan Haifeng , Yu Siyuan , Zhuang Haoyun , Yang Han , Jiang Jinlu , Yang Haihui , Ren Shuling , Luo Guoxing , Yu Xuan , Chen Shuping , Lin Yanhua , Sheng Roufang , Zhang Shiyin , Yuan Quan , Huang Chenghao , Zhang Tianying , Li Tingdong , Ge Shengxiang , Zhang Jun , Xia Ningshao
Published: July 2024

Supplementary Fig. S23. CD8+ T cells depletion study.
Supplementary Fig. S13 from Orchestrated Codelivery of Peptide Antigen and Adjuvant to Antigen-Presenting Cells by Using an Engineered Chimeric Peptide Enhances Antitumor T-Cell Immunity
Authors: Pan Haifeng , Yu Siyuan , Zhuang Haoyun , Yang Han , Jiang Jinlu , Yang Haihui , Ren Shuling , Luo Guoxing , Yu Xuan , Chen Shuping , Lin Yanhua , Sheng Roufang , Zhang Shiyin , Yuan Quan , Huang Chenghao , Zhang Tianying , Li Tingdong , Ge Shengxiang , Zhang Jun , Xia Ningshao
Published: July 2024

Supplementary Fig. S13. The modified eTAT delivery system demonstrated comparable efficiency in interacting with CpG molecules and in the co-delivery of antigen and CpG in vivo.
Figure 6 from Claudin-4 Modulates Autophagy via SLC1A5/LAT1 as a Mechanism to Regulate Micronuclei
Authors: Villagomez Fabian R. , Lang Julie , Rosario Fredrick J. , Nunez-Avellaneda Daniel , Webb Patricia , Neville Margaret , Woodruff Elizabeth R. , Bitler Benjamin G.
Published: July 2024

Association of autophagy and the activity of transporters of amino acids. The association of autophagy with the activity of SLC1A5 and LAT1 was evaluated through confocal microscopy and flow cytometry and by using both an activator of autophagy (rapamycin 8 µmol/L, 24 hours) and an inhibitor (chloroquine, 40 µmol/L, 24 hours) as well as the specific inhibition of SLC1A5 and LAT1 using GPNA (25 mmol/L) and BCH (5 mmol/L), respectively. A, Confocal images showing SLC1A5 intracellular distribution in HGSOC cells during autophagy blocking autophagy induction (B). C, Graphs indicate percentages of autophagy flux in HGSOC cells during specific inhibition of SLC1A5 activity (GNPA, 5 mmol/L) and manipulation of claudin-4 expression. D, Graphs indicate percentages of autophagy flux in HGSOC cells during specific inhibition of LAT1 (BCH, 25 mmol/L). (Two-tailed Unpaired t test and Mann–Whitney test; Kruskal–Wallis test with Dunn’s multiple comparisons; One way ANOVA and Tukey’s multiple comparison test; three independent experiments; significance, P < 0.05). Graphs show mean and SEM, scale bar, 20 µm.
Figure 5 from Claudin-4 Modulates Autophagy via SLC1A5/LAT1 as a Mechanism to Regulate Micronuclei
Authors: Villagomez Fabian R. , Lang Julie , Rosario Fredrick J. , Nunez-Avellaneda Daniel , Webb Patricia , Neville Margaret , Woodruff Elizabeth R. , Bitler Benjamin G.
Published: July 2024

Effect of claudin-4 manipulation on the intracellular distribution of transporters of amino acids. We studied the association of claudin-4 with the amino acid transporters, SLC1A5 and LAT1 (which regulate autophagy) in HGSOC cells using confocal microscopy, immunoblotting, and flow cytometry. A, Top, confocal images showing the intracellular distribution of SLC1A5 and claudin-4 in HGSOC cells; bottom, kymographs (from z-stacks and dotted yellow squares) highlighting colocalization. A similar phenotype is shown for LAT1 and claudin-4 in (B). The Pearson’s correlation coefficient for SLC1A5 and claudin-4, and LAT1 and claudin-4 is shown in (C). D, Percentage of HGSOC cells with autophagic flux during L-glutamine withdrawal measured by flow cytometry (two-tailed unpaired t test and Mann–Whitney test; three independent experiments; significance, P < 0.05). E and F, show representative confocal images (maximum projections) of the intracellular distribution of SLC1A5 before claudin-4 overexpression (OVCAR8 claudin-4) and downregulation (OVCA429 claudin-4 KD and OVCAR3 claudin-4 KD) in HGSOC cells with and without L-glutamine, respectively. Graphs show mean and SEM, scale bar, 20 µm.
Figure 4 from Claudin-4 Modulates Autophagy via SLC1A5/LAT1 as a Mechanism to Regulate Micronuclei
Authors: Villagomez Fabian R. , Lang Julie , Rosario Fredrick J. , Nunez-Avellaneda Daniel , Webb Patricia , Neville Margaret , Woodruff Elizabeth R. , Bitler Benjamin G.
Published: July 2024

Correlation of amino acids transport with the clinical significance of claudin-4 in ovarian cancer. Reported proteins interacting with claudin-4 in HGSOC cells were employed to construct PPN, aiming to identify key elements and cellular functions associated with the clinical significance of claudin-4 in HGSOC tumors. This analysis utilized publicly available data from HGSOC tumors, sourced from cBioPortal and Kaplan–Meier plotter. A, PPN (based on BioID) of claudin-4-interacting proteins (experimentally determined using STRING) and highly mutated proteins (cBioPortal) in HGSOC tumors shows clusters of proteins and distinctive associated cellular functions. B, Significantly different metabolites in OVCAR3 cells associated to claudin-4 downregulation (from global metabolomics using cell pellets and supernatants; claudin-4 KD/WT, where values close to 1 are similar results between KD and WT). It also indicates the corresponding mean fold change in the (top) of circles, (red and green; red indicates decreased while greed indicates increase of metabolites). C, Same as (B) but in OVCA429 cells. D, The median survival of HGSOC patients (criteria: p53 mutated; serous histology) was correlated with each identified cluster (based on claudin-4; continue lines) and without claudin-4 (dotted lines; significance, P < 0.05; P values and false discovery rate is indicated in Supplementary Tables S3 and S4).
Figure 3 from Claudin-4 Modulates Autophagy via SLC1A5/LAT1 as a Mechanism to Regulate Micronuclei
Authors: Villagomez Fabian R. , Lang Julie , Rosario Fredrick J. , Nunez-Avellaneda Daniel , Webb Patricia , Neville Margaret , Woodruff Elizabeth R. , Bitler Benjamin G.
Published: July 2024

In vivo association between indicators of autophagy and genomic instability during CMP treatment. Ascites was obtained from tumor-bearing mice treated or not with CMP (4 mg/kg) and prepared in histogel, followed paraffin embedding and multispectral staining (eight proteins plus DAPI). Afterward, a phenotypic characterization was performed. A, Frequency of cells obtained from ascites samples at the end of the study (30 days) showing individual markers as well as cells positive for LC3 A/B and pSTING, and LC3 A/B, pSTING, and pTBK1. B, Representative multispectral IF images (all markers used are indicated in the blue-light box) are shown, where a region of interest (white square) is amplified to show specific markers (white arrow are highlighting the overlay of nuclei and the marker of autophagy, LC3 A/B). (Multiple t test; significance; P < 0.05). Graphs show mean and SEM, scale bar, 50 µm.
Figure 2 from Claudin-4 Modulates Autophagy via SLC1A5/LAT1 as a Mechanism to Regulate Micronuclei
Authors: Villagomez Fabian R. , Lang Julie , Rosario Fredrick J. , Nunez-Avellaneda Daniel , Webb Patricia , Neville Margaret , Woodruff Elizabeth R. , Bitler Benjamin G.
Published: July 2024

Claudin-4 links genomic instability to autophagy in HGSOC cells. We analyzed the functional role of claudin-4, establishing a link between autophagy and micronuclei (indicator of genomic instability) in HGSOC cells. This analysis was conducted both in vitro (HGSOC-GFP-mCherry-LC3 expressing cells) and in vivo (PDX in a humanized mice model). The assessment involved techniques such as flow cytometry, confocal microscopy (CM), and multispectral immunofluorescence. A–C, show percentage autophagy flux in HGSOC cells (flow cytometry) during CMP treatment (400 µmol/L), and claudin-4 genetic manipulation at 24 and 48 hours of culture (four independent experiments; Dotted blue triangles suggest an increase in autophagy). D–F, show confocal images of HGSOC cells expressing GFP-mCherry-LC3 and stained with DAPI (white arrow indicates the convergence of autophagy flux (mCherry) with micronuclei. G, Top, shows confocal images (from live-cell imaging) highlighting (yellow dotted square) a micronucleus; (bottom), kymographs generated from live-cell confocal imaging (from yellow dotted square). It shows the mobility pattern over time of the same region in every channel (Hoechst, GFP, and mCherry). H, Shows a line scan that indicates the fluorescence pattern for the micronucleus and autophagosomes (mCherry) from (G). (significance, P < 0.05). Graphs show mean and SEM, scale bar, 10 and 5 µm.
Data from Claudin-4 Modulates Autophagy via SLC1A5/LAT1 as a Mechanism to Regulate Micronuclei
Authors: Villagomez Fabian R. , Lang Julie , Rosario Fredrick J. , Nunez-Avellaneda Daniel , Webb Patricia , Neville Margaret , Woodruff Elizabeth R. , Bitler Benjamin G.
Published: July 2024

Abstract
Genome instability is a hallmark of cancer crucial for tumor heterogeneity and is often a result of defects in cell division and DNA damage repair. Tumors tolerate genomic instability, but the accumulation of genetic aberrations is regulated to avoid catastrophic chromosomal alterations and cell death. In ovarian cancer tumors, claudin-4 is frequently upregulated and closely associated with genome instability and worse patient outcomes. However, its biological association with regulating genomic instability is poorly understood. Here, we used CRISPR interference and a claudin mimic peptide to modulate the claudin-4 expression and its function in vitro and in vivo. We found that claudin-4 promotes a tolerance mechanism for genomic instability through micronuclei generation in tumor cells. Disruption of claudin-4 increased autophagy and was associated with the engulfment of cytoplasm-localized DNA. Mechanistically, we observed that claudin-4 establishes a biological axis with the amino acid transporters SLC1A5 and LAT1, which regulate autophagy upstream of mTOR. Furthermore, the claudin-4/SLC1A5/LAT1 axis was linked to the transport of amino acids across the plasma membrane as one of the potential cellular processes that significantly decreased survival in ovarian cancer patients. Together, our results show that the upregulation of claudin-4 contributes to increasing the threshold of tolerance for genomic instability in ovarian tumor cells by limiting its accumulation through autophagy.
Significance:
Autophagy regulation via claudin-4/SLC1A5/LAT1 has the potential to be a targetable mechanism to interfere with genomic instability in ovarian tumor cells.
Spinoza and Blyenbergh: between the semantics of friendship and the one of evil
Authors: Vieira Douglas Nunes
Published: July 2024

Born as a promising beginning of a friendship formed between two lovers of truth, the correspondence between Spinoza and Blyenbergh turned out to be a real disappointment. Because they knew the truth through different paths, in the languages of Spinoza and Blyenbergh, the words God and evil, which underpin the entire problem of the correspondence, could only mean completely different things. Although both agreed that God is supremely perfect and the cause of all things, Blyenbergh conceived that men and women could go against God, saddening him to the point of punishing them for it, Spinoza, on the other hand, understood that God is nothing but absolute perfection. While one conceived evil as a deprivation of good, for the other, it is nothingness. For this reason, Spinoza and Blyenbergh could never communicate with each other using the language of philosophers, a necessary condition for uniting themselves for the love of truth.
An introduction to the study of the archives from "Fundo Modesto Carone"
Authors: Rodrigues Everaldo
Published: July 2024

Este artigo se debruça sobre alguns documentos de processo do escritor, poeta, crítico literário, ensaísta, tradutor e professor Modesto Carone (1937–2019), mantidos no “Fundo Modesto Carone”, pelo Centro de Documentação Cultural “Alexandre Eulalio” (CEDAE) do Instituto de Estudos da Linguagem da Universidade Estadual de Campinas (IEL/Unicamp). A partir de recortes baseados em três áreas de atuação do titular (seu trabalho como ficcionista, ensaísta e tradutor), busca-se apresentar brevemente os arquivos de Carone como uma nova fonte para os estudos de crítica genética no Brasil, lançar algumas hipóteses interpretativas a partir da análise dos espaços relacionais entre os prototextos selecionados e delinear as práticas de escrita do autor, de modo que possa se estabelecer uma base para a compreensão de suas facetas autorais, assim como das relações entre elas. O objetivo do artigo é revelar o potencial de pesquisa do fundo, com inúmeras possibilidades de estudos, desde a análise do processo de escrita, passando pela intersecção entre crítica genética e tradução, até pesquisas sobre a influência da biografia na escritura, a crítica da crítica e o estudo das correspondências.
Atrial Fibrillation: Prevalence and Association With Outcome in Patients With Stroke Undergoing Mechanical Thrombectomy in the United States
Authors: Otite Fadar Oliver , Patel Smit D. , Hoffman Haydn , Aneni Ehimen , Anikpezie Nnabuchi , Akano Emmanuel Oladele , Wee Claribel , Burke Devin , Albright Karen , Beutler Timothy , Latorre Julius Gene , Sonig Ashish , Singla Amit , Morris Nicholas , Chaturvedi Seemant , Khandelwal Priyank
Published: July 2024

Background

How the prevalence of atrial fibrillation (AF) has changed over time in various demographic subgroups of patients with acute ischemic stroke (AIS) undergoing mechanical thrombectomy (MT) in the United States is unknown. Whether in‐hospital outcomes differ between patients with AF versus patients without AF after MT remains uncertain.

Methods

We conducted a serial cross‐sectional study using all primary AIS discharges in the 2010 to 2020 National Inpatient Sample. Discharges with MT codes were identified (n = 155 277), and the proportion with AF in various age, sex, and racial subgroups were computed. We used multivariable‐adjusted negative binomial regression to compare AF prevalence between demographic subgroups and joinpoint regression to evaluate trends over time. Multivariable‐adjusted generalized linear models were used to evaluate the association of AF with in‐hospital outcomes.

Results

Across the study period, 45.0% of AIS discharges with MT had AF, but prevalence varied by age, sex, and race or ethnicity. After multivariable adjustment, AF prevalence was 4% higher in women versus men (prevalence rate ratio, 1.04 [95% CI, 1.01–1.07]) and was lower in Black versus White (prevalence rate ratio, 0.80 [95% CI, 0.77–0.84]) but higher in Asian compared with White discharges (prevalence rate ratio, 1.11 [95% CI, 1.05–1.18]). Prevalence increased with age (prevalence rate ratio for ≥80 years versus 18–39 years, 5.23 [95% CI, 4.28–6.39]). Following joinpoint regression, prevalence increased by 3.2% (95% CI, 1.3%–5.2%) annually across the period 2010 to 2015 but declined by −2.2% (95% CI −2.9% to −1.4%) from 2015 to 2020. AF was associated with 22% lower odds of in‐hospital death (odds ratio, 0.78 [95% CI, 0.71–0.85]) and 13% greater odds of routine home discharge (odds ratio, 1.13 95% CI, 1.04–1.22]) compared with no AF.

Conclusion

AF prevalence in patients undergoing MT in the United States is approximately twice that of the general AIS population. AF prevalence in MT increased from 2010 to 2015 but declined from 2015 to 2020. In the subset of patients with AIS undergoing MT, AF is associated with reduced in‐hospital death.