bluuebunny/crossref_metadata_2025 huggingface dataset:
The Development and Teaching Application of Japanese Peripheral Language Phenomenon Based on Big Data Corpus
Authors: Wei Yi
Published: October 2023

Since the introduction of the concept of big data corpus into language analysis, many scholars have conducted research on Japanese big data corpus, especially the subject, from different language views and perspectives, and have drawn many valuable conclusions. However, due to scholars' different theories and different thinking modes, their understanding of the Japanese big data corpus is still quite different. The seminar teaching method, as a teaching mode for the cultivation of innovative talents in Japanese peripheral languages, has distinctive features such as interactivity, democracy, motivation, and extension. It has been widely used in postgraduate and undergraduate courses at home and abroad and applied to A wide range of disciplines. Especially in Japan, each university has Seminar courses. Because of its strong practicality, it is conducive to cultivating students' independent learning ability, organization and coordination ability, and communication ability, so whether it can be applied and promoted in the teaching of Japanese peripheral languages, this research is carried out. Although experts have always been committed to the innovation of Japanese teaching, the advancement of teaching materials, and the continuous innovation of design, they also need the teaching practice and experimentation of front-line teachers. After years of practice in basic Japanese teaching by generations of teachers, we still encounter this problem: students cannot use the language fluently, they can only memorize words, grammar, and the usage of some fixed terms by rote; Some students with strong writing ability are not strong in conversation and expression. According to these problems in teaching, the author found that students could not use language well, probably because they did not have the awareness and desire to communicate. Sometimes the single teaching method and the boring teaching content make students uninterested in learning Japanese, and the large number of pseudonyms, Chinese characters, and complex grammatical structures make students dazzled. The experimental results show that the new teaching method proposed by the experimental model is suitable for the learning of Japanese peripheral languages, which improves the student's learning and thinking ability, which proves that the optimized NN-SLVM model is good.
Role of the Microenvironment in Glioma Pathogenesis
Authors: Jayaram Maya Anjali , Phillips Joanna J.
Published: October 2023

Gliomas are a diverse group of primary central nervous system tumors that affect both children and adults. Recent studies have revealed a dynamic cross talk that occurs between glioma cells and components of their microenvironment, including neurons, astrocytes, immune cells, and the extracellular matrix. This cross talk regulates fundamental aspects of glioma development and growth. In this review, we discuss recent discoveries about the impact of these interactions on gliomas and highlight how tumor cells actively remodel their microenvironment to promote disease. These studies provide a better understanding of the interactions in the microenvironment that are important in gliomas, offer insight into the cross talk that occurs, and identify potential therapeutic vulnerabilities that can be utilized to improve clinical outcomes.
Analysis of Microbiome Data
Authors: Peterson Christine B. , Saha Satabdi , Do Kim-Anh
Published: October 2023

The microbiome represents a hidden world of tiny organisms populating not only our surroundings but also our own bodies. By enabling comprehensive profiling of these invisible creatures, modern genomic sequencing tools have given us an unprecedented ability to characterize these populations and uncover their outsize impact on our environment and health. Statistical analysis of microbiome data is critical to infer patterns from the observed abundances. The application and development of analytical methods in this area require careful consideration of the unique aspects of microbiome profiles. We begin this review with a brief overview of microbiome data collection and processing and describe the resulting data structure. We then provide an overview of statistical methods for key tasks in microbiome data analysis, including data visualization, comparison of microbial abundance across groups, regression modeling, and network inference. We conclude with a discussion and highlight interesting future directions.
Nutritional Analysis of Elote Tamales Cooked in a Hybrid-Solar Cooker
Authors: del Río J. A. , Hernández-Medina Arnold A. , López-Ortiz Anabel
Published: October 2023

Cooking traditional meals using a solar cooker is often challenging because it may require maintaining temperatures of 63 to 180°C for extended periods. A popular Mesoamerican/Mexican dish, “tamale,” is a vapor-cooked corn dough meal/flour wrapped inside corn husk, which may be prepared in a solar cooker. However, its nutritionally rich variety, “elote tamal” prepared from ground fresh corn kernels of tender corncobs with added sugar, fresh milk, and butter, becomes unpalatable under such solar cooking. The initial slow rise in temperature leads to the fermentation of the dough-milk mix and degrades the product. We show that an auxiliary electric heater boosting the temperature at the initial period in an electric-solar hybrid cooker can overcome this limitation. Furthermore, we found significant differences in the total sugar and titratable acidity in the slow-cooked elote tamal. These differences are associated with the incipient fermentation introduced in the milk-containing dough mix during the slow heating stage in traditional solar cooking. We analyzed and compared the protein, fat, moisture content, ash, total sugars, total fibers, titratable acidity, and color of elote tamales prepared under four different cooking conditions. Milk-based tamales under solar cooking require an additional thermal booster at the initial stage to avoid fermentation and eventual loss of quality of the cooked dish. This research is also relevant to the solar cooking of other milk-based meals.
Characterization and Antimicrobial Susceptibility Patterns of Listeria monocytogenes from Raw Cow Milk in the Southern Part of Ethiopia
Authors: Hawaz Habtamu , Taye Mestawet , Muleta Diriba
Published: October 2023

Food safety remains the main health concern in the developing countries. Thus, the major purpose of the present study was to characterize and determine antibiotic susceptibility patterns of Listeria monocytogenes from raw milk samples collected from southern Ethiopia. Two hundred and forty raw cow milk samples were collected from dairy farms and smallholder dairy producers using a simple random sampling technique and analyzed by cultural and multiplex PCR methods. The antimicrobial susceptibility profile of L. monocytogenes was evaluated using the standard disk diffusion method. Over 28% of the samples were found positive for Listeria spp., of which 17 (7.08%) isolates were identified as L. monocytogenes after morphological and biochemical confirmation. The prevalence of L. monocytogenes was 6.02% in Hawassa city, 5.56% in Dale district, and 9.41% in Arsi Negele district. L. monocytogenes was higher in the wet season (9.32%) than in the dry season (4.92%). The gene for Listeria specific 16S rRNA was detected in all the 17 examined isolates, while hlyA and iapA were only found in 11 of them. Furthermore, no isolate was identified to have the prfA, actA, or plcA genes. Antimicrobial resistance profiling revealed that all the L. monocytogenes isolates were resistant to nalidixic acid (100%), followed by erythromycin (88.24%). However, all the L. monocytogenes isolates were sensitive to vancomycin, gentamicin, and sulfamethoxazole. Raw cow milk is a potential source of L. monocytogenes and it poses a threat to human and animal health. Therefore, it is crucial that dairy producers and vendors of raw milk in the study areas should take considerable precautions to prevent Listeria species from contaminating raw fresh milk.
The Differences of Quantitative Flow Ratio in Coronary Artery Stenosis with or without Atrial Fibrillation
Authors: Lu Wenbin , Zhang Xiaoguo , Yan Gaoliang , Ma Genshan
Published: October 2023

Quantitative flow ratio (QFR) is a new method for the assessment of the extent of coronary artery stenosis. But it may be obscured by the cardiac remodeling and abnormal blood flow of the coronary artery when encountering atrial fibrillation (AF). The present study aimed to examine the impact of these changed structures and blood flow of coronary arteries on QFR results in AF patients. Methods and Results. We evaluated QFR in 223 patients (112 patients with AF; 111 non-AF patients served as controls) who had undergone percutaneous coronary intervention (PCI) due to severe stenoses in coronary arteries. QFR of the target coronary was determined according to the flow rate of the contrast agent. Results showed that AF patients had significantly higher QFR values than control (0.792 ± 0.118 vs. 0.685 ± 0.167,

p
<
0.001

). We further analyzed local QFR around the stenoses (0.858 ± 0.304 vs. 0.756 ± 0.146,

p
=
0.002

), residual QFR (0.958 ± 0.055 vs. 0.929 ± 0.093,

p
=
0.005

), and index QFR (0.807 ± 0.108 vs. 0.713 ± 0.152,

p
<
0.001

) in these two groups of patients with and without AF. Further analysis revealed that QFR in AF patients was negatively correlated with coronary flow velocity (R = −0.22,

p
=
0.02

) and area of stenosis (R = −0.70,

p
<
0.001

) but positively correlated with the minimum lumen area (MLA) (R = 0.47,

p
<
0.001

). Conclusion. AF patients with coronary artery stenosis have higher QFR values, which are associated with decreased blood flow velocity, smaller stenosis, and larger MLA in AF patients upon cardiac remodeling.
Evaluation of Dioxin/Furan and Elements in Poultry from Zarqa Governorate, Jordan
Authors: Masad Mohanad , Alawaideh Samer , Nusairat Basheer , Alnawaiseh Ali , Al Shra’ah Ahmad
Published: October 2023

This study is the first to determine the concentration for 17 congeners of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs) and element contamination in poultry that is close to petroleum refinery at Al-Hashemiya Municipality, Zarqa Governorate, Jordan. Ten different samples (chicken) were collected to cover ten different locations of poultry farms in Al-Hashemiya Municipality. These locations are considered polluted areas as a result of exhaust gases produced from the refinery. The 17 PCDD/Fs congeners and elements of Pb, Cd, As, Zn, Cu, Se, Hg, Cr, and Ni were determined for three parts of each sample (liver, muscle, and gizzard). All samples were analyzed for PCDD/Fs after a Soxhlet extraction procedure and cleanup by column chromatography; then, all compounds were identified and determined using GC-MS techniques. The elements were analyzed after digestion and measured using an inductively coupled plasma optical emission spectrometer (ICP-OES) and validated with the Lab Mix24 RM NCS ZC73016 reference material. The highest total sum concentration of PCDD/Fs was found in liver samples to be 214.07 ng/kg (dry weight), while the highest sum of toxicity equivalent to PCDD/Fs of 22.54 ng TEQ/kg was found in gizzard samples. For element concentrations, the highest total sum of 16.89 mg/kg (dry weight) was found in liver samples. The concentration level of the elements of Se, Hg, Cr, and Ni for all parts of the chicken was within an acceptable range according to Jordanian standards and therefore the measured level of heavy and trace elements in the poultry samples (chicken) does not pose a danger to public health. The chickens found in poultry farms near the refinery are more likely to contain a higher concentration of PCDD/Fs congeners due to exhaust gas exposure.
Enhancing User Satisfaction in Indonesia’s e-wallet Market: A Comprehensive Analysis of Factors and Priorities
Authors: Nurcahyo Rahmat , Prabuwono Anton Satria , Fainusa Akmal Fatah , Wibowo Nurhadi , Habiburrahman Muhammad , Hindriyandhito Khairi
Published: October 2023

Research on user satisfaction is crucial because it is the key to digital business success, including e-wallet in Indonesia which is experiencing very rapid growth. This study is aimed at determining the gap between e-wallet perception and user expectations, evaluating the level of user satisfaction among e-wallet, and determining the priority of improvement of the factors that affect e-wallet user satisfaction. Data processing is divided into four stages: Kano model, processing the comparison between user satisfaction data based on the gap in the value of perceptions and user expectations, processing of satisfaction gaps between e-wallet applications, and processing for multinomial logistic regression (MLR). To measure user satisfaction with a service, the concept of SERVQUAL, which consists of tangibles, reliability, responsiveness, assurance, and empathy, was used. Data were collected using online questionnaire distributed in the areas of Jakarta, Bogor, Depok, Tangerang, and Bekasi. The results of this study show that based on a comparison between users’ perceptions and expectations, the satisfaction gap value is negative. This shows that e-wallet users are not satisfied. The comparison of satisfaction gaps between e-wallet shows significant differences for security, efficiency, reliability, application display design, and economic benefit factors, whereas no significant difference is found for the customer service factor. This study provides the priority of improvement for each e-wallet provider. The novelty of this research is the priority for improvement that is derived from a combination of expectation and perception mapping, Kano’s model, and MLR. The findings could be used to increase the user satisfaction that can lead to the success of an e-wallet application.
Facial Video‐Based Robust Measurement of Respiratory Rates in Various Environmental Conditions
Authors: Park Jinsoo , Hong Kwangseok
Published: October 2023

This paper addresses the process of respiration, which involves providing oxygen to the body’s cells, blood, and tissues. The significance of respiratory signals as predictors of diverse physical conditions, including respiratory health and disorders, is emphasized. Technologies such as pressure‐sensor belts for chest or abdominal movement detection, carbon‐dioxide sensors placed under the nose, and photoplethysmography (PPG) have been developed for real‐time monitoring of respiratory signals. However, wearable devices with direct body contact may inconvenience sleeping patients, newborns, or individuals with sensitive skin. Noncontact and noninvasive respiratory rate measurements utilizing facial videos have been explored, albeit within controlled environments. This study introduces a novel approach to measure robust respiratory signals and facial respiratory rates (FRR) using facial videos. The proposed method employs bounding box stabilization to eliminate high‐frequency components stemming from face detection. Real‐time coordinate correction is implemented to ensure accurate respiration signal calculation across varying environments. The method defines a region of interest (ROI) on the face, computes RGB data, and transforms the RGB channel into a YCgCo channel. The respiratory signal is subsequently derived by applying partial zero padding‐based fast Fourier transform (FFT) and inverse FFT (iFFT) to the Cg signal within the frequency band associated with respiration. The FRR is accurately measured by analyzing peak‐to‐peak intervals within the respiratory signal. The efficacy of the proposed method is demonstrated through a comparative analysis of respiratory rates calculated from PPG devices and facial videos across four scenarios (indoor, outdoor, car, and drone). The results highlight the reliability and precision of the suggested approach in accurately computing respiratory rates across diverse environments.
Supplementary Table 2 from Spatial Profiling of Circular RNAs in Cancer Reveals High Expression in Muscle and Stromal Cells
Authors: García-Rodríguez Juan L. , Korsgaard Ulrik , Ahmadov Ulvi , Jarlstad Olesen Morten T. , Dietrich Kim-Gwendolyn , Hansen Emma B. , Vissing Stine M. , Ulhøi Benedichte P. , Dyrskjøt Lars , Sørensen Karina D. , Kjems Jørgen , Hager Henrik , Kristensen Lasse S.
Published: October 2023

List of reference genes, tissue markers genes and top circular RNAs for which nanostring nCounter probes were designed.
Supplementary Figure 1 from Spatial Profiling of Circular RNAs in Cancer Reveals High Expression in Muscle and Stromal Cells
Authors: García-Rodríguez Juan L. , Korsgaard Ulrik , Ahmadov Ulvi , Jarlstad Olesen Morten T. , Dietrich Kim-Gwendolyn , Hansen Emma B. , Vissing Stine M. , Ulhøi Benedichte P. , Dyrskjøt Lars , Sørensen Karina D. , Kjems Jørgen , Hager Henrik , Kristensen Lasse S.
Published: October 2023

Evaluation of the most abudant circRNAs from human datasets. Boxplot showing the normalized
nCounter counts from the top 50 circRNAs extracted from publicly available human RNAseq datasets (2 normal colon, 1 tumor and paired normal adjacent tissue) (GSE77661) (A) and from the top 20 high-abundance circRNAs according to the data extracted from the three different microarray datasets comparing human tumor vs paired normal tisues (GSE126094,
GSE142837 and GSE138589) (B). C, NanoString nCounter analysis of 48 circRNA and 7 mRNA in mock and RNase R treated RNA samples from the Caco-2 cell line. Among the 48 circRNAs only 37 were expressed above cutoff levels in this cell line. D, Sanger sequencing across the backsplicing junction of the 3 circRNAs that haven't been described before. The scattered horizontal lines represent the background threshold. The box represents the interquartile range (Q1 and Q3), the median is marked with horizontral line, and whiskers represent m and maximum values.
Figure S1 from Targeting the Immunoglobulin IGSF9 Enhances Antitumor T-cell Activity and Sensitivity to Anti–PD-1 Immunotherapy
Authors: Liu Yifan , Wang Hongying , Zhao Xinyu , Zhang Jiashen , Zhao Zhiling , Lian Xia , Zhang Juan , Kong Feng , Hu Tao , Wang Ting , Li Xiaohua , Wang Lei , Wang Dapeng , Li Chunling , Luan Huiwen , Liu Xiaoli , Wang Chunyan , Jiang Yun , Li Xiaomin , Li Fangmin , Ji Shuhao , Wang Yaopeng , Li Zunling
Published: October 2023

IGSF9 expression was detected in tumor tissue arrays by immunohistochemistry.
Tables S7-S9 from Integrative Genomic Analyses Identify LncRNA Regulatory Networks across Pediatric Leukemias and Solid Tumors
Authors: Modi Apexa , Lopez Gonzalo , Conkrite Karina L. , Su Chun , Leung Tsz Ching , Ramanan Sathvik , Manduchi Elisabetta , Johnson Matthew E. , Cheung Daphne , Gadd Samantha , Zhang Jinghui , Smith Malcolm A. , Guidry Auvil Jaime M. , Meshinchi Soheil , Perlman Elizabeth J. , Hunger Stephen P. , Maris John M. , Wells Andrew D. , Grant Struan F.A. , Diskin Sharon J.
Published: October 2023

Table S7: Number of TARGET samples with WGS and SCNA events per cancer identified by GISTIC, Table S8: Differential expression of genes in samples with and without SCNA, Table S9: Number of samples with SVs in lncRNAs
Supplementary Fig. 2 from Spatial Profiling of Circular RNAs in Cancer Reveals High Expression in Muscle and Stromal Cells
Authors: García-Rodríguez Juan L. , Korsgaard Ulrik , Ahmadov Ulvi , Jarlstad Olesen Morten T. , Dietrich Kim-Gwendolyn , Hansen Emma B. , Vissing Stine M. , Ulhøi Benedichte P. , Dyrskjøt Lars , Sørensen Karina D. , Kjems Jørgen , Hager Henrik , Kristensen Lasse S.
Published: October 2023

Tissue markers specificity. Normalized NanoString counts from specific tissue markers used for sub-compartment purity assessment after laser capture microdissection. KRT8, CDX2 and SATB2 are epithelial markers. VIM is an activated stromal marker and ACTA2 and DES are muscle cell markers. Parametric t-tests were performed to compute the p-values using the values from the cancer cells as reference. The box represents the interquartile range (Q1 and Q3), the median is marked with a horizontal line, and whiskers represent minimum and maximum values.
Supplementary Data from GTP Cyclohydrolase Drives Breast Cancer Development and Promotes EMT in an Enzyme-Independent Manner
Authors: Wang Zijing , Zhang Nan , Zhang Miao , Jiang Yao , Ng Aik Seng , Bridges Esther , Zhang Wei , Zeng Xin , Luo Qi , Liang Jiabien , Győrffy Balázs , Hublitz Philip , Liang Zhu , Fischer Roman , Kerr David , Harris Adrian L. , Cai Shijie
Published: October 2023

Tables and figure legends
Data from Targeting the immunoglobulin IGSF9 enhances anti-tumor T cell activity and sensitivity to anti-PD-1 immunotherapy
Authors: Liu Yifan , Wang Hongying , Zhao Xinyu , Zhang Jiashen , Zhao Zhiling , Lian Xia , Zhang Juan , Kong Feng , Hu Tao , Wang Ting , Li Xiaohua , Wang Lei , Wang Dapeng , Li Chunling , Luan Huiwen , Liu Xiaoli , Wang Chunyan , Jiang Yun , Li Xiaomin , Li Fangmin , Ji Shuhao , Wang Yaopeng , Li Zunling
Published: October 2023

Abstract
Immune checkpoints modulate the immune response and represent important immunotherapy targets for cancer treatment. However, as many tumors are resistant to current immune checkpoint inhibitors, the discovery of novel immune checkpoints could facilitate the development of additional immunotherapeutic strategies to improve patient responses. Here, we identified increased expression of the adhesion molecule immunoglobulin superfamily member 9 (IGSF9) in tumor cells and tumor-infiltrating immune cells across multiple cancer types. IGSF9 overexpression or knockout in tumor cells did not alter cell proliferation in vitro or tumor growth in immunocompromised mice. Alternatively, IGSF9 deficient tumor cells lost the ability to suppress T cell proliferation and exhibited reduced growth in immunocompetent mice. Similarly, growth of tumor cells was reduced in IGSF9 knockout syngeneic and humanized mice, accompanied by increased tumor-infiltrating T cells. Mechanistically, the extracellular domain (ECD) of IGSF9 bound to T cells and inhibited their proliferation and activation, and the tumor promoting effect of IGSF9 ECD was reversed by CD3+ T cell depletion. Anti-IGSF9 antibody treatment inhibited tumor growth and enhanced the anti-tumor efficacy of anti-PD-1 immunotherapy. Single-cell RNA sequencing revealed tumor microenvironment remodeling from tumor-promoting to tumor-suppressive following anti-IGSF9 treatment. Together, these results indicate that IGSF9 promotes tumor immune evasion and is a candidate immune checkpoint target.
Data from Integrative Genomic Analyses Identify LncRNA Regulatory Networks across Pediatric Leukemias and Solid Tumors
Authors: Modi Apexa , Lopez Gonzalo , Conkrite Karina L. , Su Chun , Leung Tsz Ching , Ramanan Sathvik , Manduchi Elisabetta , Johnson Matthew E. , Cheung Daphne , Gadd Samantha , Zhang Jinghui , Smith Malcolm A. , Guidry Auvil Jaime M. , Meshinchi Soheil , Perlman Elizabeth J. , Hunger Stephen P. , Maris John M. , Wells Andrew D. , Grant Struan F.A. , Diskin Sharon J.
Published: October 2023

Abstract
Long noncoding RNAs (lncRNA) play an important role in gene regulation and contribute to tumorigenesis. While pan-cancer studies of lncRNA expression have been performed for adult malignancies, the lncRNA landscape across pediatric cancers remains largely uncharted. Here, we curated RNA sequencing data for 1,044 pediatric leukemia and extracranial solid tumors and integrated paired tumor whole genome sequencing and epigenetic data in relevant cell line models to explore lncRNA expression, regulation, and association with cancer. A total of 2,657 lncRNAs were robustly expressed across six pediatric cancers, including 1,142 exhibiting histotype-elevated expression. DNA copy number alterations contributed to lncRNA dysregulation at a proportion comparable to protein coding genes. Application of a multidimensional framework to identify and prioritize lncRNAs impacting gene networks revealed that lncRNAs dysregulated in pediatric cancer are associated with proliferation, metabolism, and DNA damage hallmarks. Analysis of upstream regulation via cell type–specific transcription factors further implicated distinct histotype-elevated and developmental lncRNAs. Integration of these analyses prioritized lncRNAs for experimental validation, and silencing of TBX2-AS1, the top-prioritized neuroblastoma-specific lncRNA, resulted in significant growth inhibition of neuroblastoma cells, confirming the computational predictions. Taken together, these data provide a comprehensive characterization of lncRNA regulation and function in pediatric cancers and pave the way for future mechanistic studies.
Significance:
Comprehensive characterization of lncRNAs in pediatric cancer leads to the identification of highly expressed lncRNAs across childhood cancers, annotation of lncRNAs showing histotype-specific elevated expression, and prediction of lncRNA gene regulatory networks.
Data from Radiation therapy-induced neurocognitive impairment is driven by heightened apoptotic priming in early life and prevented by blocking BAX
Authors: Singh Rumani , Yu Stacey , Osman Marwa , Inde Zintis , Fraser Cameron , Cleveland Abigail H. , Almanzar Nicole , Lim Chuan Bian , Joshi Gaurav N. , Spetz Johan , Qin Xingping , Toprani Sneh M. , Nagel Zachary , Hocking Matthew C. , Cormack Robert A. , Yock Torunn I. , Miller Jeffrey W. , Yuan Zhi-Min , Gershon Timothy , Sarosiek Kristopher A.
Published: October 2023

Abstract
Although external beam radiation therapy (xRT) is commonly used to treat central nervous system (CNS) tumors in patients of all ages, young children treated with xRT frequently experience life-altering and dose-limiting neurocognitive impairment (NI) while adults do not. The lack of understanding of mechanisms responsible for these differences has impeded the development of neuroprotective treatments. Using a newly developed mouse model of xRT-induced NI, we found that neurocognitive function is impaired by ionizing radiation in a dose- and age-dependent manner, with the youngest animals being most affected. Histological analysis revealed xRT-driven neuronal degeneration and cell death in neurogenic brain regions in young animals but not adults. BH3 profiling showed that neural stem and progenitor cells, neurons, and astrocytes in young mice are highly primed for apoptosis, rendering them hypersensitive to genotoxic damage. Analysis of single cell RNA-seq data revealed that neural cell vulnerability stems from heightened expression of pro-apoptotic genes including BAX, which is associated with developmental and mitogenic signaling by MYC. xRT induced apoptosis in primed neural cells by triggering a p53- and PUMA-initiated, pro-apoptotic feedback loop requiring cleavage of BID and culminating in BAX oligomerization and caspase activation. Notably, loss of BAX protected against apoptosis induced by pro-apoptotic signaling in vitro and prevented xRT-induced apoptosis in neural cells in vivo as well as neurocognitive sequelae. Based on these findings, preventing xRT-induced apoptosis specifically in immature neural cells by blocking BAX, BIM or BID via direct or upstream mechanisms is expected to ameliorate neurocognitive impairment in pediatric CNS tumor patients.
Data from GTP cyclohydrolase drives breast cancer development and promotes EMT in an enzyme-independent manner
Authors: Wang Zijing , Zhang Nan , Zhang Miao , Jiang Yao , Ng Aik Seng , Bridges Esther , Zhang Wei , Zeng Xin , Luo Qi , Liang Jiabien , Gyorffy Balázs , Hublitz Philip , Liang Zhu , Fischer Roman , Kerr David , Harris Adrian L. , Cai Shijie
Published: October 2023

Abstract
GTP cyclohydrolase (GCH1) is the rate-limiting enzyme for tetrahydrobiopterin (BH4) biosynthesis. The catalysis of BH4 biosynthesis is tightly regulated for physiological neurotransmission, inflammation, and vascular tone. Paradoxically, BH4 has emerged as an oncometabolite regulating tumor growth, but the effects on tumor development remain controversial. Here we found that GCH1 potentiates the growth of triple-negative breast cancer (TNBC) and HER2+ breast cancer and transforms non-tumor breast epithelial cells. Independent of BH4 production, GCH1 protein induced epithelial-to-mesenchymal transition IEMT) by binding to Vim, which was mediated by HSP90. Conversely, GCH1 ablation impaired tumor growth, suppressed Vim in TNBC, and inhibited EGFR/ERK signaling while activating the p53 pathway in estrogen receptor-positive tumor cells. GCH1 deficiency increases tumor cell sensitivity to HSP90 inhibition and endocrine treatments. Additionally, high GCH1 corelated with poor breast cancer survival. Together, this study reveals an enzyme-independent oncogenic role of GCH1, presenting it as a potential target for therapeutic development.
Supplementary Tables 1-8 from A Population of Tumor-Infiltrating CD4+ T Cells Co-Expressing CD38 and CD39 Is Associated with Checkpoint Inhibitor Resistance
Authors: Mitra Ankita , Thompson Brian , Strange Ann , Amato Carol M. , Vassallo Melinda , Dolgalev Igor , Hester-McCullough Jonathan , Muramatsu Tomoaki , Kimono Diana , Puranik Amrutesh S. , Weber Jeffrey S. , Woods David
Published: October 2023

Supplementary Tables 1 - 8
Supplementary Figure S7 from Memory-like Differentiation, Tumor-Targeting mAbs, and Chimeric Antigen Receptors Enhance Natural Killer Cell Responses to Head and Neck Cancer
Authors: Jacobs Miriam T. , Wong Pamela , Zhou Alice Y. , Becker-Hapak Michelle , Marin Nancy D. , Marsala Lynne , Foster Mark , Foltz Jennifer A. , Cubitt Celia C. , Tran Jennifer , Russler-Germain David A. , Neal Carly , Kersting-Schadek Samantha , Chang Lily , Schappe Timothy , Pence Patrick , McClain Ethan , Zevallos Jose P. , Rich Jason T. , Paniello Randal C. , Jackson Ryan S. , Pipkorn Patrik , Adkins Douglas R. , DeSelm Carl J. , Berrien-Elliott Melissa M. , Puram Sidharth V. , Fehniger Todd A.
Published: October 2023

Supplementary Figure 7. EphA2-CAR-ML NK cells require intracellular CAR signaling and have antigen specific enhanced response to HNSCC.
Supplementary Figure S2 from Memory-like Differentiation, Tumor-Targeting mAbs, and Chimeric Antigen Receptors Enhance Natural Killer Cell Responses to Head and Neck Cancer
Authors: Jacobs Miriam T. , Wong Pamela , Zhou Alice Y. , Becker-Hapak Michelle , Marin Nancy D. , Marsala Lynne , Foster Mark , Foltz Jennifer A. , Cubitt Celia C. , Tran Jennifer , Russler-Germain David A. , Neal Carly , Kersting-Schadek Samantha , Chang Lily , Schappe Timothy , Pence Patrick , McClain Ethan , Zevallos Jose P. , Rich Jason T. , Paniello Randal C. , Jackson Ryan S. , Pipkorn Patrik , Adkins Douglas R. , DeSelm Carl J. , Berrien-Elliott Melissa M. , Puram Sidharth V. , Fehniger Todd A.
Published: October 2023

Supplementary Figure 2. HNSCC cell lines and patient samples express multiple inhibitory and activating surface ligands.
Supplementary Table S11 from Single-Cell RNA Analysis Reveals Cell-Intrinsic Functions of CAR T Cells Correlating with Response in a Phase II Study of Lymphoma Patients
Authors: Sarén Tina , Ramachandran Mohanraj , Gammelgård Gustav , Lövgren Tanja , Mirabello Claudio , Björklund Åsa K. , Wikström Kristina , Hashemi Jamileh , Freyhult Eva , Ahlström Håkan , Amini Rose-Marie , Hagberg Hans , Loskog Angelica , Enblad Gunilla , Essand Magnus
Published: October 2023

List of antibodies and dyes used for flow cytometry assays
Supplementary Figure S9 from Single-Cell RNA Analysis Reveals Cell-Intrinsic Functions of CAR T Cells Correlating with Response in a Phase II Study of Lymphoma Patients
Authors: Sarén Tina , Ramachandran Mohanraj , Gammelgård Gustav , Lövgren Tanja , Mirabello Claudio , Björklund Åsa K. , Wikström Kristina , Hashemi Jamileh , Freyhult Eva , Ahlström Håkan , Amini Rose-Marie , Hagberg Hans , Loskog Angelica , Enblad Gunilla , Essand Magnus
Published: October 2023

Supplementary Figure S9. Gene expression of CD4+ CAR-Ts and relation to response
Supplementary Table S1 from Baseline Mutations and ctDNA Dynamics as Prognostic and Predictive Factors in ER-Positive/HER2-Negative Metastatic Breast Cancer Patients
Authors: Pascual Javier , Gil-Gil Miguel , Proszek Paula , Zielinski Christoph , Reay Alistair , Ruiz-Borrego Manuel , Cutts Rosalind , Ciruelos Gil Eva M. , Feber Andrew , Muñoz-Mateu Montserrat , Swift Claire , Bermejo Begoña , Herranz Jesus , Margeli Vila Mireia , Antón Antonio , Kahan Zsuzsanna , Csöszi Tibor , Liu Yuan , Fernandez-Garcia Daniel , Garcia-Murillas Isaac , Hubank Michael , Turner Nicholas C. , Martín Miguel
Published: October 2023

Supplementary Table 1. List of the 21 genes included in the breast cancer panel used for sequencing, and the targeted coding regions in each case.
Supplemental Figures 1 from Specific Targeting of Multiple Myeloma by Dual Split-signaling Chimeric Antigen Receptor T cells Directed against CD38 and CD138
Authors: van der Schans Jort J. , Wang Ziyu , van Arkel Jennemiek , van Schaik Thijs , Katsarou Afroditi , Ruiter Ruud , Baardemans Thomas , Yuan Huipin , de Bruijn Joost , Zweegman Sonja , van de Donk Niels W.C.J. , Groen Richard W.J. , Themeli Maria , Mutis Tuna
Published: October 2023

Supplemental Figures
Supplementary Table S5 from Neoantigen Targetability in Progressive Advanced Melanoma
Authors: van den Bulk Jitske , Verdegaal Els M.E. , van der Ploeg Manon , Visser Marten , Nunes Joana B. , de Ru Arnoud H. , Tjokrodirijo Rayman T.N. , Ijsselsteijn Marieke E. , Janssen Natasja I. , van der Breggen Ruud , de Bruin Linda , de Kok Pita , Janssen George M.C. , Ruano Dina , Kapiteijn Ellen H.W. , van Veelen Peter A. , de Miranda Noel F.C.C. , van der Burg Sjoerd H.
Published: October 2023

Eluted tumor-associated antigen-derived peptides.
Supplementary Figure S17 from Integrated Genomic and Transcriptomic Analysis Improves Disease Classification and Risk Stratification of MDS with Ring Sideroblasts
Authors: Todisco Gabriele , Creignou Maria , Bernard Elsa , Björklund Ann-Charlotte , Moura Pedro Luis , Tesi Bianca , Mortera-Blanco Teresa , Sander Birgitta , Jansson Monika , Walldin Gunilla , Barbosa Indira , Reinsbach Susanne E. , Hofman Isabel Juliana , Nilsson Christer , Yoshizato Tetsuichi , Dimitriou Marios , Chang David , Olafsdottir Svannildur , Venckute Larsson Sigita , Tobiasson Magnus , Malcovati Luca , Woll Petter , Jacobsen Sten Eirik W. , Papaemmanuil Elli , Hellström-Lindberg Eva
Published: October 2023

Gene set enrichment analysis on differentially expressed genes in LIN- CD34+ cells. Three MDS with RSEMK were compared to 3 MDS without RSIMP and displayed an enrichment of genes expressed in early erythroblast/megakaryocyte progenitor genes and a depletion of genes expressed in myeloid progenitors.
Supplementary Table S1 from Neoantigen Targetability in Progressive Advanced Melanoma
Authors: van den Bulk Jitske , Verdegaal Els M.E. , van der Ploeg Manon , Visser Marten , Nunes Joana B. , de Ru Arnoud H. , Tjokrodirijo Rayman T.N. , Ijsselsteijn Marieke E. , Janssen Natasja I. , van der Breggen Ruud , de Bruin Linda , de Kok Pita , Janssen George M.C. , Ruano Dina , Kapiteijn Ellen H.W. , van Veelen Peter A. , de Miranda Noel F.C.C. , van der Burg Sjoerd H.
Published: October 2023

Whole-exome sequencing strategy.
Supplementary Figure S12 from Integrated Genomic and Transcriptomic Analysis Improves Disease Classification and Risk Stratification of MDS with Ring Sideroblasts
Authors: Todisco Gabriele , Creignou Maria , Bernard Elsa , Björklund Ann-Charlotte , Moura Pedro Luis , Tesi Bianca , Mortera-Blanco Teresa , Sander Birgitta , Jansson Monika , Walldin Gunilla , Barbosa Indira , Reinsbach Susanne E. , Hofman Isabel Juliana , Nilsson Christer , Yoshizato Tetsuichi , Dimitriou Marios , Chang David , Olafsdottir Svannildur , Venckute Larsson Sigita , Tobiasson Magnus , Malcovati Luca , Woll Petter , Jacobsen Sten Eirik W. , Papaemmanuil Elli , Hellström-Lindberg Eva
Published: October 2023

Scatter plots comparing mean PSI values between the MDSRS+ and healthy donors used as normal bone marrow controls (NBM), stratified by genetic classification. Significantly associated events (FDR < 0.0001) are color coded by splicing alterations subtypes.
Figure S2 from HDACi-dependent Microenvironmental Normalization Overcomes Tumor Burden–induced T-cell Exhaustion
Authors: Nguyen Andrew , Brown Dominique , Krishnan Ramya , Bastin Donald , Deng Li , Chen Lan , Salem Omar , Walsh Scott R. , Bramson Jonathan L. , Wan Yonghong
Published: October 2023

Figure S2: Differentially expressed genes when comparing ACT+MS-275- to ACT-treated T cells
Supplementary Table S3 from Safety, Immunologic, and Clinical Activity of Durvalumab in Combination with Olaparib or Cediranib in Advanced Leiomyosarcoma: Results of the DAPPER Clinical Trial.
Authors: Salawu Abdulazeez , Wang Ben X. , Han Ming , Geady Caryn , Heirali Alya , Berman Hal K. , Pfister Thomas D. , Hernando-Calvo Alberto , Al-Ezzi Esmail Mutahar , Stayner Lee-Anne , Gupta Abha A. , Ayodele Olubukola , Lam Bernard , Hansen Aaron R. , Spreafico Anna , Bedard Philippe L. , Butler Marcus O. , Avery Lisa , Coburn Bryan , Haibe-Kains Benjamin , Siu Lillian L. , Abdul Razak Albiruni R.
Published: October 2023

Table S3: Representativeness of study participants
Supplementary Table S1 from Targeting Hedgehog Signaling with Glasdegib in Patients with Refractory Sclerotic Chronic GVHD: A Report of Two Phase I/II Trials
Authors: Rodríguez-Arbolí Eduardo , Lee Catherine J. , Caballero-Velázquez Teresa , Martínez Carmen , García-Calderón Clara , Jiménez-León María Reyes , Bermúdez-Rodríguez María Aránzazu , López-Corral Lucía , Triguero Ana , Onstad Lynn , Horwitz Mitchell E. , Sarantopoulos Stefanie , Lee Stephanie J. , Pérez-Simón José Antonio
Published: October 2023

Monoclonal antibodies used in the immunophenotypic analyses
Data from Negative Predictive Value of Circulating Tumor Tissue Modified Viral (TTMV)-HPV DNA for HPV-driven Oropharyngeal Cancer Surveillance
Authors: Hanna Glenn J. , Roof Scott A. , Jabalee James , Rettig Eleni M. , Ferrandino Rocco , Chen Sida , Posner Marshall R. , Misiukiewicz Krzysztof J. , Genden Eric M. , Chai Raymond L. , Sims John , Thrash Elaine , Stern Scott J. , Kalman Noah S. , Yarlagadda Sreenija , Raben Adam , Clements Lydia , Mendelsohn Abie , Kaczmar John M. , Pandey Yadav , Bhayani Mihir K. , Gupta Piyush , Kuperwasser Charlotte , Del Vecchio Fitz Catherine , Berger Barry M.
Published: October 2023

Abstract
Background: Human papillomavirus (HPV) is causally linked to oropharyngeal squamous cell carcinoma (OPSCC). Consensus guidelines recommend clinical exams and imaging in decreasing frequency as part of post-treatment surveillance for recurrence. Plasma tumor tissue modified viral (TTMV)-HPV DNA testing has emerged as a biomarker which can inform disease status during surveillance. Methods: This retrospective observational cohort study involved 543 patients who completed curative-intent therapy for HPV-associated OPSCC between February 2020 and January 2022 at 8 U.S. cancer care institutions. We determined the negative predictive value (NPV) of TTMV-HPV DNA for recurrence when matched to physician-reported clinical outcome data (median follow-up time: 27.9 months; range: 4.5-154). Results: The cohort included mostly men with a median age of 61 who had locoregionally advanced disease. HPV status was determined by p16 positivity in 87% of patients, with a positive HPV PCR/ISH among 55%; while pre-treatment TTMV-HPV DNA status was unknown for most (79%) patients. Patients had a mean of 2.6 tests and almost half had 3 or more TTMV-HPV DNA results during surveillance. The per-test and per-patient sensitivity of the assay was 92.5% (95%CI: 87.5-97.5) and 87.3% (95%CI: 79.1-95.5), respectively. The NPV for the assay was 99.4% (95%CI: 98.9-99.8) and 98.4% (95%CI: 97.3-99.5), respectively. Conclusions: TTMV-HPV DNA surveillance testing yields few false negative results and few missed recurrences. These data could inform decisions on when to pursue re-imaging following first disease restaging and could inform future surveillance practice. Additional study of how pre-treatment TTMV-HPV DNA status impacts sensitivity for recurrence is needed.
Data from Negative Predictive Value of Circulating Tumor Tissue Modified Viral (TTMV)-HPV DNA for HPV-driven Oropharyngeal Cancer Surveillance
Authors: Hanna Glenn J. , Roof Scott A. , Jabalee Jamie , Rettig Eleni M. , Ferrandino Rocco , Chen Sida , Posner Marshall R. , Misiukiewicz Krzysztof J. , Genden Eric M. , Chai Raymond L. , Sims John , Thrash Elaine , Stern Scott J. , Kalman Noah S. , Yarlagadda Sreenija , Raben Adam , Clements Lydia , Mendelsohn Abie , Kaczmar John M. , Pandey Yadav , Bhayani Mihir , Gupta Piyush , Kuperwasser Charlotte , Del Vecchio Fitz Catherine , Berger Barry M.
Published: October 2023

AbstractPurpose:
Human papillomavirus (HPV) is causally linked to oropharyngeal squamous cell carcinoma (OPSCC). Consensus guidelines recommend clinical exams and imaging in decreasing frequency as part of posttreatment surveillance for recurrence. Plasma tumor tissue modified viral (TTMV)-HPV DNA testing has emerged as a biomarker which can inform disease status during surveillance.
Experimental Design:
This retrospective observational cohort study involved 543 patients who completed curative-intent therapy for HPV-associated OPSCC between February 2020 and January 2022 at eight U.S. cancer care institutions. We determined the negative predictive value (NPV) of TTMV-HPV DNA for recurrence when matched to physician-reported clinical outcome data (median follow-up time: 27.9 months; range: 4.5–154).
Results:
The cohort included mostly men with a median age of 61 who had locoregionally advanced disease. HPV status was determined by p16 positivity in 87% of patients, with a positive HPV PCR/ISH among 55%; while pretreatment TTMV-HPV DNA status was unknown for most (79%) patients. Patients had a mean of 2.6 tests and almost half had three or more TTMV-HPV DNA results during surveillance. The per-test and per-patient sensitivity of the assay was 92.5% [95% confidence interval (CI): 87.5–97.5] and 87.3% (95% CI: 79.1–95.5), respectively. The NPV for the assay was 99.4% (95% CI: 98.9–99.8) and 98.4% (95% CI: 97.3–99.5), respectively.
Conclusions:
TTMV-HPV DNA surveillance testing yields few false negative results and few missed recurrences. These data could inform decisions on when to pursue reimaging following first disease restaging and could inform future surveillance practice. Additional study of how pretreatment TTMV-HPV DNA status impacts sensitivity for recurrence is needed.
Data from Preclinical efficacy of LP-184, a tumor site activated synthetic lethal therapeutic, in glioblastoma
Authors: Lal Bachchu , Kulkarni Aditya , McDermott Joseph , Rais Rana , Alt Jesse , Wu Ying , Lopez-Bertoni Hernando , Sall Sophie , Kathad Umesh , Zhou Jianli , Slusher Barbara S. , Bhatia Kishor , Laterra John
Published: October 2023

Abstract
Purpose: Glioblastoma (GBM), is the most common brain malignancy with median survival <2 yrs. Standard-of-care temozolomide (TMZ) has marginal efficacy in ~70% of patients due to MGMT expression. LP-184 is an acylfulvene-derived prodrug activated by the oxidoreductase PTGR1 that alkylates at N3-adenine, not repaired by MGMT. This paper examines LP-184 efficacy against preclinical GBM models and identifies molecular predictors of efficacy in clinical GBM. Experimental Design: LP-184 effects on GBM cell viability and DNA damage were determined using cell lines, primary patient-derived cells and neurospheres. GBM cell sensitivities to LP-184 relative to TMZ and MGMT expression were examined. Pharmacokinetics and CNS bioavailability were evaluated in mice with GBM xenografts. LP-184 effects on GBM xenograft growth and animal survival were determined. Machine learning, bioinformatic tools and clinical databases identified molecular predictors of LP-184 responsiveness. Results: LP-184 inhibited viability of multiple GBM cell isolates including TMZ-resistant and MGMT-expressing cells at IC50 = ~22-310 nM. Pharmacokinetics showed favorable AUCbrain/plasma and AUCtumor/plasma ratios of 0.11 (brain Cmax=839 nM) and 0.2 (tumor Cmax = 2,530 nM), respectively. LP-184 induced regression of GBM xenografts and prolonged survival of mice bearing orthotopic xenografts. Bioinformatic analyses identified PTGR1 elevation in clinical GBM subtypes and associated LP-184 sensitivity with EGFR signaling, low nucleotide excision repair (NER) and low ERCC3 expression. Spironolactone, that induces ERCC3 degradation, decreased LP-184 IC50 3-6 fold and enhanced GBM xenograft anti-tumor responses. Conclusions: These results establish LP-184 as a promising chemotherapeutic for GBM with enhanced efficacy in intrinsic or spironolactone-induced TC-NER deficient tumors.
Data from Integrated genomic and transcriptomic analysis improves disease classification and risk stratification of MDS with ring sideroblasts.
Authors: Todisco Gabriele , Creignou Maria , Bernard Elsa , Björklund Ann-Charlotte , Moura Pedro Luis. , Tesi Bianca , Mortera Blanco Teresa , Sander Birgitta , Jansson Monika , Walldin Gunilla , Barbosa Indira , Reinsbach Susanne E. , Hofman Isabel Juliana. , Nilsson Christer , Yoshizato Tetsuichi , Dimitriou Marios , Chang David , Olafsdottir Svanhildur , Venckute Larsson Sigita , Tobiasson Magnus , Malcovati Luca , Woll Petter , Jacobsen Sten-Eirik W. , Papaemmanuil Elli , Hellström-Lindberg Eva
Published: October 2023

Abstract
Purpose: Ring sideroblasts (RS) define the low-risk myelodysplastic neoplasm (MDS) subgroup with RS but may also reflect erythroid dysplasia in higher-risk myeloid neoplasm. The benign behavior of MDS with RS (MDSRS+) is limited to SF3B1-mutated cases without additional high-risk genetic events, but one third of MDSRS+ carry no SF3B1 mutation, suggesting that different molecular mechanisms may underlie RS formation. We integrated genomic and transcriptomic analyses to evaluate whether transcriptome profiles may improve current risk stratification. Experimental design: We studied a prospective cohort of MDSRS+ patients irrespective of WHO class with regard to somatic mutations, copy number alterations and bone marrow CD34+ cell transcriptomes to assess whether transcriptome profiles add to prognostication and provide input on disease classification. Results: SF3B1, SRSF2 or TP53 multi-hit (MH) mutations were found in 89% of MDSRS+ cases, and each mutation category was associated with distinct clinical outcome, gene expression, and alternative splicing profiles. Unsupervised clustering analysis identified three clusters with distinct hemopoietic stem and progenitor (HSPC) composition, which only partially overlapped with mutation groups. IPSS-M and the transcriptome-defined proportion of megakaryocyte/erythroid progenitors (MEP) independently predicted survival in multivariable analysis. Conclusion: These results provide essential input on the molecular basis of SF3B1-unmutated MDSRS+ and propose HSPC quantification as a prognostic marker in myeloid neoplasms with RS.