bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 6158: BGB-24714, a novel oral IAP antagonist, displayed significant anti-tumor activities in preclinical models as a monotherapy and in combination with paclitaxel
Authors: Li Jie , Hu Nan , Zhang Yilu , Yang Xiaolong , Deng Minjuan , Gong Wenfeng , Yin Longbo , Liu Yong , Gao Yajuan , Wei Wei , Wang Xing , Liang Xinyi , Ma Yanwen , Sang Xuxing , Liu Chang , Wang Jingyuan , Lu Qianqian , Song Fengtao , Yuan Xi , Wang Yibing , Li Jing , Jin Wei , Liu Xuesong , Song Xiaomin 
Published: April 2023

Abstract
Background: Evasion of apoptosis is identified as one of the essential hallmarks of cancer and upregulation of inhibitor of apoptosis proteins (IAPs) is one of the mechanisms by which tumor cells evade apoptosis. An oral SMAC mimetic and antagonist of cellular IAP1 (cIAP1) and X-linked IAP (XIAP), BGB-24714, is currently investigated in a phase 1a/1b oncology trial in patients with advanced or metastatic solid tumors (NCT05381909). Here, we evaluated the anti-tumor activity of BGB-24714 as a single agent or in combination with paclitaxel in preclinical models.
Results: BGB-24714 effectively inhibited cIAP1 by inducing its degradation in MDA-MB-231 cells, with an EC50 of 2.5 nM. BGB-24714 also potently antagonized the inhibitory interaction of XIAP with caspase-9 and induced caspase-9 autoactivation in MDA-MB-231 cells, with an EC50 of 23 nM. In a total of 25 breast cancer cell lines treated with TNFα, BGB-24714 potently inhibited the in vitro proliferation of 5 breast cancer cells with EC50 &lt; 100 nM. In pharmacodynamics studies, single dose administration of BGB-24714 significantly induced degradation of cIAP1 and antagonism of the XIAP: Smac interaction in the MDA-MB-231 xenograft model in a dose dependent manner. Using the same model, BGB-24714 exhibited dose-dependent anti-tumor activities as a single agent. The tumor growth inhibition rates were 30%, 52% and 73% in low to high dosage treatment groups. Furthermore, BGB-24714 at medium dosage level demonstrated synergized anti-tumor activity in HCC1806 xenograft model when used in combination with paclitaxel. In intermittent dosing study, BGB-24714 with the intermittent dosing schedule demonstrated significant but slightly less effective anti-tumor activity than the continuous dosing schedule. In summary, BGB-24714, as a novel oral IAP antagonist, showing significant anti-tumor activities in preclinical models, which is promising and warrants the testing of the compound in human.
Citation Format: Jie Li, Nan Hu, Yilu Zhang, Xiaolong Yang, Minjuan Deng, Wenfeng Gong, Longbo Yin, Yong Liu, Yajuan Gao, Wei Wei, Xing Wang, Xinyi Liang, Yanwen Ma, Xuxing Sang, Chang Liu, Jingyuan Wang, Qianqian Lu, Fengtao Song, Xi Yuan, Yibing Wang, Jing Li, Wei Jin, Xuesong Liu, Xiaomin Song. BGB-24714, a novel oral IAP antagonist, displayed significant anti-tumor activities in preclinical models as a monotherapy and in combination with paclitaxel [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6158.
Abstract 666: Targeting the CD47/SIRPα “Do not eat me” phagocytic pathway in macrophages to improve anti-CD47 immune therapy
Authors: Gajendran Nithya , Hernandez Maria Gracia , Yende Ashutosh , Alahmadi Zubaydah , Li Xintang , Munoz Zuleima , Suresh Manasa , Quiceno David , Tan Karen , Shibata Maho , Noonepalle Satish , Villagra Alejandro 
Published: April 2023

Abstract
The cluster of differentiation 47(CD47) is a ubiquitously expressed innate immune checkpoint transmembrane protein but is often overexpressed in cancer cells. CD47 interacts with signal regulatory protein alpha (SIRPα) on macrophages leading to tyrosine phosphatase activation and preventing myosin accumulation at the phagocytic synapse. SIRPa activation triggers the “Do not eat me” signal, negatively regulating phagocytosis in macrophages. Blockade of CD47-SIRPα is a novel immunotherapeutic approach to enhance innate antitumor responses in cancer patients, and clinical data from melanoma patients also showed promising outcomes when CD47 blockade combined with other therapeutic approaches, such as anti-PD-L1. Publications from our lab have provided compelling evidence that histone deacetylase 6 (HDAC6) inhibitors with PD1 blockade delayed tumor progression, enhanced survival, and modulated macrophage phenotype both in vitro and in vivo. The present study aimed to explore the role of HDAC 6 in the CD47/SIRPα axis in phagocytosis and innate antitumor immunity. HDAC inhibition in primary mouse bone marrow-derived macrophages and human THP1 cells enhanced the pro-inflammatory M1 macrophages while downregulating the anti-inflammatory M2 phenotype. In the subsequent studies, we found that HDAC6 inhibition diminished the expression of SIRPα and enhanced the expression of other pro-phagocytic signals, such as Lrp1, CD36, and Mfge8 in macrophages. HDAC6 inhibition also downregulated the CD47 expression in mouse and human melanoma cells. Furthermore, modulation of CD47/SIRPα by HDAC6 inhibitors leads to an increase in phagocytosis in NextA-treated macrophages, further enhanced in CD47-blocking antibodies. We also demonstrated that the combination of systemic administration of the HDAC6 inhibitor Nexturastat A and intertumoral delivery of anti-CD47 reduced SM1 melanoma growth in vivo by increasing immune cell infiltration in the tumor microenvironment. Collectively our results suggest that HDAC6 inhibitors synergize with CD47 blockade to reduce tumor growth and enhance innate antitumor immunity.
Citation Format: Nithya Gajendran, Maria Gracia Hernandez, Ashutosh Yende, Zubaydah Alahmadi, Xintang Li, Zuleima Munoz, Manasa Suresh, David Quiceno, Karen Tan, Maho Shibata, Satish Noonepalle, Alejandro Villagra. Targeting the CD47/SIRPα “Do not eat me” phagocytic pathway in macrophages to improve anti-CD47 immune therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 666.
Data Supplement from SMAD4 Suppresses AURKA-Induced Metastatic Phenotypes via Degradation of AURKA in a TGFβ-Independent Manner
Authors: Jia Lina , Lee Hun Seok , Wu Chun Fu , Kundu Juthika , Park Sang Gyu , Kim Ryong Nam , Wang Li-Hui , Erkin Özgür Cem , Choi Jong-Sun , Chae Seoung Wan , Yang Ho Bin , Choi Yoon-La , Shin Young Kee 
Published: April 2023

<p>Supplementary Figure 1C. AGS, SW480, and HeLa cells were pretreated with control siRNA (lane 1 and 2) or AURKA siRNA (10 nM, lane 3 and 4) for 48 h, and transfected with the plasmid encoding 6Myc-SMAD4 or empty vector. Cells were collected 24 h after transfection and subjected to cell migration and invasion assay (n=3). Data were presented as means {plus minus}SD obtained from three independent experiments (*P<0.05, Ã¢?Â P<0.01, Ã¢?Â¡P<0.001, compared to the control group).</p>
Figure S1, Figure S2, Figure S4, Table S1, Table S2, Table S3 from Differential Effects of Clinically Relevant N- versus C-Terminal Truncating CDKN1A Mutations on Cisplatin Sensitivity in Bladder Cancer
Authors: Sikder Rahmat K. , Ellithi Moataz , Uzzo Robert N. , Weader David J. , Metz Alexander L. , Behbahani Ali , McKenzie Erica R. , El-Deiry Wafik S. , Abbosh Philip H. 
Published: April 2023

<p>Figure	S1. A. sg12 successfully edited	the CDKN1A gene	in	SW780 with high	efficiency; chromatogram shows deletion of an adenine (A).	B. Histograms from TIDE	analysis of	single-cell clones showed that the clones have largely	homogeneous populations. Figure	S2. Cisplatin sensitivity was assessed in SW780	CRISPR clones 24h after a 3h pulse dose. Increased PARP cleavage (a marker of apoptosis) was observed in three p21-deficient sg12 clones compared to sgGFP. Figure S3: see separate document. Figure S4. TCC	cell lines harboring p53 mutations differentially regulate	p21 after cisplatin treatment (10 µM 3-hour pulse dose) Table S1: Primary antibodies used Table S2: Secondary antibodies used Table S3: sgRNA	and flanking primer sequences</p>
Supplementary Figure 6 from Targeting NAD<sup>+</sup> Biosynthesis Overcomes Panobinostat and Bortezomib-Induced Malignant Glioma Resistance
Authors: Jane Esther P. , Premkumar Daniel R. , Thambireddy Swetha , Golbourn Brian , Agnihotri Sameer , Bertrand Kelsey C. , Mack Stephen C. , Myers Max I. , Chattopadhyay Ansuman , Taylor D. Lansing , Schurdak Mark E. , Stern Andrew M. , Pollack Ian F. 
Published: April 2023

<p>Supplemental Figure 6. A. Drug naive and panobinostat and bortezomib-resistant (P + B) U87 cells were treated with gefitinib (2 µmol/L), enzastaurin (2 µmol/L), dasatinib (0.1 µmol/L), dinaciclib (0.18 µmol/L), PI 103 (1 µmol/L), PD 0325901 (2 µmol/L), HSP 990 (0.025 µmol/L), ABT 737 (2 µmol/L), JQ 1 (2 µmol/L), TP 0903 (2 µmol/L), Bay 11-7082 (2 µmol/L), YM 155 (0.025 µmol/L), cucurbitacin-I (0.2 µmol/L), vincristine (0.01 µmol/L), vinblastine (0.01 µmol/L), taxol (0.05 µmol/L), topotecan (0.025 µmol/L), temozolomide (25 µmol/L), gemcitabine (0.25 µmol/L) and 5-fluorouracil (20 µmol/L).</p>
Data from Persistent Ethnicity-Associated Disparity in Antitumor Effectiveness of Immune Checkpoint Inhibitors Despite Equal Access
Authors: Florez Marcus A. , Kemnade Jan O. , Chen Nan , Du Wendy , Sabichi Anita L. , Wang Daniel Y. , Huang Quillan , Miller-Chism Courtney N. , Jotwani Aparna , Chen Albert C. , Hernandez David , Sandulache Vlad C. 
Published: April 2023

<div><p>We reviewed response to immune checkpoint inhibitors (ICI) of 207 patients with diagnoses of lung or head and neck cancer treated with chemotherapy/ICI combination therapy and ICI monotherapy between 2015 and 2020 at one of three clinical pavilions associated with the Dan L. Duncan Comprehensive Cancer Center at Baylor College of Medicine (Houston, TX). Two of these pavilions (Harris Health System and the Michael E. DeBakey Veterans Affairs Medical Center) serve large minority populations and provide equal access to care regardless of means. 174 patients had a diagnosis of lung cancer (non–small cell or small cell) and 33 had a diagnosis of head and neck squamous cell carcinoma (HNSCC). 38% self-identified as Black, 45% as non-Hispanic White, and 18% as Hispanic. The objective response rate (ORR) was similar for patients with lung cancer (35.057%) and HNSCC (30.3%; <i>P</i> = 0.894). The ORR for Hispanic and Black patients was lower compared with non-Hispanic White patients (H 27.0%, B 32.5%, W 38.7%; H vs. W <i>P</i> = 0.209; B vs. W <i>P</i> = 0.398). When considering only patients treated with ICI monotherapy, the ORR for Hispanic patients dropped further to 20.7% while the ORR of Black and non-Hispanic White patients remained about the same (B 29.3% and W 35.9%, H vs. W <i>P</i> = 0.133; B vs. W <i>P</i> = 0.419). Immune-related adverse events were the lowest in the Hispanic population occurring in only 30% of patients compared with 40% of patients in the Black cohort and 50% of the non-Hispanic White cohorts.</p>Significance:<p>To our knowledge, this report is the first to compare ICI effectiveness within a diverse patient population with a substantial Black and Hispanic NSCLC and HNSCC patient population treated in the context of equal access to care. The data presented in this article suggests reduced effectiveness of ICI monotherapy in Hispanic patients and thereby underscores the need for improved access and representation of racial/ethnic minority patients in ICI clinical trials.</p></div>
Mitochondrial Metabolism Drives Low-density Lipoprotein-induced Breast Cancer Cell Migration
Authors: Nóbrega-Pereira Sandrina , Santos Francisco , Oliveira Santos Miguel , Serafim Teresa L. , Lopes Ana Patrícia , Coutinho Diogo , Carvalho Filipa S. , Domingues Rosário M. , Domingues Pedro , Bernardes de Jesus Bruno , Morais Vanessa A. , Dias Sérgio 
Published: April 2023

Most cancer-related deaths are due to metastases. Systemic factors, such as lipid-enriched environments [as low-density lipoprotein (LDL)-cholesterol], favor breast cancer, including triple-negative breast cancer (TNBC) metastasis formation. Mitochondria metabolism impacts TNBC invasive behavior but its involvement in a lipid-enriched setting is undisclosed. Here we show that LDL increases lipid droplets, induces CD36 and augments TNBC cells migration and invasion in vivo and in vitro. LDL induces higher mitochondrial mass and network spread in migrating cells, in an actin remodeling-dependent manner, and transcriptomic and energetic analyses revealed that LDL renders TNBC cells dependent on fatty acids (FA) usage for mitochondrial respiration. Indeed, engagement on FA transport into the mitochondria is required for LDL-induced migration and mitochondrial remodeling. Mechanistically, LDL treatment leads to mitochondrial long-chain fatty acid accumulation and increased reactive oxygen species (ROS) production. Importantly, CD36 or ROS blockade abolished LDL-induced cell migration and mitochondria metabolic adaptations. Our data suggest that LDL induces TNBC cells migration by reprogramming mitochondrial metabolism, revealing a new vulnerability in metastatic breast cancer.

Significance:
LDL induces breast cancer cell migration that relies on CD36 for mitochondrial metabolism and network remodeling, providing an antimetastatic metabolic strategy.
Study Habit and Social Media Exposure as Predictors of Grade 10 Students Academic Performance
Authors: Castillas Glenn M. 
Published: April 2023

The purpose of this study was to determine the respondents' study habits and social media exposure during the school year. 2019-2020.The study's participants were 50 grade 10 students of Alabel 4 District. The researcher administered the survey to all of the student respondents. Majority of respondents were 17 years old, and the majority of their parents had a bachelor's degree and were all employed.
The researcher administered the survey to all of the student respondents. The majority of respondents were 17 years old, and the majority of their parents had a bachelor's degree and were all employed. It also has a high correlation with respondents' social media exposure. The responses revealed that respondents' use of social media has a direct or indirect positive effect on their academic performance.
The study suggests that parents should constantly guide and supervise their children's use of social media, particularly female and younger students who are more interested in social networking. Despite the fact that this study discovered that respondents' socio-demographic characteristics have no bearing on their academic performance. It also suggests that a long-term program be implemented to assist students in constantly improving their study habits.
According to the study's findings, teachers must continue to effectively stimulate and sustain students' interests and enthusiasm for learning in order for them to consistently achieve exceptional academic performance. Teachers should receive regular service trainings and workshops to stay current on their knowledge and pedagogical skills, improve the quality of the teacher workforce, and improve students' academic achievement.
Circ‐myh8 Promotes Pulmonary Hypertension by Recruiting KAT7 to Govern Hypoxia‐Inducible Factor‐1α Expression
Authors: Xing Yan , Qi Jing , Cheng Xiaohan , Song Xinyue , Zhang Jingya , Li Songyue , Zhao Xiaoting , Gong Ting , Yang Jiaxin , Zhao Chong , Xin Wei , Zhu Daling , Zheng Xiaodong 
Published: April 2023

Background
Aberrant expression of circular RNAs (circRNAs) contributes to the initiation and progression of pulmonary hypertension (PH). Hypoxia‐inducible factor (HIF) is a well‐known modulator of hypoxia‐induced PH. The role and underlying mechanism of circRNAs in the regulation of HIF expression remains elusive.

Methods and Results
We profiled pulmonary artery transcriptomes using RNA sequencing and screened circRNAs associated with hypoxia treatment. The expression of a novel circRNA, circ_chr11_67292179–67294612 (circ‐myh8), was increased by hypoxia in a time‐dependent manner. We evaluated the effects of circ‐myh8 overexpression by adeno‐associated virus or inhibition by short hairpin RNA on proliferation and cell cycling in mice and pulmonary artery smooth muscle cells. Overexpression of circ‐myh8 promotes PH under normoxia, and disruption of circ‐myh8 by short hairpin RNA mitigates PH in chronic hypoxic mice. Biologically, circ‐myh8 induces the proliferation and cell‐cycle progression of pulmonary artery smooth muscle cells in vivo and in vitro. Mechanistically, RNA pull‐down and RNA immunoprecipitation assays were used to examine the interaction of circRNAs with the binding protein KAT7 (lysine acetyltransferase 7). The acetylation level of lysine 5 of histone H4 in the transcriptional initiation region of HIF1α was determined by chromatin immunoprecipitation assay followed by reverse transcription‐quantitative polymerase chain reaction. Circ‐myh8 acts as a modular scaffold to recruit histone acetyltransferase KAT7 to the promoters of HIF1α, which elicits acetylation of lysine 5 of histone H4 in their promoters.

Conclusions
Our findings not only reveal the pivotal roles of circ‐myh8 in governing histone modification in anti‐PH treatment but also advocate triggering the circ‐myh8/KAT7/HIF1α pathway to combat PH.
Towards Locally Embedded Beach Management Units in Tanzania for Legitimacy and Sustainability
Authors: Namkesa Faraja , Kweka Opportuna L. 
Published: April 2023

Abstract
Local embeddedness for beach management units is vital for legitimacy and sustainability. This paper employs the theory of local embeddedness to study the extent to which Beach Management Units (BMUs) will bring about the sustainability of fisheries at the community level. It draws from the perceptions of the communities living in Mtwara rural on how Beach Management Units are governed. Using key informant interviews in four villages of Mtwara rural, different levels of embeddedness were identified and measured. The findings show that although Beach Management Units were introduced to empower local communities to manage fisheries resources, they are not embedded within the community.
Lockdown, information quality, and political trust: An empirical study of the Shanghai lockdown under COVID-19
Authors: Zhai Yida , Han Guanghua 
Published: April 2023

Many countries have adopted various measures to curb the spread of the COVID-19 pandemic. The regulation measures of lockdown have triggered changes in public political trust in the government (including in its competence, benevolence and integrity). Information shapes the attitudes and values of residents; this paper aims to study the effect of a lockdown on political trust and the moderating effect from quality of government shared information. From 12 March to 31 May 2022, Shanghai implemented strict lockdown measures. In this study, we randomly sampled the participation information of 1063 participants. Data-based regression analysis shows that lockdown has had a negative impact on all subcategories of political trust. However, timely and accuracy information weakens its negative effect. The accuracy of information moderates the relationship between lockdown and political trust in competence and integrity, while a sufficient supply of information moderates the relationship between lockdown and political trust in benevolence. Points for practitioners This study explores how different dimensions of information quality affect each component public’s political trust, and thereby inspires practitioners to strategically improve information communication in crisis.
Correlation Between Diabetes and COVID-19 Indices: A Global Level Ecological Study
Authors: Mirahmadizadeh Alireza , Ghelichi-Ghojogh Mousa , Jokari Kimia , Amiri Sanaz , Moftakhar Leila , Moradian Mohammad Javad , Habibi Mohammad , Dehghani Seyed Sina , Hassani Amir Hossein , Jafari Alireza , Rezaei Fatemeh 
Published: April 2023

Introduction Coronavirus is threatening the global public health as a new and widespread crisis. The researchers must keep in mind that one of the most vulnerable groups to COVID-19 are the people with underlying diseases, especially diabetes. Objective This ecological study aimed to investigate the correlation between diabetes and the epidemiological indices of COVID-19. Methods This ecological study included 144 countries. Their available data consists of the cumulative incidence rate of cases, cumulative incidence rate of death, recovery rate, case fatality rate, and performed tests of COVID-19, and diabetes. To collect the variables, a data set was provided which included the information of 144 countries based on diabetes and COVID-19 indices. Spearman coefficients were used for assess correlation between diabetes and COVID-19 indices. Also, Scatter plots of diabetes for the studied countries were drawn based on cumulative incidence rate of cases, cumulative incidence rate of death, tests, recovery rate, and case fatality rate of COVID-19. Results The results of this ecological study showed in total countries, there was a weak positive correlation between diabetes and cumulative incidence rate of cases and also cumulative incidence rate of death. Correlation between diabetes with test of COVID-19 was very weak. Scatter plots showed a weak liner correlation between diabetes and cumulative incidence rate of cases, cumulative incidence rate of death and test of COVID-19. Conclusions In this study, there was a weak positive correlation between diabetes and cumulative incidence rate of cases, cumulative incidence rate of death, and performed test of COVID-19. This disease is an enormous challenge for health policymakers; therefore, it is necessary to develop strategies and practical guidelines specific to each region to take the necessary care, especially for diabetic patients.
Bioinformatic analysis of structures and encoding genes of Escherichia coli surface polysaccharides sheds light on the heterologous biosynthesis of glycans
Authors: Dong Ao , Liu Chengzhi , Hua Xiaoting , Yu Yunsong , Guo Yan , Wang Dongshu , Liu Xiankai , Chen Huan , Wang Hengliang , Zhu Li 
Published: April 2023

Abstract
Background
Surface polysaccharides (SPs), such as lipopolysaccharide (O antigen) and capsular polysaccharide (K antigen), play a key role in the pathogenicity of Escherichia coli (E. coli). Gene cluster for polysaccharide antigen biosynthesis encodes various glycosyltransferases (GTs), which drive the process of SP synthesis and determine the serotype.

Results
In this study, a total of 7,741 E. coli genomic sequences were chosen for systemic data mining. The monosaccharides in both O and K antigens were dominated by D-hexopyranose, and the SPs in 70–80% of the strains consisted of only the five most common hexoses (or some of them). The linkages between the two monosaccharides were mostly α-1,3 (23.15%) and β-1,3 (20.49%) bonds. Uridine diphosphate activated more than 50% of monosaccharides for glycosyltransferase reactions. These results suggest that the most common pathways could be integrated into chassis cells to promote glycan biosynthesis. We constructed a database (EcoSP, http://ecosp.dmicrobe.cn/) for browse this information, such as monosaccharide synthesis pathways. It can also be used for serotype analysis and GT annotation of known or novel E. coli sequences, thus facilitating the diagnosis and typing.

Conclusions
Summarizing and analyzing the properties of these polysaccharide antigens and GTs are of great significance for designing glycan-based vaccines and the synthetic glycobiology.