bluuebunny/crossref_metadata_2025 huggingface dataset:
Supplementary Figure S4 from A Carbonic Anhydrase IX/SLC1A5 Axis Regulates Glutamine Metabolism Dependent Ferroptosis in Hypoxic Tumor Cells
Authors: Venkateswaran Geetha , McDonald Paul C. , Chafe Shawn C. , Brown Wells S. , Gerbec Zachary J. , Awrey Shannon J. , Parker Seth J. , Dedhar Shoukat
Published: October 2023

Supplementary Figure S4 shows that the combined loss of CAIX activity and the GSH synthesis axis of Gln metabolism increases cytotoxicity of hypoxic cancer cells.
Supplementary Table S2 from MTX-13, a Novel PTK7-Directed Antibody–Drug Conjugate with Widened Therapeutic Index Shows Sustained Tumor Regressions for a Broader Spectrum of PTK7-Positive Tumors
Authors: Kong Chao , Pu Junyi , Zhao Qianqian , Weng Weining , Ma Linjie , Qian Yu , Hu Wenhao , Meng Xun , Meng Tao
Published: October 2023

Supplementary Table S2 shows the pharmacokinetic parameters of MTX-13(ADC, total antibody, free payload) for each dose
Supplementary Fig.S7 from MTX-13, a Novel PTK7-Directed Antibody–Drug Conjugate with Widened Therapeutic Index Shows Sustained Tumor Regressions for a Broader Spectrum of PTK7-Positive Tumors
Authors: Kong Chao , Pu Junyi , Zhao Qianqian , Weng Weining , Ma Linjie , Qian Yu , Hu Wenhao , Meng Xun , Meng Tao
Published: October 2023

Supplementary Fig.S7 shows MTX-13 targets squamous cell carcinoma of lung, head and neck, esophagus and cervix
Supplementary Fig.S5 from MTX-13, a Novel PTK7-Directed Antibody–Drug Conjugate with Widened Therapeutic Index Shows Sustained Tumor Regressions for a Broader Spectrum of PTK7-Positive Tumors
Authors: Kong Chao , Pu Junyi , Zhao Qianqian , Weng Weining , Ma Linjie , Qian Yu , Hu Wenhao , Meng Xun , Meng Tao
Published: October 2023

Supplementary Fig.S5 shows in vitro and in vivo efficacy of MTX-13
Supplementary Table S2 from Safety and Tolerability of a Novel Anti-HER2 Antibody–Drug Conjugate (PF-06804103) in Patients with HER2-Expressing Solid Tumors: A Phase 1 Dose-Escalation Study
Authors: Meric-Bernstam Funda , Calvo Emiliano , Lee Keun Seok , Moreno Victor , Park Yeon Hee , Rha Sun Young , Chalasani Pavani , Zhong Wei , Zhou Li , Pirie-Shepherd Steven , Leung Abraham C.F. , Curigliano Giuseppe
Published: October 2023

Supplementary Table S2 shows the PK results
Supplementary Figure S2 from Safety and Tolerability of a Novel Anti-HER2 Antibody–Drug Conjugate (PF-06804103) in Patients with HER2-Expressing Solid Tumors: A Phase 1 Dose-Escalation Study
Authors: Meric-Bernstam Funda , Calvo Emiliano , Lee Keun Seok , Moreno Victor , Park Yeon Hee , Rha Sun Young , Chalasani Pavani , Zhong Wei , Zhou Li , Pirie-Shepherd Steven , Leung Abraham C.F. , Curigliano Giuseppe
Published: October 2023

Supplementary Figure S2 shows the duration of treatment including response and tumor type (the safety analysis set)
Supplementary Figure S1 from Safety and Tolerability of a Novel Anti-HER2 Antibody–Drug Conjugate (PF-06804103) in Patients with HER2-Expressing Solid Tumors: A Phase 1 Dose-Escalation Study
Authors: Meric-Bernstam Funda , Calvo Emiliano , Lee Keun Seok , Moreno Victor , Park Yeon Hee , Rha Sun Young , Chalasani Pavani , Zhong Wei , Zhou Li , Pirie-Shepherd Steven , Leung Abraham C.F. , Curigliano Giuseppe
Published: October 2023

Supplementary Figure S1 shows the study design.
Supplementary Materials from First-in-human Study of AZD5153, A Small-molecule Inhibitor of Bromodomain Protein 4, in Patients with Relapsed/Refractory Malignant Solid Tumors and Lymphoma
Authors: Hamilton Erika P. , Wang Judy S. , Oza Amit M. , Patel Manish R. , Ulahannan Susanna V. , Bauer Todd , Karlix Janet L. , Zeron-Medina Jorge , Fabbri Giulia , Marco-Casanova Paola , Moorthy Ganesh , Hattersley Maureen M. , Littlewood Gillian M. , Mitchell Patrick , Saeh Jamal , Pouliot Gayle P. , Moore Kathleen N.
Published: October 2023

Supplementary Tables and Figures
Supplementary figures and tables legends from Conditional Dependency of LP-184 on Prostaglandin Reductase 1 is Synthetic Lethal in Pancreatic Cancers with DNA Damage Repair Deficiencies
Authors: Restifo Diana , McDermott Joseph R. , Cvetkovic Dusica , Dos Santos Troy , Ogier Charline , Surumbayeva Aizhan , Handorf Elizabeth A. , Schimke Caleb , Ma Charlie , Cai Kathy Q. , Olszanski Anthony J. , Kathad Umesh , Bhatia Kishor , Sharma Panna , Kulkarni Aditya , Astsaturov Igor
Published: October 2023

Supplementary figure legends and Tables
Supplementary Figure 2 from Conditional Dependency of LP-184 on Prostaglandin Reductase 1 is Synthetic Lethal in Pancreatic Cancers with DNA Damage Repair Deficiencies
Authors: Restifo Diana , McDermott Joseph R. , Cvetkovic Dusica , Dos Santos Troy , Ogier Charline , Surumbayeva Aizhan , Handorf Elizabeth A. , Schimke Caleb , Ma Charlie , Cai Kathy Q. , Olszanski Anthony J. , Kathad Umesh , Bhatia Kishor , Sharma Panna , Kulkarni Aditya , Astsaturov Igor
Published: October 2023

Supplementary figure 2
Data from Dual Targeting of the PDZ1 and PDZ2 Domains of MDA-9/Syntenin Inhibits Melanoma Metastasis
Authors: Pradhan Anjan K. , Modi Jinkal , Maji Santanu , Kumar Amit , Bhoopathi Praveen , Mannangatti Padmanabhan , Guo Chunqing , Afosah Daniel K. , Mochel Mark C. , Mukhopadhyay Nitai D. , Kirkwood John M. , Wang Xiang-Yang , Desai Umesh R. , Sarkar Devanand , Emdad Luni , Das Swadesh K. , Fisher Paul B.
Published: October 2023

Abstract
Genome-wide gene expression analysis and animal modeling indicate that melanoma differentiation associated gene-9 (mda-9, Syntenin, Syndecan binding protein, referred to as MDA-9/Syntenin) positively regulates melanoma metastasis. The MDA-9/Syntenin protein contains two tandem PDZ domains serving as a nexus for interactions with multiple proteins that initiate transcription of metastasis-associated genes. Although targeting either PDZ domain abrogates signaling and prometastatic phenotypes, the integrity of both domains is critical for full biological function. Fragment-based drug discovery and NMR identified PDZ1i, an inhibitor of the PDZ1 domain that effectively blocks cancer invasion in vitro and in vivo in multiple experimental animal models. To maximize disruption of MDA-9/Syntenin signaling, an inhibitor has now been developed that simultaneously binds and blocks activity of both PDZ domains. PDZ1i was joined to the second PDZ binding peptide (TNYYFV) with a PEG linker, resulting in PDZ1i/2i (IVMT-Rx-3) that engages both PDZ domains of MDA-9/Syntenin. IVMT-Rx-3 blocks MDA-9/Syntenin interaction with Src, reduces NF-κB activation, and inhibits MMP-2/MMP-9 expression, culminating in repression of melanoma metastasis. The in vivo antimetastatic properties of IVMT-Rx-3 are enhanced when combined with an immune-checkpoint inhibitor. Collectively, our results support the feasibility of engineering MDA-9 dual-PDZ inhibitors with enhanced antimetastatic activities and applications of IVMT-Rx-3 for developing novel therapeutic strategies effectively targeting melanoma and in principle, a broad spectrum of human cancers that also overexpress MDA-9/Syntenin.
Figure S4 from TRIM50 Inhibits Gastric Cancer Progression by Regulating the Ubiquitination and Nuclear Translocation of JUP
Authors: Hu Jiajia , Huang Runjie , Liang Chengcai , Wang Yingnan , Wang Min , Chen Yanxing , Wu Chenyi , Zhang Jinling , Liu Zekun , Zhao Qi , Liu Zexian , Wang Feng , Yuan Shuqiang
Published: October 2023

Figure S4: The TRIM50 and JUP binding domain predicted by I-TASSER-MTD. Blue indicated TRIM50. Green indicated JUP. Purple highlighted the interaction sites in RING and PRY/SPRY domain.
Supplementary Figure 5 from Nrf2 Drives Hepatocellular Carcinoma Progression through Acetyl-CoA–Mediated Metabolic and Epigenetic Regulatory Networks
Authors: Xi Caixia , Pang Junfeng , Barrett Amanda , Horuzsko Anatolij , Ande Satyanarayana , Mivechi Nahid F. , Zhu Xingguo
Published: October 2023

S5. Hypoxia shows no contribution to the NRF2 regulated histone acetylation.
Table S1 from HCK Promotes High-Grade Serous Ovarian Cancer Tumorigenesis through CD44 and NOTCH3 Signaling
Authors: Khella Christen A. , Franciosa Lucyann , Rodirguez-Rodriguez Lorna , Rajkarnikar Resha , Mythreye Karthikeyan , Gatza Michael L.
Published: October 2023

Summary of the IHC staining of HCK in ovarian cancer tissue microarrays.
Supplementary Figure 3 from Nrf2 Drives Hepatocellular Carcinoma Progression through Acetyl-CoA–Mediated Metabolic and Epigenetic Regulatory Networks
Authors: Xi Caixia , Pang Junfeng , Barrett Amanda , Horuzsko Anatolij , Ande Satyanarayana , Mivechi Nahid F. , Zhu Xingguo
Published: October 2023

S3. Nrf2 ablation shows no effect on the levels of acetyl-CoA or CoASH in tumor adjacent liver tissues.
Supplementary Figure 1 from Nrf2 Drives Hepatocellular Carcinoma Progression through Acetyl-CoA–Mediated Metabolic and Epigenetic Regulatory Networks
Authors: Xi Caixia , Pang Junfeng , Barrett Amanda , Horuzsko Anatolij , Ande Satyanarayana , Mivechi Nahid F. , Zhu Xingguo
Published: October 2023

S1. RF2 promotes hepatocarcinogenesis.
Supplemental Figure 6 from Allele-Specific Gene Regulation, Phenotypes, and Therapeutic Vulnerabilities in Estrogen Receptor Alpha–Mutant Endometrial Cancer
Authors: Blanchard Zannel , Rush Craig M. , Arnesen Spencer , Vahrenkamp Jeffery M. , Rodriguez Adriana C. , Jarboe Elke A. , Brown Callie , Chang Matthew E.K. , Flory Mark R. , Mohammed Hisham , Modzelewska Katarzyna , Lum David H. , Gertz Jason
Published: October 2023

Identification of novel therapeutic targets in ER active and mutant endometrial cancer
Supplemental Figure 2 from Allele-Specific Gene Regulation, Phenotypes, and Therapeutic Vulnerabilities in Estrogen Receptor Alpha–Mutant Endometrial Cancer
Authors: Blanchard Zannel , Rush Craig M. , Arnesen Spencer , Vahrenkamp Jeffery M. , Rodriguez Adriana C. , Jarboe Elke A. , Brown Callie , Chang Matthew E.K. , Flory Mark R. , Mohammed Hisham , Modzelewska Katarzyna , Lum David H. , Gertz Jason
Published: October 2023

Comparison of mutant ER regulated genes and genes regulated by sustained estrogen signaling
Supplementary Figure 5 from Simultaneous Targeting of DNA Polymerase Theta and PARP1 or RAD52 Triggers Dual Synthetic Lethality in Homologous Recombination–Deficient Leukemia Cells
Authors: Sullivan-Reed Katherine , Toma Monika M. , Drzewiecka Malgorzata , Nieborowska-Skorska Margaret , Nejati Reza , Karami Adam , Wasik Mariusz A. , Sliwinski Tomasz , Skorski Tomasz
Published: October 2023

S5. Targeting Polθ + PARP1 and Polθ + RAD52 induced dual synthetic lethality against HR-deficient leukemia cells.
Supplementary Figure 3 from Simultaneous Targeting of DNA Polymerase Theta and PARP1 or RAD52 Triggers Dual Synthetic Lethality in Homologous Recombination–Deficient Leukemia Cells
Authors: Sullivan-Reed Katherine , Toma Monika M. , Drzewiecka Malgorzata , Nieborowska-Skorska Margaret , Nejati Reza , Karami Adam , Wasik Mariusz A. , Sliwinski Tomasz , Skorski Tomasz
Published: October 2023

S3. Simultaneous inhibition of Polθ helicase and DNA polymerase
activity exerted synergistic effect against RAD54-/- leukemia cells.
Supplementary Figure 2 from Simultaneous Targeting of DNA Polymerase Theta and PARP1 or RAD52 Triggers Dual Synthetic Lethality in Homologous Recombination–Deficient Leukemia Cells
Authors: Sullivan-Reed Katherine , Toma Monika M. , Drzewiecka Malgorzata , Nieborowska-Skorska Margaret , Nejati Reza , Karami Adam , Wasik Mariusz A. , Sliwinski Tomasz , Skorski Tomasz
Published: October 2023

S2. Phenotype of Polq-/-;Parp1-/- and Polq-/-;Rad52-/- mice.
Supplementary Figure 2 from Hierarchical Phosphorylation of HOXB13 by mTOR Dictates Its Activity and Oncogenic Function in Prostate Cancer
Authors: Chen Yonghong , Dufour Catherine R. , Han Lingwei , Li Ting , Xia Hui , Giguère Vincent
Published: October 2023

Supplementary Figure 2. HOXB13 additional phosphorylation at S31 is still dependent on mTOR activity.
Supplemental Figure 9 from Mitochondrial Uncoupling Inhibits Reductive Carboxylation in Cancer Cells
Authors: Jiang Haowen , He Clifford Jiajun , Li Albert M. , He Bo , Li Yang , Zhou Meng-Ning , Ye Jiangbin
Published: October 2023

S9. ETC inhibition only inhibits proliferation, but not spheroid formation, while Mitochondrial uncoupling inhibits both.
Supplemental Figure 8 from Mitochondrial Uncoupling Inhibits Reductive Carboxylation in Cancer Cells
Authors: Jiang Haowen , He Clifford Jiajun , Li Albert M. , He Bo , Li Yang , Zhou Meng-Ning , Ye Jiangbin
Published: October 2023

S8. Mitochondrial uncoupling inhibits proliferation upon anchorage-independent growth.
Supplemental Figure 7 from Mitochondrial Uncoupling Inhibits Reductive Carboxylation in Cancer Cells
Authors: Jiang Haowen , He Clifford Jiajun , Li Albert M. , He Bo , Li Yang , Zhou Meng-Ning , Ye Jiangbin
Published: October 2023

S7. Mitochondrial uncoupling inhibits reductive carboxylation in spheroid culture.
Supplemental Figure 4 from Mitochondrial Uncoupling Inhibits Reductive Carboxylation in Cancer Cells
Authors: Jiang Haowen , He Clifford Jiajun , Li Albert M. , He Bo , Li Yang , Zhou Meng-Ning , Ye Jiangbin
Published: October 2023

S4. Mitochondrial uncoupler NEN inhibits reductive carboxylation under hypoxia.
Supplemental Figure 2 from Mitochondrial Uncoupling Inhibits Reductive Carboxylation in Cancer Cells
Authors: Jiang Haowen , He Clifford Jiajun , Li Albert M. , He Bo , Li Yang , Zhou Meng-Ning , Ye Jiangbin
Published: October 2023

S2. Mitochondrial uncoupler NEN accelerates forward TCA cycle and inhibits reductive carboxylation.
Supplemental Figure 1 from Mitochondrial Uncoupling Inhibits Reductive Carboxylation in Cancer Cells
Authors: Jiang Haowen , He Clifford Jiajun , Li Albert M. , He Bo , Li Yang , Zhou Meng-Ning , Ye Jiangbin
Published: October 2023

S1. Mitochondrial uncoupler NEN increases cellular NAD+/NADH ratio and inhibits reductive carboxylation.
Supplementary Figure 4 from LncRNA-Encoded Micropeptide ACLY-BP Drives Lipid Deposition and Cell Proliferation in Clear Cell Renal Cell Carcinoma via Maintenance of ACLY Acetylation
Authors: Zhang Shenghua , Zhang Zheng , Liu Xiaolong , Deng Yibin , Zheng Jian , Deng Jieqiong , Wang Yirong , Guo Binbin , Li Fanrong , Chen Xiaoyue , Pan Yacheng , Wang Jieyu , Lu Jiachun , Wu Siqi , Guo Qiang , Zhou Yifeng
Published: October 2023

Related information to figure 6
Table S7 from Analysis of Several Common APOBEC-type Mutations in Bladder Tumors Suggests Links to Viral Infection
Authors: Rao Nina , Starrett Gabriel J. , Piaskowski Mary L. , Butler Kelly E. , Golubeva Yelena , Yan Wusheng , Lawrence Scott M. , Dean Michael , Garcia-Closas Montserrat , Baris Dalsu , Johnson Alison , Schwenn Molly , Malats Nuria , Real Francisco X. , Kogevinas Manolis , Rothman Nathaniel , Silverman Debra T. , Dyrskjøt Lars , Buck Christopher B. , Koutros Stella , Prokunina-Olsson Ludmila
Published: October 2023

Table S7: Relationship of PyV status with FGFR3/PIK3CA-mutation status and cigarette smoking
Table S2 from Analysis of Several Common APOBEC-type Mutations in Bladder Tumors Suggests Links to Viral Infection
Authors: Rao Nina , Starrett Gabriel J. , Piaskowski Mary L. , Butler Kelly E. , Golubeva Yelena , Yan Wusheng , Lawrence Scott M. , Dean Michael , Garcia-Closas Montserrat , Baris Dalsu , Johnson Alison , Schwenn Molly , Malats Nuria , Real Francisco X. , Kogevinas Manolis , Rothman Nathaniel , Silverman Debra T. , Dyrskjøt Lars , Buck Christopher B. , Koutros Stella , Prokunina-Olsson Ludmila
Published: October 2023

Table S2: Accession numbers of viruses evaluated in RNA-seq of bladder tumors from UROMOL
TABLE 4 from Change in Neighborhood Socioeconomic Status and Adherence to the Cancer Prevention Lifestyle Guidelines in Hispanic/Latino Adults: Results from the HCHS/SOL Study
Authors: Pichardo Margaret S. , Pichardo Catherine M. , Talavera Gregory A. , Gallo Linda C. , Kuo Charlene C. , Castañeda Sheila F. , Chambers Earle C. , Daviglus Martha L. , Pirzada Amber , Perreira Krista M. , Sotres-Alvarez Daniela , Peña Ortiz Tania Yadhira , Plascak Jesse J.
Published: October 2023

Multinominal logistic regression for the associations between measures of change in neighborhood SES and individual components of the 2012 American Cancer Society Guidelines on Nutrition and Physical Activity for Cancer Prevention
Predicting Mammogram Screening Follow Through with Electronic Health Record and Geographically Linked Data
Authors: Davis Matthew , Simpson Kit , Lenert Leslie A. , Diaz Vanessa , Alekseyenko Alexander V.
Published: October 2023

Cancer is the second leading cause of death in the United States, and breast cancer is the fourth leading cause of cancer-related death, with 42,275 women dying of breast cancer in the United States in 2020. Screening is a key strategy for reducing mortality from breast cancer and is recommended by various national guidelines. This study applies machine learning classification methods to the task of predicting which patients will fail to complete a mammogram screening after having one ordered, as well as understanding the underlying features that influence predictions. The results show that a small group of patients can be identified that are very unlikely to complete mammogram screening, enabling care managers to focus resources.

Significance:

The motivation behind this study is to create an automated system that can identify a small group of individuals that are at elevated risk for not following through completing a mammogram screening. This will enable interventions to boost screening to be focused on patients least likely to complete screening.
Signal Transparency of Remote Microphone Technology in Pediatric Bone Conduction Device Users
Authors: Sanchez Chrisanda , Morgenstein Kari , Snapp Hillary
Published: October 2023

Introduction: Competing noise in the environment negatively affects speech intelligibility, particularly when listening at a distance. This is especially true for children with hearing loss in classroom environments where the signal-to-noise ratio is often poor. Remote microphone technology has been shown to be highly beneficial at improving the signal-to-noise ratio in hearing device users. Children with bone conduction devices, however, often must rely on indirect transmission of the acoustic signal for commonly used classroom-based remote microphone listening (e.g., digital adaptive microphone) which may negatively affect speech intelligibility. There are no studies on the effectiveness of using a relay method of signal delivery using remote microphone technology to improve speech intelligibility in adverse listening environments in bone conduction device users. Methods: Nine children with irresolvable conductive hearing loss and 12 adult controls with normal hearing were included for study. Controls were bilaterally plugged to simulate conductive hearing loss. All testing was conducted using the Cochlear™ Baha® 5 standard processor coupled with either the Cochlear™ Mini Microphone 2+ digital remote microphone or the Phonak Roger™ adaptive digital remote microphone. Speech intelligibility in noise was evaluated in the (1) bone conduction device processor alone, (2) bone conduction device + personal remote microphone, and (3) bone conduction device + personal remote microphone + adaptive digital remote microphone listening conditions at −10 dB, 0 dB, and +5 dB signal-to-noise ratios. Results and Conclusions: Speech intelligibility in noise improved significantly in the bone conduction device + personal remote microphone condition over the bone conduction device alone, demonstrating significant benefit for listening at poor signal-to-noise ratios in children with conductive hearing loss using bone conduction devices with personal remote microphone use. Experimental findings demonstrate poor signal transparency when using the relay method. Coupling of the adaptive digital remote microphone technology to the personal remote microphone negatively affects signal transparency, and no hearing in noise improvements are observed. Significant gains in speech intelligibility are consistently observed for direct streaming methods and are confirmed in adult controls. Behavioral findings are supported by objective verification of the signal transparency between the remote microphone and the bone conduction device.
Interventional Study of Flunarizine Therapy on Symptom Relief and Vestibular Evoked Myogenic Potential Changes in Individuals with Vestibular Migraine
Authors: Islam Farnaz Nasrin , Kumar Kaushlendra , Khadilkar Meera Niranjan , Ebenezer Anupriya , Dosemane Deviprasad
Published: October 2023

Introduction: Migraine is the third most common disease in the world with an estimated prevalence of 14.7%. The purpose of this study was to identify the characteristic changes in cervical and ocular vestibular evoked myogenic potential (VEMP) and analyse changes in symptoms and VEMP after flunarizine therapy in patients diagnosed with vestibular migraine (VM). Methods: Prospective interventional study was conducted on 31 VM patients. Cervical VEMP (cVEMP) and ocular VEMP (oVEMP) were recorded. Flunarizine (10 mg) was given once daily for two consecutive months. Prophylactic therapy was monitored with a monthly follow-up assessment of their symptoms and VEMP was repeated after 2 months. Results: Headache was the chief complaint (67.7%). Vertigo was spontaneous and mostly moderate in intensity (93%). cVEMP was absent in 1 patient and oVEMP was absent in 3 patients. Post prophylactic treatment with flunarizine, there was significant reduction in the frequency (p = 0.001) and duration (p = 0.001) of headache and frequency (p = 0.001), duration (p = 0.001), and intensity (p = 0.009) of vertigo. cVEMP and oVEMP showed no significant differences (p > 0.05) between pre- and post-treatment recordings. Conclusion: Treatment with flunarizine helps in considerably reducing the episodes and duration of headache, as well as episodes, duration, and intensity of vertigo.
The Role of Anti-mCRP Autoantibodies in Lupus Nephritis
Authors: Yuan Mo , Tan Ying , Zhao Ming-hui
Published: October 2023

Background: Lupus nephritis is characterized by multiple autoantibodies production. However, there are few autoantibodies associated with disease activity and prognosis. CRP exists in at least two conformationally distinct forms: native pentameric C-reactive protein (pCRP) and modified/monomeric CRP (mCRP). Autoantibodies against mCRP are prevalent in sera of patients with lupus nephritis and are reported to be pathogenic. Summary: The levels of serum anti-mCRP autoantibodies are associated with clinical disease activity, tubulointerstitial lesions, treatment response, and prognosis in patients with lupus nephritis. The key epitope of mCRP was amino acid 35–47. Furthermore, emerging evidence indicated that anti-mCRP autoantibodies could participate in the pathogenesis of lupus nephritis by forming in situ immune complexes or interfering with the biological functions of mCRP, such as binding to complement C1q and factor H. Key Messages: Here, we review the recent advances in the prevalence, clinical-pathological associations, and potential pathogenesis of anti-mCRP autoantibodies in lupus nephritis, which may provide a promising novel therapeutic strategy for lupus nephritis.
The Role of Adverse Childhood Experiences on People in Opiate Agonist Treatment: The Importance of Feeling Unloved
Authors: McDonagh David , de Vries Jan , Cominskey Catherine
Published: October 2023

Introduction: Adults in opiate agonist treatment (OAT) often have a background of adverse childhood experiences (ACEs) and are more likely to be exposed to a variety of risks that may trigger post-traumatic stress disorder (PTSD). Summative ACE scores are often used to identify individuals at risk of PTSD and continued substance use. What has not been addressed is whether specific ACE factors are exerting a greater influence on the individual. This study investigated whether specific ACEs predicted PTSD, and current continued substance use among adults in long-term OAT. Methods: An analysis of data that were collected at the follow-up stage of a study among 131 adults who attended OAT was conducted. Participants attended one of six OAT settings, covering 45% (n = 890) of clients in a defined area of Dublin, Ireland in 2017. Interviews were conducted with 104 participants, 66 males (63%) and 38 females (37%), with an average age of 43 years (SD = 7.4). The Adverse Childhood Questionnaire (ACQ); PTSD checklist (PCL-5); heroin; tranquilliser; cannabis; alcohol; and cocaine used in the previous 28 days were measured using the quantity used score within the Opiate Treatment Index. Socio‐demographics and age of first use of these four substances were also collected. The analysis has focussed on relating ACEs to PTSD, age of first drugs use, and current drug use of the participants. Results: Bivariate analysis showed that the summative ACQ score was significantly correlated with age of first opiate use (p = 0.004). Multiple regression analysis showed that the summative ACQ score and tranquilliser use predicted higher levels of PTSD (R2 = 0.50). Four specific ACEs predicted 54% of the variance in PTSD, these were feeling unloved (β = 0.328) living with a household member who had a problem with alcohol or used illicit street drugs (β = 0.280); verbal abuse (β = 0.219); and living with a person who had a mental illness (β = 0.197). Conclusions: While a summation of all ten ACEs predicted higher levels of PTSD, the factor “feeling unloved” as a child provided the single strongest predictor and may represent an overarching risk of PTSD and continued substance use in later life among adults in treatment for an opiate use disorder.
Nutritional Knowledge and Dietary Habits of Student-Athletes in a State University: Towards a Contextualized Nutrition Education Plan
Authors: De Jesus Ma. Jim Rushty M. , Fabian Leanne N. , Javeluna Jersey C. , Laquimin Saycell D. , Cayanan Criselda Mae D. , Dizon Stephanie G.
Published: October 2023

Sustainable Development Goal 2 aims to end hunger, achieve food security, improve nutrition, and promote healthy and sustainable diets. Student-athletes deal with unique challenges due to the demands of physical and mental requirements of their sports, making proper nutrition and dietary habits crucial for their overall health and performance. Therefore, this study aimed to analyze the relationship between nutritional knowledge and dietary habits among State Colleges and Universities Athletic Association (SCUAA) Athletes at a state university in Pampanga, Philippines, as a basis for the development of a contextualized Nutrition Education Plan (NEP). The study was grounded on a postpositivist philosophical worldview that employed a quantitative non-experimental approach, specifically a correlational design. A total of 177 student-athletes were assessed for their nutritional knowledge and dietary habits using survey questionnaires. It was determined that student-athletes’ level of nutritional knowledge was described as “knowledgeable” while their perceived dietary habits were described as “good”, but still, there is an area for continued improvement. Meanwhile, it was found that there was no significant difference between nutritional knowledge and dietary habits of student-athletes when grouped according to their demographic profile. On the other hand, there was a significant but weak positive relationship between nutritional knowledge and dietary habits of student-athletes. The results of student-athletes’ nutritional knowledge and dietary habits paved the way for a contextualized NEP anchored on the student-athlete. The study recommends generalizing the NEP and considering the other athletes who also need nutrition and dietary habits improvement.
Academic SelfAcademic Self-Handicapping and Self-Regulating Learning Strategies for Student Engagement in Performance of G-Handicapping and Self-Regulating Learning Strategies for Student Engagement in Performance of Grade 8 Students in Araling Panlipunan
Authors: Endiape Honey Kates A. , Hermosa Jherwin P.
Published: October 2023

This research aims to explore the Academic Self-Handicapping and Self-Regulating Learning Strategies employed by Grade 8 students at Godofredo M. Tan Integrated School of Arts and Trades, with a focus on understanding their impact on student engagement and academic achievement in the subject Araling Panlipunan. The study utilized a descriptive-correlational design and employed a researcher-modified questionnaire as the primary data collection method. Mean Standard Deviations were used to assess students’ perceptions of academic self-handicapping and self-regulating learning strategies, while Pearson Correlation was used to determine the relationship between Academic Self-Handicapping, Self-Regulated Learning Strategies, and students’ engagement and performance in Araling Panlipunan and Mediation Analysis to see if there is effect on the students’ performance mediated by their engagement. The result revealed a significant but weak positive correlation between students’ engagement and their performance in Araling Panlipunan. Furthermore, the students’ engagement was found to fully mediate the impact of their perceived level of academic self-handicapping and self-regulated learning strategies on their performance in the subject. As a result, the hypothesis has been rejected. This study sheds light on the factors influencing student engagement and academic achievement in Araling Panlipunan, providing valuable insights into the learning strategies adopted by Grade 8 students.
Tracer Study of the Nursing Graduates in a State College
Authors: Austria Jayson S.
Published: October 2023

Introduction: This graduate tracer study aimed to improve the nursing program in a state college. Method: It used descriptive survey collect the nursing graduates' demographic, educational, and employment profiles, as well as their feedbacks. The study used 60% representative stratified and snowball samplings. Findings presented in frequency distribution tables. Feedbacks were grouped into themes. Results: The demographic profile showed varied age from 20 to 40 years old, who were largely female. The educational profile showed fluctuating nurse licensure examination percentage, and a large number who were not actively involved in continuing professional development. The employment profile showed a large number of graduates who were not employed in nursing related jobs and without permanent employment status. Conclusion: Thus, these findings corroborated the graduates' feedbacks that to produce quality graduates for the labor market, program offering improvement in terms of faculty, curriculum and instruction, library, and physical facilities is needed.
Abstract 101: Crosstalk Of Pluripotency And Innate Immunity In Smooth Muscle Cell Phenotypic Transitions
Authors: Mahajan Aatish , Shin Junchul , Tkachenko Svyatoslav , Cherepanova Olga A
Published: October 2023

Objectives:
Smooth muscle cell (
SMC
) phenotypic transitions play a critical role in the pathogenesis of cardiovascular diseases. However, the molecular mechanisms responsible for these transitions are not well understood. We previously found that the embryonic stem cell/pluripotency factor OCT4 is reactivated in SMC in human and mouse atherosclerotic plaques and plays an atheroprotective role by regulating SMC investment into the protective fibrous cap. Loss of OCT4 in SMC is associated with SMC de-differentiation toward a macrophage-like phenotypic state resulting in increased lipid accumulation and phagocytosis. However, the endogenous molecular mechanism responsible for atheroprotective SMC-OCT4-dependent effects remains unknown.

Methods and Results:
Herein, we performed combinatory bioinformatics analyses on the
in vivo
and
in vitro
wild-type and SMC-
Oct4
knockout mouse samples and found that loss of
Oct4
in SMC resulted in up-regulation of the innate immune receptor TLR4 in numerous experimental conditions. Notably, the TLR4 promoter does not have any putative OCT4 binding sites.
First
- Using publicly available OCT4 ChIPseq datasets and long non-coding (
lnc
)RNA databases, we identified several lncRNAs, including IGF2AS, MALAT1, PLATR10, BACE1, and SRA based on the OCT4 occupancy at promoter and enhancer regions of lncRNA, which in turn, directly target TLR4. To confirm the OCT4-dependent activation of the identified lncRNAs in SMC, qRT-PCR was performed in mouse aortic SMC transfected with
Oct4
-blocking siRNA. We found that the
Oct4
knockdown in SMC led to significant decreases in all five selected lncRNAs and increases in TLR4 and its downstream gene, TRIF.
Second
- Intriguingly, we also demonstrated that TLR4 signaling, in turn, promotes hydroxymethylation of the OCT4 promoter and reactivates OCT4 in SMC.
Third
- Using a
Tlr4
-reporter and SMC-lineage tracing mouse model, we also demonstrated that medial differentiated SMC from healthy arteries, but not phenotypically modulated lesion SMC, express TLR4.

Conclusions:
Together, these results indicate a role of TLR4-signaling in SMC both upstream and downstream of OCT4, suggesting that pluripotency/innate immunity crosstalk plays a critical role in SMC phenotypic transitions.
Abstract 103: Epigenetic and Phenotypic Modulation of Adventitial Fibroblasts in Atherosclerosis by Coronary Artery Risk Gene TCF21
Authors: Gu Wenduo , Dalal Alex , Nguyen Trieu , Daniel Li , Sharma Disha , Markus Raesanen , Monteiro João P , Weldy Chad S , Palmisano Brian , Fischbein Michael P , Quertermous Thomas , Cheng Paul
Published: October 2023

The vascular adventitia has long been postulated to play a key role in the development of atherosclerosis, but the relevant adventitial cell populations and the mechanisms by which they influence atherosclerosis have remained elusive. To characterize relevant adventitial cells and their regulators, we have combined single cell multi-omic murine model and human multi-omic data with human genetics. Single cell transcriptomic and epigenetic analysis of both murine and human arterial tissue revealed a unique population of adventitial fibroblasts (AdvFib) that reside exclusively in the adventitia. Murine lineage tracing using a novel AdvFib-specific model revealed specific expansion of AdvFib in atherosclerosis. Cell-cell communication analysis demonstrated an increase in AdvFib-driven crosstalk with other cell types during early phases of atherosclerosis development. Furthermore, akin to phenotypic modulation in SMC, AdvFibs also undergo dramatic phenotypic alterations, activating pro-inflammatory (Ccl2/7/8, Lcn2, Cxcl12) and cell proliferation programs early in atherosclerosis, suggesting a key coordinating role in disease. Transcriptome and epigenome analysis revealed disproportionate enrichment for coronary artery disease (CAD) GWAS risk loci and genes in AdvFib, suggesting that AdvFib actively contributes to disease. Single cell data show that one CAD risk gene,
TCF21
, is expressed primarily in AdvFib. Alteration of TCF21 appears to be central to AdvFib activation in atherosclerosis, as its expression also changed during atherosclerosis, with corresponding epigenetic remodeling in AdvFib enriched for Tcf21 binding motifs. AdvFib-specific TCF21 loss changed AdvFib proliferation and inflammatory cell recruitment, consistent with the higher TCF21 expression in human with lower risk of myocardial infarction. Mechanistically, through histone modification cut-and-tag, we demonstrated that TCF21 regulates AdvFib activation through epigenetic reprograming of key cytokine and cell fate regulators. Collectively, our results begin to establish a role for AdvFib in atherosclerosis development and highlight regulation of TCF21 in this process through epigenetic mechanisms.
Abstract 105: Lipid Regulation of Senescent Effector CD8 T Cells in Type 2 Diabetes
Authors: Eberhardt Natalia , Kaur Ravneet , Gildea Michael , Das Dayasagar , Amadori Letizia , Fernandez Dawn , Shamailova Roza , Sajja Swathy , Jindal Manila , Rockman Caron , Maldonado Thomas , Fisher Edward , Goldberg Ira J , Berger Jeffrey , Giannarelli Chiara
Published: October 2023

Introduction:
Atherosclerotic plaques from patients with Type 2 Diabetes (T2D) present a more severe pathology than non-T2D (ND) plaques and response to cholesterol-lowering is compromised. An increased level of circulating senescent CD8 T cells in T2D patients is associated with increased risk for myocardial infarction. However, whether senescent T cells infiltrate human atherosclerotic plaques and how they are regulated by lipid lowering is unknown.

Hypothesis:
Senescent CD8+ T cells are increased in atherosclerotic plaques and circulation of T2D, and are normalized by aggressive lipid lowering in T2D.

Methods:
We performed unbiased scRNA-seq analysis (75,049 total cells) of immune cells in plaques from T2D (n=12) and ND patients (n=10) to identify senescent T cells in human atherosclerotic plaques. Using CyTOF we tested the effect of aggressive lipid lowering on circulating CD8 T cells in T2D (n=16) and ND (n=6) patients.

Results:
We identified senescent T cells within atherosclerotic plaques and found that senescent CD8 T cells largely accumulate in plaques from T2D patients (p<0.001). Plaque CD8 T cells showed a terminally differentiated effector memory phenotype with high expression of
CX3CR1
and low expression of
SELL
and
CCR7
genes. CD8 T cell clusters express senescence markers (
B3GAT1,KLRG1,KLRD1,KLRF1
) and presented senescence associated secretory phenotype with high expression of cytotoxic (
GZMB,PRF1,GNLY
) and proatherogenic (
IFNG,TNFA,CCL5
) genes. CyTOF analysis showed higher levels of circulating senescent CD57+CD28-CD8 T cells in patients with T2D vs ND controls (p<0.001). Potent lipid lowering with PCSK9 inhibitor + statin/ezetimibe, which reduced LDL-C levels by >70% in all patients at 4 weeks, normalized the frequency of circulating senescent CD8 T cells (p<0.001) in T2D patients to the levels found in ND.

Conclusion:
Our results show that senescent CD8 T cells accumulated in blood and plaques of T2D patients and that potent lipid lowering diminished circulating aged CD8 T cells, suggesting that CD8 T cell senescence can be improved by aggressive lipid control in high-risk T2D subjects. Further analyses are needed to understand the role of lipid metabolism in the T cell senescence and the impact on atherosclerosis progression.
Abstract 111: Allogeneic Mesenchymal Stromal Cells Significantly Increase Type 1 Regulatory T-cells, Decrease Effector Th17 Cells, And Decrease Aneurysm Volume In A Dose Dependent Fashion In Patients With Small Abdominal Aortic Aneurysms - Results Of The Phase I Aneurysm Repression With Mesenchymal Stromal Cells (the Arrest Trial)
Authors: Samra Humraaz , Ingram Michael , Leckie Katherin , Moldovan Leni , Wanczyk Kristen , Timsina Lava , Sinha Mithun , Mohammed Imran Khan , Mylvaganam Ravi , Motaganahalli Anush , Territo Paul , GUTWEIN Ashley , Motaganahalli Raghunandan , Murphy Michael P
Published: October 2023

Objectives:
We have previously demonstrated that patients with abdominal aortic aneurysms (AAA) have a defect in IL-10 expression, Type-1 regulatory T-cell (Tr1) function and a robust Th17 response. In this Phase 1, double blinded, placebo-controlled trial we assess the efficacy of intravenous (IV) delivery of escalating doses of allogeneic mesenchymal stromal cells (MSC)in modulating immune responses in patients with small AAA.

Methods:
Patients with AAA <5.0 cm diameter were randomized 1:1:1 to receive IV administration of placebo (Plasmalyte A), 1 million MSCs/kg, or 3 million MSCs/kg. The primary endpoint was the difference in TH17:Tr1 cells at day 30 post-treatment as measured by mass cytometry. Secondary endpoints included changes in aneurysm inflammation at Day 30 as measured by positron emission tomography and aneurysm volume at 1-year as measured by computed tomography. Changes in plasma cytokines using enzyme linked immunoassay were measured at Days 0, 7, 14, and 28 post-treatment. Treatment related adverse outcomes and adverse cardiac events were recorded.

Results:
A total of 28 patients (28 male, mean age 66 ± 4 years) with small AAA (mean diameter 3.9 ± 0.6 cm) were randomized to placebo (n =12), 1 million MSCs/kg (n=6), and 3 million MSCs/kg.( n =10) . There was a significant decrease in the percent of TH17 relative to an increase in Tr1 cells at day 30 compared to placebo in the high dose group (73.2 ± 6.9 % vs. ± -5.5 ± 20.1 % ,P<0.05) but not in the low dose group. There was a decrease in Th17 cells at Day 14 compared to placebo in the high and low dose groups ( -11.1 ± 4.3 % and -13.3 ± 4.6 % vs. 9.7± 5%, respectively, P<0.05). Compared to placebo there was a significant increase in IL-10 in the high and low dose groups ( 28.8 ± 3.2 and 42.7 ± 4.5 vs. 11.9 ± 2.1 pg./mL. P = 0.034 and 0.023 , respectively ) at day 7. There was a decrease in aneurysm volume in the high dose group compared to placebo at 1-year, but was not significant (- 7.3 ± 0.14 vs. 12.3 ± 2.6 mm3, P=0.055). There were no treatment related adverse events.

Discussion:
The ARREST study demonstrates that systemic administration of allogeneic MSCs is safe and may reduce AAA expansion. We plan a multicenter multi-dosing trial to further assess the potential of MSCs in preventing AAA expansion.
Abstract 113: Transcriptomic Profile Of Macrophage-mediated Energy Metabolism In Sporadic Aortic Aneurysms And Acute Dissections
Authors: Xu Samantha , Li Yanming , Zhang Chen , Vasquez Hernan , Rebello Kimberly , Coselli Joseph S , Milewicz Dianna M , Daugherty Alan , Lemaire Scott A , Shen Ying H
Published: October 2023

Background:
Inflammation plays a critical role in the development of ascending thoracic aortic aneurysms (ATAA) and their progression to acute dissection (ATAD). Macrophage (MΦ) activation is associated with changes in energy metabolism. To better understand the dynamic changes of MΦ function during ATAA and ATAD development, we examined transcriptomic profiles of energy metabolism in MΦs in human aortic tissue. We hypothesized that metabolic activity in MΦs is higher in ATAA and ATAD tissues compared to non-diseased controls.

Methods:
We performed single-cell RNA sequencing analysis of ascending aortic tissue from 9 patients with ATAA without dissection, 9 patients with ATAD (dissected and non-dissected areas collected separately), and 8 non-diseased organ donor control subjects (Fig. 1A). Within MΦ cluster (Fig. 1B), we compared differentially expressed metabolic genes as well as metabolic flux and metabolite accumulation using single-cell flux estimation analysis between control, ATAA, and ATAD groups.

Results:
Compared to controls, MΦs in ATAA and ATAD exhibited increased glycolytic gene expression and glycolytic activity as well as increased anaerobic respiration and lactate accumulation (Figs. 1C, 1D). We also observed upregulated fatty acid oxidation-related genes and increased fatty acid oxidation flux in ATAD compared to control, which corresponded to lower predicted metabolite levels of fatty acid in ATAD (Figs. 1C, 1D). Furthermore, tricarboxylic acid (TCA) cycle-related genes in MΦs were higher in ATAD than in control (Fig. 1C). Interestingly, mitochondria-encoded oxidative phosphorylation (OXPHOS) genes were downregulated in MΦs of ATAD while nuclear-encoded OXPHOS genes were upregulated in MΦs of ATAD compared to controls (Fig. 1C).

Conclusion:
Both aerobic and anaerobic metabolic pathways exhibited higher activity in dissection, suggesting overall energy metabolism is increased to meet the energy demands of MΦs in dissection.
Abstract 114: Glycosylation of PCSK9 Impairs its Interaction with LDLR But Assures its Stability
Authors: Pacheco-Velazquez Silvia C , Hay Joshua , Rosario Sara , Mueller Paul A , Pamir Nathalie
Published: October 2023

Proprotein convertase subtilisin/kexin type 9 (PCSK9) increases plasma LDL levels due to the degradation of the LDL receptor (LDLR). Anti PCSK9 antibody treatment leads to up to 70% reduction in plasma LDL levels. However, for poorly understood reasons, the treatment has no effect in some patients. Glycosylation is one of several PCSK9 post-translational modifications, with inconclusive effects on the protein’s stability and function. We tested the hypothesis that glycosylation increases PCSK9 plasma stability by reducing its interaction with LDLR and promoting its secretion from hepatocytes. We studied the implications of glycosylation on PCSK9 kinetics and function
in vitro
and with a patient cohort treated with Anti-PCSK9 antibodies. We analyzed the PCSK9 protein sequence to identify potential sites for N and O-glycosylation. We confirmed the N-glycosylation sequence and found 12 potential sites for O-glycosylation. To assess the effect of glycosylation on extracellular stability and function, we incubated for 24 hours: PCSK9-overexpressing HEPG2 cells with two glycosylation inhibitors and a human recombinant PCSK9 with deglycosylating enzymes. Following the ablation of the N-glycosylation, the levels of extracellular PCSK9 decreased while its affinity for LDLR increased. These results were also observed for O-glycosylation but with a lesser effect. Finally, we show that anti PCSK9 antibody treated patients, have a preponderance of circulating glycosylated PCSK9. In conclusion, N-glycosylation enhances PCSK9 stability; however, it decreases its binding to LDLR. Circulating PCSK9 glycosylation patterns and quantity might explain the differential response of patients to anti-PCSK9 treatment.
Abstract 120: Eosinophils And Eosinophil Extracellular Traps (eets) In Arterial Thrombosis In Lnk(sh2b3) Deficiency
Authors: Dou Huijuan , Wang Ranran , Tavallaie Mojdeh , Tall Alan , Wang Nan
Published: October 2023

Background and objective:
Human GWAS have shown association of a common single nucleotide polymorphism in LNK (R262W, T allele) with neutrophilia, eosinophilia, and atherothrombotic cardiovascular disease (ACD). We have shown that
LNK(TT
) reduces LNK function and LNK-deficiency promotes neutrophil extracellular traps (NETosis) and arterial thrombosis. However, the potential role of eosinophils in the
LNK(R262W)
associated risk of ACD has not been evaluated. Recent evidence suggests that eosinophils act to stabilize arterial thrombi by forming eosinophil extracellular traps (EETs). The primary goal of this study is to investigate the role of eosinophils and EETs in arterial thrombosis in hematopoietic LNK deficiency.

Methods:
We used pharmacological and genetic approaches that specifically inhibits eosinophils and EET formation. Chow-fed and WTD-fed WT and

Lnk
-/-

BMT recipient mice received eosinophil depleting antibody (anti-Siglec-F) or isotype control IgG. We also transplanted bone marrow from WT,

Lnk
-/-

,

ΔdbIGata1
-/-

or

ΔdbIGata1
-/-

/

Lnk
-/-

mice into
Ldlr
-/-
recipients, followed by 10 weeks WTD feeding.

Results:
Anti-Siglec-F completely reversed accelerated thrombosis in chow

Lnk
-/-

BMT recipient mice and partially reversed accelerated thrombosis in WTD

Lnk
-/-

BMT
Ldlr
-/-
recipients, indicating eosinophils promote arterial thrombosis in LNK deficiency. Consistently,

ΔdbIGata1
-/-

mediated selective eosinophil depletion also partially reversed arterial thrombosis in HC-LNK deficiency. Anti-Siglec-F and

ΔdbIGata1
-/-

had no significant effect on arterial thrombosis in the WT control mice. Depletion of eosinophils by both anti-Siglec-F and

ΔdbIGata1
-/-

abolished thrombotic eosinophils and EETs in WT and

Lnk
-/-

BMT recipient mice. Eosinophils and EETs were prominent in thrombi of chow diet and WTD fed

Lnk
-/-

BMT mice compared to WT. Depletion of eosinophils in LNK deficiency significantly reduced thrombotic neutrophil infiltration and NETs formation but not in WT.

Conclusions:
These results indicate that eosinophils promote atherothrombosis in hematopoietic LNK deficiency by facilitating EET and NET formation. Therapies targeting eosinophils may be beneficial for arterial thrombosis in genetically defined populations.