bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 872: Deciphering the activation mechanism of CDK4/cyclin-D complex that differs from the CDK2/cyclin-E complex
Authors: Zhang Wengang , Liu Yonglan , Zhang Mingzhen , Jang Hyunbum , Nussinov Ruth 
Published: April 2023

Abstract
Cyclin-dependent protein kinases (CDKs) regulate the eukaryotic cell cycle progression. Dysregulated cell cycle leading to unscheduled cell proliferation is a characteristic of many cancer subtypes. Since some tumor cells require specific interphase CDKs for proliferation, understanding CDKs activation mechanisms and their differential recognition of cognate cyclins and substrate proteins are essential for developing selective CDK inhibitors for cancer treatments. To date, while the crystal structure of the active CDK2 in complex with cyclin-E is available, no crystal structure for active CDK4 with its cognate cyclin-D is resolved. Here, we model the CDK4/cyclin-D complex as well as CDK2 in complex with cyclin-E to study the conformational dynamics and activation processes of G1 and G1/S phases CDKs, respectively. Extensive molecular dynamics (MD) simulations were performed for both CDK complexes with the kinases in different transition states to resolve the differences in their allosteric regulations at the atomic level. We illustrate that the inactive CDK4 in complex with cyclin-D is in the intermediate state on its pathway to activation in contrast to the fully active CDK2 in complex with cyclin-E, suggesting its activation mechanism is distinct from that of CDK2. This suggests that additional steps such as ATP binding, extension of the activation loop (A-loop), rotation of αC-helix towards “IN” conformation, phosphorylation of A-loop, and substrate binding are required for CDK4. CDK2 interacts with cyclin-E through a large interfacial area (or interface) that stabilizes the protein-protein interaction, while CDK4 has a smaller interfacial area (or interface) in the interaction with cyclin-D. Our simulations affirm experimental data on the current understanding of activation mechanisms of CDK2 and CDK4 and reveal additional atomistical characteristics of their dynamics and activations. Our works report the complete activation mechanisms of CDK2/4, providing insights into the inhibition of these complexes at an atomic level, and are useful for identifying potential targets for drug discovery in oncology.
Citation Format: Wengang Zhang, Yonglan Liu, Mingzhen Zhang, Hyunbum Jang, Ruth Nussinov. Deciphering the activation mechanism of CDK4/cyclin-D complex that differs from the CDK2/cyclin-E complex [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 872.
Abstract 889: The efficacy and safety of PD-L1-specific CAR-T in advanced gastric cancer
Authors: Park Hye-Seong , Choi Eun-Ji , Yu Jae-In , Lee Kyung-Sik , Lim Yeo-Jin , Choi Se-Ryeong , Choi Yoonjoo , Park Bum Chan , Park Jae Eun , Kim Mihwa , Lee Je-Jung , Rhee Joon Haeng 
Published: April 2023

Abstract
[Purpose] Heterogeneity and the tumor microenvironment are major obstacles to overcoming incurable advanced gastric cancer (AGC). Although Epstein-Barr virus-positive and microsatellite instability subtypes can be detected early and properly treated, they are rare in AGC. In this regard, recent combinational therapy of immune checkpoint inhibitors (ICIs) such as PD-1/PD-L1 inhibitors and other various therapeutics has been tried, but there are clinically limited doses and drug resistance. We hypothesized that CAR-T targeting PD-L1, the common tumor-associated antigen (TAA), which expresses in most advanced cancer cells, would make a significant breakthrough in curing a solid tumor. This study aimed to evaluate the killing effects of anti-PD-L1 CAR-T against gastric cancer cell lines. Removal of PD-L1-expressing cells in the AGC TME will improve the clinical outcomes of current therapies.
[Results] We constructed a second-generation PD-L1 CAR lentiviral vector targeting PD-L1, which has an intermediate affinity with PD-L1 in solid tumor TME. As the secondary signaling motif, CD28 was chosen and tested along with the CD3 zeta chain. The effector CAR-T, named Vax-CAR-T, specifically recognized the PD-L1-expressing AGC cell line, SNU638, and exhibited rapid and robust cytotoxic activity in vitro. When compared to untransduced T cells, the level of the CD25 activation marker was higher in Vax-CAR-T cells. Besides, the inhibitory markers of Tim3 and LAG3 were expressed even higher than the untransduced. Despite high Tim3 and LAG3 expression in the final manufacturing process, Vax-CAR-T cells significantly suppressed tumor growth in both bigger (&gt;95mm3) and smaller (≤50mm3) AGC xenograft NSG mouse models. More importantly, Vax-CAR-T-treated mice have well tolerated the CAR-T therapy with no significant adverse events during the CRS monitoring period, 2 weeks after Vax-CAR-T injection and have gradually recovered weight gains 5 days after CAR-T cell injection.
[Conclusion] We believe that a new autologous CAR-T targeting PD-L1 could be a promising new tool for removing heterogeneous solid tumors in TME, which would be a significant step forward in improving current conventional and immunotherapeutic strategies.
Citation Format: Hye-Seong Park, Eun-Ji Choi, Jae-In Yu, Kyung-Sik Lee, Yeo-Jin Lim, Se-Ryeong Choi, Yoonjoo Choi, Bum Chan Park, Jae Eun Park, Mihwa Kim, Je-Jung Lee, Joon Haeng Rhee. The efficacy and safety of PD-L1-specific CAR-T in advanced gastric cancer [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 889.
Abstract 920: Real-world biomarker testing patterns in metastatic castration-resistant prostate cancer patients
Authors: Blanc Simon , Adeboyeje Gboyega , Lee Liam , Gart Mike , Saunders William , Wang Brandon , Dave Poras , English Sandy , Varughese Prateesh , Sillah Arthur 
Published: April 2023

Abstract
Introduction: Homologous recombination repair mutations (HRRm) result in an accumulation of genetic aberrations and genomic instability. HRRm are estimated to be present in up to 28% of patients (pts) with advanced prostate cancer, including metastatic castration-resistant prostate cancer (mCRPC). Testing for HRRm may inform treatment choice in pts with mCRPC. The aim of the study was to assess HRRm testing rate and describe pts factors associated with testing in treated mCRPC pts.
Methods: We identified pts with mCRPC on treatment from 5/1, 2020 through 3/31, 2022 from the Integra Connect PrecisionQ de-identified database, an electronic medical record (EMR) and claims database of US cancer pts in community oncology. We defined HRRm testing as the receipt of any test for alterations in 1 or more of the following genes: BRCA 1/2, ATM, BARD1, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, RAD51B, RAD51C, RAD51D, RAD54. We described age and race at diagnosis (dx), cancer stage and Gleason score at staging, and line of therapy (LOT), Eastern Cooperative Oncology Group (ECOG) performance status, metastatic sites and prostate-specific antigen (PSA) values at date closest to mCRPC diagnosis. Categorical data were reported as counts and percentages, and continuous data were summarized as medians (IQR).
Results: The study cohort comprised 798 pts (HRRm tested, n=389, 48.7%). Most pts were white (81.7%), with a median (IQR) age of 68 (54-82) years at dx. Most pts had high-grade mCRPC, with Gleason scores of 7-8 (43.3%) or 9-10 (47.9%). The majority of pts were stage IV (74.0%), and on their first LOT (44.6%) at mCRPC diagnosis. A higher proportion of pts ≥80 years were not HRRm-tested (61.5%) vs. pts ≤59 (46.6%). Compared to white pts, a higher proportion of black/African American pts were HRRm non-tested (48.6% vs 41.5%). Tested pts had better ECOG status compared to non-tested pts (0 - 1: 91.0% vs 86.8%). 77.1% of tested pts had a bone metastasis compared to 73.4% of non-tested. A higher proportion of tested pts were diagnosed with mCRPC in a later LOT than those not tested.
Conclusion: We found a testing rate for HRRm of 49% in US mCRPC pts receiving routine care. There were modest unadjusted differences in demographic and clinical features between tested and non-tested pts. There is a need for further research to examine the value of HRRm testing in mCRPC pts.
Citation Format: Simon Blanc, Gboyega Adeboyeje, Liam Lee, Mike Gart, William Saunders, Brandon Wang, Poras Dave, Sandy English, Prateesh Varughese, Arthur Sillah. Real-world biomarker testing patterns in metastatic castration-resistant prostate cancer patients [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 920.
Supplementary Figure legends 1-7 from PPARδ Interacts with the Hippo Coactivator YAP1 to Promote SOX9 Expression and Gastric Cancer Progression
Authors: Song Shumei , Wang Zhenning , Li Yuan , Ma Lang , Jin Jiankang , Scott Ailing W. , Xu Yan , Estrella Jeannelyn Santiano , Song Yongxi , Liu Bin , Johnson Randy L. , Ajani Jaffer A. 
Published: April 2023

<p>Supplemental Figure 1. PPARÎ'ï�¤and its agonist activate SOX9 transcription, while its antagonist suppresses SOX9 transcription and expression. Supplemental Figure 2. Diagram demonstrates cloning of human YAP1 and PPARÎ'ï�¤and their major domains as depicted. Supplemental Figure 3. Sequential ChIP using YAP1 and PPARÎ'ï�¤ antibodies in PPARÎ' transfected GAC (AGS) cells. Supplemental Figure 4. Mutation of the TEAD binding site of SOX9 promoter diminished the SOX9 transcriptional activity induced by PPARÎ'ï�¤agonist GW501516. Supplemental Figure 5. PPARÎ' and its agonist GW501516 activation of YAP1 expression and increased the binding of PPARÎ' and YAP1.Supplemental Figure 6. PPARÎ'ï€ Interacts with YAP1 by Yeast two-hybrid analyses. Supplemental Figure 7. PPARÎ' promotes oncogenic functions of GAC cells in vitro and in vivo.</p>
Supplemental Table 6 from Genomic Integration of High-Risk HPV Alters Gene Expression in Oropharyngeal Squamous Cell Carcinoma
Authors: Walline Heather M. , Komarck Christine M. , McHugh Jonathan B. , Bellile Emily L. , Brenner J. Chad , Prince Mark E. , McKean Erin L. , Chepeha Douglas B. , Wolf Gregory T. , Worden Francis P. , Bradford Carol R. , Carey Thomas E. 
Published: April 2023

<p>Supplemental Table 6. Summary of genomic aberrations to identified genes with integrated HPV. The Oncomine database was used to assess genomic aberrations in all publicly available HNSCC next generation sequencing data sets including (1, 2) 1.	Agrawal N, Frederick MJ, Pickering CR, Bettegowda C, Chang K, Li RJ, Fakhry C, Xie TX, Zhang J, Wang J, Zhang N, El-Naggar AK, Jasser SA, Weinstein JN, Trevino L, Drummond JA, Muzny DM, Wu Y, Wood LD, Hruban RH, Westra WH, Koch WM, Califano JA, Gibbs RA, Sidransky D, Vogelstein B, Velculescu VE, Papadopoulos N, Wheeler DA, Kinzler KW, Myers JN. Exome sequencing of head and neck squamous cell carcinoma reveals inactivating mutations in NOTCH1. Science. 2011;333(6046):1154-7. doi: 10.1126/science.1206923. PubMed PMID: 21798897; PMCID: PMC3162986. 2.	Stransky N, Egloff AM, Tward AD, Kostic AD, Cibulskis K, Sivachenko A, Kryukov GV, Lawrence MS, Sougnez C, McKenna A, Shefler E, Ramos AH, Stojanov P, Carter SL, Voet D, Cortes ML, Auclair D, Berger MF, Saksena G, Guiducci C, Onofrio RC, Parkin M, Romkes M, Weissfeld JL, Seethala RR, Wang L, Rangel-Escareno C, Fernandez-Lopez JC, Hidalgo-Miranda A, Melendez-Zajgla J, Winckler W, Ardlie K, Gabriel SB, Meyerson M, Lander ES, Getz G, Golub TR, Garraway LA, Grandis JR. The mutational landscape of head and neck squamous cell carcinoma. Science. 2011;333(6046):1157-60. doi: 10.1126/science.1208130. PubMed PMID: 21798893; PMCID: PMC3415217.</p>
EFL Learners in Thailand: Content Analysis of Research Articles
Authors: Maravilla Wes Harven G. , Maming Jimmy Bernabe 
Published: April 2023

Due to recent shifts in the laws regulating Thailand's educational system, more study has been done on teaching English to EFL Thai pupils. Finding the frequent distribution of these studies in terms of their topics, publication years, writers, groups, and research methods is the main objective of this study. 56 articles were selected as the sample because it was discovered that they were content-specific in the context of English Language Acquisition in Thailand. Data was collected using the Article Information Rubric, and it was processed using Microsoft Excel. The following are the study's major conclusions:

"Methods and Strategies" is the subject of most articles written by ELT scholars.
The frequent distribution of publication years has changed significantly.
The majority of college students were chosen as the group using the random selection technique.
Mixed study techniques were used in the majority of the investigations.
Questionnaires and conversations were used by researchers to gather data.
The most frequently used form of data analysis in these studies is frequency and proportion charts.
Basic Education Learning Continuity Plan (BE-LCP) Implementation: Challenges and Opportunities
Authors: Sabacajan Bazil T. , Moradods Alexander N. 
Published: April 2023

The Basic Education Learning Continuity Plan (BE-LCP) was developed collaboratively by the Philippines through the Department of Education) in response to the need to continue education despite the restrictions imposed by the COVID-19 crisis. This is to ensure that education is delivered without jeopardizing the health and safety of its learners and employees. Therefore, this current study aims to determine the level of awareness and the extent of challenges and opportunities in implementing the Basic Education Learning Continuity Plan. The study was mainly quantitative by design and used the survey questionnaire and interview method to gather the necessary information. The survey questionnaire served as primary data from respondents' responses on the awareness, challenges, and opportunities of BE- LCP implementation. The result of the study indicates that the overall level of BE-LCP awareness was placed at a moderate extent, the overall extent of challenges among the respondents was penned moderate, and the overall extent of opportunities on the implementation of the BE-LCP was also moderate. Furthermore, there was a significant difference in the level of awareness on the BE-LCP implementation among the teachers, stakeholders, and students, meanwhile, the study reveals that there was no significant relationship among the variables of the study. As a result, the Division of Camiguin intends to ensure BE-LCP implementation and deliver quality education in the new normal.
“Project TUBIG PARA SA LAHAT (Water for All)”: A Community Based Action Research
Authors: Asio John Mark R. , Gadia Ediric D. , Cura Carlmaulen J. , Soriano Imelda DP. 
Published: April 2023

This paper aims to present the community extension project of local higher education in Olongapo City, Philippines. The project entitled “Project Tubig Para sa Lahat (Water for All).” is a collaborative effort of the Gordon College – Community Extension Service Unit (GC –CESU) and different Non-Government Organizations (NGOs). The project's main objective is to provide a clean water storage for every household in a far-flung community in Olongapo City. This project is an initial step towards the United Nations Sustainable Development Goals (UN SDGs) mandate, in particular SDG 6. After a series of meetings, a strategic planning, and months of preparation, the project commenced. However, there were some challenges in the logistics due to the distance and terrain of the place. Nevertheless, the project was successful and turned over to the community as a sign of community engagement to all parties involved. The whole community has full access to the water tank project, and many households benefitted from the said project.
Lack of refuge as a bottleneck for reptiles in intensive woody crops
Authors: Canós-Burguete Marta , Torrijo-Salesa Mizar , Tortosa Francisco S. , Guerrero-Casado José 
Published: April 2023

Abstract
The lack of refuge has been suggested as one of the main factors affecting reptiles in intensive crops, but this theory has not been explored to any great extent. The aim of this work is to compare the reptile abundance and species richness between traditional and intensive vineyards and olive groves, and to test the acceptance of artificial shelter due to its scarcity in the new intensive woody crop. A total of 288 transects were carried out (144 in olive groves and 144 in vineyards) in six different types of plots: traditional olive groves, traditional vineyards, intensive olive groves with and without artificial refuge, and trellis vineyards with and without artificial refuge. The results showed a greater species richness and abundance of reptiles in the traditional plots than in the intensive plots (independently of the experimental refuges added). An important number of animals were observed using the artificial refuges in olive groves. Furthermore, most of the individuals were located on or escaped to old trees in traditional systems, including an important proportion of reptiles hidden in olive trunk cavities, whereas more individuals were observed on the ground in intensive systems. Our finding suggests the importance for reptile communities of the traditional agricultural systems due to the high availability of the refuge provided by old olive tree trunks and free-standing gobelet vineyards. Our results show that providing refuge may mitigate the negative effects of woody crops intensification on reptile communities.
The Scaling Down of SAGCOT Public Private Partnerships
Authors: Pauline Noah M. , Mbande Victor , Börjeson Lowe 
Published: April 2023

Abstract
This study analyses SAGCOT’s public-private partnership policy, which anticipated attracting external investors in large-scale nucleus farms to commercialise smallholder farmers. Data were collected from a review of SAGCOT policy documents, a compilation of SAGCOT registered partners and qualitative interview data collected from private companies, government officials, farmers and outgrower associations. The majority of SAGCOT registered commercial partners are small- to medium-scale and most of them were already operating in the area before SAGCOT was established. We conclude that the SAGCOT investment strategy, in practice, has been linked to small- to medium-scale operations and also mainly to already existing enterprises, which stand in contrast to the initially envisioned model of attracting new large-scale farming enterprises to the region. We argue that there is a need for SAGCOT and policy makers to learn from this dissonance between initial policy ambition and actual outcomes of SAGCOT public-private partnerships.
On the possible functions of helical thickenings in conductive cells in wood
Authors: Costa Adriana , Wiedenhoeft Alex C. 
Published: April 2023

Summary
The career of Sherwin J. Carlquist was marked by numerous pioneering contributions to botany and especially to ecological and evolutionary wood anatomy. He developed some of the most important modern functional hypotheses for wood, including postulating a biomechanical and fluid dynamic role for helical thickenings (HT) in seasonally dry environments. Here we endeavor to honor Carlquist’s legacy by summarizing existing observations, explicitly acknowledging that HT represent a range of non-homologous and likely functionally disparate features, and exploring HT functional hypotheses in light of data from a pantropical genus, Croton, in which HT are associated with mesic rather than xeric conditions. This is noteworthy in part because HT are commonly associated with the flora of temperate mesic areas and seasonally dry areas, particularly in non-tropical regions. Based on observations in Croton, the distribution of HT around the world, and interesting advances in fluid dynamics, we propose that diversity in this feature may serve two related functions in addition to the potential mechanical role previously articulated, namely, vessel refilling after cavitation and increased hydraulic efficiency.
Deciphering the Trend and Interannual Variability of Temperature and Precipitation Extremes over Greenland during 1958–2019
Authors: Wei Ting , Zhao Shoudong , Noël Brice , Yan Qing , Qi Wei 
Published: April 2023

Abstract
Greenland experienced multiple extreme weather/climate events in recent decades that led to significant melting of the ice sheet. However, how the intensity of extreme climate events over Greenland varied under recent warming has not been fully examined. Here, we collect 176 in situ observations over Greenland and demonstrate that the observed extreme temperature/precipitation events over Greenland are well captured by the RACMO2.3p2 model, in terms of climatological distribution, interannual variability, and long-term trend. Thus, we then investigate the spatiotemporal features of extreme events over Greenland during 1958–2019, using the daily model outputs at 5.5-km resolution. The simulated annual maximum temperature exhibits a significant increasing trend (∼0.13°C decade−1) during 1958–2019, whereas there is a weakening trend (−0.24°C decade−1) in annual minimum temperature over Greenland, especially after the 1990s (−1.24°C decade−1). For the interannual variability, changes in temperature extremes between warm and cold temperature years share large similarities with the distributions of long-term trends. The extreme precipitation events measured by annual maximum daily precipitation amount show a profound increasing trend (0.52 mm day−1 decade−1) over northeastern Greenland during 1958–2019, with large interannual variability in the ice-free coastal region and southern Greenland. Additionally, the changes in extreme warm and cold events are generally linked with the variation of Greenland blocking in summer and Arctic polar vortex in winter, respectively, in terms of favorable circulation background, and the extreme precipitation events are often associated with the position of the polar jet stream.