bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract LB525: Discovery and characterization of ABSK111, a selective, CNS-penetrable, and broad-spectrum EGFR inhibitor targeting exon20 insertion, atypical and extracellular mutations
Authors: Dai Cheng , Peng Juan , Yang Fei , Deng Haibing , Zhao Yuan , Yu Hongping , Xu Yaochang , Chen Zhui , Yang Shuqun 
Published: June 2022

Abstract
Epidermal growth factor receptor (EGFR) exon20 insertion mutations and atypical mutations account for about 9% and 20% of EGFR-mutated non-small cell lung cancer (NSCLC), respectively. Currently approved EGFR tyrosine kinase inhibitors (TKIs) have shown efficacy in NSCLC patients with exon20 insertion and atypical mutations, but with limited overall response and high rate of EGFR-related severe adverse events. This may be associated with the inhibition of wild-type (WT) EGFR. ABSK111 is a highly potent, selective, and CNS-penetrable EGFR inhibitor, targeting multiple EGFR and HER2 mutations, including exon20 insertion, atypical, and extracellular mutations. Here we describe the preclinical in vitro and in vivo characterization of ABSK111. ABSK111 potently inhibited the proliferation of BA/F3 cell lines harboring EGFR exon20, atypical and extracellular mutations with higher selectivity for WT EGFR than currently approved EGFR TKIs. ABSK111 also suppressed HER2 atypical and exon20 mutations. Further, ABSK111 potently blocked the phosphorylation of EGFR exon20 insertion mutations and EGFR variant III in BA/F3 cell lines, with less inhibition of WT EGFR signal than the approved TKIs. Moreover, pharmacokinetic and pharmacodynamic studies demonstrated sustained and exposure-dependent suppression of p-ERK in tumor tissue following a single oral dose of ABSK111. Finally, ABSK111 showed dose-dependent anti-tumor activity in BA/F3 tumor models with EGFR exon20 insertion mutations and EGFR variant III without significant body weight loss. Pharmacodynamic analysis of endpoint samples from efficacy study showed sustained inhibition of p-ERK, which was superior to the approved exon20 insertion inhibitor mobocertinib. Taken together, these results demonstrate the ability of ABSK111 to inhibit a broad spectrum of EGFR and HER2 mutations, including exon20 insertions, atypical and extracellular mutations, while sparing the WT form of EGFR. In addition to the application in NSCLC, the activity against EGFR extracellular mutations and the ability to penetrate into brain suggest the application of ABSK111 in glioblastoma multiforme (GBM).
Citation Format: Cheng Dai, Juan Peng, Fei Yang, Haibing Deng, Yuan Zhao, Hongping Yu, Yaochang Xu, Zhui Chen, Shuqun Yang. Discovery and characterization of ABSK111, a selective, CNS-penetrable, and broad-spectrum EGFR inhibitor targeting exon20 insertion, atypical and extracellular mutations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB525.
Abstract LB529: Oncogenic KRas plays a significant role in regulating expression of IDO1
Authors: Lee Eunji , He Felicia , Choi Byeong Hyeok , Dai Wei 
Published: June 2022

Abstract
Ras proteins are among the most widely studied proto-oncogene products. Ras proteins are membrane-anchored GTPases that participate in multiple signaling cascades regulating crucial cellular processes including cell survival, proliferation, and differentiation. Ras mutations and/or deregulated Ras activities frequently lead to inflammation and malignant transformation. Recent studies have also shown that Ras mutations are associated with immuno-resistance by positive regulation of PD-L1 expression. Indoleamine 2,3-dioxygenases 1 (IDO1) is a heme-containing enzyme that catalyzes the rate limiting step of conversion of tryptophan into kynurenine (Kyn). Extensive research in the past has shown that IDO1 and its catalytic product Kyn mediate immune tolerance, thus promoting tumorigenesis in vivo. IDO1 expression is activated by immune cytokines including interferon-γ (IFN-γ)and interleukin-6 (IL-6). However, whether there is a mechanistic link between oncogenic KRas and IDO1 expression and how IDO1 expression contributes to immune invasion of transformed cells with KRas mutations remain unclear. Here we report that oncogenic KRas significantly enhanced IFN-γ-induced IDO1 expression. In H358 lung carcinoma cells, IDO1 expression induced by IFN-γ was at least in part dependent on ERK activation, and treatment with ARS-1620, a covalent KRasG12C inhibitor, suppressed IDO1 expression induced by IFN-γ in a concentration-dependent manner. IDO1 expression was also induced by IFN-γ in HCT116 colon carcinoma cells that harbored a KRasG12D mutant allele, but not in HCT116 cells with wild-type KRas, suggesting that IFN-γ induced IDO1 expression requires Ras activation. In addition, KRas downregulation by specific siRNAs decreased IFN-γ-induced IDO1 expression in A549 lung cancer cells. Taken together, our study strongly suggests that Ras/ERK signaling pathway plays an important role in promoting IDO1 expression induced by IFN-γ.
Citation Format: Eunji Lee, Felicia He, Byeong Hyeok Choi, Wei Dai. Oncogenic KRas plays a significant role in regulating expression of IDO1 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB529.
Abstract LB534: Development of GB2101, a novel anti-CCR8 antibody for cancer treatment
Authors: Du Qinglin , Cao Yiqi , Yang Xueyan , Lu Jing , Peng Fei , Zhou Wenming , Liang Liwen , Li James , Han Shuhua 
Published: June 2022

Abstract
Background: Regulatory T cells (Tregs) play a crucial role in suppressing immune response and maintaining hemostasis and immune tolerance. Tregs are enriched in the tumor microenvironment (TME) and suppress anti-tumor immunity. Therefore, specific depletion of Tregs in the TME is expected to reduce anti-tumor immune suppression without affecting hemostasis in the periphery. The C-C motif chemokine receptor 8 (CCR8), highly expressed on Tregs from TME but significantly lower expressed on Tregs from peripheral blood, provides an ideal target for preferentially deletion of Tregs within tumors. GB2101 is a novel anti-CCR8 monoclonal antibody generated from hybridoma. The data from in vitro and in vivo studies indicated that GB2101 is a good PCC molecule with great potential for clinical development.
Methods: GB2101 was generated by immunization of CCR8 gene plus CCR8 over-expressing cells in mice followed by hybridoma technology. The binding of the antibody to CCR8-expressing cells was detected by flow cytometry. CCL1 ligand blocking was assessed by flow cytometry and calcium flux assay. Antibody-dependent cell-mediated cytotoxicity (ADCC) function was evaluated by Jurkat-CD16A-NFAT reporter system. In vivo anti-tumor efficacy was assessed in syngeneic model using human CCR8 knock-in mice.
Results: GB2101 displayed potent binding to cells expressing CCR8. GB2101 efficiently blocked CCL1 binding and CCL1-induced signals in CCR8 expressing cells. ADCC activity against target cells was observed and afucosylated version of GB2101 improved ADCC response. GB2101 significantly inhibited tumor growth in syngeneic model.
Conclusions: GB2101 is a novel monoclonal antibody specifically binding to CCR8 with high affinity, and efficiently blocked CCL1-CCR8 pathway and suppressed tumor growth in vivo. Therefore, it is a very promising preclinical candidate that may be used in the treatment of multiple tumor types.
Citation Format: Qinglin Du, Yiqi Cao, Xueyan Yang, Jing Lu, Fei Peng, Wenming Zhou, Liwen Liang, James Li, Shuhua Han. Development of GB2101, a novel anti-CCR8 antibody for cancer treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB534.
Abstract LE03-01: Functional and computational approaches to uncover selection advantages of cancer aneuploidy
Authors: Taylor Alison Marie 
Published: June 2022

Abstract
Aneuploidy, including the gain or loss of whole chromosomes or chromosome arms, is a near-universal feature of cancer. We previously applied methods that define chromosome arm aneuploidy to over 10,000 tumors in the Cancer Genome Atlas (TCGA). Cancer subtypes are often characterized by tumor specific patterns of chromosome arm copy number alterations and breakpoints; for example, squamous cell carcinomas (SCCs) from different tissues of origin are characterized by chromosome 3p (chr3p) loss and chromosome 3q (chr3q) gain. From the TCGA aneuploidy data, we developed an algorithm called BISCUT to distinguish peak regions of aneuploidy breakpoints on each chromosome arm. BISCUT identified loci affected by broad copy number alterations that provide fitness advantages or disadvantages both within individual cancer types and across cancers. Our analyses are consistent with selection being the primary driver of aneuploidy events in cancer. Recent advances in genome engineering allow generation of large chromosomal alterations and validation of findings from patient genomic data. We used the CRISPR-Cas9 system to delete one copy of chr3p in a human immortalized lung epithelial cell line similar to the putative cell-of-origin in lung SCC. Consistent with patient data, expression of chr3p genes was decreased upon deletion, as well as increased expression of interferon response genes. Cells with chr3p deletion initially proliferated more slowly than their siblings. Interestingly, after several passages in culture, this proliferation defect was rescued in chr3p deleted cells. Genome sequencing and karyotype analyses suggested that this was partially the result of chr3 duplication, with cells transitioning to a state of chr3q gain. Isolated cells with chr3q gain show deficiencies in squamous differentiation in organoid culture. Our genome engineering approach to model chromosome arm aneuploidies provides a robust model that will address a gap in our understanding of aneuploidy in cancer.
Citation Format: Alison Marie Taylor. Functional and computational approaches to uncover selection advantages of cancer aneuploidy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LE03-01.
Multisensory Rather than Unisensory Representations Contribute to Statistical Context Learning in Tactile Search
Authors: Chen Siyi , Geyer Thomas , Zinchenko Artyom , Müller Hermann J. , Shi Zhuanghua 
Published: June 2022

Abstract
Using a combination of behavioral and EEG measures in a tactile odd-one-out search task with collocated visual items, we investigated the mechanisms underlying facilitation of search by repeated (vs. nonrepeated) spatial distractor–target configurations (“contextual cueing”) when either the tactile (same-modality) or the visual array (different-modality) context was predictive of the location of the tactile singleton target. Importantly, in both conditions, the stimulation was multisensory, consisting of tactile plus visual items, although the target was singled out in the tactile modality and so the visual items were task-irrelevant. We found that when the predictive context was tactile, facilitation of search RTs by repeated configurations was accompanied by, and correlated with, enhanced lateralized ERP markers of pre-attentive (N1, N2) and, respectively focal-attentional processing (contralateral delay activity) not only over central (“somatosensory”), but also posterior (“visual”) electrode sites, although the ERP effects were less marked over visual cortex. A similar pattern—of facilitated RTs and enhanced lateralized (N2 and contralateral delay activity) ERP components—was found when the predictive context was visual, although the ERP effects were less marked over somatosensory cortex. These findings indicate that both somatosensory and visual cortical regions contribute to the more efficient processing of the tactile target in repeated stimulus arrays, although their involvement is differentially weighted depending on the sensory modality that contains the predictive information.
Long-term Meditation Training Is Associated with Enhanced Subjective Attention and Stronger Posterior Cingulate–Rostrolateral Prefrontal Cortex Resting Connectivity
Authors: Kral Tammi R. A. , Lapate Regina C. , Imhoff-Smith Ted , Patsenko Elena , Grupe Daniel W. , Goldman Robin , Rosenkranz Melissa A. , Davidson Richard J. 
Published: June 2022

Abstract
Mindfulness meditation has been shown to increase resting-state functional connectivity (rsFC) between the posterior cingulate cortex (PCC) and dorsolateral prefrontal cortex (DLPFC), which is thought to reflect improvements in shifting attention to the present moment. However, prior research in long-term meditation practitioners lacked quantitative measures of attention that would provide a more direct behavioral correlate and interpretational anchor for PCC–DLPFC connectivity and was inherently limited by small sample sizes. Moreover, whether mindfulness meditation primarily impacts brain function locally, or impacts the dynamics of large-scale brain networks, remained unclear. Here, we sought to replicate and extend prior findings of increased PCC–DLPFC rsFC in a sample of 40 long-term meditators (average practice = 3759 hr) who also completed a behavioral assay of attention. In addition, we tested a network-based framework of changes in interregional connectivity by examining network-level connectivity. We found that meditators had stronger PCC-rostrolateral prefrontal cortex (RLPFC) rsFC, lower connector hub strength across the default mode network, and better subjective attention, compared with 124 meditation-naive controls. Orienting attention positively correlated with PCC–RLPFC connectivity and negatively correlated with default mode network connector hub strength. These findings provide novel evidence that PCC–RLPFC rsFC may support attention orienting, consistent with a role for RLPFC in the attention shifting component of metacognitive awareness that is a core component of mindfulness meditation training. Our results further demonstrate that long-term mindfulness meditation may improve attention and strengthen the underlying brain networks.
Data-to-text Generation with Variational Sequential Planning
Authors: Puduppully Ratish , Fu Yao , Lapata Mirella 
Published: June 2022

AbstractWe consider the task of data-to-text generation, which aims to create textual output from non-linguistic input. We focus on generating long-form text, that is, documents with multiple paragraphs, and propose a neural model enhanced with a planning component responsible for organizing high-level information in a coherent and meaningful way. We infer latent plans sequentially with a structured variational model, while interleaving the steps of planning and generation. Text is generated by conditioning on previous variational decisions and previously generated text. Experiments on two data-to-text benchmarks (RotoWire and MLB) show that our model outperforms strong baselines and is sample-efficient in the face of limited training data (e.g., a few hundred instances).
Cool-Season Evaluation of FV3-LAM-Based CONUS-Scale Forecasts with Physics Configurations of Experimental RRFS Ensembles
Authors: Supinie Timothy A. , Park Jun , Snook Nathan , Hu Xiao-Ming , Brewster Keith A. , Xue Ming , Carley Jacob R. 
Published: June 2022

Abstract
To help inform physics configuration decisions and help design and optimize a multi-physics Rapid Refresh Forecasting System (RRFS) ensemble to be used operationally by the National Weather Service, five FV3-LAM-based convection allowing forecasts were run on 35 cases between October 2020 and March 2021. These forecasts used ∼3-km grid spacing on a CONUS domain with physics configurations including Thompson, NSSL, and Ferrier–Aligo microphysics schemes, Noah, RUC, and NoahMP land surface models, and MYNN-EDMF, K-EDMF, and TKE-EDMF PBL schemes. All forecasts were initialized from the 0000 UTC GFS analysis and run for 84 h. Also, a subset of 8 cases were run with 15 combinations of physics options, also including the Morrison–Gettelman microphysics and Shin–Hong PBL schemes, to help attribute behaviors to individual schemes and isolate the main contributors of forecast errors. Evaluations of both sets of forecasts find that the CONUS-wide 24-h precipitation > 1 mm is positively biased across all five forecasts. NSSL microphysics displays a low bias in QPF along the Gulf Coast. Analyses show that it produces smaller raindrops prone to evaporation. Additionally, TKE-EDMF PBL in combination with Thompson microphysics displays a positive bias in precipitation over the Great Lakes and in the ocean near Florida due to higher latent heat fluxes calculated over water. Furthermore, the K-EDMF PBL scheme produces temperature errors that result in a negative bias in snowfall over the southern Mountain West. Finally, recommendations for which physics schemes to use in future suites and the RRFS ensemble are discussed.
Capacitive resistive monopolar radiofrequency at 448 kHz plus exercising versus exercising alone for subacromial pain: A sham-controlled randomized clinical trial
Authors: Avendaño-Coy Juan , Aceituno-Gómez Javier , García-Durán Sandra , Arroyo-Fernández Rubén , Blázquez-Gamallo Raquel , García-Madero Venancio Miguel , Escribá-de-la -Fuente Sara Maruxa , Fernández-Pérez Cristina 
Published: June 2022

Objective To investigate the effectiveness of thermal and sub-thermal capacitive-resistive monopolar radiofrequency at 448 kHz plus exercising compared to sham radiofrequency plus exercising on pain, functionality, and quality of life in patients with subacromial pain. Design Randomized, controlled, parallel, double-blind, three-arm clinical trial. Setting Hospital and Primary Care. Subjects Eighty-one participants with subacromial pain in three intervention groups. Interventions Three interventions with capacitive-resistive radiofrequency (thermal, sub-thermal, and sham) over 9 sessions (3 per week) plus an exercising protocol identical for all groups over 15 sessions (5 per week). Outcome measures Visual analogue scale and pressure pain threshold for pain, Shoulder Pain and Disability Index and Quick-Disabilities of the Arm, Shoulder and Hand for functionality, and quality of life via the European Quality of Life-Five Dimensions were assessed at baseline, immediately posttreatment, and 1 month and 3 months post-intervention. Results No between-group differences were found in the pain visual analogue scale (F = 1.0; P = 0.37), Shoulder Pain and Disability Index (F = 1.0; P = 0.36), European Quality of Life-Five Dimensions (F = 0.76; P = 0.47), and pressure pain (F = 0.14; P = 0.86) outcomes, with a statistical power < 0.30 for all comparisons. Between-group differences were found in the Quick-Disabilities of the Arm, Shoulder and Hand (F = 3.4; P < 0.038), with an improvement of −14.1 points (confidence interval at 95% (95% CI) −28.1 to −0.1) in the thermal versus the sham group at 1 month follow-up. The mobility dimension of European Quality of Life-Five Dimensions improved in a greater proportion of participants in the thermal group (22.2% thermal, 7.4% sub-thermal, and 0.0% sham; P = 0.02) Conclusion Adding thermal radiofrequency to exercising can further improve slightly functionality and mobility in people with subacromial pain in the short term, but not pain perception. Future studies with larger sample sizes are warranted to increase statistical power.
Relationship between emotional words in electronic medical records and leave periods of users of a return-to-work program with depression
Authors: Kutsuna Ichiro , Hoshino Aiko , Morisugi Ami , Mori Yukari , Shirato Aki , Takeda Mirai , isaji Hikari , Suwa Mami 
Published: June 2022

Introduction We attempted to score data extracted from written medical records containing assessment results using natural language processing, and to clarify the relationship between duration of sick leave and the use of emotional words among return-to-work (RTW) program users on sick leave due to mental health problems. Method Participants were users of an RTW program. We extracted textual data from their electronic medical records, and gave all words a score based on the following two considerations: positivity score (the degree of positive emotion a word has) and emotion score with respect to seven emotions (sadness, anxiety, anger, disgust, trust, surprise, and joy), with the score for each emotion measured for each word. We analyzed relationships between duration of sick leave and each score. Results Forty-two users participated. The results showed that high positive scores (β = −0.42, p < 0.00) and high sadness scores (β = −0.60, p < 0.00) were related to a shorter duration of sick leave, and high anger score (β = 0.52, p < 0.00) was related to a longer duration of sick leave. Conclusion Professional assessments based on occupational therapy and natural language processing of medical records may predict the appropriate timing of RTW.
Effect of Altmetric score on manuscript citations: A randomized-controlled trial
Authors: Peres Mario FP , Braschinsky Mark , May Arne 
Published: June 2022

Background Alternative metrics to traditional, citation-based metrics are increasingly being used. These are complementary to traditional metrics, like downloads and citations, and give information on how often a given journal article is discussed and used in professional (reference managers) and social networks, such as mainstream media and Twitter. Altmetrics is used in most journals and is available in all indexed headache medicine journals. Whether Altmetrics have an input on traditional, citation-based metrics or whether it is a stand-alone metric system is not clear. Actively promoting a paper through media channels will probably increase the Altmetric score but the question arises whether this will also increase citations and downloads of this individual paper. Methods Focusing on this point we performed a randomized study in order to test the hypothesis that a promotion intervention would improve citations and other science metric scores. We selected 48 papers published in Cephalalgia from July 2019 to January 2020 and randomized them to either receive an active promotion through social media channels or not. The primary outcome used was the difference between mean article citations with versus without intervention 12 months after the intervention period. Results The results show that the alternative metrics significantly increased for those papers randomly selected to receive an intervention compared to those who did not. This effect was observed in the first 12 months, right after the boosting strategy was performed. The higher promoted paper diffusion in social media lead to a significantly higher number of citations and downloads. Conclusion Further promotion strategies should be studied in order to tailor the best cost-benefit intervention.