bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P4-01-04: FGFR inhibitor mediated dismissal of SWI/SNF complexes from YAP-dependent enhancers induces therapeutic resistance in triple negative breast cancer
Authors: Li Yihao , Qiu Xintao , Wang Xiaoqing , Liu Hui , Geck Renee Geck , Tewari Alok , Chow Kin-Hoe , Xiao Tengfei , Cejas Paloma , Nguyen Quang-Dé , Long Henry , Liu Shirley X , Toker Alex , Brown Myles
Published: March 2022

How cancer cells adapt to evade the therapeutic effects of drugs targeting oncogenic drivers is poorly understood. Here we report an epigenetic mechanism leading to the adaptive resistance of triple-negative breast cancer (TNBC) to fibroblast growth factor receptor (FGFR) inhibitors. Prolonged FGFR inhibition suppresses the function of BRG1-dependent chromatin remodeling leading to an epigenetic state that derepresses YAP-associated enhancers. These chromatin changes induce the expression of several amino acid transporters resulting in increased intracellular levels of specific amino acids that reactivate mTORC1. Consistent with this mechanism, addition of mTORC1 or YAP inhibitors to FGFR blockade synergistically attenuated the growth of TNBC patient-derived xenografts (PDX) models. Collectively, these findings reveal a novel feedback loop involving an epigenetic state transition and metabolic reprogramming that leads to adaptive therapeutic resistance and provide new therapeutic strategies to overcome this mechanism of resistance.

Citation Format: Yihao Li, Xintao Qiu, Xiaoqing Wang, Hui Liu, Renee Geck Geck, Alok Tewari, Kin-Hoe Chow, Tengfei Xiao, Paloma Cejas, Quang-Dé Nguyen, Henry Long, Shirley X Liu, Alex Toker, Myles Brown. FGFR inhibitor mediated dismissal of SWI/SNF complexes from YAP-dependent enhancers induces therapeutic resistance in triple negative breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-01-04.
Abstract P4-01-13: Low tumor TLR9 expression results in resistance to growth inhibitory and autophagy responses to common breast cancer treatments
Authors: Selander Katri , Klaper Juha , Petruk Nataliia , Ramm Mauricio , Jukkola Arja , Eskelinen Eeva-Liisa
Published: March 2022

Background: Toll like receptor-9 (TLR9) is an intracellular, innate immune system DNA-receptor, which is widely expressed in cancers. We previously demonstrated that low tumor TLR9 protein expression is associated with poor prognosis among triple negative breast cancer (TNBC) patients. A similar result is now detected also in larger, mRNA expression based datasets (Kmplot.com), which extend our initial observation to basal and luminal B clinical subtypes. The reason for TLR9 association with poor prognosis is not known.Aim: Since poor outcomes in early breast cancer are due to adjuvant treatment failures, we studied the role of TLR9 in breast cancer chemotherapy responses, growth inhibition and autophagy. Materials and Methods: Chemotherapy effects on the growth of control shRNA and TLR9 shRNA TNBC MDA-MB-231 and estrogen receptor expressing (ER+) T47-D cells were studied with cell confluency assays in vitro and in orthotopic mouse models in vivo. Autophagy was assessed with LC3I and II Western blots. Association of tumor TLR9 status with autophagy will be further studied in a cohort of neo-adjuvant treated patients, by comparing pre-treatment TLR9 expression with post-treatment LC3 vesicular expression, with immunohistochemistry. Autophagy gene expression will also be studied with RNAseq. Results: TLR9 shRNA cells were significantly less sensitive to the growth inhibitory effects of standard breast cancer chemotherapies than the corresponding control shRNA cells in vitro. The TLR9 shRNA T47-D cells were also significantly less sensitive to tamoxifen, than corresponding control shRNA cells. Docetaxel inhibited the growth of tumors formed by control shRNA cells, but not by TLR9 shRNA MDA-MB-231 cells in an orthotopic mouse model in vivo. Further chemotherapies and autophagy responses are being tested in this model as well. Standard chemotherapies induced accumulation of LC3IIB in control shRNA cells, but not in TLR9 cells, as demonstrated with Western blots. Conclusions: Decreased expression of tumor TLR9 is associated with 1) poor prognosis among basal and luminal B subtype patient samples, and in 2) decreased growth inhibitory and 3) decreased autophagy responses to common breast cancer chemotherapies and tamoxifen. Our results suggest that treatment responses, and thereby survival of patients with low-TLR9 tumors, may be improved by enhancing TLR9-associated autophagy.

Citation Format: Katri Selander, Juha Klaper, Nataliia Petruk, Mauricio Ramm, Arja Jukkola, Eeva-Liisa Eskelinen. Low tumor TLR9 expression results in resistance to growth inhibitory and autophagy responses to common breast cancer treatments [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-01-13.
Abstract P4-01-14: The RXR agonist, IRX4204, increases the anti-tumor activity of HER2-targeted therapies in HER2-amplified breast cancer
Authors: Moyer Cassandra L , Mazumdar Abhijit , Hill Jamal , Sanders Martin E , Brown Powel
Published: March 2022

Background: HER2 targeted monoclonal antibodies and tyrosine kinase inhibitors (TKI) are effective treatments for HER2-amplified primary tumors. However, the challenge persists that primary and acquired resistance to anti-HER2 therapy is common, and that anti-HER2 targeted therapies fail to achieve a cure in the metastatic setting. There is a critical need for safe and effective therapies that can overcome anti-HER2 drug resistance and eliminate breast cancer metastases. Here, we present data demonstrating the activity of IRX4204, a highly specific agonist of the nuclear retinoid X receptor (RXR), to inhibit the growth of HER2-amplified breast cancer cell lines alone and in combination with current anti-HER2 therapies. Methods: In vitro cell growth assays were conducted to evaluate the efficacy of IRX4204 alone and in combination with trastuzumab, tucatinib, neratinib or T-DM1, using a panel of breast cancer cell lines expressing various levels of HER2. A calculated coefficient of drug interaction (CDI) and isobologram analysis was used to assess the additive, synergistic or antagonistic effects of IRX4204 with each anti-HER2 targeted therapy. Results: IRX4204 treatment alone inhibited the growth of HER2-overexpressing cell lines, SkBr3, AU565, HCC1419 and ZR75-1 in vitro, but not the growth of HER2-normal cell lines MCF7, MDA-MB-231, or HCC1143. When combined with trastuzumab, tucatinib, neratinib or T-DM1, additive or synergistic effects were observed in all of the drug-sensitive cell lines. Moreover, IRX4204 in combination with neratinib or tucatinib inhibited the growth of a TKI-resistant breast cancer cell line (HCC1954). Conclusion: These data demonstrate a novel use of an RXR agonist, IRX4204, to inhibit the growth of HER2-amplified breast cancer cell lines and to enhance the activity of anti-HER2 therapy in vitro. These results also demonstrate that IRX4204 can overcome anti-HER2 resistance to inhibit the growth of HER2-positive cells. These data demonstrate that IRX4204 can enhance the anti-cancer activity of anti-HER2 therapies even in TKI-resistant cells. In vivo experiments and mechanistic studies are ongoing.

Citation Format: Cassandra L Moyer, Abhijit Mazumdar, Jamal Hill, Martin E Sanders, Powel Brown. The RXR agonist, IRX4204, increases the anti-tumor activity of HER2-targeted therapies in HER2-amplified breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-01-14.
Abstract P4-11-10: Association of sports activity during the first five years of survival with quality of life among Chinese breast cancer survivors
Authors: Yeo Winnie , Lei Yuanyuan , Cheung Kali , Lee Roselle , Kwok Carol , Cheng Ashely , Cheng Ashely , Mo Frankie , Ho Suzanne
Published: March 2022

Background: The objective of this study was to investigate the association between participation of sports activity (SA) and quality of life (QoL) among Chinese women with early stage breast cancer (BC) during the first five years post BC diagnosis. Methods: BC survivors underwent assessment of QoL and level of SA at 3 time-points: 18-, 36- and 60-months after diagnosis. SA was measured using a validated modified Chinese Baecke questionnaire in the prior 12 months; QoL was measured using EORTC-QLQC30. Results: In total, 1289, 1125 and 1116 BC survivors were included at 18-, 36- and 60-month follow-up, respectively. At 18-month, the percentages of patients belonged to no [0 metabolic equivalent of task (MET)-hours per week], low-level (<10 MET-hours/week) and high-level (≥10 MET-hours/week) SA groups were 20.7%, 45.5% and 33.8%, respectively; the corresponding figures at 36-month were 29.4%, 38.9% and 31.6%, respectively; and tat of 60-month were 32.8%, 36.7% and 30.5%, respectively. Generalized Estimating Equations analyses showed that higher level of SA was associated with better QoL in several items, including global health status/QoL, physical functioning, role functioning and emotional functioning (P for trend < 0.05 for all), as well as less symptoms in fatigue, pain, loss of appetite and constipation (P for trend < 0.05 for all). Conclusions: Findings from the present study support the notion that SA has beneficial effect on QoL during the first 5 years of BC survivorship. Health promotion programs should encourage participation for SA after breast cancer diagnosis.Acknowledgements: This work was supported by World Cancer Research Fund International (Grant Number WCRF 2010/249 and WCRF 2014/1197) and Madam Diana Hon Fun Kong Donation for Cancer Research.

Citation Format: Winnie Yeo, Yuanyuan Lei, Kali Cheung, Roselle Lee, Carol Kwok, Ashely Cheng, Ashely Cheng, Frankie Mo, Suzanne Ho. Association of sports activity during the first five years of survival with quality of life among Chinese breast cancer survivors [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-11-10.
Abstract P5-08-12: Efficacy of futibatinib, an irreversible fibroblast growth factor receptor (FGFR) inhibitor, in breast cancer models with FGFR alterations
Authors: Saridogan Turcin , Akcakanat Argun , Zhao Ming , Evans Kurt W. , Yuca Erkan , Scott Stephen , Kirby Bryce P. , Zheng Xiaofeng , Damodaran Senthil , Meric-Bernstam Funda
Published: March 2022

Purpose: Several FGFR alterations have been found in breast cancer, however, their role as a therapeutic target in breast has been controversial. Futibatinib (TAS-120; Taiho) is a novel, selective pan-FGFR inhibitor which irreversibly binds to and inhibits FGFR1-4 at nanomolar concentrations. We sought to determine the efficacy of futibatinib in breast cancer models with differing FGFR alterations. Experimental Design: In vivo, antitumor efficacy was evaluated by tumor growth curves and event-free survival in a panel of patient-derived xenografts (PDXs) from breast cancer patients with different FGFR1-4 alterations. Genomic alterations in the PDXs were characterized by next generation sequencing. Correlation of FGFR gene expression in matched patient tumors and PDXs was analyzed by RNA sequencing. In vitro, FGFR2 Y375C mutant and FGFR2-BICC1 fusion expressing MCF10A cell lines were generated, and effect on cell proliferation, colony formation assay, and cell signaling was assessed with and without futibatinib. Frequency of FGFR mutations and FGFR2 amplification was compiled from internal and public databases. Results: Breast cancer PDXs varied in their expression of FGFR1-4. FGFR gene expression significantly correlated between matched patient tumors and PDXs derived from them, however, PDXs had higher levels of FGFR3 and FGFR4 expression compared to patient samples. Futibatinib inhibited tumor growth in three of 10 PDX models, with tumor stabilization in a FGFR2 amplified model and prolonged tumor regression (more than 110 days) in a PDX bearing a FGFR2 Y375C mutation. In vitro, expression of FGFR2 Y375C, as well as FGFR2-BICC fusion in normal-like MCF10A cells enhanced growth, colony formation ability and FGFR signaling. Cells expressing FGFR2 Y375C as well as FGFR2-BICC fusions were more sensitive to futibatinib. In the five breast cancer genomic series we analyzed, FGFR2 mutations and amplifications were found in 1.1%-2.6% and 1.4%-2.5%, respectively. Conclusions: Futibatinib had single agent activity of selected breast cancer PDX models. FGFR2 activating mutations and amplification may represent rare but promising therapeutic targets to FGFR inhibition.

Citation Format: Turcin Saridogan, Argun Akcakanat, Ming Zhao, Kurt W. Evans, Erkan Yuca, Stephen Scott, Bryce P. Kirby, Xiaofeng Zheng, Senthil Damodaran, Funda Meric-Bernstam. Efficacy of futibatinib, an irreversible fibroblast growth factor receptor (FGFR) inhibitor, in breast cancer models with FGFR alterations [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-08-12.
Abstract P5-10-07: A preclinical evaluation of the isoform-specific PI3K inhibitor in HER2+ breast cancer models with resistance to trastuzumab
Authors: De Pradip , Aske Jennifer Carlson , Dey Nandini
Published: March 2022

Background: The PI3K pathway mediates trastuzumab resistance. However, early attempts to indirectly target this signaling pathway with everolimus had limited success. We hypothesize that isoform-specific PI3K inhibitors may enhance the efficacy of anti-HER2 therapy. Methods: We conducted a preclinical proof-of-concept in vitro study of the selective PI3K alpha/delta inhibitor copanlisib or PI3K alpha inhibitor alpelisib alone and in combination with either trastuzumab (hmAB) or tucatinib (HER2-specific kinase inhibitor) in HER2 amplified breast cancer cell lines including trastuzumab-resistant (BT474HR), PIK3CA mutated/HER2 amplified (HCC1954 & MDA-MB453) and PIK3CA wild type/HER2 amplified (SKBR3). Results: When used alone or in combination with the HER2 targeted therapies trastuzumab or tucatinib, copanlisib and alpelisib have anti-proliferative effects in real-time cell proliferation or 3D-ON-TOP assays. Both isoform-specific inhibitors dose-dependently inhibited PI3K signaling and were effective regardless of trastuzumab-resistant and PIK3CA status. Compared to alpelisib, copanlisib was more effective in inducing apoptosis by Annexin V staining. Tucantinib dose-dependently blocked HER2 phosphorylation and p-HER2-SHC-GRB2-mediated MAPK signaling. Significantly, the combination of HER2-targeted therapy (trastuzumab or tucatinib) and copanlisib/alpelisib more effectively inhibited both 3D-ON-TOP colony formation and the HER2 downstream signaling cascade than either drug alone. Conclusion: Our study shows that blocking the PI3K pathway is an essential determinant of response to anti-HER2 regimens in trastuzumab-resistant breast cancers.

Citation Format: Pradip De, Jennifer Carlson Aske, Nandini Dey. A preclinical evaluation of the isoform-specific PI3K inhibitor in HER2+ breast cancer models with resistance to trastuzumab [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-10-07.
Abstract P5-15-09: A LINE Bot mobile app module to augment long-term and real-time follow-up of patients with breast cancer
Authors: Lien Pei-Ju , Huang Chi-Cheng , Tseng Ling-Ming
Published: March 2022

Purpose: Female breast cancer is one of the most frequent cancer types in Taiwan, and several novel therapeutic options have been introduced in recent years. Patients usually received a combination of treatment modalities based on the pathological type, cancer staging and personal preferences. Due to the complexity of treatment involved, specifically associated adverse reactions and variable treatment duration, assessment of quality of life (QoL), long-term and real-time surveillance are difficult to achieve. To overcome the above limitations, we developed a LINE Bot module to augment the follow-up of patients with breast cancer. Materials and Methods: The LINE Bot is comprised of personal information including disease characteristics, therapeutic timeframe, a quality-of-life measuring instrument, the EORTC QLQ-C30 and QLQ-BR23, knowledge and guidance concerning breast cancer. The mobile app also serves as a platform for the patients to interact with their conducting physicians. Results: During the nine-month enrollment period, 108 patients who had received breast cancer therapies at our institute were identified on hospitalization or outpatient basis. Invitation was made in person, and an access to the mobile app or a direct link to online quality-of-life questionnaire was provided. Patients with ECOG=0 reported better global health/Global quality of life status (62 versus 14, P<0.01), physical function (90 versus 73, P<0.05), cognitive function (81 versus 28, P<0.01), less pain (24 versus 67, P<0.01) and dyspnea (10 versus 67, P<0.01) compared to those with ECOG>1. Patients in the status of follow-up had better role function than those undergoing active treatment (92 versus 78, P<0.05). Conclusion: The establishment of the LINE Bot module could improve outcomes assessment for patients themselves and physicians in charge. It provided an opportunity to reflect quality-of-life influenced by each treatment modality and disease status as these patients could repeat the questionnaire at any timing. The platform for interaction could also contribute to enhancing the quality of care.

Citation Format: Pei-Ju Lien, Chi-Cheng Huang, Ling-Ming Tseng. A LINE Bot mobile app module to augment long-term and real-time follow-up of patients with breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-15-09.
Abstract PD3-04: Multi-omics characterization of triple-negative breast cancer identifies therapeutic vulnerabilities and epigenetic immune suppression in the mesenchymal subtype
Authors: Lehmann Brian D , Colaprico Antonio , Silva Tiago C , Chen Jianjiao , An Hanbing , Ban Yuguang , Wang Lily , James Jamaal L , Balko Justin , Gonzalez-Ericsson Paula I , Sanders Melinda E , Zhang Bing , Pietenpol Jennifer A , Chen Xi S
Published: March 2022

Triple-negative breast cancer (TNBC) is a collection of biologically diverse cancers characterized by distinct transcriptional patterns, biology and immune composition. TNBCs display transcriptional diversity with at least four tumor-intrinsic subtypes that include two basal-like (BL1, BL2), a mesenchymal (M) and a luminal androgen receptor (LAR) subtype. Using integrative analyses of transcriptomic, epigenetic, proteomic and phospho-proteomic patterns we have identified subtype-specific vulnerabilities, which advanced our understanding of the cellular origins of TNBC subtypes. In mesenchymal subtype tumors we observed high mutation load and genomic instability, absence of immune cells, low PD-L1 expression, loss of global DNA methylation and transcriptional repression of antigen presentation genes through the polycomb repressor complex 2 (PRC2). Using cell line models, we demonstrate that MHC-I expression is epigenetically silenced by the PRC2 in mesenchymal TNBC cell lines and inhibition of EZH2 restores expression. Pharmacological inhibition of EZH2 enhances chemotherapy efficacy in syngeneic murine tumor models providing a rationale for using PRC2 inhibitors in PD-L1 negative mesenchymal tumors.

Citation Format: Brian D Lehmann, Antonio Colaprico, Tiago C Silva, Jianjiao Chen, Hanbing An, Yuguang Ban, Lily Wang, Jamaal L James, Justin Balko, Paula I Gonzalez-Ericsson, Melinda E Sanders, Bing Zhang, Jennifer A Pietenpol, Xi S Chen. Multi-omics characterization of triple-negative breast cancer identifies therapeutic vulnerabilities and epigenetic immune suppression in the mesenchymal subtype [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD3-04.
Abstract PL1: Genomic Profiling in Early Stage ER Positive Breast Cancers/Precision Medicine
Authors: Dowsett M
Published: March 2022

Genomic profiling has become mainstream for the management of early ER+ breast cancer and has become a favoured approach for research into pathways that govern prognosis and response and resistance to medical therapies.Management: Several commercial tests are available for the assessment of residual risk of recurrence of patients receiving hormonal therapies. We have compared several of these in postmenopausal patients treated with anastrozole or tamoxifen in the ATAC trial, including OncotypeDX (ODX), Prosigna (PAM50) and EndoPredict (EP). While PAM50 and EP provide estimates of risk that by design integrate tumour size and nodal status, estimates from ODX are also improved substantially by integration with clinicopathologic factors. The 3 tests include genes related to proliferation and to dependence on estrogen signalling with the ODX being dominated by the latter and PAM50 by the former. This may explain the better performance of the PAM50 than ODX at cessation of endocrine treatment after 5 years when the outcome for patients with high ER appears to worsen. While the tests have largely been validated in postmenopausal cases they are used in premenopausal cases as well. We found that while individual gene modules varied in expression across the menstrual cycle there was little systemic variability in the overall estimates of risk. Our recent work has indicated that mutations in TP53 add significant prognostic information to that from the commercial profiling tests.Research: We have conducted genomic analyses during presurgical therapy of ER+ breast cancer to determine the key pathways of endocrine resistance using change in Ki67 as the end-point of response. Very few tumours with low levels of ER by IHC (<10% positive cells) or rtPCR showed a Ki67 response. A group of the most widely studied genes in breast cancer including FOS and JUN show very marked increases in expression during surgical procedures and can lead to erroneous interpretation in the absence of controls. Considering intrinsic subtypes, tumours categorised as basal-like or HER2-enriched have little chance of Ki67 response; luminal B tumours showed a slightly lower chance of response. GSEA revealed that several hallmarks reflecting immune signalling were those most strongly associated poor Ki67 response with the interferon gamma and alpha and IL6-JAK-STAT3 signalling hallmarks being particularly involved. TME deconvolution indicated a broad involvement of many immune cell types. Other hallmarks of resistance included E2F target genes and hypoxia. Mutation of TP53 was strongly associated with Ki67 poor response. RNAseq profiling of patients treated with palbociclb as well as letrozole revealed high CCNE1 expression as associated with endocrine resistance.

Citation Format: M Dowsett. Genomic Profiling in Early Stage ER Positive Breast Cancers/Precision Medicine [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PL1.
Abstract TF2-1: A journey through the life of HER2: How did we get here and where are we going?
Authors: Blenman K
Published: March 2022

After the discovery in the early 1980s that human epidermal growth factor receptor 2 (HER2; ERBB2) could trigger exaggerated cell growth and division, it eventually became clear that blocking this protein could slow or stop some types of breast cancer. Since then, several HER2 inhibitors have been USA FDA approved. However, despite this breakthrough success, many HER2-positive breast cancer patients do not benefit from these therapies, or they initially benefit but become resistant over time. Here we discuss the details of the heterogeneity in response, resistance mechanisms/signaling, alternative HER2q activation mechanisms (mutation), and heterogeneity in amplicon structure and does it matter.

Citation Format: K Blenman. A journey through the life of HER2: How did we get here and where are we going? [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr TF2-1.
Priority of Gender and Racial Disparity in Neurology Journals: A Bibliometric Analysis, 2016–2021
Authors: Mohammed Sumayya , Siddiqi Javed
Published: March 2022

Introduction: Medicine and the field of neurology are not immune to gender and racial disparities present more broadly in society. Even within academia there remains a persistent lack of representation of women and racial minorities, but with the recent spotlight on discrimination it is more necessary than ever that prevailing disparities are acknowledged by medical journals and reflected in their publication priorities. This bibliometric study assesses whether social justice trends have influenced the number of articles published that discuss gender and racial disparity in the past 5 years within the top three leading neurological journals. Our assumption is that any trend towards more publications related to gender and racial disparities are reflective of the publication priorities of, and thus the perceived relevance to, the editorial boards of the chosen journals. Methods: Using key word search of “gender,” “race,” and “disparity” in the title or context of published papers, the archives of Lancet Neurology, Nature Reviews Neurology, and Alzheimer’s & Dementia were reviewed. Results: The results indicated that although there was a slight overall increase in coverage of the aforementioned topics, it was negligible compared to the broad impact of current social justice movements. Conclusion: Our data suggest an inadequate publication priority for scholarly work on gender and racial disparity in the chosen journals, over the latest 5 years reviewed.
Ways and Means of Cellular Reconditioning for Kidney Regeneration
Authors: Ishiko Shinya , Goligorsky Michael S.
Published: March 2022

Background: Mitochondrial, lysosomal, and peroxisomal dysfunction; defective autophagy; mitophagy; and pexophagy, as well as the loss of glycocalyx integrity are known contributors to initiation and progression of diverse kidney diseases. Those cellular organelles are tightly interactive in health, and during development of a disease, damage in one may propagate to others. By extension, it follows that restoring an individual defect may culminate in a broader restorative spectrum and improvement of cell and organ functions. Summary: A novel strategy of reconditioning cellular organellar dysfunction, which we define as refurbishment of pathogenically pivotal intra- or extracellular elements, damaged in the course of disease and impeding restoration, is briefly outlined in this overview. Individual therapeutic reconditioning approaches targeting selected organelles are cataloged. We anticipate that the proposed reconditioning strategy in the future may enrich the arsenal of regenerative medicine and nephrology. Key Message: The arsenal of regenerative medicine and nephrology consisting of organ transplantation, use of stem cells, cell-free approaches, cell reprogramming strategies, and organ engineering has been enriched by the reconditioning strategy. The latter is based on the recognition of two facts that (a) impairment of diverse cellular organelles contributes to pathogenesis of kidney disease and (b) individual organelles are functionally interactively coupled, which explains the “domino effect” leading to their dysfunction. Reconditioning takes advantage of these facts and, while initially directed to restore the function of individual cellular organelles, culminates in the propagation of a therapeutic intervention to account for improved cell and organ function. Examples of such interventions are briefly summarized along the presentation of defective cellular organelles contributing to pathogenesis of kidney disease.
Expression Analyses of Cep152, a Responsible Gene Product for Autosomal Recessive Primary Microcephaly, during Mouse Brain Development
Authors: Hamada Nanako , Noda Mariko , Ito Hidenori , Iwamoto Ikuko , Nagata Koh-ichi
Published: March 2022

Centrosomal protein 152 (Cep152) regulates centriole duplication as a molecular scaffold during the cell cycle. Its gene abnormalities are responsible for autosomal recessive primary microcephaly 9 and Seckel syndrome. In this study, we prepared an antibody against mouse Cep152, anti-Cep152, and performed expression analyses focusing on mouse brain development. Western blotting analyses revealed that Cep152 with a molecular mass of ∼150 kDa was expressed strongly at embryonic day (E)13 and then gradually decreased during the brain development process. Instead, protein bands of ∼80 kDa and ∼60 kDa came to be recognized after postnatal day (P)15 and P30, respectively. In immunohistochemical analyses, Cep152 was enriched in the centrosome of neuronal progenitors in the ventricular zone at E14, whereas it was diffusely distributed mainly in the cytoplasm of cortical neurons at P18. In developing cerebellum at P7, Cep152 was localized at the centrosome in the external granular layer, where neurogenesis takes place. Notably, biochemical analysis revealed that Cep152 was also present in the postsynaptic density fraction. Subsequent immunofluorescent analyses showed co-localization of Cep152 with excitatory synaptic markers, PSD95 and synaptophysin, but not with an inhibitory synaptic marker gephyrin in differentiated primary cultured hippocampal neurons. The obtained results suggest that Cep152 takes part not only in neurogenesis during corticogenesis but also in the regulation of synaptic function in differentiated neurons.
Carotid Intima-Media Thickness Percentiles in Adolescence and Young Adulthood and Their Association With Obesity and Hypertensive Blood Pressure in a Population Cohort
Authors: Neuhauser Hannelore K. , Büschges Julia , Schaffrath Rosario Angelika , Schienkiewitz Anja , Sarganas Giselle , Königstein Karsten , Schweizer Dieter , Schmidt-Trucksäss Arno
Published: March 2022

Background:

This study aimed to derive carotid intima media thickness (CIMT) percentiles from a population-based sample of adolescents and young adults using improved technology, standardization and quality control, and to investigate the association of CIMT with hypertensive blood pressure (BP) and obesity.

Methods:

Four thousand seven hundred nine 14- to 28-year-old participants of the German KiGGS cohort 11-year follow-up, which was based on a nationwide population sample, had B-mode ultrasound CIMT measurement with semi-automated edge-detection and automatic ECG-gated real-time quality control. CIMT percentiles were estimated from far wall CIMT during 2 to 6 heart cycles using the GAMLSS statistical model. Hypertensive BP, overweight, obesity, and a risk score from added Z scores of triglycerides, total/HDL (high-density lipoprotein)-cholesterol ratio, and glycated hemoglobin were based on standardized measurements at baseline and follow-up.

Results:

CIMT differed by sex at all ages, furthermore by age and height in a nonlinear fashion. Percentiles were estimated simultaneously by age and height. Hypertensive BP and obesity were associated cross-sectionally and longitudinally with a higher risk of CIMT ≥75th percentile in log-binomial regression models adjusted for age, sex, height, current smoking, and cardiovascular risk score. For CIMT ≥90th percentile, the relative risk effect estimates were consistently >1 but often had large confidence intervals including 1, largest adjusted relative risk 3.37 (95% CI, 1.41–8.04) for the combination of hypertensive BP and obesity at follow-up.

Conclusions:

Based on state-of-the-art measurements and statistical techniques, these population-based CIMT percentiles by sex, age and height add unbiased evidence for the association of subclinical atherosclerosis with hypertensive BP and obesity in the young.
Ethics Sheet for Automatic Emotion Recognition and Sentiment Analysis
Authors: Mohammad Saif M.
Published: March 2022

The importance and pervasiveness of emotions in our lives makes affective computing a tremendously important and vibrant line of work. Systems for automatic emotion recognition (AER) and sentiment analysis can be facilitators of enormous progress (e.g., in improving public health and commerce) but also enablers of great harm (e.g., for suppressing dissidents and manipulating voters). Thus, it is imperative that the affective computing community actively engage with the ethical ramifications of their creations. In this article, I have synthesized and organized information from AI Ethics and Emotion Recognition literature to present fifty ethical considerations relevant to AER. Notably, this ethics sheet fleshes out assumptions hidden in how AER is commonly framed, and in the choices often made regarding the data, method, and evaluation. Special attention is paid to the implications of AER on privacy and social groups. Along the way, key recommendations are made for responsible AER. The objective of the ethics sheet is to facilitate and encourage more thoughtfulness on why to automate, how to automate, and how to judge success well before the building of AER systems. Additionally, the ethics sheet acts as a useful introductory document on emotion recognition (complementing survey articles).
Domain Adaptation with Pre-trained Transformers for Query-Focused Abstractive Text Summarization
Authors: Laskar Md Tahmid Rahman , Hoque Enamul , Huang Jimmy Xiangji
Published: March 2022

The Query-Focused Text Summarization (QFTS) task aims at building systems that generate the summary of the text document(s) based on the given query. A key challenge in addressing this task is the lack of large labeled data for training the summarization model. In this article, we address this challenge by exploring a series of domain adaptation techniques. Given the recent success of pre-trained transformer models in a wide range of natural language processing tasks, we utilize such models to generate abstractive summaries for the QFTS task for both single-document and multi-document scenarios. For domain adaptation, we apply a variety of techniques using pre-trained transformer-based summarization models including transfer learning, weakly supervised learning, and distant supervision. Extensive experiments on six datasets show that our proposed approach is very effective in generating abstractive summaries for the QFTS task while setting a new state-of-the-art result in several datasets across a set of automatic and human evaluation metrics.
Dual Attention Model for Citation Recommendation with Analyses on Explainability of Attention Mechanisms and Qualitative Experiments
Authors: Zhang Yang , Ma Qiang
Published: March 2022

Based on an exponentially increasing number of academic articles, discovering and citing comprehensive and appropriate resources have become non-trivial tasks. Conventional citation recommendation methods suffer from severe information losses. For example, they do not consider the section header of the paper that the author is writing and for which they need to find a citation, the relatedness between the words in the local context (the text span that describes a citation), or the importance of each word from the local context. These shortcomings make such methods insufficient for recommending adequate citations to academic manuscripts. In this study, we propose a novel embedding-based neural network called dual attention model for citation recommendation (DACR) to recommend citations during manuscript preparation. Our method adapts the embedding of three semantic pieces of information: words in the local context, structural contexts,1 and the section on which the author is working. A neural network model is designed to maximize the similarity between the embedding of the three inputs (local context words, section headers, and structural contexts) and the target citation appearing in the context. The core of the neural network model comprises self-attention and additive attention; the former aims to capture the relatedness between the contextual words and structural context, and the latter aims to learn their importance. Recommendation experiments on real-world datasets demonstrate the effectiveness of the proposed approach. To seek explainability on DACR, particularly the two attention mechanisms, the learned weights from them are investigated to determine how the attention mechanisms interpret “relatedness” and “importance” through the learned weights. In addition, qualitative analyses were conducted to testify that DACR could find necessary citations that were not noticed by the authors in the past due to the limitations of the keyword-based searching.
Boring Problems Are Sometimes the Most Interesting
Authors: Sproat Richard
Published: March 2022

In a recent position paper, Turing Award Winners Yoshua Bengio, Geoffrey Hinton, and Yann LeCun make the case that symbolic methods are not needed in AI and that, while there are still many issues to be resolved, AI will be solved using purely neural methods. In this piece I issue a challenge: Demonstrate that a purely neural approach to the problem of text normalization is possible. Various groups have tried, but so far nobody has eliminated the problem of unrecoverable errors, errors where, due to insufficient training data or faulty generalization, the system substitutes some other reading for the correct one. Solutions have been proposed that involve a marriage of traditional finite-state methods with neural models, but thus far nobody has shown that the problem can be solved using neural methods alone. Though text normalization is hardly an “exciting” problem, I argue that until one can solve “boring” problems like that using purely AI methods, one cannot claim that AI is a success.
Response of different crops and weeds to three biotypes of Meloidogyne graminicola: crop rotation and succession strategies for irrigated rice fields
Authors: Soares Mayra R.C. , Carneiro Regina M.D.G. , Dias-Arieira Claudia R.
Published: March 2022

Rice, one of the most consumed cereal crops worldwide, is commonly grown under flooded conditions, which directly influences the nematode community. Meloidogyne graminicola is the predominant species in rice fields, causing significant damage and requiring integrated management practices. This study aimed to investigate the response of different Poaceae crops, soybean, and common weeds of rice to three biotypes of M. graminicola (G1, G2 and G3) recently detected in Brazil. The highest reproduction factor (RF) for the three nematode populations was detected in the weeds Echinochloa colonum and E. crus-galli, followed by rice and Italian ryegrass. Wheat ‘TBio Sonic’ and millet ‘ADR 500’ served as poor hosts to the nematodes, whereas black oat, white oat, signalgrass, millet ‘ADR 905’, maize, wheat ‘TBio Toruk’, and soybean acted as non-hosts (RF < 1) in both experiments. Of the three M. graminicola biotypes, G1 was the most aggressive, followed by G3 and G2 (lowest RF values). The findings of the current study can support the selection of crop rotation or succession approaches for the management of different biotypes of M. graminicola in irrigated rice fields.
Shame, Sin and the Seminary
Authors: Folland Paul
Published: March 2022

The intention of this paper, through a literature based reflective methodology, is to consider the role and implications of shame within the Christian community of a theological college, and suggest mitigating factors that could support the development of a mutually accountable community that would facilitate discipleship growth. Within Regents Theological College in the UK, the aim is to educate students – the majority of whom are 18–30 years old – to go on to serve Jesus in a variety of roles both inside and outside the Church. Our aspiration then, is not just to teach theological and practical skills, but also to raise up disciples of Jesus, willing to serve Him with their heads, hands and hearts. The outcomes suggested by this paper have implications not only for seminary environments, but also for churches and youth groups.
A new species of Arthrographis (Eremomycetaceae, Dothideomycetes), from the soil in Guizhou, China
Authors: LI XIN , ZHANG ZHI-YUAN , CHEN WAN-HAO , LIANG JIAN-DONG , HUANG JIAN-ZHONG , HAN YAN-FENG , LIANG ZONG-QI
Published: March 2022

During a survey of keratinolytic fungi in China, a new species, Arthrographis multiformispora was isolated from soil samples. Morphologically, A. multiformispora differs from other species in the genus by the presence of globose or subglobose chlamydospores and cylindrical arthroconidia. Phylogenetically, our four strains were clustered together with high support values and separated from other clades. We provided a description, illustrations, and phylogenetic tree for the new species.
A new crinipelloid species (Marasmiaceae, Agaricales) from Pakistan
Authors: IZHAR AIMAN , ASIF MUHAMMAD , NIAZI ABDUL REHMAN , KHALID ABDUL NASIR
Published: March 2022

Moniliophthora pakistanica sp. nov. is described from Punjab, Pakistan, based on micro- and morphological characteristics and phylogenetic analysis. The taxon is characterized by a creamy to brownish basidiomes, a depressed or subumbonate and tomentose pileus with distinct orange to brown zones, a hairy stipe, oblong to ellipsoid basidiospores (4.7–8.5 × 4–6 μm), frequent clavate to flexuous cheilo- and pleurocystidia with apical projections, common long setiform terminal hairs in both pileipellis and stipitipellis, rhizomophs, and growth on fallen plant debris. A detailed description of macro- and microscopic characters and field photographs of collections are given. Based on our phylogenetic analysis, M. iopus is found to be a close relative of the new species. Two phylograms inferred from the datasets of nrITS and nrLSU sequences, and a comparison with phylogenetically closely related species are provided.
Revision of the genus Doratura Sahlberg (Hemiptera, Cicadellidae, Deltocephalinae) with particular regard to its distribution in Italy and description of four new species
Authors: BÜCKLE CHRISTOPH , GUGLIELMINO ADALGISA
Published: March 2022

The genus Doratura is revised. Twenty-three valid species are discriminated including four new species: D. lobele sp. nov., D. jole sp. nov., D. roesle sp. nov., and D. vefele sp. nov. The following five species are treated as new synonyms: D. ivanovi Kusnezov, 1928 syn. nov. of D. impudica Horváth, 1897, D. veneta Dlabola, 1959 syn. nov. of D. paludosa Melichar, 1897, D. astrachanica Vilbaste, 1961 syn. nov. of D. rusaevi Kusnezov, 1928, D. littoralis Kuntze, 1937 syn. nov. of D. homophyla (Flor, 1861), and D. arenicola Logvinenko, 1975 syn. nov. of D. caucasica Melichar, 1913. D. paludosa is redescribed. For each species, its habitus and genital morphology are illustrated, a short diagnosis is given, its distribution is outlined and distribution maps are added. If available, data on ecology and phenology are furnished. The Doratura species are distributed in six groups with the exception of D. salina Horváth, 1903, D. horvathi W. Wagner, 1939, and D. lobele sp. nov. For males, an identification key to all Doratura taxa is presented. For females, a preliminary key is proposed. Some other Chiasmini genera are examined in order to suggest possible apomorphic characters in the genus Doratura. Relationships among the Doratura species and the different species groups, distribution patterns, possible hybrids, dispersal strategies in the context of brachyptery, and intraspecific variability in adults and nymphs are discussed.
Optical Characterization of Bitumen: Inspecting the Quantum Size Effect in the Nanostructured Phase
Authors: Duarte Celso de Araujo , Gepiak Allan Ricardo
Published: March 2022

Bitumen (BIT) is an oil sub-product with many applications. A variety of literature reports the analysis of its optical properties, as the fluorescence and the Fourier transform infrared (FT-IR) optical transmittance (OT). We have performed photoluminescence (PL) on the visible region of the spectrum and OT on the visible-NIR in solutions of BIT in toluene at different concentrations. The results revealed a nonlinear, concentration-dependent effect attributed to intermolecular solvent–solute interactions. PL analysis of pure BIT as a function of the temperature and the laser pumping power pointed to the existence of nanosized crystalline inclusions on the amorphous BIT matrix with noticeable optical properties. The inference was confronted with the results of X-ray diffraction studies and literature reports. The possibility of the occurrence of a quantum size effect governing the luminescence is considered.
Explaining the timeliness of implementation of truth commission recommendations
Authors: Martín Héctor Centeno , Wiebelhaus-Brahm Eric , Nieto-Librero Ana Belén , Wright Dylan
Published: March 2022

Truth commissions are widely seen as important peacebuilding tools partially because they issue recommendations that seek to prompt further justice initiatives to address past abuses and promote institutional reforms that encourage non-repetition. Yet, despite growing interest in truth commissions among academics, policymakers, and activists, little attention has been paid to the recommendations that they outline in their final reports. In this article, we examine the factors that shape whether and when truth commission recommendations are enacted. Thus, we seek to explain not only whether recommendations are implemented, but also how quickly they are implemented. We use survival analysis to test the effects of a range of political and economic country-level variables, commission-specific qualities, and recommendation characteristics on the implementation record of nearly 700 recommendations formulated by ten Latin American truth commissions that operated between 1984 and 2014. The analysis yields interesting results, including that implementation proceeds more quickly in wealthier countries and when recommendations are issued by commissions created immediately after transitions, when the transitions occurred in which one side was victorious, and when commissions are created by an executive order. Moreover, recommendations that are directed towards the past are implemented more slowly than future-oriented measures.
The Hollow Men of Liyanage Amarakeerthi: The Nexus Between Nationalism and Capitalism in the Sri Lankan Media
Authors: Ratnayake Madhubhashini Disanayaka
Published: March 2022

Liyanage Amarakeerthi, Kurulu Hadawatha [The Heart of a Bird], Fast Publishing Pvt Ltd., Colombo, Sri Lanka, 2013, pp. 366, SL ₹500, ISBN-978-9556772548 (Paperback)

Liyanage Amarakeerthi, Rathu Iri Adina Atha [The Hand that Underlines in Red], Vidarshana Publishers, Dehiwala, Sri Lanka, 2019, pp. 211, SL ₹500, ISBN 9786245087099 (Paperback)