bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mieloma múltiple. Experiencia de 9 años en el Hospital Naval Almirante Nef
Authors: Cortés Saavedra Magdalena , Figueroa Carolina , Varela Roxana , Valdivia-Cortés Karla , Barría Katherine , Salvo Carla 
Published: July 2021

Introducción: el mieloma múltiple (MM) continúa siendo una enfermedad incurable sin embargo el trasplante autólogo de médula ósea (TAH) y las drogas antineoplásicas han permitido mejorar la sobrevida global (SG) de los pacientes. Materiales y métodos: estudio de cohorte retrospectivo de 50 pacientes con diagnóstico de MM en el hospital Naval Almirante Nef, desde 2005 a 2013. Los pacientes se dividieron en dos cohortes, según la eligibilidad a trasplante, y analizados acordes a la primera línea de tratamiento y la sobrevida global (SG) hasta abril de 2019. Resultados: mediana de edad 73 años (47-88 años), SG 49 meses, y 50% en etapa-II del IIS. La SG de los 39 no candidatos a TAH fue 46 meses; con un mayor número de respuestas completas y sobrevida, con el esquema melfalán-prednisona-talidomida. La SG de los 11 candidatos a TAH fue 66 meses, siendo el esquema bortezomib-ciclofosfamida-dexametasona el que concentró un mayor número de respuestas completas libres de progresión. Se trasplantó el 45% de los candidatos, con una mediana de sobrevida de 79 meses versus a los 51 meses de aquellos no trasplantados. Tres casos de neuropatía asociada a talidomida y uno a bortezomib. La SG a los seis meses y a los cinco años de todos los pacientes fue 86% y 44%, respectivamente. Conclusión: la incorporación de nuevos fármacos permitió obtener mejores resultados de sobrevida lo que se condice con estudios nacionales e internacionales.
Abstract 1360: Exposure-response safety analysis of avelumab in patients with locally advanced or metastatic urothelial carcinoma
Authors: Li Jerry , Bello Carlo , Khandelwal Akash , Vugmeyster Yulia , Nickens Dana , Lin Swan 
Published: July 2021

Abstract
BACKGROUND: Avelumab is a human IgG1 monoclonal antibody targeting PD-L1 that is approved in the US for second-line locally advanced or metastatic urothelial carcinoma (UC) and first-line maintenance (1LM) treatment of patients with UC that has not progressed with first-line platinum-containing chemotherapy. The current analysis was conducted to evaluate the relationships between avelumab exposure and the probability of experiencing adverse events in 1LM-UC patients.
METHODS: Avelumab exposures following 10-mg/kg every-2-weeks (Q2W) dosing in 1LM-UC patients were derived from post hoc parameter estimates from a population pharmacokinetic model. Safety endpoints included grade ≥3 treatment-emergent adverse events (TEAEs), any-grade infusion-related reactions (IRRs), and any-grade immune-related adverse events (irAEs). For each safety endpoint, avelumab exposures were assessed by univariate screen followed by a full model including influence of all potential covariates and a final model that retained statistically significant covariates (α=0.01) after backwards elimination. Safety analyses were performed with R version 3.5.0 by binomial logistic regression.
RESULTS: A total of 344 1LM-UC patients treated with avelumab were included in the analyses. Of these patients, 163 (47%), 101 (29%), and 74 (21.5%) experienced grade ≥3 TEAE, any-grade IRR, and any-grade irAE, respectively. Avelumab exposure did not demonstrate statistically significant relationships with grade ≥3 TEAE or any-grade irAE. Any-grade IRR demonstrated a potentially confounded inverse relationship with avelumab exposure (p=0.009), a trend also seen in patients with advanced renal cell carcinoma. In all models, immunogenicity and PD-L1 status were tested as covariates but were not predictors for any safety endpoint.
CONCLUSIONS: The exposure range associated with avelumab 10-mg/kg Q2W dosing demonstrated no clinically meaningful relationships with any of the safety endpoints. Given the similarity in avelumab exposures between the flat 800-mg Q2W and weight-based 10-mg/kg dosing, the findings of this analysis support the use of the flat-dosing regimen for 1LM-UC patients.
Citation Format: Jerry Li, Carlo Bello, Akash Khandelwal, Yulia Vugmeyster, Dana Nickens, Swan Lin. Exposure-response safety analysis of avelumab in patients with locally advanced or metastatic urothelial carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1360.
Abstract 1568: A2aR inhibition enhances the antitumor activity of CTLA4 blockade in mouse Pten-deficient prostate cancer
Authors: De Velasco Marco A. , Kura Yurie , Sako Noriko , Ando Naomi , Sakai Kazuko , Schuller Alwin , Fujita Kazutoshi , Nozawa Masahiro , Yoshimura Kazuhiro , Nishio Kazuto , Uemura Hirotsugu 
Published: July 2021

Abstract
Extracellular adenosine impairs immune function in tumors and limits the efficacy of anti-CTAL4 immune checkpoint blockade. We previously showed that adenosine 2A receptor (A2aR) blockade with AZD4635 moderately inhibited tumor growth, in part by improving antigen presentation and cytotoxic T cell (CTL) activity in mouse Pten-deficient prostate cancer. Here, we continue to investigate the antitumor activity of AZD4635 and its effects when combined with CTLA4 blockade (aCTLA4) in preclinical models of Pten-deficient prostate cancer. Prostate tumors from Pten conditional knockout (KO) mice treated with aCTLA4 for five days had increased expression levels of adenosinergic genes. Furthermore, gene expression, flow cytometric and IHC analyses showed increased T regulatory cell differentiation and accumulation that was offset with the addition of AZD4635. Moreover, expression levels of genes associated with Th 1 cell differentiation and T cell-mediated cytotoxicity were increased in AZD4635/aCTLA4 treated tumors. Adding AZD4635 to a four-week regimen of aCTLA4 therapy improved the antitumor response by two-fold in an early-stage intervention model of Pten-deficient prostate cancer. Androgen deprivation (AD) has the potential to promote T cell infiltration in prostate tumors and using the AZD4635/aCTLA4 treatment combination as neoadjuvant therapy to AD via surgical castration led to a greater antitumor response. The antitumor activity of this treatment combination was further examined and confirmed in a subcutaneous syngeneic genome-derived allograft model using tumor-bearing conditional Pten-deficient knockout mice grafted with Pten-deficient CRPC tumor fragments. In a Pten/Trp53 conditional double knockout (DKO) mouse model of advanced prostate cancer, the AZD4635/aCTLA4 treatment combination did not improve overall survival rates. However, when AZD4635/aCTLA4 was used as neoadjuvant therapy to AR inhibition with the anti-androgen apalutamide, it improved median survival time from 21 days in monotherapy treated mice to 34 days in AZD4635/aCTLA4 treated mice. These results provide preclinical evidence to support the rational combination of A2AR blockade with AZD4635 and aCTLA4 immune checkpoint inhibition for PTEN-deficient prostate cancer.
Citation Format: Marco A. De Velasco, Yurie Kura, Noriko Sako, Naomi Ando, Kazuko Sakai, Alwin Schuller, Kazutoshi Fujita, Masahiro Nozawa, Kazuhiro Yoshimura, Kazuto Nishio, Hirotsugu Uemura. A2aR inhibition enhances the antitumor activity of CTLA4 blockade in mouse Pten-deficient prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1568.
Abstract 1861: Advancing bispecific antibody discovery using common light chain immunoglobulin humanized mouse
Authors: Hui Li , Lu Hui , Zhang Yabo , Huang Shuwen , Zhang Ping , Zhao Huizhen , Chang Ruifang , Yang Bing , Zhang Fengqian , Yang Wendong , Yang Fang , Yang Hao , Yao Jiawei , Chen Lei , Lin Qingcong 
Published: July 2021

Abstract
The common challenges of bispecific therapeutic antibody discovery are immunogenicity and chain mispairing issues. Biocytogen's RenLiteTM immunoglobulin humanized mouse is designed not only to overcome these two issues, but also to provide a full human heavy chain repertoire diversity. RenLiteTM mouse carries full human heavy chain VDJ loci and a fixed common human light chain VJ gene. The derived antibodies share the same light chain with different heavy chain variable domain. This technology dramatically simplifies the following heavy and light chain pairing process. Antibodies generated by RenLiteTM mice underwent natural selection, differentiation, and affinity maturation in vivo utilizing a human heavy chain repertoire, the potential of immunogenicity is minimized. RenLiteTM mice show robust immune response comparable to wild type mice and RenLiteTM mice derived antibodies have high binding affinity at subnanomolar range. RenLiteTM antibodies also showed strong in vivo efficacy against tumor growth in xenograft mouse models. In summary, RenLiteTM mouse is a powerful tool for advancing current bispecific or multispecific antibody discovery.
Citation Format: Li Hui, Hui Lu, Yabo Zhang, Shuwen Huang, Ping Zhang, Huizhen Zhao, Ruifang Chang, Bing Yang, Fengqian Zhang, Wendong Yang, Fang Yang, Hao Yang, Jiawei Yao, Lei Chen, Qingcong Lin. Advancing bispecific antibody discovery using common light chain immunoglobulin humanized mouse [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1861.
Abstract 2886: The mechanistic effect of DHA on FABP7 associated membrane lipid order & nanodomain distribution in glioblastoma migration
Authors: Xu Xia , Wang Yixiong , Choi Wonshik , Godbout Roseline 
Published: July 2021

Abstract
Glioblastoma (GBM) is the most common primary brain malignancy. Brain fatty acid binding protein (B-FABP, FABP7) promotes glioblastoma (GBM) migration and correlates to dismal prognosis in GBM patients. Long chain polyunsaturated fatty acids (PUFAs) such as docosahexaenoic acid (DHA) and arachidonic acid (AA) are abundant in brain cell membranes. DHA and AA are preferred ligands of FABP7, with DHA having the stronger affinity for FABP7. Previous studies have shown that DHA inhibits GBM migration in an FABP7-dependent manner. In the current study, we have demonstrated that DHA dramatically altered membrane FABP7 nanoscale distribution pattern, which resulting from plasma membrane lipid ordered domain disruption in GBM cells and neurosphere cultures. We used quantitative membrane order assay to show that FABP7-expressing cells has increased membrane lipid order which is tightly correlated with higher GBM migration property. Using stimulated emission depletion (STED) microscopy, we observed lipid ordered domain was associated with FABP7 nanoscale domain formation. Interestingly, super-resolution microscopy quantitative image analysis revealed that FABP7 membrane nanodomains distribution was dramatically altered upon DHA treatment, which is associated with DHA inhibitory effect on membrane lipid order. Furthermore, STED microscopy has also revealed that reduced FABP7 nanodomain formation in slow migrating GBM cells are similar as FABP7-expressing GBM cells upon DHA treatment. Therefore, we hypothesize that these alterations are likely to be the mechanism of FABP7-mediated DHA inhibitory role in GBM migration.
Citation Format: Xia Xu, Yixiong Wang, Wonshik Choi, Roseline Godbout. The mechanistic effect of DHA on FABP7 associated membrane lipid order & nanodomain distribution in glioblastoma migration [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2886.
Abstract 3094: Estrogen receptor β agonist depletes ovarian cancer stem cells via repressing epithelial to mesenchymal transition
Authors: Banerjee Ananya , Cai Shurui , Li Na , Lavudi Kousalya , Pal Tejinder , Bai Xuetao , Wang Qi-En 
Published: July 2021

Abstract
Ovarian cancer is considered a hormone sensitive tumor. A healthy ovary expresses both Estrogen Receptors alpha (ERα) and beta (ERβ). However, although expression of ERα fairly remains constant, the expression of ERβ gradually decreases as the cells undergo malignant transformation and furthers with the progression of cancer. ERα is thought to promote expression of genes associated with cell survival and proliferation enhancing tumor growth. In contrast, the ability of ERβ to suppress orthotropic ovarian xenograft development supported the role of ERβ as a ‘tumor suppressor' in EOC tumorigenesis. Thus, use of ERβ agonists might prove to be therapeutically beneficial in ovarian cancer. Our studies reveal that activation of ERβ by using a newly developed ERβ agonist, WT-IV-012, is able to suppress the subpopulation of ovarian cancer stem cells. Mechanistically, WT-IV-012 inhibits epithelial to mesenchymal transition (EMT)-mediated CSC expansion, probably by downregulating ERα, which is a key regulator in the maintenance of stemness of CSCs. Taken together, our data indicate that suppressed expression of ERβ is critical to maintaining stemness of ovarian cancer stem cells, in turn, contributing to cancer relapse and chemoresistance. ERβ agonist would be able to limit the CSC subpopulation and prevent tumor relapse and metastasis.
Citation Format: Ananya Banerjee, Shurui Cai, Na Li, Kousalya Lavudi, Tejinder Pal, Xuetao Bai, Qi-En Wang. Estrogen receptor β agonist depletes ovarian cancer stem cells via repressing epithelial to mesenchymal transition [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 3094.
Abstract 882: Associations of genetically predicted blood protein biomarkers with pancreatic ductal adenocarcinoma risk: A study using comprehensive protein genetic prediction models
Authors: Ghoneim Dalia , Zhu Jingjing , Ha Jihwan , Surendran Praveen , Yao Qizhi Cathy , Liu Tao , Fahle Sarah , Butterworth Adam , Wu Chong , Wu Lang 
Published: July 2021

Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with few known risk factors and biomarkers. Identification of biomarkers is critical for understanding the pathogenesis of this deadly cancer and identifying high-risk individuals for close surveillance. Several blood protein biomarkers have been linked to PDAC in previous studies, but these studies have assessed only a limited number of protein biomarkers usually in small set(s) of samples. To identify novel circulating protein biomarkers of PDAC, we studied 8,275 cases and 6,723 controls of European descent from the Pancreatic Cancer Cohort Consortium and the Pancreatic Cancer Case-Control Consortium.
Leveraging genome and plasma proteome data of 2,841 healthy European descendants included in the INTERVAL study, we established models using four methods (best linear unbiased predictor, elastic net, LASSO, and top1) to predict protein levels based on genetic variants. For each protein, of the four sets of models developed, the model showing the highest prediction performance (R2) was retained. We selected 2,164 built protein models with a prediction performance (R2) of &gt;0.01 for association analyses with PDAC risk.
We observed associations between predicted concentrations of 14 proteins and PDAC risk at a false discovery rate of &lt; 0.05, including those of eight proteins that showed a significant association after Bonferroni correction (2.31 × 10-5). These include Histo-blood group ABO system transferase encoded by ABO, which has been previously implicated as a potential target gene of PDAC risk variant identified in GWAS. Besides eight proteins that were previously reported in our earlier study using protein quantitative trait loci as instruments, we identified six novel proteins which have not been identified in previous studies. Six of the identified proteins showed positive associations and eight showed inverse associations (P-values from 2.62 × 10-4 to 5.71 × 10-21).
In conclusion, we identified 14 protein biomarker candidates for PDAC risk, which if validated in future studies, may contribute to the etiological understanding of PDAC development.
Citation Format: Dalia Ghoneim, Jingjing Zhu, Jihwan Ha, Praveen Surendran, Qizhi Cathy Yao, Tao Liu, Sarah Fahle, Adam Butterworth, Chong Wu, Lang Wu. Associations of genetically predicted blood protein biomarkers with pancreatic ductal adenocarcinoma risk: A study using comprehensive protein genetic prediction models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 882.
Abstract 104: Barriers and Facilitators to Integrating Breast and Cervical Cancer Screening Programs in Outpatient Clinics in Western Kenya
Authors: Diala Prisca , Randa Magdalene , Odhiambo Jackline , Ganda Gregory , Cohen Craig , Mungo Chemtai 
Published: July 2021

Abstract
Purpose: Nearly 50% of Kenyan women with breast cancer present with advanced disease – owing partially to limited patient awareness of the importance of breast cancer screening and financial limitations of screening in low- and middle-income countries. With increasing access to nurse-led cervical cancer screening in government clinics in Kenya, we investigated provider-perceived barriers and facilitators to integrating breast cancer screening into ongoing cervical cancer screening programs in Kisumu County, Kenya.
Methods: Providers offering cervical cancer screening within Ministry of Health Clinics in Kisumu County were recruited to participate in a two-phase, sequential, mixed methods study. Providers' knowledge of breast cancer screening guidelines was assessed with a questionnaire based on the 2018 Kenya National Cancer Guidelines. Providers with significant cervical and breast cancer screening experience were invited to complete a 1-on-1 interview to discuss barriers and facilitators to integration.
Results: Sixty-nine nurses and clinical officers from 20 randomly selected facilities participated in the survey. Providers all agreed that breast cancer screening was very important. While 93% said they routinely offered clinical breast examinations, only 22% of these providers screened at least 8 of their last 10 patients. Forty-four percent correctly identified 4 or more of 5 signs and symptoms of breast cancer and 45% correctly identified the recommended screening frequency for women aged 40-55 years. While providers showed enthusiasm for integration, several barriers were identified and grouped into four themes: 1) fragmentation of services; 2) staffing shortage and inadequate on-job training; 3) limited space and referral system challenges; 4) limited patient awareness on need for cancer screening.
Conclusion: Addressing providers' concerns by providing routine on-job clinical training, strengthening the diagnostic and treatment referral pathway, and increasing patient education are some of the first steps in facilitating integration of breast and cervical cancer screening services in primary care clinics in Kenya.
Citation Format: Prisca Diala, Magdalene Randa, Jackline Odhiambo, Gregory Ganda, Craig Cohen, Chemtai Mungo. Barriers and Facilitators to Integrating Breast and Cervical Cancer Screening Programs in Outpatient Clinics in Western Kenya [abstract]. In: Proceedings of the 9th Annual Symposium on Global Cancer Research; Global Cancer Research and Control: Looking Back and Charting a Path Forward; 2021 Mar 10-11. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2021;30(7 Suppl):Abstract nr 104.
Abstract 46: Clinical Outcomes and Quality Metrics of Cervical Cancer Treatment in Rwanda
Authors: Umutoni Victoria , Shyirambere Cyprien , Katznelson Ethan , Nguyen Cam , Bigirimana Jean Bosco , Umwizerwa Aline , Paciorek Alan , Bazzett-Matabele Lisa , Ntasumbumuyange Diomede , Triedman Scott , Shulman Lawrence , Mpunga Tharcisse , DeBoer Rebecca 
Published: July 2021

Abstract
Purpose: Cervical cancer is a leading cause of cancer-related mortality in Africa. As treatment capacity expands, it is critical to evaluate outcomes and identify targets for quality improvement. We describe a cohort of cervical cancer patients at Butaro Cancer Center (BCCOE) in rural Rwanda, many co-managed by gynecologic specialists at the national referral hospital and a subset referred for definitive chemoradiotherapy plus brachytherapy (CRT) in Nairobi based on available funds and estimated curability.
Methosd: We conducted a retrospective cohort study of all patients with cervical cancer seen at BCCOE between 6/2016 and 6/2018. Data were extracted from clinical charts and analyzed using descriptive statistics and Kaplan Meier method.
Results: 377 patients were included; median age 54 years, 21% HIV positive. Most patients (85%) had squamous cell carcinoma. A majority (67%) had stage III or IV disease at presentation. Several early stage patients underwent radical hysterectomy (n=34). 114 (30%) received CRT, representing 45% of eligible candidates. Of these, 30 (26%) received upfront CRT after a median 126 days from diagnosis, and 83 (73%) received “temporizing” carboplatin/paclitaxel while awaiting CRT, with a median 56 days from diagnosis to chemotherapy. Patients sent for upfront CRT were younger (p &lt;0.001) and more likely stage II (p &lt;0.001). Nevertheless, there was no survival difference between upfront CRT versus temporizing chemotherapy before CRT. Most chemotherapy recipients (77%) reported improvement in symptoms. Estimated 3-year overall survival was 94% with radical hysterectomy (95% CI 63-99%), 66% with CRT (95% CI 54-75%), 11% with chemotherapy only (95% CI 5-19%), and 7% with no treatment (95% CI 2-17%) (p&lt;0.001).
Conclusion: Multi-modality treatment of cervical cancer is effective in low resource settings through coordinated care and pragmatic approaches. Our data support a role for temporizing chemotherapy if delays to CRT are anticipated. Expanded and timely access to radiation is urgently needed.
Citation Format: Victoria Umutoni, Cyprien Shyirambere, Ethan Katznelson, Cam Nguyen, Jean Bosco Bigirimana, Aline Umwizerwa, Alan Paciorek, Lisa Bazzett-Matabele, Diomede Ntasumbumuyange, Scott Triedman, Lawrence Shulman, Tharcisse Mpunga, Rebecca DeBoer. Clinical Outcomes and Quality Metrics of Cervical Cancer Treatment in Rwanda [abstract]. In: Proceedings of the 9th Annual Symposium on Global Cancer Research; Global Cancer Research and Control: Looking Back and Charting a Path Forward; 2021 Mar 10-11. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2021;30(7 Suppl):Abstract nr 46.
Підготовка щелепно-лицевих хірургів в Україні: проект моделі
Authors: Маланчук В. О. , Кульбашна Я. А. , Нагірний Я. П. , Шувалов С. М. 
Published: June 2021

Резюме. У статті розкрито актуальність підготовки фахівців із щелепно-лицевої хірургії в Україні та упровадження фаху «Щелепно-лицева хірургія». Обговорюються існуючі у світі моделі підготовки на базі як загальномедичної, так і стоматологічної освіти, яка в Україні забезпечує високий рівень компетентності з базових і загальномедичних дисциплін.
Мета дослідження – розробити проект моделі підготовки фахівців із фаху «Щелепно-лицева хірургія».
Результати досліджень та їх обговорення. Підготовка щелепно-лицевих хірургів – це тривалий і відповідальний процес, який залежить як від особистісних якостей і компетентності лікаря, так і умов та спроможностей держави. На основі аналізу нормативних документів визначено спеціальності, поглиблені знання з яких необхідні для підготовки щелепно-лицевих хірургів, а також терміни з їх вивчення у рамках спеціалізації. Представлено проект моделі підготовки щелепно-лицевого хірурга на базі вищої медичної стоматологічної освіти кваліфікаційного рівня «лікар-стоматолог» і освітнього рівня «магістр стоматології» (термін навчання 6 років і захист науково-дослідницької роботи), один рік інтернатури і двох років резидентури.