bluuebunny/crossref_metadata_2025 huggingface dataset:
Real-world analysis of the EGFR mutation detection in plasma ctDNA from patients with non-small cell lung cancer.
Authors: Long Chaolian , Li Kun , Liu Zichen , Zhang Nana , Xing Xuya , Xu Liming , Gai Fei , Che Nanying
Published: June 2022

e21069

Background: Plasma sample has emerged as a promising surrogate sample for EGFR mutation detection in advanced non-small cell lung cancer (NSCLC). In clinical practice, whether EGFR variants in pretreatment plasma ctDNA of advanced lung cancer can predict prognosis in addition to guiding targeted therapy remains to be further explored. Methods: In this study, we retrospectively enrolled 315 NSCLC patients from Beijing Chest Hospital, 94.9% of whom were in stage IIIB-IV. EGFR gene mutation data from tissue detected by ARMS-PCR (Amoy Diagnostics, Xiamen, China) and paired plasma samples within one month of admission detected by SuperARMS-PCR (Amoy Diagnostics, Xiamen, China) were collected. The patients’ clinicopathological characteristics and treatment information were also collected for further analysis. Differences in PFS of targeted therapy between patients with positive and negative pretreatment plasma ctDNA EGFR mutation were compared. Results: EGFR-positive rate of tissue and plasma ctDNA was 65.1% (205/315) and 43.8% (138/315), respectively. L858R, 19-DEL, T790M, G719X, 20-INS, and L861Q mutations were detected in both samples. The sensitivity, specificity, PPV, NPV and concordance of ctDNA detection was 65.4%,96.4%, 97.1%, 59.9%, and 76.2%, respectively. In the study, patients’ pathological subtype was the factor affected plasma ctDNA EGFR alteration detection accuracy. The concordance in adenocarcinoma patients was obviously higher than that in non-adenocarcinoma (p = 0.02). 92 treatment naïve advanced patients with tissue EGFR mutation were received first and second-generation EGFR tyrosine kinase inhibitors (TKIs) therapies. 59.8% (55/92) patients also had EGFR mutation in plasma ctDNA, 40.2% (37/92) patients had no detectable EGFR mutations in plasma ctDNA. The median PFS in plasma ctDNA EGFR positive patients was 7.0 months versus 14.0 month in plasma ctDNA EGFR negative patients, with significantly difference (p = 0.004). Conclusions: Plasma sample could be a surrogate sample for molecular test when tissue sample was unavailable. The poor prognosis was observed in treatment naïve advanced NSCLC patients with baseline plasma EGFR mutation.
Glycoproteomics as a powerful liquid biopsy-based screening tool for non-small cell lung cancer.
Authors: Mitchell Alan , Pickering Chad , Xu Gege , Rice Rachel , Castellanos Alyn , Bhadra Ranjan , Brcic Luka , Lindenmann Joerg , Smolle Freyja , Lindpaintner Klaus , Serie Danie
Published: June 2022

e21148

Background: Protein glycosylation is the most abundant and complex form of post-translational protein modification. Glycosylation profoundly affects protein structure, conformation, and function. The elucidation of the potential role of differential protein glycosylation as biomarkers has so far been limited by the technical complexity of generating and interpreting this information. We have recently established a novel, powerful platform that combines liquid chromatography/mass spectrometry with a proprietary artificial-intelligence-based data processing engine that allows, for the first time, highly scalable interrogation of the glycoproteome. Methods: Using this platform, we interrogated 694 glycopeptide (GP) and non-glycosylated peptide transitions derived from 74 serum proteins in pre-treatment peripheral blood samples from a cohort of 316 individuals with non-small-cell lung cancer (NSCLC) (128 females, 187 males, 1 with unknown sex, median age 66 years, age range 31-89 years, stage 0-4 N’s: 1 / 99 / 80 / 84 / 49, 3 missing) and a comparison cohort of 194 healthy control samples (102 females, 92 males, median age 52 years, age range 30-63 years). Age- and sex-adjusted differential expression analysis for 596 normalized biomarkers were performed to evaluate statistically significant differential abundances using an FDR-adjusted q-value of 0.05 as a cutoff. Repeated five-fold cross-validated LASSO-regularized logistic regression was performed to create a multivariable classifier that predicts whether a serum sample belongs to the healthy or NSCLC cohort. Results: We identified 432 biomarkers with significant abundance differences at FDR ≤ 0.05 between samples with NSCLC and healthy controls. Using 70% of the complete cohort (balanced by case/control membership, NSCLC stage, sex, and age quartile) as a training set, we selected a total of 375 glycopeptide and non-glycosylated peptide biomarker features that remained differentially expressed at FDR-adjusted q-value ≤ 0.05 as input into a LASSO-regularized multivariable classifier. This resulting in a 19-biomarker model exhibiting an accuracy of 94.8% (96.9% sensitivity, 91.2% specificity) and AUC of 0.989. This classifier was validated in an independent test set comprising the remaining 30% of subjects, yielding an accuracy of 94.5% (95.5% sensitivity, 93.0% specificity) and AUC of 0.975. Sensitivity in the test set was 100% / 96% / 99% / 96% / 94% / 10%, in stages 0-4 and missing, respectively. Conclusions: Our results indicate that glycoproteomic biomarkers can be leveraged as a strong liquid biopsy-based screening tool for patients at high risk of NSCLC, as an alternative to imaging modalities.
Whose mitochondria are more stable, male or female ones? Response of neurosteroid status of mitochondria of cerebral cortex cells to melanoma development in presense of chronic pain.
Authors: Neskubina Irina V. , Frantsiyants Elena M. , Kaplieva Irina V. , Shikhlyarova Alla I. , Surikova Ekaterina I. , Cheryarina Natalia D. , Bandovkina Valeria A. , Pogorelova Yulia A. , Kuchkina Ludmila P. , Snezhko Aleksandr V. , Rozenko Dmitry A. , Ausheva Tatiana V. , Kit Oleg I.
Published: June 2022

e21559

Background: Gender differences in brain physiology and gender differences in pathology are usually recognized, but often are disregarded in clinical and experimental studies, resulting in numerous inaccuracies in data interpretation. The purpose of this study was to analyze levels of neurosteroid hormones in mitochondria of the cerebral cortex cells in C57BL/6 mice with subcutaneous B16/F10 melanoma growing in presence of chronic neurogenic pain (CNP). Methods: The study included male and female C57BL/6 mice (n = 336) aged 8 weeks initially weighing 21-22 g. Experimental groups were: intact animals; controls with a CNP model created by bilateral sciatic nerve ligation; comparison group 3 weeks after subcutaneous inoculation of 0.5 ml suspension of B16/F10 melanoma cells diluted 1:10; main group 3 weeks after subcutaneous melanoma growth in presence of CNP (CNP+B16/F10). Levels of estradiol (pg/g protein), estrone (pg/g protein) (DBC, Canada); progesterone (ng/g protein), total and free testosterone (pg/g protein) (XEMA, Russia) were measured in mitochondrial samples by ELISA (Tecan Infinite F50 analyzer, Austria). Results: Levels of estradiol in intact females were 3.1 times higher than in males, while estrone, progesterone, total and free testosterone were lower by 6.4, 2.7, 2.0 and 2.5 times, respectively. Only in females with CNP estradiol decreased by 3.4 times, compared to intact values, and estrone increased by 1.7 times (p<0.05), testosterone by 3.9 times. Estradiol in animals with B16/F10 decreased compared with intact values by 3.1 times in females and by 1.5 times in males (p<0.05). Females with B16/F10 showed the highest levels of progesterone exceeding intact values by 3.1 times. In the group with CNP+B16/F10, females showed lower levels of estradiol and estrone (by 1.4 times, p<0.05) and free testosterone (by 1.6 times, p<0.05), compared to the levels in CNP; on the opposite, males had 1.5 times (p<0.05) higher estrone and 2.9 times lower progesterone. Conclusions: Low levels of estradiol involved in the protective mechanism of neurosteroids were the dominant factor in mitochondria of cerebral cortex cells in females with CNP and malignant neoplasms. Males did not demonstrate such dominant factor. In animals with CNP+B16/F10, the response nature of cerebral cortex mitochondria changed: all defense mechanisms in the brain of females were suppressed by the 3rd week of tumor development in presence of pain. In males, mitochondria of cerebral cortex cells were more resistant to the influence of two pathologies, and only few changes in the neurosteroid status were recorded.
Dietary fish oil augments the tumor immune microenvironment in anti-PD-1 treated melanoma.
Authors: Chacon Alexander C , Qin Shuyang Sue , Melucci Alexa , Jackson Katherine M. , Burchard Paul R. , Dave Yatee A. , Jewell Rachel , Belt Brian A. , Tabayoyong William , Prieto Peter A.
Published: June 2022

e21564

Background: Less than half of metastatic melanoma patients experience objective responses to first line anti-PD-1 immune checkpoint inhibition (αPD-1 ICI). Omega-3 fatty acids in dietary fish oil (FO) shift myeloid and T-cell populations to anti-inflammatory, pro-resolution phenotypes in immunity and cancer. We investigated whether dietary FO supplementation could augment tumor microenvironment (TME) immune profiles and improve ICI response in melanoma. Methods: C57-BL6/J mice were injected with YUMM 1.7 melanoma in the flank. Mice were fed control chow (CTL) or omega-3 rich (FO) chow (10% w/w, 30%kcal/kcal) starting 7 days post tumor implantation. Intraperitoneal αPD1 or IgG2a vehicle were injected q3-4 days starting day 12. To assess the temporal flux of TME immune populations, tumors from mice in analogous experiments were assessed for growth, harvested on day 12, day 22, or day 32, and characterized via flow cytometry. Results: In multiple models, FO decreased YUMM tumor growth vs. CTL by day 32 (> 21% for all models). FO halved tumor associated macrophage content, including M2 macrophages (Arg1+, CD206+, CD68+, F480+), at day 12. Conversely, FO increased M2 macrophages at day 22, leveling even with CTL at day 32. At all three timepoints, FO increased TME monocytes (Ly6C+, Ly6G-). In the T cell compartment, FO decreased TME CD4 and CD8 T cell content (including PD1+ CD4 and PD1+ CD8) at day 12, an effect which was reversed by day 22 (increased CD4 and CD8s vs CTL). FO increased PD-L1+ CD4 T cells and CD8+ T cells, including PD1+ CD8 T cells, on day 32. When fish oil diets were started on day 12 (concurrent with immunotherapy), FO decreased tumor volume, increased monocytes (and PD-L1+ monocytes), and increased CD4 and PD1+ CD8 T cells by day 32, all less significantly than when starting diets 5 days prior to initiation of immunotherapy. All results significant (p < 0.05) by 2-way ANOVA or t-test unless specified. Food eaten, water imbibed, and weight change did not vary between groups. Conclusions: Fish oil impairs in vivo murine melanoma tumor growth with and without αPD-1 ICI. Fish oil modulated myeloid and T cell lineages via delaying M2 macrophage and CD4 / CD8 T-cell appearance in the tumor microenvironment, with concomitant increases in monocytes and key T cell effectors involved in αPD-1 ICI responsiveness by the time decrements in tumor growth were noted. Dietary fish oil may benefit patients with advanced melanoma treated with αPD-1 immunotherapy; further study in humans is warranted.
Survey of Uruguayan women on knowledge related to the prevention of breast cancer.
Authors: Camejo Natalia , Castillo Cecilia , Amarillo Dahiana , Bernate Moira , Burguez Florencia , Darino Eliana , Deleon Adrian , Milwa Tatiana , Barcia Maria , Krygier Gabriel David
Published: June 2022

e22504

Background: In Uruguay, breast cancer has the highest incidence and mortality of all cancer in women. Methods: To assess the knowledge of Uruguayan women about breast cancer screening for the early detection of BC. Material and Methods: This is a descriptive and observational study. A survey was applied to womwn, it was disseminated through social networks. Informed consent was requested at the beginning of the survey as an exclusive requirement to be able to carry it out. In the statistical analysis, the anonymity of the patients was maintained and the approval of the Ethics Committee of the Hospital de Clínicas was obtained. Results: 1859 women participated. 75.1% (1396) of those surveyed recognize BC as the one with the highest mortality in women. 52% (967) believe that 3 out of 10 women are at risk of developing BC, and 18.4% (342) do not know its prevalence. 60.2% (1119) recognize mammography as a test that has managed to reduce mortality from BC. 64.2% (1193) believe that it is done after 40 years of age. Regarding the frequency, 60.5% (1125) consider that it is carried out annually. The most considered risk factors for developing BC were smoking (60.9%, 1132), obesity (57%, 1.060) and sedentary lifestyle (56.8%, 1056). Conclusions: Our results show that the respondents are adequately informed about the importance of CM and the performance of screening mammography.
Deciphering possible mechanisms of action in pathophysiology of osteosarcoma: PI3K-Akt/MAPK pathways contribute to tumorigenesis versus FoxO/mTOR/HIF-1 pathways involved in metastasis.
Authors: Zou Changye , Zhao Zhiqiang , Xu Mingxian , Guo Weitang , Huang Jintao , Zhang Xin , You Dong , Shen Jingnan
Published: June 2022

e23515

Background: Osteosarcoma is a kind of primary bone malignancies with high invasiveness and poor prognosis. However, effective therapy for osteosarcoma is still lacking. In fact, the advancement of clinical practice and innovative therapy was hindered by the limited understanding of the genetic characteristics and the mechanism of metastasis. Exploration of the mutational and evolutionary features of osteosarcoma is warranted. Methods: A total of 24 samples of matched primary and metastatic lesions were collected from 12 osteosarcoma patients. Targeted sequencing including 672 cancer-related genes was conducted in 9 patients while whole exome sequencing was performed in 3 patients. Results: High-frequency mutation genes were TP53 (42%), FLCN (33%), GID4 (33%), ATRX (25%), CCND3 (25%) in primary osteosarcoma, comparing to FLCN (42%), GID4 (42%), CCNE1 (25%), MYO15A (25%), ATRX (25%) in metastatic lesion. The PI3K-Akt and MAPK signaling pathway was significantly enriched in both primary (PI3K, p < 0.001; MAPK, p < 0.001) and metastatic lesions. (PI3K, p < 0.001; MAPK, p < 0.001), Additionally, chromosome region 17p11.2, including the driver genes NCOR1, MAP2K4, ALOX12B, AURKB, CDK12, was significantly amplified in primary (G-score = 1.9, q-value = 0.06) and metastatic lesions (G-score = 3.2, q-value < 0.001). These data suggested that changes of PI3K and MAPK pathways and amplification of region 17p11.2 may contribute to initial osteosarcoma tumorigenesis and possibly early metastasis. In contrast, the FoxO, mTOR and HIF-1 signaling pathway were only enriched in metastatic lesions (FOXO, p < 0.001; mTOR, p < 0.05; HIF-1, p < 0.001), implying that these pathways may be critical for osteosarcoma metastatic occurrence. Finally, clonality analysis showed that cellular clonal prevalence (CCF) of subclones including diver genes of ATRX, MYO15A and MYB, were increased ( ATRX: P, CCF = 0.59, M, CCF = 0.74; MYO15A: P, CCF = 0.43, M, CCF = 0.52; MYB: P, CCF = 0.11, M, CCF = 0.52) in metastatic lesions, which further confirmed that alterations of ATRX and MYO15A were considerably vital for osteosarcoma. Conclusions: The abnormal changes of PI3K-Akt and MAPK signaling pathway as well as the amplification of 17p11.2 chromosome region may contribute to osteosarcoma tumorigenesis and possibly early metastasis; whereas pathways of FoxO, mTOR, HIF-1 and driver genes including ATRX, MYO15A and MYB, may play a key role in the metastasis of osteosarcoma.
Tumor thrombosis in extremity soft tissue sarcomas.
Authors: Katelnitskaya Oksana V. , Nepomnyashchaya Evgeniya M. , Ausheva Tatiana V. , Barashev Artem A. , Vashchenko Larisa N. , Chernogorov Pavel V. , Kit Oleg I.
Published: June 2022

e23551

Background: Malignant tumors of bones and soft tissues often reach large sizes, compress and invade the major vessels, leading to the development of venous thrombosis. Venous thrombosis is difficult to distinguish from tumor thrombosis in the preoperative period. However, the management differs. Both conditions require anticoagulant therapy, but tumor thrombosis requires expanding intervention with the thrombus removal and major venous resection. The major vessel involvement complicates surgery. It is much more difficult to achieve negative resection margins. The risk of damage to the main vessels during tumor mobilization increases and, as a result, the risk of hemorrhagic complications increases as well. An interdisciplinary approach reduces the risk of surgical complications and helps achieve radical tumor resection. Our purpose was to analyze the rates of tumor thrombosis in malignant tumors of bones and soft tissues and evaluate the results of surgical treatment. Methods: 115 patients (mean age 46 years) with malignant tumors of bones and soft tissues received surgical treatment in 2020-2021. The most common histological subtypes were synovial sarcoma (25.3%), pleomorphic sarcoma (18.2%), and liposarcoma (15.6%). Venous thrombosis of the lower extremity veins was diagnosed at the stage of preoperative preparation in 17 patients (14.8%), the femoral segment was more often affected (70.6%). All patients received anticoagulant therapy. The tumor genesis of a thrombus was confirmed intraoperatively in 7 patients. Thus, the incidence of tumor thrombosis in malignant tumors of bones and soft tissues was 6%. All patients underwent tumor removal, thrombectomy, and the femoral or iliac venous segment resection. Results: The following complications were observed in the postoperative period: seroma - 5 cases (29.4%), lymphorrhea - 12 (70.5%), swelling of the lower limb - 12 cases (70.5%). Conclusions: Tumor thrombosis in malignant tumors of bones and soft tissues of the lower extremities is not a rare complication, it requires timely diagnosis and an expanded intervention to achieve negative resection margins and reduce the risk of embolism.
Differential outcome of females with uterine versus extra-uterine leiomyosarcomas, a retrospective analysis.
Authors: Hana Caroline , Akinbobuyi Olufunke , Wadhawan Ashna , Samuels Shenae , Hussein Atif Mahmoud
Published: June 2022

e23557

Background: Leiomyosarcomas, are aggressive sarcomas with survival rates among the lowest of all soft tissue sarcomas. Patients with uterine leiomyosarcoma (ULMS) have worse overall survival (OS) than those with extra-uterine leiomyosarcoma (EULMS). The effect of several clinical factors on OS have been investigated, including age, tumor size, grade, stage, and use of chemotherapy. Looking at the epigenetics of the 2 diseases, differentially methylated regions (DMRs) were statistically significant between the 2 groups. Methods: The 2004-2016 National Cancer Database was queried for females with ULMS and EULMS. We investigated several factors as predictors of binary survival status (alive or dead): patient’s age, race, year at diagnosis, tumor grade, size and stage, receipt of surgical treatment, chemotherapy, palliative care, surgical margins and time to treatment in days. Univariate and backward stepwise multivariate logistic regression models were used to determine prognostic factors associated with survival in each group. Kaplan-Meier (KM) method with log-rank test was used to compare OS rates between the 2 groups. All analyses were conducted using Stata/SE 15.1. Results: The total number of subjects was 16883. The median OS was 36.7 months in ULMS vs 57.2 in EULMS (P < 0.001). Older age was associated with a lower likelihood of survival in both groups (OR = 0.95, P = 0.018 in ULMS; OR = 0.97, P < 0.001 in EULMS). Lymphovascular invasion and receipt of palliative care were associated with a relatively large decrease in survival in ULMS only (OR = 0.25, P < 0.001; OR = 0.13, P = 0.015 respectively). In the EULMS group, increased likelihood of survival was associated with later years of diagnosis (OR = 1.27; P < 0.001). Larger tumor size (OR = 0.39; P = 0.001), stages II-IV or unstageable disease (OR = 0.56; P < 0.001), positive surgical margins or margins that were unevaluable (OR = 0.87; P = 0.009) and receipt of systemic therapy (OR = 0.85; P = 0.016) were associated with a lower likelihood of survival. Conclusions: Our study reiterated that females with ULMS had worse OS than those with EULMS. this difference can be attributed to certain clinical risk factors, however, it may also be secondary to genetic and epigenetic factors. Surprisingly, the use of palliative care in this study was associated with poorer OS in the EULMS group. Further studies are needed to investigate the genetic map of these diseases and highlight certain potentially targetable prognostic and predictive factors. Study limitations: Our study did not stratify ULMS and EULMS according to the stage to examine if the aforementioned factors would still be relevant in the limited versus metastatic setting.
Evaluating cancer awareness months and cancer screening tests through internet search big data.
Authors: Tawfik Bernard
Published: June 2022

e24038

Background: Cancer Awareness Months (CAMs) aim to increase public recognition of specific cancers through education and screening promotion, but their effectiveness is uncertain. This study was designed to characterize the relationship between internet search interest (ISI) of breast, colon, lung, and prostate cancers and related screening test terms with their respective CAMs with the goal of better understanding CAM effectiveness across time and geographic scale. Methods: ISI was collected from sampled Google Search data from Google Trends on a national, state, and metropolitan level between 2004 and 2021. The ISI for cancer and cancer screening terms for each respective CAM was compared to ISI for nonadjacent months and across regionality. Results: Breast CAM was associated with increased ISI for both cancer (p > 0.001) and cancer screening (p > 0.001) terms. Colon CAM was associated with higher cancer term ISI (p = 0.004), but had mixed effects on screening ISI across terms. Lung CAM was not associated with a change in cancer term ISI (p = 0.573) and had mixed effects across screening terms. Prostate CAM was not linked to ISI changes for any associated terms. Regional variation in ISI was found in all cases. Conclusions: Given the high accessibility and scalability of Google Trends, this tool can be used to practically evaluate and guide the strategies of CAM campaigns across cancer type and geographic scale. Future directions include broadening the geographic scope and comparatively assessing specific CAM campaign strategies.
“The Oizys Study”: Prevalence and impact of scan-related anxiety on QoL among Greek cancer patients and their caregivers.
Authors: Koinis Filippos , Leontopoulou Vasiliki , Chantzara Evangelia , Kotsakis Athanasios
Published: June 2022

e24118

Background: Diagnostic imaging may be a major source of distress in patients with advanced cancer, a condition known as “scanxiety”. Scanxiety represents a complex array of negative and stressful emotions linked with cancer scans, and the uncertainties and fears that may accompany them. We aimed to evaluate the prevalence and characterize risk factors for scanxiety among cancer patients and their caregivers and evaluate the impact of scanxiety on quality of life (QoL), during the COVID-era. Methods: We conducted a cross-sectional survey study of metastatic cancer patients treated at the University Hospital of Larisa and their caregivers. Eligible patients met the following inclusion criteria: age > 18 years old, ability to speak and write fluently in Greek, having had at least one imaging study during the period of the study ( seven days before the survey), approval of the patient’s oncologist to approach the patient. Patients/caregivers with pre-existing (prior to cancer diagnosis anxiety disorder) were excluded from the study. After completion of the informed consent process, patients/caregivers completed all survey items. We used a modified version of the Greek version of the Impact of Event Scale-Revised (IES-R-Gr) to specifically assess distress associated with scans, and QoL was measured using the EORTC QLQ-C30 questionnaire. Results: 218 patients with metastatic cancer and their caregivers were included in the study. Patient's mean age was 66 years (range 35-88). The majority were men (61%) and were diagnosed with Non-Small-Cell Lung Cancer. 71% had an IES-R-Gr score that was suggestive of scanxiety. Their symptoms were more severe symptoms while waiting for the results. Patients with a recent diagnosis (< 6 months) had higher levels. Interestingly, 16% of the patients had postponed a check-up due to scanxiety, while 77% reported that stress does not decrease over time. The majority of caregivers (81%) reported scanxiety, without a strong correlation with the score of the respective patients. Unlike patients, the majority of caregivers reported an increase in stress during the COVID-19 period. The presence of scanxiety was associated with decreased QoL in patients (p = 0.004). Conclusions: Scanxiety is a common problem among patients with metastatic cancer and is associated with impaired QoL. To our knowledge this is the first study implying that caregivers also experience scanxiety and may be a persistent problem.
A first-in-human, phase I, open-label study of a novel cancer vaccine labvax 3(22)-23 and adjuvant GM-CSF in patients with advanced stage adenocarcinomas.
Authors: Ma Weijie , Chen Shuai , Ogihara Nancy L. , Huynh Jasmine , Yen Ariel , Kelly Karen , Lara Primo "Lucky" N. , Radosevich James A. , Babich Michael , Li Tianhong
Published: June 2022

TPS2700

Background: Adenocarcinoma is the most common histologic type of solid tumors and can arise from almost anywhere in the body. Labyrinthin is a novel tumor-specific protein expressed on the cell surface of the majority of adenocarcinomas of various cancer types. Several therapeutic strategies targeting labyrinthin are under development. We hypothesize that vaccination against labyrinthin can elicit strong immune responses against the labyrinthin-positive adenocarcinomas in cancer patients. LabVax 3(22)-23 is a novel anti-tumor vaccine that contains 4 synthetic labyrinthin-based peptides designed to elicit both B-cell and T-cell responses. Sargramostim, a recombinant granulocyte macrophage colony-stimulating factor (GM-CSF), is given as an immunostimulator with LabVax 3(22)-23 to boost the antitumor immune response. Preclinical studies showed that LabVax 3(22)-23 significantly inhibited tumor growth that was augmented by GM-CSF without any significant toxicity in C57/BL6 transgenic mice expressing human PD-1/PD-L1 implanted with the murine colon adenocarcinoma cell line MC-38-huPD-L1. This single institution, first-in-human, phase I trial (UCDCC#296) evaluates LabVax 3(22)-23 and adjuvant sargramostim in patients with labyrinthin-positive metastatic or recurrent adenocarcinoma of any primary tumor site after all standard-of-care therapies. Methods: The primary objective is to assess the toxicity of LabVax 3(22)-23 and adjuvant sargramostim according to NCI CTCAE V5.0. The primary endpoint is dose limiting toxicity (DLT), which is defined as grade ≥ 2 allergic and autoimmune reaction, grade ≥ 3 injection site reaction, any grade 3 toxicities lasting >1 week, or any grade ≥ 4 toxicities. With a sample size of 10 patients, there is 89-97% of chance to observe ≥1 DLT if the true event rate is 20-30%. A secondary endpoint is the preliminary assessment of tumor response rate by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Exploratory objectives measure the effect of LabVax 3(22)-23 on various immune responses (cytokines, anti-labyrinthin antibody production) and the correlation between the level of labyrinthin expression and the efficacy of LabVax 3(22)-23. Eligible patients are required to have labyrinthin expression on their tumor cells by immunohistochemistry and adequate organ function. Patients receive sargramostim subcutaneously and LabVax 3(22)-23 intradermally on weeks 1, 2, 4, 8, and 12 in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 3 months for 1 year. Two patients are enrolled at the time of submission. Clinical trial information: NCT05101356.
AGO-OVAR 2.29 (ENGOT-ov34): Atezolizumab in combination with bevacizumab and chemotherapy versus bevacizumab and chemotherapy in recurrent ovarian cancer (ROC).
Authors: Harter Philipp , Marmé Frederik , Pautier Patricia , Reuss Alexander , Lindemann Kristina , Kurzeder Christian , Van Nieuwenhuysen Els , Schmitt Clemens , Cron Nadin , Redondo Andres
Published: June 2022

TPS5611

Background: Paclitaxel or pegylated liposomal doxorubicin in combination with bevacizumab constitutes a standard treatment option in patients with relapsed ovarian cancer who are not considered candidate for platinum, but responses are short-lived. Immune checkpoint inhibitors like atezolizumab as single agents have limited activity in ovarian cancer. There is a biologic rationale to combine checkpoint inhibitors with chemotherapy and bevacizumab, however, the role of such combination for the management of ovarian cancer is so far undefined. Because of the intimate relationship between angiogenesis and immunosuppression, it is expected that the inhibition of both pathways could lead to synergism and more durable clinical benefit. The addition of a chemotherapeutic agent is expected to lead to the release of tumor antigens and enhance the efficacy of immunotherapy in turn. Therefore, we aim to test the efficacy of atezolizumab in combination with non-platinum-based chemotherapy and bevacizumab vs the combination of a non-platinum-based chemotherapy and bevacizumab alone. Methods: AGO-OVAR 2.29 is a randomized (1:1), double blinded, phase III trial evaluating the efficacy and safety of atezolizumab plus bevacizumab and chemotherapy (weekly paclitaxel or pegylated liposomal doxorubicin) compared with placebo plus bevacizumab and chemotherapy in patients with recurrent ovarian, fallopian tube, or primary peritoneal cancer with 1st or 2nd relapse within 6 months after completing platinum-based chemotherapy or 3rd relapse. A de novo tumor biopsy to determine the PD-L1 expression status prior to randomization for stratification is mandatory. Patients are treated with chemotherapy plus bevacizumab + atezolizumab/placebo until progression or unacceptable toxicity. Co-primary endpoints are overall survival and progression-free survival. It is planned to randomize approximately 664 patients. Safety interim analyses were performed after inclusion of 24 and an additional 60 and 120 patients who had completed at least one treatment cycle. As of 09th February 2022, 461 patients have been randomized. Clinical trial information: NCT03353831.
Anlotinib plus tislelizumab combined with chemotherapy as neoadjuvant treatment in triple-negative breast cancer: A prospective, single-arm, open-label phase II study.
Authors: Luo Jing
Published: June 2022

TPS618

Background: Neoadjuvant anti-PD-(L)1 therapy confers an improvement in pathological complete response (pCR) rate in unselected triple-negative breast cancer (TNBC). Combination of antiangiogenic agent plus immune checkpoint inhibitor and chemotherapy therapy for advanced TNBC is reported as a promising anti-tumor strategy presented in the FUTURE-C-PLUS study. Tislelizumab is a humanized immunoglobulin G4 anti-PD-1 monoclonal antibody engineered to minimize binding to FcγR on macrophages. Anlotinib is a novel multi-target tyrosine kinase inhibitor that effectively inhibit VEGFR, FGFR, c-KIT, c-MET and RET. Previous studies have proven the efficacy of both anlotinib monotherapy and combination with immune checkpoint inhibitor in advanced breast cancer. This phase II study aims to evaluate the efficacy and safety of anlotinib plus tislelizumab combined with chemotherapy as neoadjuvant treatment in TNBC. Methods: This is a prospective, single-arm, open-label, phase II trial. Eligible patients (pts) were women, aged 18-75 years, ECOG status 0-1, previously untreated invasive TNBC with histologically confirmed (cT1N1-2M0 or cT2-4N0-2M0). 32 pts will be enrolled and received 5 cycles of anlotinib (8 mg qd, d1-14; 21 days per cycle) with 6 cycles of tislelizumab (200 mg, once every 3 weeks) plus nab-paclitaxel (260 mg/m2, once every 3 weeks) and anthracycline (epirubicin 75 mg/m2 or doxorubicin 60 mg/m2), followed by surgery. The primary endpoint is pathological complete response rate (pCR, ypT0/Tis ypN0) and the secondary endpoints include invasive disease-free survival (iDFS), event-free survival (EFS), overall survival (OS), and safety. A sample size of 32 patients was estimated to provide a 80% power to detect a difference of 25% in pCR at a significance level of α = 0.05. The study was initiated in August 2021. Clinical trial information: NCT04914390.
A phase II study of CPX-351 in younger patients < 60 years old with secondary acute myeloid leukemia: Trial in progress.
Authors: Swaminathan Mahesh , Fazal Salman , Griffiths Elizabeth A. , Thompson James E. , Sung Pamela Jeannette , Green Steven Daniel , Li Emily , Said Meriem , Belko Krista , Mattice Emmalyn , Attwood Kristopher , Wang Eunice S. , Przespolewski Amanda
Published: June 2022

TPS7073

Background: Patients (pts) with secondary acute myeloid leukemia (s-AML) and therapy-related AML (t-AML) have poor long-term outcomes following standard induction 7+3 chemotherapy. CPX-351, a liposomal formulation of cytarabine and daunorubicin fixed at the synergistic ratio of 5:1, is indicated for the treatment of pts with newly diagnosed s-AML and t-AML based on the results of a phase III trial favorably comparing CPX-351 to 7+3. Although the trial only enrolled pts aged 60-75 years (Y), CPX-351 is approved by the United States Food and Drug Administration for all adult pts with t-AML and AML with myelodysplasia-related changes (AML-MRC). In a prior retrospective analysis of CPX-351 in pts <60 Y with s-AML, we noted that the outcomes of these younger pts appeared inferior to those reported in older pts (60-75 Y) in the phase III trial (Przespolewski et al. Blood 2018 p.2677). Therefore, we designed this prospective study to evaluate the efficacy of CPX-351 in pts <60 Y with untreated s-AML and t-AML. Methods: In this phase II single-arm multi-institutional study, pts aged 18-59 Y with untreated t-AML or AML-MRC, adequate organ function, and ECOG performance status ≤ 2 are eligible. Pts with active central nervous system disease and infections were excluded. CPX-351 will be dosed at 100 mg/m2 cytarabine and 44 mg/m2 daunorubicin on days 1, 3, and 5 during induction. Bone marrow biopsy will be performed between days 14-21 to assess response. If needed, re-induction CPX-351 dose will be 44 mg/m2 daunorubicin/100 mg/m2 cytarabine on days 1 and 3. Pts achieving a complete remission (CR) following induction can receive up to 2 cycles of consolidation CPX-351 dosed as cytarabine 65 mg/m2 and daunorubicin 29 mg/m2 on days 1 and 3. The primary endpoint of the study is overall response rates defined as CR and CR with incomplete blood count recovery (CRi)) within 45 days of beginning therapy. Secondary endpoints are duration of response, event-free survival, overall survival, rate of allogeneic stem cell transplant, and adverse events. A maximum of 46 pts will be enrolled at 4 U.S. sites with 5-year follow-up from the start of CPX-351.The study is open and has enrolled 4 pts to date. Clinical trial information: NCT04269213.
Frontline treatment of follicular lymphoma with atezolizumab and obinutuzumab, with and without radiotherapy (The FLUORO study).
Authors: Hawkes Eliza Anne , Manos Kate , Khor Richard , Douglas Genevieve , Lee Sze Ting , Lee Denise , Campbell Belinda , Grobler Anneke , Gilbertson Michael , Palmer Jodie , Chong Geoff
Published: June 2022

TPS7587

Background: Follicular lymphoma (FL) is the commonest indolent lymphoma, comprising 20% of non-Hodgkin Lymphoma, with approximately 80% of patients (pts) requiring therapy. At present, advanced stage is incurable; most pts require >1 treatment. Overall response rates (ORR) to standard chemoimmunotherapy (bendamustine or CHOP with rituximab or obinutuzumab) approximate 85% with considerable toxicity (grade 3-5 in 69-75%) (Hiddemann 2018). With the FL population predominantly >65 years, 10-year median survival and need for further therapy, efficacious treatments with low toxicity are desirable. PD1/PDL1 axis inhibitors are active in FL. A phase I study of obinutuzumab (O) + atezolizumab (A) induced 57% ORR in pts with rituximab-refractory FL (Palomba 2017). Our phase II ‘1st FLOR’ study, combining nivolumab + rituximab in treatment naïve FL yielded 92% ORR, (54% Complete Response, CR). Toxicity profiles compared favourably with conventional chemotherapy: 41% grade 3-5 events (Hawkes 2021). FL is sensitive to low dose radiotherapy (RT), with abscopal effects reported, and potential to improve treatment efficacy with minimal additional toxicity when combined with PD1/PDL1 inhibitors (Sharabi 2015). This investigator initiated, multicentre single-arm phase II PET-adapted trial aims to assess the response of O + A +/- RT for treatment-naïve FL, reducing treatment-related toxicity using a chemotherapy-free, multi-modality, synergistic regimen. Methods: Eligible pts are >18 years, ECOG 0-2 with untreated, biopsy proven, grade 1-3A stage II-IV FL. Exclusions are significant compressive symptoms, autoimmune disease, pneumonitis and treatment urgency. All pts receive 6 cycles (q21 days) of O 1000mg + A 1200mg (plus O given on days 8 & 15 of cycle 1). Interim PET-CT is performed post cycle 2. Pts with less than CR will undergo RT (4Gy) to residual disease after cycle 3. At end of induction, responding patients will receive maintenance O (up to 12 cycles, 1000mg Q8W). Pts with significant progression will be taken off study. Total follow-up is 2 years post treatment. Primary endpoint is CR rate following 6 x O&A +/- RT. Secondary endpoints include ORR, PFS, OS and adverse events. PET centres are ARTnet accredited with central analysis. An extensive exploratory biomarker substudy is planned. Sample size is 46 according to a Simon’s 2-stage design. If ≥5 positive responses (CR +/- PR) without prohibitive toxicity are seen in the first 15 pts, 31 further pts will be recruited.The trial has currently enrolled 7 pts from 4 Australian sites. Clinical trial information: NCT04962126.
Evaluation of seroprevalence and associated risk factors of Toxoplasmosis in sheep and goats in District Jhang-Pakistan
Authors: Zafar Muhammad Awais , Shafique Muhammad , Zahoor Muhammad Asif , Saqalein Muhammad , Aslam Bilal , Arshad Muhammad Imran , Waheed Usman , Kashif Muhammad
Published: June 2022

Toxoplasmosis is a zoonotic infection caused by a pathogenic protozoan, Toxoplasma gondii, responsible for huge economic and health losses in developing countries. The current study was conducted to assess the seroprevalence of Toxoplasmosis and associated risk factors in sheep and goats in District Jhang, Punjab, Pakistan. Blood samples (n=400) were collected from both genders of goats (n=219) and sheep (n=181) from four Tehsils of District Jhang alongwith a comprehensive questionnaire to evaluate the risk factors associated with the disease endemicity and spread. For assessing the seroprevalence, the samples were  examined using Latex agglutination test. Additional data regarding hygienic conditions, water source, gender, breed, age of animal was also collected on a predesigned questionnaire. The overall seroprevalence of Toxoplasma gondii was found  34.25% (137/400) in District Jhang. Higher seroprevalence was recorded in goats {36.52% (80/219)} as compared to sheep {31.49% (57/181)}, however, it was non-significant (p>0.05). Gender-wise seroprevalence was found 32.59% (44/135) and 35.09% (93/265) in male and female animals, respectively (p>0.05). Further, the association of Toxoplasmosis between different age groups was significantly higher in older animals having age >24 months 42.75% (62/145) than younger animals with age <12 months 26.60% (29/109) and 11-24 months 31.50% (46/146) (p<0.05). The seroprevalence was also higher 40.81% (80/196) in animals drinking water from outdoor water source than in animals drinking from indoor water source 27.94% (57/204) (p<0.05). Moreover, seroprevalence was significantly higher 43.11% (97/225) in animals  kept in vicinity of cats than in absence of cats 22.85% (40/175) (p<0.05). However, reproductive status, breeds, flock size had non-significant impact on the prevalence of T. gondii.  Thus, it is concluded that the presence of cats near animals, larger flock size, older age of animals, and poor hygienic conditions are main risk factors of Toxoplasmosis in sheep and goats and these could be a potential threat of infection for livestock industry and public health.
Medical waste generation, handling and crime statistics' analysis in this activity field: a case study of the Poltava region (Ukraine)
Authors: Hanoshenko Olena , Vambol Viola , Vambol Sergij , Yeremenko Sergiy , Fialka Mykhailo , Bodnar Ihor , Inozemtseva Oksana
Published: June 2022

The medical waste problem has swept the whole world. Medical waste accounting and management is urgently needed to reduce the threat of the infections spread and sustainably manage environmental hazards. It is the solution of these issues on the Poltava region example that is this study purpose. Source data have been provided by the Main Department of Statistics in the Poltava region. This data is not available on the open Internet. The predictive dynamics of medical waste generation for 2010-2019 indicates a high probability of an increase in the amount of medical waste to 2030 to the volume of about 71 tons per year. The main sources are Poltava region medical institutions of which 52.3% of the total waste amount is generated in Poltava. To assess the possibility of influencing the situation with medical waste, the crime statistics in this field in the period from 2017 to 2021 was analyzed, which demonstrates an increase in offenses by more than 2.35 times. Ukrainian legislation in the field of offenses for improper handling of medical waste should be revised and articles should be developed and implemented criminal liability for offenses in this activity field.
Heterogeneous Multi-resource Allocation with Subset Demand Requests
Authors: Baxter Arden , Keskinocak Pinar , Singh Mohit
Published: June 2022

We consider the problem of allocating multiple heterogeneous resources geographically and over time to meet demands that require some subset of the available resource types simultaneously at a specified time, location, and duration. The objective is to maximize the total reward accrued from meeting (a subset of) demands. We model this problem as an integer program, show that it is NP-hard, and analyze the complexity of various special cases. We introduce approximation algorithms and an extension to our problem that considers travel costs. Finally, we test the performance of the integer programming model in an extensive computational study.
THE HISTORY OF POLITICAL REPRESENTATION OF TURKISH WOMEN IN THE PARLIAMENT (1935-1980)
Authors: ÇİNİ ŞİMŞEK Derya
Published: June 2022

While women constitute half of the world's population and electorate, many countries of the world are not adequately represented in political institutions and this creates the problem of equality. In order to talk about a real democracy and to ensure social development, the active participation of women in political representation and decision-making processes, on an equal basis with men, is of vital importance. The process of women gaining equal social and political rights with men intensified in the late 19th century. The first movement on women's rights in Turkish society was with the Tanzimat Edict of 1839, and although some rights were given to women in the Ottoman Empire, which engaged in innovation movements, it is seen that Turkish women were given the social and political rights they deserved in the first years of the Republic. Women who were granted the right to be elected to the Municipality in 1930 and to the village headman and committees in 1933; The right to elect and be elected as a deputy was given on 5 December 1934. While the representation rate of women, who won the power of representation in the Turkish Grand National Assembly in the 1935 elections, compared to male deputies in the parliament, was 4.5%, there was no such increase in the 45-year period until the September 12, 1980 coup, even below it. In the study, the adventure of women's political representation in the parliament from 1935 to 1980 will be presented on the basis of the political environment of the period.
KAZAK HALKININ AİTYS SANATI
Authors: MURSALİMOVA Nasihat , ORALBEK Almas , AÇA Mehmet
Published: June 2022

Aytıs sanatı, Kazak halkının göçebe hayatını, ulusal kimliğini, manevi doğasını ve bozkır kültürünü yansıtan, bu özelliklerle bağlı bir şekilde ortaya çıkıp gelişen eşsiz bir geleneksel mirastır. Kazak sözlü edebiyatının kahramanlık ve aşk destanları, türküleriyle birlikte gelişmiş, hatta tür ve içerik açısından bu türler üzerinde olumlu etkilerde bulunmuştur. Çalışmada, günümüze kadar yaşatılan Kazak halk edebiyatında eşsiz bir sanat olan aytısın bazı meselelerini ele aldık. Özellikle doğaçlama sanatı, kökeni, oluşumu, gelişimi, dağılımı, türü, sanatsal niteliği, Kazak kültürü ve edebiyatındaki rolüyle ulusal maneviyattaki öneminden bahsettik. İç tarz türleri ve işlevlerini, bazılarının eskime nedenlerini, yeniden oluşturulma ve ülke yararına dönüştürülme yollarını bilimsel olarak inceledik. Aytıs türlerinin toplanması, saklanması, sistemleştirilmesi, araştırılması, yayınlanması, çok yönlü yapıları, toplumun tarihsel ve sosyal koşullarına bağlı olarak farklı dönemlerdeki değişiklikler vb. konulara dikkat çektik. Çalışmada yazılı kaynaklardan elde edilen verileri kullandık. Çalışmanın sonuç kısmında, aytıs sanatının mevcut durumu ve söz konusu sanatın yaşatılması için yapılması gereken çalışmalar hakkında önerilerde bulunduk. Zaman zaman akamete uğratılan aytıs sanatının bayrağı, 20. yüzyılda Jambıl, Şaşıbay, Doskey, Nartay, Sat, Nurkan, Kayıp, Köşen, Kenen, Sayadil, Ümbetali gibi akınlar tarafından yükseltmişlerdir. Gelenek günümüzde de yaşatılmaktadır, fakat geleneğin modern ortamlarda korunamamaktadır. Aytıs şairleri, ünlü akınların aytıslarını ritimlerine uyumadan aktarmaktalar ve yüzyıllardır yaşayagelen bölge okullarının müzik geleneklerine saygı göstermemektedirler. Dolayısıyla bu gibi durumlar, modern aytıs sanatının çözülmemiş sorunlarındandır.
UMUT SARIKAYA’NIN KARİKATÜRLERİNDE KÖROĞLU’NUN YENİDEN YARATIMI
Authors: YILMAZ Berk
Published: June 2022

Mizah/karikatür dergileri, yayımlandıkları dönemlerin mizah anlayışını belirleyen ve belgeleyen en önemli unsurlardan biridir. Karikatürler, geçmişten günümüze kadar toplumun neye güldüğünün en canlı örneklerini oluşturmaktadır. Umut Sarıkaya, “Kemik”, “Lombak”, “Penguen”, “Uykusuz” ve “Naber” gibi dergilerde karikatürleri ve mizahî yazıları ile yer almış bir karikatüristtir. Karikatürlerinde insan ilişkilerine, metropollerde ve taşrada gündelik yaşama, toplumsal ve siyasi güncel konulara değinmektedir. Ayrıca yazılarında ve karikatürlerinde Türk halk bilimine göndermeler yapmaktadır. Sarıkaya’nın bu çalışmaya konu olan 4 adet karikatüründe ise Köroğlu anlatıları bulunmaktadır. Bu karikatürlerde “gözleri kör ederek cezalandırma” motifi ve Köroğlu’nun Bolu Beyi ile olan mücadelesi yer almaktadır. Köroğlu, babası ve Bolu Beyi’ni anlatılardaki özelliklerinin tam tersi bir biçimde parodileştirilerek çizilmiştir. Zaman, mekân, kişilerin konuşmalarında, giyimlerinde ve karakter özelliklerindeki uyumsuzluk, bu karikatürlerdeki mizahı oluşturmaktadır. Umut Sarıkaya bu yolla okuyucuda, Köroğlu’nun esas anlatısına merak uyandırmaktadır. Kendi zamanından, mizah okuyucusunun zamanına değişerek gelen Köroğlu’nun yarattığı ilgi, halkbilimi öğelerinin korunması ve sonraki nesillere aktarılması için son derece önem taşımaktadır.