bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oncometabolite profiling identifying estrogen-responsive genes in breast cancer.
Authors: Talukdar Joyeeta , Srivastava Tryambak Pratap , Gogoi Gayatri , Rai Avdhesh , Dhar Ruby , Karmakar Subhradip 
Published: June 2022

e13611 Background: Metabolomic profiling in breast cancer (BC) is an emerging avenue to identify clinically actionable biomarkers as well as targeted therapeutics. Altered metabolic pathways has been identified in BC. Studies have discovered an association between oncometabolite levels, DNA methylation and other epigenetic changes, with prognosis in BC. Changes in cancer cells metabolism may thus indicate disease aggressiveness and its response to therapy. Methods: An in-silico based oncometabolite profiling was performed in ER +ve and TNBC (ER-/PR-/Her2-) data sets using NCBO-GEO tools. . Inclusion criteria included studies on Human subjects, having at least 2 ER+ PR+ and TNBC samples. After manually filtering the top 250 most significant differentially expressed genes in all studies, those with clear metabolic functions as per the GO category were pooled together, which included both the overexpressed and downregulated genes. 15 unique genes were cherry-picked and taken for further analysis out of which six were downregulated, and nine were upregulated. The identified genes harbouring ERE in their upstream 1000bp region were further analysed to identify CpG islands. In addition, we also performed a Bio-Reader based Text Mining Tool to streamline Pubmed abstracts with the positive strings “oncometabolite,” “breast cancer,” “stem cells” “survival”. We also queried against negative strings “sequencing,” “mutations,” “infections,” “drug-resistance” to develop a list of highly focused abstracts. Results: Novel estrogen-regulated oncometabolite that were differentially expressed in ER+ve vs TNBC BC were identified. Further, we reinforced the fact that 4 out of 7 targets had upstream CpG islands within 1000bp n Both upregulated AMY2A, B3GNT5, PNPLA3 and 2HG whereas and downregulated genes in PLCD4, FBP1 and CA12 along with one target identified from the literature were selectively expressed in ER+ve BC. Conclusions: Our study has identified estrogen-responsive metabolic genes involved in BC. We are currently validating our results in a wet lab setup from breast cancer patient samples. Validated targets may be tested for therapeutic intervention in BC.
Addressing unmet needs of cancer care in a lower middle income country by establishing an electronic hospital based cancer registry.
Authors: Gunasekera Sanjeeva , Seneviratne Sanjeewa , Pramod Hasitha , Carson Laura M. , Berry Scott , Booth Christopher M. , Wijeratne Thiwanka 
Published: June 2022

e13621 Background: Sri Lanka (SL) is a Lower Middle Income Country (LMIC) which has seen its cancer incidence double in the last 25 years. National Cancer Institute Sri Lanka (NCISL) is the only dedicated cancer hospital in SL and provide care to around 40% of all patients diagnosed with cancer in the country. The existing SL Cancer Registry, primarily contains only socio-demographic data and there was no systematic method to capture cancer treatment and outcome data This presents a missed opportunity in identifying and bridging gaps in cancer care delivery and health equities in an effective manner. Methods: We built an electronic hospital based cancer registry using the “free to use” cloud based District Health Information System (DHIS2) software platform and prospectively collected disease, demographic, treatment and outcome data on selected cancers treated at the NCISL from 2016 onwards. This platform is easily adaptable and will allow downloading data to standard statistical software directly for data analysis and can be integrated with other existing health information systems. its easily adaptable . The variables captured were identified through focus group sessions with both healthcare workers and patient representatives. Results: To date, data from over 5,000 breast, 1500 colorectal and 600 thyroid cancer patients have been captured. From this database data on disease characteristics, demographic details, survival rates, treatment toxicities, referral pathways, health care seeking patterns, comorbidity data, health care related quality of life, treatment guideline concordance, out of pocket expenses incurred while on treatment, palliative care delivery, cancer care equity gaps can be elicited. Conclusions: Our database demonstrates that it is feasible to build low cost, easy to maintain yet good quality custom made data bases to collect cancer care related data. Careful selection of variables will allow health systems to identify existing gaps which is the key initial step in addressing them with a view of improving cancer related outcomes. Integrating demographic and outcome data within the same database will help in identifying health system inequities. Continuous data collection will allow assessing the efficacy of any intervention launched to bridge these gaps in the future. This database can also be adapted with minimal change by other LMICs to generate real world data to inform national cancer control policy planning.
Understanding disparities in research publications in high-impact factor journals by cancer site.
Authors: Sinha Nikita , McDonald Amanda , Barry Danika , Barber Emma Longley 
Published: June 2022

e13626 Background: Prior studies have shown disparities in funding allocation for gynecologic cancers after accounting for their mortality, incidence, and person-years of life lost. Whether disparities exist in high impact factor journals is unknown. The purpose of this study is to analyze research publication trends in high impact factor journals comparing gynecologic cancers to other cancers from 2000 to 2018. Methods: Abstracts from the top 55 impact factor journals, as measured by Clarivate, from 2000 to 2018 were extracted from PubMed. We developed an algorithm to search the title of the abstract to determine whether the abstract was about cancer and identify the cancer type. The algorithm was validated against the gold standard of human review in 1143 abstracts and yielded a sensitivity of 97% and a specificity of 100% for identifying cancer abstracts and an accuracy of 95% for identifying cancer site. Using NCI’s SEER database, site-specific mortality to incidence ratios were calculated and multiplied by person-years of life lost to derive cancer-specific lethality for 19 cancer sites. An article proportion for each cancer site was calculated. Article proportion was divided by lethality to calculate Article to Lethality scores for gynecologic malignancies and compared to the other cancer sites. Results: We identified 128,377 articles; 31,045 (24%) were about cancer and 1,189 (3.8%) were about gynecologic cancers. Ovarian, uterine, and cervical cancers ranked 12th (score 21.9), 13th (20.9), and 18th (10.1) out of 19 cancers for median Article to Lethality scores. The highest scores were for breast cancer (score 427) and prostate cancer (234). Ovarian and uterine cancers had lower Article to Lethality scores compared to 11 other cancers, while cervical cancer was lower than 16 other cancers (p < 0.01 for all comparisons). Analyses of the trends for gynecologic cancers over the last 18 years showed no change in Article to Lethality scores. Conclusions: Article to Lethality scores for gynecologic cancers are significantly lower than other cancer sites, indicating a disparity in research publications in high impact factor journals that persists over the last 18 years. Increased funding is essential to ensure continued advancement and progress in research for women with gynecologic cancers.[Table: see text]
Modeling analysis of COVID 19-related delays in colorectal cancer screening on simulated clinical outcomes.
Authors: Miller-Wilson Lesley-Ann , Vahdat Vahab , Brooks Durado , Limburg Paul J. 
Published: June 2022

e13631 Background: Colorectal cancer (CRC) screening disruptions have been observed with the COVID-19 pandemic, putting patients at risk for more advanced-stage disease at the time of diagnosis. We estimated the impact of increased use of stool-based tests for screening during the COVID-19 pandemic on near-term clinical outcomes in a simulated United States (US) population. Methods: A previously developed budget impact model was adapted to assess the impact of increasing use of multi-target stool DNA [mt-sDNA] or fecal immunochemical [FIT] tests to offset the COVID-19 related disruption in colonoscopy screening. Adults, ages 50 – 75 years, at average risk for CRC were included over a 3-year time horizon (2020 – 2023) to explore the impact of increased screening for CRC using mt-sDNA or FIT, from the perspective of a US payer. Compared to the base case (S0; 85% colonoscopy and 15% non-invasive tests), the estimated number of missed CRCs and advanced adenomas (AAs) were determined for four COVID-19-affected screening scenarios: S1, 9 months of CRC screening at 50% capacity, followed by 21 months at 75% capacity; S2, S1 followed by increasing stool-based testing by an average of 10% over 3-years; S3, 18 months of CRC screening at 50% capacity, followed by 12 months of 75% capacity; and S4, S3 followed by increasing stool-based testing by an average of 13% over 3-years. Results: Increasing the proportional use of mt-sDNA, the detection of AAs improved by 6.0% (Scenario 2 versus 1) to 8.4% (Scenario 4 versus 3) and the number of missed CRCs decreased by 15.1% to 17.3% respectively. Increasing FIT utilization improved the detection of AAs by 3.3% (Scenario 2 versus 1) to 4.6% (Scenario 4 versus 3) and the number of missed CRCs decreased by 12.9% (Scenario 2 versus 1) to 14.9% (Scenario 4 versus 3). Across all scenarios, the number of AAs detected was higher for mt-sDNA than for FIT, and the number of missed CRCs was lower for mt-sDNA than for FIT. Conclusions: Using home-based stool tests for average-risk CRC screening can mitigate the consequences of reduced colonoscopy screening resulting from the COVID-19 pandemic. Use of mt-sDNA led to fewer missed CRCs and more AAs detected, compared to FIT.
Txagorrapid: Ultrarapid infusion in 30 minutes of the biosimilar of rituximab truxima—A cohort study.
Authors: Perez Persona Ernesto , Cuevas Palomares Laida , Unamunzaga Cilaurren Ariane , Gutierrez López de Gutierrez Xabier , Buendía Ureña Buenaventura , Molinillo Fernández Carmen Luisa , Benito Ibarrondo Begoña , Cordero Osua Ana Isabel , Benítez Delgado Beatriz , Andrés Moralejo Miguel Angel , García Albás Juan José , Guinea de Castro José María 
Published: June 2022

e13638 Background: Rituximab (anti-CD20 Ab) is the cornerstone of the treatment of non-Hodgkin B lymphomas. Infusion-related reactions (IRR) are the most common adverse effects. To reduce them, intravenous premedication with antihistamine and acetaminophen is administered prior to rituximab. If no IRR after first infusion, subsequent infusions time takes 3-6 hours. Many centers use the rapid 90-minute infusion (off-label). Since 2017 subcutaneous rituximab formulation is available, that takes 5 minutes of administration. Nevertheless, in order to reduce cost, due to approval of biosimilars, some health providers continue using intravenous rituximab. On the other hand, with COVID pandemic, an effort to reduce visits and day-care hospitals stays has been made. In the current situation, it would be convenient to reduce day-care stay and the nursing care burden. We wanted to evaluate the safety of an ultrarapid infusion of biosimilar rituximab in a total time of 30 minutes by analyzing IRR and adverse events (AE). Methods: Since November 2021, 3 cohorts of ultrafast infusion have been studied as follows: One cohort (Cohort 1) with intravenous premedication with dexchlorpheniramine and acetaminophen, followed by rituximab infusion over 1 hour, and 2 cohorts with rituximab infusion over 30 minutes: Cohort 2: with intravenous premedication, and cohort 3 with oral premedication. IRR and adverse events have been independently reviewed and graded using Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 (November 27, 2017). Results: 34 patients have been included receiving 48 rituximab infusions (16 infusions in each cohort). Median age was 64 years old (range: 51-91). Diagnostic of NHL were as follows: large b cell: 10; follicular: 13; marginal: 7; mantle cell: 1, Waldeström: 1; Ritcher transformation: 2. Rituximab infusion was in monotherapy (21), and in combination (27) with: bendamustine: 9, CHOP: 17, GEMOX: 1. Considering safety, no IRR has been observed in cohort 1 (1 hour infusion), and 1 IRR grade II in cohort 3 (30 minutes, oral premedication). Other AE were: hypertension grade I and hypotension grade I, both in cohort 2. Conclusions: Ultrarapid rituximab infusion is safe. Oral premedication is feasibly allowing a total infusion time of 30 minutes. This infusion rate alleviates day-care burden saving between 75-90% of time in each rituximab infusion, reduce day-care stay and is comfortable for the patients. Clinical trial information: NCT05191225.
A feasibility study of remote patient monitoring among vulnerable patients with cancer.
Authors: Kessler Alaina J , Besculides Melanie , Kisswany Carol , Liu Mark , Berkalieva Asem , Mazumdar Madhu , Smith Cardinale B. , Gorbenko Ksenia O. 
Published: June 2022

e13652 Background: Patients with cancer have high rates of healthcare utilization due to complications of disease and treatment. Early identification of patient illness may help reduce acute care use and improve quality of care. Remote patient monitoring (RPM), a type of telemedicine involving collection and transmission of health data from a patient’s home to clinicians, has promise to alleviate disparities by providing timely access and early intervention, particularly during the COVID-19 pandemic. Studies of digital interventions in oncology have demonstrated reduction in symptom distress and unplanned hospitalizations but lack focus on minority patients whereas studies of telehealth aiming to address disparities have not focused on patients with cancer. In this pilot study, we aimed to evaluate the feasibility of RPM among patients with cancer at a large urban medical center serving a racially and socioeconomically diverse population. Methods: We partnered with a secure HIPAA-compliant platform and FDA-approved RPM device, Current Health, which monitored heart rate, temperature, respiration, oxygen saturation, and blood pressure. The kit included broadband access and a tablet to provide telehealth services. Oncology Clinicians determined clinical inclusion and exclusion criteria of RPM initiation for patients on the bone marrow transplant service and patients with myeloma and lung cancer. A centralized team of Nurse Practitioners (NPs) monitored alarms. Clinical alarms indicated abnormal vital signs; technical alarms indicated no data transmission for a 12-hour period. We measured feasibility by recruitment and retention, and used descriptive statistics to describe the study population, time enrolled on RPM, and alarms. Results: To date, we enrolled 30 patients on the RPM platform over a 10-month period with a weekly census of 9-10 patients undergoing RPM monitoring. Of the 30 patients, 17 (57%) were white, 7 (23%) Black, and 2 (7%) Asian; 2 patients (7%) identified as Hispanic. The average age was 57.4 years. The majority of patients (93%) had hematologic malignancies, all of whom were enrolled on hospital discharge. Of the 2 patients with lung cancer, 1 patient was enrolled from the outpatient setting and 1 following hospital discharge. The mean length of time per patient enrolled with the device was 21.7 days. Over 10 months, there were 393 technical and 62 clinical alarms with an average of 3 clinical alarms per week addressed by NPs by phone, indicating low clinician burden. Conclusions: This pilot study demonstrated the feasibility of RPM monitoring in patients with cancer. Future studies should evaluate patient-reported and healthcare utilization outcomes, as well as barriers to reimbursement. The identification of best practices in telemedicine implementation can accelerate adoption and increase high quality, timely, and equitable cancer care.
The effects of vascular endothelial cells on regulating post-irradiation microglia phenotype in irradiation-induced brain injury.
Authors: Wang Jiaojiao , Tong Fan , Lin Zhenyu , Dong Xiaorong 
Published: June 2022

e14001 Background: The purpose was to elucidate the mechanism behind functional relevance between microglia and injured blood vessels after CRT and the role of fractalkine (FKN) for the dynamics in the microglia phenotype, hoping to provide a theoretical rationale for the therapeutic strategy of Radiation-induced brain injury (RIBI). Methods: The ultrastructural blood vessels in the hippocampus were examined by transmission electron microscopy. EMSA and dual-luciferase assays were used to confirm the activation of NF-κB induced by irradiation in. Migration and co-culture assays were used to investigate the the association between HUVEC and BV-2 cells after irradiation. We constructed CX3CR1-knockdown (receptor of FKN) lentiviral vector to produce CX3CR1-knockdown BV-2 cell lines. After cultured for 3h with/without FKN, BV-2 cells (Sh-NC/ Sh-CX3CR1) received 10-Gy irradiation. The CX3CR1wide-type/knockdownmice were used and subjected to lateral ventricular injection (ICV) of 5 μl FKN lentivirus or vector before CRT. The in vitro and in vivo phenotype transformation of microglia and its inflammatory factors release were detected by WB, real-time PCR, ELISA, and IF at different time-points after irradiation. Morris water maze test was used to test mice's cognitive function. Results: In the hippocampus of the CRT group, significant pathological changes were seen in ultrastructure of blood vessels.The NF-κB pathway was activated in vascular endothelial cells (ECs) after10-Gy irradiation. In vitro migration and Co-culture assays found that molecular signals, secreted by ECs via the NF-κB pathway, leading to the activation of microglia and their recruitment to blood vessels. ELISA and qRT-PCR revealed that 10-Gy irradiation promoted the secretion of FKN from the vascular ECs via activating the NF-κB pathway. Western blotting and Flow cytometry showed that pretreatment with exogenous FKN, before 10-Gy irradiation, promoted microglia M2 phenotype transformation, diminished radiation-induced pro-inflammatory factors, and enhanced phagocytosis capacity. In addition, in vivo experiments showed that up-regulation of FKN via FKN lentivirus promoted radiation-induced microglial M2 transformation in the hippocampus, and diminished the spatial memory injury of radiated mice. Lastly, while inhibiting the CX3CR1, which is exclusively expressed on microglia in the brain, the regulatory effect of FKN on microglia and cognitive ability of mice disappeared after radiation. Conclusions: FKN, mainly secreted by vascular ECs via the NF-κB pathway after radiation, may attenuate RIBI through microglia polarization toward M2 phenotype by binding to CX3CR1 on microglia. Our study has unveiled an important and novel role of FKN/CX3CR1 in RIBI, providing evidence to validate that promotion of the FKN/CX3CR1 axis could be a promising therapeutic strategy for the treatment of RIBI.
Outcomes and prognostic factors in patients with HER2-positive metastatic breast cancer with brain metastasis.
Authors: Dogan Izzet , Yirgin Inci Kizildag , Ozkurt Selnur , Ibıs Kamuran , Vatansever Sezai , Saip Pinar , Aydiner Adnan 
Published: June 2022

e14002 Background: Breast cancer is the most common malignancy in females. Brain metastasis is a poor prognostic factor in breast cancer. Brain metastasis can develop in about half of the HER2- positive metastatic breast cancer patients. The study was aimed to determine outcomes and prognostic factors in HER2 positive metastatic breast cancer patients who had brain metastasis. Methods: We evaluated the HER2-positive metastatic breast cancer patients with brain metastasis between 2008 and 2018. Data of the patients were recorded retrospectively. Kaplan Meier and Cox regression analysis were used for survival analysis and prognostic factors. Results: Eighty-three patients were included in the study. The median age was 49 (range, 25-76). Thirty-two (38.6%) patients had de-novo metastatic disease at diagnosis. The most common histopathological type was invasive ductal carcinoma (88.4%). The estrogen receptor and progesterone receptor positivity ratios were 42.2% and 28.9%, respectively. At the beginning of brain metastasis, the median number of extra-cranial metastasis was 2 (range, 0-4). The most common extra-cranial metastasis sites were bone (63.9%), liver (41%), and lung (34.9%), respectively. Twenty-eight patients (41.8%) had solitary brain metastasis. The median size of brain metastasis was 16 mm (range, 5-63) at diagnosis. All patients had treated with trastuzumab-based chemotherapy, 29 patients (34.9%) TDM-1, and 73 patients (88%) lapatinib+capesitabine combination. Seventeen patients (20.5%) had undergone craniotomy, and 82 patients (98.8%) received brain radiotherapy. The patients also received hormonotherapy (41%) and bisphosphonates (56.6%). At a median follow-up of 36 months (range 5.9-177.7) from beginning metastasis, the median overall survival was 34.9 months (95% CI, range 24.6-45.2). In multivariate analysis, age at diagnosis (p = 0.005), presence of five and over brain metastasis (p = 0.016), the number of chemotherapy used with trastuzumab (p = 0.017), and receiving three different HER2-targetted therapy (p = 0.032) were statistically significant for overall survival. However, size of brain metastasis (p = 0.091), lung metastasis (p = 0.428), liver metastasis (p = 0.338), bone metastasis (p = 0.132), and hormone positivity of tumor (p = 0.238) were not. Conclusions: Real-life outcomes of HER2-positive breast cancer patients with brain metastases were presented in this study. We showed that age at diagnosis, number of brain metastasis, number of chemotherapy received with trastuzumab, and had received three different HER2 targetted therapy was prognostic factors for overall survival.