bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictive value of DNA methylation patterns in AML patients treated with an azacytidine containing induction regimen
Authors: Schmutz Maximilian , Zucknick Manuela , Schlenk Richard F. , Mertens Daniel , Benner Axel , Weichenhan Dieter , Mücke Oliver , Döhner Konstanze , Plass Christoph , Bullinger Lars , Claus Rainer 
Published: October 2023

Abstract
Background
Acute myeloid leukemia (AML) is a heterogeneous disease with a poor prognosis. Dysregulation of the epigenetic machinery is a significant contributor to disease development. Some AML patients benefit from treatment with hypomethylating agents (HMAs), but no predictive biomarkers for therapy response exist. Here, we investigated whether unbiased genome-wide assessment of pre-treatment DNA-methylation profiles in AML bone marrow blasts can help to identify patients who will achieve a remission after an azacytidine-containing induction regimen.

Results
A total of n = 155 patients with newly diagnosed AML treated in the AMLSG 12-09 trial were randomly assigned to a screening and a refinement and validation cohort. The cohorts were divided according to azacytidine-containing induction regimens and response status. Methylation status was assessed for 664,227 500-bp-regions using methyl-CpG immunoprecipitation-seq, resulting in 1755 differentially methylated regions (DMRs). Top regions were distilled and included genes such as WNT10A and GATA3. 80% of regions identified as a hit were represented on HumanMethlyation 450k Bead Chips. Quantitative methylation analysis confirmed 90% of these regions (36 of 40 DMRs). A classifier was trained using penalized logistic regression and fivefold cross validation containing 17 CpGs. Validation based on mass spectra generated by MALDI-TOF failed (AUC 0.59). However, discriminative ability was maintained by adding neighboring CpGs. A recomposed classifier with 12 CpGs resulted in an AUC of 0.77. When evaluated in the non-azacytidine containing group, the AUC was 0.76.

Conclusions
Our analysis evaluated the value of a whole genome methyl-CpG screening assay for the identification of informative methylation changes. We also compared the informative content and discriminatory power of regions and single CpGs for predicting response to therapy. The relevance of the identified DMRs is supported by their association with key regulatory processes of oncogenic transformation and support the idea of relevant DMRs being enriched at distinct loci rather than evenly distribution across the genome.
Predictive response to therapy could be established but lacked specificity for treatment with azacytidine. Our results suggest that a predictive epigenotype carries its methylation information at a complex, genome-wide level, that is confined to regions, rather than to single CpGs. With increasing application of combinatorial regimens, response prediction may become even more complicated.
Cultured meat acceptance for global food security: a systematic literature review and future research directions
Authors: Lewisch Leonore , Riefler Petra 
Published: October 2023

AbstractCultured meat is a novel technology-based meat alternative with the potential to complement protein supply for a growing world population. An increasing body of consumer research has investigated personal factors explaining consumers’ acceptance of cultured meat. Research on cultural and economic drivers impacting consumer responses across countries, however, is scant. In this light, this article aims to provide a cross-cultural perspective on cultured meat acceptance and guide future empirical research in this domain. First, this article proposes a framework to explain cross-national differences in cultured meat acceptance comprising societal factors (i.e., culture and religion), indicators of the food environment (i.e., meat production and consumption), and economic market parameters (i.e., gross domestic product, carbon dioxide emissions, and population growth). Second, the paper applies a systematic literature review, including 105 empirical consumer studies related to cultured meat. Third, the identified papers are analyzed according to the proposed framework. The findings of this descriptive analysis demonstrate that empirical research to date has predominately been conducted in countries that produce and consume high amounts of meat and are characterized by high gross domestic products per capita. Many of these surveyed countries harbor secular-rational and self-expressional cultural value orientations. Other country types have been less prominently explored, although they represent potentially relevant target markets for cultured meat in the future. Cross-cultural research aiming to explain differences across countries is scarce. To guide future research, the paper develops research propositions relating societal factors, food environment, and market-related factors to consumer acceptance of cultured meat across countries.
Bacterial survival in radiopharmaceutical solutions: a critical impact on current practices
Authors: Leenhardt Julien , Choisnard Luc , Plasse Maelle , Ardisson Valérie , de Leiris Nicolas , Djaileb Loic , Bedouch Pierrick , Brunet Marie-Dominique 
Published: October 2023

Abstract
Background
The aim of this brief communication is to highlight the potential bacteriological risk linked to the processes control of radiopharmaceutical preparations made in a radiopharmacy laboratory. Survival rate of Pseudomonas aeruginosa (ATCC: 27853) or Staphylococcus aureus (ATCC: 25923) or Staphylococcus epidermidis (ATCC: 1228) in multidose technetium-99 m solution was studied.

Results
Depending on the nature and level of contamination by pathogenic bacteria, the lethal effect of radioactivity is not systematically observed. We found that P. aeruginosa was indeed affected by radioactivity. However, this was not the case for S. epidermidis, as the quantity of bacteria found in both solutions (radioactive and non-radioactive) was rapidly reduced, probably due to a lack of nutrients. Finally, the example of S. aureus is an intermediate case where we observed that high radioactivity affected the bacteria, as did the absence of nutrients in the reaction medium. The results were discussed in the light of current practices on the sterility test method, which recommends waiting for radioactivity to decay before carrying out the sterility test.

Conclusion
In terms of patient safety, the results run counter to current practice and the latest EANM recommendation of 2021 that radiopharmaceutical preparations should be decayed before sterility testing.
The role of mild stressors in children’s cognition and inflammation: positive and negative impacts depend on timing of exposure
Authors: Francesconi Marta , Minichino Amedeo , Flouri Eirini 
Published: October 2023

Abstract
Although the impact of stressful life events (SLEs) on mental health is well-established, the research on the impact of such stressors on cognitive outcomes has produced mixed results. Arguably, the timing and severity of exposure may play a key role. In this study, we shed light on the relationship between timing of exposure to relatively minor SLEs and cognitive ability in children, while taking into account the role of a plausible biological mediator: inflammation. Using data from the Avon Longitudinal Study of Parents and Children, a general population birth cohort, we explored the role of relatively minor SLEs, experienced during two crucial developmental stages: up to transition to school (1–4.5 years) and up to transition to puberty (5.5–8.5 years). We then tested if they may impact differently on inflammatory markers (serum C-reactive protein [CRP] and interleukin 6 [IL-6]) at age 9 and general intelligence, measured with the Wechsler Abbreviated Scale of Intelligence at age 15. Data (n = 4,525) were analyzed using path analysis while controlling for covariates. We found that when relatively minor stressful events were experienced up to transition to school they were significantly associated with higher IQ at age 15, whereas when experienced up to transition to puberty they were significantly associated with higher levels of IL-6 at age 9. Results were robust to adjustment for relevant covariates, including IQ at age 8. Mild stressors in childhood may result in positive (i.e., improved cognition) or negative (i.e., inflammation) outcomes depending on the timing of exposure.
Survival Trends Among Adolescents and Young Adults Diagnosed With Cancer in the United States: Comparisons With Children and Older Adults
Authors: Keegan Theresa H.M. , Abrahão Renata , Alvarez Elysia M. 
Published: October 2023

PURPOSE Although data from 1975 to 1997 revealed a gap in cancer survival improvement in adolescents and young adults (AYAs; 15-39 years) compared with children and older adults, more recent studies have reported improvements in AYA cancer survival overall. The current analysis provides an update of 5-year relative survival and cancer survival trends among AYAs compared with children and older adults. METHODS We obtained data from the National Cancer Institute Surveillance, Epidemiology, and End Results Program for 17 regions to obtain recent (2010-2018) 5-year relative survival estimates by cancer type, stage, sex, and race/ethnicity by age group. In addition, we calculated 5-year relative survival trends during 2000-2014. RESULTS Across 33 common AYA cancers, AYAs and children had high 5-year relative survival (86%) and experienced similar survival improvements over time (average absolute change: AYAs, 0.33%; children 0.36%). Among AYAs, 73% of cancers had improvement in 5-year relative survival since 2000. Despite this overall progress, we identified cancers where survival was worse in AYAs than younger or older patients and cancers that have had either a lack of improvement (osteosarcoma and male breast) or decreases in survival (cervical and female bladder) over time. Furthermore, males had inferior survival to females for all cancers, except Kaposi sarcoma and bladder cancer, and non-Hispanic Black/African American AYAs experienced worse survival than other racial/ethnic groups for many cancers considered in this study. CONCLUSION Future studies should focus on identifying factors affecting survival disparities by age, sex, and race/ethnicity. Differences in biology, clinical trial enrollment, delivery of treatment according to clinical guidelines, and supportive and long-term survivorship care may account for the survival disparities we observed and warrant further investigation.
Growth factor use in patients with breast cancer treated with docetaxel, carboplatin, trastuzumab, and pertuzumab (TCHP) regimen: Cost implications in a safety-net system.
Authors: Kashanian Sarah , Kanjwal Shifa , Brown Steven , Li Hsiao Ching , Unni Nisha , Delgado Ramos Glenda Maria , Syed Samira K. , Sadeghi Navid 
Published: October 2023

10 Background: Growth factor (G-CSF) support has been shown to reduce the incidence of neutropenic complications after chemotherapy; however, it can be associated with a significant increase in cost of care. Here, we reviewed G-CSF use in breast cancer patients receiving docetaxel, carboplatin, trastuzumab, and pertuzumab (TCHP) regimen at a safety-net system. Methods: Parkland Health is the safety-net system that provides care to primarily uninsured/underinsured patients in Dallas County, Texas. The majority of patients treated at Parkland belong to racial and ethnic minorities. We reviewed electronic medical records of patients with HER-2 positive breast cancer who were treated with TCHP between 01/01/2017 and 12/31/2022 at Parkland. Data on patient demographics, treatment history, laboratory values, and treatment related complications were collected. Results: A total of 171 consecutive patients underwent neoadjuvant/adjuvant treatment with TCHP for HER-2 positive breast cancer. Forty-one patients (24.0%) received G-CSF for primary prophylaxis, as per discretion of treating physician. In the 130 patients (76.0%) who did not receive primary prophylaxis, G-CSF was added later in 41 patients (32.5%). Febrile neutropenia (FN), neutropenic treatment delays, and infections not meeting FN criteria accounted for the majority of cases where G-CSF was added later in the course of treatment. Overall, 529 cycles of TCHP were administered without G-CSF vs. 372 cycles with G-CSF. Without primary prophylaxis, 18.5% (24/130) of the patients developed FN vs 2.4% (1/41) for those who received primary prophylaxis, p=0.011. FN was a complication in 4.5% (24/529) of chemotherapy cycles without G-CSF vs. 1.1% (4/372) of cycles administered with G-CSF, p=0.003. In patients treated without G-CSF, the majority of FN episodes (71%) occurred within the first 3 cycles. FN resulted in a total of 150 days (median 5 days) of hospital stay resulting in $1.2 million (M) in charges (median $36,000 per admission). Universal G-CSF use in our patient population could have prevented 21 episodes of febrile neutropenia with an estimated saving of $1.05 M (hospital admission charges), at an extra cost of $1.8M (based on the pegfilgrastim Medicare average sales price (ASP) from 2017-2022). However, based on the 2023 Medicare ASP, by substituting pegfilgrastim for biosimilars, the estimated cost would have been $603,000. Conclusions: Our study did not show an FN rate >20% to warrant routine addition of G-CSF for primary prophylaxis as recommended by the NCCN. During the study period, the cost of G-CSF was prohibitive for its universal use. However, the recent introduction of G-CSF biosimilars has significantly reduced the cost burden and justifies routine G-CSF prophylaxis as a cost saving measure.
Absolute neutrophil count (ANC) cutoff in cancer clinical trials: Implications for minority accrual in the United States (US).
Authors: Gunaratne Madugodaralalage , Abeykoon Jithma P. , Wolanskyj-Spinner Alexandra P. , Sridharan Meera , Hook Carl C. , Rouse Rachelle , Elliott Michelle A. , Ashrani Aneel A. , Pardanani Animesh Dev , Pruthi Rajiv , Go Ronald S. 
Published: October 2023

101 Background: In the US, minority patients are underrepresented in cancer clinical trials. This is due to multiple factors, including socioeconomic barriers, limited medical insurance coverage and restrictive clinical trial eligibility, e.g., ANC cutoff. For the latter, conservative ANC cutoff disadvantages Black patients. Two-in-three Black individuals have a Duffy-null phenotype, that is associated with lower ANC with 5% prevalence of ANC <1,500 cells/µl. To improve Black patient accrual to cancer clinical trials, lowering the ANC cutoff was proposed as a potential solution over a decade ago. Its implementation is not known. This study evaluates the ANC cutoff values as part of the eligibility criteria for cancer clinical trials. Methods: We accessed the Clinicaltrials.gov website on 5/25/2023 and obtained the ANC cutoff of cancer clinical trials conducted in the US. We included adult therapeutic trials in the phases of recruiting, not yet recruiting, enrolling by invitation, and active-not yet recruiting. Trials with drug interventions were selected. Those focusing on surgical, behavioral, nutritional and radiotherapeutic interventions were excluded. All ANC cutoff values were converted to “cells/µl” for analysis. Results: A total of 911 trials were evaluated, and 470 met the eligibility criteria. Of the 470 trials, 366 (78%) involved solid malignancies, and 104 (22%) involved hematologic malignancies. Hematologic trials have significantly lower ANC cutoffs compared to solid tumor trials with median ANC cutoff of 1,000 (range, 250-2000) vs. 1,500 (range 250-3,000); p=<0.001. In all, 323 trials (68.7%) required patients to have ANC >1,500, and 116 trials (24.6%), primarily hematologic, required patients to have ANC >1,000. For myeloma and prostate cancer, two cancers with higher incidence among Blacks, 12.9% and 86.4% of the trials require ANC >1,500, respectively. All genitourinary, breast, head & neck, sarcoma, lung, skin, and neuroendocrine tumor trials excluded patients with ANC <1,000. Conclusions: Most hematologic malignancy trials have a more liberal ANC cutoff allowing patients with ANC <1,500 to participate. However, solid tumor trials remain more conservative, with 4 in 5 trials requiring an ANC cutoff of >1,500. A strict ANC cutoff remains a barrier to minority accrual.[Table: see text]
Exploring the role of decentralized clinical trials in oncology: Insights from cancer centers.
Authors: Beg Shaalan , Werner Theresa Louise , George Thomas J. , Williams Erin Lee , Cameron Kendra , Honeycutt Hailey , Shaw Kate , Rahimi Asal Shoushtari , Lin Tara L. 
Published: October 2023

105 Background: Decentralized clinical trials (DCT) involve conducting some or all trial-related activities at a location separate from the investigator's site. DCT can help reduce the burden on patients, sites, and sponsors while improving patient accrual and retention rates and increasing the diversity of trial participants. While DCT methods provide patient-centric trial flexibilities, they can impact trial operations. This survey aimed to gain insights into the perspectives and experiences of cancer centers regarding DCT in the field of oncology. Methods: A 13-question survey that addressed prior experience, perceived benefits, and challenges in implementing DCT was developed by members of the Association of American Cancer Institutes (AACI) Clinical Research Innovation (CRI) Steering Committee. The survey was sent via email to the AACI CRI listserv, which consists of members of 90 cancer research centers in North America. Respondents were asked to consider their activity related to treatment and non-treatment interventional trials. Results: There were 75 total responses from members affiliated with 55 individual cancer centers. Of these centers, 73% were NCI-designated cancer centers. Of the individual respondents, 57% were clinical trial office administrators. The issues of highest concern by respondents were 1) meeting study timelines, 2) patient recruitment and 3) cost (83%, 65%, 44% respectively). All respondents had prior experience with DCT tools with the most common components being the use of local facilities for labs/imaging, telemedicine and e-consent (89%, 69%, 68% respectively). The areas of most perceived benefit from DCT include reduced participant burden, increased diversity and participant retention (81%, 80%, 68% respectively) while areas of perceived challenges include quality control, regulatory compliance and cost (61%, 59%, 49% respectively). While 92% respondents agreed/strongly agreed that DCT can improve clinical trial access, 92% agreed/strongly agreed that additional site staff training is required for successful DCT implementation. Conclusions: DCT tools have been widely implemented in oncology trials with all surveyed sites reporting prior experience. This survey emphasizes the perceived benefits of DCT in oncology, while underscoring the importance of addressing challenges and meeting the specific requirements of cancer centers. Future work should identify specific areas that require additional staff training to enable DCT readiness.
One size does not fit all: Clinical trial investigator perspectives of disparities in racial/ethnic minority participation in oncology clinical trials.
Authors: Bransky Natalie Perle , Walling Anne M. , Klomhaus Alexandra M , Glaspy John A. , Garcia-Jimenez Maria De Lourdes 
Published: October 2023

108 Background: Thirty years after the NIH Revitalization Act, racial/ethnic minority (REM) patients remain underrepresented in oncology clinical trials. Little is known about clinical trial investigator perspectives of REM participation in clinical trials. To our knowledge no published studies exist assessing differences in investigator perspectives based on their primary role in the clinical trial process. We hypothesized that differences exist in investigator perspectives regarding REM participation in oncology clinical trials based on having a more design-oriented (principal (PI)/co-investigator (co-I)) or recruitment-oriented role (sub-investigator (sub-I)). Methods: We conducted a cross-sectional, anonymous, pilot survey of oncology clinical trial investigators at an academic center. Over 5 weeks, 107 individuals received a survey assessing 6 domains about disparities in REM participation in clinical trials, including knowledge, attitudes, and prior training. Modified, previously validated items were used if possible. We performed a subset analysis of mid- and late-career investigators (>/= 10 years of experience) comparing those who opened at least 1 clinical trial in the past year as PI or co-I to those who did not (sub-I). Results: There were 60 respondents (56% response rate). Average time as a clinical trialist was 14 years (2-40). Average number of trials opened in the last year as PI/co-I was 4 (1-30). Among all respondents, 83% strongly agreed disparities exist in REM clinical trial participation and that lack of diversity is problematic (75%). Notably, 45% agreed this is a problem they cannot directly address. Among mid- and late-career investigators, those who opened at least 1 trial as PI/co-I were more likely to have received training about barriers/facilitators (OR=3.56; 95% CI=1.05, 12.04; p=.04) to REM clinical trial participation and about strategies for improving participation (OR=3.75; 95% CI=1.06, 13.29; p=.04). Despite this, they were more likely to endorse wanting help to improve in this area (OR=4.95; 95% CI=1.17, 21.02; p=.03). Conclusions: Our results suggest there is awareness among clinical trial investigators of disparities in REM clinical trial participation, but investigators do not feel they can directly address these. Investigators who are more involved in clinical trial design are more likely to want help to improve their ability to address disparities in REM trial participation despite being more likely to have received prior training on the topic. Our findings suggest training alone is inadequate support for investigators involved in designing clinical trials. More studies eliciting the needs of investigators with varying roles in the clinical trial process are needed to inform targeted interventions to enhance investigators’ self-efficacy for improving REM participation in clinical trials.