bluuebunny/crossref_metadata_2025_split huggingface dataset:
Piloting “From the Inside Out” — a toolkit addressing tuberculosis-related self-stigma
Authors: Macdonald Stephen H.-F. , France Nadine Ferris , Hodgson Ian , Ali Fadhil , Dewi Christa , Abdurrakhman Iman , Runtu Yeremia Mozart , Juan Alva , Sugiharto Jhon , Byrne Elaine , Conroy Ronan M. 
Published: June 2024

Abstract
Background
Self-stigma among people who have tuberculosis (TB) can contribute to non-adherence to medication and disengagement from care. It can manifest in feelings of worthlessness, shame, and guilt, leading to social withdrawal and disengagement from life opportunities. Self-stigma may also affect families of those who have TB, or healthcare workers who treat them. However, few interventions addressing TB self-stigma exist to date.

Methods
We piloted the delivery of a toolkit of psychosocial interventions using a “training-of-trainers” approach with six staff members of a TB-focused NGO (Non-Governmental Organisation) and partner organisations in Jakarta, Indonesia. These trainers could then disseminate the toolkit among community partner organisations. Local staff involvement throughout the study supported translation and adaptation to enhance cultural and language appropriateness. Over a 2-day training-of-trainers workshop, the NGO staff were familiarised with the mode of delivery of the toolkit, which they then delivered via a four-day participatory workshop with 22 people who have TB/TB survivors, who were representatives of partner organisations working among communities affected by TB.

Results
The newly-trained local facilitators delivered the toolkit to the participants, who self-reported significant increases in knowledge and efficacy around TB self-stigma post-intervention compared to baseline (Z = 1.991, p = 0.047, Wilcoxon signed-rank test). The participants’ levels of self-compassion were also significantly higher post-workshop (Z = 2.096, p = 0.036, Wilcoxon signed-rank test); however, these effects were not maintained at 3-month timepoint. There was also a significant increase post-workshop in one of the participants’ Ryff dimensions of psychological wellbeing, that of positive relationships with others (Z = 2.509, p = 0.012, Wilcoxon signed-rank test) but this was also not maintained at the 3-month timepoint.

Conclusions
The observed changes in recipients’ self-reported levels of knowledge and efficacy, self-compassion, and psychological wellbeing may warrant further investigation into the best modalities for toolkit delivery (frequency, dose, duration) and support for individuals as they progress through the TB treatment journey.
Conflict of Interest Disclosure in Oncology: Preliminary Insights From the Global ONCOTRUST-1 Cross-Sectional Study
Authors: El Bairi Khalid , Najem Salma , Chowdhury Arman Reza , Omar Abeid , Abdihamid Omar , Teuwen Laure-Anne , Benhima Nada , Madariaga Ainhoa , Elkefi Safa , Diaz Fernando Cristobal , Hussain Sadaqat , Jenei Kristina , Hammad Nazik , Mutebi Miriam , Rubagumya Fidel , Trapani Dario , El Kadmiri Nadia , Laouali Nasser , Fourtassi Maryam 
Published: June 2024

PURPOSE Conflicts of interest (COIs) between oncologists and industry might considerably influence how the presentation of the research results is delivered, ultimately affecting clinical decisions and policy-making. Although there are many regulations on reporting COI in high-income countries (HICs), little is known about their reporting in low- and middle-income countries (LMICs). Oncology Transparency Under Scrutiny and Tracking (ONCOTRUST-1) is a pilot global survey to explore the knowledge and perceptions of oncologists regarding COI. MATERIALS AND METHODS We designed an online 27-question–based survey in the English language to explore the perceptions and knowledge of oncologists regarding COI, with an emphasis on LMICs. Descriptive statistics and the Consensus-Based Checklist for Reporting of Survey Studies guidelines were used to report the findings. RESULTS ONCOTRUST-1 surveyed 200 oncologists, 70.9% of them practicing in LMICs. Median age of the respondents was 36 (range, 26-84) years; 47.5% of them were women. Of the respondents, 40.5% reported weekly visits by pharmaceutical representatives to their institutions. Regarding oncologists' perceptions of COI that require disclosure, direct financial benefits, such as honoraria, ranked highest (58.5%), followed by gifts from pharmaceutical representatives (50%) and travel grants for attending conferences (44.5%). By contrast, personal or institutional research funding, sample drugs, consulting or advisory board, expert testimony, and food and beverage funded by pharmaceutical industry were less frequently considered as COI. Moreover, only 24% of surveyed oncologists could correctly categorize all situations representing a COI. CONCLUSION These findings underscore the importance of clear guidelines, education, and transparency in reporting COI in oncology. This hypothesis-generating pilot survey provided the rationale for ONCOTRUST-2 study, which will compare perceptions of COI among oncologists in LMICs and HICs.
AI/ML-derived mechanistically interpretable whole-genome biomarkers of patient survival in pre-treatment primary neuroblastoma tumors and whole blood.
Authors: Alter Orly , Newman Elizabeth , Ponnapalli Sri Priya , Tsai Jessica W. 
Published: June 2024

10043 Background: Prediction, understanding, and management, of neuroblastoma (NBL) outcomes, from spontaneous regression to relapse and death, remain limited, and rely mostly on the International Neuroblastoma Staging System (INSS) stage, age, and the one-gene test for MYCN amplification. The entire multi-ome affects every aspect of the disease. But typical artificial intelligence and machine learning (AI/ML) cannot discover effective biomarkers from real-life, small-cohort, multi-omic, and noisy data. Methods: We use our AI/ML to identify two whole-genome biomarkers from open-source pre-treatment NBL patient-matched primary tumor and whole blood DNA copy numbers, and primary tumor mRNA expression. Our data-agnostic, unsupervised algorithms extend the mathematics that underlies quantum mechanics to overcome the limitations of typical AI/ML [1,2]. Our platform- and reference genome-agnostic biomarkers in astrocytoma, including glioblastoma, and lung, ovarian, and uterine adenocarcinomas, were mathematically discovered, and computationally and experimentally validated, repeatedly, in federated, imbalanced datasets from as few as 50–100 patients [3]. Results: We discover the biomarkers in “skinny” datasets of minimally preprocessed ≈3M-bin whole-genome sequences from tumors and blood of a set of 101 patients. Blindly, i.e., label-free, we separate both biomarkers from the normal X chromosome-number variation, demonstrating sex-agnostic learning. Combined, the biomarkers are statistically independent of all standard-of-care indicators, with the univariate Cox hazard ratio of 4.0 (log-rank P-value=2.3×10–5) within the 95% confidence intervals of the bivariate ratios. The risk that the tumor’s whole genome confers upon outcome, as is reflected by the bivariate ratios, is greater than that conferred by all standard-of-care indicators, including DNA ploidy, the Children’s Oncology Group (COG) risk, and the mitosis-karyorrhexis index (MKI), except for histopathology. We validate the biomarkers in ≈10K-bin target-capture sequences of a mutually-exclusive set of 419 patients, demonstrating generalizability as well as site-, platform-, and protocol-agnostic transfer learning. At 73–80% concordance, in both the tumor and blood profiles of both the discovery and validation sets, the biomarkers combined are more accurate than MYCN. We show that the biomarkers identify known and previously unrecognized disease mechanisms and druggable gene alterations, including co-amplification of MYCN with genes encoding for extra-embryonic transcripts, as well as the hijacking of embryonic development toward aneuploidy, which can spontaneously regress via embryonic self-correction. Conclusions: Our AI/ML is uniquely suited for personalized medicine. 1. doi: 10.1063/1.5099268 2. doi: 10.1073/pnas.0530258100 3. doi: 10.1063/1.5142559.
The effects of oral nutritional supplements on functional outcomes and body composition in patients with solid cancer undergoing systemic chemotherapy: A pilot study.
Authors: kang sora , Koh Jeong Suk , Lee Myungwon , Song Ik-Chan , Lee Hyo Jin , Yun Hwan-Jung , Jo Deog Yeon , Ryu Hyewon 
Published: June 2024

10074 Background: Cancer cachexia is a complex syndrome characterized by significant weight loss and depletion of skeletal muscle mass. Despite its profound impact on the well-being of cancer patients, the effective management of cancer cachexia remains a challenging and underexplored aspect of oncology. This study aims to investigate the potential benefits of oral nutritional supplements (ONS) to cancer patients undergoing chemotherapy. Methods: This is single-arm, prospective pilot study. Patients with cancer cachexia undergoing chemotherapy were included. Patients received ONS twice a day for 8 weeks. The ONS contained 200 kcal, 22.5 gram of carbohydrates, 7.5 gram of fat, and 12.5 gram of protein per 200 mL. Primary endpoints were improvements of lean body mass and physical performance. The secondary endpoints were changes of health-care related quality-of-life (HRQoL), nutritional status, and gut microbiomes profiles. EORTC-QLQ-C30 questionnaire, body composition analysis, 4-meter-walk test, hand grip strength test, and fecal microbiome analysis were conducted at baseline and after 8 weeks. The bacterial 16S rRNA gene (V3 and V4 region) was amplified using PCR and sequenced on the Illumina MiSeq platform. The QIIME 2 pipelines were used to analyze the raw data. Results: From January 2023 to October 2023, total of 10 patients were included. There were no significant differences of the mean daily energy intake (p=0.62) and calf-circumferences (p=0.2) between baseline and after 8 weeks. However, participants exhibited a statistically significant improvement in hand-grip strength (p=0.002) and 4-meter walk test (p=0.021) after 8 weeks. In the body composition analysis using dual-energy X-ray absorptiometry, no differences were observed in body weight (p=0.43), fat mass (p=0.62), fat-free mass (p=0.27), and fat-free mass index (p=0.38). Also, no significant differences were detected in the results of HRQoL survey (p=0.85). In the microbiome analysis, no differences of microbiome composition at phylum and genus levels, α-diversity, and β-diversity were observed between baseline and after 8 weeks. Conclusions: While ONS have shown potential in enhancing physical functions of patients with cancer cachexia undergoing chemotherapy, this did not correlate with the anticipated microbiome changes or improvements in body composition. The absence of expected microbiome alterations, despite enriched protein and dietary fiber, underscores the complexity of cachexia and indicates that its management may extend beyond nutritional supplementation alone. Further research should explore the broader context of cachexia, including nutrition, metabolic processes, and the impact of chemotherapy.
Breast cancer polygenic risk score and patient survival outcomes in the Pathways study.
Authors: Roy Arya Mariam , Zeinomar Nur , Sheng Haiyang , Roh Janise M. , Laurent Cecile , Ergas Isaac J. , Delmerico Jennifer , Zhu Qianqian , Kwan Marilyn L. , Kushi Lawrence H. , Ambrosone Christine B. , Yao Song 
Published: June 2024

10502 Background: Many common, low-penetrance variants have been identified for breast cancer risk through genome-wide association studies, leading to the development of polygenic scores (PGS) to aggregate the effects of individual variants for risk prediction. Much less is known about genetic determinants of breast cancer-related outcomes. We hypothesized that breast cancer patients with high breast cancer PGS are at risk of a second breast-related adverse event, such as recurrence, contralateral breast cancer, or death. Methods: The Pathways Study is a prospective cohort study of breast cancer survivors enrolled shortly after diagnosis in 2006-2013 at Kaiser Permanente Northern California, with ongoing follow-up. Genome-wide genotype data were available from 3,995 patients for calculation of 4 PGS, including PGS313, PGS4k, PGS5k, and PGS6m. Scores were categorized into tertiles to investigate their associations with 7 survival outcomes including recurrence, contralateral second primary breast cancer, other second primary cancer, and death. Hazard ratios (HR) and 95% confidence intervals (CI) were derived from multivariable Cox proportional hazards regression models. Results: The median age at diagnosis was 60 (23.6-94.8) years, and most (68%) self-identified as White. Many women had estrogen receptor (ER)+ (83.4%), stage I and II tumors (89%), with 13.3% HER2+ tumors. The majority (60%) received lumpectomy and some type of adjuvant therapy (44.3% radiotherapy, 47.0% chemotherapy, and 74.6% received hormonal therapy). By December 31, 2021, the median follow-up time was 10.5 (0.2-14.2) years, with 504 recurrences, 419 total second primary cancers, 146 contralateral second primary breast cancers, 237 non-breast second primary cancers, and 762 deaths (352 breast cancer-specific deaths) observed. In Table 1, patients with medium (T2) and high (T3) PGS313 had higher risk of recurrence, but not contralateral breast cancer or other second primary cancer. They also had higher risk of all-cause death, breast cancer-specific death, total breast cancer event, and invasive disease. The other 3 PGS were not associated with survival outcomes examined. Conclusions: Our study reveals that breast cancer patients with higher PGS313 had higher risk of recurrence, total breast cancer and invasive breast cancer events, and death. These findings highlight a potential role of breast cancer PGS for prognosis, warranting further exploration. [Table: see text]
Association between rare pathogenic variants in established cancer risk genes and the diagnosis of single and multiple common cancers: A UK Biobank study.
Authors: Shevach Jeffrey , Xu Jianfeng , Snyder Nathan , Wei Jun , Shi Zhuqing , Tran Huy , Zheng S. Lilly , Schwartz Ann G. , Beebe-Dimmer Jennifer Lynn , Cooney Kathleen A. 
Published: June 2024

10505 Background: Much of our understanding of cancer risk attributable to rare pathogenic variants (RPV) is derived from family-based and case-only cohort studies, which may be limited by ascertainment bias. We sought to identify associations between RPVs and cancer diagnoses in a large population-based study. Methods: We conducted a case-control study using the UK Biobank. We performed gene-based aggregate testing to examine the relationship between RPVs (defined as pathogenic or likely pathogenic variants) in 96 genes implicated in cancer risk and the diagnosis of 11 common cancers using the combined optimal unified sequence kernel association test (SKAT-O). Odds ratios (OR) and 95% confidence intervals (CI) were then calculated using Firth logistic regression. Results were adjusted for age, sex and genetic ancestry. Bonferroni-adjusted p-values were used to determine statistical significance. Variant pathogenicity was determined by American College of Medical Genetics criteria. Results: We identified 24 genes in which RPVs were statistically significantly associated with at least one of 11 common cancers among 183,626 individuals. The presence of an RPV in one of these 24 genes was associated with increased odds of one cancer (OR 1.8; 95% CI: 1.7-2.0), and multiple cancers (OR 2.5; 95% CI: 2.2-2.9). Conclusions: This large population-based study identified 24 established cancer risk genes in which RPVs were associated with common cancers. We identified both known and novel associations between cancer and RPVs. Some associations—i.e. renal/pancreas and MEN1—may be due to ascertainment and/or misclassification bias. We also show that individuals with RPVs in cancer risk genes not only have higher odds of one cancer diagnosis, but also multiple cancers.[Table: see text]
Blood type as a risk factor for pancreatic ductal adenocarcinoma.
Authors: Rahimi Larki Navid , Skanderson Melissa , Tate Janet , Levinson Rachel , Hauser Ronald G , Brandt Cynthia , Yang Yu-Xiao , Justice Amy C. , Wang Louise 
Published: June 2024

10559 Background: Non-O blood type has been associated with increased risk of pancreatic ductal adenocarcinoma (PDAC), the third leading cause of cancer death in the United States (US), in largely white populations. We aimed to explore PDAC risk across blood types in the racially diverse Veteran’s Health Administration (VA), the largest integrated healthcare system in the US. Methods: We included all individuals in the VA from 2002 - 2022 with at least one inpatient or outpatient encounter and a non-missing race. We defined the index date as 1.5 years after the initial VA encounter and excluded individuals with prior PDAC. We defined the exposure by non-O (A, B, AB) or type O blood type. We defined PDAC based on a previously validated algorithm of ≥2 sources (cancer registry, hospitalizations, or outpatient oncology encounters) with 95% positive predictive value. Using time to PDAC as the outcome in a multivariable Cox regression, we evaluated the association between blood type and PDAC risk, adjusting for age, sex, BMI, smoking, alcohol use, Hepatitis C (HCV) and diabetes. We censored at time of death, 1.5 years after the last VA encounter, or the end of the study period. We performed a subgroup analysis to evaluate the association of blood type by race. Results: Of the 2.5 million individuals with an available blood type, 1.35 million (52.6%) had a non-O blood type (Table) and over a quarter of our cohort (28.2%, 725,878) were over baseline age 50. Median time to PDAC diagnosis was 8.6 years. There were 877 PDAC cases (0.03%), with 530 (60.4%) of those having a non-O blood type. Compared to those with type O blood, risk of PDAC for individuals with non-O blood type was higher overall [adjusted HR = 1.37 (95% CI 1.20-1.57)], and higher among Whites (n=1,689,092, HR 1.52, 95% CI 1.27-1.82) than Black patients (n=525,666, HR 1.15, 95% CI 0.90-1.48), though this was limited by smaller sample size. Conclusions: Non-O blood type was associated with higher risk of PDAC in a diverse population. Given the potential differences between races, we will further explore the impact of neighborhood-level socioeconomic data on PDAC risk. [Table: see text]
Association between wildfire PM2.5 and genitourinary cancer survival in California.
Authors: Gulati Shuchi , Alaniz Mariela , Mitsiades Nicholas , Parikh Mamta , Raffuse Sean , Keegan Theresa , Hertz-Picciotto Irva , Lara Primo N , Hussain Shehnaz K 
Published: June 2024

10567 Background: Aerosolized particulate matter (PM) 2.5 (i.e., particles ≤ 2.5 µm in diameter or fine particles), including those that emanate from wildfires, has been previously associated with cancer risk and survival. While prior studies have focused primarily on etiology, little is known about the effects of wildfire PM2.5 on cancer prognosis. We sought to explore the effects of wildfire PM2.5 on genitourinary (GU) cancer survival in the state of California where episodic wildfires are considered a component of its climate. Methods: Using the California Cancer Registry, we identified incident prostate (n=81,261), urothelial (n=26,689), and kidney (n=26,303) cancers diagnosed between 2017-2020. Daily PM2.5 was estimated over the same period. Random forests regression was used to fuse diverse datasets (official air quality monitoring, satellite observations, meteorological modeling, predictive smoke modeling, and low-cost sensor networks [PurpleAir]) and produce a consensus estimate of PM2.5 for each centroid of a 1-square kilometer grid across California. We used home address at the time of cancer diagnosis to map each cancer case to the nearest centroid, and averaged PM2.5 exposures over the 6 months preceding cancer diagnosis for each case. Cox-proportional hazards regression was used to quantify the hazard ratio (HR) for death from any cause following cancer diagnosis associated with PM2.5, adjusting for key covariates including age, sex, race/ethnicity, neighborhood socioeconomic status, comorbidity, smoking status, rural/urban residence, and stage at diagnosis. Results: In patients with prostate cancer, a 10 µg/m³ increase in PM2.5 concentration was associated with an 18% increased hazard of death (HR=1.18; 95% confidence interval (CI)= 1.02-1.36, p=0.023). When stratified by stage at diagnosis, the association of PM2.5 and survival was limited to stages I, II, and III (HR=1.39; CI= 1.11-1.74, p=0.005) versus stage IV (HR=1.06; CI= 0.87-1.27, p=0.566). For urothelial cancer, a 10 µg/m³ increase in PM2.5 concentration was associated with a non-statistically significant 11% increased hazard of death (HR=1.11; CI= 0.96-1.29, p=0.151), which did not differ by stage at diagnosis. Kidney cancer survival was not associated with PM2.5 (HR= 0.94; CI= 0.79-1.11, p= 0.44). Conclusions: These findings suggest that higher PM2.5 exposure could influence prostate and urothelial cancer prognosis, perhaps through alteration of physiological pathways relevant to cancer aggressiveness or impairing response to treatment, including cellular immune response, inflammation, angiogenesis, or cell-signaling pathways. Further studies should look into the mechanisms and design mitigating strategies in patients diagnosed with these high-risk cancers who have been exposed to wildfire PM2.5.
Clinical and economic benefit of genomic testing strategies to guide the treatment of patients with HR+/HER2- breast cancer in the US.
Authors: Gouldson Mark , Berdunov Vlad , Le Quang Anh , Millen Steve , Racz Jennifer M. , Arrick Bradley A. , Hartzfeld Deborah , Thakkar Snehal Govind , Heald Brandie , Russell Christy A , Eymere Sebastien , Moyon Camille , Simmons Harriet , Cuyun Carter Gebra 
Published: June 2024

10584 Background: Multiple testing technologies are available to inform treatment decisions for hormone receptor positive (HR+) and human epidermal growth factor receptor 2 negative (HER2-) early-stage breast cancer, including tumor profiling and germline genetic testing (GGT). The 21-gene assay provides an estimate of distant recurrence risk and potential clinical benefit of chemotherapy. GGT identifies pathogenic variants which inform lifetime cancer risk as well may inform therapy options. This study explored the potential synergy of utilizing both tests by assessing the cost-effectiveness of this strategy compared to no testing from a societal perspective. Methods: A health economic model was developed using best practices to assess a patient cohort with HR+/HER2-, node-negative (N0) or node-positive (N1) breast cancer that was guided to surgical and adjuvant treatment by GGT ( ATM, BRCA1/2, CDH1, CHEK2, PALB2, PTEN,and TP53) and the 21-gene assay. Treatment effectiveness was informed by clinical trials (TAILORx and RxPONDER); costs for treatment, monitoring, and health utilities were sourced from literature. Clinical expert opinion and guidelines informed current US clinical practice. The base case analysis evaluated lifetime total costs, life-years, and quality-adjusted life years (QALYs) versus no testing. Scenario and sensitivity analyses were performed to evaluate model robustness. Results: The testing strategy was dominant (lower cost and higher QALYs gained) compared to no testing leading to a QALY improvement of 0.286 and cost savings of $16,463 in the N0 population (Table) and a 0.099 QALY improvement and $299 cost savings in the N1 population. Scenario analyses indicated that while the 21-gene assay was the primary driver of results, there were synergistic effects when tests were combined. Sensitivity analysis supported cost-effectiveness at most willingness-to-pay thresholds and identified the probability of chemotherapy and rate of distant recurrence as the most impactful model inputs. Conclusions: Using a testing strategy including both the 21-gene assay and GGT enables optimization of treatment decisions in early HR+/HER2- breast cancer, improving patient outcomes at reduced costs. [Table: see text]