bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Brain-Lung Immunotherapy Prognostic (BLIP) Score: A Novel Robust Tool for Prognostication in Non-Small Cell Lung Cancer Patients with Brain Metastases
Authors: Skribek Marcus , Livanou Maria-Effrosyni , Vathiotis Ioannis , Strandman Viktor , Thorell Axel , Koulouris Andreas , Syrigos Konstantinos , Ekman Simon , Tsakonas Georgios 
Published: September 2024

AbstractBackgroundLung cancer remains the leading cause of cancer-related mortality, with brain metastases (BMs) significantly worsening prognosis and quality of life. The advent of immune checkpoint inhibitors (ICIs) has revolutionized the treatment landscape for non-small cell lung cancer (NSCLC). However, precise prognostic tools are essential to optimize clinical decision-making in this context.MethodsThe Brain-Lung Immunotherapy Prognostic (BLIP) score was developed based on a retrospective cohort of NSCLC patients treated with ICIs at Karolinska University Hospital, Sweden. Prognostic factors were identified using both univariate and multivariate Cox regression analyses. Internal validation was conducted using bootstrap resampling, penalized Cox regression, k-fold cross-validation, and receiver operating characteristics (ROC) analysis. External validation was performed using an independent cohort from Sotiria Thoracic Diseases Hospital of Athens, Greece.ResultsFrom a total cohort of 1844 patients screened across both study sites, 152 patients from Karolinska University Hospital and 116 from Sotiria Thoracic Diseases Hospital of Athens, Greece, were included in the final analysis. Key prognostic factors influencing outcomes included histology, actionable mutations, age at BM diagnosis, and the number of BMs. The BLIP score effectively stratified patients into two prognostic groups: “Good” and “Poor”, with a median overall survival (OS) of 15 and 7 months, respectively (hazard ratio [HR]: 0.4;p< 0.0001). External validation confirmed these findings, showing a significantly lower risk of death for the “Good” group compared to the “Poor” group (HR: 0.49;p= 0.0063). The model’s robust prognostic performance was confirmed with an area under the ROC curve of 0.87, highlighting its accuracy in predicting survival outcomes.ConclusionThe BLIP score provides a reliable, validated prognostic tool for NSCLC patients with BMs undergoing ICI therapy. By integrating both molecular and clinical variables, it offers significant improvements over existing models. Prospective validation could further support its use in personalized treatment strategies, improving clinical outcomes and patient management.HighlightsThe BLIP score is a new prognostic tool for NSCLC.It focuses on patients with brain metastases undergoing immunotherapy.The score integrates clinical and molecular factors.Internal validation showed strong prognostic power and reliability.External validation confirmed effectiveness across diverse patient populations.Key factors include histology, actionable mutations, age, and brain metastases count.The score stratifies patients into “Good” and “Poor” groups.The BLIP score aids in personalized treatment decision-making.
DrugOn: A Comprehensive Drug Ontology for Precision Oncology
Authors: Kornrumpf Kevin , Gnaß Vera , Holm Myrine , Beißbarth Tim , Koch Raphael , Dönitz Jürgen 
Published: September 2024

AbstractIntroductionPrecision oncology and biomedical cancer research increasingly rely on tools to select optimal drugs targeting specific genetic alterations in cancer. A major challenge for bioinformatic tools supporting drug selection is to standardize different annotations (substance, drug name, drug class) to a common level, typically the drug class. While manual classification is time-consuming and potentially biased, existing resources often lack completeness, granularity, or mix up drug classes and drug targets. A structured, automatically built drug ontology such as DrugOn fills these gaps, improving decision support and data-driven research.MethodsDrugOn integrates information from multiple sources to create a comprehensive drug ontology. It includes categories, molecular targets and additional annotations from DrugBank, ATC, MesH, KEGG and ClueIO. The combination of this data enables accurate identification of drug categories for each drug.ResultsDrugOn’s effectiveness was demonstrated by classifying 336 drugs from CIViC. It agreed with manually curated database-derived classifications for 268 out of 282 drugs assessed in translational lymphoma research. In 54 cases, classification was not possible due to data gaps. DrugOn provides a REST API and a front-end application for ontology exploration and automated drug queries.ConclusionDrugOn, a unified drug ontology, is derived from public datasets and refined by precise processing rules to ensure a reliable, updatable resource for drug information, in precision medicine. It uniquely categorizes drug classes and target proteins, and its structured format, complemented by an accessible API, allows for easy integration into data driven pipelines. Initially tailored for lymphoma research, DrugOn’s adaptable nature supports broader cancer research applications and potential data source expansions. DrugOn is accessible athttps://mtb.bioinf.med.uni-goettingen.de/drugon-web.
Prognostic Value of CD8+ T-Cells at the Invasive Margin is Comparable to Immune Score in Non-Metastatic Colorectal Cancer: Prospective Multicenter Cohort Study
Authors: Wankhede Durgesh , Halama Niels , Kloor Matthias , Edelmann Dominic , Brenner Hermann , Hoffmeister Michael 
Published: September 2024

AbstractBackgroundThe Immunoscore® is a validated tool for predicting colorectal cancer (CRC) prognosis, yet its adoption is impeded by complex commercial software and patient reimbursement challenges. Utilizing open-source methods, this study aimed to explore whether an immune cell score can be facilitated by focusing on single T-cell markers, to provide a simplified prognostic model in non-metastatic CRC.MethodsA multicentric prospective cohort study was conducted in non-metastatic CRC patients who underwent curative surgical resection. CD3+ and CD8+ tumor infiltrating lymphocytes (TILs) were quantified in both invasive margin (IM) and tumor core (TC) using QuPath. A composite score, termed immune cell score, mirroring the methods employed for the Immunoscore®, was calculated based on the TIL densities (CD3-IM, CD8-IM, CD3-TC, CD8-TC]. We used a split sample approach (70:30) to estimate adjusted hazard ratios of cancer-specific survival (CSS) in a training and a validation set. Classification and regression tree analysis (CART) was performed to select the most prognostic TIL. The model incorporating the CART-selected TIL was compared to a two-tiered immune cell score model for overall performance (Brier score) and discrimination (concordance probability estimate, CPE).ResultsDuring a median follow-up time of 9.0 years, among 1260 patients, there were 203 CRC specific deaths. CART-selected CD8-IM was the most prognostic TIL at a cut-off of 231 cells/mm2. Patients with CD8-IMHihad better CSS than CD8-IMLowin both training (HR 0.58, 95% CI 0.40-0.84) and validation sets (HR 0.35, 95% CI 0.21-0.60). Brier scores of CD-8IM and immune cell score survival models were comparable in both training and validation cohort, whereas the survival discrimination of CD8-IM slightly outperformed the immune cell score in the validation set (CPE: CD8-IM 0.748, IS 0.730).ConclusionA single TIL marker, specifically CD8-IM, provided prognostic information comparable to the immune cell score. Simplified and cost-effective TIL assessments could enhance their bench to bedside translation and may guide adjuvant therapy in early-stage CRC.
Characterizing Highly Fermentable Carbohydrate Foods in the Diets of Children with Disorders of Gut-Brain Interaction and Healthy Children
Authors: Narayana Vishnu , Chang Jocelyn , McMeans Ann R. , Levy Rona L. , Shulman Robert J. , Chumpitazi Bruno P. 
Published: September 2024

AbstractObjectivesRestricting fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) intake can alleviate symptoms in children with gut-brain interaction disorders (DGBI). Due to the restrictive nature of the low FODMAP diet (LFD), the less restrictive FODMAP Gentle diet (FGD) has been suggested. However, the types of high FODMAP foods and carbohydrates commonly consumed by US children are unknown, as is the impact of the FGD on a typical diet. This project aimed to identify the high FODMAP foods and proportions of FODMAP carbohydrates consumed by children with DGBI and healthy children (HC), and to determine which usually ingested FODMAPs would be restricted on the FGD.MethodsThree-day diet records from both HC and children with DGBI were analyzed to assess the type of high FODMAP foods and carbohydrates ingested. Results were compared between the groups. The ingested FODMAPs that would be restricted on the FGD was determined.ResultsThe number of foods ingested daily was similar between children with DGBI and HC (12.3 ± 4.2 vs 12.9 ± 3.4, respectively); high FODMAP foods comprised most foods eaten in both groups. Children with DGBI (vs HC) ate less high FODMAP foods per day (6.5 ± 2.3 vs 8.7 ± 2.4, P<0.0001, respectively). Fructans were the most consumed FODMAP carbohydrate in both groups and children with DGBI (vs HC) consumed fewer fructans, lactose, fructose, and polyols (all P<0.0001). The top 3 food categories consumed in both groups were wheat-containing foods, dairy, and fruits and 100% fruit juices. In children with DGBI, 80.9% of the high FODMAP foods consumed would be limited on the FGD.DiscussionChildren with DGBI consume significantly fewer high FODMAP foods and carbohydrates than HC. In both groups, the top consumed FODMAP carbohydrates are fructans, lactose, and fructose. A FODMAP Gentle diet would restrict a large majority of high FODMAP foods consumed by children with DGBI.
Surgical strategy for atrial functional mitral regurgitation with atrial fibrillation
Authors: Bao Chunrong , Wei Ke , Zhao Dongfang , Zhang Junwen , Mei Ju , Ma Nan 
Published: September 2024

AbstractBackgroundWith the growing prevalence of atrial fibrillation (AF), atrial functional mitral regurgitation (AFMR) combined with AF is expected to become a common clinical issue. We have summarized various surgical treatment strategies based on the degree of mitral regurgitation (MR) alongside rhythm control therapy for patients with AFMR and AF.MethodsThis retrospective study included 145 patients with AF and MR from January 2017 to January 2023. 33 patients with AF and moderate AFMR were designated as the moderate atrial regurgitation (MAR) group. 56 patients with AF and severe AFMR were designated as the severe atrial regurgitation (SAR) group. The remaining 56 patients with AF and severe primary MR were designated as the severe primary regurgitation (SPR) group. All patients in the MAR group underwent thoracoscopic AF procedure via a unilateral approach. Patients in the SAR and SPR groups underwent mitral valvuloplasty plus the Cox Maze IV procedure (CMP IV). Descriptive characteristics and outcomes were analysed.ResultsTwenty-three patients maintained sinus rhythm (SR) following thoracoscopic AF procedure in the MAR group at average 2.6±1.1 years follow-up. The degree of regurgitation improved in 26 patients, remained unchanged in 6 patients, and worsened in 1 patient. SR maintenance benefits MR reduction (P<0.0001) compared to the non-SR patients. There was no significant difference in the rate of SR maintenance following mitral valvuloplasty plus CMP IV between SAR (43 patients, 79.6%) and SPR (49 patients, 87.5%) groups. At the last follow-up, echocardiography in the SAR group showed 47 cases with no mitral regurgitation, 4 cases with mild regurgitation, and 1 case with moderate regurgitation. The left atrial diameter in the SAR group remained larger than in the SPR group (P<0.001).ConclusionsRhythm control therapy is the cornerstone treatment for AFMR patients with AF. Thoracoscopic AF procedure is effective and minimally invasive for moderate AFMR patients with AF. For severe AFMR patients with AF, we recommend CMP IV plus mitral valvuloplasty for safety and effectiveness.
Resource presentation dictates genetic and phenotypic adaptation in yeast
Authors: Ahlawat Neetika , Mahilkar Anjali , Saini Supreet 
Published: September 2024

AbstractEnvironments shape adaptive trajectories of populations, often leading to adaptive parallelism in identical, and divergence in different environments. However, how does the likelihood of these possibilities change with minute changes in the environment? In this study, we evolveSaccharomyces cerevisiaein environments which only differed in how sugar source is presented to the population. In one set of populations, carbon was presented as a mixture of glucose-galactose, and in the other, as melibiose, a glucose-galactose disaccharide. Since the two environments only differ in how the two monosaccharides are packaged, we call these environments „synonymous‟. Our results show that subtle changes in environments change the targets of selection between the two sets of evolved populations. However, despite different adaptive responses, pleiotropic effects of adaptation are largely predictable. Genome sequencing results demonstrate that small changes in the environment also strongly dictates the genetic basis of adaptation.
AQP1- A regulatory factor associated with brown adipose tissue-silencing
Authors: Cheng Chloe M , Blay Christopher J , Tsai Pei-Yin , Li Muying , Edwards Kaydine , Qu Yue , Liu Yang , Buettner Nina , Walter Claire , Snyder Mary , Costa Ines PD , Devuyst Olivier , Barrow Joeva J 
Published: September 2024

AbstractThe activation of non-shivering thermogenesis (NST) in brown adipose tissue (BAT) by environmental cold challenge yields strong metabolic benefit in the face of diet-induced obesity (DIO). Yet, a critical barrier to leveraging brown fat NST for therapeutic use against metabolic disease is that BAT is silenced and inactive at physiological ambient temperature conditions in humans. The mechanisms that govern this silencing process remain poorly understood. Here, we identified a putative BAT-silencing factor, aquaporin-1 (AQP1), in brown fat from wild-type (WT) mice via proteomics analysis. We generated the first BAT-specific AQP1 knockout mice (AQP1-KO) and revealed that AQP1-KO could activate NST under BAT silencing environmental conditions and that the AQP1-KO mice were significantly protected against DIO and metabolic dysfunction compared to Flox controls. We found that AQP1-KO mice on high fat diet (HFD) had reduced weight gain through reductions in fat mass, improved glucose tolerance, and increased whole body energy expenditure compared to Flox control mice. Mechanistically, we show that AQP1 ablation in mice had upregulated gene expression related to the electron transport chain (ETC) and mitochondrial translation contributing to the activation of NST under BAT environmental silenced conditions.Significance StatementNovel strategies to combat obesity-associated metabolic dysfunction are urgently needed to curb the growing obesity epidemic. Investigation of brown adipose tissue (BAT) silencing mechanisms may reveal novel therapeutic targets that when ablated, can activate BAT to increase energy expenditure and protect subjects against the metabolic dysfunction associated with obesity. We have identified Aquaporin 1 (AQP1) as a putative BAT silencer regulatory factor and show through the generation of the first BAT-specific aquaporin-1 knockout (AQP1-KO) mouse that BAT can be activated under environmental silencing conditions. We further show that these mice are protected against diet-induced obesity, with improved glucose tolerance, and increased energy expenditure. These findings highlight AQP1 as a promising therapeutic target in the emerging research field of BAT silencers.
Cross omics risk scores of inflammation markers are associated with all-cause mortality: The Canadian Longitudinal Study on Aging
Authors: Meir Anat Yaskolka , Yun Huan , Hu Jie , Li Jun , Liu Jiaxuan , Bever Alaina , Ratanatharathorn Andrew , Song Mingyang , Heather Eliassen A. , Chibnik Lori , Koenen Karestan , Pare Guillaume , Stampfer Meir J , Liang Liming 
Published: September 2024

AbstractInflammation is a critical component of chronic diseases, aging progression, and lifespan. Omics signatures may characterize inflammation status beyond blood biomarkers. We leveraged genetics (Polygenic-Risk-Score; PRS), metabolomics (Metabolomic-Risk-Score; MRS), and epigenetics (Epigenetic-Risk-Score; ERS) to build multi-omics-multi-marker risk scores for inflammation status represented by the level of circulating C-reactive protein (CRP), interleukin 6 (IL6), and tumor necrosis factor alpha (TNFa). We found that multi-omics risk-scores generally outperformed single-omics risk scores in prediction of all-cause mortality in the Canadian Longitudinal Study on Aging. Compared with circulating inflammation biomarkers, some multi-omics risk scores had a higher HR for all cause-mortality when including both score and circulating IL6 in the same model (1-SD IL6 MRS-ERS: HR=1.77 [1.15-2.72] vs. 1-SD circulating IL6 HR=1.11 [0.75,1.66]; 1-SD IL6 PRS-MRS: HR=1.32 [1.21,1.45] vs. 1-SD circulating IL6 HR=1.31 [1.12, 1.53]; 1-SD PRS-MRS-ERS: HR=1.62 [1.04, 2.53] vs. 1-SD circulating IL6: HR=1.16 [0.77, 1.74]). In the Nurses’ Health Study (NHS), NHS II, and Health Professional Follow-up Study with available omics, 1-SD of IL6 PRS and 1-SD IL6 PRS-MRS had HR=1.13 [1.00,1.27] and HR=1.13 [1.01,1.27], among individuals >65years without mutual adjustment of the score and circulating IL6. Our study demonstrated that some multi-omics scores for inflammation markers may characterize important inflammation burden for an individual beyond those represented by blood biomarkers and improve our prediction capability for aging process and lifespan.
Leveraging the electronic health record to identify delivery of goal-concordant care
Authors: Auriemma Catherine L , Song Anne , Walsh Lake , Han Jason , Yapalater Sophia , Bain Alexander , Haines Lindsay , Scott Stefania , Whitman Casey , Taylor Stephanie P , Weissman Gary E. , Gonzales Matthew J , Weerasinghe Roshanthi , Wendt Staci J , Courtright Katherine R 
Published: September 2024

AbstractBackgroundGoal-concordant care (GCC) is recognized as the highest quality of care and most important outcome measure for serious illness research, yet there is no agreed-upon or validated method to measure it.ObjectiveAssess feasibility of measuring GCC using clinical documentation in the electronic health record (EHR).DesignRetrospective chart review study.ParticipantsAdults with ≥50% predicted six-month mortality risk admitted to three urban hospitals in a single health system. All participants had goals-of-care (GOC) discussions documented in the EHR 6 months before and 6 months after admission manually classified into one of four categories of goals: (1) comfort-focused, (2) maintain or improve function, (3) life-extension, or (4) unclear.Main MeasuresPairs of physician-coders independently reviewed EHR notes from 6 months before through 6 months after admission to identify and classify care received between each documented GOC discussion into one of the four goals categories. Epochs between GOC discussions were then coded as goal-concordant if GOC and care received classifications were aligned, goal-discordant if they were misaligned, or uncertain if either classification was unclear or not documented. Coder inter-rater reliability was assessed using kappa statistics.Key ResultsInter-rater reliability for classifying care received was almost perfect (95% interrater agreement; Cohen’s kappa=0.92; 95% CI, 0.86-0.99). Of 398 total epochs across 109 unique patients, 198 (50%) were goal-concordant, 112 (28%) were of uncertain concordance, and 88 (22%) were goal-discordant. Eighty (73%) patients received care of uncertain concordance during at least one epoch. Forty-eight (44%) patients received goal-discordant care during at least one epoch.ConclusionsClinician chart review was a feasible method for measuring GCC and can inform natural language processing and machine learning methods to improve the clinical and research utility of this method. More work is needed to understand the driving factors underlying the high rate of uncertain concordance and goal-discordant care identified among this seriously ill cohort.
Dental health of childhood cancer survivors – a report from the Swiss Childhood Cancer Survivor Study (SCCSS)
Authors: Nigg C , Matti C , Jörger P , von Bueren AO , Filippi C , Diesch-Furlanetto T , Tomášiková Z , Kuehni CE , Sommer G 
Published: September 2024

AbstractBackgroundCancer and its treatments can affect dental health of childhood cancer survivors. We aimed to evaluate prevalence of dental problems in survivors, compare them to their siblings, and investigate cancer-related risk factors.MethodsAs part of the population-based Swiss Childhood Cancer Survivors Study, we sent questionnaires inquiring about dental problems to survivors aged 5-19 years and their siblings. We retrieved cancer-relevant information from the Swiss Childhood Cancer Registry and used logistic regressions to compare dental problems between survivors and siblings and to investigate cancer-related risk factors.ResultsWe included 735 survivors and 144 siblings. Almost half of survivors and siblings reported at least one dental problem. Compared to siblings, survivors had a greater risk for hypo- or microdontia (OR 1.7; 95%CI 0.9-3.2) and enamel hypoplasia (2.2; 0.8-6.0), but similar risk for cavities or cavity-related tooth loss (0.8; 0.6-1.3). Chemotherapy was associated with enamel hypoplasia (3.0; 1.2-10.4), cavities or cavity-related tooth loss (1.5; 1.0-2.3), and gum problems during (23.0; 9.4-76.2) and after (4.6; 2.0-13.5) treatment. Hematopoietic stem cell transplantation (HSCT) was related to hypo- or microdontia (5.4; 2.6-10.7), cavities or cavity-related tooth loss (2.1; 1.2-3.6), and gum problems during treatment (2.0; 1.2-3.6). For hypo- or microdontia and cavities, associations with treatment were driven by patients diagnosed <5 years.ConclusionChildhood cancer patients treated with chemotherapy or HSCT, especially at a young age, were at higher risk for dental problems. Regular dental check-ups guided by healthcare teams and dental hygiene habits can mitigate risks and promote survivor’s long-term dental health.