bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of two automated oxygen controllers in oxygen targeting in preterm infants during admission: an observational study
Authors: Salverda Hylke H , Dekker Janneke , Lopriore Enrico , Dargaville Peter A , Pauws Steffen C , te Pas Arjan B 
Published: January 2023

ObjectiveTo compare the effect of two different automated oxygen control devices on time preterm infants spent in different oxygen saturation (SpO2) ranges during their entire stay in the neonatal intensive care unit (NICU).DesignRetrospective cohort study of prospectively collected data.SettingTertiary level neonatal unit in the Netherlands.PatientsPreterm infants (OxyGenie 75 infants, CLiO2111 infants) born at 24–29 weeks’ gestation receiving at least 72 hours of respiratory support between October 2015 and November 2020.InterventionsInspired oxygen concentration was titrated by the OxyGenie controller (SLE6000 ventilator) between February 2019 and November 2020 and the CLiO2controller (AVEA ventilator) between October 2015 and December 2018 as standard of care.Main outcome measuresTime spent within SpO2target range (TR, 91–95% for either epoch) and other SpO2ranges.ResultsTime spent within the SpO2TR when receiving supplemental oxygen was higher during OxyGenie control (median 71.5 [IQR 64.6–77.0]% vs 51.3 [47.3–58.5]%, p<0.001). Infants under OxyGenie control spent less time in hypoxic and hyperoxic ranges (SpO2<80%: 0.7 [0.4–1.4]% vs 1.2 [0.7–2.3]%, p<0.001; SpO2>98%: 1.0 [0.5–2.4]% vs 4.0 [2.0–7.9]%, p<0.001). Both groups received a similar FiO2(29.5 [28.0–33.2]% vs 29.6 [27.7–32.1]%, p=not significant).ConclusionsOxygen saturation targeting was significantly different in the OxyGenie epoch in preterm infants, with less time in hypoxic and hyperoxic SpO2ranges during their stay in the NICU.
Diagnostic accuracy of FibroScan-AST (FAST) score for the non-invasive identification of patients with fibrotic non-alcoholic steatohepatitis: a systematic review and meta-analysis
Authors: Ravaioli Federico , Dajti Elton , Mantovani Alessandro , Newsome Philip Noel , Targher Giovanni , Colecchia Antonio 
Published: January 2023

ObjectiveA simple combined score with liver stiffness, controlled attenuation parameter and serum aspartate aminotransferase (AST), the FibroScan-AST (FAST) score, has been proposed to non-invasively identify patients with fibrotic non-alcoholic steatohepatitis (NASH). We performed a systematic review and meta-analysis of published studies to evaluate the overall diagnostic accuracy of the FAST score in identifying patients with fibrotic NASH.DesignWe systematically searched MEDLINE, Ovid Embase, Scopus and Cochrane Library electronic databases for full-text published articles in any language between 3 February 2020 and 30 April 2022. We included original articles that reported data for the calculation of sensitivity and specificity of the FAST score for identifying adult patients with fibrotic NASH adults, according to previously described rule-out (≤0.35) and rule-in (≥0.67) cut-offs.ResultsWe included 12 observational studies for a total of 5835 participants with biopsy-confirmed non-alcoholic fatty liver disease. The pooled prevalence of fibrotic NASH was 28% (95% CI 21% to 34%). The FAST score’s pooled sensitivity was 89% (95% CI 82% to 93%), and the pooled specificity was 89% (95% CI 83% to 94%) according to the aforementioned rule-in/rule-out cut-offs. The negative predictive value and positive predictive value of the FAST score were 92% (95% CI 91% to 95%) and 65% (95% CI 53% to 68%), respectively. Subgroup analyses and influential bias analyses did not alter these findings.ConclusionThe results of our meta-analysis show that the FAST score has a good performance for non-invasive diagnosis of fibrotic NASH. Therefore, this score can be used to efficiently identify patients who should be referred for a conclusive liver biopsy and/or consideration for treatment with emerging pharmacotherapies.PROSPERO registration numberCRD42022350945.
Human soft tissue sarcomas harbor an intratumoral viral microbiome which is linked with natural killer cell infiltrate and prognosis
Authors: Perry Lauren M , Cruz Sylvia M , Kleber Kara T , Judge Sean J , Darrow Morgan A , Jones Louis B , Basmaci Ugur N , Joshi Nikhil , Settles Matthew L , Durbin-Johnson Blythe P , Gingrich Alicia A , Monjazeb Arta Monir , Carr-Ascher Janai , Thorpe Steve W , Murphy William J , Eisen Jonathan A , Canter Robert J 
Published: January 2023

BackgroundGroundbreaking studies have linked the gut microbiome with immune homeostasis and antitumor immune responses. Mounting evidence has also demonstrated an intratumoral microbiome, including in soft tissue sarcomas (STS), although detailed characterization of the STS intratumoral microbiome is limited. We sought to characterize the intratumoral microbiome in patients with STS undergoing preoperative radiotherapy and surgery, hypothesizing the presence of a distinct intratumoral microbiome with potentially clinically significant microbial signatures.MethodsWe prospectively obtained tumor and stool samples from adult patients with non-metastatic STS using a strict sterile collection protocol to minimize contamination. Metagenomic classification was used to estimate abundance using genus and species taxonomic levels across all classified organisms, and data were analyzed with respect to clinicopathologic factors.ResultsFifteen patients were enrolled. Most tumors were located at an extremity (67%) and were histologic grade 3 (87%). 40% were well-differentiated/dedifferentiated liposarcoma histology. With a median follow-up of 24 months, 4 (27%) patients developed metastases, and 3 (20%) died. Despite overwhelming human DNA (>99%) intratumorally, we detected a small but consistent proportion of bacterial DNA (0.02–0.03%) in all tumors, includingProteobacteria, Bacteroidetes,andFirmicutes, as well as viral species. In the tumor microenvironment, we observed a strong positive correlation between viral relative abundance and natural killer (NK) infiltration, and higher NK infiltration was associated with superior metastasis-free and overall survival by immunohistochemical, flow cytometry, and multiplex immunofluorescence analyses.ConclusionsWe prospectively demonstrate the presence of a distinct and measurable intratumoral microbiome in patients with STS at multiple time points. Our data suggest that the STS tumor microbiome has prognostic significance with viral relative abundance associated with NK infiltration and oncologic outcome. Additional studies are warranted to further assess the clinical impact of these findings.
Genetic load in incomplete lupus erythematosus
Authors: Slief Matt , Kheir Joseph M , Smith Miles , Mowery Colin , Macwana Susan , DeJager Wade , Wagner Catriona A , Aberle Teresa , James Judith A , Guthridge Joel M 
Published: January 2023

ObjectivePatients with incomplete lupus erythematosus (ILE) have lupus features but insufficient criteria for SLE classification. Some patients with ILE transition to SLE, but most avoid major organ involvement. This study tested whether the milder disease course in ILE is influenced by reduced SLE risk allele genetic load.MethodsWe calculated the genetic load based on 99 SLE-associated risk alleles in European American patients with SLE (≥4 American College of Rheumatology (ACR) 1997 criteria, n=170), patients with ILE (3 ACR 1997 criteria, n=169), a subset of patients with ILE not meeting Systemic Lupus International Collaborating Clinics (SLICC) classification (ILESLICC, n=119) and healthy controls (n=133). Unweighted genetic loads were calculated as the total sum of risk alleles for each individual, while weighted genetic loads were defined as the sum of risk alleles multiplied by the natural logarithm of the previously published OR of each risk allele for SLE susceptibility.ResultsThe median unweighted and weighted SLE risk allele genetic load was significantly greater in patients with ILE (unweighted: 81, p value=0.01; weighted: 16.3, p value=0.001) and patients with SLE (80, p value=0.02; 16.29, p value=0.0006) compared with healthy controls (78, 15.76). Patients with ILESLICCtrended towards an increased genetic load, although not statistically significant (unweighted: 80, p value=0.14; weighted: 16.05, p value=0.07). However, the median genetic load did not significantly differ between ILE and SLE, and genetic load did not differentiate patients with ILE and SLE (area under the curve=0.51, p=0.78) by receiver operator characteristic analysis.ConclusionsPatients with ILE and SLE have comparable genetic loads of SLE risk loci, suggesting similar genetic predispositions between these conditions. Phenotypical differences between SLE and ILE may instead be influenced by ILE-specific variants and gene–environment interactions.
The Relation between ACE Gene Polymorphism and the Severity of COVID-19 Infection
Authors: El-Sayed Marei Yara , Abdallah Bayoumy Ahmed , Mohamed Abulazm Nassar Hassnaa , Mansour Bassam , Bakeir Hamady Asmaa 
Published: January 2023

Introduction. The coronavirus disease 2019 (COVID-19) pandemic, which emerged in China at the end of 2019, rapidly spread worldwide. The angiotensin-converting enzyme (ACE) gene contains an insertion/deletion (I/D) polymorphism that leads to a higher serum ACE level which is associated with several diseases and also with a high mortality rate in SARS. Therefore, this study aimed at assessing the association between ACE gene polymorphism and the risk and severity of COVID-19 disease in patients. Methodology. Forty-five SARS-CoV-2 infected patients and another random control group of 45 healthy individuals were included. The detection of ACE I/D gene polymorphism in both groups was done by PCR. Results. 53% of infected patients with SARS-CoV-2 had an ACE deletion/deletion genotype (D/D), 27% had an ACE deletion/insertion genotype (D/I), and 20% had an ACE insertion/insertion genotype (I/I). On the one hand, the D/D variant was significantly detected in the COVID-19 patients compared to the control subjects, whereas the I/I variant was significantly detected in the control subjects compared to the COVID-19 patients (

p

= 0.004). The D/D variant subgroup showed the lowest lymphocytic count compared to the D/I or I/I subgroups. In addition, the C-reactive protein was significantly higher and the oxygen saturation was significantly lower in patients with the D/D allele compared to the other subgroups. Conclusions. ACE gene polymorphism, particularly the DD genotype, was observed to affect the severity of COVID-19 infection.
Molecular Pathways and Mechanisms of TGFβ in Cancer Therapy
Authors: Barcellos-Hoff Mary Helen , Gulley James L. 
Published: January 2023

Abstract
Even though the number of agents that inhibit TGFβ being tested in patients with cancer has grown substantially, clinical benefit from TGFβ inhibition has not yet been achieved. The myriad mechanisms in which TGFβ is protumorigenic may be a key obstacle to its effective deployment; cancer cells frequently employ TGFβ-regulated programs that engender plasticity, enable a permissive tumor microenvironment, and profoundly suppress immune recognition, which is the target of most current early-phase trials of TGFβ inhibitors. Here we discuss the implications of a less well-recognized aspect of TGFβ biology regulating DNA repair that mediates responses to radiation and chemotherapy. In cancers that are TGFβ signaling competent, TGFβ promotes effective DNA repair and suppresses error-prone repair, thus conferring resistance to genotoxic therapies and limiting tumor control. Cancers in which TGFβ signaling is intrinsically compromised are more responsive to standard genotoxic therapy. Recognition that TGFβ is a key moderator of both DNA repair and immunosuppression might be used to synergize combinations of genotoxic therapy and immunotherapy to benefit patients with cancer.
Benign Breast Disease, NSAIDs, and Postmenopausal Breast Cancer Risk in the CPS-II Cohort
Authors: Sherman Mark E. , Vierkant Robert A. , Masters Matthew , Radisky Derek C. , Winham Stacey J. , Degnim Amy C. , Vachon Celine M. , Patel Alpa V. , Teras Lauren R. 
Published: January 2023

AbstractNonsteroidal anti-inflammatory agents (NSAID) are associated with modest inconsistent reductions in breast cancer risk in population-based cohorts, whereas two focused studies of patients with benign breast disease (BBD) have found lower risk with NSAID use. Given that BBD includes fibroinflammatory lesions linked to elevated breast cancer risk, we assessed whether NSAID use was associated with lower breast cancer risk among patients with BBD.Participants were postmenopausal women in the Cancer Prevention Study-II (CPS-II), a prospective study of cancer incidence and mortality, who completed follow-up surveys in 1997 with follow-up through June 30, 2015. History of BBD, NSAID use, and covariate data were updated biennially. This analysis included 23,615 patients with BBD and 36,751 patients with non-BBD, including 3,896 incident breast cancers over an average of 12.72 years of follow-up among participants. NSAID use, overall and by formulation, recency, duration, and pills per month was analyzed versus breast cancer risk overall and by BBD status using multivariable-adjusted Cox models; BBD status and NSAID use were modeled as time-dependent exposures.Patients with BBD who reported using NSAIDs experienced lower breast cancer risk (HR, 0.87; 95% CI, 0.78–0.97), with similar effects for estrogen receptor (ER)-positive breast cancers [HR, 0.85; 95% confidence interval (CI), 0.74–0.97] and ER-negative breast cancers (HR, 0.87; 95% CI, 0.59–1.29); among women without BBD, NSAID use was unrelated to risk (HR, 1.02; 95% CI, 0.92–1.13; Pinteraction = 0.04). Associations stratified by age, obesity, menopausal hormone use, and cardiovascular disease were similar.Among patients with BBD, NSAID use appears linked to lower breast cancer risk. Further studies to assess the value of NSAID use among patients with BBD are warranted.Prevention Relevance:We examined whether NSAID use, a modifiable exposure, is associated with breast cancer risk in postmenopausal women from the Cancer Prevention Study-II with self-reported benign breast disease, an often inflammatory condition associated with higher rates of breast cancer.
Abstract IA002: Optimizing the public’s health through prevention and early detection (precision and otherwise)
Authors: Rebbeck Timothy 
Published: January 2023

Abstract
Cancer prevention and early detection have the greatest potential for reducing incidence, suffering, and death from cancer of any modality we have available. HPV and HBV vaccination, as well as exposure avoidance (e.g., smoking cessation) are well documented to reduce cancer risks. Approaches such as mammography, colonoscopy and low-dose CT screening clearly provide mortality reductions. While these tools are effective, they are under-used and thus their potential for cancer reduction is sub-optimal. The field is also at a critical phase of development: we have substantial mechanistic understanding of cancer and novel technologies that provide new opportunities for prevention and early detection. We must consider a series of factors in order for effective translation and implementation of this knowledge to occur. Multisector involvement of academia, business, policymakers, biotech, community members, and others are required to build a common language and pathways from discovery to implementation. Diverse data and input from end used communities are required to ensure that these novel approaches do not induce or exacerbate disparities and can benefit all populations equitably. Increased compliance with existing population-based tools that are known to minimize cancer mortality must be improved, while new “precision” methods are developed and implemented. The field has the opportunity to disrupt the landscape of state of cancer by developing and implementing mechanism-based tools and technologies that will be used in novel prevention and early detection strategies.
Citation Format: Timothy Rebbeck. Optimizing the public’s health through prevention and early detection (precision and otherwise). [abstract]. In: Proceedings of the AACR Special Conference: Precision Prevention, Early Detection, and Interception of Cancer; 2022 Nov 17-19; Austin, TX. Philadelphia (PA): AACR; Can Prev Res 2023;16(1 Suppl): Abstract nr IA002.
Abstract IA018: Opportunity for interception as a driver of benefit in cancer early detection: implications for multi-cancer early detection testing
Authors: Etzioni Ruth , Gulati Roman , Owens Lukas , Lange Jane , Ryser Marc D. 
Published: January 2023

Abstract
Early detection cannot succeed unless there is adequate opportunity for cancer to be diagnosed and intercepted within its early preclinical phase. An understanding of opportunity for early detection and interception is therefore critical in predicting potential mortality reduction due to screening. Opportunity is not directly observable but may be learned using data from prospectively screened cohorts and populations. In this presentation I will share a history of methods for learning about early detection opportunity and will present examples of how we have built on this work to study opportunity for early detection in prostate and breast cancer. I will describe a generic model of how opportunity and sensitivity combine to produce stage shift and mortality reduction and will briefly explore whether a lack of opportunity may have been behind the results of the UCKCTOCS trial. I will use this learning to motivate why I believe a prospective study to investigate opportunity for multi-cancer detection and interception is warranted before or alongside ongoing and planned screening trials. This work in in collaboration with Roman Gulat i and Lukas Owens (Fred Hutch), Jane Lange (OHSU) and Marc Ryser (Duke University). We acknowledge funding from the National Cancer Institute and collaboration with and data from the Breast Cancer Surveillance Consortium
Citation Format: Ruth Etzioni, Roman Gulati, Lukas Owens, Jane Lange, Marc D. Ryser. Opportunity for interception as a driver of benefit in cancer early detection: implications for multi-cancer early detection testing. [abstract]. In: Proceedings of the AACR Special Conference: Precision Prevention, Early Detection, and Interception of Cancer; 2022 Nov 17-19; Austin, TX. Philadelphia (PA): AACR; Can Prev Res 2023;16(1 Suppl): Abstract nr IA018.
Abstract IA022: Assessing implementation of a multi-cancer early detection blood test for population screening in a clinical practice setting: prospective PATHFINDER cohort study
Authors: Klein Eric , Beer Tomasz 
Published: January 2023

Abstract
Background: A validated blood-based multi-cancer early detection (MCED) test uses cfDNA and machine learning to detect a shared cancer signal across &gt;50 cancer types and predict cancer signal origin. PATHFINDER is a prospective study in a screening population to evaluate the clinical feasibility of MCED testing. Methods: Between December 2019 and 2020, 6662 adults aged ≥50 years with or without additional cancer risk factors (smoking history, genetic predisposition, prior cancer diagnosis) were enrolled from 7 US health systems’ outpatient practices. Blood samples were collected, cfDNA was analyzed, and MCED test results were returned. Diagnostic evaluation was conducted at the discretion of the physician. Cancer status was ascertained after one year. Primary outcomes were extent of diagnostic testing and time to diagnostic resolution. Performance measures included signal detection rate, accuracy of predicted cancer signal origin, specificity, and positive and negative predictive values. Findings: Of the 6621 (99.4%) with analyzable samples, cancer signal was detected in 92 (1.4%), 91 reached diagnostic resolution, 90 were evaluable for the primary outcome, and 35 were true positives (TP). Median time to diagnostic resolution was 79 days overall and 57 days in TPs; 73% of TPs achieved resolution in &lt;3 months. Among TPs, signal origin was predicted accurately for 33/34 (97.1%). Specificity was 99.1% (6235/6290), positive predictive value was 38.0% (35/92), and negative predictive value was 98.6% (6235/6321). Adverse events were rare (0.06%); none due to confirmatory diagnostic procedures. Interpretation: A blood-based assay to screen for multiple cancers was safely implemented in adults ≥50 years with and without additional cancer risk. It is feasible to use MCED testing for early detection of cancer in routine outpatient practice.
Citation Format: Eric Klein, Tomasz Beer. Assessing implementation of a multi-cancer early detection blood test for population screening in a clinical practice setting: prospective PATHFINDER cohort study. [abstract]. In: Proceedings of the AACR Special Conference: Precision Prevention, Early Detection, and Interception of Cancer; 2022 Nov 17-19; Austin, TX. Philadelphia (PA): AACR; Can Prev Res 2023;16(1 Suppl): Abstract nr IA022.
Abstract P031: Glycerolipid metabolism is a key early-detection biomarker for spontaneous ovarian cancer onset
Authors: Ellwood Kathryn , Taylor Ashley , Dutta Aditya 
Published: January 2023

Abstract
Ovarian cancer (OVC) is the fifth leading cause of cancer death in women and the most lethal gynecological cancer due to its inability to be diagnosed early. OVC is very treatable in its early stages, however, it is usually not identified until it’s at a later stage and survivability is low. Early symptoms of OVC such as abdominal pain, bloating, and changes in diet or bathroom habits are nonspecific and thus OVC is a challenge to diagnose early. Identification of early-detection blood biomarker(s) will allow for quicker and more informed treatment decisions and have a direct bearing on enhancing the survival rate. To this end, we use the chicken model of OVC to model spontaneous human OVC initiation and progression. Egg-laying hens develop OVC in much the same way as humans do; spontaneously and without known genetic predisposition. The layer hen has a fully sequenced genome with ~60% gene correspondence and ~99% gene similarity to humans. This combined with reproductive similarities to humans such as repetitive ovulation, gene function, and ovarian cellular makeup are what have validated the hen as an accurate model for OVC study. Moreover, disease presentation and disease grade are highly similar across the two species. Monthly blood draws were performed on specific-pathogen-free (SPF) hens during their entire lifecycle from reproductive prime to spontaneous development of OVC. Blood plasma from young, high laying hens (exhibiting repetitive ovulation, similar to the reproductive prime in women) and older, low-laying hens (those with slowing ovulation, similar to menopausal women) were analyzed for ~550 different metabolites using mass spectrometry. Glycerolipid metabolism was identified as a key early indicator of ovarian health. OVC requires lipid-rich nutrients for growth and spread, as is seen with metastasis often occurring to the omentum, a fat-rich organ. Our results also revealed that steroid biosynthesis was another major pathway in differentiating the cohorts. Upregulated fatty acid metabolism and regulation are associated with increased risk of cancer development as they have roles in cell support, structure, and signaling. Uncovering these early-stage diagnostic and prognostic biomarkers will have a direct bearing on enhancing patient survival rates and improve quality of life.
Citation Format: Kathryn Ellwood, Ashley Taylor, Aditya Dutta. Glycerolipid metabolism is a key early-detection biomarker for spontaneous ovarian cancer onset. [abstract]. In: Proceedings of the AACR Special Conference: Precision Prevention, Early Detection, and Interception of Cancer; 2022 Nov 17-19; Austin, TX. Philadelphia (PA): AACR; Can Prev Res 2023;16(1 Suppl): Abstract nr P031.