bluuebunny/crossref_metadata_2025_split huggingface dataset:
Discovery of novel DNA methylation biomarker panels for the diagnosis and differentiation between common adenocarcinomas and their liver metastases
Authors: Draškovič Tina , Hauptman Nina 
Published: February 2024

AbstractDifferentiation between adenocarcinomas is sometimes challenging. The promising avenue for discovering new biomarkers lies in bioinformatics using DNA methylation analysis. Utilizing a 2853-sample identification dataset and a 782-sample independent verification dataset, we have identified diagnostic DNA methylation biomarkers that are hypermethylated in cancer and differentiate between breast invasive carcinoma, cholangiocarcinoma, colorectal cancer, hepatocellular carcinoma, lung adenocarcinoma, pancreatic adenocarcinoma and stomach adenocarcinoma. The best panels for cancer type exhibit sensitivity of 77.8–95.9%, a specificity of 92.7–97.5% for tumors, a specificity of 91.5–97.7% for tumors and normal tissues and a diagnostic accuracy of 85.3–96.4%. We have shown that the results can be extended from the primary cancers to their liver metastases, as the best panels diagnose and differentiate between pancreatic adenocarcinoma liver metastases and breast invasive carcinoma liver metastases with a sensitivity and specificity of 83.3–100% and a diagnostic accuracy of 86.8–91.9%. Moreover, the panels could detect hypermethylation of selected regions in the cell-free DNA of patients with liver metastases. At the same time, these were unmethylated in the cell-free DNA of healthy donors, confirming their applicability for liquid biopsies.
ZFP36 disruption is insufficient to enhance the function of mesothelin-targeting human CAR-T cells
Authors: Mai David , Boyce Tifara , Mehta Aakash , Reff Jordan , Scholler John , Sheppard Neil C. , June Carl H. 
Published: February 2024

AbstractLoss of inflammatory effector function, such as cytokine production and proliferation, is a fundamental driver of failure in T cell therapies against solid tumors. Here, we used CRISPR/Cas9 to genetically disrupt ZFP36, an RNA binding protein that regulates the stability of mRNAs involved in T cell inflammatory function, such as the cytokines IL2 and IFNγ, in human T cells engineered with a clinical-stage mesothelin-targeting CAR to determine whether its disruption could enhance antitumor responses. ZFP36 disruption slightly increased antigen-independent activation and cytokine responses but did not enhance overall performance in vitro or in vivo in a xenograft tumor model with NSG mice. While ZFP36 disruption does not reduce the function of CAR-T cells, these results suggest that singular disruption of ZFP36 is not sufficient to improve their function and may benefit from a multiplexed approach.
History of the streptothricin antibiotics and evidence for the neglect of the streptothricin resistome
Authors: Franck Ezabelle , Crofts Terence S. 
Published: February 2024

AbstractThe streptothricin antibiotics were among the first antibiotics to be discovered from the environment and remain some of the most recovered antimicrobials in natural product screens. Increasing rates of antibiotic resistance and recognition that streptothricin antibiotics may play a role in countering so-called super-bugs has led to the re-evaluation of their clinical potential. Here we will review the current state of knowledge of streptothricins and their resistance in bacteria, with a focus on the potential for new resistance mechanisms and determinants to emerge in the context of potential widespread clinical adoption of this antibiotic class.
Feasibility of an Adaptive Version of the Everyday Conversational Sentences in Noise Test
Authors: Miles Kelly , Best Virginia , Buchholz Jörg M. 
Published: February 2024

Purpose:To investigate potential reasons for the mismatch between laboratory/clinic-based sentence-in-noise performance and real-world listening abilities, we recently developed a corpus of natural, spontaneously spoken speech with three vocal effort levels (Everyday Conversational Sentences in Noise [ECO-SiN]). Here, we examined the feasibility of using the ECO-SiN corpus for adaptive speech-in-noise testing, which might be a desirable format in certain situations (e.g., during a clinical visit).Method:Ten young, normal-hearing adults, along with 20 older adults with hearing loss participated in the study. Speech reception thresholds (SRTs) were obtained using ECO-SiN sentences, which were systematically compared to the SRTs obtained using traditional Bamford-Kowal-Bench–like sentences.Results:Results demonstrated the properties of the test compared favorably with those of a standard test based on scripted and clearly spoken sentences. Moreover, whereas normal-hearing listeners received a benefit from an increase in vocal effort, the participants with hearing loss showed a disbenefit that increased with increasing hearing loss.Conclusion:The adaptive version of the ECO-SiN test is feasible for research and clinical testing.Supplemental Material:https://doi.org/10.23641/asha.25146338
Reduced Interhemispheric Coherence and Cognition in Children with Fetal Alcohol Spectrum Disorder (FASD)—A Quantitative EEG Study
Authors: Gerstner Thorsten , Henning Oliver , Løhaugen Gro , Skranes Jon 
Published: February 2024

Abstract
Background Magnetic resonance imaging in fetal alcohol spectrum disorder (FASD) children showed altered connectivity, suggesting underlying deficits in networks, which may be related to cognitive outcome. Functional connectivity has been of interest in neurophysiological research with quantitative electroencephalography (QEEG) as useful tool for measuring pathology, not detectable by normal EEG. The aim of this study was to investigate differences in the EEG interhemispheric coherence (ICoh) in children diagnosed with FASD compared with healthy controls and to relate the results to cognitive scores.
Method Analysis of ICoh in 81 FASD children (4-Digit Code) compared with 31 controls. The children underwent cognitive assessment, and EEG was performed and used for analysis. Group comparisons and analysis of covariance interaction models were used to test for differences between FASD and controls but also to look for differences between FASD subgroups. Significant findings were correlated to cognitive scores.
Results Lower ICoh was found in the frontal and temporal derivations in the FASD group. When comparing FASD subgroups, children with fetal alcohol syndrome had lower ICoh occipital. Reduced ICoh in the temporal alpha band was correlated with lower performance IQ in the FASD group.
Conclusion Our findings could imply hypoconnectivity between the hemispheres with impact on cognition. We suggest that EEG coherence analysis could be a sensitive parameter in the detection of electrophysiological abnormalities in FASD with possible clinical relevance. These results may indicate that QEEG could be used as biomarker for FASD. However, further research is needed to determine the role of QEEG analysis in the diagnosis of FASD.
Impact of Age on the Relationship between Cross-Clamp Time and Mortality in Cardiac Surgery
Authors: Mukharyamov Murat , Kirov Hristo , Caldonazo Tulio , Doenst Torsten 
Published: February 2024

AbstractAge is an independent risk factor for mortality even when all known comorbidities are considered. Thus, other factors may additionally contribute to the age-associated risk. We performed a systematic literature search and identified 161 manuscripts, of which 32 studies (18,256 patients) were analyzed. Cross-clamp time correlated with observed mortality. The increase in mortality risk with cross-clamp time was much greater in older patients than in younger patients. The log odds ratio (OR) for age and cross-clamp time was 0.07 and 0.01, respectively, which was highly significant for both independent risk factors. Age accelerates the increase in mortality risk with increasing aortic cross-clamp times.
Oncologic outcomes of screen-detected and non-screen-detected T1 colorectal cancers
Authors: Laclé Miangela M. , Moons Leon M. G. , van der Schee Lisa , Haasnoot Krijn J. C. , Elias Sjoerd G. , Gijsbers Kim M. , Alderlieste Yasser A. , Backes Yara , van Berkel Anne-Marie , Boersma Femke , ter Borg Frank , Breekveldt Emilie C.H. , Kessels Koen , Koopman Miriam , Lansdorp-Vogelaar Iris , van Leerdam Monique E. , Rasschaert Gertjan , Schreuder Ramon-Michel , Schrauwen Ruud W.M. , Seerden Tom C.J. , Spanier Marcel B.W. , Terhaar sive Droste Jochim S. , Toes-Zoutendijk Esther , Tuynman Jurriaan B. , Vink Geraldine R. , de Vos tot Nederveen Cappel Wouter H. , Vleggaar Frank P. 
Published: February 2024

Abstract
Background The incidence of T1 colorectal cancer (CRC) has increased with the implementation of CRC screening programs. It is unknown whether the outcomes and risk models for T1 CRC based on non-screen-detected patients can be extrapolated to screen-detected T1 CRC. This study aimed to compare the stage distribution and oncologic outcomes of T1 CRC patients within and outside the screening program.
Methods Data from T1 CRC patients diagnosed between 2014 and 2017 were collected from 12 hospitals in the Netherlands. The presence of lymph node metastasis (LNM) at diagnosis was compared between screen-detected and non-screen-detected patients using multivariable logistic regression. Cox proportional hazard regression was used to analyze differences in the time to recurrence (TTR), metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival. Additionally, the performance of conventional risk factors for LNM was evaluated across the groups.
Results 1803 patients were included (1114 [62%] screen-detected), with median follow-up of 51 months (interquartile range 30). The proportion of LNM did not significantly differ between screen- and non-screen-detected patients (12.6% vs. 8.9%; odds ratio 1.41; 95%CI 0.89–2.23); a prediction model for LNM performed equally in both groups. The 3- and 5-year TTR, MFS, and CSS were similar for patients within and outside the screening program. However, overall survival was significantly longer in screen-detected T1 CRC patients (adjusted hazard ratio 0.51; 95%CI 0.38–0.68).
Conclusions Screen-detected and non-screen-detected T1 CRCs have similar stage distributions and oncologic outcomes and can therefore be treated equally. However, screen-detected T1 CRC patients exhibit a lower rate of non-CRC-related mortality, resulting in longer overall survival.
Noninvasive diagnostic imaging of pelvic venous disorders
Authors: Szkodziak Filip , Wozniak Slawomir , Szkodziak Piotr Robert , Pyra Krzysztof , Paszkowski Tomasz 
Published: February 2024

AbstractIt is estimated that chronic pelvic pain (CPP) may affect up to 24% of women. Unfortunately, very often, despite extensive diagnostics, the cause of CPP remains unknown. The pathophysiology of CPP could be explained to a large extent by the occurrence of pelvic venous disorders (PVD). Although pelvic venography is still considered the gold standard for the diagnosis of PVD, noninvasive diagnostic imaging techniques seem to be instrumental in the initial identification of patients with PVD. This literature review aimed to analyze and evaluate the usefulness of noninvasive diagnostic imaging techniques like transvaginal ultrasonography, transabdominal ultrasonography, magnetic resonance, and computed tomography in the diagnosis and identification of patients with PVD. Forty-one articles published between 1984 and 2023 were included in this literature review. Based on this literature review, we conclude that the clinical application of noninvasive diagnostic techniques in the diagnosis of PVD seems to be very promising. Future studies investigating the role of noninvasive diagnostic imaging techniques in the diagnosis of PVD are required.
487 - Adult atopic dermatitis is associated with impaired oral health and oral dysbiosis - a case-control study
Authors: Shahin Aaya , Leshem Yael A , Taieb Yossi , Baum Sharon , Barzilai Aviv , Jedda Danielle , Sharon Efrat , Koren Omry , Coppenhagen-Glazer Shunit , Hazan Ronen , Houri-Haddad Yael , Greenberger Shoshana 
Published: February 2024

Abstract

Background
Previous studies linked chronic oral diseases to skin disorders such as psoriasis. However, data about oral health and oral microbiota in atopic dermatitis (AD) is sparse.

Objectives
To compare the oral health status and oral microbiota of AD patients and healthy controls.

Methods
This was a prospective sex and age- matched case-control study comparing adult participants with and without dermatologist-verified AD. Exclusion criteria included recent use of oral, topical, or systemic medication that could affect oral health or microbiome assessment. Oral health indices including Gingival Index, Plaque Index, Oral Hygiene Index, Caries Severity Index and prosthodontics status, were assessed by a dentist. Samples of oral flora were collected and subjected to high-throughput 16S rRNA gene sequencing analysis for microbiome analysis.

Results
Forty-five AD participants and 41 non-AD controls were recruited. The two groups had no significant differences in terms of their demographic and clinical characteristics, except for the higher rate of atopic co-morbidities in the AD group (p&lt;.001). Compared to the control group, participants with AD had significantly poorer plaque (p=0.04) and oral hygiene indices (p=0.04) and a trend towards higher gingival index (p=0.05). The results of the Faith phylogenetic diversity (FDR) test indicated that the oral microbial diversity in the AD group was significantly higher (α-diversity, FDR-adjusted p=0.0007) when compared with the control group. Characterization of the similarities and differences in the composition of the microbial communities between the samples (β-diversity) from the AD patients and controls indicated that they clustered separately. The groups showed significant dissimilarity and distinct clustering of microbial abundance (FDR-adjusted p=0.001). Importantly, higher community diversity was previously linked to periodontitis and gingival disease. Furthermore, AD patients had a significantly increased abundance of taxa correlated with oral diseases and decreased abundance of oral health-associated bacteria.

Conclusion
AD appears to be associated with poorer oral health and oral dysbiosis, and thus, there is a need to increase the awareness of both patients and physicians about oral health.
524 - Efficacy of upadacitinib and dupilumab on achieving stringent and composite skin and itch outcomes: an indirect comparison of adults with moderate-to-severe atopic dermatitis
Authors: Armstrong April W , Hong H Chih-Ho , Calimlim Brian M , Buessing Marric G , Crowell Marjorie M , Silverberg Jonathan I 
Published: February 2024

Abstract

Introduction/Background
Efficacy of upadacitinib has been assessed in trials including Measure Up 1 (NCT03569293), Measure Up 2 (NCT03607422), and Heads Up (NCT03738397). Measure Up 1 and Measure Up 2 assessed efficacy of upadacitinib 30mg and upadacitinib 15mg against placebo, while Heads Up assessed efficacy of upadacitinib 30mg in a head-to-head trial against dupilumab 300mg. Network meta-analysis has shown that upadacitinib 30mg and upadacitinib 15mg are among the most efficacious targeted systemic therapies, but prior indirect comparisons have not evaluated stringent and composite measures of efficacy.

Objectives
To indirectly compare upadacitinib and dupilumab on stringent and composite measures of skin clearance and itch resolution.

Methods
A population-adjusted indirect comparison using covariate adjustment as a treatment effect calibration was conducted using individual patient data from Measure Up 1 and 2 and Heads Up. Specifically, the indirect comparison model estimated how upadacitinib 15 mg would have performed if included in Heads Up by adjusting for patient-level covariates (age, gender, race, country, previous use of systemic therapy, disease duration, baseline validated Investigator Global Assessment scale for AD score, and baseline Eczema Area and Severity Index [EASI]). Absolute response rates at weeks 4 and 16 were estimated for the following outcomes: no/minimal itch (Worst Pruritus Numerical Rating Scale [WP-NRS] score of 0/1), 100% improvement in EASI (EASI 100), achievement of both ≥90% improvement in EASI (EASI 90) and WP-NRS 0/1, and achievement of both EASI 100 and WP-NRS 0/1. The analysis was conducted on adult patients, aligned with the intention-to-treat population for the clinical trials, and utilized non-responder imputation.

Results
Across all outcomes assessed, the estimated absolute response rates were greatest for upadacitinib 30 mg, followed by upadacitinib 15 mg, and then dupilumab. This pattern was observed at week 4 on the achievement of WP-NRS 0/1 (upadacitinib 30 mg: 34.2% | upadacitinib 15 mg: 18.2% | dupilumab: 7.9%), EASI 100 (8.5% | 4.7% | 1.8%), EASI 90 & WP-NRS 0/1 (21.9% | 10.6% | 3.3%), and EASI 100 & WP-NRS 0/1 (6.4% | 3.5% | 1.2%). This ranking was maintained at week 16 for WP-NRS 0/1 (35.4% | 22.5% | 16.2%), EASI 100 (28.4% | 22.2% | 7.9%), EASI 90 & WP-NRS 0/1 (32.2% | 19.6% | 12.4%), and EASI 100 & WP-NRS 0/1 (19.6% | 12.7% | 4.2%).

Conclusions
For adults with moderate-to-severe AD, upadacitinib 30 mg appears to be the most efficacious treatment in attaining stringent and composite outcomes after 4 and 16 weeks, followed by upadacitinib 15 mg, and then dupilumab.
526 - Efficacy of upadacitinib vs dupilumab for moderate-to-severe atopic dermatitis: analysis of time spent in itch response state from the Heads Up study
Authors: Blauvelt Andrew , de Bruin-Weller Marjolein , Kwatra Shawn G , Gooderham Melinda J , Kim Brian , Liu Yingyi , Chu Alvina D , Ofori Sarah , Platt Andrew , Calimlim Brian M , Silverberg Jonathan I 
Published: February 2024

Abstract

Introduction/Background
Atopic dermatitis is a chronic inflammatory skin disease characterized by intense and debilitating pruritus – its most burdensome symptom – and requires long-term control. Results from the Heads Up trial (NCT03738397) found that upadacitinib (UPA) 30 mg was superior to dupilumab (DUPI) 300 mg for improving itch as indicated by increases in the percent of improvement from baseline for Worst Pruritus NRS scores (WP-NRS).

Objective
This analysis compared the proportion of days patients treated with UPA or DUPI spent in itch response states indicated by WP-NRS.

Methods
Heads Up was a 24-week head-to-head phase 3b multicenter, randomized, double-blind study comparing UPA 30 mg to DUPI 300 mg in adults with moderate-to-severe AD. We compared the proportion of days patients treated with UPA or DUPI spent in an improved-itch state (WP-NRS improvement ≥4 relative to baseline; among patients with baseline WP-NRS ≥4) or a state of no/minimal itch (WP-NRS 0/1; among patients with baseline WP-NRS &gt;1).

Results
Participants included 673 patients randomized into two groups: those taking UPA (N=342) or DUPI (N=331). At 4 and 16 weeks, patients treated with UPA vs DUPI spent a greater proportion of days in an improved-itch state (week 4: 50.0% vs 19.3%; week 16: 60.4% vs 35.7%), and in a state of no/minimal itch (week 4: 22.1% vs 4.3%; week 16: 34.4% vs 11.4%).

Conclusions
Treatment of moderate-to-severe AD with UPA 30 mg daily resulted in a greater proportion of days spent with meaningful itch improvement (WP-NRS improvement ≥4) and more time with no/minimal itch (WP-NRS 0/1) compared to treatment with DUPI over 4 and 16 weeks.
544 - Cost-per-responder analysis of tralokinumab versus dupilumab in patients with moderate-to-severe atopic dermatitis in the US and Canada
Authors: Wu Jashin J , Balu Sanjeev , Larsen Nikolaj Birk , Pulleyblank Ryan , Strømkjær Liv , Quah Aron , Wiseman Marni 
Published: February 2024

Abstract

Introduction/Background
Biologic treatments such as tralokinumab and dupilumab are therapeutic options for adult patients with moderate-to-­severe atopic dermatitis (AD) who do not achieve adequate control with topical treatments or phototherapy. To date, no trials have been conducted to directly evaluate the relative efficacy of these biologic treatments.

Objectives
Applying indirect comparison of efficacy, we examined the cost-per-responder of tralokinumab compared to dupilumab in combination with topical corticosteroids (TCS) for the treatment of moderate-to-serve AD in the United States (US) and Canada.

Methods
A cost-per-responder analysis was undertaken considering the Eczema Area and Severity Index 75 (EASI-75) and Investigator’s Global Assessment (IGA-0/1) response criteria over a 32-week period. For each treatment, the cost-per-­responder was computed by multiplying the treatment cost by the number needed to treat (NNT). Efficacy data were derived from an unanchored matching-adjusted indirect comparison (MAIC) utilizing patient-level data from ECZTRA-3 (tralokinumab) and aggregate data from LIBERTY AD CHRONOS (dupilumab). Treatment cost was defined as the drug cost of the biologic treatment with a duration corresponding to 32 weeks. TCS cost was not considered. Treatments were assumed to be administered every 2 weeks (Q2W). The costs were estimated based on Wholesale Acquisition Costs (WAC) from the US and ex-factory prices via the McKesson price list for Canada. All prices were converted to US dollars ($). Sensitivity analyses (SA) were conducted with every 4 week (Q4W) dosing beginning at week 16 for 10% and 20% of patients treated with tralokinumab.

Results
For the US, the average cost-per-responder was $62,714 (Q4W SA: 10%: $61,239; 20%: $59,763) for tralokinumab versus $63,993 for dupilumab considering the EASI-75 response criteria, while the average cost-per-responder was $82,419 (Q4W SA: 10%: $80,480; 20%: $78,450) for tralokinumab versus $118,835 for dupilumab considering the IGA 0/1 response criteria. For Canada, the average cost-per-responder was $22,846 (Q4W SA: 10%: $22,308; 20%: $21,771) for tralokinumab versus $26,475 for dupilumab considering the EASI-75 response criteria, while the average cost-per-responder was $30,024 (Q4W SA: 10%: $29,317; 20%: $28,611) for tralokinumab versus $49,165 for dupilumab considering the IGA 0/1 response criteria.

Conclusions
Assessing EASI-75 and IGA-0/1 response criteria at 32 weeks, this analysis indicates that tralokinumab in combination with TCS is associated with lower costs-per-responder compared with dupilumab in combination with TCS in the treatment of moderate-to-severe AD in the US and Canada.