bluuebunny/crossref_metadata_2025_split huggingface dataset:
PI3Kδ activation, IL-6 overexpression, and CD37 loss cause resistance to naratuximab emtansine in lymphomas
Authors: Arribas Alberto J. , Napoli Sara , Gaudio Eugenio , Herbaux Charles , Cannas Eleonora , Tarantelli Chiara , Bordone-Pittau Roberta , Cascione Luciano , Munz Nicolas , Aresu Luca , Sgrignani Jacopo , Rinaldi Andrea , Kwee Ivo , Rossi Davide , Cavalli Andrea , Zucca Emanuele , Stussi Georg , Stathis Anastasios , Sloss Callum , Davids Matthew S. , Bertoni Francesco 
Published: October 2024

Abstract
CD37-directed antibody and cellular-based approaches have shown preclinical and promising early clinical activity. Naratuximab emtansine (Debio 1562; IMGN529) is an antibody-drug conjugate (ADC) incorporating an anti-CD37 monoclonal antibody conjugated to the maytansinoid DM1 as payload, with activity as a single agent and in combination with rituximab in patients with lymphoma. We studied naratuximab emtansine and its free payload in 54 lymphoma models, correlated its activity with CD37 expression, characterized two resistance mechanisms, and identified combination partners providing synergy. The activity, primarily cytotoxic, was more potent in B- than T-cell lymphoma cell lines. After prolonged exposure to the ADC, one diffuse large B-cell lymphoma (DLBCL) cell line developed resistance to the ADC due to the CD37 gene biallelic loss. After CD37 loss, we also observed upregulation of interleukin-6 (IL-6) and related transcripts. Recombinant IL-6 led to resistance. Anti-IL-6 antibody tocilizumab improved the ADC’s cytotoxic activity in CD37+ cells. In a second model, resistance was sustained by a PIK3CD activating mutation, with increased sensitivity to PI3Kδ inhibition and a functional dependence switch from MCL1 to BCL2. Adding idelalisib or venetoclax overcame resistance in the resistant derivative and improved cytotoxic activity in the parental cells. In conclusion, targeting B-cell lymphoma with the naratuximab emtansine showed vigorous antitumor activity as a single agent, which was also observed in models bearing genetic lesions associated with inferior outcomes, such as Myc Proto-Oncogene (MYC) translocations and TP53 inactivation or R-CHOP (rituximab, cyclophosphamide, doxorubicin, Oncovin [vincristine], and prednisone) resistance. Resistant DLBCL models identified active combinations of naratuximab emtansine with drugs targeting IL-6, PI3Kδ, and BCL2.
Measurable residual disease as predictor of post–day +100 relapses after allografting in adult AML
Authors: Ali Naveed , Othus Megan , Rodríguez-Arbolí Eduardo , Orvain Corentin , Milano Filippo , Sandmaier Brenda M. , Davis Chris , Basom Ryan S. , Appelbaum Frederick R. , Walter Roland B. 
Published: October 2024

Abstract
Measurable residual disease (MRD) by multiparametric flow cytometry (MFC) before allogeneic hematopoietic cell transplantation (HCT) identifies patients at high risk of acute myeloid leukemia (AML) relapse, often occurring early after allografting. To examine the role of MFC MRD testing to predict later relapses, we examined 935 adults with AML or myelodysplastic neoplasm/AML transplanted in first or second morphologic remission who underwent bone marrow restaging studies between day 70 and 100 after HCT and were alive and without relapse by day +100. Of 935 adults, 136 (15%) had MRD before HCT, whereas only 11 (1%) had MRD at day +70 to +100. In day +100 landmark analyses, pre-HCT and day +70 to +100 MFC MRD were both associated with relapse (both P &lt; .001), relapse-free survival (RFS; both P &lt; .001) overall survival (OS; both P &lt; .001), and, for post-HCT MRD, nonrelapse mortality (P = .001) after multivariable adjustment. Importantly, although 126/136 patients (92%) with MRD before HCT tested negative for MRD at day +70 to +100, their outcomes were inferior to those without MRD before HCT and at day +70 to +100, with 3-year relapse risk of 40% vs 15% (P &lt; .001), 3-year RFS of 50% vs 72% (P &lt; .001), and 3-year OS of 56% vs 76% (P &lt; .001), whereas 3-year nonrelapse mortality estimates were similar (P = .53). Thus, despite high MRD conversion rates, outcomes MRD positive/MRD negative (MRDneg) patients are inferior to those of MRDneg/MRDneg patients, suggesting all patients with pre-HCT MRD should be considered for preemptive therapies after allografting.
The effectiveness of simulation-based learning (SBL) on students’ knowledge and skills in nursing programs: a systematic review
Authors: Alharbi Ali , Nurfianti Arina , Mullen Rosemary F. , McClure John D. , Miller William H. 
Published: October 2024

Abstract
Background
Simulation-Based Learning (SBL) serves as a valuable pedagogical approach in nursing education, encompassing varying levels of fidelity. While previous reviews have highlighted the potential effectiveness of SBL in enhancing nursing students’ competencies, a gap persists in the evidence-base addressing the long-term retention of these competencies. This systematic review aimed to evaluate the impact of SBL on nursing students’ knowledge and skill acquisition and retention.

Method
A comprehensive search of electronic databases, including CINAHL, PubMed, Embase, Scopus, and Eric, was conducted from 2017 to 2023 to identify relevant studies. The Joanna Briggs critical appraisal tools were used to assess the methodological quality of the included studies. A total of 33 studies (15 RCTs and 18 quasi-experimental) met the inclusion criteria and were included in the review. A descriptive narrative synthesis method was used to extract relevant data.

Results
The cumulative sample size of participants across the included studies was 3,670. Most of the studies focused on the impact of SBL on life-saving skills like cardiopulmonary resuscitation (CPR) or other life-support skills. The remaining studies examined the impact of SBL on critical care skills or clinical decision-making skills. The analysis highlighted consistent and significant improvements in knowledge and skills. However, the evidence base had several limitations, including the heterogeneity of study designs, risk of bias, and lack of long-term follow-up.

Conclusion
This systematic review supports the use of SBL as a potent teaching strategy within nursing education and highlights the importance of the ongoing evaluation and refinement of this approach. While current evidence indicates enhancing knowledge and skill acquisition, limited studies evaluated the retention beyond five months, constraining generalisable claims regarding durability. Further research is essential to build on the current evidence and address gaps in knowledge related to the retention, optimal design, implementation, and evaluation of SBL interventions in nursing education.
Quantifying the magnitude of the general contextual effect in a multilevel study of SARS-CoV-2 infection in Ontario, Canada: application of the median rate ratio in population health research
Authors: Watson Tristan , Kwong Jeffrey C. , Kornas Kathy , Mishra Sharmistha , Rosella Laura C. 
Published: October 2024

Abstract
Background
Regional variations in SARS-CoV-2 infection were observed in Canada and other countries. Studies have used multilevel analyses to examine how a context, such as a neighbourhood, can affect the SARS-CoV-2 infection rates of the people within it. However, few multilevel studies have quantified the magnitude of the general contextual effect (GCE) in SARS-CoV-2 infection rates and assessed how it may be associated with individual- and area-level characteristics. To address this gap, we will illustrate the application of the median rate ratio (MRR) in a multilevel Poisson analysis for quantifying the GCE in SARS-CoV-2 infection rates in Ontario, Canada.

Methods
We conducted a population-based, two-level multilevel observational study where individuals were nested into regions (i.e., forward sortation areas [FSAs]). The study population included community-dwelling adults in Ontario, Canada, between March 1, 2020, and May 1, 2021. The model included seven individual-level variables (age, sex, asthma, diabetes, hypertension, congestive heart failure, and chronic obstructive pulmonary disease) and four FSA census-based variables (household size, household income, employment, and driving to work). The MRR is a median value of the rate ratios comparing two patients with identical characteristics randomly selected from two different regions ordered by rate. We examined the attenuation of the MRR after including individual-level and FSA census-based variables to assess their role in explaining the variation in rates between regions.

Results
Of the 11 789 128 Ontario adult community-dwelling residents, 343 787 had at least one SARS-CoV-2 infection during the study period. After adjusting for individual-level and FSA census-based variables, the MRR was attenuated to 1.67 (39% reduction from unadjusted MRR). The strongest FSA census-based associations were household size (RR = 1.88, 95% CI: 1.71–1.97) and driving to work (RR = 0.68, 95% CI: 0.65–0.71).

Conclusions
The individual- and area-level characteristics in our study accounted for approximately 40% of the between-region variation in SARS-CoV-2 infection rates measured by MRR in Ontario, Canada. These findings suggest that population-based policies to address social determinants of health that attenuate the MRR may reduce the observed between-region heterogeneity in SARS-CoV-2 infection rates.
Research training during radiology residency: findings from the ESR Radiology Trainee Forum survey
Authors: Klontzas Michail E. , Reim Martin , Afat Saif , Podzniakova Viktoria , Snoeckx Annemiek , Becker Minerva ,   European Society of Radiology (ESR)
Published: October 2024

Abstract
Objectives
To elucidate the research training exposure of radiology residents across ESR country members.

Methods
A 30-question survey was constructed by the Radiology Trainee Forum and was distributed among residents and subspecialty fellows of countries members of the ESR. The survey examined the training environment, the status of research training and publications among trainees, the conditions under which research was conducted, and the exposure to activities such as grant proposal preparation and manuscript reviewing. Descriptive statistics and the chi-square test were used to assess the responses to survey questions and evaluate factors related to these responses.

Results
A total of 159 participants from 29 countries provided fully completed questionnaires. Only 12/159 trainees already had a PhD degree and nearly half had never published a PubMed-indexed manuscript (76/159, 47.8%). Among those who published their papers during radiology training, most did so in the first or second year of residency (n = 26 and n = 20 participants, respectively). Most participants (79%) did not receive further statistical training during residency, fifty-five out of 159 (34.59%) respondents never had any guidance/training on how to read a paper and 58 out of 159 (36.48%) had never been encouraged to participate in any research. Most of them had worked after hours to carry out research at least a few times (47/159, 29.56%) or always (82/159, 51.57%).

Conclusion
Analysis of research training among radiology trainees was performed. Areas for improvement were identified that can prompt changes in training curricula to prepare a highly competent European workforce.

Critical relevance statement
This survey has identified deficits in research training of radiology residents across countries members of ESR, pinpointing areas for improvement to fortify the future of radiology in Europe.

Key Points

Research exposure and training of radiology residents varies across countries and members of ESR.

Radiology residents largely lack systematic research training, dedicated research time, and guidance.

Areas for improvement in research training of radiology residents have been identified, aiding the fortification of radiology research across Europe.

Graphical Abstract
Clinical implications of CT-detected ascites in gastric cancer: association with peritoneal metastasis and systemic inflammatory response
Authors: Xu Mengying , Liu Dan , Wang Le , Sun Shuangshuang , Liu Song , Zhou Zhengyang 
Published: October 2024

Abstract
Objectives
This study aimed to evaluate the diagnostic significance of computed tomography (CT) detected ascites in gastric cancer (GC) with peritoneal metastasis (PM) and investigate its association with systemic inflammatory response.

Methods
This retrospective study included 111 GCs with ascites (PM: n = 51; No PM: n = 60). Systemic inflammatory indexes, tumor markers, and the CT-assessed characteristics of ascites were collected. The differences in parameters between the two groups were analyzed. Diagnostic performance was obtained by receiver operating characteristic curve analysis. The association between the volume of ascites and clinical characteristics was evaluated with correlation analysis.

Results
In this study, over half of GCs with ascites were not involved with PM. The systemic immune-inflammation index (SII), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), five tumor markers, and the characteristics of ascites showed significant differences between the two groups (all p < 0.05). Among them, SII, NLR, PLR, and the volume of ascites achieved the areas under the curve of 0.700, 0.698, 0.704, and 0.903, respectively. Moreover, the volumes of ascites showed positive correlations with SII, NLR, and PLR in GCs with PM, and the volumes of ascites detected in the upper abdomen were more strongly correlated with CA125 level (all p < 0.05).

Conclusion
Many GCs with CT-detected ascites did not occur with synchronous PM. The presence of upper abdominal ascites had certain clinical significance for diagnosing PM in GCs. Systemic inflammatory indexes were elevated and positively correlated with the volume of ascites in GCs with PM, which might suggest the enhanced systemic inflammatory response.

Critical relevance statement
CT-detected ascites in the upper abdomen played an indicative role in identifying synchronous PM in GCs, and the systemic inflammatory response was enhanced in GCs with PM, which might be helpful for clinical evaluation.

Key Points

Many GCs with CT-detected ascites did not occur with synchronous PM.

CT-detected ascites in the upper abdomen help in identifying PM in GCs.

GCs with PM showed elevated systemic inflammatory indexes and enhanced systemic inflammatory response.

Graphical Abstract
Female-bias in systemic lupus erythematosus: How much is the X chromosome to blame?
Authors: Vieira Adriana A. , Almada-Correia Inês , Inácio Joana , Costa-Reis Patrícia , da Rocha S. T. 
Published: October 2024

AbstractSystemic lupus erythematosus (SLE or lupus) is an immune-mediated disease associated with substantial medical burden. Notably, lupus exhibits a striking female bias, with women having significantly higher susceptibility compared to men, up to 14-fold higher in some ethnicities. Supernumerary X chromosome syndromes, like Klinefelter (XXY) and Triple X syndrome (XXX), also present higher SLE prevalence, whereas Turner syndrome (XO) displays lower prevalence. Taken together, SLE prevalence in different X chromosome dosage sceneries denotes a relationship between the number of X chromosomes and the risk of developing lupus. The dosage of X-linked genes, many of which play roles in the immune system, is compensated between males and females through the inactivation of one of the two X chromosomes in female cells. X-chromosome inactivation (XCI) initiates early in development with a random selection of which X chromosome to inactivate, a choice that is then epigenetically maintained in the daughter cells. This process is regulated by the X-Inactive-Specific Transcript (XIST), encoding for a long non-coding RNA, exclusively expressed from the inactive X chromosome (Xi). XIST interacts with various RNA binding proteins and chromatin modifiers to form a ribonucleoprotein (RNP) complex responsible for the transcriptional silencing and heterochromatinization of the Xi. This ensures stable silencing of most genes on the X chromosome, with only a few genes able to escape this process. Recent findings suggest that the molecular components involved in XCI, or their dysregulation, contribute to the pathogenesis of lupus. Indeed, nonrandom XCI, elevated gene escape from XCI, and the autoimmune potential of the XIST RNP complex have been suggested to contribute to auto-immune diseases, such as lupus. This review examines these current hypotheses concerning how this dosage compensation mechanism might impact the development of lupus, shedding light on potential mechanisms underlying the pathogenesis of the disease.
Bitter peptide prediction using graph neural networks
Authors: Srivastava Prashant , Steuer Alexandra , Ferri Francesco , Nicoli Alessandro , Schultz Kristian , Bej Saptarshi , Di Pizio Antonella , Wolkenhauer Olaf 
Published: October 2024

AbstractBitter taste is an unpleasant taste modality that affects food consumption. Bitter peptides are generated during enzymatic processes that produce functional, bioactive protein hydrolysates or during the aging process of fermented products such as cheese, soybean protein, and wine. Understanding the underlying peptide sequences responsible for bitter taste can pave the way for more efficient identification of these peptides. This paper presents BitterPep-GCN, a feature-agnostic graph convolution network for bitter peptide prediction. The graph-based model learns the embedding of amino acids in the bitter peptide sequences and uses mixed pooling for bitter classification. BitterPep-GCN was benchmarked using BTP640, a publicly available bitter peptide dataset. The latent peptide embeddings generated by the trained model were used to analyze the activity of sequence motifs responsible for the bitter taste of the peptides. Particularly, we calculated the activity for individual amino acids and dipeptide, tripeptide, and tetrapeptide sequence motifs present in the peptides. Our analyses pinpoint specific amino acids, such as F, G, P, and R, as well as sequence motifs, notably tripeptide and tetrapeptide motifs containing FF, as key bitter signatures in peptides. This work not only provides a new predictor of bitter taste for a more efficient identification of bitter peptides in various food products but also gives a hint into the molecular basis of bitterness.Scientific ContributionOur work provides the first application of Graph Neural Networks for the prediction of peptide bitter taste. The best-developed model, BitterPep-GCN, learns the embedding of amino acids in the bitter peptide sequences and uses mixed pooling for bitter classification. The embeddings were used to analyze the sequence motifs responsible for the bitter taste.
Alkali-Silica Reaction and Residual Mechanical Properties of High-Strength Mortar Containing Waste Glass Fine Aggregate and Supplementary Cementitious Materials
Authors: Eu Hamin , Kim Gyuyong , Son Minjae , Sasui Sasui , Lee Yaechan , Choi Hyeonggil , Kang Sukpyo , Nam Jeongsoo 
Published: October 2024

AbstractThis paper presents the influence of supplementary cementitious materials (SCMs), such as fly ash (FA), silica fume (SF), ground granulated blast furnace slag (GGBS), and waste glass fine aggregate (GA), on the alkali-silica reaction (ASR) in high-strength and normal-strength mortar using an accelerated mortar bar test (AMBT). Residual mechanical properties and scanning electron micrographs were used to assess the changes in the matrix. GA reduced the mechanical properties of both normal-strength (NGA_OPC) and high-strength mortars (HGA_OPC), contributing to a decline in overall performance. This phenomenon was a result of the slipping of the GA from the matrix owing to its smooth surface. However, the inclusion of reactive SF and GGBS in the HGA improved the slip phenomenon of the GA, leading to a significant enhancement in its mechanical properties. Following the ASR expansion measurement, HGA_OPC demonstrated an ASR expansion rate approximately three times higher than that of NGA_OPC. This was attributed to the dense structure of HGA_OPC, which resulted in greater expansion than that of NGA_OPC. However, with the incorporation of SCMs into both HGA and NGA, a significant reduction in ASR expansion was observed. This was attributed to the delayed ASR of GA due to alkali activation or the pozzolanic reaction of the SCMs. Continuous exposure to the AMBT environment can lead to the destruction of GA. This was caused by the inner ASR that originated from the surface crack of the GA, which resulted in a reduction in the flexural strength of the mortar. The HGA with SF exhibited the highest resistance to ASR expansion and residual mechanical properties’ degradation. Therefore, various durability and long-term performance-monitoring studies on ultra-high-performance concrete or high-strength cementitious composites with very high SF contents and GA can be conducted.
Viromes vs. mixed community metagenomes: choice of method dictates interpretation of viral community ecology
Authors: Kosmopoulos James C. , Klier Katherine M. , Langwig Marguerite V. , Tran Patricia Q. , Anantharaman Karthik 
Published: October 2024

Abstract
Background
Viruses, the majority of which are uncultivated, are among the most abundant biological entities on Earth. From altering microbial physiology to driving community dynamics, viruses are fundamental members of microbiomes. While the number of studies leveraging viral metagenomics (viromics) for studying uncultivated viruses is growing, standards for viromics research are lacking. Viromics can utilize computational discovery of viruses from total metagenomes of all community members (hereafter metagenomes) or use physical separation of virus-specific fractions (hereafter viromes). However, differences in the recovery and interpretation of viruses from metagenomes and viromes obtained from the same samples remain understudied.

Results
Here, we compare viral communities from paired viromes and metagenomes obtained from 60 diverse samples across human gut, soil, freshwater, and marine ecosystems. Overall, viral communities obtained from viromes had greater species richness and total viral genome abundances than those obtained from metagenomes, although there were some exceptions. Despite this, metagenomes still contained many viral genomes not detected in viromes. We also found notable differences in the predicted lytic state of viruses detected in viromes vs metagenomes at the time of sequencing. Other forms of variation observed include genome presence/absence, genome quality, and encoded protein content between viromes and metagenomes, but the magnitude of these differences varied by environment.

Conclusions
Overall, our results show that the choice of method can lead to differing interpretations of viral community ecology. We suggest that the choice of whether to target a metagenome or virome to study viral communities should be dependent on the environmental context and ecological questions being asked. However, our overall recommendation to researchers investigating viral ecology and evolution is to pair both approaches to maximize their respective benefits.