bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disease activity trajectories from childhood to adulthood in the population-based Nordic juvenile idiopathic arthritis cohort
Authors: Rypdal Veronika , Glerup Mia , Rypdal Martin , Arnstad Ellen , Aalto Kristiina , Berntson Lillemor , Fasth Anders , Herlin Troels , Myrup Charlotte , Peltoniemi Suvi , Rygg Marite , Nordal Ellen Berit 
Published: March 2024

ObjectivesTo identify long-term disease activity trajectories from childhood to adulthood by using the clinical Juvenile Arthritis Disease Activity Score (cJADAS10) in juvenile idiopathic arthritis (JIA). Second, to evaluate the contribution of the cJADAS10 components and explore characteristics associated with active disease at the 18-year follow-up.MethodsPatients with onset of JIA in 1997–2000 were followed for 18 years in the population-based Nordic JIA cohort. We used a discrete mixture model for longitudinal clustering of the cJADAS10 and its components. We assessed factors potentially associated with higher scores on the patient’s global assessment of well-being (PaGA) by hierarchical clustering and correlation analysis.ResultsFour disease activity trajectories were identified based on the cJADAS10 components among 427 patients. In trajectory-group 2, the PaGA and the physician’s global assessment of disease activity (PhGA) increased significantly during the course, but not the active joint count. The increase in the PaGA was significantly higher than the increases in the PhGA and the active joint count (p<0.0001). A similar pattern was found among all the patients with active disease in the total cohort. Patients with higher PaGA scores had unfavourable scores on several other patient-reported outcomes.ConclusionsWe have identified groups of patients based on long-term disease activity trajectories. In our study the PaGA was the most important driver of disease activity into adulthood assessed by cJADAS10. We need to better understand how our patients interpret global well-being and implement strategies to achieve inactive disease perceived both by the patient and the physician.
Failure rates of nonoperative management of low-grade splenic injuries with active extravasation: an Eastern Association for the Surgery of Trauma multicenter study
Authors: Spoor Kristen , Cull John David , Otaibi Banan W , Hazelton Joshua P , Chipko John , Reynolds Jessica , Fugate Sam , Pederson Claire , Zier Linda B , Jacobson Lewis E , Williams Jamie M , Easterday Thomas S , Byerly Saskya , Mentzer Caleb , Hawke Edward , Cullinane Daniel C , Ontengco Julianne B , Bugaev Nikolay , LeClair Madison , Udekwu Pascal , Josephs Cooper , Noorbaksh Matthew , Babowice James , Velopulos Catherine Garrison , Urban Shane , Goldenberg Anna , Ghobrial Gaby , Pickering John M , Quarfordt Steven D , Aunchman Alia F , LaRiccia Aimee K , Spalding Chance , Catalano Richard D , Basham Jordan E , Edmundson Philip M , Nahmias Jeffry , Tay Erika , Norwood Scott H , Meadows Katelyn , Wong Yee , Hardman Claire 
Published: March 2024

ObjectivesThere is little evidence guiding the management of grade I–II traumatic splenic injuries with contrast blush (CB). We aimed to analyze the failure rate of nonoperative management (NOM) of grade I–II splenic injuries with CB in hemodynamically stable patients.MethodsA multicenter, retrospective cohort study examining all grade I–II splenic injuries with CB was performed at 21 institutions from January 1, 2014, to October 31, 2019. Patients >18 years old with grade I or II splenic injury due to blunt trauma with CB on CT were included. The primary outcome was the failure of NOM requiring angioembolization/operation. We determined the failure rate of NOM for grade I versus grade II splenic injuries. We then performed bivariate comparisons of patients who failed NOM with those who did not.ResultsA total of 145 patients were included. Median Injury Severity Score was 17. The combined rate of failure for grade I–II injuries was 20.0%. There was no statistical difference in failure of NOM between grade I and II injuries with CB (18.2% vs 21.1%, p>0.05). Patients who failed NOM had an increased median hospital length of stay (p=0.024) and increased need for blood transfusion (p=0.004) and massive transfusion (p=0.030). Five patients (3.4%) died and 96 (66.2%) were discharged home, with no differences between those who failed and those who did not fail NOM (both p>0.05).ConclusionNOM of grade I–II splenic injuries with CB fails in 20% of patients.Level of evidenceIV.
The utility of monitoring snow for microplastics in the Arctic: a pilot study from Iqaluktuuttiaq, Nunavut
Authors: Hamilton Bonnie M. , Harris Les N. , Provencher Jennifer F. , Rochman Chelsea M. 
Published: March 2024

Plastic pollution, including microplastics (<5 mm) has been identified as an emerging contaminant of Arctic concern and has been observed in wildlife, water, sediment, air, and snow. Because snow is relatively easy to sample and process for microplastics, it may be a useful compartment to monitor to assess patterns of microplastic contamination in polar regions. Microplastics can enter the Arctic through both long-range transport pathways and from local sources. By sampling snow across spatial scales, and multiple distances from local communities, researchers can explore local and distant sources of microplastics, thereby informing management strategies. With this in mind, we aimed to quantify mass concentrations of microplastics in snow samples collected north-east of Iqaluktuuttiaq, Nunavut. We sampled five sites in a transect moving away from town and quantified microplastics using Pyrolysis/gas chromatography with mass spectrometry. We found microplastics at every location, but patterns along the transect were unclear. We observed differences in polymer types at sampling sites closer to the community compared to sites further away suggesting the presence of local inputs. Overall, we highlight the use of snow as a local monitoring tool to assess contamination and sources of microplastics in the Arctic to inform future long-term monitoring programs.
Large-scale digital signatures of emotional response to the COVID-19 vaccination campaign
Authors: Bertani Anna , Gallotti Riccardo , Menini Stefano , Sacco Pierluigi , De Domenico Manlio 
Published: March 2024

AbstractThe same individuals can express very different emotions in online social media with respect to face-to-face interactions, partially because of intrinsic limitations of the digital environments and partially because of their algorithmic design, which is optimized to maximize engagement. Such differences become even more pronounced for topics concerning socially sensitive and polarizing issues, such as massive pharmaceutical interventions. Here, we investigate how online emotional responses change during the large-scale COVID-19 vaccination campaign with respect to a baseline in which no specific contentious topic dominates. We show that the online discussions during the pandemic generate a vast spectrum of emotional response compared to the baseline, especially when we take into account the characteristics of the users and the type of information shared in the online platform. Furthermore, we analyze the role of the political orientation of shared news, whose circulation seems to be driven not only by their actual informational content but also by the social need to strengthen one’s affiliation to, and positioning within, a specific online community by means of emotionally arousing posts. Our findings stress the importance of better understanding the emotional reactions to contentious topics at scale from digital signatures, while providing a more quantitative assessment of the ongoing online social dynamics to build a faithful picture of offline social implications.
Diagenetic products, settings and evolution of the pre-salt succession in the Northern Campos Basin, Brazil
Authors: Strugale Michael , Lima Bruno Eustáquio Moreira , Day Christopher , Omma Jenny , Rushton Jeremy , Olivito João Paulo Roncolatto , Bouch Jon , Robb Laurence , Roberts Nick , Cartwright Joe 
Published: March 2024

Abstract
Despite all the effort made towards an understanding of the sedimentary, tectonic and diagenetic evolution of the pre-salt sequence and the Pre-Salt reservoirs of the Northern Campos Basin (East Brazil), two knowledge gaps have yet to be filled: (1) a detailed study of diagenesis in the crystalline basement and rift phases; and (2) the timing of diagenetic events that affected the pre-salt succession. In this study, samples from these geologic units were analysed for mineral composition and paragenetic evolution, fluid temperature and salinity, stable isotope compositions and laser ablation inductively coupled plasma mass spectrometer derived U–Pb ages of carbonate phases. The U–Pb ages of replacive and vein-filling cements reveal three tectono-diagenetic events, named the Barremian–Aptian (BADE, 125–117 Ma), the Albo–Cenomanian (ACDE, 103–98 Ma) and the Campanian–Maastrichtian (CMDE, 83–70 Ma). Each phase is characterized by distinct minerals, precipitation temperatures and burial conditions. The hydrothermal qualifier, identified by the temperature contrast between fluid and host rock, was initially high during BADE, then diminished over time (through ACDE) until it achieved equilibrium with the host rocks during CMDE. Diagenetic events are not coeval with magmatism but do coincide with known regional tectonic events described in the literature and are interpreted to be the result of increasing intraplate stresses. Multidisciplinary studies that include diagenetic events constrained by geochronological data will certainly lead to more robust conceptual geologic models, and, therefore, to a more reliable management of resources and strategies such as enhanced oil recovery, carbon capture, utilization and storage, and drinking water.
A Phase II Open-Label Randomized Clinical Trial of Preoperative Durvalumab or Durvalumab plus Tremelimumab in Resectable Head and Neck Squamous Cell Carcinoma
Authors: Kim Chang Gon , Hong Min Hee , Kim Dahee , Lee Brian Hyohyoung , Kim Hyunwook , Ock Chan-Young , Kelly Geoffrey , Bang Yoon Ji , Kim Gamin , Lee Jung Eun , Kim Chaeyeon , Kim Se-Heon , Hong Hyun Jun , Park Young Min , Sim Nam Suk , Park Heejung , Park Jin Woo , Lee Chang Geol , Kim Kyung Hwan , Park Goeun , Jung Inkyung , Han Dawoon , Kim Jong Hoon , Cha Junha , Lee Insuk , Kang Mingu , Song Heon , Oum Chiyoon , Kim Seulki , Kim Sukjun , Lim Yoojoo , Kim-Schulze Seunghee , Merad Miriam , Yoon Sun Och , Kim Hyun Je , Koh Yoon Woo , Kim Hye Ryun 
Published: March 2024

Abstract

Purpose:
Clinical implications of neoadjuvant immunotherapy in patients with locally advanced but resectable head and neck squamous cell carcinoma (HNSCC) remain largely unexplored.

Patients and Methods:
Patients with resectable HNSCC were randomized to receive a single dose of preoperative durvalumab (D) with or without tremelimumab (T) before resection, followed by postoperative (chemo)radiotherapy based on multidisciplinary discretion and 1-year D treatment. Artificial intelligence (AI)–powered spatial distribution analysis of tumor-infiltrating lymphocytes and high-dimensional profiling of circulating immune cells tracked dynamic intratumoral and systemic immune responses.

Results:
Of the 48 patients enrolled (D, 24 patients; D+T, 24 patients), 45 underwent surgical resection per protocol (D, 21 patients; D+T, 24 patients). D±T had a favorable safety profile and did not delay surgery. Distant recurrence-free survival (DRFS) was significantly better in patients treated with D+T than in those treated with D monotherapy. AI-powered whole-slide image analysis demonstrated that D+T significantly reshaped the tumor microenvironment toward immune-inflamed phenotypes, in contrast with the D monotherapy or cytotoxic chemotherapy. High-dimensional profiling of circulating immune cells revealed a significant expansion of T-cell subsets characterized by proliferation and activation in response to D+T therapy, which was rare following D monotherapy. Importantly, expansion of specific clusters in CD8+ T cells and non-regulatory CD4+ T cells with activation and exhaustion programs was associated with prolonged DRFS in patients treated with D+T.

Conclusions:
Preoperative D±T is feasible and may benefit patients with resectable HNSCC. Distinct changes in the tumor microenvironment and circulating immune cells were induced by each treatment regimen, warranting further investigation.
Large-scale Pan-cancer Cell Line Screening Identifies Actionable and Effective Drug Combinations
Authors: Bashi Azadeh C. , Coker Elizabeth A. , Bulusu Krishna C. , Jaaks Patricia , Crafter Claire , Lightfoot Howard , Milo Marta , McCarten Katrina , Jenkins David F. , van der Meer Dieudonne , Lynch James T. , Barthorpe Syd , Andersen Courtney L. , Barry Simon T. , Beck Alexandra , Cidado Justin , Gordon Jacob A. , Hall Caitlin , Hall James , Mali Iman , Mironenko Tatiana , Mongeon Kevin , Morris James , Richardson Laura , Smith Paul D. , Tavana Omid , Tolley Charlotte , Thomas Frances , Willis Brandon S. , Yang Wanjuan , O'Connor Mark J. , McDermott Ultan , Critchlow Susan E. , Drew Lisa , Fawell Stephen E. , Mettetal Jerome T. , Garnett Mathew J. 
Published: March 2024

Abstract

Oncology drug combinations can improve therapeutic responses and increase treatment options for patients. The number of possible combinations is vast and responses can be context-specific. Systematic screens can identify clinically relevant, actionable combinations in defined patient subtypes. We present data for 109 anticancer drug combinations from AstraZeneca's oncology small molecule portfolio screened in 755 pan-cancer cell lines. Combinations were screened in a 7 × 7 concentration matrix, with more than 4 million measurements of sensitivity, producing an exceptionally data-rich resource. We implement a new approach using combination Emax (viability effect) and highest single agent (HSA) to assess combination benefit. We designed a clinical translatability workflow to identify combinations with clearly defined patient populations, rationale for tolerability based on tumor type and combination-specific “emergent” biomarkers, and exposures relevant to clinical doses. We describe three actionable combinations in defined cancer types, confirmed in vitro and in vivo, with a focus on hematologic cancers and apoptotic targets.

Significance:
We present the largest cancer drug combination screen published to date with 7 × 7 concentration response matrices for 109 combinations in more than 750 cell lines, complemented by multi-omics predictors of response and identification of “emergent” combination biomarkers. We prioritize hits to optimize clinical translatability, and experimentally validate novel combination hypotheses.
This article is featured in Selected Articles from This Issue, p. 695
Thrombocytopenia Independently Leads to Changes in Monocyte Immune Function
Authors: Li Chen , Ture Sara K. , Nieves-Lopez Benjamin , Blick-Nitko Sara K. , Maurya Preeti , Livada Alison C. , Stahl Tyler J. , Kim Minsoo , Pietropaoli Anthony P. , Morrell Craig N. 
Published: March 2024

BACKGROUND:
While platelets have well-studied hemostatic functions, platelets are immune cells that circulate at the interface between the vascular wall and white blood cells. The physiological implications of these constant transient interactions are poorly understood. Activated platelets induce and amplify immune responses, but platelets may also maintain immune homeostasis in healthy conditions, including maintaining vascular integrity and T helper cell differentiation, meaning that platelets are central to both immune responses and immune quiescence. Clinical data have shown an association between low platelet counts (thrombocytopenia) and immune dysfunction in patients with sepsis and extracorporeal membrane oxygenation, further implicating platelets as more holistic immune regulators, but studies of platelet immune functions in nondisease contexts have had limited study.

METHODS:
We used in vivo models of thrombocytopenia and in vitro models of platelet and monocyte interactions, as well as RNA-seq and ATAC-seq (assay for transposase-accessible chromatin with sequencing), to mechanistically determine how resting platelet and monocyte interactions immune program monocytes.

RESULTS:
Circulating platelets and monocytes interact in a CD47-dependent manner to regulate monocyte metabolism, histone methylation, and gene expression. Resting platelet-monocyte interactions limit TLR (toll-like receptor) signaling responses in healthy conditions in an innate immune training-like manner. In both human patients with sepsis and mouse sepsis models, thrombocytopenia exacerbated monocyte immune dysfunction, including increased cytokine production.

CONCLUSIONS:
Thrombocytopenia immune programs monocytes in a manner that may lead to immune dysfunction in the context of sepsis. This is the first demonstration that sterile, endogenous cell interactions between resting platelets and monocytes regulate monocyte metabolism and pathogen responses, demonstrating platelets to be immune rheostats in both health and disease.
Mendelian Randomization Study With Clinical Follow‐Up Links Metabolites to Risk and Severity of Pulmonary Arterial Hypertension
Authors: Alhathli Elham , Julian Thomas , Girach Zain Ul Abideen , Thompson A. A. Roger , Rhodes Christopher , Gräf Stefan , Errington Niamh , Wilkins Martin R. , Lawrie Allan , Wang Dennis , Cooper‐Knock Johnathan 
Published: March 2024

Background
Pulmonary arterial hypertension (PAH) exhibits phenotypic heterogeneity and variable response to therapy. The metabolome has been implicated in the pathogenesis of PAH, but previous works have lacked power to implicate specific metabolites. Mendelian randomization (MR) is a method for causal inference between exposures and outcomes.

Methods and Results

Using genome‐wide association study summary statistics, we implemented MR analysis to test for potential causal relationships between serum concentration of 575 metabolites and PAH. Five metabolites were causally associated with the risk of PAH after multiple testing correction. Next, we measured serum concentration of candidate metabolites in an independent clinical cohort of 449 patients with PAH to check whether metabolite concentrations are correlated with markers of disease severity. Of the 5 candidates nominated by our MR work, serine was negatively associated and homostachydrine was positively associated with clinical severity of PAH via direct measurement in this independent clinical cohort. Finally we used conditional and orthogonal approaches to explore the biology underlying our lead metabolites. Rare variant burden testing was carried out using whole exome sequencing data from 578 PAH cases and 361 675 controls. Multivariable MR is an extension of MR that uses a single set of instrumental single‐nucleotide polymorphisms to measure multiple exposures; multivariable MR is used to determine interdependence between the effects of different exposures on a single outcome. Rare variant analysis demonstrated that loss‐of‐function mutations within activating transcription factor 4, a transcription factor responsible for upregulation of serine synthesis under conditions of serine starvation, are associated with higher risk for PAH. Homostachydrine is a xenobiotic metabolite that is structurally related to
l
‐proline betaine, which has previously been linked to modulation of inflammation and tissue remodeling in PAH. Our multivariable MR analysis suggests that the effect of
l
‐proline betaine is actually mediated indirectly via homostachydrine.

Conclusions
Our data present a method for study of the metabolome in the context of PAH, and suggests several candidates for further evaluation and translational research.
Feasibility Value of Right Ventricular Longitudinal Shortening Fraction and the Prognostic Implications in Patients With Heart Transplantation
Authors: Ji Xiang , Zhang Yiwei , Xie Yuji , Wang Wenyuan , Tan Yuting , Xie Mingxing , Zhang Li 
Published: March 2024

Background
Right ventricular longitudinal shortening fraction (RVLSF) is a 2‐dimensional speckle tracking echocardiography parameter based on tricuspid annular displacement analysis that could be used to assess right ventricular (RV) systolic function. The value of RVLSF in the assessment of RV systolic function in recipients of heart transplantation (HT) and whether RVLSF can replace strain parameters remains unknown.

Methods and Results

A total of 153 adult patients who underwent HT were consecutively enrolled in this prospective longitudinal study. All subjects were examined by conventional transthoracic 2‐dimensional echocardiography and 2‐dimensional speckle tracking echocardiography to evaluate the RV end‐diastolic basal diameter, RV end‐diastolic area, fractional area change, peak systolic velocity of tricuspid annulus, tricuspid annular plane systolic excursion, RV free wall strain, and RVLSF. Cox proportional hazards regression was used to test if the parameters of interest had independent prognostic value for adverse outcome prediction in patients who underwent HT. A significant positive correlation was found between the measurements of RVLSF and RV free wall strain (
r
=0.927,
P
<0.001). Compared with the event‐free group, the adverse outcome group displayed reduced RVLSF and RV free wall strain and higher age (
P
<0.001, <0.001, =0.016, respectively) in patients who underwent HT. RVLSF and RV free wall strain were independently associated with poor prognosis in multivariable analysis (both
P
<0.001).

Conclusions
RVLSF assessment provides an effective evaluation of RV longitudinal systolic function in the transplanted hearts and has prognostic value for adverse outcomes in patients undergoing HT.
Instance-Specific Model Perturbation Improves Generalized Zero-Shot Learning
Authors: Yang Guanyu , Huang Kaizhu , Zhang Rui , Yang Xi 
Published: March 2024

Abstract
Zero-shot learning (ZSL) refers to the design of predictive functions on new classes (unseen classes) of data that have never been seen during training. In a more practical scenario, generalized zero-shot learning (GZSL) requires predicting both seen and unseen classes accurately. In the absence of target samples, many GZSL models may overfit training data and are inclined to predict individuals as categories that have been seen in training. To alleviate this problem, we develop a parameter-wise adversarial training process that promotes robust recognition of seen classes while designing during the test a novel model perturbation mechanism to ensure sufficient sensitivity to unseen classes. Concretely, adversarial perturbation is conducted on the model to obtain instance-specific parameters so that predictions can be biased to unseen classes in the test. Meanwhile, the robust training encourages the model robustness, leading to nearly unaffected prediction for seen classes. Moreover, perturbations in the parameter space, computed from multiple individuals simultaneously, can be used to avoid the effect of perturbations that are too extreme and ruin the predictions. Comparison results on four benchmark ZSL data sets show the effective improvement that the proposed framework made on zero-shot methods with learned metrics.