bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patient data for commercial companies? An ethical framework for sharing patients’ data with for-profit companies for research
Authors: Winkler Eva C , Jungkunz Martin , Thorogood Adrian , Lotz Vincent , Schickhardt Christoph 
Published: May 2023

BackgroundResearch using data from medical care promises to advance medical science and improve healthcare. Academia is not the only sector that expects such research to be of great benefit. The research-based health industry is also interested in so-called ‘real-world’ health data to develop new drugs, medical technologies or data-based health applications. While access to medical data is handled very differently in different countries, and some empirical data suggest people are uncomfortable with the idea of companies accessing health information, this paper aims to advance the ethical debate about secondary use of medical data generated in the public healthcare sector by for-profit companies for medical research (ReuseForPro).MethodsWe first clarify some basic concepts and our ethical-normative approach, then discuss and ethically evaluate potential claims and interests of relevant stakeholders: patients as data subjects in the public healthcare system, for-profit companies, the public, and physicians and their healthcare institutions. Finally, we address the tensions between legitimate claims of different stakeholders in order to suggest conditions that might ensure ethically sound ReuseForPro.ResultsWe conclude that there are good reasons to grant for-profit companies access to medical data if they meet certain conditions: among others they need to respect patients’ informational rights and their actions need to be compatible with the public’s interest in health benefit from ReuseForPro.
Evaluation of predictive models of aneurysm focal growth and bleb development using machine learning techniques
Authors: Hadad Sara , Mut Fernando , Slawski Martin , Robertson Anne M , Cebral Juan R 
Published: May 2023

BackgroundThe presence of blebs increases the rupture risk of intracranial aneurysms (IAs).ObjectiveTo evaluate whether cross-sectional bleb formation models can identify aneurysms with focalized enlargement in longitudinal series.MethodsHemodynamic, geometric, and anatomical variables derived from computational fluid dynamics models of 2265 IAs from a cross-sectional dataset were used to train machine learning (ML) models for bleb development. ML algorithms, including logistic regression, random forest, bagging method, support vector machine, and K-nearest neighbors, were validated using an independent cross-sectional dataset of 266 IAs. The models' ability to identify aneurysms with focalized enlargement was evaluated using a separate longitudinal dataset of 174 IAs. Model performance was quantified by the area under the receiving operating characteristic curve (AUC), the sensitivity and specificity, positive predictive value, negative predictive value, F1 score, balanced accuracy, and misclassification error.ResultsThe final model, with three hemodynamic and four geometrical variables, along with aneurysm location and morphology, identified strong inflow jets, non-uniform wall shear stress with high peaks, larger sizes, and elongated shapes as indicators of a higher risk of focal growth over time. The logistic regression model demonstrated the best performance on the longitudinal series, achieving an AUC of 0.9, sensitivity of 85%, specificity of 75%, balanced accuracy of 80%, and a misclassification error of 21%.ConclusionsModels trained with cross-sectional data can identify aneurysms prone to future focalized growth with good accuracy. These models could potentially be used as early indicators of future risk in clinical practice.
Systemic Alterations in Type-2 Conventional Dendritic Cells Lead to Impaired Tumor Immunity in Pancreatic Cancer
Authors: James C. Alston , Baer John M. , Zou Chong , Panni Usman Y. , Knolhoff Brett L. , Hogg Graham D. , Kingston Natalie L. , Kang Liang-I. , Lander Varintra E. , Luo Jingqin , Tao Yu , Watson Mark A. , Aft Rebecca , Fields Ryan C. , Hawkins William G. , DeNardo David G. 
Published: May 2023

Abstract
Intratumoral T-cell dysfunction is a hallmark of pancreatic tumors, and efforts to improve dendritic cell (DC)–mediated T-cell activation may be critical in treating these immune therapy unresponsive tumors. Recent evidence indicates that mechanisms that induce dysfunction of type 1 conventional DCs (cDC1) in pancreatic adenocarcinomas (PDAC) are drivers of the lack of responsiveness to checkpoint immunotherapy. However, the impact of PDAC on systemic type 2 cDC2 development and function has not been well studied. Herein, we report the analysis of 3 cohorts, totaling 106 samples, of human blood and bone marrow (BM) from patients with PDAC for changes in cDCs. We found that circulating cDC2s and their progenitors were significantly decreased in the blood of patients with PDAC, and repressed numbers of cDC2s were associated with poor prognosis. Serum cytokine analyses identified IL6 as significantly elevated in patients with PDAC and negatively correlated with cDC numbers. In vitro, IL6 impaired the differentiation of cDC1s and cDC2s from BM progenitors. Single-cell RNA sequencing analysis of human cDC progenitors in the BM and blood of patients with PDAC showed an upregulation of the IL6/STAT3 pathway and a corresponding impairment of antigen processing and presentation. These results suggested that cDC2s were systemically suppressed by inflammatory cytokines, which was linked to impaired antitumor immunity.
Mitochondria Transfer from Mesenchymal Stem Cells Confers Chemoresistance to Glioblastoma Stem Cells through Metabolic Rewiring
Authors: Nakhle Jean , Khattar Khattar , Özkan Tülin , Boughlita Adel , Abba Moussa Daouda , Darlix Amélie , Lorcy Frédérique , Rigau Valérie , Bauchet Luc , Gerbal-Chaloin Sabine , Daujat-Chavanieu Martine , Bellvert Floriant , Turchi Laurent , Virolle Thierry , Hugnot Jean-Philippe , Buisine Nicolas , Galloni Mireille , Dardalhon Valérie , Rodriguez Anne-Marie , Vignais Marie-Luce 
Published: May 2023

Glioblastomas (GBM) are heterogeneous tumors with high metabolic plasticity. Their poor prognosis is linked to the presence of glioblastoma stem cells (GSC), which support resistance to therapy, notably to temozolomide (TMZ). Mesenchymal stem cells (MSC) recruitment to GBM contributes to GSC chemoresistance, by mechanisms still poorly understood. Here, we provide evidence that MSCs transfer mitochondria to GSCs through tunneling nanotubes, which enhances GSCs resistance to TMZ. More precisely, our metabolomics analyses reveal that MSC mitochondria induce GSCs metabolic reprograming, with a nutrient shift from glucose to glutamine, a rewiring of the tricarboxylic acid cycle from glutaminolysis to reductive carboxylation and increase in orotate turnover as well as in pyrimidine and purine synthesis. Metabolomics analysis of GBM patient tissues at relapse after TMZ treatment documents increased concentrations of AMP, CMP, GMP, and UMP nucleotides and thus corroborate our in vitro analyses. Finally, we provide a mechanism whereby mitochondrial transfer from MSCs to GSCs contributes to GBM resistance to TMZ therapy, by demonstrating that inhibition of orotate production by Brequinar (BRQ) restores TMZ sensitivity in GSCs with acquired mitochondria. Altogether, these results identify a mechanism for GBM resistance to TMZ and reveal a metabolic dependency of chemoresistant GBM following the acquisition of exogenous mitochondria, which opens therapeutic perspectives based on synthetic lethality between TMZ and BRQ.Significance:Mitochondria acquired from MSCs enhance the chemoresistance of GBMs. The discovery that they also generate metabolic vulnerability in GSCs paves the way for novel therapeutic approaches.
Intravenous Thrombolysis in Patients With White Matter Hyperintensities in the WAKE-UP Trial
Authors: Frey Benedikt M. , Shenas Farhad , Boutitie Florent , Cheng Bastian , Cho Tae-Hee , Ebinger Martin , Endres Matthias , Fiebach Jochen B. , Fiehler Jens , Galinovic Ivana , Barow Ewgenia , Königsberg Alina , Schlemm Eckhard , Pedraza Salvador , Lemmens Robin , Thijs Vincent , Muir Keith W. , Nighoghossian Norbert , Simonsen Claus Z. , Gerloff Christian , Thomalla Götz ,   on behalf of the WAKE-UP Investigators
Published: May 2023

BACKGROUND:
White matter hyperintensities of presumed vascular origin (WMH) are the most prominent imaging feature of cerebral small vessel disease (cSVD). Previous studies suggest a link between cSVD burden and intracerebral hemorrhage and worse functional outcome after thrombolysis in acute ischemic stroke. We aimed to determine the impact of WMH burden on efficacy and safety of thrombolysis in the MRI-based randomized controlled WAKE-UP trial of intravenous alteplase in unknown onset stroke.

METHODS:
The design of this post hoc study was an observational cohort design of a secondary analysis of a randomized trial. WMH volume was quantified on baseline fluid-attenuated inversion recovery images of patients randomized to either alteplase or placebo in the WAKE-UP trial. Excellent outcome was defined as score of 0-1 on the modified Rankin Scale after 90 days. Hemorrhagic transformation was assessed on follow-up imaging 24-36 hours after randomization. Treatment effect and safety were analyzed by fitting multivariable logistic regression models.

RESULTS:

Quality of scans was sufficient in 441 of 503 randomized patients to delineate WMH. Median age was 68 years, 151 patients were female, and 222 patients were assigned to receive alteplase. Median WMH volume was 11.4 mL. Independent from treatment, WMH burden was statistically significantly associated with worse functional outcome (odds ratio, 0.72 [95% CI, 0.57–0.92]), but not with higher chances of any hemorrhagic transformation (odds ratio, 0.78 [95% CI, 0.60–1.01]). There was no interaction of WMH burden and treatment group for the likelihood of excellent outcome (
P
=0.443) or any hemorrhagic transformation (
P
=0.151). In a subgroup of 166 patients with severe WMH, intravenous thrombolysis was associated with higher odds of excellent outcome (odds ratio, 2.40 [95% CI, 1.19–4.84]) with no significant increase in the rate of hemorrhagic transformation (odds ratio, 1.96 [95% CI, 0.80–4.81]).

CONCLUSIONS:
Although WMH burden is associated with worse functional outcome, there is no association with treatment effect or safety of intravenous thrombolysis in patients with ischemic stroke of unknown onset.

REGISTRATION:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT01525290.
The Development of Relational Reasoning: An Eyetracking Analysis of Strategy Use and Adaptation in Children and Adults Performing Matrix Completion
Authors: Niebaum Jesse , Munakata Yuko 
Published: May 2023

Abstract
Relational reasoning is a key component of fluid intelligence and an important predictor of academic achievement. Relational reasoning is commonly assessed using matrix completion tasks, in which participants see an incomplete matrix of items that vary on different dimensions and select a response that best completes the matrix based on the relations among items. Performance on such assessments increases dramatically across childhood into adulthood. However, despite widespread use, little is known about the strategies associated with good or poor matrix completion performance in childhood. This study examined the strategies children and adults use to solve matrix completion problems, how those strategies change with age, and whether children and adults adapt strategies to difficulty. We used eyetracking to infer matrix completion strategy use in 6- and 9-year-old children and adults. Across ages, scanning across matrix rows and columns predicted good overall performance, and quicker and higher rates of consulting potential answers predicted poor performance, indicating that optimal matrix completion strategies are similar across development. Indices of good strategy use increased across childhood. As problems increased in difficulty, children and adults increased their scanning of matrix rows and columns, and adults and 9-year-olds also shifted strategies to rely more on consulting potential answers. Adapting strategies to matrix difficulty, particularly increased scanning of rows and columns, was associated with good overall performance in both children and adults. These findings underscore the importance of both spontaneous and adaptive strategy use in individual differences in relational reasoning and its development.
Functional traits including interspecific sociality affect mobbing behaviour in a bird community of southern China
Authors: Jiang Demeng , Hua Fangyuan , Goodale Eben 
Published: May 2023

Abstract
Mobbing is a prevalent anti-predatory behaviour in birds where prey actively engage in harassing predators. Functional traits have been shown to affect prey species’ tendency to engage in mobbing, but empirical studies have largely neglected to assess the influence of some other potentially important functional traits, such as intraspecific and interspecific sociality, on mobbing or measured different aspects of the behaviour. In this study, we performed playback experiments that elicited mobbing responses from a forest bird community in southern China, to investigate the influence of body mass, foraging strata, as well as intra- and interspecific sociality, on the prevalence of mobbing, as well as the intensity of aggression and vocalness. We found that species with small body masses engaged in more frequent and intense mobbing behaviours. Notably, interspecific sociality was negatively associated with birds’ mobbing prevalence and tended to be negatively associated with vocalness.
Ficophagus annulatae n. sp. (Nematoda: Aphelenchoididae), an associate of Ficus annulata in China
Authors: Zeng Yongsan , Zhang Dayuan , Giblin-Davis Robin M. , Roberts Joseph A. 
Published: May 2023

Summary
A new species of the genus Ficophagus was recovered from the syconia of Ficus annulata from Xishuangbanna, Yunnan province, China. It is described herein as Ficophagus annulatae n. sp. and is characterised by possessing the combined characters of a short PUS (9-18 μm or 0.3-0.6 VBD long), an excretory pore (EP) located at the level between stylet basal knobs and metacorpus, presence of crustaformeria, amoeboid sperm, three pairs of subventral papillae on the male tail (one pair just adcloacal (P2), one pair halfway between cloacal aperture and tail terminus (P3), and one pair near tail tip (P4)), rounded male tail tip without mucron, absence of gubernaculum and bow-shaped spicule with indistinct rostrum. Ficophagus annulatae n. sp. was differentiated from other sequenced species by the partial small subunit (SSU) rRNA gene and D2-D3 expansion segments of the large subunit (LSU) rRNA gene. Phylogenetic analysis with the LSU D2-D3 expansion segment sequence suggested that F. annulatae n. sp. is clustered in the same highly supported monophyletic clade with F. benjamina, F. curtipes and F. microcarpus. It differs morphologically from these species in EP position, spicule and uterus morphology, and some morphometric characters.
Atmospheric Pattern–Based Predictions of S2S Sea Level Anomalies for Two Selected U.S. Locations
Authors: Lee Cameron C. , Sheridan Scott C. , Dusek Gregory P. , Pirhalla Douglas E. 
Published: May 2023

Abstract
With climate change causing rising sea levels around the globe, multiple recent efforts in the United States have focused on the prediction of various meteorological factors that can lead to periods of anomalously high tides despite seemingly benign atmospheric conditions. As part of these efforts, this research explores monthly scale relationships between sea level variability and atmospheric circulation patterns and demonstrates two options for subseasonal to seasonal (S2S) predictions of anomalous sea levels using these patterns as inputs to artificial neural network (ANN) models. Results on the monthly scale are similar to previous research on the daily scale, with above-average sea levels and an increased risk of high-water events on days with anomalously low atmospheric pressure patterns and wind patterns leading to onshore or downwelling-producing wind stress. Some wind patterns show risks of high-water events to be over 6 times higher than baseline risk and exhibit an average water level anomaly of +94 mm above normal. In terms of forecasting, nonlinear autoregressive ANN models with exogenous input (NARX models) and pattern-based lagged ANN (PLANN) models show skill over postprocessed numerical forecast model output, and simple climatology. Damped-persistence forecasts and PLANN models show nearly the same skill in terms of predicting anomalous sea levels out to 9 months of lead time, with a slight edge to PLANN models, especially with regard to error statistics. This perspective on forecasting—using predefined circulation patterns along with ANN models—should aid in the real-time prediction of coastal flooding events, among other applications.
The Effects of Climate Change on Outdoor Recreation Participation in the United States: Projections for the Twenty-First Century
Authors: Willwerth Jacqueline , Sheahan Megan , Chan Nathan , Fant Charles , Martinich Jeremy , Kolian Michael 
Published: May 2023

Abstract
Climate change is expected to impact individuals’ recreation choices, as changing temperatures and precipitation patterns influence participation in outdoor recreation and alternative activities. This paper empirically investigates the relationship between weather and outdoor recreation using nationally representative data from the contiguous United States. We find that across most outdoor recreation activities, participation is lowest on the coldest days [<35°F (1.7°C)] and highest at moderately high temperatures [80°–90°F (27°–32°C)]. Notable exceptions to this trend include water sports and snow and ice sports, for which participation peaks at the highest and lowest temperatures, respectively. If individuals continue to respond to temperature changes the same way that they have in the recent past, in a future climate that has fewer cool days and more moderate and hot days, our model anticipates net participation across all outdoor recreation activities will increase by 88 million trips annually at 1°C of warming (CONUS) and by up to 401 million trips at 6°C of warming, valued between $3.2 and $15.6 billion in consumer surplus annually (2010 population). The increase in trips is driven by participation in water sports; excluding water sports from future projections decreases the consumer surplus gains by approximately 75% across all modeled degrees of warming. If individuals in northern regions respond to temperature like people in southern regions currently do (a proxy for adaptation), total outdoor recreation trips will increase by an additional 17% in comparison with no adaptation at 6°C of warming. This benefit is generally not seen at lower degrees of warming.

Significance Statement
We extend the extant literature in four key ways. First, we probe how impacts vary by region of the United States, revealing disparate impacts across geographies. Second, we analyze substitution patterns between alternative activity categories, which sheds light on the broader implications beyond participation in outdoor recreation. Third, we add depth to the future projection of climate impacts by considering how our projections might change under empirically informed scenarios of adaptation and acclimatization. Fourth, our analysis showcases one way in which climate change results in net benefits.
Pathologic Tumor Regression is Associated With Improved Survival in Pancreatic Cancer
Authors: Nicolais Laura M. , Caron Molly , Verdini Nicholas , Fitzgerald Timothy L. 
Published: May 2023

Objectives The advent of effective chemotherapy regimens has increased the use of neoadjuvant multiagent chemotherapy in pancreatic cancer. However, the effect of tumor downstaging with neoadjuvant treatment on survival is unclear. Methods Retrospective study included all resected patients with pancreatic adenocarcinoma who underwent neoadjuvant chemotherapy with FOLFIRINOX or gemcitabine/Abraxane. Downstaging was quantified using (1) difference between presenting AJCC clinical and final pathologic stage and (2) College of American Pathologists (CAP) Tumor Regression Grading Schema. Results Eighty-seven patients met inclusion criteria. FOLFIRINOX was the most common regimen, 63.2% vs 21.8%. Change in regimen occurred in 15% of patients. Downstaging based on a difference in AJCC stage group occurred in only 4.6%. In contrast, 45.2% were classified as downstaged by the CAP Tumor Regression of 0-2. Downstaging was similar for FOLFIRINOX gemcitabine/Abraxane (64.7 vs 53.6, P = .12) using the CAP criteria. On univariate analysis, treatment regimen (gemcitabine/Abraxane vs FOLFIRINOX, median survival 27 vs 29 mo; HR 1.57, P = .2) had similar survival. Downstaging by the AJCC stage was not associated with improved survival (HR 1.51, P = .4). However, there was a survival benefit for those downstaged by the CAP Tumor Regression Grading Schema, the median survival of 41 mo vs 25 mo; HR 3.05, P = .009. Improved survival 3.32 (1.35-8.16), P = .009) was maintained on multivariate analysis. Conclusion Survival is significantly improved in those downstaged, as assessed by the CAP Tumor Regression Schema. Downstaging is an important prognostic variable that can help with joint decision making for clinicians and patients.
Traumatic Amputations Treated in US Emergency Departments: A Review of the NEISS Database
Authors: Sadoma Brittany R. , Sheets Nicholas W. , Plurad David S. , Dubina Emily D. 
Published: May 2023

Background Trauma is the second most common cause of limb loss in the United States (US), second only to vascular disease. The aim of this study was to evaluate the demographics and commercial products associated with traumatic amputations in the United States. Methods The National Electronic Injury Surveillance System (NEISS) database was analyzed from 2012 to 2021 to identify patients presenting to the Emergency Department (ED) with the diagnosis of amputation. Additional variables included patient demographics, body part amputated, commercial products associated with amputation, and ED treatment disposition. Results A total of 7323 patients diagnosed with amputation were identified in the NEISS database. Amputations were most frequent in the 0-5 years age group, followed by 51-55 years. More males than females suffered an amputation during the study period (77% vs 22%). Most patients were Caucasian. Fingers were most frequently amputated (91%), followed by toes (5%). Most injuries occurred in the home (56%). The top commercial product behind these traumatic amputations was doors (18%), followed by bench or table saws (14%) and power lawn mowers (6%). Over 70% of patients were able to be treated and released from the ED, while 22% required hospitalization and 5% were transferred to another facility. Discussion Traumatic amputations can cause significant injuries. A better understanding of the incidence and mechanisms behind traumatic amputations may help with injury prevention. Pediatric patients had a high incidence of traumatic amputations, which warrants further research and dedication to injury prevention in this vulnerable group.