bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activated regulatory T-cells promote duodenal bacterial translocation into necrotic areas in severe acute pancreatitis
Authors: Glaubitz Juliane , Wilden Anika , Frost Fabian , Ameling Sabine , Homuth Georg , Mazloum Hala , Rühlemann Malte Christoph , Bang Corinna , Aghdassi Ali A , Budde Christoph , Pickartz Tilmann , Franke Andre , Bröker Barbara M , Voelker Uwe , Mayerle Julia , Lerch Markus M , Weiss Frank-Ulrich , Sendler Matthias 
Published: January 2023

ObjectiveIn acute pancreatitis (AP), bacterial translocation and subsequent infection of pancreatic necrosis are the main risk factors for severe disease and late death. Understanding how immunological host defence mechanisms fail to protect the intestinal barrier is of great importance in reducing the mortality risk of the disease. Here, we studied the role of the Treg/Th17 balance for maintaining the intestinal barrier function in a mouse model of severe AP.DesignAP was induced by partial duct ligation in C57Bl/6 or DEREG mice, in which regulatory T-cells (Treg) were depleted by intraperitoneal injection of diphtheria toxin. By flow cytometry, functional suppression assays and transcriptional profiling we analysed Tregactivation and characterised T-cells of the lamina propria as well as intraepithelial lymphocytes (IELs) regarding their activation and differentiation. Microbiota composition was examined in intestinal samples as well as in murine and human pancreatic necrosis by 16S rRNA gene sequencing.ResultsThe prophylactic Treg-depletion enhanced the proinflammatory response in an experimental mouse model of AP but stabilised the intestinal immunological barrier function of Th17 cells and CD8+/γδTCR+IELs. Tregdepleted animals developed less bacterial translocation to the pancreas. Duodenal overgrowth of the facultative pathogenic taxaEscherichia/Shigellawhich associates with severe disease and infected necrosis was diminished in Tregdepleted animals.ConclusionTregsplay a crucial role in the counterbalance against systemic inflammatory response syndrome. In AP, Treg-activation disturbs the duodenal barrier function and permits translocation of commensal bacteria into pancreatic necrosis. Targeting Tregsin AP may help to ameliorate the disease course.
Coronary low-attenuation plaque and high-sensitivity cardiac troponin
Authors: Meah Mohammed N , Wereski Ryan , Bularga Anda , van Beek Edwin J R , Dweck Marc R , Mills Nicholas L , Newby David E , Dey Damini , Williams Michelle Claire , Lee Kuan Ken 
Published: January 2023

ObjectiveIn patients with acute chest pain who have had myocardial infarction excluded, plasma cardiac troponin I concentrations ≥5 ng/L are associated with risk of future adverse cardiovascular events. We aim to evaluate the association between cardiac troponin and coronary plaque composition in such patients.MethodsIn a prespecified secondary analysis of a prospective cohort study, blinded quantitative plaque analysis was performed on 242 CT coronary angiograms of patients with acute chest pain in whom myocardial infarction was excluded. Patients were stratified by peak plasma cardiac troponin I concentration ≥5 ng/L or <5 ng/L. Associations were assessed using univariable and multivariable logistic regression analyses.ResultsThe cohort was predominantly middle-aged (62±12 years) men (69%). Patients with plasma cardiac troponin I concentration ≥5 ng/L (n=161) had a higher total (median 33% (IQR 0–47) vs 0% (IQR 0–33)), non-calcified (27% (IQR 0–37) vs 0% (IQR 0–28)), calcified (2% (IQR 0–8) vs 0% (IQR 0–3)) and low-attenuation (1% (IQR 0–3) vs 0% (IQR 0–1)) coronary plaque burden compared with those with concentrations <5 ng/L (n=81; p≤0.001 for all). Low-attenuation plaque burden was independently associated with plasma cardiac troponin I concentration ≥5 ng/L after adjustment for clinical characteristics (adjusted OR per doubling 1.62 (95% CI 1.17 to 2.32), p=0.005) or presence of any visible coronary artery disease (adjusted OR per doubling 1.57 (95% CI 1.07 to 2.37), p=0.026).ConclusionIn patients with acute chest pain but without myocardial infarction, plasma cardiac troponin I concentrations ≥5 ng/L are associated with greater burden of low-attenuation coronary plaque.
Intratumoral BO-112 in combination with radiotherapy synergizes to achieve CD8 T-cell-mediated local tumor control
Authors: Rodriguez-Ruiz Maria E , Serrano-Mendioroz Irantzu , Garate-Soraluze Eneko , Sánchez-Mateos Paloma , Barrio-Alonso Celia , Rodríguez López Inmaculada , Diaz Pascual Victor , Arbea Moreno Leire , Alvarez Maite , Sanmamed Miguel F , Perez-Gracia Jose Luis , Escuin-Ordinas Helena , Quintero Marisol , Melero Ignacio 
Published: January 2023

BackgroundRadioimmunotherapy combines irradiation of tumor lesions with immunotherapy to achieve local and abscopal control of cancer. Most immunotherapy agents are given systemically, but strategies for delivering immunotherapy locally are under clinical scrutiny to maximize efficacy and avoid toxicity. Local immunotherapy, by injecting various pathogen-associated molecular patterns, has shown efficacy both preclinically and clinically. BO-112 is a viral mimetic based on nanoplexed double-stranded RNA (poly I:C) which exerts immune-mediated antitumor effects in mice and humans on intratumoral delivery. BO-112 and focal irradiation were used to make the proof-of-concept for local immunotherapy plus radiation therapy combinations.MethodsMurine transplantable tumor cell lines (TS/A, MC38 and B16-OVA) were used to show increased immunogenic features under irradiation, as well as in bilateral tumor models in which only one of the lesions was irradiated or/and injected with BO-112. Flow cytometry and multiplex tissue immunofluorescence were used to determine the effects on antitumor immunity. Depletions of immune cell populations and knockout mice for the IFNAR and BATF-3 genes were used to delineate the immune system requirements for efficacy.ResultsIn cultures of TS/A breast cancer cells, the combination of irradiation and BO-112 showed more prominent features of immunogenic tumor cell death in terms of calreticulin exposure. Injection of BO-112 into the tumor lesion receiving radiation achieved excellent control of the treated tumor and modest delays in contralateral tumor progression. Local effects were associated with more prominent infiltrates of antitumor cytotoxic tumor lymphocytes (CTLs). Importantly, local irradiation plus BO-112 in one of the tumor lesions that enhanced the therapeutic effects of radiotherapy on distant irradiated lesions that were not injected with BO-112. Hence, this beneficial effect of local irradiation plus BO-112 on a tumor lesion enhanced the therapeutic response to radiotherapy on distant non-injected lesions.ConclusionThis study demonstrates that local BO-112 immunotherapy and focal irradiation may act in synergy to achieve local tumor control. Irradiation plus BO-112 in one of the tumor lesions enhanced the therapeutic effects on distant irradiated lesions that were not injected with BO-112, suggesting strategies to treat oligometastatic patients with lesions susceptible to radiotherapy and with at least one tumor accessible for repeated BO-112 intratumoral injections.
Metabolic features and glucocorticoid-induced comorbidities in patients with giant cell arteritis and polymyalgia rheumatica in a Dutch and Danish cohort
Authors: Esen Idil , Arends Suzanne , Dalsgaard Nielsen Berit , Therkildsen Philip , Hansen Ib , van 't Ende Anna , Heeringa Peter , Boots Annemieke , Hauge Ellen , Brouwer Elisabeth , van Sleen Yannick 
Published: January 2023

ObjectivesGiant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are age-associated inflammatory diseases that frequently overlap. Both diseases require long-term treatment with glucocorticoids (GCs), often associated with comorbidities. Previous population-based cohort studies reported that an unhealthier metabolic profile might prevent the development of GCA. Here, we report metabolic features before start of treatment and during treatment in patients with GCA and PMR.MethodsIn the Dutch GCA/PMR/SENEX (GPS) cohort, we analysed metabolic features and prevalence of comorbidities (type 2 diabetes, hypercholesterolaemia, hypertension, obesity and cataract) in treatment-naïve patients with GCA (n=50) and PMR (n=42), and compared those with the population-based Lifelines cohort (n=91). To compare our findings in the GPS cohort, we included data from patients with GCA (n=52) and PMR (n=25) from the Aarhus cohort. Laboratory measurements, comorbidities and GC use were recorded for up to 5 years in the GPS cohort.ResultsGlycated haemoglobin levels tended to be higher in treatment-naïve patients with GCA, whereas high-density lipoprotein, low-density lipoprotein and cholesterol levels were lower compared with the Lifelines population. Data from the Aarhus cohort were aligned with the findings obtained in the GPS cohort. Presence of comorbidities at baseline did not predict long-term GC requirement. The incidence of diabetes, obesity and cataract among patients with GCA increased upon initiation of GC treatment.ConclusionData from the GCA and PMR cohorts imply a metabolic dysregulation in treatment-naïve patients with GCA, but not in patients with PMR. Treatment with GCs led to the rise of comorbidities and an unhealthier metabolic profile, stressing the need for prednisone-sparing targeted treatment in these vulnerable patients.
Differentiable Neural Network Pruning to Enable Smart Applications on Microcontrollers
Authors: Liberis Edgar , Lane Nicholas D. 
Published: January 2023

Wearable, embedded, and IoT devices are a centrepiece of many ubiquitous computing applications, such as fitness tracking, health monitoring, home security and voice assistants. By gathering user data through a variety of sensors and leveraging machine learning (ML), applications can adapt their behaviour: in other words, devices become "smart". Such devices are typically powered by microcontroller units (MCUs). As MCUs continue to improve, smart devices become capable of performing a non-trivial amount of sensing and data processing, including machine learning inference, which results in a greater degree of user data privacy and autonomy, compared to offloading the execution of ML models to another device.
Advanced predictive capabilities across many tasks make neural networks an attractive ML model for ubiquitous computing applications; however, on-device inference on MCUs remains extremely challenging. Orders of magnitude less storage, memory and computational ability, compared to what is typically required to execute neural networks, impose strict structural constraints on the network architecture and call for specialist model compression methodology. In this work, we present a differentiable structured pruning method for convolutional neural networks, which integrates a model's MCU-specific resource usage and parameter importance feedback to obtain highly compressed yet accurate models. Compared to related network pruning work, compressed models are more accurate due to better use of MCU resource budget, and compared to MCU specialist work, compressed models are produced faster. The user only needs to specify the amount of available computational resources and the pruning algorithm will automatically compress the network during training to satisfy them.
We evaluate our methodology using benchmark image and audio classification tasks and find that it (a) improves key resource usage of neural networks up to 80x; (b) has little to no overhead or even improves model training time; (c) produces compressed models with matching or improved resource usage up to 1.4x in less time compared to prior MCU-specific model compression methods.
Choice Trees: Representing Nondeterministic, Recursive, and Impure Programs in Coq
Authors: Chappe Nicolas , He Paul , Henrio Ludovic , Zakowski Yannick , Zdancewic Steve 
Published: January 2023

This paper introduces ctrees, a monad for modeling nondeterministic, recursive, and impure programs in Coq. Inspired by Xia et al.'s itrees, this novel data structure embeds computations into coinductive trees with three kind of nodes: external events, and two variants of nondeterministic branching. This apparent redundancy allows us to provide shallow embedding of denotational models with internal choice in the style of CCS, while recovering an inductive LTS view of the computation. ctrees inherit a vast collection of bisimulation and refinement tools, with respect to which we establish a rich equational theory.
We connect ctrees to the itree infrastructure by showing how a monad morphism embedding the former into the latter permits to use ctrees to implement nondeterministic effects. We demonstrate the utility of ctrees by using them to model concurrency semantics in two case studies: CCS and cooperative multithreading.
SSA Translation Is an Abstract Interpretation
Authors: Lemerre Matthieu 
Published: January 2023

Static single assignment (SSA) form is a popular intermediate representation that helps implement useful static analyses, including global value numbering (GVN), sparse dataflow analyses, or SMT-based abstract interpretation or model checking. However, the precision of the SSA translation itself depends on static analyses, and a priori static analysis is even indispensable in the case of low-level input languages like machine code.To solve this chicken-and-egg problem, we propose to turn the SSA translation into a standard static analysis based on abstract interpretation. This allows the SSA translation to be combined with other static analyses in a single pass, taking advantage of the fact that it is more precise to combine analyses than applying passes in sequence.We illustrate the practicality of these results by writing a simple dataflow analysis that performs SSA translation, optimistic global value numbering, sparse conditional constant propagation, and loop-invariant code motion in a single small pass; and by presenting a multi-language static analyzer for both C and machine code that uses the SSA abstract domain as its main intermediate representation.
Adult Low-Hypodiploid Acute Lymphoblastic Leukemia Emerges from PreleukemicTP53-Mutant Clonal Hematopoiesis
Authors: Kim Rathana , Bergugnat Hugo , Larcher Lise , Duchmann Matthieu , Passet Marie , Gachet Stéphanie , Cuccuini Wendy , Lafage-Pochitaloff Marina , Pastoret Cédric , Grardel Nathalie , Asnafi Vahid , Schäfer Beat W. , Delabesse Eric , Itzykson Raphaël , Adès Lionel , Hicheri Yosr , Chalandon Yves , Graux Carlos , Chevallier Patrice , Hunault Mathilde , Leguay Thibaut , Huguet Françoise , Lhéritier Véronique , Dombret Hervé , Soulier Jean , Rousselot Philippe , Boissel Nicolas , Clappier Emmanuelle 
Published: January 2023

AbstractLow hypodiploidy defines a rare subtype of B-cell acute lymphoblastic leukemia (B-ALL) with a dismal outcome. To investigate the genomic basis of low-hypodiploid ALL (LH-ALL) in adults, we analyzed copy-number aberrations, loss of heterozygosity, mutations, and cytogenetics data in a prospective cohort of Philadelphia (Ph)-negative B-ALL patients (n = 591, ages 18–84 years), allowing us to identify 80 LH-ALL cases (14%). Genomic analysis was critical for evidencing low hypodiploidy in many cases missed by cytogenetics. The proportion of LH-ALL within Ph-negative B-ALL dramatically increased with age, from 3% in the youngest patients (under 40 years old) to 32% in the oldest (over 55 years old). Somatic TP53 biallelic inactivation was the hallmark of adult LH-ALL, present in virtually all cases (98%). Strikingly, we detected TP53 mutations in posttreatment remission samples in 34% of patients. Single-cell proteogenomics of diagnosis and remission bone marrow samples evidenced a preleukemic, multilineage, TP53-mutant clone, reminiscent of age-related clonal hematopoiesis.Significance:We show that low-hypodiploid ALL is a frequent entity within B-ALL in older adults, relying on somatic TP53 biallelic alteration. Our study unveils a link between aging and low-hypodiploid ALL, with TP53-mutant clonal hematopoiesis representing a preleukemic reservoir that can give rise to aneuploidy and B-ALL.See related commentary by Saiki and Ogawa, p. 102.This article is highlighted in the In This Issue feature, p. 101
Economia Criativa nos países do Mercosul: breve análise conjuntural
Authors: Moraes Isaías Albertin de , Aguiar Mônica Heinzelmann Portella de 
Published: January 2023

O presente artigo tem como objetivo pesquisar a situação do setor de Indústria Criativa nos países membros do Mercado Comum do Sul (Mercosul) no período que vai de 2012 a 2015. No que tange à metodologia, optou-se pela análise crítica de dados bibliográficos e documentais, trabalhando com estatísticas coletadas na UNCTAD, BID e FIRJAN e conceitos de Economia Criativa (EC) elaborados por autores renomados como Howkins, Florida e Throsby. O trabalho está dividido em duas partes: na primeira, apresenta-se a evolução operacional do conceito de EC e, na segunda, examinam-se os dados referentes ao setor da EC no Mercosul. A conclusão, comparando com outros países do mundo, é de que a EC é uma alternativa promissora de desenvolvimento econômico, porém ainda pouco explorada pelo Mercosul.
The Contributions of the Cerebellar Peduncles and the Frontal Aslant Tract in Mediating Speech Fluency
Authors: Jossinger Sivan , Yablonski Maya , Amir Ofer , Ben-Shachar Michal 
Published: January 2023

Abstract
Fluent speech production is a complex task that spans multiple processes, from conceptual framing and lexical access, through phonological encoding, to articulatory control. For the most part, imaging studies portraying the neural correlates of speech fluency tend to examine clinical populations sustaining speech impairments and focus on either lexical access or articulatory control, but not both. Here, we evaluated the contribution of the cerebellar peduncles to speech fluency by measuring the different components of the process in a sample of 45 neurotypical adults. Participants underwent an unstructured interview to assess their natural speaking rate and articulation rate, and completed timed semantic and phonemic fluency tasks to assess their verbal fluency. Diffusion magnetic resonance imaging with probabilistic tractography was used to segment the bilateral cerebellar peduncles (CPs) and frontal aslant tract (FAT), previously associated with speech production in clinical populations. Our results demonstrate distinct patterns of white matter associations with different fluency components. Specifically, verbal fluency is associated with the right superior CP, whereas speaking rate is associated with the right middle CP and bilateral FAT. No association is found with articulation rate in these pathways, in contrast to previous findings in persons who stutter. Our findings support the contribution of the cerebellum to aspects of speech production that go beyond articulatory control, such as lexical access, pragmatic or syntactic generation. Further, we demonstrate that distinct cerebellar pathways dissociate different components of speech fluency in neurotypical speakers.
Metrics for Evaluating Cyber Security Data Visualizations in Virtual Reality
Authors: Harris Daniel , Miknis Marius , Smith Connor , Wilson Ian 
Published: January 2023

Abstract
Cyber security analysts use data visualizations to speed up ingestion of security data. These visualizations typically take the form of 2D graphics displayed on computer monitors. Virtual reality has the potential to improve these visualizations with immersive 3D environments and unique interaction mechanics. However, research into this newly synergized area lacks evaluation, leading to unfounded claims of effectiveness. A potential cause for these missing evaluations was identified as a lack of guidance detailing how evaluations should be conducted in this area. Additionally, the small amount of research that does include evaluation incorrectly relies on subjective participant opinions to objectively measure system effectiveness. An example of this misuse is asking participants which system they thought was quicker, rather than timing them. The objective of this article is to propose a solution to these issues in the form of a surveyed, categorized, and analyzed set of evaluation metrics. A total of 49 metrics was identified from 41 papers. The presented metrics detail which dependent variables should be considered when evaluating works in the combined fields of cyber security, data visualization, and virtual reality. These metrics can be used to produce more accurate evaluations in future works in this area.
Libertarian Control and Ultimate Responsibility
Authors: Montminy Martin 
Published: January 2023

Abstract
I raise three new objections against Robert Kane’s account of ultimate responsibility based on what he calls self-forming actions (sfa s). First, the ultimate responsibility that we have for our character is very limited, since, according to Kane’s model of character development, our character is shaped by sfa s for which we are only minimally responsible. Second, it is not desirable to rely on sfa s to shape our character. There are much better alternatives. Third, given what typically motivates our sfa s, we only rarely satisfy the conditions on responsibility for the changes in character that our sfa s give rise to.
The Journal of Jesuit Studies: First Decade
Authors: van Dijk Arjan 
Published: January 2023

Abstract
On the occasion of its tenth anniversary, this article looks back on the genesis and subsequent development of the Journal of Jesuit Studies, its conversion to open access, and the role of its founding editor, Robert Aleksander Maryks. It also highlights a number of other Brill resources in Jesuit Studies conceived and edited by Robert Maryks.
Jesuits, Conspiracies, and Conspiracy Theories
Authors: McKenzie-McHarg Andrew 
Published: January 2023

Abstract
This introductory article explores the thematic affinity linking the Society of Jesus with conspiracies and conspiracy theories. After giving a short overview of the historiography devoted to anti-Jesuitism, it draws attention to how anti-Jesuits vilified the order over the centuries on the basis of alleged conspiracies whose extent varied from the episodic to the all-encompassing and that were imagined and posited in ways that tended to be themselves highly conspiratorial. In this manner, it foregrounds aspects of anti-Jesuitism and conspiracy theories that will recur in the individual contributions to this special issue of the Journal of Jesuit Studies.
How the Chinese in the Spanish Philippines Negotiated Commercial Boundaries in the Colonial Economy
Authors: Clemente Tina S. 
Published: January 2023

Abstract
While various dimensions of Chinese commercial achievement have gained longstanding attention in the literature, this article argues for the reconsideration of Chinese commercial performance in the Spanish Philippines based on the confluence of various factors, including the altered conditions of economic engagement in the islands, the character of political economy during the colonial period, and the gaps in provisioning the colony. Against the backdrop of the socio-political and economic dynamics of the Spanish empire, I analyze narratives that emanate from the interests of the colonial authorities, the clergy, and the Chinese traders themselves. I utilize sixteenth-to-eighteenth-century historical accounts and consider these narratives as frames of various motivations by the different actors. I examine these representations and underscore how the Chinese negotiated various parameters set against them that limited their access to commercial opportunities and settlement.