bluuebunny/crossref_metadata_2025_split huggingface dataset:
MFPMiner: Mining Meaningful Frequent Patterns from Spatio-textual Trajectories
Authors: Valdes Fabio 
Published: March 2022

In the second decade of this century, technical progress has led to a worldwide proliferation of devices for tracking the movement behavior of a person, a vehicle, or another kind of entity. One of the consequences of this development is a massive and still growing amount of movement and movement-related data recorded by cellphones, automobiles, vessels, aircraft, and further GPS-enabled entities. As a result, the requirements for managing and analyzing movement records also increase, serving commercial, administrative, or private purposes. Since the development of hardware components cannot keep pace with the data growth, exploring methods of analyzing such trajectory datasets has become a very active and influential research field.
For many application scenarios, besides the spatial trajectory of an entity, it is desirable to take additional semantic information into consideration. These descriptions also change with time and may represent, e.g., the course of streets passed by a bus, the sequence of region names traversed by an aircraft, or the points of interest in proximity of the positions of a taxi. Such data may be directly recorded by a sensor (such as the altitude of an aircraft) or computed from the spatial trajectory combined with some underlying information (for example, street names). It is often helpful or even necessary to focus on such semantic information for efficient analyses, as changes usually occur less frequently than it is the case for the spatial trajectory, where data points usually arrive in very close temporal distances. However, any kind of querying requires a deep semantic knowledge of the dataset at hand, particularly for retrieving the set of trajectories that match a certain mobility pattern, that is, a sequence of temporal, spatial, and semantic specifications.

In this article, we introduce a framework named MFPMiner

1

for retrieving all mobility patterns fulfilling a user-specified frequency threshold from a spatio-textual trajectory dataset. The resulting patterns and their relative frequency can be regarded as a knowledge base of the considered data. They may be directly visualized or applied for a pattern matching query yielding the set of matching trajectories. We demonstrate the functionality of our approach in an application scenario and provide an experimental evaluation of its performance on real and synthetic datasets by comparing it to three competitive methods. The framework has been fully implemented in a DBMS environment and is freely available open source software.
Exploiting LRRC15 as a Novel Therapeutic Target in Cancer
Authors: Ray Upasana , Pathoulas Christopher L. , Thirusangu Prabhu , Purcell James W. , Kannan Nagarajan , Shridhar Viji 
Published: March 2022

Abstract
Abundant fibrotic stroma is a typical feature of most solid tumors, and stromal activation promotes oncogenesis, therapy resistance, and metastatic dissemination of cancer cells. Therefore, targeting the tumor stroma in combination with standard-of-care therapies has become a promising therapeutic strategy in recent years. The leucine-rich repeat-containing protein 15 (LRRC15) is involved in cell–cell and cell–matrix interactions and came into focus as a promising anticancer target owing to its overexpression in mesenchymal-derived tumors such as sarcoma, glioblastoma, and melanoma and in cancer-associated fibroblasts in the microenvironment of breast, head and neck, lung, and pancreatic tumors. Effective targeting of LRRC15 using specific antibody–drug conjugates (ADC) has the potential to improve the outcome of patients with LRRC15-positive (LRRC15+) cancers of mesenchymal origin or stromal desmoplasia. Moreover, LRRC15 expression may serve as a predictive biomarker that could be utilized in the preclinical assessment of cancer patients to support personalized clinical outcomes. This review focuses on the role of LRRC15 in cancer, including clinical trials involving LRRC15-targeted therapies, such as the ABBV-085 ADC for patients with LRRC15+ tumors. This review spans perceived knowledge gaps and highlights the clinical avenues that need to be explored to provide better therapeutic outcomes in patients.
IL15 and Anti–PD-1 Augment the Efficacy of Agonistic Intratumoral Anti-CD40 in a Mouse Model with Multiple TRAMP-C2 Tumors
Authors: Chen Wei , Bamford Richard N. , Edmondson Elijah F. , Waldmann Thomas A. 
Published: March 2022

Abstract

Purpose:
IL15 promotes activation and maintenance of natural killer (NK) and CD8+ T effector memory cells making it a potential immunotherapeutic agent for the treatment of cancer. However, monotherapy with IL15 was ineffective in patients with cancer, indicating that it would have to be used in combination with other anticancer agents. The administration of high doses of common gamma chain cytokines, such as IL15, is associated with the generation of “helpless” antigen-nonspecific CD8 T cells. The generation of the tumor-specific cytotoxic T cells can be mediated by CD40 signaling via agonistic anti-CD40 antibodies. Nevertheless, parenteral administration of anti-CD40 antibodies is associated with unacceptable side effects, such as thrombocytopenia and hepatic toxicity, which can be avoided by intratumoral administration.

Experimental Design:
We investigated the combination of IL15 with an intratumoral anti-CD40 monoclonal antibody (mAb) in a dual tumor TRAMP-C2 murine prostate cancer model and expanded the regimen to include an anti–PD-1 mAb.

Results:
Here we demonstrated that anti-CD40 given intratumorally not only showed significant antitumor activity in treated tumors, but also noninjected contralateral tumors, indicative of abscopal efficacy. The combination of IL15 with intratumoral anti-CD40 showed an additive immune response with an increase in the number of tumor-specific tetramer-positive CD8 T cells. Furthermore, the addition of anti–PD-1 further improved efficacy mediated by the anti-CD40/IL15 combination.

Conclusions:
These studies support the initiation of a clinical trial in patients with cancer using IL15 in association with the checkpoint inhibitor, anti–PD-1, and intratumoral optimized anti-CD40.
Melanoma-Secreted Amyloid Beta Suppresses Neuroinflammation and Promotes Brain Metastasis
Authors: Kleffman Kevin , Levinson Grace , Rose Indigo V.L. , Blumenberg Lili M. , Shadaloey Sorin A.A. , Dhabaria Avantika , Wong Eitan , Galán-Echevarría Francisco , Karz Alcida , Argibay Diana , Von Itter Richard , Floristán Alfredo , Baptiste Gillian , Eskow Nicole M. , Tranos James A. , Chen Jenny , Vega y Saenz de Miera Eleazar C. , Call Melissa , Rogers Robert , Jour George , Wadghiri Youssef Zaim , Osman Iman , Li Yue-Ming , Mathews Paul , DeMattos Ronald B. , Ueberheide Beatrix , Ruggles Kelly V. , Liddelow Shane A. , Schneider Robert J. , Hernando Eva 
Published: March 2022

Abstract

Brain metastasis is a significant cause of morbidity and mortality in multiple cancer types and represents an unmet clinical need. The mechanisms that mediate metastatic cancer growth in the brain parenchyma are largely unknown. Melanoma, which has the highest rate of brain metastasis among common cancer types, is an ideal model to study how cancer cells adapt to the brain parenchyma. Our unbiased proteomics analysis of melanoma short-term cultures revealed that proteins implicated in neurodegenerative pathologies are differentially expressed in melanoma cells explanted from brain metastases compared with those derived from extracranial metastases. We showed that melanoma cells require amyloid beta (Aβ) for growth and survival in the brain parenchyma. Melanoma-secreted Aβ activates surrounding astrocytes to a prometastatic, anti-inflammatory phenotype and prevents phagocytosis of melanoma by microglia. Finally, we demonstrate that pharmacologic inhibition of Aβ decreases brain metastatic burden.

Significance:
Our results reveal a novel mechanistic connection between brain metastasis and Alzheimer's disease, two previously unrelated pathologies; establish Aβ as a promising therapeutic target for brain metastasis; and demonstrate suppression of neuroinflammation as a critical feature of metastatic adaptation to the brain parenchyma.
This article is highlighted in the In This Issue feature, p. 1171
Circulating Tregs Accumulate in Omental Tumors and Acquire Adipose-Resident Features
Authors: Liu Mingyong , Starenki Dmytro , Scharer Christopher D. , Silva-Sanchez Aaron , Molina Patrick A. , Pollock Jennifer S. , Cooper Sara J. , Arend Rebecca C. , Rosenberg Alexander F. , Randall Troy D. , Meza-Perez Selene 
Published: March 2022

Abstract

Tumors that metastasize in the peritoneal cavity typically end up in the omental adipose tissue, a particularly immune-suppressive environment that includes specialized adipose-resident regulatory T cells (Treg). Tregs rapidly accumulate in the omentum after tumor implantation and potently suppress antitumor immunity. However, it is unclear whether these Tregs are recruited from the circulation or derived from preexisting adipose-resident Tregs by clonal expansion. Here we show that Tregs in tumor-bearing omenta predominantly have thymus-derived characteristics. Moreover, naïve tumor antigen-specific CD4+ T cells fail to differentiate into Tregs in tumor-bearing omenta. In fact, Tregs derived from the pretumor repertoire are sufficient to suppress antitumor immunity and promote tumor growth. However, tumor implantation in the omentum does not promote Treg clonal expansion, but instead leads to increased clonal diversity. Parabiosis experiments show that despite tissue-resident (noncirculating) characteristics of omental Tregs in naïve mice, tumor implantation promotes a rapid influx of circulating Tregs, many of which come from the spleen. Finally, we show that newly recruited Tregs rapidly acquire characteristics of adipose-resident Tregs in tumor-bearing omenta. These data demonstrate that most Tregs in omental tumors are recruited from the circulation and adapt to their environment by altering their homing, transcriptional, and metabolic properties.
Efeitos de um programa de exercícios físicos baseado no método Pilates solo sobre a atividade física, capacidade locomotora e qualidade de vida em homens com amputação de membro inferior
Authors: Rudolpho Sara Maria Soffiatti , Luza Lisiane Piazza , Pires Greicy Kelly Wosniak , Silva Franciele Cascaes da , Lima David Braga de , Oliveira Laiana Cândido de , Caviquioni Thamara , Silva Rudney da 
Published: March 2022

Objetivo: Avaliar os efeitos de um programa de exercícios físicos de 12 semanas baseado no método Pilates Solo sobre atividade física, equilíbrio, capacidade locomotora e qualidade de vida em homens com amputação unilateral de membro inferior. Método: Participaram do estudo 14 pessoas com amputação unilateral de membro inferior, divididos em 2 grupos: Grupo Intervenção – GI (participantes expostos ao protocolo de exercícios baseados no método Pilates Solo) e Grupo Controle – GC (participantes não expostos ao protocolo de exercícios baseados no método Pilates Solo). Foram aplicados os seguintes instrumentos: a) ficha para caracterização dos participantes; b) Physical Activity Scale for Individuals with Physical Disabilities (PASIPD); c) Escala de Equilíbrio de Berg; d) Medida Funcional para Amputados (MFA); e e) Short Form Health Survey (SF-36). Os dados foram analisados por meio da estatística descritiva e inferencial sendo considerados significativos os resultados com p menor ou igual a 0,05. Resultados: Com base nas análises foi possível observar diferença significativa no equilíbrio após o período experimental (p=0,008), a favor do grupo intervenção. Além disso, pode-se observar diferença significativa na média do grupo intervenção para equilíbrio e para aspectos físicos na qualidade de vida (SF-36), assim como o d de Cohen mostrou efeitos de grande magnitude sobre essas variáveis. Conclusão: Logo, os resultados apresentam efeitos positivos na prática do programa de exercícios físicos sobre o equilíbrio dinâmico e estático e na qualidade de vida de pessoas amputadas.
Nietzsche, mentor da Primeira Guerra Mundial?: O que dizem jornais e revistas brasileiros sobre o filósofo (1910-1920)
Authors: Barroso Antonio Vinícius Lomeu Teixeira 
Published: March 2022

O presente artigo pretende examinar como os jornais e revistas brasileiros, entre os anos de 1910 e 1920, vincularam o pensamento do filósofo alemão Friedrich Nietzsche (1844-1900) à Grande Guerra (1914-1918). Desse modo, buscaremos compreender de que maneira o pensador foi associado ao conflito, destacando, as opiniões que salientam seu papel de incitador da guerra. Para tanto, realizaremos um breve percurso historiográfico dessa associação e, posteriormente, a análise dos periódicos do Brasil nessa época.
O sentido da história: considerações sobre o historicismo em Karl Popper
Authors: Souza Romário Ney Rodrigues de Souza 
Published: March 2022

As experiências traumáticas desencadeadas pelos regimes totalitários na primeira metade do século XX deram impulso à crítica de Karl Popper (1992 – 1994) aos sistemas de ideias que abrigam a crença, quer por leis ou por alguma razão histórica, no ordenamento dos destinos dos indivíduos. Objetivamos apresentar a crítica de Popper ao conjunto de ideias nomeadas por ele de historicismo, isto é, a visão de que caberia às Ciências Sociais a função de fazer predições a partir da compreensão das leis de uma história teleológica. As linhas que norteiam as principais teses de Popper serão apontadas nas obras: The Poverty of Historicism (1944-45) e The Open Society and Its Enemies (1945), além do diálogo com autores como Raymond Aron (1905-1983), Isaiah Berlin (1909-1997) e François Furet (1927-1997). Ao mostrar a impossibilidade de se fazer predições por processos de seleção interpretativos a partir da multiplicidade dos temas que constituem os eventos históricos, Popper põe em xeque as leis que determinariam o enredo de uma história teleológica, ao mesmo tempo em que afirma sua crença nas possibilidades da agência humana.
Prevalence, Predictors, Progression, and Prognosis of Hypertension Subtypes in the Framingham Heart Study
Authors: Bourdillon Maximillian T. , Song Rebecca J. , Musa Yola Ibrahim , Xanthakis Vanessa , Vasan Ramachandran S. 
Published: March 2022

Background
The epidemiology of hypertension subtypes has not been well characterized in the recent era.

Methods and Results
We delineated the prevalence, predictors, progression, and prognostic significance of hypertension subtypes in 8198 Framingham Heart Study participants (mean age, 46.5 years; 54% women). The prevalence of hypertension subtypes was as follows: nonhypertensive (systolic blood pressure [SBP] <140 mm Hg and diastolic blood pressure [DBP] <90 mm Hg), 79%; isolated systolic hypertension (ISH; SBP ≥140 mm Hg and DBP <90 mm Hg), 8%; isolated diastolic hypertension (SBP <140 mm Hg and DBP ≥90 mm Hg), 4%; and systolic‐diastolic hypertension (SDH; SBP ≥140 mm Hg and DBP ≥90 mm Hg), 9%. The prevalence of ISH and SDH increased with age. Analysis of a subsample of nonhypertensive participants demonstrated that increasing age, female sex, higher heart rate, left ventricular mass, and greater left ventricular concentricity were predictors of incident ISH and SDH. Higher baseline DBP was associated with the risk of developing isolated diastolic hypertension and SDH, whereas higher SBP was associated with all 3 hypertension subtypes. On follow‐up (median, 5.5 years), isolated diastolic hypertension often reverted to nonhypertensive BP (in 42% of participants) and ISH progressed to SDH (in 26% of participants), whereas SDH frequently transitioned to ISH (in 20% of participants). During follow‐up (median, 14.6 years), 889 participants developed cardiovascular disease. Compared with the nonhypertensive group (referent), ISH (adjusted hazard ratio [HR], 1.57; 95% CI, 1.30–1.90) and SDH (HR, 1.66; 95% CI, 1.36–2.01) were associated with increased cardiovascular disease risk, whereas isolated diastolic hypertension was not (HR, 1.03; 95% CI, 0.68–1.57).

Conclusions
Hypertension subtypes vary in prevalence with age, are dynamic during short‐term follow‐up, and exhibit distinctive prognoses, underscoring the importance of blood pressure subphenotyping.
Is Resettlement Still a Durable Solution? An Analysis in Light of the Proposal for a Regulation Establishing a Union Resettlement Framework
Authors: Ineli-Ciger Meltem 
Published: March 2022

Abstract
Resettlement is generally regarded as a permanent or durable solution for refugees. Resettled refugees classically are granted permanent settlement with the opportunity for eventual citizenship. However, this classic understanding might be changing. In 2016, the European Commission proposed a Regulation establishing a Union Resettlement Framework with a view to creating a more structured, harmonized, and permanent framework for resettlement across the Union. According to the Proposal, resettled persons are to be granted either the refugee status or the subsidiary protection status in the Member States. Similar to the Proposal, more and more states including Denmark and the United States grant resettled refugees and other displaced persons statuses that fall short of the refugee status. In light of these recent developments, this article questions whether resettlement is still a permanent and durable solution for refugees. In doing so, the article also examines duties owed by states towards resettled refugees and other forcibly displaced persons in international law and reviews shortcomings of the Commission Proposal for a Regulation establishing a Union Resettlement Framework.
Resolving Residence of a Company for Tax Purposes in Tanzania: Is ‘Management and Control’ Test Still Relevant?
Authors: Kiunsi Helen B. 
Published: March 2022

Abstract
It is an accepted principle that countries have the right to tax residents and nonresidents on their income from business on source or residence. The determination of the residence of a company for tax purposes based on the “management and control” and ‘place of effective management’ may pose challenges in establishing tax liability of a dual resident corporation. Such challenges cause problems on corporate taxes and transfer pricing between related parties. Similarly, multinational companies may face challenges in ascertaining their tax liability. The new criteria for determination of residence of a company based on mutual agreement under the OECD and UN Models of 2017, have ramification over the two tests. This article analyses residence of a company on the basis of the two tests in Tanzania. It argues that the two tests as used in Tanzania are superseded by new criteria. Finally, it offers a modest proposal for determination of dual resident of a company in Tanzania.
Contested Vision
Authors: Mackenzie Pamela 
Published: March 2022

Abstract
In the seventeenth century, an early member of the Royal Society named Nehemiah Grew (1641–1712) was among the first naturalists to produce illustrations of microscopic plant life. These images were completed according to a set of visual conventions that were informed by his peers but also reflect a distinctive set of concerns and a particular understanding of the natural world. In order to better understand the specificity of Grew’s representations of the microscopic world, this article considers his work in relationship to that of his direct contemporary, the Italian naturalist and physician Marcello Malpighi (1628–1694).
Pacis Encomium
Authors: Hackenbracht Ryan 
Published: March 2022

Abstract
Virgil’s Georgics was a source of pacifistic thinking for Erasmus, More, and Vives, who used figurative readings of the poem to reinforce their notions about the incompatibility of war and Christian society. In doing so, they furthered an interpretive tradition begun by Mancinelli, Valeriano, Landino, and other humanists of the Quattrocento, who were intrigued by the poem’s political potential. In the Enchiridion, Querela Pacis, Utopia, and de Concordia et Discordia, the Georgics functioned as a heuristic for thinking through current events and critiquing violence within Christendom. From soils to trees to cattle and bees, Virgil’s poem supplied Erasmus, More, and Vives with diverse tools for deflating militaristic ideology and imagining alternatives to the status quo. At a time when late scholastics were debating the finer points of iustum bellum, the humanists were moving the discussion into an entirely new direction, using Virgil to envision the abolition of war between Christian states.
Global City Agency and Multilevel Governance in China
Authors: Thürmer Amelie , Meyer-Clement Elena 
Published: March 2022

Abstract
Over the past few decades, cities have become increasingly active in global climate governance. Although most research on city agency has focused on democratic (often Western) cities, the climate-related activities of Chinese cities in global city networks have also expanded, raising the question of whether cities from nondemocratic political systems can be international actors or whether they are merely extensions of their national governments. This article examines how the Chinese Party-state’s institutions and governing instruments shape cities’ global agency and how these structures impact the work of various city networks operating in China. To this end, it analyzes policy reports, documents, and original interview data collected from city network representatives. The findings demonstrate that city networks in China walk a fine line between their door-opening function for cities to global climate governance and their role as transmitters of the central government’s gatekeeping function, thereby sustaining the hierarchical control structures of the Chinese Party-state.
The “Missing Middle”
Authors: Weiss Thomas G. , Wilkinson Rorden 
Published: March 2022

Abstract
This article focuses on the vast number of people who make global governance happen. It probes the role of the unknown people in the “middle” who are largely absent from scholarly gaze: professionals, service teams, and others who act behind the scenes. They are not at the top of public and private organizations (“global governors” in the literature), but they keep the lights on. They accomplish the policy, operational, and support work to move the needle of global governance institutions of all varieties from the local to global. These largely invisible and unheard populations—at least in the scholarly and policy literatures—make global governance work. The “missing middle” is not confined to the everyday contributions of professionals in intergovernmental secretariats because contemporary global governance is not synonymous with international organization, but concerns networked forms of public authority that may or may not include secretariats or states.