bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Clinically Applicable 24-Protein Model for Classifying Risk Subgroups in Pancreatic Ductal Adenocarcinomas using Multiple Reaction Monitoring-Mass Spectrometry
Authors: Son Minsoo , Kim Hongbeom , Han Dohyun , Kim Yoseop , Huh Iksoo , Han Youngmin , Hong Seung-Mo , Kwon Wooil , Kim Haeryoung , Jang Jin-Young , Kim Youngsoo 
Published: February 2021

AbstractPurpose:Pancreatic ductal adenocarcinoma (PDAC) subtypes have been identified using various methodologies. However, it is a challenge to develop classification system applicable to routine clinical evaluation. We aimed to identify risk subgroups based on molecular features and develop a classification model that was more suited for clinical applications.Experimental Design:We collected whole dissected specimens from 225 patients who underwent surgery at Seoul National University Hospital [Seoul, Republic of Korea (South)], between October 2009 and February 2018. Target proteins with potential relevance to tumor progression or prognosis were quantified with robust quality controls. We used hierarchical clustering analysis to identify risk subgroups. A random forest classification model was developed to predict the identified risk subgroups, and the model was validated using transcriptomic datasets from external cohorts (N = 700), with survival analysis.Results:We identified 24 protein features that could classify the four risk subgroups associated with patient outcomes: stable, exocrine-like; activated, and extracellular matrix (ECM) remodeling. The “stable” risk subgroup was characterized by proteins that were associated with differentiation and tumor suppressors. “Exocrine-like” tumors highly expressed pancreatic enzymes. Two high-risk subgroups, “activated” and “ECM remodeling,” were enriched in terms such as cell cycle, angiogenesis, immunocompetence, tumor invasion metastasis, and metabolic reprogramming. The classification model that included these features made prognoses with relative accuracy and precision in multiple cohorts.Conclusions:We proposed PDAC risk subgroups and developed a classification model that may potentially be useful for routine clinical implementations, at the individual level. This clinical system may improve the accuracy of risk prediction and treatment guidelines.See related commentary by Thakur and Singh, p. 3272
A Uniform Computational Approach Improved on Existing Pipelines to Reveal Microbiome Biomarkers of Nonresponse to Immune Checkpoint Inhibitors
Authors: Shaikh Fyza Y. , White James R. , Gills Joell J. , Hakozaki Taiki , Richard Corentin , Routy Bertrand , Okuma Yusuke , Usyk Mykhaylo , Pandey Abhishek , Weber Jeffrey S. , Ahn Jiyoung , Lipson Evan J. , Naidoo Jarushka , Pardoll Drew M. , Sears Cynthia L. 
Published: February 2021

Abstract

Purpose:
While immune checkpoint inhibitors (ICI) have revolutionized the treatment of cancer by producing durable antitumor responses, only 10%–30% of treated patients respond and the ability to predict clinical benefit remains elusive. Several studies, small in size and using variable analytic methods, suggest the gut microbiome may be a novel, modifiable biomarker for tumor response rates, but the specific bacteria or bacterial communities putatively impacting ICI responses have been inconsistent across the studied populations.

Experimental Design:
We have reanalyzed the available raw 16S rRNA amplicon and metagenomic sequencing data across five recently published ICI studies (n = 303 unique patients) using a uniform computational approach.

Results:
Herein, we identify novel bacterial signals associated with clinical responders (R) or nonresponders (NR) and develop an integrated microbiome prediction index. Unexpectedly, the NR-associated integrated index shows the strongest and most consistent signal using a random effects model and in a sensitivity and specificity analysis (P &lt; 0.01). We subsequently tested the integrated index using validation cohorts across three distinct and diverse cancers (n = 105).

Conclusions:
Our analysis highlights the development of biomarkers for nonresponse, rather than response, in predicting ICI outcomes and suggests a new approach to identify patients who would benefit from microbiome-based interventions to improve response rates.
AraC-FdUMP[10] Is a Next-Generation Fluoropyrimidine with Potent Antitumor Activity in PDAC and Synergy with PARG Inhibition
Authors: Haber Alex O. , Jain Aditi , Mani Chinnadurai , Nevler Avinoam , Agostini Lebaron C. , Golan Talia , Palle Komaraiah , Yeo Charles J. , Gmeiner William H. , Brody Jonathan R. 
Published: February 2021

Abstract

AraC-FdUMP[10] (CF10) is a second-generation polymeric fluoropyrimidine that targets both thymidylate synthase (TS), the target of 5-fluorouracil (5-FU), and DNA topoisomerase 1 (Top1), the target of irinotecan, two drugs that are key components of FOLFIRNOX, a standard-of-care regimen for pancreatic ductal adenocarcinoma (PDAC). We demonstrated that F10 and CF10 are potent inhibitors of PDAC cell survival (in multiple cell lines including patient-derived lines) with IC50s in the nanomolar range and are nearly 1,000-fold more potent than 5-FU. The increased potency of CF10 relative to 5-FU correlated with enhanced TS inhibition and strong Top1 cleavage complex formation. Furthermore, CF10 displayed single-agent activity in PDAC murine xenografts without inducing weight loss. Through a focused drug synergy screen, we identified that combining CF10 with targeting the DNA repair enzyme, poly (ADP-ribose) glycohydrolase, induces substantial DNA damage and apoptosis. This work moves CF10 closer to a clinical trial for the treatment of PDAC.

Implications:
CF10 is a promising polymeric fluoropyrimidine with dual mechanisms of action (i.e., TS and Top1 inhibition) for the treatment of PDAC and synergizes with targeting of DNA repair.
Practical Application of Patient-Reported Health Status Measures for Transcatheter Valve Therapies
Authors: Hejjaji Vittal , Cohen David J. , Carroll John D. , Li Zhuokai , Manandhar Pratik , Vemulapalli Sreekanth , Nelson Adam J. , Malik Ali O. , Mack Michael J. , Spertus John A. , Arnold Suzanne V. 
Published: February 2021

Background:
Health status assessment is essential for documenting the benefit of transcatheter aortic valve replacement (TAVR) or transcatheter mitral valve repair on patients’ symptoms, function, and quality of life. Health status can also be a powerful marker for subsequent clinical outcomes, but its prognostic importance around the time of both TAVR and transcatheter mitral valve repair has not been fully defined.

Methods:
Among 73 699 patients who underwent transfemoral TAVR or transcatheter mitral valve repair between 2011 and 2018 (mean age, 81.9±7.0 years, 53% men, 92% TAVR), we constructed sequential models examining the association of health status (as assessed with the Kansas City Cardiomyopathy Questionnaire–Overall Summary Score; KCCQ-OS) at baseline, 30 days, change from baseline to 30 days, and combinations of these assessments with death and heart failure (HF) hospitalization from 30 days to 1 year.

Results:
Although higher baseline KCCQ-OS and 30-day KCCQ-OS scores were each associated with lower risk of death and HF hospitalization (in individual models and in a model including both measures), the 30-day KCCQ-OS was most predictive (death: hazard ratio, 0.89 per 5-point increase [95% CI, 0.89–0.90]; HF hospitalization: hazard ratio, 0.91 [95% CI, 0.90–0.91]). The 30-day KCCQ-OS also was most predictive when included in a separate model with change in KCCQ from baseline to 30 days. Similar findings were noted for the outcomes of death and of HF hospitalization, unadjusted and adjusted for patient factors. All interaction terms between procedure type and KCCQ were not significant, suggesting that health status provided similar prognostic information in both procedures.

Conclusions:
The patient’s assessment of their health status immediately before and 30 days after TAVR and transcatheter mitral valve repair is associated with subsequent risk of death and HF hospitalization, with the 30-day assessment being most strongly associated with outcomes. Our findings support the routine use of KCCQ data as a prognostic tool.
Does Intravenous Thrombolysis Within 4.5 to 9 Hours Increase Clot Migration Leading to Endovascular Inaccessibility?
Authors: Lim Jeremy C. , Churilov Leonid , Bivard Andrew , Ma Henry , Dowling Richard J. , Campbell Bruce C.V. , Parsons Mark W. , Davis Stephen M. , Donnan Geoffrey A. , Mitchell Peter J. , Yan Bernard 
Published: February 2021

Background and Purpose:
Distal clot migration is a recognized event following intravenous thrombolysis (IVT) in the setting of acute ischemic stroke. Of note, clots that were initially retrievable by endovascular thrombectomy may migrate to a distal nonretrievable location and compromise clinical outcome. We investigated the incidence of clot migration leading to clot inaccessibility following IVT in the time window of 4.5 to 9 hours.

Methods:
We performed a retrospective analysis of the EXTEND trial (Extending the Time for Thrombolysis in Emergency Neurological Deficits) data. Baseline and 12- to 24-hour follow-up clot location was determined on computed tomography angiogram or magnetic resonance angiogram. The incidence of clot migration leading to a change from retrievable to nonretrievable location was identified and compared between the two treatment groups (IVT versus placebo).

Results:

Two hundred twenty patients were assessed. Clot migration from a retrievable to nonretrievable location occurred in 37 patients: 21 patients (19.3%) in the placebo group and 16 patients (14.4%) in the IVT group. No significant difference was identified in the incidence of clot migration leading to inaccessibility between groups (
P
=0.336).

Conclusions:
Our results did not show increased clot migration leading to clot inaccessibility in patients treated with IVT.
Body Mass Index and Arterial Stiffness Are Associated With Greater Beat-to-Beat Blood Pressure Variability After Transient Ischemic Attack or Minor Stroke
Authors: Webb Alastair J.S. , Lawson Amy , Mazzucco Sara , Li Linxin , Rothwell Peter M. ,   for the Oxford Vascular Study Phenotyped Cohort
Published: February 2021

Background and Purpose:
Blood pressure variability (BPV) from beat to beat is associated with an increased risk of cardiovascular events and enables rapid assessment of BPV, but the underlying causes of elevated BPV are unclear.

Methods:
In consecutive patients within 4 to 6 weeks of transient ischemic attack or nondisabling stroke (OXVASC [Oxford Vascular Study]), continuous noninvasive blood pressure was measured beat to beat over 5 minutes (Finometer). Arterial stiffness was measured by carotid-femoral pulse wave velocity (Sphygmocor). After automated and manual data cleaning, associations between BPV (residual coefficient of variation), demographic factors, and arterial stiffness were determined for both systolic and diastolic blood pressure, by ANOVA and linear models. Relationships between demographic factors and arterial stiffness were determined by interaction terms and mediation.

Results:

Among 1013 patients, 54 (5.3%) were in AF, and 51 (5%) had low-quality recordings. In a general linear model including the remaining 908 participants, systolic BPV (SBPV) was most strongly associated with age (
P
=0.00003), body mass index (BMI;
P
=0.003), and arterial stiffness (
P
=0.008), with weaker independent associations with current smoking (
P
=0.01) and a low diastolic blood pressure (
P
=0.046). However, while there was a linear increase in SBPV with BMI in men, in women, SBPV was lowest for a BMI in the normal range but was greater below 20 or above 30 (ANOVA,
P
=0.012; BMI-sex interaction,
P
=0.03). Although BMI and pulse wave velocity were partially independent, increased pulse wave velocity mediated ≈32% of the relationship between increased BMI and SBPV (
P
<0.001).

Conclusions:
Vascular aging, manifest as arterial stiffness, was a strong determinant of increased SBPV and partially mediated the effect of increased BMI. However, although high BMI was independently associated with SBPV in both sexes, a low BMI was associated with increased SBPV only in women. SBPV may partially mediate the relationship between BMI and cardiovascular events, while obesity may provide a modifiable target to reduce SBPV and cardiovascular events.
Two-State Kinetic Model of Rates of Stroke Recurrence in the POINT Study Population
Authors: Brorson James R. , Bulwa Zachary B. 
Published: February 2021

Background and Purpose:
Following an acute ischemic stroke or transient ischemic attack, 2 rates of stroke recurrence are suggested by data from trials of acute secondary prevention treatments: a transient rapid rate followed by a persisting slower rate of stroke.

Methods:
A kinetic model was constructed based on underlying vulnerable and stabilized states of patients following acute ischemic events related by fixed transition rates. Its predictions were fitted by nonlinear regression to the observed timing of outcome events in patients in the POINT trial (Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke).

Results:
The modeled survivor function produced a close fit to the observed data. The model's predicted kinetic rates suggest that, among subjects in the control group, the event rate was 100-fold higher in the vulnerable state than in the stabilized state. Active treatment halved this rapid rate and had little effect on event rates in the stabilized state. If at least one-tenth of the study population began in the vulnerable state, the rate of transition from the vulnerable to the stabilized state was still faster, with a half-life of only 1 to 2 days.

Conclusions:
Examination of kinetics of stroke occurrence, and of the rates associated with modeled state transitions, may provide insights into the underlying pathophysiological events that are targets for acute secondary prevention of stroke.
Diversity and population densities of plant-parasitic nematodes in commercial and smallholder pineapple production in Kenya
Authors: Kiriga Agnes W. , Coyne Danny , Atandi Janet G. , Beek Nikolai V. , Haukeland Solveig 
Published: February 2021

Summary
Plant-parasitic nematodes (PPN) cause significant yield reduction in commercial pineapple (Ananas comosus) worldwide. In Kenya, few nematode studies have been conducted, although the main commercial pineapple producer has sole dispensation to use Telone II (1,3-Dichloropropene) indicating the magnitude of the nematode problem. This study was conducted with the aim to investigate the population densities and diversity of nematodes in two commercial plantations with two contrasting management practices. We additionally assessed the influence of crop age and compared this with nearby smallholder pineapple production systems. Soil and root samples were collected from fields of different ages in each commercial plantation and from 29 smallholder fields. A total of 18 genera were associated with pineapple, with a relatively greater diversity found in smallholder than commercial farms. The most prevalent genus was Meloidogyne spp. (M. javanica) followed by Helicotylenchus spp., Tylenchus spp. and Aphelenchoides spp. PPN densities were higher in relatively older fields of 24 and 36 months than from fallow and 3-month-old fields. Regression analysis additionally demonstrated the rise of PPN densities with age of pineapple fields, especially Meloidogyne spp., while free-living nematode densities declined. This study provides an indication of the high level of PPN infection in pineapple in Kenya, which would constitute an important factor contributing to low yields. The study confirms an obvious need for pineapple producers to control PPN to improve crop yields.
Traces of Late Medieval Jewish Scotism: A Catalan Translation in Hebrew Script of De distinctione predicamentorum by Petrus Thomae
Authors: Baum Ilil 
Published: February 2021

Abstract
Jewish-Christian intellectual relations in late medieval Spain are discussed in light of a curious fragment in Hebrew script from the Vatican Library. The fragment contains an unknown translation from Latin to Catalan (in Hebrew characters) of the work of the Catalan Franciscan monk Petrus Thomae, De distinctione predicamentorum. This translation is also compared with Thomae’s Tractatus brevis de modis distinctionum as it demonstrates an intermediate version between these two works by Petrus Thomae, though it resembles the first more closely. These traces invite a discussion on the existence of “Jewish Scotism” among the Jews of Catalonia, and after the expulsion, among their descendants, who probably made their way to Italy. The text is among the latest evidence of the use of Catalan in Hebrew characters on the cusp of the sixteenth century.
Nationaliteit in Belgisch Congo: Constructie en Verbeelding
Authors: De Meester Tom 
Published: February 2021

Nationality in the Belgian Congo: Construction and Imagination
This article discusses nationality law in the Belgian Congo and analyses theoretical disputes in the contemporary legal literature concerning issues of nationality and racial segregation in colonial society. The Belgian nationality of the black inhabitants of the Congo region is depicted as mere rhetoric, since it did not protect them from racial segregation and severe discrimination. The minor importance of national boundaries in colonial society and the domination of social reality by a hegemonic racial idiom were reflected in an insufficient and inaccurate nationality law. Colonial law and regulations moreover, were built around racial categories the mutual boundaries of which were not clearly defined.
De Eigennaam en het “Zelflofdicht” in de Afrikaanse Orale Literatuur
Authors: Kabuta Ngo Semzara 
Published: February 2021

The proper name and “selfpraise poetry” in the African oral literature
There is a particular poetic genre in African oral literature, based on selfpraise. Selfpraise poetry is built on proper names and formulas, with the metaphor and hyperbole as central style figures. In this article, we situate the proper name inside African culture and show the link between the proper name and selfpraise. Furthermore, we try to grasp the meaning of praising oneself in African culture. The study relies essentially on Cilubà and Kilubà data, but references are made to other languages, in order to show that the genre is not limited to the Lubà oral literature. The first part concentrates on name giving and its meaning. The second part is an analysis of selfpraise poetry, with examples in different languages.
War as Exit from Exclusion? The Formation of Mayi-Mayi Militias in Eastern Congo
Authors: Vlassenroot Koen , Van Acker Frank 
Published: February 2021

War as Exit from Exclusion? The Formation of Mayi-Mayi Militias in Eastern Congo
In eastern Congo scores of young and marginalized people have been increasingly attracted to the mobilising efforts of new local actors. The inquiry into this phenomenon traces the emergence of the first militias to the end of the eighties. These first generation militias were a result of the growing willingness of marginalized youngsters and school drop-outs to form groups of under-aged combatants acting against every representative of modern political authority and against their desperate feelings of exclusion, for which both their political and social environment were held responsible. As they had nothing more to lose than their marginalization, rebellion became an option, both as a survival strategy and as a strategy of self-defence against a predatory political and social order. The shiftiness of their ideological basis and allies only further proved what these first militias were about: a search for alternatives to a situation of acute deprivation.
This article reveals that the present RCD rebellion that rages through the eastern parts of the Democratic Republic of Congo has had an escalating effect on the proliferation of new militias. Before, the Kabila-led AFDL rebellion had already offered the already existing militias a new cause: that of an anti-Tutsi force fighting against foreign occupation. In resistance to the effects of state collapse and armed foreign interventions, rural and urban youth today have combined former traditions and newly developed patterns of mobility in an interpretation of customary and national defence. This has not meant that they link up with the traditional emanations of authority. Rather, a crisis in the social fabric has meant a shift in authority towards these combatants and the use of violence. In addition, shared feelings of antipathy towards the ‘Tutsi-aggressors’ have facilitated the creation of links between these diverse local groupings and other, foreign, factions of armed militia roaming the local countryside. Consolidation, however, remains unlikely as this shared ideology does not run very deep and alliances continuously change.
The question remains what the future impact of these militias might be on the local social order. On the one hand, for several years now in some remote areas these armed groupings have become the only representatives of any authority structure, even if this structure is based on violence. Contrary to other cases, these militias in South Kivu are still closely linked to the rural population and have not turned against them. On the other hand, the dynamic of the Inter-Congolese Dialogue has forced their leaders to present their grievances to the outside world.
The Place of Sub-Sahara Africa in the Worldsportsystem
Authors: Dejonghe Trudo 
Published: February 2021

The place of Sub-Sahara Africa in the Worldsportsystem
The contemporary world sportsystem is developed through globalisation with its homogenisation and heterogenisation processes. The result of these opposite forces is the division of the world in 6 classes. Sub-Sahara Africa underwent, with the exception of South-Africa, Namibia and Zimbabwe, a total and passive acceptance of the western (British) modern sports. The place of that part of Africa is analogue to and correlates with its place in Wallerstein’s worldsystem periphery. The introduction of modern sports is associated with the spatial diffusion of the 19th century British hegemonic cultural imperialism. The purpose of this policy was a transformation of the traditional society into a modern functional world-culture and the incorporation of that part of the world in the world-system. The anti-western feelings after the independence resulted in a political Pan-Africanism. However, sport and more specific soccer, a typical product of the western domination, has not been rejected. On the contrary, local politicians used it to create a national identity. The strong link between soccer and soil resulted in a strong form of topophily. This connection was transformed into sportnationalism and created in the, through artificial borders developed, nations a unity and a national pride. The outcome of sport games was used to demonstrate the successes in politics and economics. The absence of any political platform on which the Third World had a strong voice brought about that the international sport scene, such as the FIFA, was used for the unification of the Third World against the former colonial powers. Nowadays, the globalisation processes result in an increasing labour migration of African football players to the rich core competitions in Europe. This form of migration can be classified as another form of “cash crop” or in this case “foot drain..”
“As Roman imperialism laid the foundation of modern civilisation and led wild barbarians of these islands (Britain) along the path of progress, so in Africa today we are repaying the debt, and bringing to the dark places of the earth – the abode of barbarism and cruelty – the torch of culture and progress… we hold these countries because it is the genius of our race to colonise, to trade and to govern” (quote by the English educationist Sir Frederick Lugard (1858-1954) in Mandell, 1986: p.102).