bluuebunny/crossref_metadata_2025 huggingface dataset:
Supplemental Material: Ice-sheet melt drove methane emissions in the Arctic during the last two interglacials
Authors: Dessandier Pierre-Antoine , al. et
Published: March 2021

Supplemental methods on micropaleontolgy, dating and MeBo drilling and supplemental notes on chronology and foraminiferal preservation.
Electroacupuncture for pain relief in labour inhibits spinal p38 MAPK-mediated prostaglandin E2 release and uterine prostaglandin E2 receptor expression in rats
Authors: Jiang Gui-Xiu , Jiang Qiu-Yan , Mo Hai-Xia , Li Li , Wang Meng-Ying
Published: March 2021

Background:

p38 mitogen-activated protein kinase (p38 MAPK) activation involves the release of prostaglandin E2 (PGE2) and hyperalgesia. We have previously reported that electroacupuncture (EA) relieves labour pain, but the potential mechanisms remain unclear.

Objective:

To observe the effects of EA on labour pain intensity, serum PGE2 levels and the p38 MAPK signalling pathway in rats during labour.

Methods:

Female rats copulated with male rats to induce pregnancy, and then received castor oil to trigger labour. During labour, rats remained untreated (Control group, n=30) or were treated with remifentanil (n=30) or EA at Jiaji (n=30) or SP6+LI4 (n=30), respectively. The warm water tail-flick test was used to assess labour pain. Serum PGE2 levels were measured by ELISA. Protein expression of prostaglandin E2 receptor (PGER2), p38 MAPK and phospholipase A2 (PLA2) were analysed by Western blotting, and mRNA levels were measured by real-time PCR.

Results:

EA treatment at Jiaji or SP6+LI4 significantly relieved labour pain, decreased serum PGE2 levels and inhibited protein and gene expression of PGER2 in the myometrium. Moreover, EA reduced protein expression of PLA2 and p38 MAPK, and inhibited phosphorylation of p38 MAPK in the lumbar spinal cord but not in the cerebral grey matter. Additionally, EA markedly decreased mRNA levels of p38 MAPK in the lumbar spinal cord and significantly reduced PLA2-IV mRNA levels in both the lumbar spinal cord and cerebral grey matter.

Conclusions:

This study indicates that EA relieves labour pain through, at least in part, inhibition of spinal p38 MAPK-mediated PGE2 release and uterine PGER2 expression in rats.
Genomic characterisation of multiple myeloma: study of a Portuguese cohort
Authors: Couto Oliveira Alexandra , Ribeiro Ilda Patrícia , Pires Luís Miguel , Gonçalves Ana Cristina , Paiva Artur , Geraldes Catarina , Roque Adriana , Sarmento-Ribeiro Ana Bela , Barbosa de Melo Joana , Carreira Isabel Marques
Published: March 2021

Multiple myeloma (MM) genomic complexity reflects in the variable patients’ clinical presentation. Genome-wide studies seem to be a reasonable alternative to identify critical genomic lesions. In the current study, we have performed the genomic characterisation of a Portuguese cohort of patients with MM by array comparative genomic hybridisation. Overall, the most frequently detected alterations were 13q deletions, gains of 1q, 19p, 15q, 5p and 7p and trisomy 9. Even though some identified genomic alterations were previously associated with a prognostic value, other abnormalities remain with unknown, but putative significance for patients’ clinical practice. These genomic alterations should be further assessed as possible biomarkers.
The Severe Respiratory Insufficiency Application (SRI App): a pilot randomised controlled trial
Authors: Majorski Daniel Sebastian , Schwarz Sarah Bettina , Magnet Friederike Sophie , Ahmad Rebar , Mathes Tim , Windisch Wolfram
Published: March 2021

An application (app) for the Severe Respiratory Insufficiency Questionnaire (SRI) has been designed and developed for mobile devices. In a randomised controlled trial comprising 60 patients with chronic respiratory failure, the app was compared with the classic paper SRI. Thereby, it was shown that the SRI app is a practical tool that is well accepted. Missing values can be completely avoided by using the SRI app. Finally, reliability, convergent and discriminant validities were established. Accordingly, for the individual SRI subscales, Cronbach’s alpha ranged between 0.56 and 0.81 (app) and between 0.54 and 0.83 (paper), respectively. The multilingual SRI app is accessible free of charge for non-profit research purposes.
Airborne occupational exposures and the risk of developing respiratory symptoms and airway obstruction in the Lifelines Cohort Study
Authors: Faruque Md Omar , Boezen H Marike , Kromhout Hans , Vermeulen Roel , Bültmann Ute , Vonk Judith M
Published: March 2021

Objectives

To date, only a few studies have investigated the associations between occupational exposures and respiratory outcomes longitudinally in the general population. We investigated the associations between occupational exposures and the development of respiratory symptoms and airway obstruction in the Lifelines Cohort Study.

Methods

We included 35 739 occupationally active subjects with data on chronic cough, chronic phlegm, chronic bronchitis or airway obstruction at baseline and approximately 4.5 years follow-up. Exposures to biological dust, mineral dust, gases/fumes, pesticides, solvents and metals in the current job at baseline were estimated with the ALOHA+job-exposure matrix (JEM). Airway obstruction was defined as FEV1/FVC below the lower limit of normal. Logistic regression analysis adjusted for baseline covariates was used to investigate the associations.

Results

At follow-up, 1888 (6.0%), 1495 (4.7%), 710 (2.5%) and 508 (4.5%) subjects had developed chronic cough, chronic phlegm, chronic bronchitis and airway obstruction, respectively. High exposure to biological dust was associated with a higher odds to develop chronic cough and chronic bronchitis. High exposure to pesticides was associated with a higher odds for the development of all respiratory symptoms and airway obstruction. In the multiple exposures analyses, only the association between pesticides exposure and respiratory symptoms remained.

Conclusions

Subjects exposed to high pesticides had a higher odds to develop respiratory symptoms on average 4.5 years later. Control measures should be taken to reduce pesticides exposure among the working population to prevent respiratory symptoms and airway obstruction.
A comprehensive economic assessment of the health effects of tobacco use and implications for tobacco control in Bangladesh
Authors: Nargis Nigar , Faruque Golam Mohiuddin , Ahmed Maruf , Huq Iftekharul , Parven Rehana , Wadood Syed Naimul , Hussain AKM Ghulam , Drope Jeffrey
Published: March 2021

Background

Despite modest progress in reducing tobacco use, tobacco remains one of the major risk factors for non-communicable diseases in Bangladesh.

Methods

Using disease-specific, prevalence-based, cost-of-illness approach, this research estimated the economic costs of tobacco use and exposure to secondhand smoke based on data collected from a nationally representative survey of 10 119 households in 2018.

Results

The study estimated that 1.5 million adults were suffering from tobacco-attributable diseases and 61 000 children were suffering from diseases due to exposure to secondhand smoke in Bangladesh in 2018. Tobacco use caused 125 718 deaths in that year, accounting for 13.5% of all-cause deaths. The total economic cost was 305.6 billion Bangladeshi taka (BDT) (equivalent to 1.4% of gross domestic product or US$3.61 billion), including direct costs (private and public health expenditures) of BDT83.9 billion and indirect costs (productivity loss due to morbidity and premature mortality) of BDT221.7 billion. The total economic cost of tobacco more than doubled since 2004.

Conclusion

Tobacco use imposes a significant and increasing disease and financial burden on society. The enormous tobacco-attributable healthcare costs and productivity loss underscore the need to strengthen the implementation of tobacco control policies to curb the epidemic.
Homogeneous almost complex manifolds and their compact quotients
Authors: Kim Kang-Tae , Lee Kang-Hyurk , Nagata Yoshikazu
Published: March 2021

This paper investigates the (non)existence of compact quotients of the homogeneous almost-complex strongly-pseudoconvex manifolds discovered and classified by Gaussier–Sukhov [Wong–Rosay theorem in almost complex manifolds, http:www.arXiv.org:math.CV/0307335 ; On the geometry of model almost complex manifolds with boundary, Math. Z. 254(3) (2006) 567–589] and Lee [Domains in almost complex manifolds with an automorphism orbit accumulating at a strongly pseudoconvex boundary point, Michigan Math. J. 54(1) (2006) 179–205; Strongly pseudoconvex homogeneous domains in almost complex manifolds, J. Reine Angew. Math. 623 (2008) 123–160].
EFFECT OF ANISOTROPIC SURFACE TENSION ON THE GROWTH OF COLUMNAR CRYSTALS IN TERNARY UNDERCOOLED MELTS
Authors: FAN HAILONG , SHAN YANYAN , CHEN MINGWEN
Published: March 2021

The effect of anisotropic surface tension on the growth of columnar crystals in ternary melt is studied, and the approximate analytical solution of the growth morphology of columnar crystals is given. It is found that in the initial stage of growth, some parts of the interface grow outward, while some parts first grow inward, and grow outward together with other parts after reaching a certain depth, which makes the columnar crystal interface form a remarkable concave and convex formation. Compared with the case in the pure melt and ternary alloy melt, the component added in the ternary alloy melt decreases the effect of the anisotropic surface tension.
Elastic-Plastic Buckling and Postbuckling Finite Element Analysis of Plates Using Higher-Order Theory
Authors: Taczała Maciej , Buczkowski Ryszard , Kleiber Michal
Published: March 2021

In this paper, some of the displacement-based plate theories are used to investigate the elastic-plastic analysis of plates in the framework of the finite element method including the buckling and postbuckling effects with the focus on the general third-order plate theory (GTPT). The plate calculation results were compared with the results obtained using 64-nodes solid elements involving Lobatto integration scheme. The problem is solved using the Newton–Raphson method applying modified Crisfield constant arc-length procedure. The results show good agreement of results and the GTPT can be acknowledged to fulfill essential criteria for application to the elastic-plastic analysis of thin and thick plates.
On the oriented Thompson subgroup F→3 and its relatives in higher Brown–Thompson groups
Authors: Aiello Valeriano , Nagnibeda Tatiana
Published: March 2021

A few years ago the so-called oriented subgroup [Formula: see text] of the Thompson group [Formula: see text] was introduced by V. Jones while investigating the connections between subfactors and conformal field theories. In the coding of links and knots by elements of [Formula: see text] it corresponds exactly to the oriented ones. Thanks to the work of Golan and Sapir, [Formula: see text] provided the first example of a maximal subgroup of infinite index in [Formula: see text] different from the parabolic subgroups that fix a point in [Formula: see text]. In this paper we investigate possible analogues of [Formula: see text] in higher Thompson groups [Formula: see text], with [Formula: see text], introduced by Brown. Most notably, we study algebraic properties of the oriented subgroup [Formula: see text] of [Formula: see text], as described recently by Jones, and prove in particular that it gives rise to a non-parabolic maximal subgroup of infinite index in [Formula: see text] and that the corresponding quasi-regular representation is irreducible.
Soft Int-Field Extension
Authors: Ghosh Jayanta , Mandal Dhananjoy , Samanta Tapas Kumar
Published: March 2021

The relation between soft element-wise field and soft int-field has been established and then some properties of soft int-field are studied. We define the notions of soft algebraic element and soft purely inseparable element of a soft int-field extension. Some characterizations of soft algebraic and soft purely inseparable int-field extensions are given. Lastly, we define soft separable algebraic int-field extension and study some of its properties.
Solving Portfolio Optimization Problems Using MOEA/D and Lévy Flight
Authors: He Yifan , Aranha Claus
Published: March 2021

Portfolio optimization is a financial task which requires the allocation of capital on a set of financial assets to achieve a better trade-off between return and risk. To solve this problem, recent studies applied multi-objective evolutionary algorithms (MOEAs) for its natural bi-objective structure. This paper presents a method injecting a distribution-based mutation method named Lévy Flight into a decomposition based MOEA named MOEA/D. The proposed algorithm is compared with three MOEA/D-like algorithms, NSGA-II, and other distribution-based mutation methods on five portfolio optimization benchmarks sized from 31 to 225 in OR library without constraints, assessing with six metrics. Numerical results and statistical test indicate that this method can outperform comparison methods in most cases. We analyze how Lévy Flight contributes to this improvement by promoting global search early in the optimization. We explain this improvement by considering the interaction between mutation method and the property of the problem. We additionally show that our method perform well with a round-lot constraint on Nikkei.
Predictive Accuracy of a Polygenic Risk Score for Postoperative Atrial Fibrillation After Cardiac Surgery
Authors: Kertai Miklos D. , Mosley Jonathan D. , He Jing , Ramakrishnan Abinaya , Abdelmalak Mark J. , Hong Yurim , Shoemaker M. Benjamin , Roden Dan M. , Bastarache Lisa
Published: March 2021

Background:

Postoperative atrial fibrillation (PoAF) remains a significant risk factor for increased morbidity and mortality after cardiac surgery. The ability to accurately identify patients at risk through clinical risk factors is limited. There is growing evidence that polygenic risk contributes significantly to PoAF and incorporating measures of genetic risk could enhance prediction.

Methods:

A retrospective cohort study of 1047 patients of White European ancestry who underwent either coronary artery bypass grafting or valve surgery at a tertiary academic center and were free from a history or persistent preoperative atrial fibrillation. The primary outcome was defined as PoAF based on postoperative ECG reports, medical record documentation, and changes in medication. The exposure was a polygenic risk score (PRS) comprising 2746 single-nucleotide polymorphisms previously associated with atrial fibrillation risk. The prediction of PoAF risk was assessed using measures of model discrimination, calibration, and net reclassification improvement.

Results:

A total of 259 patients (24.7%) developed PoAF. The PRS was significantly associated with a higher risk for PoAF (odds ratio, 1.63 per SD increase in PRS [95% CI, 1.41–1.90]). Addition of PRS to patient- and procedure-related predictors of PoAF significantly increased the C statistic from 0.742 to 0.782 (change in C statistic, 0.040 [95% CI, 0.021–0.060]) while maintaining good calibration. The addition of the PRS to patient- and procedure-related predictors of PoAF improved model fit (likelihood ratio test,
P
=2.8×10
−15
) and significantly improved measures of reclassification (net reclassification improvement, 0.158 [95% CI, 0.066–0.274]).

Conclusions:

The PRS for PoAF was associated with improved discrimination, calibration, and risk reclassification compared with conventional clinical predictors suggesting that a PoAF PRS may enhance risk prediction of PoAF in patients undergoing coronary artery bypass grafting or valve surgery.
Advancing human rights in legally plural Africa: the role of development actors in the justice sector
Authors: Corradi Giselle
Published: March 2021

This dissertation examines the role of justice sector aid in sub-Saharan Africa regarding the relationship between human rights and local legal orders from a normative and empirical point of view. At the normative level, it explores how socio-legal theory on legal pluralism and human rights’ cross-contextual implementation may inform the practice of development actors in the justice sector. Based on case studies in Sierra Leone and Mozambique, the research applies this body of knowledge to the analysis of empirical data on development actors' policies and interventions. The conclusion argues that the following issues deserve particular attention: the adoption of a users' perspective regarding which local justice providers are targeted by policies and interventions, consideration of how different modes of dispute processing relate to the implementation of human rights, engagement with local knowledge and a critical approach to human rights cross-contextual application.
Arbuscular mycorrhizal fungi associated with shade trees and Coffea arabica L. in a coffee-based agroforestry system in Bonga, Southwestern Ethiopia
Authors: Sewnet Tadesse Chanie , Tuju Fassil Assefa
Published: March 2021

In a first step to understand the interactions between Colfea arabica L. trees and mycorrhizae in Ethiopia, an investigation of the current mycorrhizal colonization status of roots was undertaken. We sampled 14 shade tree species occurring in coffee populations in Bonga forest, Ethiopia. Milletia ferruginea, Schefflera abyssinica, Croton macrostachyus, Ficus vasta, F. sur, Albizia gummifera, Olea capensis, Cordia africana, Ehretia abyssinica, Pouteria adolfi-friederici, Pavetta oliveriana, Prunus africana, Phoenix reclinata and Polyscias fulva. Coffee trees sampled under each shade tree were all shown to be colonized by arbuscular mycorrhizal fungi (AM fungi). Four genera and 9 different species of AM fungi were found in the soils. Glomus (Sp1, Sp2, & Sp3 & Sp4), Scutellospora (Sp1 & Sp2) and Gigaspora (Sp1 & Sp2) were found under all 14 shade tree species, whereas Acaulospora (Sp1) occurred only in slightly acidic soils, within a pH range of 4.93-5.75. Generally, roots of the coffee trees were colonized by arbuscules to a greater degree than those of their shade trees, the arbuscular colonization percentage (AC%) of the former being higher than the latter (significant difference at 0.05 level). Though differences were not statistically significant, the overall hyphal colonization percentage (HC%) and mycorrhizal hyphal colonization percentage (MHC%) were shown to be slightly higher under coffee trees than under their shade trees. However, the differences were statistically significant at 0.05 level in the case of HC% values of coffee trees under Pouteria adolf-friederici and MHC% under Cordia africana. Spore density and all types of proportional root colonization parameters (HC%, MHC%, AC% and vesicular colonization percentage, VC%) for both coffee and shade trees were negatively and significantly correlated with organic soil carbon, total N, available P, EC and Zn. Correlation between arbuscular colonization for coffee (AC%) and organic carbon was not significantly positive at a 0.05 level. Incidence of specific spore morphotypes was also correlated with physical and chemical soil properties. Results indicate that AM fungi could potentially be important in aforestation and help to promote coffee production activities in Ethiopia providing an alternative to expensive chemical fertilizer use, and would offer management methods that take advantage of natural systems dynamics that could potentially preserve and enhance coffee production.
Estimation of N20 and NO emission from a tropical highland forest in Rwanda
Authors: Ghehi Nasrin Gharahi
Published: March 2021

The research of this work fits within the broad subject of greenhouse gas emissions and climate change. More specifically, this work focuses on the contribution of tropical forest soils to the atmospheric N20 and NO budgets. Nitrous oxide has a global warming potential of 310 relative to CO2 and is one of the main greenhouse gases covered by the United Nations Framework Convention on Climate Change (UNFCCC). Nitrous oxide also plays a key role in modulating the stratospheric ozone layer. Tropical forest soils are considered to be the largest natural source of N20. Additionally, they can produce considerable amounts of NO. Estimates of the contribution of tropical rainforest ecosystems, which cover u50 x ro6 ha of the global land surface, to atmospheric N20 and NO have a high uncertainty. Despite the fact that tropical forest soils are considered to be a key source of N20 and NO2 only a relatively small number of detailed studies investigating the temporal and spatial variability of the N20 and NO soil-atmosphere exchange are available, particularly for Africa. Therefore the general objective of this research was to improve N20 and NO emission predictions from tropical forest. The research has been carried out in the Nyungwe forest in Rwanda for which a large number of legacy data are available. The results of this thesis led to (i) a better understanding of the N20 and NO source strength of a central African tropical forest soil, (ii) improved NO and N2O emission estimates from a central African tropical highland forest and more insight into the importance of soil properties controlling N20 and NO emissions and (iii) a better insight in those parameters that preferentially should be monitored to allow better global simulations of N20 and NO emissions from tropical forests.
Characteristics of participants in an HIV prevention intervention for youth in Rwanda: results from a longitudinal study
Authors: Celis Hanne , Jingwa Brian A. , Degomme Olivier , Van Rossem Ronan , Temmerman Marleen , Michielsen Kristien
Published: March 2021

Introduction. This paper studies determinants of participation in a peer-led school-based HIV prevention intervention in Rwanda. Methods. A baseline survey among 1071 students (mean age 17 years) assessed potential determinants of participation, while a follow-up six months in the intervention measured actual participation in the intervention. Statistical models were built using multivariate linear and multinomial regression analysis predicting overall participation, participation in group discussions and individual counseling. Results. Those who recently had sex, had been tested for HIV, feel more susceptible to HIV, have a higher sexual self-concept, a more positive future perspective (only for non-sexually active), and boys, were more likely to participate in group activities. Also students from the same class as the peer educator and boarding school students were more likely to participate in group activities. Older students and those with low external health locus of control participated more in individual counseling. Discussion. Participation could be increased by investing in general well-being of young people, organizing girls-only activities, and diversifying activities.
Conceptualizing Illness: Nodding Syndrome in Northern Uganda
Authors: van Bemmel Karin
Published: March 2021

This paper presents an ethnographic study of conceptualizations of nodding syndrome (NS) in Uganda. NS is a poorly understood condition characterized by repetitive nodding of the head, mental retardation and stunted growth, which affects thousands of children in northern Uganda, South Sudan and Tanzania. Although extensive research for causative agents has been conducted, no convincing single cause has been reported. This study establishes an understanding of different representations of NS and argues that the episodes of head nodding are related to the socio-political body in which they are manifested. Three interwoven approaches towards NS take main stage whereby the syndrome is presented as a biomedical, spiritual and/or political problem. The conceptualizations are linked to different notions of healing and affected families combine various forms of therapy. Through the examination of different narratives, this study disrupts the idea of a singular perspective on illness and pleads for a focus on motion and plurality.
Jesuits and Conversos as a “Tragic Couple”: Introductory Remarks
Authors: Stuczynski Claude B.
Published: March 2021

This article introduces the phenomenon of Jesuit-converso interactions, mostly in the early modern Iberian world. It summarizes the shifting attitudes of the Society of Jesus vis-à-vis New Christians of Jewish origin as actual or potential Jesuits and maps the multifaceted and variegated interplay between Jesuit priests and converso laymen, understood as a “tragic couple” relationship. This brief survey emphasizes the historiographical contribution of the last generations of Jesuit scholars, and of the five articles included in this special issue of the Journal of Jesuit Studies, to disclose a more overt “historical memory” of the Society of Jesus.
4. Jordan
Authors: Tweissi Basim
Published: March 2021

This chapter will shed light on the main features of the Jordanian media system and how it relates to the political, economic, and legal systems. It focuses on the efforts to develop a sustainable media industry under difficult circumstances. For many decades, Jordan navigated the turbulent waters of the Middle East, the scene of devastating regional wars, civil wars, uprisings, and political instability, all of which undermined the efforts for political reform and the development of a healthy, robust media.
8. Qatar
Authors: Galal Ehab
Published: March 2021

The State of Qatar is a new, small, and extremely rich country, ruled by the Al-Thani family and with a population of which a majority are non-Qatari nationals. It is also a country mostly known for the satellite channel Al-Jazeera. This cocktail of smallness, royal rule, and money is crucial for understanding the media landscape in Qatar, which in basic terms must be divided between the national media and the global satellite consortium of Al-Jazeera. Despite their different audiences, both media types are used and managed to consolidate and strengthen the rule and influence of Qatar and the Al-Thani family.
10. Kuwait
Authors: Alsalem Fatima
Published: March 2021

The media in Kuwait is relatively free and includes a wide variety of viewpoints expressing disparate views in a unique competitive culture. The press in Kuwait has always been privately-owned by influential elites, allowing for wide range of opinion expression, but it has been limited to some degree by censorship and media laws. Nevertheless, the press exerts a strong influence on public opinion. Private broadcast media emerged in 2004 when the state ban was removed. Although private TV and radio stations enjoy a fair amount of freedom in Kuwait, especially when compared with other Gulf states, they are subject to government laws and regulations.
18. Morocco
Authors: Zaid Bouziane , Ibahrine Mohammed
Published: March 2021

The chapter provides an account of why the media structure in Morocco is an uneven playing field with the State having the advantage. It argues that observable configurations of power over media are mainly tied to a repressive media culture and heritage that can be fairly described as a competitive authoritarian regime. Argumentation is grounded in an analysis of history and the political economy of media.
Conclusion
Authors: Richter Carola , Kozman Claudia
Published: March 2021

What do we learn from comparing the individual media systems of Arab countries? We consciously refrained from building a typology for the eighteen Arab countries that are examined in this book. Instead, we have opted for highlighting major themes that we detected when carefully reviewing the seven dimensions that each author used in the analysis of the respective countries. These themes comprise 1) The state’s approach to media, 2) Media ownership, 3) Fragmentation and polarization, 4) Technological advancement and innovation, and 5) Transnational mobility and connection. We explain how the media systems examined differ or concur with regard to these five themes.
The pathobiology of thrombosis, microvascular disease, and hemorrhage in the myeloproliferative neoplasms
Authors: Hasselbalch Hans Carl , Elvers Margitta , Schafer Andrew I.
Published: March 2021

Thrombotic, vascular, and bleeding complications are the most common causes of morbidity and mortality in the Philadelphia chromosome–negative myeloproliferative neoplasms (MPNs). In these disorders, circulating red cells, leukocytes, and platelets, as well as some vascular endothelial cells, each have abnormalities that are cell-intrinsic to the MPN driver mutations they harbor (eg, JAK2 V617F). When these cells are activated in the MPNs, their interactions with each other create a highly proadhesive and prothrombotic milieu in the circulation that predisposes patients with MPN to venous, arterial, and microvascular thrombosis and occlusive disease. Bleeding problems in the MPNs are caused by the MPN blood cell-initiated development of acquired von Willebrand disease. The inflammatory state created by MPN stem cells in their microenvironment extends systemically to amplify the clinical thrombotic tendency and, at the same time, preferentially promote further MPN stem cell clonal expansion, thereby generating a vicious cycle that favors a prothrombotic state in these diseases.
Annual incidence and severity of acute episodes in hereditary thrombotic thrombocytopenic purpura
Authors: Tarasco Erika , Bütikofer Lukas , Friedman Kenneth D. , George James N. , Hrachovinova Ingrid , Knöbl Paul N. , Matsumoto Masanori , von Krogh Anne Sophie , Aebi-Huber Isabella , Cermakova Zuzana , Górska-Kosicka Magdalena , Jalowiec Katarzyna A. , Largiadèr Carlo R. , Prohászka Zoltán , Sinkovits György , Windyga Jerzy , Lämmle Bernhard , Kremer Hovinga Johanna A.
Published: March 2021

Hereditary thrombotic thrombocytopenic purpura (hTTP) is a rare thrombotic microangiopathy characterized by severe congenital ADAMTS13 deficiency and recurring acute episodes causing morbidity and premature death. Information on the annual incidence and severity of acute episodes in patients with hTTP is largely lacking. This study reports prospective data on 87 patients from the Hereditary TTP Registry (clinicaltrials.gov #NCT01257269) for survival, frequency, and severity of acute episodes from enrollment until December 2019. The 87 patients, followed up for a median of 4.2 years (range, 0.01-15 years), had a median age at overt disease onset and at clinical diagnosis of 4.6 years and 18 years (range, 0.0-70 years for both), respectively. Forty-three patients received regular plasma prophylaxis, whereas 22 did not, and treatment changed over time or was unknown in the remaining 22. Forty-three patients experienced 131 acute episodes, of which 91 (69%) occurred in patients receiving regular prophylaxis. This resulted in an annual incidence of acute episodes of 0.36 (95% confidence interval [CI], 0.29-0.44) with regular plasma treatment and of 0.41 (95% CI, 0.30-0.56) without regular plasma treatment. More than one-third of acute episodes (n = 51) were documented in children <10 years of age at enrollment and were often triggered by infections. Their annual incidence of acute episodes was significantly higher than in patients aged >40 years (1.18 [95% CI, 0.88-1.55] vs 0.14 [95% CI, 0.08-0.23]). The prophylactic plasma infusion regimens used were insufficient to prevent acute episodes in many patients. Such regimens are burdensome, and caregivers, patients, and their guardians are reluctant to start regular plasma infusions, from which children particularly would benefit.
A BCMAxCD3 bispecific T cell–engaging antibody demonstrates robust antitumor efficacy similar to that of anti-BCMA CAR T cells
Authors: DiLillo David J. , Olson Kara , Mohrs Katja , Meagher Thomas Craig , Bray Kevin , Sineshchekova Olga , Startz Thomas , Kuhnert Jessica , Retter Marc W. , Godin Stephen , Sharma Prachi , Delfino Frank , Lin John , Smith Eric , Thurston Gavin , Kirshner Jessica R.
Published: March 2021

CD3-engaging bispecific antibodies (bsAbs) and chimeric antigen receptor (CAR) T cells are potent therapeutic approaches for redirecting patient T cells to recognize and kill tumors. Here we describe a fully human bsAb (REGN5458) that binds to B-cell maturation antigen (BCMA) and CD3, and compare its antitumor activities vs those of anti-BCMA CAR T cells to identify differences in efficacy and mechanism of action. In vitro, BCMAxCD3 bsAb efficiently induced polyclonal T-cell killing of primary human plasma cells and multiple myeloma (MM) cell lines expressing a range of BCMA cell surface densities. In vivo, BCMAxCD3 bsAb suppressed the growth of human MM tumors in murine xenogeneic models and showed potent combinatorial efficacy with programmed cell death protein 1 blockade. BCMAxCD3 bsAb administration to cynomolgus monkeys was well tolerated, resulting in the depletion of BCMA+ cells and mild inflammatory responses characterized by transient increases in C-reactive protein and serum cytokines. The antitumor efficacy of BCMAxCD3 bsAb was compared with BCMA-specific CAR T cells containing a BCMA-binding single-chain variable fragment derived from REGN5458. Both BCMAxCD3 bsAb and anti-BCMA CAR T cells showed similar targeted cytotoxicity of MM cell lines and primary MM cells in vitro. In head-to-head in vivo studies, BCMAxCD3 bsAb rapidly cleared established systemic MM tumors, whereas CAR T cells cleared tumors with slower kinetics. Thus, using the same BCMA-binding domain, these results suggest that BCMAxCD3 bsAb rapidly exerts its therapeutic effects by engaging T cells already in place at the tumor site, whereas anti-BCMA CAR T cells require time to traffic to the tumor site, activate, and numerically expand before exerting antitumor effects.
Effect of delignification on thermal degradation reactivities of hemicellulose and cellulose in wood cell walls
Authors: Wang Jiawei , Minami Eiji , Asmadi Mohd , Kawamoto Haruo
Published: March 2021

The thermal degradation reactivities of cellulose and hemicellulose are substantially different in Japanese cedar (Cryptomeria japonica, a softwood) and Japanese beech (Fagus crenata, a hardwood). Uronic acid and its salts act as acid and base catalysts, respectively, and their specific placement in the cell walls has been considered a factor that influences degradation reactivity. In this study, the role of lignin in degradation reactivity was investigated using holocellulose prepared from cedar and beech woods. The thermal degradation reactivities of cellulose and hemicellulose in holocellulose were evaluated according to the recovery of hydrolyzable sugars from heat-treated samples and compared with those of wood samples. Results show that the reactivities of xylan and glucomannan in both woods became similar to those of the corresponding isolated samples when lignin was removed. By contrast, the cellulose in both woods became more reactive when lignin was removed, and the degradation could be separated into two modes depending on the reactivity. These results were analyzed in terms of the effect of lignin on the matrix of cell walls and the interaction between the matrix and surface molecules of cellulose microfibrils. Differential thermogravimetric curves of the holocellulose samples were obtained and explained in terms of the degradation of hemicellulose and cellulose. The reported findings will provide insights into the research fields of wood pyrolysis and cell wall ultrastructures.
Identifying the unique characteristics of the Chinese indigenous pig breeds in the Yangtze River Delta region for precise conservation
Authors: Zhao Qing-bo , Oyelami Favour Oluwapelumi , Qadri Qamar Raza , Sun Hao , Xu Zhong , Wang Qi-shan , Pan Yu-chun
Published: March 2021

Background

China is the country with the most abundant swine genetic resources in the world. Through thousands of years of domestication and natural selection, most of pigs in China have developed unique genetic characteristics. Finding the unique genetic characteristics and modules of each breed is an essential part of their precise conservation.

Results

In this study, we used the partial least squares method to identify the significant specific SNPs of 19 local Chinese pig breeds and 5 Western pig breeds. A total of 37,514 significant specific SNPs (p < 0.01) were obtained from these breeds, and the Chinese local pig breed with the most significant SNPs was Hongdenglong (HD), followed by Jiaxing black (JX), Huaibei (HB), Bihu (BH), small Meishan (SMS), Shengxian Hua (SH), Jiangquhai (JQ), Mi (MI), Chunan (CA), Chalu (CL), Jinhualiangtouwu (JHL), Fengjing (FJ), middle Meishan (MMS), Shanzhu (SZ), Pudong white (PD), Dongchuan (DC), Erhualian (EH), Shawutou (SW) and Lanxi Hua (LX) pig.

Furthermore, we identified the breeds with the most significant genes, GO terms, pathways, and networks using KOBAS and IPA and then ranked them separately. The results showed that the breeds with the highest number of interaction networks were Hongdenglong (12) and Huaibei (12) pigs. In contrast, the breeds with the lowest interaction networks were Shawutou (4) and Lanxi Hua pigs (3), indicating that Hongdenglong and Huaibei pigs might have the most significant genetic modules in their genome, whereas Shawutou and Lanxi Hua pigs may have the least unique characteristics. To some degree, the identified specific pathways and networks are related to the number of genes and SNPs linked to the specific breeds, but they do not appear to be the same. Most importantly, more significant modules were found to be related to the development and function of the digestive system, regulation of diseases, and metabolism of amino acids in the local Chinese pig breeds, whereas more significant modules were found to be related to the growth rate in the Western pig breeds.

Conclusion

Our results show that each breed has some relatively unique structural modules and functional characteristics. These modules allow us to better understand the genetic differences among local Chinese and Western pig breeds and therefore implement precise conservation methods. This study could provide a basis for formulating more effective strategies for managing and protecting these genetic resources in the future.
Effects of a multimodal exercise intervention on physical and cognitive functions in patients with chronic low back pain (MultiMove): study protocol for a randomized controlled trial
Authors: Schega Lutz , Kaps Britta , Broscheid Kim-Charline , Bielitzki Robert , Behrens Martin , Meiler Katharina , Drange Steffen , Franke Jörg
Published: March 2021

Background

Chronic low back pain (CLBP) is a common medical condition in adults over the age of 50. It is associated with severe disability, ranging from physical impairments to psychosocial distress. Since current treatments provide only small to moderate short-term effects, alternative interventions are required, whereby guidelines recommended multimodal approaches. Dancing can be considered as an inherently multimodal approach, as it requires a combination of physical and cognitive functions. Furthermore, it has already been applied effectively in neurorehabilitation. Therefore, it seems promising to merge a dance-therapeutic component together with motor-cognitive, strength and flexibility exercises in a novel multimodal treatment (MultiMove) to target the impaired everyday mobility and cognition of CLBP patients. The aim of this study is to analyse specific physical, cognitive and psychosocial effects of MultiMove in CLBP patients.

Methods

A prospective, two-arm, single-blinded, randomized controlled trial will be conducted with an estimated sample size of 100 CLBP patients, assigned to either the MultiMove group or a control group. The intervention group will receive MultiMove twice a week for 60 min each over a period of 12 weeks. The primary outcome will be the mobility and function of the lower extremities assessed by the Timed Up-and-Go Test. Secondary outcomes comprise further physical and physiological functions (e.g. gait variability and haemodynamic response in the prefrontal cortex during motor-cognitive dual tasks), subjective health state (e.g. disability in daily life), executive functions (e.g. cognitive flexibility) and psychosocial aspects (e.g. kinesiophobia). Measures will be taken at baseline, after the intervention and at a 12-week follow-up. It is assumed that MultiMove improves the mentioned outcome parameters.

Discussion

The combined assessment of changes in physical and cognitive functions as well as neuropsychological aspects in response to MultiMove will allow a better understanding of the motor-cognitive adaptations induced by multimodal exercises in CLBP patients. The specific conclusions will lead to recommendations for the conservative treatment approach in this clinically relevant patient group.

Trial registration

German Clinical Trial Register (ID: DRKS00021696 / 10.07.2020), https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00021696
Real world duration of curative intent breast, colorectal, non-small cell lung, and prostate cancer treatment
Authors: Wong Selina K. , Hamm Jeremy , Shokoohi Aria , McGahan Colleen E. , Ho Cheryl
Published: March 2021

Background

Advances in curative treatment for breast, colorectal, NSCLC and prostate cancer have led to improvements in cancer survival. Cancer treatment and recovery time can vary depending on the recommended modalities and intensity of therapy. Our objective was to determine the current real world duration of curative treatments for the four common cancers.

Methods

A retrospective review was completed of patients referred to BC Cancer from 2010 to 2016, ≤ 65 years old, newly diagnosed with stage I-III breast, colorectal, NSCLC or prostate cancer who received curative intent treatment. Information was collected on baseline characteristics, date of diagnosis, surgery, type, duration and intent of both radiotherapy and chemotherapy.

Results

In total, 22,275 patients were included: 55.7% breast, 22.4% colorectal, 9.2% NSCLC, 12.7% prostate cancer. Stage I/II/III at diagnosis: breast 47.2/38.7/14.1%, colorectal 26.5/30.1/43.5%, NSCLC 46.5/18.1/35.4%, prostate 7.7/62.9/29.4%. Patients treated with definitive surgery only: breast 35.9%, colorectal 58%, NSCLC 52.2%, prostate 40.1%. The median duration of multimodality treatment was breast 24.6 weeks, colorectal 26.7 weeks, NSCLC 9.1 weeks, and prostate 6.0 weeks.

Conclusions

Approximately half of patients who undergo curative cancer treatment require definitive radiotherapy or multimodality treatment. The median duration of therapy for the most commonly treated cancers ranged from 6.0–26.7 weeks. Multimodality curative treatment can be prolonged for selected cancers when accounting for the duration of adjuvant chemotherapy and radiotherapy and recovery time between modalities.
Assessment of violence risk in 440 psychiatric patients in China: examining the feasibility and acceptability of a novel and scalable approach (FoVOx)
Authors: Zhong Shaoling , Yu Rongqin , Cornish Robert , Wang Xiaoping , Fazel Seena ,   FoVOx group, Chen Chen , Li Chun , Zhang Dengke , Wang Jun , Li Shenci , Zhang Simei , Zhu Xiaomin , Lv Ying , Wu Zhimei
Published: March 2021

Background

Violence risk assessment is a routine part of clinical services in mental health, and in particular secure psychiatric hospitals. The use of prediction models and risk tools can assist clinical decision-making on risk management, including decisions about further assessments, referral, hospitalization and treatment. In recent years, scalable evidence-based tools, such as Forensic Psychiatry and Violent Oxford (FoVOx), have been developed and validated for patients with mental illness. However, their acceptability and utility in clinical settings is not known. Therefore, we conducted a clinical impact study in multiple institutions that provided specialist mental health service.

Methods

We followed a two-step mixed-methods design. In phase one, we examined baseline risk factors on 330 psychiatric patients from seven forensic psychiatric institutes in China. In phase two, we conducted semi-structured interviews with 11 clinicians regarding violence risk assessment from ten mental health centres. We compared the FoVOx score on each admission (n = 110) to unstructured clinical risk assessment and used a thematic analysis to assess clinician views on the accuracy and utility of this tool.

Results

The median estimated probability of violent reoffending (FoVOx score) within 1 year was 7% (range 1–40%). There was fair agreement (72/99, 73% agreement) on the risk categories between FoVOx and clinicians’ assessment on risk categories, and moderate agreement (10/12, 83% agreement) when examining low and high risk categories. In a majority of cases (56/101, 55%), clinicians thought the FoVOx score was an accurate representation of the violent risk of an individual patient. Clinicians suggested some additional clinical, social and criminal risk factors should be considered during any comprehensive assessment. In addition, FoVOx was considered to be helpful in assisting clinical decision-making and individual risk assessment. Ten out of 11 clinicians reported that FoVOx was easy to use, eight out of 11 was practical, and all clinicians would consider using it in the future.

Conclusions

Clinicians found that violence risk assessment could be improved by using a simple, scalable tool, and that FoVOx was feasible and practical to use.
The association between eosinophilic exacerbation and eosinophilic levels in stable COPD
Authors: Kang Hye Seon , Kim Sung Kyoung , Kim Yong Hyun , Kim Jin Woo , Lee Sang Haak , Yoon Hyung Kyu , Rhee Chin Kook
Published: March 2021

Background

Blood eosinophil count may predict treatment response in patients with chronic obstructive pulmonary disease (COPD) during acute exacerbations (AE). However, the ability and thresholds of blood eosinophil counts in stable status to predict eosinophilic AECOPD have not been completely investigated.

Methods

This was a retrospective multicenter study performed January 2010 to December 2014. COPD subjects hospitalized with exacerbations, were included. Blood samples were obtained at the time of AE and stable disease at outpatient clinic before or after admission. We identified a blood eosinophil count cut-off point at stable COPD, either taken as a percentage or as absolute value, for identification of eosinophilic exacerbation.

Results

There was significant positive correlation of eosinophil counts between stable COPD and AECOPD. The best cut-off value of blood eosinophil count in stable status for the prediction of eosinophilic COPD exacerbation based on blood eosinophil count ≥ 2% was 300 cells/µL (area under the ROC curve [AUC] 0.614, P = 0.001, 39% sensitivity, 83.8% specificity). When the eosinophilic COPD exacerbation was based on blood eosinophil count ≥ 300 cells/µL, the best cut-off value of blood eosinophil count in stable status for the prediction of eosinophilic COPD exacerbation was also 300 cells/uL (AUC 0.634, P = 0.046, 45.8% sensitivity, 80.9% specificity).

Conclusions

We demonstrated association between blood eosinophil counts at stable COPD and those with AECOPD. The thresholds of blood counts at stable COPD to predict eosinophilic exacerbations was 300 cells/µL. Further and prospective studies in other populations should validate our results.