bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antiplatelet Drug Use and Breast Cancer Risk in a Prospective Cohort of Postmenopausal Women
Authors: Cairat Manon , Al Rahmoun Marie , Gunter Marc J. , Severi Gianluca , Dossus Laure , Fournier Agnès 
Published: February 2021

Abstract

Background:
Epidemiologic evidence is insufficient to draw conclusions on the impact of low-dose aspirin use on breast cancer risk, and the potential impact of other antiplatelet drugs such as clopidogrel needs to be explored.

Methods:
We investigated the association between breast cancer risk and low-dose aspirin or clopidogrel use in the E3N cohort, which includes 98,995 women, with information on breast cancer risk factors collected from biennial questionnaires matched with drug reimbursement data available from 2004. Women with at least two reimbursements of the drug of interest in any previous 3-month period were considered “ever” exposed. Exposure was considered as time-varying and multivariable Cox regression models were used to estimate HRs of breast cancer.

Results:
Among 62,512 postmenopausal women followed during 9 years on average, 2,864 breast cancer cases were identified. Compared with never use, a transient higher breast cancer risk was observed during the third year of low-dose aspirin use [HR2–≤3 years of use = 1.49 (1.08–2.07)], followed by a lower risk [HR4+ years of use = 0.72 (0.52–0.99)]. Clopidogrel ever use was associated with a higher breast cancer risk [HR, 1.30 (1.02–1.68)], restricted to estrogen receptor negative (ER−) tumors [HRER+ = 1.14 (0.83–1.57), HRER− = 3.07 (1.64–5.76), Phomogeneity = 0.01].

Conclusions:
Low-dose aspirin was associated with a lower breast cancer risk only after several years of use, while ever use of clopidogrel was associated with a higher ER− breast cancer risk.

Impact:
Antiplatelet drugs are not good pharmacologic candidates for breast cancer prevention.
Therapeutic Manipulation of Tumor-associated Macrophages: Facts and Hopes from a Clinical and Translational Perspective
Authors: Allavena Paola , Anfray Clément , Ummarino Aldo , Andón Fernando Torres 
Published: February 2021

AbstractThe stroma of most solid tumors is populated by myeloid cells, which mostly represent macrophages. Tumor-associated macrophages (TAMs), strongly influenced by cancer cell–derived factors, are key drivers of immunosuppression and support tumor growth and spread to distant sites. Their accurate quantification and characterization in the tumor microenvironment are gaining prognostic value: increasing evidence demonstrates their ability to hamper cancer patients' response to chemotherapy, as well as to immunotherapies based on checkpoint inhibition. Therefore, strategies to counteract their negative effects are nowadays gaining momentum at preclinical, translational, and clinical levels. Our knowledge of the biology of TAMs has greatly advanced in the last years; several strategies to target and reprogram their functions to become antitumor effectors have proven successful in experimental preclinical tumor models; on the other hand, few approaches have so far been effectively translated into clinic practice. A growing interest in the therapeutic manipulation of TAMs is evidenced by numerous early-phase clinical trials, which are continuously fueled by new discoveries from basic research. This gives us hope that the targeting and sustained reprogramming of TAMs will be more specific to synergize with current therapies and maximize antitumor responses in patients.
Lower Airway Dysbiosis Exacerbates Lung Cancer
Authors: Zitvogel Laurence , Kroemer Guido 
Published: February 2021

Abstract

Summary:
Accumulating evidence supports the impact of the gut microbiota on the clinical efficacy of cancer immunotherapies against extraintestinal tumors, but it has not yet been addressed whether local commensals could also dictate the prognosis of patients with cancer. In this issue of Cancer Discovery, Tsay and colleagues demonstrate that the lower airway microbiota may harbor oral commensals that turn on IL17-mediated inflammatory pathways and reprogram host transcription to exacerbate lung cancer progression.
See related article by Tsay et al., p. 293.
The R1-weighted connectome: complementing brain networks with a myelin-sensitive measure
Authors: Boshkovski Tommy , Kocarev Ljupco , Cohen-Adad Julien , Mišić Bratislav , Lehéricy Stéphane , Stikov Nikola , Mancini Matteo 
Published: February 2021

AbstractMyelin plays a crucial role in how well information travels between brain regions. Complementing the structural connectome, obtained with diffusion MRI tractography, with a myelin-sensitive measure could result in a more complete model of structural brain connectivity and give better insight into white-matter myeloarchitecture. In this work we weight the connectome by the longitudinal relaxation rate (R1), a measure sensitive to myelin, and then we assess its added value by comparing it with connectomes weighted by the number of streamlines (NOS). Our analysis reveals differences between the two connectomes both in the distribution of their weights and the modular organization. Additionally, the rank-based analysis shows that R1 can be used to separate transmodal regions (responsible for higher-order functions) from unimodal regions (responsible for low-order functions). Overall, the R1-weighted connectome provides a different perspective on structural connectivity taking into account white matter myeloarchitecture.
Les Missionnaires Belges en Afrique Centrale, Fin 19e-20e Siecle
Authors: Blondeel William 
Published: February 2021

Belgian Missionaries in Central Africa, At the End of the 19th and in the 20th Century. Evangelization: Not a World Apart.
This contribution is an attempt to define in rather general terms the field in which Belgian catholic missionaries were active in Central Africa at the end of the 19th and in the 20th century. It is not an acceptable synthesis, but rather a “tour d’horizon”. The image of the missionary is examined as a consistent whole as well as in its different aspects, such as teacher, medical agent, social worker and researcher. The relation between the mission on the one hand and the whole community life on the other appears as a central issue.
Boerenhuishoudens Tegenover Markt en Staat in Tanzania
Authors: Coudere Hugo 
Published: February 2021

The economic reality of the peasant households in Tanzania is situated at the convergence of three spheres:
1. the economy of affection, based on the peasant mode of production;
2. the market, which is dominated by parallel circuits;
3. the Tanzanian state, which is expanding continuously. Each of these spheres has its own logic with its own beneficiaries. The economy of affection redistributes income, often at the expense of market laws and official economic policies. The parallel circuits in the market system only benefit the black marketeers and the well-off. The state has expanded, sometimes in favour of peasant-farmers and workers, but most of the time for its own sake.
Bruikbaarheid van Alternatieve Energiesystemen ter Vervanging van Hout en Kolen in Afrika.
Authors: Baert Daniel , Bangurambona Bonaventure , Kuyken Hugo 
Published: February 2021

Alternative Energy-Sources to Replace Wood and Coal in Africa
In the article, the possibility of the use of alternative energy sources (a.e.) in Africa is discussed. The authors give some criteria which have to be fulfilled before a.e. sources can succesfully be applicated.
Geometric Constraints on Glacial Fjord–Shelf Exchange
Authors: Zhao Ken X. , Stewart Andrew L. , McWilliams James C. 
Published: February 2021

AbstractThe oceanic connections between tidewater glaciers and continental shelf waters are modulated and controlled by geometrically complex fjords. These fjords exhibit both overturning circulations and horizontal recirculations, driven by a combination of water mass transformation at the head of the fjord, variability on the continental shelf, and atmospheric forcing. However, it remains unclear which geometric and forcing parameters are the most important in exerting control on the overturning and horizontal recirculation. To address this, idealized numerical simulations are conducted using an isopycnal model of a fjord connected to a continental shelf, which is representative of regions in Greenland and the West Antarctic Peninsula. A range of sensitivity experiments demonstrate that sill height, wind direction/strength, subglacial discharge strength, and depth of offshore warm water are of first-order importance to the overturning circulation, while fjord width is also of leading importance to the horizontal recirculation. Dynamical predictions are developed and tested for the overturning circulation of the entire shelf-to-glacier-face domain, subdivided into three regions: the continental shelf extending from the open ocean to the fjord mouth, the sill overflow at the fjord mouth, and the plume-driven water mass transformation at the fjord head. A vorticity budget is also developed to predict the strength of the horizontal recirculation, which provides a scaling in terms of the overturning and bottom friction. Based on these theories, we may predict glacial melt rates that take into account overturning and recirculation, which may be used to refine estimates of ocean-driven melting of the Greenland and Antarctic ice sheets.
Loss of the exocyst complex component EXOC3 promotes hemostasis and accelerates arterial thrombosis
Authors: Walsh Tony G. , Li Yong , Williams Christopher M. , Aitken Elizabeth W. , Andrews Robert K. , Poole Alastair W. 
Published: February 2021

Abstract
The exocyst is an octameric complex comprising 8 distinct protein subunits, exocyst complex components (EXOC) 1 to 8. It has an established role in tethering secretory vesicles to the plasma membrane, but its relevance to platelet granule secretion and function remains to be determined. Here, EXOC3 conditional knockout (KO) mice in the megakaryocyte/platelet lineage were generated to assess exocyst function in platelets. Significant defects in platelet aggregation, integrin activation, α-granule (P-selectin and platelet factor 4), dense granule, and lysosomal granule secretion were detected in EXOC3 KO platelets after treatment with a glycoprotein VI (GPVI)-selective agonist, collagen-related peptide (CRP). Except for P-selectin exposure, these defects were completely recovered by maximal CRP concentrations. GPVI surface levels were also significantly decreased by 14.5% in KO platelets, whereas defects in proximal GPVI signaling responses, Syk and LAT phosphorylation, and calcium mobilization were also detected, implying an indirect mechanism for these recoverable defects due to decreased surface GPVI. Paradoxically, dense granule secretion, integrin activation, and changes in surface expression of integrin αIIb (CD41) were significantly increased in KO platelets after protease-activated receptor 4 activation, but calcium responses were unaltered. Elevated integrin activation responses were completely suppressed with a P2Y12 receptor antagonist, suggesting enhanced dense granule secretion of adenosine 5′-diphosphate as a critical mediator of these responses. Finally, arterial thrombosis was significantly accelerated in KO mice, which also displayed improved hemostasis determined by reduced tail bleeding times. These findings reveal a regulatory role for the exocyst in controlling critical aspects of platelet function pertinent to thrombosis and hemostasis.
Socioeconomic and lifestyle determinants of the prevalence of hypertension among elderly individuals in rural southwest China: a structural equation modelling approach
Authors: Xiao Li , Le Cai , Wang Gui-Yi , Fan Lu-Ming , Cui Wen-Long , Liu Ying-Nan , Shen Jing-Rong , Golden Allison Rabkin 
Published: February 2021

Abstract
Background
This study examines the association between socioeconomic and lifestyle factors and the prevalence of hypertension among elderly individuals in rural Southwest China.

Methods
A cross-sectional survey of 4833 consenting adults aged ≥ 60 years in rural regions of Yunnan Province, China, was conducted in 2017. Data on individual socioeconomic status, sleep quality, physical activity level, and family history of hypertension were collected with a standardized questionnaire. Blood pressure, fasting blood glucose, height, weight, and waist circumference were also measured. An individual socioeconomic position (SEP) index was constructed using principal component analysis. Structural equation modelling (SEM) was applied to analyse the association between socioeconomic and lifestyle factors and the prevalence of hypertension.

Results
The overall prevalence of hypertension was 50.6% in the study population. Body fat distribution, including measures of obesity and central obesity, had the greatest total effect on hypertension (0.21), followed by family history of hypertension (0.14), biological sex (0.08), sleep quality (− 0.07), SEP (− 0.06), physical inactivity (0.06), and diabetes (0.06). Body fat distribution, SEP, and family history of hypertension had both direct and indirect effects on hypertension, whereas physical inactivity, diabetes, and sleep quality were directly associated with the prevalence of hypertension. Biological sex was indirectly associated with the prevalence of hypertension.

Conclusions
SEP, body fat distribution, physical inactivity, diabetes, and sleep quality critically influence the prevalence of hypertension. Future interventions to prevent and control hypertension should give increased attention to individuals with low SEP and should focus on controlling diabetes and obesity, increasing physical activity levels, and improving quality of sleep among older adults aged ≥ 60 years in rural Southwest China.
Association of human platelet alloantigens encoding gene polymorphisms with the risk of Coronary artery disease in Iranian patients
Authors: Malakootikhah Farideh , Naghavi Hossein , Firouzabadi Negar , Maadani Mohsen , Shafiei Massoumeh , Tajik Nader 
Published: February 2021

Abstract
Background
Coronary artery disease (CAD) is characterized by narrowing/ blockade of coronary arteries that is mainly caused by atherosclerotic plaques. Considering the involvement of platelet abnormalities, such as defective aggregation and adhesion, in the cardiovascular-related disorders, genetic variations in human platelet alloantigens (HPA) have been implicated in the CAD susceptibility. Herein, we intended to determine the association of HPA-1 to -6, -9, and -15 biallelic polymorphisms with CAD in an Iranian population.

Methods
In this retrospective case–control study, 200 CAD subjects and 100 matched healthy individuals were enrolled. DNA samples were isolated from peripheral blood samples and genotyping of HPA polymorphisms was accomplished using polymerase chain reaction-sequence-specific primers.

Results
The alleles and genotypes of studied HPA polymorphisms were equally distributed among cases and controls and therefore no statistically significant differences were detected. Univariate analysis identified no association of combined haplotypes with CAD risk. However, multivariate analysis showed a positive association of the‌ HPA1b/2a/3b haplotype with CAD after adjustment for some covariates (including BMI, TG, LDL, FBS and blood pressure) that conferred a CAD susceptibility haplotype (P = 0.015; OR = 2.792; 95% CI 1.45–8.59).

Conclusions
Although alleles, genotypes, and haplotypes of HPA polymorphisms were not associated with CAD risk, HPA1b/2a/3b haplotype was found to be a dependent disease risk haplotype in Iranian population after correcting for confounding factors.
Increased multiple sclerosis disease activity in patients transitioned from fingolimod to dimethyl fumarate: a case series
Authors: Delgado Silvia , Hernandez Jeffrey , Tornes Leticia , Rammohan Kottil 
Published: February 2021

Abstract
Background
Fingolimod is a S1P1 receptor modulator that prevents activated lymphocyte egress from lymphoid tissues causing lymphopenia, mainly affecting CD4+ T lymphocytes. Withdrawal from fingolimod can be followed by severe disease reactivation, and this coincides with return of autoreactive lymphocytes into circulation. The CD8+ T cytotoxic population returns prior to the regulatory CD4+ T lymphocytes leading to a state of dysregulation, which may contribute to the rebound and severity of clinical relapses. On the other hand, dimethyl fumarate (DMF) preferentially reduces CD8+ T lymphocytes, has the same efficacy as fingolimod, and therefore, was expected to be a suitable oral alternative to reduce the rebound associated with fingolimod withdrawal.

Case presentation
We present six patients with relapsing-remitting MS who developed an unexpected increase in disease activity after transitioning from fingolimod to DMF. All patients were clinically and radiologically stable on fingolimod for at least 1 year. The switch in therapy was due to significantly low CD4+ T lymphocyte count ≤65 cells/ul (normal range 490–1740 cells/ul), after discussing the results with the patients and the potential risk for opportunistic infections including cryptococcal infections. DMF was introduced following a washout period of 5 to 11 weeks to allow reconstitution of the immune system and for the absolute lymphocyte count to reach ≥500 cells/ul. Every patient who experienced a relapse had several enhancing lesions in the brain and/or spinal cord between 12 to 23 weeks after cessation of fingolimod and 1 to 18 weeks after starting DMF. All relapses were treated with intravenous methylprednisolone with good clinical responses.

Conclusion
The anticipated beneficial response of DMF treatment to mitigate rebound after fingolimod therapy cessation was not observed. Our patients experienced rebound disease despite being on treatment with DMF. Additional studies are necessary to understand which treatments are most effective to transition to after discontinuing fingolimod.
Knowledge and understanding of obstetric danger signs among pregnant women attending the antenatal clinic at the National Referral Hospital in Thimphu, Bhutan: a cross-sectional study
Authors: Tamang Saran Tenzin , Dorji Thinley , Yoezer Sonam , Phuntsho Thinley , Dorji Phurb 
Published: February 2021

Abstract
Background
The third Sustainable Development Goal for 2030 development agenda aims to reduce maternal and newborn deaths. Pregnant women’s understanding of danger signs is an important factor in seeking timely care during emergencies. We assessed knowledge of obstetric danger signs using both recall and understanding of appropriate action required during obstetric emergencies.

Methods
This was a cross-sectional study among pregnant women attending antenatal clinic at Bhutan’s largest hospital in Thimphu. Recall was assessed against seven obstetric danger signs outlined in the Mother and Child Health Handbook (7 points). Understanding of danger signs was tested using 13 multiple choice questions (13 points). Knowledge was scored out of 20 points and reported as ‘good’ (≥80%), ‘satisfactory’ (60–79%) and ‘poor’ (< 60%). Correlation between participant characteristics and knowledge score as well as number of danger signs recalled was tested using Pearson’s correlation coefficient. Association between knowledge score and participant characteristics was tested using t-tests (and Kruskal-Wallis test) for numeric variables. Socio-demographic and clinical characteristics associated with the level of knowledge ('good’ versus ‘satisfactory’ and ‘poor’ combined) were assessed with odds ratios using a log-binomial regression model. All results with p < 0.05 were considered significant.

Results
Four hundred and twenty-two women responded to the survey (response rate = 96.0%). Mean (±SD) knowledge score was 12 (±2.5). Twenty women (4.7%) had ‘good’ knowledge, 245 (58.1%) had ‘satisfactory’ knowledge and 157 (37.2%) had ‘poor’ knowledge. The median number of danger signs recalled was 2 (IQR 1, 3) while 68 women (20.3%) could not recall any danger signs. Most women were knowledgeable about pre-labour rupture of membranes (96.0%) while very few women were knowledgeable about spotting during pregnancy (19.9%). Both knowledge score and number of danger signs recalled had significant correlation with the period of gestation. Women with previous surgery on the reproductive tract had higher odds of having ‘good’ level of knowledge.

Conclusions
Most pregnant women had ‘satisfactory’ knowledge score with poor explicit recall of danger signs. However, women recognized obstetric emergencies and identified the appropriate action warranted.
Late ANC initiation and factors associated with sub-optimal uptake of sulphadoxine-pyrimethamine in pregnancy: a preliminary study in Cape Coast Metropolis, Ghana
Authors: Amoako Benjamin Kwasi , Anto Francis 
Published: February 2021

Abstract
Background
Malaria infection during pregnancy is of public health importance as it poses risk to the pregnant woman, her foetus and the newborn child. Intermittent preventive treatment during pregnancy using sulphadoxine-pyrimethamine is one way of reducing the effect of the disease on pregnancy outcomes. The study determined factors associated with uptake of sulphadoxine-pyrimethamine during pregnancy in the Cape Coast Metropolis of Ghana.

Methods
A health facility-based cross-sectional study involving pregnant women of ≥36 weeks gestation visiting antenatal clinics in three selected health facilities in the Cape Coast Metropolis was conducted. Participants were consecutively recruited using a structured questionnaire over a 6-week period from May to June, 2018. Descriptive statistics was used to summarize the data whilst Pearson’s chi-square/Fisher exact test was performed to determine associations and logistic regression done to determine the strength of the associations.

Results
A total of 212 pregnant women participated in the study. Formal education, initiating ANC early, taking first dose of SP during second trimester, not experiencing side effects of SP, having knowledge about schedule for taking SP and making ≥4 ANC visits were factors associated with uptake of ≥3 doses of IPTp-SP. Logistic regression analysis revealed that, mothers who made ≥4 ANC visits were 53.77 times more likely to take ≥3 doses of SP compared with those who made < 4 ANC visits (p <  0.001). Those who initiated ANC during the first trimester were 3.60 times more likely to receive ≥5 doses compared with those who initiated ANC during the second or third trimester (p = 0.022). Making ≥8 ANC visits did not increase the chances of taking ≥5 doses of SP.

Conclusion
Health promotion programmes targeting mothers with no formal education could increase their awareness about the importance of ANC services including uptake of IPTp-SP.