bluuebunny/crossref_metadata_2025_split huggingface dataset:
Principal component analysis, a useful tool to study cyclin-dependent kinase-inhibitor’s effect on cerebral ischaemia
Authors: Le Roy Lucas , Amara Ahmed , Le Roux Cloé , Bocher Ozvan , Létondor Anne , Benz Nathalie , Timsit Serge 
Published: August 2020

AbstractStroke is a leading cause of acute death related in part to brain oedema, blood–brain barrier disruption and glial inflammation. A cyclin-dependant kinase inhibitor, (S)-roscovitine, was administered 90 min after onset on a model of rat focal cerebral ischaemia. Brain swelling and Evans Blue tissue extravasation were quantified after Evans Blue injection. Combined tissue Evans Blue fluorescence and immunofluorescence of endothelial cells (RECA1), microglia (isolectin-IB4) and astrocytes (glial fibrillary acidic protein) were analysed. Using a Student’s t-test or Mann–Whitney test, (S)-roscovitine improved recovery by more than 50% compared to vehicle (Mann–Whitney, P &lt; 0.001), decreased significantly brain swelling by 50% (t-test, P = 0.0128) mostly in the rostral part of the brain. Main analysis was therefore performed on rostral cut for immunofluorescence to maximize biological observations (cut B). Evans Blue fluorescence decreased in (S)-roscovitine group compared to vehicle (60%, t-test, P = 0.049) and was further supported by spectrophotometer analysis (Mann–Whitney, P = 0.0002) and Evans Blue macroscopic photonic analysis (t-test, P = 0.07). An increase of RECA-1 intensity was observed in the ischaemic hemisphere compared to non-ischaemic hemisphere. Further study showed, in the ischaemic hemisphere that (S)-roscovitine treated group compared to vehicle, showed a decrease of: (i) endothelial RECA-1 intensity of about 20% globally, mainly located in the cortex (−28.5%, t-test, P = 0.03); (ii) Microglia’s number by 55% (t-test, P = 0.006) and modulated reactive astrocytes through a trend toward less astrocytes number (15%, t-test, P = 0.05) and astrogliosis (21%, t-test, P = 0.076). To decipher the complex relationship of these components, we analysed the six biological quantitative variables of our study by principal component analysis from immunofluorescence studies of the same animals. Principal component analysis differentiated treated from non-treated animals on dimension 1 with negative values in the treated animals, and positive values in the non-treated animals. Interestingly, stroke recovery presented a negative correlation with this dimension, while all other biological variables showed a positive correlation. Dimensions 1 and 2 allowed the identification of two groups of co-varying variables: endothelial cells, microglia number and Evans Blue with positive values on both dimensions, and astrocyte number, astrogliosis and brain swelling with negative values on dimension 2. This partition suggests different mechanisms. Correlation matrix analysis was concordant with principal component analysis results. Because of its pleiotropic complex action on different elements of the NeuroVascular Unit response, (S)-roscovitine may represent an effective treatment against oedema in stroke.
5′ValCAC tRNA fragment generated as part of a protective angiogenin response provides prognostic value in amyotrophic lateral sclerosis
Authors: Hogg Marion C , Rayner Megan , Susdalzew Sergej , Monsefi Naser , Crivello Martin , Woods Ina , Resler Alexa , Blackbourn Lisle , Fabbrizio Paola , Trolese Maria Chiara , Nardo Giovanni , Bendotti Caterina , van den Berg Leonard H , van Es Michael A , Prehn Jochen H M 
Published: August 2020

Abstract
Loss-of-function mutations in the ribonuclease angiogenin are associated with amyotrophic lateral sclerosis. Angiogenin has been shown to cleave transfer RNAs during stress to produce ‘transfer-derived stress-induced RNAs’. Stress-induced tRNA cleavage is preserved from single-celled organisms to humans indicating it represents part of a highly conserved stress response. However, to date, the role of tRNA cleavage in amyotrophic lateral sclerosis remains to be fully elucidated. To this end, we performed small RNA sequencing on a human astrocytoma cell line to identify the complete repertoire of tRNA fragments generated by angiogenin. We found that only a specific subset of tRNAs is cleaved by angiogenin and identified 5′ValCAC transfer-derived stress-induced RNA to be secreted from neural cells. 5′ValCAC was quantified in spinal cord and serum from SOD1G93A amyotrophic lateral sclerosis mouse models where we found it to be significantly elevated at symptom onset correlating with increased angiogenin expression, imbalanced protein translation initiation factors and slower disease progression. In amyotrophic lateral sclerosis patient serum samples, we found 5′ValCAC to be significantly higher in patients with slow disease progression, and interestingly, we find 5′ValCAC to hold prognostic value for amyotrophic lateral sclerosis patients. Here, we report that angiogenin cleaves a specific subset of tRNAs and provide evidence for 5′ValCAC as a prognostic biomarker in amyotrophic lateral sclerosis. We propose that increased serum 5′ValCAC levels indicate an enhanced angiogenin-mediated stress response within motor neurons that correlates with increased survival. These data suggest that the previously reported beneficial effects of angiogenin in SOD1G93A mice may result from elevated levels of 5′ValCAC transfer RNA fragment.
Pyk2 overexpression in postsynaptic neurons blocks amyloid β1–42-induced synaptotoxicity in microfluidic co-cultures
Authors: Kilinc Devrim , Vreulx Anaïs-Camille , Mendes Tiago , Flaig Amandine , Marques-Coelho Diego , Verschoore Maxime , Demiautte Florie , Amouyel Philippe ,   Neuro-CEB Brain Bank, Eysert Fanny , Dourlen Pierre , Chapuis Julien , Costa Marcos R , Malmanche Nicolas , Checler Frédéric , Lambert Jean-Charles 
Published: August 2020

Abstract
Recent meta-analyses of genome-wide association studies identified a number of genetic risk factors of Alzheimer’s disease; however, little is known about the mechanisms by which they contribute to the pathological process. As synapse loss is observed at the earliest stage of Alzheimer’s disease, deciphering the impact of Alzheimer’s risk genes on synapse formation and maintenance is of great interest. In this article, we report a microfluidic co-culture device that physically isolates synapses from pre- and postsynaptic neurons and chronically exposes them to toxic amyloid β peptides secreted by model cell lines overexpressing wild-type or mutated (V717I) amyloid precursor protein. Co-culture with cells overexpressing mutated amyloid precursor protein exposed the synapses of primary hippocampal neurons to amyloid β1–42 molecules at nanomolar concentrations and induced a significant decrease in synaptic connectivity, as evidenced by distance-based assignment of postsynaptic puncta to presynaptic puncta. Treating the cells with antibodies that target different forms of amyloid β suggested that low molecular weight oligomers are the likely culprit. As proof of concept, we demonstrate that overexpression of protein tyrosine kinase 2 beta—an Alzheimer’s disease genetic risk factor involved in synaptic plasticity and shown to decrease in Alzheimer’s disease brains at gene expression and protein levels—selectively in postsynaptic neurons is protective against amyloid β1–42-induced synaptotoxicity. In summary, our lab-on-a-chip device provides a physiologically relevant model of Alzheimer’s disease-related synaptotoxicity, optimal for assessing the impact of risk genes in pre- and postsynaptic compartments.
Machine learning and structural econometrics: contrasts and synergies
Authors: Iskhakov Fedor , Rust John , Schjerning Bertel 
Published: August 2020

SummaryWe contrast machine learning (ML) and structural econometrics (SE), focusing on areas where ML can advance the goals of SE. Our views have been informed and inspired by the contributions to this special issue and by papers presented at the second conference on dynamic structural econometrics at the University of Copenhagen in 2018, ‘Methodology and Applications of Structural Dynamic Models and Machine Learning'. ML offers a promising class of techniques that can significantly extend the set of questions we can analyse in SE. The scope, relevance and impact of empirical work in SE can be improved by following the lead of ML in questioning and relaxing the assumption of unbounded rationality. For the foreseeable future, however, ML is unlikely to replace the essential role of human creativity and knowledge in model building and inference, particularly with respect to the key goal of SE, counterfactual prediction.
Debiased machine learning of conditional average treatment effects and other causal functions
Authors: Semenova Vira , Chernozhukov Victor 
Published: August 2020

Summary
This paper provides estimation and inference methods for the best linear predictor (approximation) of a structural function, such as conditional average structural and treatment effects, and structural derivatives, based on modern machine learning tools. We represent this structural function as a conditional expectation of an unbiased signal that depends on a nuisance parameter, which we estimate by modern machine learning techniques. We first adjust the signal to make it insensitive (Neyman-orthogonal) with respect to the first-stage regularisation bias. We then project the signal onto a set of basis functions, which grow with sample size, to get the best linear predictor of the structural function. We derive a complete set of results for estimation and simultaneous inference on all parameters of the best linear predictor, conducting inference by Gaussian bootstrap. When the structural function is smooth and the basis is sufficiently rich, our estimation and inference results automatically target this function. When basis functions are group indicators, the best linear predictor reduces to the group average treatment/structural effect, and our inference automatically targets these parameters. We demonstrate our method by estimating uniform confidence bands for the average price elasticity of gasoline demand conditional on income.
May Measurement Month 2018: an analysis of blood pressure screening in Libya
Authors: Beaney Thomas , Ster Anca Chis , Poulter Neil R , Xia Xin , Fageh Hatem , Msalam Omar , Derbi Hawa A , Osman Afaf M , Aghilla Mohamed , Bettamer Zaki A , Fhail Alboum Mabroukah O , Elsari Osama T , Elhemali Emhemed M , Zidan Rabea A , Musbah Abdunnabi , Eltawell Hazem , Ben Masaud Hesham A ,   The MMM Data collectors
Published: August 2020

Abstract
Elevated blood pressure (BP) is an important public health concern and leads to several adverse cardiovascular outcomes. In the stepwise survey done in Libya by the Libyan Cardiac Society and National Centre for Disease Control in 2009, the percentage of hypertension was 40.6%. To raise awareness of high BP and to highlight the size of the problem and the need for screening. A cross-sectional opportunistic study included men and women aged ≥18 years. Blood pressure was measured three times and a questionnaire was completed. Hypertension was defined as BP ≥140/90 mmHg based on the mean of the 2nd and 3rd readings, or on antihypertensive treatment. Among 7279 participants, the mean age was 44.3 ± 14.8 years, 57.8% male, 2567 (35.3%) of the participants had hypertension of whom 63.4% were aware of having hypertension, 55.8% on medication, and of those on medication 50.9% had controlled BP. This survey identified a high proportion of individuals with high BP, which highlights the need for a more strategic approach to fighting hypertension.
May Measurement Month 2018: an analysis of blood pressure screening results from Albania
Authors: Burazeri Genc , Qirjako Gentiana , Beaney Thomas , Ster Anca Chis , Xia Xin , Ylli Alban , Muja Herion , Cumashi Rudina , Dika Qamil , Roshi Enver , Poulter Neil R 
Published: August 2020

Abstract
This article reports on May Measurement Month (MMM) 2018, which consisted of the 2nd round of the hypertension screening campaign conducted in Albania, a former communist country in South Eastern Europe. The hypertension screening campaign in Albania was conducted during the period 13–31 May 2018. Overall, there were eight sites from seven districts of the country involving 7046 participants aged ≥18 years (61% women and 39% men; overall mean age 46.8 ± 15.7 years). Blood pressure was measured with OMRON sphygmomanometers (Omron Healthcare, Kyoto, Japan). Hypertension was defined as systolic blood pressure (SBP) ≥140 mmHg, or diastolic blood pressure (DBP) ≥90 mmHg, or on treatment for hypertension. Self-reported information included height and weight, diabetes, smoking status, and alcohol intake. The proportion of participants with hypertension was 37.2% of whom only 52.1% exhibited awareness. Furthermore, only a quarter of hypertensive individuals were properly treated and controlled. Significant predictors of high SBP and/or high DBP included a previous diagnosis of hypertension, being on antihypertensive medication, frequent alcohol intake, and being overweight and obese. The MMM 2018 campaign in Albania had a unique value for early detection of hypertension, particularly among younger adults. Policymakers and decision-makers in Albania and elsewhere should also rely on the MMM screening campaigns which have a great potential for prevention and control of hypertension in the general population.
May Measurement Month 2018: an analysis of blood pressure screening results from Angola
Authors: Victória Pereira Savarino , Neto Marisa , Feijão Ana , Oliveira Pombalino , Brandão Maria , Soito Ermelinda , Mbala Claudio , João Armando , Manuel Carlos , Mundombe Leonardo , Muela Henrique , Beaney Thomas , Ster Anca Chis , Poulter Neil R , Fernandes Mário 
Published: August 2020

Abstract
Elevated blood pressure (BP) is a growing burden worldwide with high prevalence in the world and with a huge impact on public health. May Measurement Month (MMM) is a global initiative aimed at raising awareness of high BP and to act as a temporary solution to the lack of screening programmes. An opportunistic cross-sectional survey of volunteers aged ≥18 was carried out in May 2018. Blood pressure measurement, the definition of hypertension and statistical analysis followed the standard MMM protocol. In Angola 14 433 individuals (mean age 38.6 years; 53.7% female; 99.9% black) in 6 of 18 provinces were screened. In total, 99.0% of screenees provided three BP readings with an average BP from 2nd and 3rd reading of 126/80 mmHg. After imputation, 4844 (33.6%) had hypertension of whom 54.2% were aware of their diagnosis and 46.3% were on antihypertensive medication. Of those medicated, 42.6% were controlled and of all hypertensive individuals, 19.7% were controlled. We screened 2603 individuals with untreated hypertension and 1285 with inadequately treated hypertension. Angolan MMM18 emerges as a continuation of the Angolan MMM17 study, the largest BP screening campaign undertaken in Angola, enabling us to compare the 2 years. This year’s results also showed a high percentage of hypertensive individuals and almost 3900 adults with untreated or inadequately treated hypertension, demonstrating that there is still a long way to go but also that the Angolan MMM is being effective at raising awareness at least among these individuals.
May Measurement Month 2018: an analysis of blood pressure screening results from Argentinean cohort
Authors: Espeche Walter G , Rojas Cristina , Stisman Diego , Fuentes Analia , Fita Mariana , Lacunza Carlos Diego , Marquez Diego , Grosse Pedro , Bueno Dennis , Zilberman Judith , Beaney Thomas , Ster Anca Chis , Poulter Neil R , Marín Marcos , Ennis Irene L 
Published: August 2020

Abstract
Hypertension continues to be the leading cause of death and disability in the industrialized world, with a high level of unawareness and unacceptably poor control. Therefore, the Argentinian Society of Hypertension, in agreement with the May Measurement Month (MMM) initiative of the International Society of Hypertension, implemented for the second consecutive year an educational campaign during the month of May 2018. A volunteer cross-sectional survey was carried out in public spaces and health centres during the month of May 2018 across 33 cities in Argentina. Hypertension was defined as systolic blood pressure (BP) ≥140 mmHg or diastolic BP ≥90 mmHg based on the mean of the 2nd and 3rd of three consecutive BP measurements, or in those on treatment for high BP. Statistical analysis including multiple imputation followed the MMM protocol. A total of 70 418 individuals were screened during MMM18, after excluding those under 18 years old. Of the total, 43.8% of participants were classified as hypertensive, 77.7% were aware of their diagnosis, 69.1% were on pharmacological treatment, and 38.7% were controlled. Of those on antihypertensive medication, 56.0% were controlled. It is necessary to reinforce strategies not only to increase the awareness and control of hypertension but also to identify the population groups, in which these strategies would have the greatest impact, helping to reduce the enormous health burden attributed to hypertension.
An analysis of blood pressure screening of 21 112 participants in Armenia: May Measurement Month 2018
Authors: Zelveian Parounak , Avagyan Avag , Minasyan Arsen , Hayrumyan Samvel , Gourgenyan Svetlana , Hakobyan Zoya , Kzhdryan Hovhannes , Hakobjanyan Vahan , Ustyan Tsiala , Gharibyan Heghine , Melkonyan Arevik , Aroyan Siranush , Vatinyan Susanna , Beaney Thomas , Ster Anca Chis , Poulter Neil R 
Published: August 2020

Abstract
Elevated blood pressure (BP) is a growing burden worldwide and is the leading cause of mortality and disability-adjusted life years all over the world. May Measurement Month (MMM) is a global initiative aimed to raise awareness of high BP and to act as a temporary solution to the lack of screening programmes worldwide. An opportunistic cross-sectional survey of volunteers aged ≥18 was carried out in May to July 2018. Blood pressure measurement, the definition of hypertension (HTN) and statistical analysis followed the standard MMM protocol. The study was conducted in public areas (17 sites in Yerevan and 22 in regions), both indoor and outdoor, as well as in 78 primary care centres. A total of 21 112 individuals were screened during MMM18, of which 20 732 had three BP measurements available. The mean age of screened individuals was 46.2 ± 17.3 years, 57.8% were female. At the time of screening, 26.1% were on antihypertensive medication. After imputation, the percentage of participants with HTN was 38.7%, and 76.7% of them were aware of their high BP. Of participants receiving treatment, 47.1% had a controlled BP. MMM18 was the largest BP screening campaign undertaken in Armenia. We found that the proportion of HTN is substantial in Armenia, which may be a vital contributor to the growing burden of non-communicable diseases. Our results also suggest that untreated HTN is common and when treated still not adequately controlled in Armenia. The current situation, with an insufficient control rate of HTN, must be changed as soon as possible.
May Measurement Month 2018: an analysis of blood pressure screening results from Australia
Authors: Carnagarin Revathy , Fonseca Ricardo , Brockman Derrin , Critchley Sue , Tan Isabella , Trengove Naomi , Tan Kearney , Lambert Gavin W , Cowley Diane , Burrell Louise M , Poulter Neil R , Beaney Thomas , Ster Anca Chis , Xia Xin , Schlaich Markus P 
Published: August 2020

Abstract
May Measurement Month (MMM), originally initiated as a temporary solution to address the lack of blood pressure (BP) screening programs worldwide, emerged as an effective annual campaign to increase the awareness of hypertension. MMM18, a cross-sectional survey of volunteers aged ≥18 years was carried out during May 2018 predominantly in capital cities across Australia following the standard MMM protocol. Blood pressure screening along with additional information including anthropometric data and responses to questionnaires on demographic, lifestyle, and environmental factors were collected from 3 352 individuals across Australia. After multiple imputation, 1 026 (30.6%) adult Australians had hypertension. Of the 2 936 individuals not on antihypertensive treatment, 610 (20.8%) were hypertensive, and 237 (57.1%) of the 416 individuals receiving antihypertensive treatment had uncontrolled BP. In line with MMM17 results and other previous surveys, MMM18 revealed that close to one-third of the screened population (30.6%) had hypertension, 57.1% of individuals treated with BP-lowering medication remained uncontrolled indicating suboptimal management of the condition in the majority of patients. Most importantly, only 49.0% of those with hypertension were aware of their elevated BP, highlighting lack of awareness of elevated BP in nearly half of the affected population. Elevated BP was directly associated with alcohol consumption, overweight, and obesity. Our findings demonstrate the need for (i) continued efforts to increase BP awareness in the population, (ii) optimization of BP management strategies, and (iii) tackling some of the major contributors to BP elevation, including alcohol consumption and obesity.
May Measurement Month 2018: an analysis of blood pressure screening results from Botswana
Authors: Masupe Tiny , Tlhakanelo John Thato , Tiro Mary Banyana , Motlhatlhedi Keneilwe , Mamela Abraham , Makwati Obuile , Kololo Masego , Phuswane Orapeleng , Lesetedi Onalethata , Motlhagodi Amogelang , Beaney Thomas , Ster Anca Chis , Poulter Neil R , Xia Xin , Mosepele Mosepele 
Published: August 2020

Abstract
During the May Measurement Month 2018 (MMM18) campaign, we aimed to raise hypertension awareness and measure blood pressure (BP) across different communities in Botswana. Study sites included four large villages and Gaborone (capital city). Screening sites were shopping malls, train stations, churches, and workplaces. Individuals aged ≥18 years were recruited through fliers, word of mouth, and as volunteer walk-ins at the sites. Demographic and risk factor data were collected through a questionnaire prior to measuring three BP readings per participant. Weight was measured while height was usually estimated. Hypertension was defined as: systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg or taking antihypertensive medication. The mean of readings 2 and 3 was used and was estimated using multiple imputation where missing. Amongst 4599 participants whose BPs were measured, 54.5% were female, while mean age was 35.9 years. A total of 1510 (32.8%) participants were hypertensive and of those, 712 (47.1%) were aware of the hypertension. Only 35.2% of hypertensives were on antihypertensive treatment with 54.4% had controlled BP. Amongst all hypertensives, only 19.1% had controlled BP. Risk factors associated with higher BP included obesity, more than 1 unit of alcohol/week and BP measured on Sunday. Less than half (47.1%) of those identified as having hypertension during MMM18 were aware of their condition, despite the escalating prevalence of hypertension in the country. Regular BP awareness and opportunistic BP measurement campaigns like MMM are recommended to improve detection and control of hypertension and other cardiovascular risk factors.