bluuebunny/crossref_metadata_2025_split huggingface dataset:
Collision-avoidance path planning for multi-ship encounters considering ship manoeuvrability and COLREGs
Authors: He Yixiong , Li Zhaoran , Mou Junmin , Hu Weixuan , Li Liling , Wang Bing 
Published: April 2021

Abstract
Ship collision prevention has always been a hot topic of research for navigation safety. Recently, autonomous ships have gained much attention as a means of solving collision problems by machine control with a collision-avoidance algorithm. An important question is how to determine optimal path planning for autonomous ships. This paper proposes a path-planning method of collision avoidance for multi-ship encounters that is easy to realize for autonomous ships. The ship course-control system uses fuzzy adaptive proportion-integral-derivative (PID) control to achieve real-time control of the system. The automatic course-altering process of the ship is predicted by combining the ship-motion model and PID controller. According to the COLREGs, ships should take different actions in different encounter situations. Therefore, a scene-identification model is established to identify these situations. To avoid all the TSs, the applicable course-altering range of the OS is obtained by using the improved velocity obstacle model. The optimal path of collision avoidance can be determined from an applicable course-altering range combined with a scene-identification model. Then, the path planning of collision avoidance is realized in the multi-ship environment, and the simulation results show a good effect. The method conforms to navigation practice and provides an effective method for the study of collision avoidance.
Sensitivity of Rhizoctonia solani Anastomosis Group 2-2 Isolates from Soybean and Sugar Beet to Selected SDHI and QoI Fungicides
Authors: Sharma Pratibha , Malvick Dean K. , Chanda Ashok K. 
Published: April 2021

Rhizoctonia solani causes root and stem diseases on soybean and sugar beet, and fungicides are commonly used to manage these diseases. Quinone outside inhibitor (QoI) fungicides (pyraclostrobin and azoxystrobin) have been used for in-furrow and postemergence application since 2000. Succinate dehydrogenase inhibitor (SDHI) fungicides (sedaxane, penthiopyrad, and fluxapyroxad) became popular seed treatments after their registration in Minnesota and North Dakota between 2012 and 2016. Periodic monitoring of sensitivity to these fungicides in R. solani anastomosis group (AG) 2-2 is important to detect potential shifts in sensitivity over time. R. solani AG 2-2 isolates (n = 35) collected from soybean and sugar beet in Minnesota and North Dakota were evaluated in vitro for sensitivity. Isolates were considered as baseline or nonbaseline for the above-mentioned fungicides based on previous potential exposure. The effective concentration (EC50) required to suppress radial fungal growth by 50% was determined. The mean EC50 values for sedaxane, penthiopyrad, fluxapyroxad, and pyraclostrobin were 0.1, 0.15, 0.16, and 0.25 (µg ml−1), respectively. The mean EC50 value for azoxystrobin for 22 isolates was 0.76 to 1.56 µg ml−1; and EC50 could not be determined for 13 isolates because of <50% inhibition at the highest concentrations used. The EC50 values for the QoI fungicides did not differ significantly between baseline and nonbaseline isolates. EC50 values for SDHI fungicides were significantly higher for isolates collected from soybean than from sugar beet, and isolates collected from both crops had similar EC50 values for pyraclostrobin. All SDHI fungicides and pyraclostrobin effectively suppressed R. solani isolates from soybean and sugar beet at low concentrations in vitro.
BRAIN PERIVASCULAR MACROPHAGES CONTRIBUTE TO THE DEVELOPMENT OF HYPERTENSION THROUGH SYMPATHETIC ACTIVATION IN STROKE-PRONE SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Shinohara Keisuke , Iyonaga Takeshi , Hirooka Yoshitaka , Tsutsui Hiroyuki 
Published: April 2021

Objective:
Hypertension is associated with systemic inflammation. The activation of the sympathetic nervous system is critically involved in the pathogenesis of hypertension. Brain perivascular macrophages (PVMs) can be affected by circulating inflammatory cytokines and contribute to sympathoexcitaion in a heart failure model. We thus investigated whether brain PVMs contribute to the development of hypertension through sympathoexcitation.

Design and method:
We measured blood pressure and evaluated the number of brain PVMs and the plasma levels of proinflammatory cytokines in stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar–Kyoto rats (WKY) at the ages of 4, 8, and 12 weeks. To determine the contribution of brain PVMs to blood pressure elevation, we intracerebroventricularly injected liposome-encapsulated clodronate, which eliminates macrophages by inducing apoptosis, or vehicle into 8-week-old SHRSP and WKY; we then assessed its effects in 10-week-old rats. We also investigated the effects of clodronate treatment on responses to the acute intravenous injection of proinflammatory cytokines in WKY.

Results:
SHRSP developed hypertension over 8 weeks from 4 to 12 weeks of age. The number of brain PVMs and plasma interleukin-1β levels significantly increased at the ages of 8 and 12 weeks in SHRSP compared with WKY. Clodronate treatment attenuated the increase in blood pressure in SHRSP (δmean blood pressure, 11.6 ± 3.8 mmHg vs. 23.8 ± 1.9 mmHg; clodronate vs. vehicle, n = 7, p < 0.05) but not in WKY. Clodronate treatment reduced the depressor effect of hexamethonium, an index of sympathetic activity; it also reduced the neuronal activity marker c-Fos in sympathetic regulatory nuclei such as the hypothalamic paraventricular nucleus and rostral ventrolateral medulla and reduced the expression of cyclooxygenase-2 and prostaglandin E2, a downstream pathway in activated macrophages, in SHRSP but not in WKY. Furthermore, clodronate treatment attenuated the increase in blood pressure and renal sympathetic nerve activity (RSNA) in response to an acute intravenous injection of interleukin-1β in WKY (δmean blood pressure, 8.8 ± 2.5 mmHg vs. 21.2 ± 4.6 mmHg; integrated RSNA, 125.6 ± 10.4 % vs. 213.1 ± 22.2 %; clodronate vs vehicle, n = 5, p < 0.05).

Conclusions:
Brain PVMs contribute to the development of hypertension via sympathetic activation. PVMs may be activated by increased levels of circulating interleukin-1β.
ORTHOSTATIC BLOOD PRESSURE CHANGES AND SUBCLINICAL MARKERS OF ATHEROSCLEROSIS IN NORMOTENSIVE ADULTS. RESULTS FROM A NATIONAL-REPRESENTATIVE SURVEY
Authors: Fronea Oana Florentina Gheorghe , Darabont Roxana , Pop Calin , Dorobantu Maria 
Published: April 2021

Objective:
To evaluate the relationship between orthostatic upright postural blood pressure (BP) changes and subclinical markers of atherosclerosis in normotensive subjects using a simple 3-minutes standing up test.

Design and method:
A total of 1081 normotensive subjects enrolled in SEPHAR III national-representative survey, aged 18–80 years (42,4 ± 16.7 years, 55,3% females) underwent a simple 3 standing-up test involving BP measurement in supine position followed by BP measurements at 1 minute and 3 minutes after standing. We measured: aortic pulse wave velocity (PWVao) using a sfigmomanometric method (Arteriograph), body mass index (BMI), serum lipids, glyceated hemoglobin (HbA1c), urinary albumin-to-creatinine ratio (UACR) in morning spot urine and mean carotid intima-media thickness (IMT) by B-mode Doppler ultrasound. Orthostatic hypotension (OH) was defined by SBP decrease of at least 20mmHg and/or DBP decrease of at least 10mmHg, at 3 minutes after standing.

Results:
SBP and DBP increased when standing, with an average increase of SBP/DBP values when changing position of 3.7 ± 19.5 mm Hg / 9.6 ± 13.5 mm Hg at 1 minutes and 2.9 ± 19.2 mm Hg / 10.1 ± 13.2 mm Hg. Orthostatic hypotension (OH) was recoded in 130 subjects representing 12,4% of the study sample. The PWVao was significantly higher in OH subjects than in those without OH (9,12 ± 2.13m/s vs 8.08 ± 1.86m/s, p = 0,032). Stepwise regression analysis adjusted for age, sex, BMI, baseline SBP, triglycerides, HDL- cholesterol, LDL- cholesterol, fasting glucose, HbA1c, IMT, UACR and PWVao confirmed that PWVao, LDL-cholesterol and TG were independently related to orthostatic BP changes. Multiple regression analyses showed that age, baseline SBP, decrease in SBP at 3-minutes, BMI and fasting glucose were independent determinants of PWVao.

Conclusions:
Our results have shown that increased arterial stiffness is associated with OH during a 3- minutes standing-up test. Also, arterial stiffness may contribute to greater BP responses to postural changes from standing in normotensive subjects.
CIRCULATING METABOLIC BIOMARKERS AS POTENTIAL LEADS FOR GLOBAL PREVENTION OF RENAL DYSFUNCTION – A FLEMISH COHORT STUDY
Authors: Zhang Zhen -Yu , Marrachelli Vannina , Yang Wen-Yi , Thijs Lutgarde , Monleon Daniel , Verhamme Peter , Redón Josep , Staessen Jan 
Published: April 2021

Objective:
Studies of people with normal or slightly impaired renal function offer a unique setting to explore the metabolic profiles associated with the early renal dysfunction.

Design and method:
In 578 randomly recruited Flemish, we assessed at a 5 year interval the multivariable-adjusted associations of estimated glomerular filtration rate (eGFR, ml/min/1.73 m2) with 43 circulating metabolites quantified by non-targeted nuclear magnetic resonance spectroscopy. Significance of associations, expressed per 1-SD increment in the metabolites, were Bonferroni corrected.

Results:
At baseline (2005–2010), glycine was associated with a 1.81 lower eGFR (P = 0.011). At follow-up (2009–2013), threonine (-2.14) and glycine (-1.73) were cross-sectionally associated with lower eGFR (P < = 0.02) and aspartate (+2.23), leucine (+2.30) and 2 aminobutyrate (+2.12) with higher eGFR (P < = 0.0033). At follow-up, the odds ratio of having eGFR < 60 was 1.62 for threonine and 1.44 for glycine (P < = 0.039). Partial least squares analyses of baseline and follow-up data were confirmatory. For baseline glycan N acetylglucosamine residues (GlycA), a marker of systemic inflammation, the odds ratio of progressing towards follow-up eGFR < 60 vs. non-progressing (n = 49 vs. 529) was 1.85 (P = 0.0086). Baseline GlycA was a better predictor than 24 h microalbuminuria, increasing (P < = 0.0001) the integrated discrimination (+3.4%) and net reclassification (+40.1%) indexes. Pathway analysis pointed to aminoacyl-tRNA biosynthesis, glycine, serine and threonine metabolism, valine, leucine and isoleucine metabolism, and glycolysis or gluconeogenesis.

Conclusions:
The glycine to threonine pathway and systemic inflammation as reflected by GlycA are markers of early renal dysfunction, whereas protection against oxidative stress and anaplerotic energy supply from the catabolism of branched amino acids (leucine) might be protective.
THE ERYTHROCYTE MEMBRANES BETA-ADRENOREACTIVITY CHANGES AFTER RENAL DENERVATION AS A PROGNOSTIC FACTOR FOR THE LONG-TERM ANTIHYPERTENSIVE EFFICACY OF THE INTERVENTION
Authors: Zyubanova Irina , Falkovskaya Alla , Mordovin Viktor , Manukyan Masheg , Pekarskiy Stanislav , Lichikaki Valeria , Rebrova Tatyana , Afanasiev Sergej 
Published: April 2021

Objective:
To study the functional state of the sympathoadrenal system (SAS) assessed by the erythrocyte membranes beta-adrenoreactivity (beta-ARM) level, 7 days and 2 years after renal denervation (RD), to assess the prognostic capabilities of this indicator in relation to the long-term antihypertensive efficacy of the treatment.

Design and method:
The study included 48 patients, 18 men and 30 women with resistant hypertension (RH) on stable antihypertensive therapy. The levels of mean daily systolic (SBP) and diastolic blood pressure (DBP), and level of beta-ARM at baseline, 7 days and 2 years after RD were studied. The beta-ARM determination based on erythrocytes hemolysis inhibition by the beta-blocker adding in hypoosmotic medium, that prevents their destruction by binding to erythrocyte membranes beta-adrenergic receptors. An increase in the beta-ARM value reflects a decrease in erythrocyte membranes beta-adrenergic receptors number on the background of prolonged sympathetic hyperactivation.

Results:
The average daily blood pressure levels decreased from 160.4 ± 16.0/88.1 ± 14.6 mm Hg to 145.3 ± 19.3/79.4 ± 13.6 mm Hg (p = 0.000) for 2 years. The beta-ARM dynamics was as follows: 43.8 ± 19.9 conventional units (CE) initially, decreased to 40.5 ± 17.0 CE after 7 days (p > 0.05), and increased to 55.3 ± 19.0 CE (p = 0.008) after 2 years. At the same time, the beta-ARM decrease after 7 days was significant in the responders group (p = 0.028), whose blood pressure after 2 years decreased by 10 mm Hg or more, and was absent in the non-responders group. There was a correlation between the dynamics of beta-ARM after 7 days and SBP and DBP after 2 years (r = -0.54, p < 0.05). This makes it possible to predict the RD long-term effectiveness.

Conclusions:
The decrease in beta-ARM 7 after RD indicates the effectiveness of the procedure and allows us to expect a significant blood pressure decrease in the long term after surgery. Nevertheless, 2 years after RD a decrease in the erythrocyte membranes adrenergic receptors density is observed, probably through a negative feedback mechanism in response to ongoing sympathetic stimulation even against the background of a blood pressure decrease
LONG TERM BENEFITS OF BLOOD PRESSURE TREATMENT ON THE INCIDENCE OF ATRIAL FIBRILLATION, HEART FAILURE AND CARDIOVASCULAR MORBIDITY AND MORTALITY: 20-YEARS FOLLOW-UP OF ASCOT-LEGACY
Authors: Gupta Ajay , Whiteley William , Godec Thomas , Rostamian Somayeh , Whitehouse Andrew , Mackay Judith , Sever Peter 
Published: April 2021

Objective:
Previously, we reported 16-year cardiovascular (CV) mortality associated with either atenolol- or amlodipine-based treatment regimen; but without data on non-fatal CV events. We now report longer morbidity and mortality including the impact of BP-treatment on the incidence of atrial fibrillation and heart failure

Design and method:
In the ASCOT-Legacy Study, 8580 hypertensive patients (4275 assigned to atenolol+/-diuretic-based and 4305 to amlodipine+/-perindopril-based treatment) were followed in the UK for the maximum duration of 21 years (IQR: 9.1–19.3 years). All fatal/non-fatal CV events during the trial period and the post-trial mortality events were independently adjudicated. Post-trial morbidity events were evaluated using electronic health records. Cox proportional hazards were estimated for the first occurrence of atrial fibrillation, fatal/non-fatal HF, non-fatal/fatal stroke (stroke), non-fatal /fatal-coronary heart disease (CHD), total coronary events and total CV events in two treatment arms. Analyses were adjusted for a-priori confounders (See table). Interaction, if any, with associated statin therapy was evaluated. We also did a sensitivity analysis using only post-trial data.

Results:
During the in-trial period of 5.5 years, the cumulative mean SBP was marginally higher for those on atenolol-based treatment compared to those on amlodipine-based treatment (138.0 [SD,10.8] and 136.3 [9.9] mm Hg, respectively). Table 1 shows the crude and adjusted hazard ratios (HRs) associated with the two treatment regimens. Those on amlodipine-based (vs. atenolol-based) treatment had significantly reduced risk of atrial fibrillation [0.91, 95% CI, 0.83 to 0.99], total coronary events [092, 0.86 to 0.99], stroke [0.82, 0.72 to 0.93] and total CV events [0.93, 0.88 to 0.98]. There was no significant difference in the incidence of heart failure or CHD, although there was a nominal reduction. No evidence of interaction with statin therapy was noted. Post-trial significant differences were apparent for stroke, total coronary events and total CV events.

Conclusions:
Allocation to an amlodipine-based treatment has a long-term beneficial CV effect, particularly on stroke and total coronary and CV events. Reduction in the risk new-onset atrial fibrillation may be an important mediator of this legacy effect.
SAFETY, PHARMACODYNAMICS, AND BLOOD PRESSURE EFFECTS OF ALN-AGT, AN RNA INTERFERENCE THERAPEUTIC TARGETING ANGIOTENSINOGEN, IN A RANDOMIZED SINGLE ASCENDING DOSE STUDY OF HYPERTENSIVE ADULTS
Authors: Huang Stephen A. , Taubel Jorg , Fiore Giuseppe , Dewland Peter , Webb David J. , Bakris George L. , Desai Akshay S. , Cheng Yansong , Agarwal Sagar , Harrop Jamie , Nguyen Huy V. , Lu Jiandong , Foster Don , Fujita Kenji 
Published: April 2021

Objective:
Angiotensinogen (AGT) is the sole precursor of all angiotensin peptides and plays a key role in hypertension pathogenesis. We evaluated the effect of ALN-AGT, a subcutaneous investigational RNA interference (RNAi) therapeutic targeting hepatic AGT synthesis, on blood pressure in hypertensive patients.

Design and Method:
As part of a phase 1 program designed to assess the safety and tolerability of ALN-AGT, we conducted a multicenter study randomizing patients aged 18–65 years with mild to moderate hypertension (mean seated systolic blood pressure [SBP] of > 130 and ?165 mmHg after washout of antihypertensive medication) 2:1 to ascending single doses of ALN-AGT or placebo. Change from baseline in BP at 8 weeks was measured by ambulatory BP monitoring (ABPM). We report interim results as of Oct 27, 2020.

Design and method:
Eighty-four patients (mean age 53 years, 39% female, mean baseline 24 h SBP 139.7 +/- 8.9 mm Hg) were enrolled in ascending dose cohorts of 10 mg, 25 mg, 50 mg, 100 mg, 200 mg, 400 mg or 800 mg. Dose-related reductions in serum AGT levels were observed (figure), with mean reductions of > 90% at doses ?100 mg. AGT remained durably reduced through 12 weeks after single dose administration (data pending for 800 mg cohort). Concomitant reductions in BP from baseline were observed with AGT knockdown, with mean reductions in 24-hour SBP of > 10 mm Hg observed at Week 8 after single doses of 100 mg or higher. No treatment-related serious adverse events or clinically significant elevations in blood creatinine or potassium were seen. No patient required intervention for low blood pressure.

Results:
Single dose administration of ALN-AGT to hypertensive patients was generally well tolerated and resulted in dose-related reductions in serum AGT and BP over 8 weeks. Durable AGT knockdown to 12 weeks supports further evaluation of once quarterly or potentially less frequent dose administration.
SELF-MONITORING OF BLOOD PRESSURE IN WOMEN WITH PREGNANCY HYPERTENSION: THE BUMP2 MULTICENTRE RANDOMISED CONTROLLED TRIAL
Authors: Chappell Lucy , Tucker Katherine , Yu Ly-Mee , Mcmanus Richard 
Published: April 2021

Objective:
Self-monitoring of blood pressure (BP), in conjunction with co-interventions, is associated with clinically significant BP reduction in the general adult population. No adequately powered trials have been conducted in women with pregnancy hypertension. The BUMP2 trial aimed to evaluate whether BP self-monitoring in women with pregnancy hypertension improved BP control.

Design and method:
This multicentre, non-masked, randomised controlled trial recruited pregnant women with chronic or gestational hypertension up to 37 weeks’ gestation. Participating women were randomised to either BP self-monitoring with telemonitoring and usual care or usual care alone. An app provided real time feedback advising women of appropriate actions to take at each blood pressure threshold. The primary outcome was mean systolic BP between baseline and delivery recorded by a healthcare professional. Secondary outcomes included maternal and perinatal outcomes, quality of life, and adverse maternal and fetal events. A sample size of 512 (256/group) at 90% power was required to detect a 5 mm Hg difference in systolic BP between groups (SD 16 mmHg), assuming 15% attrition, subsequently inflated to allow for analysis by hypertension type. Trial Registration: NCT03334149

Results:
850 women (454 with chronic hypertension (CH) and 396 with gestational hypertension (GH)) were randomised to either BP self-monitoring (CH n = 233; GH n = 197) or usual care (CH n = 221; GH n = 199). Primary outcome data were available from 821 (97%) women. Baseline characteristics were similar. Mean systolic BP between randomisation and delivery was not significantly different in women with chronic hypertension between self-monitoring (mean 133.8 (SD 10.3) mmHg) and usual care (133.6 (11.1) mmHg) groups; mean difference 0.03 (-1.73 to 1.79), p = 0.97 or in women with gestational hypertension (137.6 (12.1) mmHg vs. 137.2 (10.8) mmHg; mean difference -0.03 (-2.29 to 2.24), p = 0.98. There were no differences in other maternal and fetal outcomes or in Serious Adverse Events.

Conclusions:
BP self-monitoring in women with pregnancy hypertension does not improve BP control, but appears to be safe when used alongside usual care. Further work will elucidate whether empowering some women with BP self-monitoring may alter behaviour of clinicians or women in initiating or titrating antihypertensive medications.
ESTABLISHING SERUM REFERENCE RANGES OF ANTIHYPERTENSIVE DRUGS
Authors: Rognstad Stine , Søraas Camilla Lund , Bergland Ola Undrum , Høieggen Aud , Strømmen Magnus , Helland Arne , Opdal Mimi Stokke 
Published: April 2021

Objective:
Therapeutic drug monitoring (TDM) is the measurement of serum drug concentrations to optimize pharmacotherapy. Traditionally, blood pressure measurements alone, and not TDM, have been used to evaluate the antihypertensive drug response. However, approximately 50 % of hypertensive patients treated by lifestyle changes and antihypertensive drugs fail to achieve blood pressure control. Serum drug concentration measurements could be useful to select the optimal drugs in adjusted doses and to identify non-adherence. Implementation of TDM in clinical routine for antihypertensive drugs depends on established serum reference ranges.

Design and method:
Commonly used antihypertensive drugs were identified based on prescription data. The authors performed a review of authoritative literature on reported serum drug concentrations and calculated expected concentrations from previously reported pharmacokinetic parameters with commonly prescribed daily doses. Finally, serum drug concentrations in samples from patients undergoing antihypertensive treatment were measured.

Results:
Serum reference ranges for 24 frequently used antihypertensive drugs were established based on results from three approaches and are shown in the table.

Conclusions:
Serum drug concentrations, interpreted in light of the established reference ranges, together with blood pressure measurements and other clinical data, may help identify non-adherent patients and tailor individual antihypertensive treatment when deviant drug responses appear, in line with the concept of personalized medicine.