bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dietary nitrate supplementation to enhance exercise capacity in hypoxic COPD: EDEN-OX, a double-blind, placebo-controlled, randomised cross-over study
Authors: Pavitt Matthew J , Lewis Adam , Buttery Sara C , Fernandez Bernadette O , Mikus-Lelinska Monika , Banya Winston A S , Feelisch Martin , Polkey Michael I , Hopkinson Nicholas S 
Published: December 2021

RationaleDietary nitrate supplementation improves skeletal muscle oxygen utilisation and vascular endothelial function. We hypothesised that these effects might be sufficient to improve exercise performance in patients with COPD and hypoxia severe enough to require supplemental oxygen.MethodsWe conducted a single-centre, double-blind, placebo-controlled, cross-over study, enrolling adults with COPD who were established users of long-term oxygen therapy. Participants performed an endurance shuttle walk test, using their prescribed oxygen, 3 hours after consuming either 140 mL of nitrate-rich beetroot juice (BRJ) (12.9 mmol nitrate) or placebo (nitrate-depleted BRJ). Treatment order was allocated (1:1) by computer-generated block randomisation.MeasurementsThe primary outcome was endurance shuttle walk test time. The secondary outcomes included area under the curve to isotime for fingertip oxygen saturation and heart rate parameters during the test, blood pressure, and endothelial function assessed using flow-mediated dilatation. Plasma nitrate and nitrite levels as well as FENOwere also measured.Main results20 participants were recruited and all completed the study. Nitrate-rich BRJ supplementation prolonged exercise endurance time in all participants as compared with placebo: median (IQR) 194.6 (147.5–411.7) s vs 159.1 (121.9–298.5) s, estimated treatment effect 62 (33–106) s (p<0.0001). Supplementation also improved endothelial function: NR-BRJ group +4.1% (−1.1% to 14.8%) vs placebo BRJ group −5.0% (−10.6% to –0.6%) (p=0.0003).ConclusionAcute dietary nitrate supplementation increases exercise endurance in patients with COPD who require supplemental oxygen.Trial registration numberISRCTN14888729.
Risk factors for developing COVID-19: a population-based longitudinal study (COVIDENCE UK)
Authors: Holt Hayley , Talaei Mohammad , Greenig Matthew , Zenner Dominik , Symons Jane , Relton Clare , Young Katherine S , Davies Molly R , Thompson Katherine N , Ashman Jed , Rajpoot Sultan Saeed , Kayyale Ahmed Ali , El Rifai Sarah , Lloyd Philippa J , Jolliffe David , Timmis Olivia , Finer Sarah , Iliodromiti Stamatina , Miners Alec , Hopkinson Nicholas S , Alam Bodrul , Lloyd-Jones Graham , Dietrich Thomas , Chapple Iain , Pfeffer Paul E , McCoy David , Davies Gwyneth , Lyons Ronan A , Griffiths Christopher , Kee Frank , Sheikh Aziz , Breen Gerome , Shaheen Seif O , Martineau Adrian R 
Published: December 2021

BackgroundRisk factors for severe COVID-19 include older age, male sex, obesity, black or Asian ethnicity and underlying medical conditions. Whether these factors also influence susceptibility to developing COVID-19 is uncertain.MethodsWe undertook a prospective, population-based cohort study (COVIDENCE UK) from 1 May 2020 to 5 February 2021. Baseline information on potential risk factors was captured by an online questionnaire. Monthly follow-up questionnaires captured incident COVID-19. We used logistic regression models to estimate multivariable-adjusted ORs (aORs) for associations between potential risk factors and odds of COVID-19.ResultsWe recorded 446 incident cases of COVID-19 in 15 227 participants (2.9%). Increased odds of developing COVID-19 were independently associated with Asian/Asian British versus white ethnicity (aOR 2.28, 95% CI 1.33 to 3.91), household overcrowding (aOR per additional 0.5 people/bedroom 1.26, 1.11 to 1.43), any versus no visits to/from other households in previous week (aOR 1.31, 1.06 to 1.62), number of visits to indoor public places (aOR per extra visit per week 1.05, 1.02 to 1.09), frontline occupation excluding health/social care versus no frontline occupation (aOR 1.49, 1.12 to 1.98) and raised body mass index (BMI) (aOR 1.50 (1.19 to 1.89) for BMI 25.0–30.0 kg/m2and 1.39 (1.06 to 1.84) for BMI >30.0 kg/m2versus BMI <25.0 kg/m2). Atopic disease was independently associated with decreased odds (aOR 0.75, 0.59 to 0.97). No independent associations were seen for age, sex, other medical conditions, diet or micronutrient supplement use.ConclusionsAfter rigorous adjustment for factors influencing exposure to SARS-CoV-2, Asian/Asian British ethnicity and raised BMI were associated with increased odds of developing COVID-19, while atopic disease was associated with decreased odds.Trial registration numberClinicalTrials.gov Registry (NCT04330599).
Investigation of the lightest hybrid meson candidate with a coupled-channel analysis of $${{\bar{p}}p}$$-, $$\pi ^- p$$- and $${\pi \pi }$$-Data
Authors: Kopf B. , Albrecht M. , Koch H. , Küßner M. , Pychy J. , Qin X. , Wiedner U. 
Published: December 2021

AbstractA sophisticated coupled-channel analysis is presented that combines different processes: the channels $${\pi ^0\pi ^0\eta }$$

π
0

π
0

η

, $${\pi ^0\eta \eta }$$

π
0

η
η

and $${K^+K^-\pi ^0}$$

K
+

K
-

π
0

from $${{\bar{p}}p}$$

p

¯

p

annihilations, the P- and D-wave amplitudes of the $$\pi \eta $$

π
η

and $$\pi \eta ^\prime $$

π

η
′

systems produced in $$\pi ^-p$$

π
-

p

scattering, and data from $${\pi \pi }$$

π
π

-scattering reactions. Hence our analysis combines the data sets used in two independent previous analyses published by the Crystal Barrel experiment and by the JPAC group. Based on the new insights from these studies, this paper aims at a better understanding of the spin-exotic $$\pi _1$$

π
1

resonances in the light-meson sector. By utilizing the K-matrix approach and realizing the analyticity via Chew-Mandelstam functions the amplitude of the spin-exotic wave can be well described by a single $$\pi _1$$

π
1

pole for both systems, $$\pi \eta $$

π
η

and $$\pi \eta ^\prime $$

π

η
′

. The mass and the width of the $$\pi _1$$

π
1

-pole are measured to be $$(1623 \, \pm \, 47 \, ^{+24}_{-75})\, \mathrm {MeV/}c^2$$

(
1623

±

47

-
75

+
24

)

MeV
/

c
2

and $$(455 \, \pm 88 \, ^{+144}_{-175})\, \mathrm {MeV}$$

(
455

±
88

-
175

+
144

)

MeV

.
Sodium dichloroacetate stimulates cardiac mitochondrial metabolism and improves cardiac conduction in the ovine fetus during labor
Authors: Joseph Serene , Li Mengchen , Zhang Sicong , Horne Lloyd , Stacpoole Peter. W. , Wohlgemuth Stephanie E. , Edison Arthur S. , Wood Charles , Keller-Wood Maureen 
Published: December 2021

Previous studies in our laboratory have suggested that the increase in stillbirth in pregnancies complicated by chronic maternal stress or hypercortisolemia is associated with cardiac dysfunction in late stages of labor and delivery. Transcriptomics analysis of the overly represented differentially expressed genes in the fetal heart of hypercortisolemic ewes indicated involvement of mitochondrial function. Sodium dichloroacetate (DCA) has been used to improve mitochondrial function in several disease states. We hypothesized that administration of DCA to laboring ewes would improve both cardiac mitochondrial activity and cardiac function in their fetuses. Four groups of ewes and their fetuses were studied: control, cortisol-infused (1 g/kg/day from 115 to term; CORT), DCA-treated (over 24 h), and DCA + CORT-treated; oxytocin was delivered starting 48 h before the DCA treatment. DCA significantly decreased cardiac lactate, alanine, and glucose/glucose-6-phosphate and increased acetylcarnitine/isobutyryl-carnitine. DCA increased mitochondrial activity, increasing oxidative phosphorylation ( PCI, PCI + II) per tissue weight or per unit of citrate synthase. DCA also decreased the duration of the QRS, attenuating the prolongation of the QRS observed in CORT fetuses. The effect to reduce QRS duration with DCA treatment correlated with increased glycerophosphocholine and serine and decreased phosphorylcholine after DCA treatment. There were negative correlations of acetylcarnitine/isobutyryl-carnitine to both heart rate (HR) and mean arterial pressure (MAP). These results suggest that improvements in mitochondrial respiration with DCA produced changes in the cardiac lipid metabolism that favor improved conduction in the heart. DCA may therefore be an effective treatment of fetal cardiac metabolic disturbances in labor that can contribute to impairments of fetal cardiac conduction.
Survival Trends of Right- and Left-Sided Colon Cancer across Four Decades: A Norwegian Population-Based Study
Authors: Hamfjord Julian , Myklebust Tor Åge , Larsen Inger Kristin , Kure Elin H. , Glimelius Bengt , Guren Tormod K. , Tveit Kjell M. , Guren Marianne G. 
Published: December 2021

Abstract

Background:
Patients with right-sided colon cancer (RCC) and left-sided colon cancer (LCC) differ clinically and molecularly. The main objective was to investigate stage-stratified survival and recurrence of RCC and LCC across four 10-year periods.

Methods:
Patients diagnosed from 1977 to 2016 with colon adenocarcinoma were included from the Cancer Registry of Norway. Primary tumor location (PTL) was defined as RCC if proximal and LCC if distal to the splenic flexure. Multivariable regressions were used to estimate HRs for overall survival (OS), recurrence-free survival (RFS), survival after recurrence (SAR), and excess HRs (eHR) for relative survival (RS).

Results:
72,224 patients were eligible for analyses [55.1% (n = 39,769/72,224) had RCC]. In 1977 to 1986, there was no difference between LCC and RCC in OS [HR, 1.01; 95% confidence interval (CI), 0.97–1.06; P = 0.581] or RS (eHR, 0.96; 95% CI, 0.90–1.02; P = 0.179). In 2007 to 2016, LCC had significantly better OS (HR, 0.84; 95% CI, 0.80–0.87; P &lt; 0.001) and RS (eHR, 0.76; 95% CI, 0.72–0.81; P &lt; 0.001) compared with RCC. The gradually diverging and significantly favorable prognosis for LCC was evident for distant disease across all time periods and for regional disease from 2007 onward. There was no difference in RFS between LCC and RCC in patients less than 75 years during 2007 to 2016 (HR, 0.99; 95% CI, 0.91–1.08; P = 0.819); however, SAR was significantly better for LCC (HR, 0.61; 95% CI, 0.53–0.71; P &lt; 0.001).

Conclusions:
A gradually diverging and increasingly favorable prognosis was observed for patients with LCC with advanced disease over the past four decades.

Impact:
Current PTL survival disparities stress the need for further exploring targetable molecular subgroups across and within different PTLs to further improve patient outcomes.
Brief Consent Methods Enable Rapid Enrollment in Acute Stroke Trial: Results From the TICH-2 Randomized Controlled Trial
Authors: Law Zhe Kang , Appleton Jason P. , Scutt Polly , Roberts Ian , Al-Shahi Salman Rustam , England Timothy J. , Werring David J. , Robinson Thompson , Krishnan Kailash , Dineen Robert A. , Laska Ann Charlotte , Lyrer Philippe A. , Egea-Guerrero Juan Jose , Karlinski Michal , Christensen Hanne , Roffe Christine , Bereczki Daniel , Ozturk Serefnur , Thanabalan Jegan , Collins Ronan , Beridze Maia , Ciccone Alfonso , Duley Lelia , Shone Angela , Bath Philip M. , Sprigg Nikola ,   the TICH-2 Investigators
Published: December 2021

Background:
Seeking consent rapidly in acute stroke trials is crucial as interventions are time sensitive. We explored the association between consent pathways and time to enrollment in the TICH-2 (Tranexamic Acid in Intracerebral Haemorrhage-2) randomized controlled trial.

Methods:
Consent was provided by patients or by a relative or an independent doctor in incapacitated patients, using a 1-stage (full written consent) or 2-stage (initial brief consent followed by full written consent post-randomization) approach. The computed tomography-to-randomization time according to consent pathways was compared using the Kruskal-Wallis test. Multivariable logistic regression was performed to identify variables associated with onset-to-randomization time of ≤3 hours.

Results:

Of 2325 patients, 817 (35%) gave self-consent using 1-stage (557; 68%) or 2-stage consent (260; 32%). For 1507 (65%), consent was provided by a relative (1 stage, 996 [66%]; 2 stage, 323 [21%]) or a doctor (all 2-stage, 188 [12%]). One patient did not record prerandomization consent, with written consent obtained subsequently. The median (interquartile range) computed tomography-to-randomization time was 55 (38–93) minutes for doctor consent, 55 (37–95) minutes for 2-stage patient, 69 (43–110) minutes for 2-stage relative, 75 (48–124) minutes for 1-stage patient, and 90 (56–155) minutes for 1-stage relative consents (
P
<0.001). Two-stage consent was associated with onset-to-randomization time of ≤3 hours compared with 1-stage consent (adjusted odds ratio, 1.9 [95% CI, 1.5–2.4]). Doctor consent increased the odds (adjusted odds ratio, 2.3 [1.5–3.5]) while relative consent reduced the odds of randomization ≤3 hours (adjusted odds ratio, 0.10 [0.03–0.34]) compared with patient consent. Only 2 of 771 patients (0.3%) in the 2-stage pathways withdrew consent when full consent was sought later. Two-stage consent process did not result in higher withdrawal rates or loss to follow-up.

Conclusions:
The use of initial brief consent was associated with shorter times to enrollment, while maintaining good participant retention. Seeking written consent from relatives was associated with significant delays.

Registration:

URL:
https://www.isrctn.com
; Unique identifier: ISRCTN93732214.
Who cares for the eggs? Analysis of egg attendance behaviour in Ranitomeya imitator, a poison frog with biparental care
Authors: Schulte Lisa M. , Summers Kyle 
Published: December 2021

Abstract
Dendrobatid poison frogs are known for their diverse parental care behaviours, including terrestrial egg attendance. While usually this behaviour is conducted by males, this study compared the pre-hatching investment of males and females in Ranitomeya imitator, a species with biparental care. Although males tended to spend more time with their eggs overall, there was no difference between sexes when comparing different types of care behaviour. Furthermore, both sexes increased general care behaviour when caring for more than one clutch. The finding that the sexes are relatively equal in their contribution to basic parental care forms provides a basis to understand why biparental care is stable in this species.
Improving a pest management tool for scenario analysis of economic populations of Globodera pallida
Authors: Koehler Ann-Kristin , Bell Christopher A. , Back Matthew A. , Urwin Peter E. , Atkinson Howard J. 
Published: December 2021

Summary
Globodera pallida is the most damaging pest of potato in the UK. This work underpins enhancement of a well-established, web-based scenario analysis tool for its management by recommending additions and modifications of its required inputs and a change in the basis of yield loss estimates. The required annual decline rate of the dormant egg population is determined at the individual field sample level to help define the required rotation length by comparing the viable egg content of recovered cysts to that of newly formed cysts for the same projected area. The mean annual decline was 20.4 ± 1.4% but ranged from 4.0 to 39.7% annum−1 at the field level. Further changes were based on meta-analysis of previous field trials. Spring rainfall in the region where a field is located and cultivar tolerance influence yield loss. Tolerance has proved difficult to define for many UK potato cultivars in field trials but uncertainty can be avoided without detriment by replacing it with determinacy integers. They are already determined to support optimisation of nitrogen application rates. Multiple linear regression estimates that loss caused by pre-plant populations of up to 20 viable eggs (g soil)−1 varies from ca 0.2 to 2.0% (viable egg)−1 (g soil)−1 depending on cultivar determinacy and spring rainfall. Reliability of the outcomes from scenario analysis requires validation in field trials with population densities over which planting is advisable.
Brain atrophy in acute ischaemic stroke patients treated with reperfusion therapy: a systematic review
Authors: Rastogi Aarushi , Weissert Robert , Bhaskar Sonu MM 
Published: December 2021

Background Brain atrophy (BA) may have a role in acute ischemic stroke (AIS) in mediating outcomes after reperfusion therapy. The extent of this association is not well understood. Purpose : To examine the impact of pre-existing BA on functional outcome, survival, symptomatic intracerebral hemorrhage (sICH), and early neurological change in patients with AIS treated with intravenous thrombolysis (IVT) and/or endovascular thrombectomy (EVT). Material and Methods PubMed, EMBASE, and the Cochrane library were searched for studies on BA in AIS receiving reperfusion therapy. Studies were included if: (i) patients were aged ≥18 years; (ii) patients had been diagnosed with AIS; (iii) patients received IVT and/or EVT; (iv) studies reported on BA; (v) studies reported on post-reperfusion outcomes; and (vi) studies had a sample size of >25 patients. Results A total of 4444 patients from eight studies were included. Four out of seven studies reporting on 90-day functional outcome found pre-existing BA to be significantly associated with poor functional outcome. Moreover, two out of four studies found BA to be a significant predictor of 90-day mortality. None of the included studies reported a significant association of BA with sICH or early neurological deterioration. Conclusion This systematic review indicates a potential prognostic role of BA in AIS. Quantitative analysis of association of BA with outcomes in AIS is not possible given the heterogeneity in BA assessment and reporting across studies. Future studies using standardized BA assessment are warranted to clarify its association with clinical and safety outcomes in AIS.
Preparation, characterization, and in vitro release kinetics of doxorubicin-loaded magnetosomes
Authors: Zhang Shuang , Fan Xinxin , Zhang Guojing , Wang Weidong , Yan Lei 
Published: December 2021

The doxorubicin (DOX) was successfully coupled to the magnetosomes from Acidithiobacillus ferrooxidans ( At. ferrooxidans) by genipin bridging. The parameters (magnetosome concentration, DOX concentration, genipin concentration-, and cross-link time) expected for temperature significantly influenced the coupling rate. Bacterial magnetosome-doxorubicin complexes (BMDCs) were characterized by transmission electron microscope (TEM), particle size analyzer and Fourier transform infrared spectroscopy. Results indicated that BMDCs exhibited a mean particle size of 83.98 mm and displayed a negative charge. The chemical reaction occurring between CO and NH group and the physical adsorption predominated by electrostatic interaction were found to involve in coupling. BMDCs can release 40% of DOX in simulated gastrointestinal conditions within 38 h. Kinetic models including Higuchi, Korsmeyer–Peppas, Zero order, First order, Hixon-Crowell, Baker-Lonsdale, and Weibull and Gompertz were utilized to explore the release mechanism of DOX from BMDCs. All models were found to fit well (r2 ≥ 0.8144) with the release data and the Gompertz was the best fit model (r2 = 0.9742), implying that the complex mechanisms involving Fickian and Gompertz diffusion contributed to the release. These findings suggested that magnetosomes from At. ferrooxidans have great potential applications in biomedical and clinical fields as the carrier of target drug delivery systems in the future.
A latent-class heteroskedastic hurdle trajectory model: patterns of adherence in obstructive sleep apnea patients on CPAP therapy
Authors: P. Den Teuling Niek G. , van den Heuvel Edwin R. , Aloia Mark S. , Pauws Steffen C. 
Published: December 2021

Abstract
Background
Sleep apnea patients on CPAP therapy exhibit differences in how they adhere to the therapy. Previous studies have demonstrated the benefit of describing adherence in terms of discernible longitudinal patterns. However, these analyses have been done on a limited number of patients, and did not properly represent the temporal characteristics and heterogeneity of adherence.

Methods
We illustrate the potential of identifying patterns of adherence with a latent-class heteroskedastic hurdle trajectory approach using generalized additive modeling. The model represents the adherence trajectories on three aspects over time: the daily hurdle of using the therapy, the daily time spent on therapy, and the day-to-day variability. The combination of these three characteristics has not been studied before.

Results
Applying the proposed model to a dataset of 10,000 patients in their first three months of therapy resulted in nine adherence groups, among which 49% of patients exhibited a change in adherence over time. The identified group trajectories revealed a non-linear association between the change in the daily hurdle of using the therapy, and the average time on therapy. The largest difference between groups was observed in the patient motivation score. The adherence patterns were also associated with different levels of high residual AHI, and day-to-day variability in leakage.

Conclusion
The inclusion of the hurdle model and the heteroskedastic model into the mixture model enabled the discovery of additional adherence patterns, and a more descriptive representation of patient behavior over time. Therapy adherence was mostly affected by a lack of attempts over time, suggesting that encouraging these patients to attempt therapy on a daily basis, irrespective of the number of hours used, could drive adherence. We believe the methodology is applicable to other domains of therapy or medication adherence.