bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intermediate-risk pulmonary embolism: echocardiography predictors of clinical deterioration
Authors: Weekes Anthony J. , Fraga Denise N. , Belyshev Vitaliy , Bost William , Gardner Christopher A. , O’Connell Nathaniel S. 
Published: June 2022

AbstractBackgroundWe determine the predictive value of transthoracic echocardiographic (TTE) metrics for clinical deterioration within 5 days in adults with intermediate-risk pulmonary embolism (PE).MethodsThis was a prospective observational study of intermediate-risk PE patients. To determine associations of TTE and clinical predictors with clinical deterioration, we used univariable analysis, Youden’s index for optimal thresholds, and multivariable analyses to report odds ratios (ORs) or area under the curve (AUC).ResultsOf 306 intermediate-risk PE patients, 115 (37.6%) experienced clinical deterioration. PE patients who had clinical deterioration within 5 days had greater baseline right ventricle (RV) dilatation and worse systolic function than the group without clinical deterioration as indicated by the following: RV basal diameter 4.46 ± 0.77 versus 4.20 ± 0.77 cm; RV/LV basal width ratio 1.14 ± 0.29 versus 1.02 ± 0.24; tricuspid annular plane systolic excursion (TAPSE) 1.56 ± 0.55 versus 1.80 ± 0.52 cm; and RV systolic excursion velocity 10.40 ± 3.58 versus 12.1 ± 12.5 cm/s, respectively. Optimal thresholds for predicting clinical deterioration were: RV basal width 3.9 cm (OR 2.85 [1.64, 4.97]), RV-to-left ventricle (RV/LV) ratio 1.08 (OR 3.32 [2.07, 5.33]), TAPSE 1.98 cm (OR 3.3 [2.06, 5.3]), systolic excursion velocity 10.10 cm/s (OR 2.85 [1.75, 4.63]), and natriuretic peptide 190 pg/mL (OR 2.89 [1.81, 4.62]). Significant independent predictors were: transient hypotension 6.1 (2.2, 18.9), highest heart rate 1.02 (1.00, 1.03), highest respiratory rate 1.02 (1.00, 1.04), and RV/LV ratio 1.29 (1.14, 1.47). By logistic regression and random forest analyses, AUCs were 0.80 (0.73, 0.87) and 0.78 (0.70, 0.85), respectively.ConclusionsBasal RV, RV/LV ratio, and RV systolic function measurements were significantly different between intermediate-risk PE patients grouped by subsequent clinical deterioration.
Association of annual hospital septic shock case volume and hospital mortality
Authors: Chen Yan , Ma Xu-dong , Kang Xiao-hui , Gao Si-fa , Peng Jin-min , Li Shan , Liu Da-wei , Zhou Xiang , Weng Li , Du Bin ,   China National Critical Care Quality Control Center Group
Published: June 2022

Abstract
Background
The burden of sepsis remains high in China. The relationship between case volume and hospital mortality among patients with septic shock, the most severe complication of sepsis, is unknown in China.

Methods
In this retrospective cohort study, we analyzed surveillance data from a national quality improvement program in intensive care units (ICUs) in China in 2020. Association between septic shock case volume and hospital mortality was analyzed using multivariate linear regression and restricted cubic splines.

Results
We enrolled a total of 134,046 septic shock cases in ICUs from 1902 hospitals in China during 2020. In this septic shock cohort, the median septic shock volume per hospital was 33 cases (interquartile range 14–76 cases), 41.4% were female, and more than half of the patients were over 61 years old, with average hospital mortality of 21.2%. An increase in case volume was associated with improved survival among septic shock cases. In the linear regression model, the highest quartile of septic shock volume was associated with lower hospital mortality compared with the lowest quartile (β − 0.86; 95% CI − 0.98, − 0.74; p < 0.001). Similar differences were found in hospitals of respective geographic locations and hospital levels. With case volume modeled as a continuous variable in a restricted cubic spline, a lower volume threshold of 40 cases before which a substantial reduction of the hospital mortality rate was observed.

Conclusions
The findings suggest that hospitals with higher septic shock case volume have lower hospital mortality in China. Further research is needed to explain the mechanism of this volume–outcome relationship.
Intravenous tocilizumab for the treatment of giant cell arteritis: a phase Ib dose-ranging pharmacokinetic bridging study
Authors: Schmitt Christophe , Brockwell Laura , Giraudon Mylène , Zucchetto Mauro , Christ Lisa , Bannert Bettina , Daikeler Thomas , Villiger Peter M. 
Published: June 2022

Abstract
Background
Subcutaneous tocilizumab (TCZ SC) is approved globally for giant cell arteritis (GCA). This phase Ib study investigated the pharmacokinetics, pharmacodynamics, safety, and exploratory efficacy of intravenous (IV) TCZ 6 and 7 mg/kg in patients with GCA. This study explored an IV dose resulting in a minimum exposure level within the range of effective trough concentrations achieved with TCZ SC dosing in GCA and not exceeding the exposure of the well-tolerated 8 mg/kg IV every 4 weeks (Q4W) in rheumatoid arthritis (RA).

Methods
Patients with GCA who had received ≥ 5 doses of TCZ IV 8 mg/kg Q4W and achieved remission were enrolled. Patients received 5 doses of TCZ IV 7 mg/kg Q4W in period 1 and, if still in remission, 5 doses of 6 mg/kg Q4W in period 2. Pharmacokinetic endpoints were maximum concentration (Cmax), minimum concentration (Ctrough), area under the curve over a dosing interval (AUCτ), and mean concentration (Cmean) of TCZ after the last dose of each period. Other endpoints included pharmacodynamic markers, safety, and exploratory efficacy.

Results
In 24 patients, the median (range) age was 65.5 (57–90) years, and 62.5% were female. TCZ exposures (Cmax and AUCτ) were 11.2% and 20.0% lower at the 6- than 7-mg/kg dose. The mean interleukin 6 (IL-6) serum concentrations were elevated at baseline and remained elevated, with slightly higher concentrations in period 1 than in period 2. The mean serum soluble IL-6 receptor concentrations were elevated at baseline and comparable between the 2 doses at steady state. C-reactive protein levels and most erythrocyte sedimentation rates were within normal ranges throughout the study. Overall, 22 patients (91.7%) had ≥ 1 adverse event, and 4 (16.7%) had a serious adverse event. No patients experienced a GCA flare, and all remained in remission throughout the study.

Conclusions
Both doses of TCZ IV Q4W were generally well tolerated in patients with GCA. The Cmax and Cmean achieved with 6 mg/kg IV Q4W in patients with GCA were similar to those in patients with RA treated with 8 mg/kg IV Q4W, and Ctrough was within the range observed in patients with GCA treated with SC dosing every week or every 2 weeks.

Trial registration
ClinicalTrials.gov, NCT03923738
Quantification of SNAP-25 with mass spectrometry and Simoa: a method comparison in Alzheimer’s disease
Authors: Nilsson Johanna , Ashton Nicholas J. , Benedet Andrea L. , Montoliu-Gaya Laia , Gobom Johan , Pascoal Tharick A. , Chamoun Mira , Portelius Erik , Jeromin Andreas , Mendes Muriel , Zetterberg Henrik , Rosa-Neto Pedro , Brinkmalm Ann , Blennow Kaj 
Published: June 2022

Abstract
Background
Synaptic dysfunction and degeneration are central to Alzheimer’s disease (AD) and have been found to correlate strongly with cognitive decline. Thus, studying cerebrospinal fluid (CSF) biomarkers reflecting synaptic degeneration, such as the presynaptic protein synaptosomal-associated protein 25 (SNAP-25), is of importance to better understand the AD pathophysiology.

Methods
We compared a newly developed Single molecule array (Simoa) immunoassay for SNAP-25 with an in-house immunoprecipitation mass spectrometry (IP-MS) method in a well-characterized clinical cohort (n = 70) consisting of cognitively unimpaired (CU) and cognitively impaired (CI) individuals with and without Aβ pathology (Aβ+ and Aβ−).

Results
A strong correlation (Spearman’s rank correlation coefficient (rs) > 0.88; p < 0.0001) was found between the Simoa and IP-MS methods, and no statistically significant difference was found for their clinical performance to identify AD pathophysiology in the form of Aβ pathology. Increased CSF SNAP-25 levels in CI Aβ+ compared with CU Aβ− (Simoa, p ≤ 0.01; IP-MS, p ≤ 0.05) and CI Aβ− (Simoa, p ≤ 0.01; IP-MS, p ≤ 0.05) were observed. In independent blood samples (n = 32), the Simoa SNAP-25 assay was found to lack analytical sensitivity for quantification of SNAP-25 in plasma.

Conclusions
These results indicate that the Simoa SNAP-25 method can be used interchangeably with the IP-MS method for the quantification of SNAP-25 in CSF. Additionally, these results confirm that CSF SNAP-25 is increased in relation to amyloid pathology in the AD continuum.
Incidental findings on coronary computed tomography in women with selected reproductive disorders
Authors: van der Ham Kim , van Zwol-Janssens Charissa , Velthuis Birgitta K. , Koster Maria P. H. , Louwers Yvonne V. , Goei Dustin , Blomjous Maurits S. H. , Franx Arie , Fauser Bart C. J. M. , Boersma Eric , Laven Joop S. E. , Budde Ricardo P. J. ,   the CREW Consortium
Published: June 2022

Abstract
Objective
To determine the prevalence of incidental findings (IFs) on coronary computed tomography (CCT) in women aged 45–55 years and previously diagnosed with reproductive disorders such as polycystic ovary syndrome (PCOS), premature ovarian insufficiency (POI) or preeclampsia (PE).

Methods
A total of 486 middle-aged women with PCOS (n = 101), POI (n = 97) or a history of PE (n = 288) underwent a CCT as part of a prior prospective study. IFs were categorized by their significance (minor, moderate and major). Follow-up information was collected from patients’ records. To investigate the impact of different field of views (FOVs), a subset of scans was analyzed in full FOV and small FOV.

Results
In 96/486 (19.8%) women, one or more IFs were detected, of which 54/486 (11.1%) were classified as moderate/major and 48/486 (9.9%) required follow-up. A moderate/major IF was detected in 16/101 (15.9%) women with PCOS, 13/97 (13.4%) women with POI and 25/288 (8.7%) women with a history of PE. In 78 women with an IF detected in the full FOV, the IF was still visible in 60 (76.9%) women in the small FOV. In the full FOV, 46 women required follow-up, but using the small FOV this was reduced to 30 women.

Conclusion
Using CCT as a cardiovascular disease screening tool in women with selected reproductive disorders increases the probability of detecting IFs that can cause anxiety and may generate extra costs, but can also reveal clinically relevant findings. Using a small FOV centered around the heart resulted in a lower prevalence of IFs and required less follow-up.
Appetite ratings and ghrelin concentrations in young adults after administration of a balanced meal. Does sex matter?
Authors: Leone Alessandro , De Amicis Ramona , Pellizzari Marta , Bertoli Simona , Ravella Simone , Battezzati Alberto 
Published: June 2022

Abstract
Background
Sex-based differences in appetite ratings have been observed previously. Ghrelin is the only known orexigenic peptide hormone. Sex differences in postprandial ghrelin responses may underlie different perceptions of hunger and satiety, but results are conflicting. We conducted a parallel study to evaluate sex differences in postprandial appetite ratings and ghrelin concentration after administration of a physiological meal among students of University of Milan.

Methods
Twenty-four healthy, normal weight volunteers (12 men and 12 women) aged 18–35 years were recruited. A balanced mixed meal meeting 40% of the estimated daily energy expenditure and providing 60% of calories from carbohydrates, 25% from lipids and 15% from protein was administrated. Sex differences in appetite ratings (satiety, hunger, fullness and desire to eat) and magnitude of ghrelin suppression during postprandial period (up to 180 min) were determined.

Results
In the fasting state, men and women did not differ in appetite ratings and ghrelin concentrations. After feeding, women tended to reach peak of satiety earlier than men, who in turn reached the nadir of hunger later than women (median: 30 min, interquartile range (IQR): 1; 120 vs. 1 min, IQR 1; 1, p = 0.007). Ghrelin suppression was greater in women (median decremental AUC − 95, IQR − 122; − 66) than in men (median decremental AUC − 47, IQR − 87; − 31, p = 0.041).

Conclusions
These findings suggest sex differences in the postprandial appetite regulation that might be important for nutritional strategy to prevent and treat obesity and eating disorders.
The diagnostic potential of oxidative stress biomarkers for preeclampsia: systematic review and meta-analysis
Authors: Afrose Dinara , Chen Hao , Ranashinghe Amali , Liu Chia-chi , Henessy Annemarie , Hansbro Philip M. , McClements Lana 
Published: June 2022

Abstract
Background
Preeclampsia is a multifactorial cardiovascular disorder of pregnancy. If left untreated, it can lead to severe maternal and fetal outcomes. Hence, timely diagnosis and management of preeclampsia are extremely important. Biomarkers of oxidative stress are associated with the pathogenesis of preeclampsia and therefore could be indicative of evolving preeclampsia and utilized for timely diagnosis. In this study, we conducted a systematic review and meta-analysis to determine the most reliable oxidative stress biomarkers in preeclampsia, based on their diagnostic sensitivities and specificities as well as their positive and negative predictive values.

Methods
A systematic search using PubMed, ScienceDirect, ResearchGate, and PLOS databases (1900 to March 2021) identified nine relevant studies including a total of 343 women with preeclampsia and 354 normotensive controls.

Results
Ischemia-modified albumin (IMA), uric acid (UA), and malondialdehyde (MDA) were associated with 3.38 (95% CI 2.23, 4.53), 3.05 (95% CI 2.39, 3.71), and 2.37 (95% CI 1.03, 3.70) odds ratios for preeclampsia diagnosis, respectively. The IMA showed the most promising diagnostic potential with the positive predictive ratio (PPV) of 0.852 (95% CI 0.728, 0.929) and negative predictive ratio (NPV) of 0.811 (95% CI 0.683, 0.890) for preeclampsia. Minor between-study heterogeneity was reported for these biomarkers (Higgins’ I2 = 0–15.879%).

Conclusions
This systematic review and meta-analysis identified IMA, UA, and MDA as the most promising oxidative stress biomarkers associated with established preeclampsia. IMA as a biomarker of tissue damage exhibited the best diagnostic test accuracy. Thus, these oxidative stress biomarkers should be further explored in larger cohorts for preeclampsia diagnosis.

Graphical Abstract
Major mistakes and errors in the use of Trial Sequential Analysis in systematic reviews or meta-analyses – protocol for a systematic review
Authors: Riberholt Christian Gunge , Olsen Markus Harboe , Milan Joachim Birch , Gluud Christian 
Published: June 2022

Abstract
Background
Adequately conducted systematic reviews with meta-analyses are considered the highest level of evidence and thus directly defines many clinical guidelines. However, the risks of type I and II errors in meta-analyses are substantial. Trial Sequential Analysis is a method for controlling these risks. Erroneous use of the method might lead to research waste or misleading conclusions.

Methods
The current protocol describes a systematic review aimed to identify common and major mistakes and errors in the use of Trial Sequential Analysis by evaluating published systematic reviews and meta-analyses that include this method. We plan to include all studies using Trial Sequential Analysis published from January 2018 to January 2022, an estimated 400 to 600 publications. We will search Medical Literature Analysis and Retrieval System Online and the Cochrane Database of Systematic Reviews, including studies with all types of participants, interventions, and outcomes. Two independent reviewers will screen titles and abstracts, include relevant full text articles, extract data from the studies into a predefined checklist, and evaluate the methodological quality of the study using the AMSTAR 2, assessing the methodological quality of the systematic reviews.

Discussion
This protocol follows the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P). The identified mistakes and errors will be published in peer reviewed articles and form the basis of a reviewed guideline for the use of Trial Sequential Analysis. Appropriately controlling for type I and II errors might reduce research waste and improve quality and precision of the evidence that clinical guidelines are based upon.
R-convexity in R-vector spaces
Authors: Ebrahimi Meymand Ali , Alijani Azadeh 
Published: June 2022

AbstractIn this paper, for every relation R on a vector space V, we consider the R-vector space $(V,R)$
(
V
,
R
)
and define the notions of R-convexity, R-convex hull, and R-extreme point in this space. Some examples are provided to compare them with the reference cases. The effects of some operations on R-convex sets are investigated. In particular, it is shown that the R-interior of an R-convex set is also an R-convex set under some restrictions on R. Also, we give some equivalent conditions for R-extremeness. Moreover, the notions of R-convex and R-affine maps on R-vector spaces are defined, and some results that assert the relation between an R-convex map f and its R-epigraph under some limitations on R are considered. Several propositions, such as R-continuous maps preserve R-compact sets and R-affine maps preserve R-convex sets, are presented, and some results on the composition of R-convex and R-affine maps are considered. Finally, some applications of R-convexity are investigated in optimization. More precisely, we show that the extrema values of R-affine R-continuous maps are reached on R-extreme points. Moreover, local and global minimum points of an R-convex map f on R-convex set K are considered.
On some bounds on the perturbation of invariant subspaces of normal matrices with application to a graph connection problem
Authors: Bhattacharya Subhrajit 
Published: June 2022

AbstractWe provide upper bounds on the perturbation of invariant subspaces of normal matrices measured using a metric on the space of vector subspaces of $\mathbb{C}^{n}$

C
n

in terms of the spectrum of both unperturbed and perturbed matrices as well as the spectrum of the unperturbed matrix only. The results presented give tighter bounds than the Davis–Kahan sinΘ theorem. We apply the result to a graph perturbation problem.
Complex symmetric Toeplitz operators on the generalized derivative Hardy space
Authors: Ko Eungil , Lee Ji Eun , Lee Jongrak 
Published: June 2022

AbstractThe generalized derivative Hardy space $S^{2}_{\alpha ,\beta}(\mathbb{D})$

S

α
,
β

2

(
D
)
consists of all functions whose derivatives are in the Hardy and Bergman spaces as follows:for positive integers α, β, $$ S^{2}_{\alpha ,\beta}(\mathbb{D})= \biggl\{ f\in H(\mathbb{D}) : \Vert {f} \Vert ^{2}_{S^{2}_{ \alpha ,\beta}}= \Vert {f} \Vert ^{2}_{H^{2}}+{ \frac{{\alpha +\beta}}{\alpha \beta}} \bigl\Vert {f'} \bigr\Vert ^{2}_{A^{2}}+ \frac{1}{\alpha \beta} \bigl\Vert {f'} \bigr\Vert ^{2}_{H^{2}}< \infty \biggr\} , $$

S

α
,
β

2

(
D
)
=

{
f
∈
H
(
D
)
:

∥
f
∥

S

α
,
β

2

2

=

∥
f
∥

H
2

2

+

α
+
β

α
β

∥

f
′

∥

A
2

2

+

1

α
β

∥

f
′

∥

H
2

2

<
∞
}

,
where $H({\mathbb{D}})$
H
(
D
)
denotes the space of all functions analytic on the open unit disk ${\mathbb{D}}$
D
. In this paper, we study characterizations for Toeplitz operators to be complex symmetric on the generalized derivative Hardy space $S^{2}_{\alpha ,\beta}(\mathbb{D})$

S

α
,
β

2

(
D
)
with respect to some conjugations $C_{\xi}$

C
ξ

, $C_{\mu , \lambda}$

C

μ
,
λ

. Moreover, for any conjugation C, we consider the necessary and sufficient conditions for complex symmetric Toeplitz operators with the symbol φ of the form $\varphi (z)=\sum_{n=1}^{\infty}\overline{\hat{\varphi}(-n)} \overline{z}^{n}+\sum_{n=0}^{\infty}\hat{\varphi}(n)z^{n}$
φ
(
z
)
=

∑

n
=
1

∞

φ
ˆ

(
−
n
)

‾

z
‾

n

+

∑

n
=
0

∞

φ
ˆ

(
n
)

z
n

. Next, we also study complex symmetric Toeplitz operators with non-harmonic symbols on the generalized derivative Hardy space $S^{2}_{\alpha ,\beta}(\mathbb{D})$

S

α
,
β

2

(
D
)
.
Post COVID-19 condition and its physical, mental and social implications: protocol of a 2-year longitudinal cohort study in the Belgian adult population
Authors: Smith Pierre , Proesmans Kristiaan , Van Cauteren Dieter , Demarest Stefaan , Drieskens Sabine , De Pauw Robby , Cornelissen Laura , De Ridder Karin , Charafeddine Rana 
Published: June 2022

Abstract
Background
Since the onset of the COVID-19 pandemic, most research has focused on the pathophysiology and management of the acute symptoms of COVID-19, yet some people tend to experience symptoms beyond the acute phase of infection, that is, Post COVID-19 condition (PCC). However, evidence on the long-term health impacts of a COVID-19 infection are still scarce. The purpose of this paper is to describe the COVIMPACT study, which aims to set up a cohort of people who have been tested positive for COVID-19 and study the evolution of their physical, mental and social health over the medium (3 months) and long term (two years), and the factors associated with an (un)favorable evolution.

Methods
COVIMPACT is a longitudinal cohort study organised over a two-years period between April 2021 and April 2023. The eligible population is all people aged 18 years and older, living in Belgium, with a recent COVID-19 infection and contacted by the health authorities for contact tracing. Two questionnaires are used: a baseline questionnaire that aims to assess the initial health status of the participants and their status during the acute phase of the illness, and a follow-up questionnaire that is sent every three months after participants enter into the cohort. A matched non-COVID-19 control group was also selected. As of November 1, 2021, 10,708 people completed the baseline questionnaire (5% of the eligible population) and the follow-up participation rate was 79%. In total, 48% of the cohort participants appeared to fit the proposed case definition of PCC (i.e. report at least one symptom related to their COVID-19 infection three months afterwards).

Discussion
This study was designed to provide timely information on the short and long term impact of a COVID-19 infection, to stakeholders such as policymakers, health practitioners and people with PCC. Although the follow-up participation rate was good (79%), the participation rate of the eligible population was low (5%). Compared to other studies, this study has a large sample, of non-hospitalised and hospitalised people, who will be followed over a long period of 3 months to two years post infection, and with a global approach to their health.