bluuebunny/crossref_metadata_2025 huggingface dataset:
A comparison of cone beam computed tomography, standard computed tomography and plain radiographs in the evaluation of medial epicondyle humerus fractures
Authors: Rupp Garrett E. , Farnsworth Christine L. , Hughes Jessica L. , Upasani Vidyadhar V. , Pennock Andrew T. , Bomar James D. , Edmonds Eric W.
Published: October 2021

The ideal technique to measure medial epicondyle humerus fracture displacement minimizes radiation exposure while maximizing measurement accuracy and reliability. This study compares the radiation exposure and accuracy of displacement measurements of the four-view X-ray examination (XR), computed tomography (CT) and in-clinic cone-beam CT (CBCT). A cadaveric humerus underwent medial epicondyle osteotomy. The fragment was fixed to the humerus at clinically relevant displacements (6 to 18 mm). Dosimeters were placed around the distal humerus and simulating thyroid location. XR, CT and CBCT were performed at each displacement. Four pediatric orthopedists measured the maximum linear displacement on each XR and 3D reconstruction of the CT and CBCT images. Focal (elbow location) and thyroid radiation exposure was compared between modalities. Intra- and interclass correlation coefficients (ICC) for displacement measurements were determined. Mean focal radiation exposures for XR, CT and CBCT were 0.008, 2.061 and 0.478 rad, respectively (P = 0.001). Exposures 10 inches from the elbow for XR, CT and CBCT were 0.001, 0.066 and 0.010 rad, respectively (P = 0.006). At 12 inches, there was no significant difference in exposure between XR and CBCT (P = 0.114). Intra- and interobserver reliabilities were excellent for all measures, except lateral x-ray. CBCT and CT had significantly less deviation from the actual displacement compared to XR (P < 0.05). In-office CBCT of the elbow exposes patients to significantly less radiation than conventional CT. All X-ray images (except lateral), CT and CBCT had equal reliability in evaluating medial epicondyle fractures, which contrasts with previous evidence.
Instrumented Versus Noninstrumented Spinal Fusion for Degenerative Lumbar Spondylolisthesis
Authors: Hirase Takashi , Ling Jeremiah F. , Haghshenas Varan , Weiner Bradley K.
Published: October 2021

Study Design:

Systematic review.

Objective:

This systematic review compares radiographic and clinical outcomes between instrumented and noninstrumented posterolateral lumbar spine fusions for the treatment of degenerative lumbar spondylolisthesis.

Summary of Background Data:

The optimal method of fusion for instability from degenerative lumbar spondylolisthesis remains to be an area of debate amongst spine surgeons. There are no prior comprehensive systematic review of comparative studies that compares outcomes between instrumented and noninstrumented posterolateral spine fusions for the treatment of degenerative lumbar spondylolisthesis.

Materials and Methods:

A systematic review was registered with PROSPERO and performed according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines using the PubMed, SCOPUS, and Ovid MEDLINE databases. All level I–III comparative studies published in the English language investigating the clinical outcomes between instrumented and noninstrumented posterolateral spine fusions for the treatment of degenerative lumbar spondylolisthesis were included.

Results:

Seven studies (672 patients, 274 noninstrumented, 398 instrumented) were analyzed. One randomized study was level I evidence, 2 randomized studies were level II, and 4 nonrandomized studies were level III. Mean follow-up ranged from 1.4 to 5.9 years. Instrumented patients had a higher rate of solid fusion (87.6% vs. 77.1%, P=0.023) and a lower rate of definitive pseudarthrosis (5.3% vs. 19.9%, P<0.001). However, there was no difference in overall functional improvement at final follow-up between the 2 treatment groups (75.0% vs. 81.7%, P=0.258). In addition, there was no difference in reoperation or complication rates.

Conclusions:

For the treatment of degenerative lumbar spondylolisthesis, there are significantly higher rates of fusion among patients undergoing instrumented posterolateral fusion compared with noninstrumented posterolateral fusion. However, there is no difference in overall functional improvement, pain-related outcome scores, reoperation rates, or complication rates between the 2 treatment groups.

Level of Evidence:

Level III—systematic review of level I–III studies.
Comparison of Outcomes Between Percutaneous Vertebroplasty and Percutaneous Kyphoplasty for the Treatment of Kümmell’s Disease
Authors: Huang Xusheng , Chang Hong , Xu Hualiang , Chen Xiang , Wang Hua , Song Yancheng
Published: October 2021

Study Design:

A meta-analysis.

Objective:

The aim is to compare the efficacy of percutaneous vertebroplasty (PVP) and percutaneous kyphoplasty (PKP) in treating Kümmell’s disease (KD) without neurological deficits.

Summary of Background Data:

PVP and PKP are routine methods for the treatment of KD without neurological deficits; however, whether PVP or PKP is superior is a matter of debate.

Materials and Methods:

According to the Cochrane Handbook for Systematic Reviews of Interventions, PubMed, Embase, the Cochrane Library, and Web of Knowledge were searched for eligible randomized controlled trials or cohort studies. Two authors independently collected data and assessed the methodologic quality of the included studies. Intraoperative and postoperative clinical outcomes, cement leakage, refracture rate, and the costs during hospitalization were evaluated.

Results:

Five observational studies comparing 119 PVP and 128 PKP patients were included in qualitative and quantitative reviews. All of the included s studies had evidence of good quality, as assessed by the Newcastle-Ottawa scale. On the basis of meta-analysis the operation time [weighted mean difference: −10.65; 95% confidence interval (95% CI): −11.94 to −9.35; P<0.00001] and hospitalization cost (weighted mean difference: −2.38; 95% CI: −2.87 to −1.89; P<0.00001) were less for PVP, while the cement leakage rate was lower for PKP (odds ratio: 3.03; 95% CI: 1.58–5.82; P<0.001). Together, the data indicated that the differences in cement volume, visual analog scale score, Oswestry disability index score, Cobb angle, anterior vertebral height, and refracture rate were not significantly different.

Conclusion:

The findings of this study suggest that PVP and PKP are safe and effective for the treatment of KD. PVP required less operative time and was more affordable, but PKP was superior given the lower cement leakage rate. Additional high-quality randomized controlled trials designed to support these findings are warranted.
Kirsten rat sarcoma inhibitors in clinical development against nonsmall cell lung cancer
Authors: Li Yunchang , Hu Lanlin , Xu Chuan
Published: October 2021

Purpose of review

The unique structure made Kirsten rat sarcoma (KRAS) ‘undruggable’ for quite an extended period. The functional mechanism of this small protein is well illustrated. However, there is no precision medicine for nonsmall cell lung cancer (NSCLC) patients burden with KRAS mutation. The attempts made by scientists to make challenge history against KRAS mutation and their druggable targets are worth elucidating.

Recent findings

The appearance of orphan drug AMG510 in the market specifically targeting KRASG12C is a tremendous breakthrough. Several KRAS inhibitors are under development now. More studies focus on combo treatment of KRAS inhibition and immune checkpoint inhibitors (ICIs). Recent preclinical and clinical investigations have been reported that NSCLC patients with KRAS mutation can benefit from ICIs.

The current review elucidates the development of KRAS inhibitors from basic research to clinical precision medicines. We retrospectively analyze the development of KRAS mutation targeting drugs and discuss the investigations for future development of KRAS inhibitors.
Incorporating G6PD genotyping to identify patients with G6PD deficiency
Authors: Morris Sarah A. , Crews Kristine R. , Hayden Randall T. , Takemoto Clifford M. , Yang Wenjian , Baker Donald K. , Broeckel Ulrich , Relling Mary V. , Haidar Cyrine E.
Published: October 2021

Glucose-6-phosphate-dehydrogenase (G6PD) deficiency is a common X-linked enzyme disorder associated with hemolytic anemia after exposure to fava beans or certain medications. Activity testing is the gold standard for detecting G6PD deficiency; however, this test is affected by various hematologic parameters. Clinical G6PD genotyping is now included in pharmacogenetic arrays and clinical sequencing efforts and may be reconciled with activity results. Patients (n = 1391) enrolled on an institutional pharmacogenetic testing protocol underwent clinical G6PD genotyping for 164 G6PD variants. An algorithm accounting for known interferences with the activity assay is proposed. We developed clinical decision support alerts to inform prescribers when high-risk medications were prescribed, warning of gene–drug interactions and recommending therapy alteration. Of 1391 patients with genotype results, 1334 (95.9%) patients were predicted to have normal G6PD activity, 30 (2.1%) were predicted to have variable G6PD activity and 27 (2%) were predicted to have deficient G6PD activity. Of the 417 patients with a normal genotype and an activity result, 415 (99.5%) had a concordant normal G6PD phenotype. Of the 21 patients with a deficient genotype and an activity result, 18 (85.7%) had a concordant deficient activity result. Genotyping reassigned phenotype in five patients with discordant genotype and activity results: three switched from normal to deficient, and two switched from deficient to normal. G6PD activity and genotyping are two independent testing methods that can be used in conjunction to assign a more informed G6PD phenotype than either method alone.
Beyond the 21-cm Notch-to-nipple Myth: Golden Proportions in Breast Aesthetics
Authors: Sandberg Lars Johan , Tønseth Kim Alexander , Kloster-Jensen Kristine , Liu Jun , Reece Gregory , Halle Martin , Edsander-Nord Åsa , Höckerstedt Anna , Kauhanen Susanna , Tindholdt Tyge Tind , Gunnarsson Gudjon Leifur , Selber Jesse Creed
Published: October 2021

Background:

The 21-cm notch-to-nipple distance has been accepted without academic scrutiny as a key measure in breast aesthetics. The Fibonacci sequence and phi ratio occur frequently in nature. They have previously been used to assess aesthetics of the face, but not the breast. This study aims to assess if the static 21-cm measure or the proportional phi ratio is associated with ideal breast aesthetics.

Method:

Subclavicular-breast height and breast width were used to calculate the aesthetic ratio. Subjects were subsequently aesthetically rated. A one-sample t-test was used to determine if the ratio for each breast differed from phi. Breast scores with one, both, or no breasts were compared with an optimal phi ratio. Analysis of variance was performed. Tukey–Kramer adjustment for multiple comparisons was used when pairwise comparisons were conducted.

Results:

Five subjects (14%) had bilateral optimal phi ratio breasts. Four subjects (11%) had one breast with an optimal phi ratio. Subjects with bilateral optimal phi ratios had significantly higher overall breast scores than those with only one optimal breast (Δ = 0.86, P = 0.025) or no optimal breast (Δ = 0.73, P = 0.008). Distance from optimal Fibonacci nipple position was moderately to strongly correlated with aesthetic score (−0.630, P = 0.016). No correlation was found between 21-cm notch-to-nipple distance and aesthetic score.

Conclusion:

The bilateral optimal phi ratio is correlated with high overall aesthetic scores, as is the optimal Fibonacci nipple position. No correlation was found between 21-cm notch-to-nipple distance and overall aesthetic score.
Low Mean Nocturnal Baseline Impedance is Associated With a Pathological Acid Exposure Time in Children
Authors: Rosado‐Arias Yolainis , Toro‐Monjaraz Erick Manuel , Cervantes‐Bustamante Roberto , Zarate‐Mondragon Flora , Cadena‐Leon Jose , Ignorosa‐Arellano Karen , Loredo‐Mayer Alejandro , Ramírez‐Mayans Jaime
Published: October 2021

Background:

The baseline impedance (BI) and the mean nocturnal baseline impedance (MNBI) serve as markers of mucosal integrity in patients with pathologic acid exposure time (AET). This work aims to investigate the association between the BI and MNBI with the AET in children.

Methodology:

A retrospective study was performed in children ⩽18 years old with suspicion of gastroesophageal reflux disease who underwent both endoscopy and pH‐impedance monitoring (pH‐MII). Esophagitis was graded according to the Los Angeles classification. The pathological AET was determined depending on the age (≥5% in patients >1 year and ≥10% in those ages ⩽1 year). For the BI, 60 s measurements were taken every 4 h, and for the MNBI, 3 10 min measurements were taken between 1.00 and 3:00 AM; then, they were averaged. The means of BI and MNBI were compared with each other, with the AET, and other variables.

Results:

Sixty‐eight patients were included, 25% of patients presented pathological AET. The mean of the MNBI was higher than BI in channels 6 (2195 vs 1997 Ω, P = 0.011) and 5 (2393 vs 2228 Ω, P = 0.013). BI and MNBI at channel 6 were lower in patients with pathological AET than in those with normal AET (1573 vs 2138 Ω, P = 0.007) and (1592 vs 2396 Ω, P = 0.004), respectively.

Conclusions:

Children with pathological AET had lower impedance values than those with normal AET. BI and MNBI measurements should be part of the routine MII‐pH assessment in children.
Effects of Esterified Hyaluronic Acid, Adipose Tissue, and Blood Glue on Survival of Diced Cartilage Grafts
Authors: Ozturk Semra Kulekci , Habesoglu Tulay Erden , Ihvan Aysenur , Palaoglu Ibrahim , Cokay Baris Ilke , Habesoglu Mehmet Ozgur
Published: October 2021

Objectives:

Diced cartilage grafts are used for correcting nasal dorsal deformities and irregularities. However, cartilage resorption is among most common problems after rhinoplasty. The purpose of this experimental study was to investigate the effects of esterified hyaluronic acid, adipose tissue, and blood glue on the viability of diced cartilage grafts.

Methods:

A total of 24 Wistar albino rats were used for the study. Cartilage grafts were obtained from 1 side ear and diced. The rats were divided into 4 groups (6 in each group): bare diced cartilage (group 1), diced cartilage wrapped with adipose tissue (group 2), diced cartilage blended with blood glue (group 3), and diced cartilage wrapped with esterified hyaluronic acid (group 4). The grafts were inserted into the subcutaneous pockets of the back of same rat. After 2 months follow-up specimens were harvested for histopathological and dimensional examination. The sections were stained with Hematoxylin and Eosin, Masson-Trichrome, and Elastic Van-Gieson. Chronic inflammation, loss of chondrocyte nucleus, vascularization, foreign body reaction, collagen content of matrix, and extent of elastic fiber were assessed under light microscopy.

Results:

Foreign body reaction in adipose tissue and blood group was significantly higher than bare cartilage and esterified hyaluronic acid group (P = 0.001). With respect to loss of chondrocyte nucleus esterified hyaluronic acid group had significant higher rate of nucleus loss than other groups (P = 0.002).

Conclusions:

This study suggests that blood glue, esterified hyaluronic acid and autologous adipose tissue have not beneficial effects in improving viability of diced cartilage grafts.
The Effectiveness of Methylprednisolone as a Premedication Among the Pediatric Population for Preventing Infusion-Related Reactions to Infliximab
Authors: Zeng-Wang Yiping Maggie , Cares Kristen , Thomas Ronald , El-Baba Mohammad
Published: October 2021

Administering medications prior to infliximab infusions to prevent infusion-related infliximab reactions is a common practice in the United States. However, the premedication protocol varies among different institutions. The purpose of this study was to demonstrate whether the use of methylprednisolone was effective as a premedication to prevent infusion reactions while infliximab was administered to children with inflammatory bowel disease. The effect of concurrent use of other immunomodulators on the rate of reaction incidents was also studied. This was a retrospective chart review, assessing children younger than 21 years diagnosed with inflammatory bowel disease from January 2008 to April 2018. The incident rate of infusion reactions was also compared between two cohorts: those who received the premedication of methylprednisolone and those who did not. Subgroup analysis of concomitant immunomodulators, infliximab dose and frequency, and anti-infliximab assay were also performed. A total of 34 subjects received methylprednisolone as a premedication and 151 subjects did not. No statistically significant difference of allergic reactions was found between the two groups (p = .727). Concomitant immunomodulator therapy lowered the likelihood of developing reactions (p = .048). This study was conducted to help pediatric gastroenterology and infusion nurses better understand and implement evidence-based approaches in the premedication protocol for infusions of anti-tumor necrosis factor-α (anti-TNF-α) antibody products.
Assessment of long-range cross-correlations in cardiorespiratory and cardiovascular interactions
Authors: Nakata Akio , Kaneko Miki , Taki Chinami , Evans Naoko , Shigematsu Taiki , Kimura Tetsuya , Kiyono Ken
Published: October 2021

We propose higher-order detrending moving-average cross-correlation analysis (DMCA) to assess the long-range cross-correlations in cardiorespiratory and cardiovascular interactions. Although the original (zeroth-order) DMCA employs a simple moving-average detrending filter to remove non-stationary trends embedded in the observed time series, our approach incorporates a Savitzky–Golay filter as a higher-order detrending method. Because the non-stationary trends can adversely affect the long-range correlation assessment, the higher-order detrending serves to improve accuracy. To achieve a more reliable characterization of the long-range cross-correlations, we demonstrate the importance of the following steps: correcting the time scale, confirming the consistency of different order DMCAs, and estimating the time lag between time series. We applied this methodological framework to cardiorespiratory and cardiovascular time series analysis. In the cardiorespiratory interaction, respiratory and heart rate variability (HRV) showed long-range auto-correlations; however, no factor was shared between them. In the cardiovascular interaction, beat-to-beat systolic blood pressure and HRV showed long-range auto-correlations and shared a common long-range, cross-correlated factor.

This article is part of the theme issue ‘Advanced computation in cardiovascular physiology: new challenges and opportunities’.
Optimizing phase variability threshold for automated synchrogram analysis of cardiorespiratory interactions in amateur cyclists
Authors: Cairo Beatrice , de Abreu Raphael Martins , Bari Vlasta , Gelpi Francesca , De Maria Beatrice , Rehder-Santos Patrícia , Sakaguchi Camila Akemi , da Silva Claudio Donisete , De Favari Signini Étore , Catai Aparecida Maria , Porta Alberto
Published: October 2021

We propose a procedure suitable for automated synchrogram analysis for setting the threshold below which phase variability between two marker event series is of such a negligible amount that the null hypothesis of phase desynchronization can be rejected. The procedure exploits the principle of maximizing the likelihood of detecting phase synchronization epochs and it is grounded on a surrogate data approach testing the null hypothesis of phase uncoupling. The approach was applied to assess cardiorespiratory phase interactions between heartbeat and inspiratory onset in amateur cyclists before and after 11-week inspiratory muscle training (IMT) at different intensities and compared to a more traditional approach to set phase variability threshold. The proposed procedure was able to detect the decrease in cardiorespiratory phase locking strength during vagal withdrawal induced by the modification of posture from supine to standing. IMT had very limited effects on cardiorespiratory phase synchronization strength and this result held regardless of the training intensity. In amateur athletes training, the inspiratory muscles did not limit the decrease in cardiorespiratory phase synchronization observed in the upright position as a likely consequence of the modest impact of this respiratory exercise, regardless of its intensity, on cardiac vagal control.

This article is part of the theme issue 'Advanced computation in cardiovascular physiology: new challenges and opportunities'.
Opening the black box: interpretability of machine learning algorithms in electrocardiography
Authors: Bodini Matteo , Rivolta Massimo W. , Sassi Roberto
Published: October 2021

Recent studies have suggested that cardiac abnormalities can be detected from the electrocardiogram (ECG) using deep machine learning (DL) models. However, most DL algorithms lack interpretability, since they do not provide any justification for their decisions. In this study, we designed two new frameworks to interpret the classification results of DL algorithms trained for 12-lead ECG classification. The frameworks allow us to highlight not only the ECG samples that contributed most to the classification, but also which between the P-wave, QRS complex and T-wave, hereafter simply called ‘waves’, were the most relevant for the diagnosis. The frameworks were designed to be compatible with any DL model, including the ones already trained. The frameworks were tested on a selected Deep Neural Network, trained on a publicly available dataset, to automatically classify 24 cardiac abnormalities from 12-lead ECG signals. Experimental results showed that the frameworks were able to detect the most relevant ECG waves contributing to the classification. Often the network relied on portions of the ECG which are also considered by cardiologists to detect the same cardiac abnormalities, but this was not always the case. In conclusion, the proposed frameworks may unveil whether the network relies on features which are clinically significant for the detection of cardiac abnormalities from 12-lead ECG signals, thus increasing the trust in the DL models.

This article is part of the theme issue ‘Advanced computation in cardiovascular physiology: new challenges and opportunities’.
Multiscale assessment of the degree of multifractality for physiological time series
Authors: Faini Andrea , Parati Gianfranco , Castiglioni Paolo
Published: October 2021

Recent advancements in detrended fluctuation analysis (DFA) allow evaluating multifractal coefficients scale-by-scale, a promising approach for assessing the complexity of biomedical signals. The multifractality degree is typically quantified by the singularity spectrum width (
W
SS
), a method that is critically unstable in multiscale applications. Thus, we aim to propose a robust multiscale index of multifractality, compare it with
W
SS
and illustrate its performance on real biosignals. The proposed index is the cumulative function of squared increments between consecutive DFA coefficients at each scale
n
:
α
CF
(
n
). We compared it with
W
SS
calculated scale-by-scale considering monofractal/monoscale, monofractal/multiscale, multifractal/monoscale and multifractal/multiscale random processes. The two indices provided qualitatively similar descriptions of multifractality, but
α
CF
(
n
) differentiated better the multifractal components from artefacts due to crossovers or detrending overfitting. Applied on 24 h heart rate recordings of 14 participants, the singularity spectrum failed to always satisfy the concavity requirement for providing meaningful
W
SS
, while
α
CF
(
n
) demonstrated a statistically significant heart rate multifractality at night in the scale ranges 16–100 and 256–680 s. Furthermore,
α
CF
(
n
) did not reject the hypothesis of monofractality at daytime, coherently with previous reports of lower nonlinearity and monoscale multifractality during the day. Thus,
α
CF
(
n
) appears a robust index of multiscale multifractality that is useful for quantifying complexity alterations of physiological series.

This article is part of the theme issue ‘Advanced computation in cardiovascular physiology: new challenges and opportunities’.
Echo state network models for nonlinear Granger causality
Authors: Duggento Andrea , Guerrisi Maria , Toschi Nicola
Published: October 2021

While Granger causality (GC) has been often employed in network neuroscience, most GC applications are based on linear multivariate autoregressive (MVAR) models. However, real-life systems like biological networks exhibit notable nonlinear behaviour, hence undermining the validity of MVAR-based GC (MVAR-GC). Most nonlinear GC estimators only cater for additive nonlinearities or, alternatively, are based on recurrent neural networks or long short-term memory networks, which present considerable training difficulties and tailoring needs. We reformulate the GC framework in terms of echo-state networks-based models for arbitrarily complex networks, and characterize its ability to capture nonlinear causal relations in a network of noisy Duffing oscillators, showing a net advantage of echo state GC (ES-GC) in detecting nonlinear, causal links. We then explore the structure of ES-GC networks in the human brain employing functional MRI data from 1003 healthy subjects drawn from the human connectome project, demonstrating the existence of previously unknown directed within-brain interactions. In addition, we examine joint brain-heart signals in 15 subjects where we explore directed interaction between brain networks and central vagal cardiac control in order to investigate the so-called central autonomic network in a causal manner.

This article is part of the theme issue ‘Advanced computation in cardiovascular physiology: new challenges and opportunities’.
QT variability unrelated to RR variability during stress testing for identification of coronary artery disease
Authors: del Castillo Marta González , Hernando David , Orini Michele , Laguna Pablo , Viik Jari , Bailón Raquel , Pueyo Esther
Published: October 2021

Stress test electrocardiogram (ECG) analysis is widely used for coronary artery disease (CAD) diagnosis despite its limited accuracy. Alterations in autonomic modulation of cardiac electrical activity have been reported in CAD patients during acute ischemia. We hypothesized that those alterations could be reflected in changes in ventricular repolarization dynamics during stress testing that could be measured through QT interval variability (QTV). However, QTV is largely dependent on RR interval variability (RRV), which might hinder intrinsic ventricular repolarization dynamics. In this study, we investigated whether different markers accounting for low-frequency (LF) oscillations of QTV unrelated to RRV during stress testing could be used to separate patients with and without CAD. Power spectral density of QTV unrelated to RRV was obtained based on time-frequency coherence estimation. Instantaneous LF power of QTV and QTV unrelated to RRV were obtained. LF power of QTV unrelated to RRV normalized by LF power of QTV was also studied. Stress test ECG of 100 patients were analysed. Patients referred to coronary angiography were classified into non-CAD or CAD group. LF oscillations in QTV did not show significant differences between CAD and non-CAD groups. However, LF oscillations in QTV unrelated to RRV were significantly higher in the CAD group as compared with the non-CAD group when measured during the first phases of exercise and last phases of recovery. ROC analysis of these indices revealed area under the curve values ranging from 61 to 73%. Binomial logistic regression analysis revealed LF power of QTV unrelated to RRV, both during the first phase of exercise and last phase of recovery, as independent predictors of CAD. In conclusion, this study highlights the importance of removing the influence of RRV when measuring QTV during stress testing for CAD identification and supports the added value of LF oscillations of QTV unrelated to RRV to diagnose CAD from the first minutes of exercise.

This article is part of the theme issue ‘Advanced computation in cardiovascular physiology: new challenges and opportunities’.
Extending the spectral decomposition of Granger causality to include instantaneous influences: application to the control mechanisms of heart rate variability
Authors: Nuzzi D. , Stramaglia S. , Javorka M. , Marinazzo D. , Porta A. , Faes Luca
Published: October 2021

Assessing Granger causality (GC) intended as the influence, in terms of reduction of variance of surprise, that a driver variable exerts on a given target, requires a suitable treatment of ‘instantaneous’ effects, i.e. influences due to interactions whose time scale is much faster than the time resolution of the measurements, due to unobserved confounders or insufficient sampling rate that cannot be increased because the mechanism of generation of the variable is inherently slow (e.g. the heartbeat). We exploit a recently proposed framework for the estimation of causal influences in the spectral domain and include instantaneous interactions in the modelling, thus obtaining (i) a novel index of undirected instantaneous causality and (ii) a novel measure of GC including instantaneous effects. An effective procedure to speed up the optimization of parameters in this frame is also presented. After illustrating the proposed formalism in a theoretical example, we apply it to two datasets of cardiovascular and respiratory time series and compare the values obtained within the frequency bands of physiological interest by the proposed total measure of causality with those derived from the standard GC analysis. We find that the inclusion of instantaneous causality allows us to correctly disentangle the baroreflex mechanism from the effects related to cardiorespiratory interactions. Moreover, studying how controlling the respiratory rhythm acts on cardiovascular interactions, we document an increase of the direct (non-baroreflex mediated) influence of respiration on the heart rate in the respiratory frequency band when switching from spontaneous to paced breathing.

This article is part of the theme issue ‘Advanced computation in cardiovascular physiology: new challenges and opportunities’.
Bovine apo-lactoferrin affects the secretion of proteases in Mannheimia haemolytica A2
Authors: Ramírez-Rico Gerardo , Martinez-Castillo Moises , Avalos-Gómez Christian , de la Garza Mireya
Published: October 2021

Mannheimia haemolytica

serotype A2 is the main bacterial causative agent of ovine mannheimiosis, a disease that leads to substantial economic losses for livestock farmers. Several virulence factors allow

M. haemolytica

to colonize the lungs and establish infection. Virulence factors can be directly secreted into the environment by bacteria but are also released through outer membrane vesicles (OMVs). In addition, due to the abuse of antibiotics in the treatment of this disease, multidrug-resistant bacterial strains of

M. haemolytica

have emerged. One therapeutic alternative to antibiotics or an adjuvant to be used in combination with antibiotics could be lactoferrin (Lf), a multifunctional cationic glycoprotein of the mammalian innate immune system to which no bacterial resistance has been reported. The aim of this work was to determine the effect of bovine iron-free Lf (apo-BLf) on the production and secretion of proteases into culture supernatant (CS) and on their release in OMVs. Zymography assays showed that addition of sub-MIC concentrations of apo-BLf to

M. haemolytica

cultures inhibited protease secretion without affecting culture growth. Biochemical characterization revealed that these proteases were mainly cysteine- and metalloproteases. The secretion of a 100 kDa metalloprotease was inhibited by sub-MIC concentrations of apo-BLf since this protease was present in the cytoplasm and OMVs but not in CS proteins, as corroborated by Western blotting. On the other hand, proteases produced by

M. haemolytica

caused cleavage of apo-BLf. However, when Lf is cleaved, peptides known as lactoferricins, which are more bactericidal than natural Lf, can be produced.

M. haemolytica

A2 protease-mediated degradation of host tissue proteins could be an important virulence factor during the infectious process of pneumonia in ovines. The mechanism of

M. haemolytica

protease secretion could be inhibited by treatment with apo-BLf in animals.
Does the environmental Kuznets curve for deforestation exist for Ghana? Evidence from the bootstrap rolling window Granger causality test approach
Authors: Minlah Michael Kaku , Zhang Xibao , Ganyoh Philipine Nelly , Bibi Ayesha
Published: October 2021

Purpose

This study investigates the existence of the environmental Kuznets curve (EKC) for deforestation for Ghana over the 1962–2018 the time period.

Design/methodology/approach

The study employs a time-varying approach, the bootstrap rolling window Granger causality test to achieve its set objectives.

Findings

The results from our study reveals an inverted “N” shape EKC for deforestation, implying that deforestation will initially decrease with increases in economic growth up to a certain income threshold and increases with further increases in economic growth beyond this income threshold up to a higher income threshold and then decrease with further increases in economic beyond the higher income threshold.

Practical implications

The results from the study project show that over time economic growth can serve as a natural panacea to cure and mitigate the ills of deforestation that have plagued Ghana's forests over the years.

Social implications

The results further highlight the important role of strong institutions in fighting the deforestation menace.

Originality/value

The originality of this study lies in its methodology which allows for feedback from deforestation to the economy. This is in contrast to earlier studies on the EKC for deforestation which allowed causality only from deforestation to the economy.
A linear mixed model to estimate COVID‐19‐induced excess mortality
Authors: Verbeeck Johan , Faes Christel , Neyens Thomas , Hens Niel , Verbeke Geert , Deboosere Patrick , Molenberghs Geert
Published: October 2021

The Corona Virus Disease (COVID‐19) pandemic has increased mortality in countries worldwide. To evaluate the impact of the pandemic on mortality, the use of excess mortality rather than reported COVID‐19 deaths has been suggested. Excess mortality, however, requires estimation of mortality under nonpandemic conditions. Although many methods exist to forecast mortality, they are either complex to apply, require many sources of information, ignore serial correlation, and/or are influenced by historical excess mortality. We propose a linear mixed model that is easy to apply, requires only historical mortality data, allows for serial correlation, and down‐weighs the influence of historical excess mortality. Appropriateness of the linear mixed model is evaluated with fit statistics and forecasting accuracy measures for Belgium and the Netherlands. Unlike the commonly used 5‐year weekly average, the linear mixed model is forecasting the year‐specific mortality, and as a result improves the estimation of excess mortality for Belgium and the Netherlands.
The syn‐rift tectono‐stratigraphic record of rifted margins (Part II): A new model to break through the proximal/distal interpretation frontier
Authors: Chenin Pauline , Manatschal Gianreto , Ghienne Jean‐François , Chao Peng
Published: October 2021

One fundamental lesson from the last decade's research into rifted margins is that stratigraphic horizons cannot be simply correlated from the proximal into distal domain, which makes the interpretation of poorly calibrated and largely inaccessible distal margins difficult. In this contribution, we propose a new tectono‐stratigraphic model to help break through the proximal/distal interpretation frontier. After reviewing the scientific advances on rifted margins achieved during the last century, we describe the primary spatio‐temporal evolution of active deformation during rifting. We show that different rift domains are associated with specific (1) periods of active deformation; (2) tectonic structures and related stratigraphic architecture; (3) amounts of accommodation creation owing to specific ranges of horizontal widening and vertical deepening and (4) depositional environments. We demonstrate that the sequential localization of extension during rifting results in a younging of the base of passive infill (i.e. sediment deposited in a non‐tectonic setting) oceanward. We propose a panel of few to few tens of My time intervals related to specific tectonic events—our Tectonic Sequences—that may be correlated more or less easily and continuously across rifted margins. This study underlines the value of an iterative approach between fieldwork on fossil rifted margins and offshore geophysical studies, where field studies offer easy‐to‐access and high‐resolution calibration of dismembered rifted margin remnants, while geophysical studies provide comparatively low‐resolution imaging of entire, intact but largely inaccessible, rifted margins. It also highlights the necessity of jettisoning outdated dogma on rifted margins and changing our routines when interpreting seismic sections and outcrops.
Phenotyping of productivity and resilience in sweetpotato under water stress through UAV‐based multispectral and thermal imagery in Mozambique
Authors: Ramírez David A. , Grüneberg Wolfgang , I. Andrade Maria , De Boeck Bert , Loayza Hildo , S. Makunde Godwill , Ninanya Johan , Rinza Javier , Heck Simon , Campos Hugo
Published: October 2021

Sweetpotato is a crucial crop to guarantee food security in sub‐Saharan Africa, and drought events are considered one of the most critical factors affecting sweetpotato productivity in this region. In this study, airborne imagery based on reflectance (NDVI, CIred‐edge) and canopy temperature minus air temperature (dT) indices was used to characterize sweetpotato genotypes under drought treatments in Mozambique. Two field experiments established in rainy/hot (Trial A) and dry/cool (Trial B) seasons were assessed. In Trial A, 24 genotypes were subjected to early‐ (ESD), mid‐ (MSD) and late‐season (LSD) drought stress treatments and compared against a control. In Trial B, 120 genotypes were subjected to LSD only. The percentage of reduction in vine weight (PRVW) under drought was related primarily to temporal variation of NDVI and CI, regardless of drought treatment and seasons. dT in relation to control (dTAmp) was associated with PRVW in ESD‐Trial A and LSD‐Trial B, whereas under LSD‐Trial A, dTAmp was related to total fresh storage root weight (TRW). During the rainy/hot season, higher TRW reduction was promoted under ESD; however, under LSD, it was possible to identify productive genotypes able to withstand drought stress, highlighting their relevance for drought‐tolerance selection purposes.
Tracking the xeric biomes of South America: The spatiotemporal diversification of Mandacaru cactus
Authors: Amaral Danilo Trabuco , Minhós‐Yano Isis , Oliveira João Victor M. , Romeiro‐Brito Monique , Bonatelli Isabel Aparecida Silva , Taylor Nigel Paul , Zappi Daniela Cristina , Moraes Evandro Marsola , Eaton Deren A. R. , Franco Fernando Faria
Published: October 2021

Aim

The interconnectedness and biotic interchange among Neotropical biomes are thought to play an important role in driving adaptation and diversification. However, how these processes are in synteny to trait evolution in species of open and xeric areas is poorly studied. Here, we investigate the spatial and temporal dimensions of evolution and candidate traits associated with biome shifts in xeric vegetation, focusing on the family Cactaceae.

Location

Xeric and open areas of South America.

Taxon

Genus Cereus Mill. (Cactaceae, Cereeae).

Methods

We applied biogeographical reconstructions on a time‐calibrated phylogeny inferred from multilocus data (ddRAD‐Seq) using Bayesian analyses on BEAST2, species distribution modelling in Maxent, the reconstruction of biome affinities and niche shift analyses based on abiotic traits (climate and soil) using Mk‐model in BioGeoBEARS, and phenotypic trait‐based analysis in Mesquite.

Results

The Cerrado domain is the ancestral area of Cereus, with most diversification events occurring in a time of intense orogenesis, climatic changes, and marine regressions within the last 5 Mya. Events of biome transition from the seasonally dry tropical forest (SDTF) were also associated with trait and niche shifts.

Main conclusions

The diversification of the xerophyte genus Cereus is associated with the climatic and geomorphological instabilities of the Pliocene and Pleistocene epochs. The Cerrado domain states an important region of dispersal for the genus. Some geographical range movements involved biome shifts associated with niche evolution while others were restricted to a simple biogeographical transition without niche change. Particular clades that experienced biome shifts displayed some phenotypic state changes, suggesting a role of biotic traits for environment transition. The results observed in Cereus may be a biogeographical pattern that should be tested with other cactus species, such as Pilosocereus spp., or species of xeric habitats, such as Annonaceae and Vochysiaceae.
Genesis of Re‐rich Molybdenite in the Baishan Mo deposit, Eastern Tianshan, Xinjiang, Northwest China
Authors: Ye Longxiang , Zhang Dayu , Wang Shiwei , Zhou Taofa , Yuan Feng , White Noel C. , Xiao Wenjiao
Published: October 2021

The Baishan molybdenum deposit is located in the central part of the Eastern Tianshan‐Beishan tectonic belt, NW China. The deposit is hosted in early Carboniferous Gandun Formation biotite‐rich hornfels and is genetically related to unexposed granodiorite porphyry beneath the orebodies. The molybdenite occurs in three different types from early to late stage: Molybdenite ‐ Fe‐Cu‐sulfides ‐ K‐feldspar ‐ quartz veins (Group 1); Molybdenite ‐ Fe‐Cu‐sulfides ‐ quartz veins (Group 2); and disseminated molybdenite in the wall rock (Group 3). Rhenium concentrations in the molybdenite grains range from 108 to 277 ppm in Group 1, 69–121 ppm in Group 2 and 46–135 ppm in Group 3. The Re concentrations of molybdenite in the Baishan Mo deposit decrease from early to late and from the center to periphery, and molybdenite types vary from the 2H1 poly‐type in Groups 1 and 2 to the 2H1 + 3R2H1 poly‐type in Group 3, based on X‐ray diffraction results. The Re‐enriched molybdenite probably formed from an oxidized magmatic fluid that separated from a highly oxidized and H2O‐ and volatile‐enriched adakitic intrusion generated in the lower crust.
Assessing Antibiotic Tolerance of Staphylococcus aureus Derived Directly from Patients by the Replica Plating Tolerance Isolation System (REPTIS)
Authors: Herren Sebastian C. , Huemer Markus , Acevedo Claudio T. , Gómez-Mejia Alejandro , Andreoni Federica , Mairpady Shambat Srikanth , Hasse Barbara , Zbinden Reinhard , Brugger Silvio D. , Zinkernagel Annelies S.
Published: October 2021

Antibiotic-tolerant
Staphylococcus aureus
poses a great challenge to clinicians as well as to microbiological laboratories and is one reason for treatment failure. Antibiotic-tolerant strains survive transient antibiotic exposure despite being fully susceptible
in vitro
.
The Newcastle ENDOPREM™: a validated patient reported experience measure for gastrointestinal endoscopy
Authors: Neilson Laura J , Sharp Linda , Patterson Joanne M , von Wagner Christian , Hewitson Paul , McGregor Lesley M , Rees Colin J
Published: October 2021

Objectives

Measuring patient experience of gastrointestinal (GI) procedures is a key component of evaluation of quality of care. Current measures of patient experience within GI endoscopy are largely clinician derived and measured; however, these do not fully represent the experiences of patients themselves. It is important to measure the entirety of experience and not just experience directly during the procedure. We aimed to develop a patient-reported experience measure (PREM) for GI procedures.

Design

Phase 1: semi-structured interviews were conducted in patients who had recently undergone GI endoscopy or CT colonography (CTC) (included as a comparator). Thematic analysis identified the aspects of experience important to patients. Phase 2: a question bank was developed from phase 1 findings, and iteratively refined through rounds of cognitive interviews with patients who had undergone GI procedures, resulting in a pilot PREM. Phase 3: patients who had attended for GI endoscopy or CTC were invited to complete the PREM. Psychometric properties were investigated. Phase 4 involved item reduction and refinement.

Results

Phase 1: interviews with 35 patients identified six overarching themes: anxiety, expectations, information & communication, embarrassment & dignity, choice & control and comfort. Phase 2: cognitive interviews refined questionnaire items and response options. Phase 3: the PREM was distributed to 1650 patients with 799 completing (48%). Psychometric properties were found to be robust. Phase 4: final questionnaire refined including 54 questions assessing patient experience across five temporal procedural stages.

Conclusion

This manuscript gives an overview of the development and validation of the Newcastle ENDOPREM™, which assesses all aspects of the GI procedure experience from the patient perspective. It may be used to measure patient experience in clinical care and, in research, to compare patients’ experiences of different endoscopic interventions.
Virological measures and factors associated with outcomes, and missing outcome data in HIV clinical trials: a methodological study
Authors: Youssef Mark , Zani Babalwa , Olaiya Oluwatobi , Soliman Michael , Mbuagbaw Lawrence
Published: October 2021

Background

To evaluate the definition of HIV virological outcomes in the literature and factors associated with outcomes and missing outcome data.

Methods

We conducted a methodological review of HIV RCTs using a search (2009–2019) of PubMed, Embase and the Cochrane Central Register of Controlled Trials.

Only full-text, peer-reviewed, randomised controlled trials (RCTs) that measured virological outcomes in people living with HIV, and published in English were included.

We extracted study details and outcomes. We used logistic regression to identify factors associated with a viral threshold ≤50 copies/mL and linear regression to identify factors associated with missing outcome data.

Results

Our search yielded 5847 articles; 180 were included. A virological outcome was the primary outcome in 73.5% of studies. 89 studies (49.4%) used virological success. The remaining used change in viral load (VL) (33 studies, 18.3%); virological failure (59 studies, 32.8%); or virological rebound (9 studies, 5.0%). 96 studies (53.3%) set the threshold at ≤50 copies/mL; and 33.1% used multiple measures.

Compared with government and privately funded studies, RCTs with industry funding (adjusted OR 6.39; 95% CI 2.15 to 19.00; p<0.01) were significantly associated with higher odds of using a VL threshold of ≤50 copies/mL. Publication year, intervention type, income level and number of patients were not associated with a threshold of ≤50 copies/mL. Trials with pharmacological interventions had less missing data (β=−11.04; 95% CI −20.02 to −1.87; p=0.02).

Discussion

Country source of funding was associated with VL threshold choice and studies with pharmacological interventions had less missing data, which may in part explain heterogeneous virological outcomes across studies. Multiple measures of VL were not associated with missing data. The development of formal guidelines on virological outcome reporting in RCTs is needed.