bluuebunny/crossref_metadata_2025 huggingface dataset:
Top-Down Modulation of Early Visual Processing in V1: Dissociable Neurophysiological Effects of Spatial Attention, Attentional Load and Task-Relevance
Authors: Wolf Maren-Isabel , Bruchmann Maximilian , Pourtois Gilles , Schindler Sebastian , Straube Thomas
Published: September 2021

Until today, there is an ongoing discussion if attention processes interact with the information processing stream already at the level of the C1, the earliest visual electrophysiological response of the cortex. We used two highly powered experiments (each N = 52) and examined the effects of task relevance, spatial attention, and attentional load on individual C1 amplitudes for the upper or lower visual hemifield. Bayesian models revealed evidence for the absence of load effects but substantial modulations by task-relevance and spatial attention. When the C1-eliciting stimulus was a task-irrelevant, interfering distracter, we observed increased C1 amplitudes for spatially unattended stimuli. For spatially attended stimuli, different effects of task-relevance for the two experiments were found. Follow-up exploratory single-trial analyses revealed that subtle but systematic deviations from the eye-gaze position at stimulus onset between conditions substantially influenced the effects of attention and task relevance on C1 amplitudes, especially for the upper visual field. For the subsequent P1 component, attentional modulations were clearly expressed and remained unaffected by these deviations. Collectively, these results suggest that spatial attention, unlike load or task relevance, can exert dissociable top-down modulatory effects at the C1 and P1 levels.
Brain Responses to Surprising Stimulus Offsets: Phenomenology and Functional Significance
Authors: Somervail R , Bufacchi R J , Salvatori C , Neary-Zajiczek L , Guo Y , Novembre G , Iannetti G D
Published: September 2021

Abrupt increases of sensory input (onsets) likely reflect the occurrence of novel events or objects in the environment, potentially requiring immediate behavioral responses. Accordingly, onsets elicit a transient and widespread modulation of ongoing electrocortical activity: the Vertex Potential (VP), which is likely related to the optimisation of rapid behavioral responses. In contrast, the functional significance of the brain response elicited by abrupt decreases of sensory input (offsets) is more elusive, and a detailed comparison of onset and offset VPs is lacking. In four experiments conducted on 44 humans, we observed that onset and offset VPs share several phenomenological and functional properties: they (1) have highly similar scalp topographies across time, (2) are both largely comprised of supramodal neural activity, (3) are both highly sensitive to surprise and (4) co-occur with similar modulations of ongoing motor output. These results demonstrate that the onset and offset VPs largely reflect the activity of a common supramodal brain network, likely consequent to the activation of the extralemniscal sensory system which runs in parallel with core sensory pathways. The transient activation of this system has clear implications in optimizing the behavioral responses to surprising environmental changes.
Reorganization of the Neurobiology of Language After Sentence Overlearning
Authors: Skipper Jeremy I , Aliko Sarah , Brown Stephen , Jo Yoon Ju , Lo Serena , Molimpakis Emilia , Lametti Daniel R
Published: September 2021

It is assumed that there are a static set of “language regions” in the brain. Yet, language comprehension engages regions well beyond these, and patients regularly produce familiar “formulaic” expressions when language regions are severely damaged. These suggest that the neurobiology of language is not fixed but varies with experiences, like the extent of word sequence learning. We hypothesized that perceiving overlearned sentences is supported by speech production and not putative language regions. Participants underwent 2 sessions of behavioral testing and functional magnetic resonance imaging (fMRI). During the intervening 15 days, they repeated 2 sentences 30 times each, twice a day. In both fMRI sessions, they “passively” listened to those sentences, novel sentences, and produced sentences. Behaviorally, evidence for overlearning included a 2.1-s decrease in reaction times to predict the final word in overlearned sentences. This corresponded to the recruitment of sensorimotor regions involved in sentence production, inactivation of temporal and inferior frontal regions involved in novel sentence listening, and a 45% change in global network organization. Thus, there was a profound whole-brain reorganization following sentence overlearning, out of “language” and into sensorimotor regions. The latter are generally preserved in aphasia and Alzheimer’s disease, perhaps explaining residual abilities with formulaic expressions in both.
Aberrant Subnetwork and Hub Dysconnectivity in Adult Bipolar Disorder: A Multicenter Graph Theory Analysis
Authors: Nabulsi Leila , McPhilemy Genevieve , O’Donoghue Stefani , Cannon Dara M , Kilmartin Liam , O’Hora Denis , Sarrazin Samuel , Poupon Cyril , D’Albis Marc-Antoine , Versace Amelia , Delavest Marine , Linke Julia , Wessa Michèle , Phillips Mary L , Houenou Josselin , McDonald Colm
Published: September 2021

Neuroimaging evidence implicates structural network-level abnormalities in bipolar disorder (BD); however, there remain conflicting results in the current literature hampered by sample size limitations and clinical heterogeneity. Here, we set out to perform a multisite graph theory analysis to assess the extent of neuroanatomical dysconnectivity in a large representative study of individuals with BD.

This cross-sectional multicenter international study assessed structural and diffusion-weighted magnetic resonance imaging data obtained from 109 subjects with BD type 1 and 103 psychiatrically healthy volunteers.

Whole-brain metrics, permutation-based statistics, and connectivity of highly connected nodes were used to compare network-level connectivity patterns in individuals with BD compared with controls.

The BD group displayed longer characteristic path length, a weakly connected left frontotemporal network, and increased rich-club dysconnectivity compared with healthy controls.

Our multisite findings implicate emotion and reward networks dysconnectivity in bipolar illness and may guide larger scale global efforts in understanding how human brain architecture impacts mood regulation in BD.
Neonatal Hypoxia-Ischemia Causes Persistent Intracortical Circuit Changes in Layer 4 of Rat Auditory Cortex
Authors: Sheikh Aminah , Meng Xiangying , Kao Joseph P Y , Kanold Patrick O
Published: September 2021

The connection between early brain injury and subsequent development of disorders is unknown. Neonatal hypoxia-ischemia (HI) alters circuits associated with subplate neurons (SPNs). SPNs are among the first maturing cortical neurons, project to thalamorecipient layer 4 (L4), and are required for the development of thalamocortical connections. Thus, early HI might influence L4 and such influence might persist. We investigated functional circuits to L4 neurons in neonatal rat HI models of different severities (mild and moderate) shortly after injury and at adolescence. We used laser-scanning photostimulation in slices of auditory cortex during P5–10 and P18–23. Mild injuries did not initially (P6/P7) alter the convergence of excitatory inputs from L2/3, but hyperconnectivity emerged by P8–10. Inputs from L4 showed initial hypoconnectivity which resolved by P8–10. Moderate injuries resulted in initial hypoconnectivity from both layers which resolved by P8–10 and led to persistent strengthening of connections. Inhibitory inputs to L4 cells showed similar changes. Functional changes were mirrored by reduced dendritic complexity. We also observed a persistent increase in similarity of L4 circuits, suggesting that HI interferes with developmental circuit refinement and diversification. Altogether, our results show that neonatal HI injuries lead to persistent changes in intracortical connections.
A review of the flavor profile of metal salts: understanding the complexity of metallic sensation
Authors: Ecarma Michelle J Y , Nolden Alissa A
Published: September 2021

The oral sensation of metallic is a complex experience. Much of our current understanding of metallic sensation is from the investigation of metal salts, which elicit diverse sensations, including taste, smell, and chemesthetic sensations, and therefore meet the definition of a flavor rather than a taste. Due to the involvement of multiple chemosensory systems, it can be challenging to define and characterize metallic sensation. Here, we provide a comprehensive review of the psychophysical studies quantifying and characterizing metallic sensation, focusing on metal salts. We examine the factors that impact perception, including anion complex, concentration, nasal occlusion, and pH. In addition, we summarize the receptors thought to be involved in the perception of metallic sensation (i.e., TRPV1, T1R3, TRPA1, and T2R7) either as a result of in vitro assays or from studies in knock-out mice. By enhancing our scientific understanding of metallic sensation and its transduction pathways, it has the potential to improve food and pharmaceuticals, help identify suppression or masking strategies, and improve the ability to characterize individual differences in metallic sensation. It also has the potential to translate to clinical populations by addressing the disparities in knowledge and treatment options for individuals suffering from metallic taste disorder (i.e., phantom taste or “metal mouth”). Future psychophysical studies investigating the sensory perception of metal salts should include a range of compounds and diverse food matrices, coupled with modern sensory methods, which will help to provide a more comprehensive understanding of metallic sensation.
Determination of Voriconazole in Human Plasma Using RP-HPLC/UV-VIS Detection: Method Development and Validation; Subsequently Evaluation of Voriconazole Pharmacokinetic Profile in Pakistani Healthy Male Volunteers
Authors: Mushtaq Mehwish , Shah Yasar , Samiullah   , Nasir Fazli , Khan Haroon , Faheem Muhammad , Nadeem Atif , Khan Sundas , Khan Sumaira Irum , Abbas Muhammad , Khuda Fazli , Iftikhar Tayyaba
Published: September 2021

In this research work, an isocratic, reversed-phase high-performance liquid chromatography-ultraviolet/visible detector method was developed for analysis of voriconazole standard (stock-solution) and in plasma samples. Optimization and validation of the method was carried out as per international guidelines. The method offered a simple liquid–liquid extraction technique, which exhibited best recovery of voriconazole along with fluconazole, i.e., internal standard. Different experimental conditions were tried and ultimately, the best outcomes were accomplished utilizing C-18 Perkin-Elmer® column with particulars of 150 mm length, 4.6 mm inner diameter and 5 μm particle size, protected by an RP-18 Perkin-Elmer® Pre-column guard cartridge with specifications of 10 μm particle size, 30 mm length and 4.6 mm inner diameter, utilizing mobile-phase of acetonitrile-water (ACN: H2O) in proportion of 60: 40 v/v, having a flow rate of 1.5 mL/min, and wavelength of 254 nm. All the analytes were observed to be separated in ≤7 min. A linear calibration curve was obtained at concentration range of 01–10 μg/mL of voriconazole. The correlation coefficient of voriconazole was observed to be 0.999, and average recovery (in percent) was 97.4%, whereas the relative standard deviation value was ≤2%. The lower limit of detection was 0.01 μg/mL, whereas, lower limit of quantification was 0.03 μg/mL, respectively. This developed method provided outstanding results of all validation parameters, i.e., recovery, accuracy, selectivity, precision and reproducibility. The method proposed for voriconazole analysis was applied effectively for further research investigation of voriconazole in human-plasma samples (to assess the pharmacokinetic parameters), pharmaceutical formulations and pharmacokinetic drug–drug interaction’s.
A New, Rapid and Simple RP-HPLC Method for Stability Quantification of a Protease Inhibitor in Tablets
Authors: Rossi Rochele Cassanta , Moura Josué Guilherme Lisbôa , Mossmann Vanessa , Weimer Patrícia , Fröehlich Pedro Eduardo
Published: September 2021

Fosamprenavir calcium is a protease inhibitor widely used in the treatment and prevention of human immunodeficiency virus and acquired immunodeficiency syndrome. This protease inhibitor serves as a prodrug of amprenavir, offering better oral bioavailability. Although this drug was approved by the FDA in 2003, there are few methods established for quantifying the stability for quality control analysis of fosamprenavir-coated tablets. The purpose of the study was to develop and validate a method for determining the stability of fosamprenavir-coated tablets (Telzir®) that may be applied by any quality control laboratory. Chromatographic separation was performed using a Vertical RP-18 column programmed to run a gradient elution with sodium acetate buffer and acetonitrile. Flow rate was 1.2 mL min−1 for a total run time of 15 min. Ultraviolet detection was set at 264 nm and the use of a photodiode array detector in scan mode allowed selectivity confirmation by peak purity evaluation. The analyte peak was found to be adequately separated from degradation products generated during forced degradation studies. Thus, the proposed method was found to accurately indicate stability and was sufficient for routine quantitative analysis of fosamprenavir in coated tablets without interference from major degradation products and excipients.
Two Validated Chromatographic Methods for Determination of Ciprofloxacin HCl, One of its Specified Impurities and Fluocinolone Acetonide in Newly Approved Otic Solution
Authors: Tantawy Mahmoud A , Wahba Israa A , Saad Samah S , Ramadan Nesrin K
Published: September 2021

Two sensitive, selective and precise chromatographic methods have been established for concomitant quantification of ciprofloxacin HCl (CIP), fluocinolone acetonide (FLU) along with ciprofloxacin impurity A (CIP-imp A). The first method was thin-layer chromatography (TLC-densitometry) where separation was accomplished using TLC silica plates 60 G.F254 as a stationary phase and chloroform–methanol–33%ammonia (4.6:4.4:1, by volume) as a developing system. The obtained plates were scanned at 260 nm over concentration ranges of 1.0–40.0, 0.6–20.0 and 1.0–40.0 μg band−1 for CIP, FLU and CIP-imp A, respectively. The second method was based on high-performance liquid chromatography using a Zorbax ODS column (5 μm, 150 × 4.6 mm i.d.) where adequate separation was achieved through a mobile phase composed of phosphate buffer pH 3.6–acetonitrile (45:55, v/v) at flow rate 1.0 mL min−1 with ultraviolet detection at 254 nm. Linear regressions were obtained in the range of 1.0–40.0 μg mL−1 for CIP, 0.6–20.0 μg mL−1 for FLU and 1.0–40.0 μg mL−1 for CIP-imp A. The suggested methods were validated in compliance with the International Conference on Harmonization guidelines and were successfully applied for determination of CIP and FLU in bulk powder and newly marketed otic solution.
Development and Validation of a Reversed-Phase High-Performance Liquid Chromatography (RP-HPLC) Method for Identification, Assay and Estimation of Related Substances of Ivermectin in Bulk Drug Batches of Ivermectin Drug Substance
Authors: Zhao Daoli , Wimalasinghe Rasangi M , Wang Lin , Rustum Abu M
Published: September 2021

A reversed-phase high-performance liquid chromatography (RP-HPLC) method has been developed and validated for the identification and assay of Ivermectin, including the identification and estimation of its process-related impurities and degradation products in bulk drug substance of Ivermectin. Analytes were separated on a HALO C18 column (100 mm × 4.6 mm I.D., 2.7 μm particle size) maintained at 40 °C (column temperature) with gradient elution. All analytes of interests were adequately separated within 25 min. All degradation products, process-related impurities and assay were monitored by ultraviolet detection at 254 nm. The new HPLC method described here successfully separated an isomer peak of the active pharmaceutical ingredient (API) from the major API peak. This newly separated isomer peak is around 1.2 to 1.5% (peak area) in typical API samples, and coelutes with the major API peak by all current HPLC methods. Quantitation limit of the HPLC method is 0.1% of target analytical concentration (~1.0 μg/mL). This method has been demonstrated to be accurate, robust, significantly higher degree of selectivity compared to the HPLC methods of Ivermectin drug substance reported in the literature and in the compendial HPLC methods prescribed in the current USA and European Pharmacopeia.
A Hybrid Machine Learning Approach for Performance Modeling of Cloud-Based Big Data Applications
Authors: Ataie Ehsan , Evangelinou Athanasia , Gianniti Eugenio , Ardagna Danilo
Published: September 2021

Nowadays, Apache Hadoop and Apache Spark are two of the most prominent distributed solutions for processing big data applications on the market. Since in many cases these frameworks are adopted to support business critical activities, it is often important to predict with fair confidence the execution time of submitted applications, for instance when service-level agreements are established with end-users. In this work, we propose and validate a hybrid approach for the performance prediction of big data applications running on clouds, which exploits both analytical modeling and machine learning (ML) techniques and it is able to achieve a good accuracy without too many time consuming and costly experiments on a real setup. The experimental results show how the proposed approach attains improvement in accuracy, number of experiments to be run on the operational system and cost over applying ML techniques without any support from analytical models. Moreover, we compare our approach with Ernest, an ML-based technique proposed in the literature by the Spark inventors. Experiments show that Ernest can accurately estimate the performance in interpolating scenarios while it fails to predict the performance when configurations with increasing number of cores are considered. Finally, a comparison with a similar hybrid approach proposed in the literature demonstrates how our approach significantly reduce prediction errors especially when few experiments on the real system are performed.
Estimating the correlation in network disturbance models
Authors: Barbour A D , Reinert Gesine
Published: September 2021

The network disturbance model of P. Doreian (1989), expresses the dependency between observations taken at the vertices of a network by modelling the correlation between neighbouring vertices, using a single correlation parameter $\rho$. It has been observed that estimation of $\rho$ in dense graphs, using the method of maximum likelihood, leads to results that can be both biased and very unstable. In this article, we sketch why this is the case, showing that the variability cannot be avoided, no matter how large the network. We also propose a more intuitive estimator of $\rho$, which shows little bias. The related network effects model is briefly discussed.
Hellenism, philhellenism and classical reception: commemorating the 1821 revolution
Authors: Wallace Jennifer , Lambropoulos Vassilis
Published: September 2021

The Greek Revolution of 1821–1829 mobilized the ideas of classical reception and Philhellenism developed over the previous century to appeal for international support for the war. These complicated ideas influenced the ways both Greeks and non-Greeks thought about the nation, its political character, language, literature, history, culture and landscape. How the revolution and post-revolutionary Greece have been interpreted has shifted over the past 40 years, reflecting changes in both critical theory and also in the geopolitical circumstances in the Eastern Mediterranean and globally. The bicentenary celebrations of 2021 have highlighted the complex, competing claims for the authority to give the dominant account of the founding of modern Greece. Reviewing the scholarship on both Western and Greek Hellenism over the past four decades, our article considers the relationship between classical reception, revolution and the act of commemoration and reveals the hybridity of Hellas in 1821 and 2021.
Mitral annular calcification and valvular dysfunction: multimodality imaging evaluation, grading, and management
Authors: Xu Bo , Kocyigit Duygu , Wang Tom Kai Ming , Tan Carmela D , Rodriguez E Rene , Pettersson Gösta B , Unai Shinya , Griffin Brian P
Published: September 2021

Mitral annular calcification (MAC) refers to calcium deposition in the fibrous skeleton of the mitral valve. It has many cardiovascular associations, including mitral valve dysfunction, elevated cardiovascular risk, arrhythmias, and endocarditis. Echocardiography conventionally is the first-line imaging modality for anatomic assessment, and evaluation of mitral valve function. Cardiac computed tomography (CT) has demonstrated importance as an imaging modality for the evaluation and planning of related procedures. It also holds promise in quantitative grading of MAC. Currently, there is no universally accepted definition or classification system of MAC severity. We review the multimodality imaging evaluation of MAC and associated valvular dysfunction and propose a novel classification system based on qualitative and quantitative measurements derived from echocardiography and cardiac CT.
Outcomes after coronary artery bypass grafting and percutaneous coronary intervention in diabetic and non-diabetic patients
Authors: Lehto Hanna-Riikka , Winell Klas , Pietilä Arto , Niiranen Teemu J , Lommi Jyri , Salomaa Veikko
Published: September 2021

Aims

To assess the prognosis of patients with coronary heart disease (CHD) after first myocardial revascularisation procedure in real-world practice and to compare the differences in outcomes of coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) among diabetic and non-diabetic patients.

Methods and results

A database was compiled from the national hospital discharge register to collect data on all cardiac revascularisations performed in Finland in 2000–2015. The outcomes (all-cause deaths, cardiovascular (CV) deaths, major CV events and need for repeat revascularisation) after the first revascularisation were identified from the national registers at 28 day, 1 year, and 3 year time points.

A total of 139 242 first-time revascularisations (89 493 PCI and 49 749 CABG) were performed during the study period. Of all the revascularised patients, 24% had diabetes, and 76% were non-diabetic patients. At day 28, the risk of fatal outcomes was lower after PCI than after CABG among non-diabetic patients, whereas no difference was seen among diabetic patients. In long-term follow-up the situation was reversed with PCI showing higher risk compared with CABG for most of the outcomes. In particular, at 3 year follow-up the risk of all-cause deaths was elevated among diabetic patients [HR 1.30 (95% CI 1.22–1.38) comparing PCI with CABG] more than among non-diabetic patients [HR 1.09 (1.04–1.15)]. The same was true for CV deaths [HR 1.29 (1.20–1.38) among diabetic patients, and HR 1.03 (0.98–1.08) among non-diabetic patients].

Conclusion

Although PCI was associated with better 28 day prognosis, CABG seemed to produce better long-term prognosis especially among diabetic patients.
Comparative efficacy and safety of different catheter ablation strategies for persistent atrial fibrillation: a network meta-analysis of randomized clinical trials
Authors: Saglietto Andrea , Ballatore Andrea , Gaita Fiorenzo , Scaglione Marco , De Ponti Roberto , De Ferrari Gaetano Maria , Anselmino Matteo
Published: September 2021

Aims

Whereas pulmonary vein isolation (PVI) is the universally agreed target in catheter ablation of paroxysmal atrial fibrillation (AF), an ideal ablation set in persistent AF remains questioned. Aim of this study is to conduct a network meta-analysis (NMA) of randomized clinical trials (RCTs) comparing different ablation strategies in persistent AF patients.

Methods and results

Network meta-analysis was performed in a frequentist framework with the different ablation strategies constituting the competitive arms of interest. Primary efficacy endpoint was recurrences of atrial tachyarrhythmia (AF, atrial flutter, and/or organized atrial tachycardia). Secondary endpoints included major peri-procedural complications, procedure, and fluoroscopy duration. PubMED/MEDLINE and EMBASE databases were searched through June 2020. 2548 records were screened and 57 full-text articles assessed. Eventually 24 RCTs were included, encompassing 3245 patients (median follow-up 15 months, IQR 12–18). Compared to PVI alone, PVI plus linear lesions in the left atrium and elimination of extra-PV sources was the only strategy associated with a reduced risk of arrhythmia recurrence (RR 0.49, 95%CI 0.27–0.88). Most treatment arms were associated with longer procedural time compared with PVI; however, major peri-procedural complications and fluoroscopy time did not differ.

Conclusion

A comprehensive strategy including PVI, linear lesions in the left atrium, and elimination of extra-PV sources (constrained by a heterogeneous definition across studies) was associated with reduced risk of recurrent atrial tachyarrhythmias compared to PVI alone. All investigated treatment arms yielded similar safety profiles. Further research should rely on enhanced substrate-based approach definitions to solve one of the most evident knowledge gaps in interventional electrophysiology.
Erosion of State Power, Corruption Control and Fiscal Capacity
Authors: Li Weijia , Roland Gérard , Xie Yang
Published: September 2021

We model how corruption erodes state power, that is, the state’s ability to keep its apparatus under control in crises. Under a general assumption about fat-tailed risk of crisis, we show that given strong fiscal capacity, the head of the state will control local corruption at such a level that its power is secured; given weaker capacity, the state will over-tolerate corruption to retain officials, risking control in crises; moreover, a state may be trapped with too weak fiscal capacity, rampant corruption, and the state losing control in any real crisis, while having little incentive to invest in fiscal capacity. By developing historical narratives, we show that these theoretical results are consistent with experience from the Roman Empire, New Kingdom of Egypt, Ming China and many other powerful states in history.
Orthognathic speech pathology: impacts of Class III malocclusion on speech
Authors: Lathrop-Marshall Hillary , Keyser Mary Morgan B , Jhingree Samantha , Giduz Natalie , Bocklage Clare , Couldwell Sandrine , Edwards Haley , Glesener Tim , Moss Kevin , Frazier-Bowers Sylvia , Phillips Ceib , Turvey Timothy , Blakey George , White Ray , Mielke Jeff , Zajac David , Jacox Laura A
Published: September 2021

Introduction

Patients with dentofacial disharmonies (DFDs) seek orthodontic care and orthognathic surgery to address issues with mastication, esthetics, and speech. Speech distortions are seen 18 times more frequently in Class III DFD patients than the general population, with unclear causality. We hypothesize there are significant differences in spectral properties of stop (/t/ or /k/), fricative (/s/ or /ʃ/), and affricate (/tʃ/) consonants and that severity of Class III disharmony correlates with the degree of speech abnormality.

Methods

To understand how jaw disharmonies influence speech, orthodontic records and audio recordings were collected from Class III surgical candidates and reference subjects (n = 102 Class III, 62 controls). A speech pathologist evaluated subjects and recordings were quantitatively analysed by Spectral Moment Analysis for frequency distortions.

Results

A majority of Class III subjects exhibit speech distortions. A significant increase in the centroid frequency (M1) and spectral spread (M2) was seen in several consonants of Class III subjects compared to controls. Using regression analysis, correlations between Class III skeletal severity (assessed by cephalometric measures) and spectral distortion were found for /t/ and /k/ phones.

Conclusions

Class III DFD patients have a higher prevalence of articulation errors and significant spectral distortions in consonants relative to controls. This is the first demonstration that severity of malocclusion is quantitatively correlated with the degree of speech distortion for consonants, suggesting causation. These findings offer insight into the complex relationship between craniofacial structures and speech distortions.
Do longitudinal orthodontic trials use appropriate statistical analyses? A meta-epidemiological study
Authors: Mheissen Samer , Khan Haris , Almuzian Mohammed , Alzoubi Emad Eddin , Pandis Nikolaos
Published: September 2021

Background

In orthodontic trials, longitudinal designs with multiple outcome measurements over time are common. The aim of this epidemiological study was to examine whether optimal statistical analysis approaches have been used in longitudinal orthodontic trials.

Methods

Pubmed was searched in August 2021 for longitudinal orthodontic trials with at least three time points of outcome assessment published in the 2017–20 period. Study selection and data extraction were done independently and in duplicate. The analysis approaches undertaken were tabulated and associations between study characteristics and the use of optimal analysis or not were assessed using Fisher’s exact test and logistic regression.

Results

One hundred forty-seven out of 563 unique records were deemed eligible for inclusion. Only 26.50% of these trials used an optimal statistical analysis for longitudinal data where the data structure is accounted for. None of the study characteristics except the statistical significance of the results were associated with the appropriateness of the statistical analysis. The odds of significant results in studies with suboptimal analyses were higher than that in studies with optimal longitudinal analyses (odds ratio: 3.48, 95% confidence interval: 1.62, 7.46, P = 0.001). For the studies with optimal analysis, the most frequent test was repeated-measure analysis of variance (RM-ANOVA). The reporting of the statistical analysis section was suboptimal in the majority of the trials.

Conclusion

Most longitudinal orthodontic trials are not analysed using optimal statistical approaches. Inferences and interpretation of their results are likely to be compromised.
Towards personalized antithrombotic management with drugs and devices across the cardiovascular spectrum
Authors: Lüscher Thomas F , Davies Allan , Beer Juerg H , Valgimigli Marco , Nienaber Christoph A , Camm John A , Baumgartner Iris , Diener Hans-Christoph , Konstantinides Stavros V
Published: September 2021

Intravascular thrombus formation and embolization are among the most frequent events leading to a number of cardiovascular conditions with high morbidity and mortality. The underlying causes are stasis of the circulating blood, genetic and acquired coagulation disorders, and reduced antithrombotic or prothrombotic properties of the vascular wall (Virchow’s triad). In the venous system, intravascular thrombi can cause venous thrombosis and pulmonary and even peripheral embolism including ischaemic stroke [through a patent foramen ovale (PFO)]. Thrombi in the left atrium and its appendage or ventricle form in the context of atrial fibrillation and infarction, respectively. Furthermore, thrombi can form on native or prosthetic aortic valves, within the aorta (in particular at sites of ulcers, aortic dissection, and abdominal aneurysms), and in cerebral and peripheral arteries causing stroke and critical limb ischaemia, respectively. Finally, thrombotic occlusion may occur in arteries supplying vital organs such the heart, brain, kidney, and extremities. Thrombus formation and embolization can be managed with anticoagulants and devices depending on where they form and embolize and on patient characteristics. Vitamin K antagonists are preferred in patients with mechanical valves, while novel oral anticoagulants are first choice in most other cardiovascular conditions, in particular venous thromboembolism and atrial fibrillation. As anticoagulants are associated with a risk of bleeding, devices such as occluders of a PFO or the left atrial appendage are preferred in patients with an increased bleeding risk. Platelet inhibitors such as aspirin and/or P2Y12 antagonists are preferred in the secondary prevention of coronary artery disease, stroke, and peripheral artery disease either alone or in combination depending on the clinical condition. A differential and personalized use of anticoagulants, platelet inhibitors, and devices is recommended and reviewed in this article.
Decision aids for shared decision-making and appropriate anticoagulation therapy in patients with atrial fibrillation: a systematic review and meta-analysis
Authors: Song Dan , Zhou Jie , Fan Tianli , Chang Jing , Qiu Yuzhen , Zhuang Zexiang , Ma Juanjuan , Zeng Li
Published: September 2021

Aims

Underuse of oral anticoagulants (OACs) is commonly observed among patients with atrial fibrillation (AF), which hinders stroke prevention in AF. Shared decision-making (SDM) can help enhance adherence by minimizing patients’ misunderstanding of treatment and aligning care with their preferences. Decision aids (DAs) have been developed to facilitate the SDM process. This study aimed to: (i) evaluate the effects of DAs on AF patients’ knowledge, decisional conflict, OAC uptake, and adherence and on the incidence of stroke and bleeding; and (ii) explore characterizing factors associated with enhanced DA effectiveness.

Methods and results

Five databases were searched. Meta-analysis was conducted using RevMan 5.3 when data were available. Comparative analysis between effective and ineffective DAs was conducted to determine the DA designs associated with better effects. Ten studies were included. Pooling results indicated that DAs reduce decisional conflict related to warfarin use [mean difference = −0.10; 95% confidence interval (CI): −0.18 to −0.02; P = 0.01] and enhance OAC uptake [risk ratio: 1.03; 95% CI: 1.01–1.05; P = 0.004]. The effects of DAs on adherence and incidence of stroke and bleeding were unclear. Comparative analysis revealed that DAs with key elements of SDM (situation diagnosis, choice awareness, option clarification, benefits and disadvantages, and patient’s preference) and pre-consultation delivery are more likely to be effective in promoting SDM and OAC uptake.

Conclusions

DAs are promising in promoting SDM and OAC uptake in patients with AF. The evidence on adherence and incidence of stroke and bleeding remains uncertain. More trials with rigorous study design and longer follow-up are necessary to obtain evidence.
Lead fixation mechanism impacts outcome of transvenous lead extraction: data from the European Lead Extraction ConTRolled Registry
Authors: Levi Nir , Bongiorni Maria Grazia , Rav Acha Moshe , Tovia-Brodie Oholi , Kennergren Charles , Auricchio Angelo , Maggioni Aldo Pietro , Rinaldi Christopher A , Nof Eyal , Ilan Michael , Blomstrom-Lundqvist Carina , Deharo Jean-Claude , Leclercq Christophe , Glikson Michael , Michowitz Yoav
Published: September 2021

Aims

The aims of this study is to characterize the transvenous lead extraction (TLE) population with active (A) compared with passive fixation (PFix) leads and to compare the safety, efficacy, and ease of extracting active fixation (AFix) compared with PFix right atrial (RA) and right ventricular (RV) leads.

Methods and results

The European Lead Extraction ConTRolled Registry (ELECTRa) was analysed. Patients were divided into three groups; those with only AFix, only PFix, and combined Fix leads. Three outcomes were defined. Difficult extraction, complete radiological, and clinical success. Multivariate model was used to analyse the independent effect of Fix mechanism on these outcomes. The study included 2815 patients, 1456 (51.7%) with only AFix leads, 982 (34.9%) with only PFix leads, and 377 (13.4%) with combined Fix leads. Patients with AFix leads were younger with shorter lead dwelling time. Infection was the leading cause for TLE among the combined Fix group with lowest rates among AFix group. No difference in complications rates was noted between patients with only AFix vs. PFix leads. Overall, there were 1689 RA (1046 AFix and 643 PFix) and 2617 RV leads (1441 AFix and 1176 PFix). Multivariate model demonstrated that PFix is independently associated with more difficult extraction for both RA and RV leads, lower radiological success in the RA but has no effect on clinical success.

Conclusion

Mechanism of Fix impact the ease of TLE of RA and RV leads and rates of complete radiological success in the RA but not clinical success. These findings should be considered during implantation and TLE procedures.
Ensuring the continuation of routine primary care during the COVID-19 pandemic: a review of the international literature
Authors: Matenge Sethunya , Sturgiss Elizabeth , Desborough Jane , Hall Dykgraaf Sally , Dut Garang , Kidd Michael
Published: September 2021

Background

The COVID-19 pandemic has resulted in the diversion of health resources away from routine primary care delivery. This disruption of health services has necessitated new approaches to providing care to ensure continuity.

Objectives

To summarize changes to the provision of routine primary care services during the pandemic.

Methods

Rapid literature review using PubMed/MEDLINE, SCOPUS, and Cochrane. Eligible studies were based in primary care and described practice-level changes in the provision of routine care in response to COVID-19. Relevant data addressing changes to routine primary care delivery, impact on primary care functions and challenges experienced in adjusting to new approaches to providing care, were obtained from included studies. A narrative summary was guided by Burns et al.’s framework for primary care provision in disasters.

Results

Seventeen of 1,699 identified papers were included. Studies reported on telehealth use and public health measures to maintain safe access to routine primary care, including providing COVID-19 screening, and establishing dedicated care pathways for non-COVID and COVID-related issues. Acute and urgent care were prioritized, causing disruptions to chronic disease management and preventive care. Challenges included telehealth use including disparities in access and practical difficulties in assessing patients, personal protective equipment shortages, and financial solvency of medical practices.

Conclusions

Substantial disruptions to routine primary care occurred due to the COVID-19 pandemic. Primary care practices’ rapid adaptation, often with limited resources and support, demonstrates agility and innovative capacity. Findings underscore the need for timely guidance and support from authorities to optimize the provision of comprehensive routine care during pandemics.
A retrospective, observational study on medication for opioid use disorder during pregnancy and risk for neonatal abstinence syndrome
Authors: Sujan Ayesha , Cleary Emma , Douglas Edie , Aujla Rubin , Boyars Lisa , Smith Claire , Guille Constance
Published: September 2021

Objectives

The prevalence of opioid use disorder (OUD) among pregnant women is increasing. Research consistently demonstrates the efficacy of medications for OUD (MOUD); however, researchers have called for additional studies evaluating the safety of MOUD during pregnancy, particularly the relative safety of two commonly used MOUD medications—methadone and buprenorphine. This study aimed to evaluate the consequences of MOUD exposure during pregnancy on risk for neonatal abstinence syndrome (NAS).

Methods

In a clinical sample of infants born to women with OUD, we evaluated the risk of NAS among those exposed to (i) methadone and (ii) buprenorphine compared with those unexposed to MOUD, as well as the risk of NAS among those exposed to (i) methadone compared with those exposed to (ii) buprenorphine.

Results

Compared with buprenorphine-exposed infants (n = 37), methadone-exposed infants (n = 27) were at increased risk for NAS (odds ratio [OR] = 4.67, 95% confidence interval [CI]: 1.03, 21.17). Compared with unexposed infants (n = 43), buprenorphine-exposed infants were at decreased risk for NAS (OR = 0.45, 95% CI: 0.14, 1.39) and methadone-exposed infants were at increased risk for NAS (OR = 2.64, 95% CI: 0.79, 8.76), though these associations were not statistically significant.

Conclusions

Our study suggests that when methadone and buprenorphine are equally appropriate options for the treatment of OUD in pregnant women, buprenorphine may add the additional benefit of reduced risk of newborn NAS.
The teacher, the institution and the war: primary schooling in France, 1913–1924
Authors: Saint-Fuscien Emmanuel
Published: September 2021

What if not only the new pedagogy emerging in Europe during the interwar years, but the institutional development of the school in the twentieth century owed something to educational experience in the era of the First World War? This is the question posed by this article, which aims to address the way in which the school represented the war, asking in turn how the war transformed the school. It aims to interrogate changes in pedagogical practice and interaction within the school during wartime, but also to examine the changes brought about after the return of peace.
Sharp Increase of Problematic Mitogenomes of Birds: Causes, Consequences, and Remedies
Authors: Sangster George , Luksenburg Jolanda A
Published: September 2021

Authentic DNA sequences are crucial for reliable evolutionary inference. Concerns about the identification of DNA sequences have been voiced several times in the past but few quantitative studies exist. Mitogenomes play important roles in phylogenetics, phylogeography, population genetics, and DNA identification. However, the large number of mitogenomes being published routinely, often in brief data papers, has raised questions about their authenticity. In this study, we quantify problematic mitogenomes of birds and their reusage in other papers. Of 1,876 complete or partial mitogenomes of birds published until January 1, 2020, the authenticity of 1,559 could be assessed with sequences of conspecifics. Of these, 78 (5.0%) were found to be problematic, including 45 curated reference sequences. Problems were due to misidentification (33), chimeras of two or three species (23), sequencing errors/numts (18), incorrect sequence assembly (1), mislabeling at GenBank but not in the final paper (2), or vice versa (1). The number of problematic mitogenomes has increased sharply since 2012. Worryingly, these problematic sequences have been reused 436 times in other papers, including 385 times in phylogenies. No less than 53% of all mitogenomic phylogenies/networks published until January 1, 2020 included at least one problematic mitogenome. Problematic mitogenomes have resulted in incorrect phylogenetic hypotheses and proposals for unwarranted taxonomic revision, and may have compromised comparative analyses and measurements of divergence times. Our results indicate that a major upgrade of quality control measures is warranted. We propose a comprehensive set of measures that may serve as a new standard for publishing mitogenome sequences.
VC@Scale: Scalable and high-performance variant calling on cluster environments
Authors: Ahmad Tanveer , Al Ars Zaid , Hofstee H Peter
Published: September 2021

Background

Recently many new deep learning–based variant-calling methods like DeepVariant have emerged as more accurate compared with conventional variant-calling algorithms such as GATK HaplotypeCaller, Sterlka2, and Freebayes albeit at higher computational costs. Therefore, there is a need for more scalable and higher performance workflows of these deep learning methods. Almost all existing cluster-scaled variant-calling workflows that use Apache Spark/Hadoop as big data frameworks loosely integrate existing single-node pre-processing and variant-calling applications. Using Apache Spark just for distributing/scheduling data among loosely coupled applications or using I/O-based storage for storing the output of intermediate applications does not exploit the full benefit of Apache Spark in-memory processing. To achieve this, we propose a native Spark-based workflow that uses Python and Apache Arrow to enable efficient transfer of data between different workflow stages. This benefits from the ease of programmability of Python and the high efficiency of Arrow’s columnar in-memory data transformations.

Results

Here we present a scalable, parallel, and efficient implementation of next-generation sequencing data pre-processing and variant-calling workflows. Our design tightly integrates most pre-processing workflow stages, using Spark built-in functions to sort reads by coordinates and mark duplicates efficiently. Our approach outperforms state-of-the-art implementations by >2 times for the pre-processing stages, creating a scalable and high-performance solution for DeepVariant for both CPU-only and CPU + GPU clusters.

Conclusions

We show the feasibility and easy scalability of our approach to achieve high performance and efficient resource utilization for variant-calling analysis on high-performance computing clusters using the standardized Apache Arrow data representations. All codes, scripts, and configurations used to run our implementations are publicly available and open sourced; see https://github.com/abs-tudelft/variant-calling-at-scale.
Magmatic fluid pathways in the upper crust: insights from dense magnetotelluric observations around the Kuju Volcanoes, Japan
Authors: Aizawa Koki , Utsugi Mitsuru , Kitamura Keigo , Koyama Takao , Uyeshima Makoto , Matsushima Nobuo , Takakura Shinichi , Inagaki Haruhiro , Saito Hiroki , Fujimitsu Yasuhiro
Published: September 2021

Magnetotelluric (MT) observations have revealed subvertical electrical conductors that extend from shallow depths into the mid-crust at various geothermal zones, active volcanoes and active faults worldwide. These deeply rooted subvertical conductors have typically been interpreted to represent entire zones of dedicated fluid transport through the crust. We estimate the high-resolution 3-D crustal resistivity structure below the Kuju Volcanoes, Japan, using dense observations from 153 broad-band MT measurement sites and 40 telluric measurement sites. The resistivity structure highlights subvertical conductors that merge into a deep conductor to the north of the volcanoes, with deep low-frequency earthquakes occurring near the southeastern edge of this subvertical conductor at 10–30 km depth. This deep conductor branches into several subvertical conductors at 2–10 km depth, coinciding with a shallow zone where tectonic earthquakes rarely occur. The surface expressions of active geothermal areas and past volcanic eruptions are all located above the edges of the conductors at 2–6 km depth. Widespread conductive layers exist around the volcanoes above 2 km depth, and their distribution approximately corresponds to a low-gravity-anomaly zone. We discuss the nature of these subvertical conductors, the potential causes of their complex structure and their relationship to local magmatic fluid transport. These subvertical conductors, a shallow clay-rich layer, developed fracture systems and high-strength solidified magma may all contribute to magmatic fluid transport to the surface at the Kuju Volcanoes. In this study, we add the possibility that the edges of these subvertical conductors act as important magmatic fluid pathways.