bluuebunny/crossref_metadata_2025 huggingface dataset:
Anais Cerci Forceps: A Novel Instrument for Shaping the Nasal Dome Before Transdomal Suture Placement
Authors: Çerçi Özkan Aret
Published: February 2020

One of the most important components of an attractive nasal tip is the cephalocaudally conical form of the dome at the sagittal plane. With respect to this fact, the author tried to design a new forceps which holds the dome in a convex shape on a transverse plane and cephalocaudally conical in shape on the sagittal plane. Before grasping the dome in the desired position with Anais Cerci forceps, some degree of lateral steal is suggested and can be performed to increase the tip rotation and projection. With the help of its specific shape and template forming function, this novel instrument may also help to prevent the excess strain of transdomal suture which is crucially important to prevent the formation of pinching. This newly designed forceps can also help to provide the opportunity of the required acute angle between two domes. Slight oblique grasping of the dome reciprocally provides nice acute angle between 2 domes. Additionally, this forceps may also help to provide formation of symmetrically and reciprocally designed dome curvatures. In several secondary rhinoplasty cases with highly destroyed lower lateral cartilages, septal, auricular or costal cartilages are used for alar reconstruction. Mimicking the lower lateral cartilage anatomy from a straight cartilage graft piece is not an easy way of restoration. In such cases, Anais Cerci forceps may facilitate reshaping of the dome from an amorphous cartilage graft.
Cephalometric and Anthropometric Changes and Their Relation to Patients’ Satisfaction After Orthognathic Surgery
Authors: Geramy Allahyar , Sheikhzade Sedighe , Nazarifar Arezoo Mazaheri
Published: February 2020

Objective:

The aim of this prospective study was to evaluate the correlation between cephalometric and anthropometric facial changes and satisfaction level of class III patients after bimaxillary orthognathic surgery.

Methods and materials:

Totally, 29 class III patients (mean age = 24.23 ± 4.2) undergoing one-piece Lefort 1 osteotomy and mandibular setback were included. Pre- and postoperative lateral cephalograms were taken. Thirteen cephalometric and 17 anthropometric facial measurements were evaluated. A 6-item questionnaire of Rustemeyer's study was used to assess patient's satisfaction after surgery. The Wilcoxon signed-rank test, paired sample t test and Spearman's correlation analysis were used as statistical analysis.

Results:

Facial aesthetic and masticatory improvement was highly significant (P < 0.001), while opinion differences between patients and relatives/friends were not significant (P = 0.334). Increased upper lip length (P = 0.037) and decreased nasal tip protrusion-nose height index (P = 0.017) correlated positively with aesthetic improvements after surgery.

Conclusion:

Although the association between parameters and satisfaction questionnaire was found, other influential factors should be considered before surgery as well.
Panfacial Fractures Management
Authors: Koraitim Mohamed
Published: February 2020

Introduction:

Panfacial fracture represent a challenge for maxillofacial surgeons due to paucity of useful landmark and stable bone that can be used for fixation. Nowadays, with the availability of rigid and semi rigid fixations, understanding of the importance of the facial buttresses, bone grafting, and early intervention, the functional and cosmetic outcomes showed a significant improvement. Many treatment sequences exist in the literature including top to bottom, bottom to top, lateral to medial, and medial to lateral approach.

Aim of the Study:

To evaluate the outcome of “bottom to top, lateral to medial” sequence that we used in the management of panfacial fractures in term of function and cosmesis.

Patients and Methods:

This study included 73 patients with panfacial fractures admitted to the Maxillofacial and Plastic Surgery Department, Alexandria University.

Results:

Most of the patients (n = 52, 71.23%) were aged between 21 and 40 years old. 83.56% (n = 61) of patients were male. Road traffic accidents was the most common cause of trauma (n = 57). The most common site involved in panfacial fracture was the middle and lower third (58%). The common complication observed was malocclusion (n = 6). Of these, 5 patients had minor malocclusion that was corrected orthodontically and only one patient required surgical intervention.

Conclusion:

The “bottom to top, lateral to medial" sequence for reduction and fixation of panfacial fractures is reliable with satisfactory results in term of function and cosmesis.
Reconstruction of Hair-Bearing Areas
Authors: Kilinc Hidir , Algan Mehmet Fatih
Published: February 2020

Hair-bearing areas reconstruction is a difficult field because of limited donor area. Various techniques have been described for hair-bearing areas reconstruction, but the choice of the flap is variable depending on surgeons and patients. In this study, the authors present 7 patients who underwent soft tissue reconstruction with the pedicled superficial temporal artery-based flaps in the hair-bearing areas. No postoperative complications like bleeding, flap congestion, wound dehiscence, and flap necrosis were observed. This flap can be an alternative to the other methods because it is compatible with the face by the flap color and thickness, it can be easily harvested, it has a reliable circulation and minimum donor site scar.
Bilateral Cephalohematoma With Sagittal Synostosis and Scaphocephaly
Authors: Kopacz Avery , Nagy Laszlo , Demke Joshua
Published: February 2020

Inappropriate fusion of the cranial sutures leads to craniosynostosis and the subsequent skull rigidity can cause many developmental and structural problems. Cephalohematoma is a subperiosteal collection of blood commonly associated with birth trauma or instrument-assisted delivery and is one of the most frequently reported fetal injuries in Caesarian section procedures. There have been very few cases reported of patients with both scaphocephaly due to sagittal craniosynostosis and cephalohematoma and no reports of scaphocephaly with bilateral cephalohematoma as of the date of this report. The current literature suggests that the two conditions are potentially associated, either through mechanical pathways involving trauma or through a complex interplay of growth factors. The authors present a case of bilateral cephalohematoma with scaphocephaly secondary to progressive sagittal craniosynostosis.
Spontaneous Repositioning of Isolated Blow-In Orbital Roof Fracture: Could Wait and See Be a Strategy in Asymptomatic Cases?
Authors: Lofrese Giorgio , Mongardi Lorenzo , De Bonis Pasquale , Scerrati Alba , Nicassio Nicola , Cultrera Francesco
Published: February 2020

Background:

Treatment of isolated blow-in orbital roof fractures is still debated due to their anatomical complexity and the potential ocular and neurological related injuries. Surgery is advised in symptomatic cases while there is still controversy regarding the preferred treatment for those patients asymptomatic.

Objective:

To explore the suitability of a conservative management with close imaging follow-up in asymptomatic isolated blow-in orbital roof fractures.

Methods:

A single-case experience has been integrated into a systematic review of the literature to support the discussion on this specific traumatic lesion. Studies written in English and pertaining adult human subjects were further filtered according to the following eligibility criteria: clear definition of fracture's pattern, absence of concomitant cranio-facial injuries requiring management, proper description of treatment timing and outcome.

Results:

The literature regarding treatment of isolated orbital roof fractures is of poor quality partly due to the rarity of such lesions. A total of 4 studies limited to small case series with 13 patients in total discuss thoroughly management options and timing of treatment. In particular, displaced blow-in fractures were treated conservatively in 4 patients with only 2 benefitting from this approach. Our patient showed a spontaneous realignment of a posttraumatic blow-in orbital roof deformity and at 12-month follow-up conservative management appeared a safe and effective strategy. A short-term wait-and-see approach with aggressive follow-up imaging could probably represent a reasonable option for treatment of isolated blow-in orbital roof fractures without neurological or ocular symptoms. Since literature remains confined to limited case series, future multicenter studies adopting shared evaluation parameters would help in standardizing the indications for this subset of craniofacial injuries.
Quick Method for Presurgical Volumetric Analysis of Alveolar Cleft Defects
Authors: Chen Shuxiu , Liu Bing , Liu Jing , Yin Ningbei , Wang Yongqian
Published: February 2020

Presurgical evaluation of the alveolar cleft defect is an essential and crucial step for procedural success. This study proposes a method for rapid and precise volumetric assessment of alveolar cleft defects using computed tomography data and computer-aided engineering (CAE) software. For comparison, 3-dimensional-printed models of the alveolar bone were also made. A simulated graft was used on the models and the graft volume was measured using the water displacement technique. We then compared the CAE software-derived volumes with the actual volumes of the simulated grafts. The intraclass correlation coefficient ranged from 0.95 to 0.97 (intraobserver) and 0.94 to 0.98 (interobserver), indicating a high level of reliability and reproducibility of the CAE measurements. The mean time spent to calculate an alveolar cleft defect volume was 8.4 minutes. The average volume of the simulated bone grafts of 3-dimensional-printed models was 1.39 mL, which was lower than the mean volume of 1.42 mL calculated using the CAE software. The paired Student t-test showed no statistically significant difference between the volumes derived from the 2 methods. This study demonstrates that this quick assessment method is a useful adjunct to busy clinical practice.
Characterization of Bilateral Parietal Thinning
Authors: Sanati-Mehrizy Paymon , Graziano Francis D. , Naidich Thomas , Taub Peter J.
Published: February 2020

Background:

Bilateral parietal thinning (BPT) of the calvarium is uncommon but can lead to significant morbidity, including pain or communication through the thinned bone. This study aimed to define and characterize a novel grading system for BPT.

Methods:

Coronal CT scans of patients with BPT were retrospectively analyzed and anatomic measurements were taken including (1) thinning ratio, defined as calvarial thickness at the thinnest point divided by the average thickness of the surrounding bone and (2) width of the defect. In addition, patient demographics and comorbidities were collected.

Results:

Forty-three patients were identified with BPT, with an average age of 73 ± 16 years and 74% were female. The authors’ novel grading scheme based on depth of calvarium involvement was found to be significantly correlated to thinning ratio (P < 0.001) and width (P < 0.001). When controlling for comorbidities, increasing age (P = 0.044) was the only significant independent risk factor associated with thinning ratio. With respect to defect size, when controlling for comorbidities, both hypertension (P = 0.025) and increasing age (P = 0.024) were found to be significant independent risk factors related to increasing defect size. Twenty patients (47%) had multiple CT scans (range 5 month–5 year interval). In this group, patients had an average of 0.66 ± 0.11 mm decrease in parietal thickness per each year of increasing age, showing progressive parietal thinning with time.

Conclusion:

This study proposes a novel quantitatively-characterized grading scheme for BPT. The authors’ results indicate that when controlling for comorbidities, BPT thinning is associated with increasing age, while defect width is associated with increasing age and hypertension. This grading scheme can help to diagnose, classify, and monitor patients with parietal bone thinning.
Full Digital Workflow of Nasoalveolar Molding Treatment in Infants With Cleft Lip and Palate
Authors: Gong Xin , Dang Renxing , Xu Ting , Yu Quan , Zheng Jiawei
Published: February 2020

Objectives:

The aim of this pilot study was to illustrate the feasibility of a full digital workflow to design and manufacturing a consecutive series of customized nasoalveolar molding (NAM) appliances in advance for presurgical unilateral and bilateral cleft lip and palate (CLP) treatment.

Methods:

The full digital workflow consisted of acquisition of 3D image data of an infant's maxilla by using intraoral scanner (TRIOS; 3Shape, Copenhagen, Denmark); the initial data were imported into an appropriate computer-aided design (CAD) software environment, the digital model was virtual modified to achieve a harmonic alveolar arch, and generated a consecutive of digital models of each movement stage; the digital model of NAM appliance was designed based on the virtual modified model; bio-compatible material MED610 was used to manufacturing the real NAM appliances by 3D printing. A consecutive series of NAM appliances was delivered to CLP infant before lip surgery.

Results:

Intraoral scanning was harmless and safer than conventional impression technique for CLP infants. The CAD/3D printing procedures allowed a series of NAM appliances to be designed and manufactured in advance. The clinical results showed that this full digital workflow was efficient, viable and able to estimate the treatment objective. By the end of presurgical NAM treatment, the malposition alveolar segments had been aligned normally, the surrounding soft tissues repositioned.

Conclusions:

The full digital workflow presented has provided the potential for presurgical NAM treatment of infants with cleft lip and palate. Intraoral scanning served as a starting point, so subsequent virtual treatment planning and CAD/3D printing procedures could realize the full digital workflow, a whole series of customized NAM appliances was manufactured in advance. This method brings the benefits of safety, affectivity and time-saving.
Efficacy and Safety of Direct Oral Anticoagulants in Kidney Transplantation: A Single-center Pilot Experience
Authors: Leon Juliette , Sabbah Laurent , Aubert Olivier , Anglicheau Dany , Delavenne Xavier , Zuber Julien , Amrouche Lucile , Scemla Anne , Giura Geltrude , Divard Gillian , Legendre Christophe , Sberro-Soussan Rebecca
Published: February 2020

Background.

Oral anticoagulation therapy is frequently prescribed to kidney transplant recipients (KTRs) for prevention and treatment of thrombotic events. Over the past 10 y, direct oral anticoagulants (DOACs) have shown similar efficacy with a safety profile equal or superior to that of vitamin K antagonist anticoagulants (VKAs) in the general population. However, little data are available on kidney transplantation.

Methods.

We investigated the efficacy (thrombotic events) and safety (hemorrhagic and other adverse events and graft outcomes) of DOACs in a cohort of KTRs with a renal function >30 mL/min. We then compared these patients to a control group treated by VKA.

Results.

Fifty-two KTRs treated by DOACs between 2013 and 2018 at Necker Hospital were included. Patients were with a mean age of 62 ± 13 y old and a mean glomerular filtration rate of 59 ± 20 mL/min/1.73m2. The major indication was atrial fibrillation (n = 31 [60%]). Apixaban was the most commonly used agent (n = 36 [69%]). No thrombotic complications were reported under DOAC until last follow-up (14.1 ± 13 mo). In comparison to 50 controls under VKA during the same period, the bleeding rate under DOAC was significantly lower (11.5 versus 22.9 per 100 patient-y, P = 0.037) with a hazard ratio of 0.39 (95% confidence interval, 0.19-0.85, P = 0.041). No significant changes in kidney function, rejection rate, or hemoglobin level were reported.

Conclusions.

DOACs appear to be effective and safe anticoagulants in KTRs with stable renal function.
Kidney Transplantation in Systemic Amyloidosis
Authors: Angel-Korman Avital , Havasi Andrea
Published: February 2020

The present review discusses current developments and outcomes of renal transplantation in systemic amyloidosis. Amyloidosis can wreak havoc on the architecture and functioning of the kidneys, leading to end-stage renal disease. In recent years, the available treatments, especially for light-chain amyloidosis but also for several of the underlying inflammatory diseases that cause amyloid A amyloidosis have expanded leading to prolonged survival albeit frequently with renal failure. At the same time, there are also increasing numbers of patients diagnosed with one of the inherited forms of amyloidosis for which currently there is no targeted treatment available and, in some cases, renal failure is unavoidable. Due to the complex nature of the pathophysiology and treatment of these diseases, it can be very challenging for the clinician to determine whether or not it is appropriate to refer an affected individual for kidney transplantation. Determining eligibility criteria, as well as peritransplant and posttransplant management, requires a multidisciplinary approach with close monitoring and follow-up.
Localizing the epileptogenic zone
Authors: Frauscher Birgit
Published: February 2020

Purpose of review

Epilepsy surgery is the therapy of choice for 30–40% of people with focal drug-resistant epilepsy. Currently only ∼60% of well selected patients become postsurgically seizure-free underlining the need for better tools to identify the epileptogenic zone. This article reviews the latest neurophysiological advances for EZ localization with emphasis on ictal EZ identification, interictal EZ markers, and noninvasive neurophysiological mapping procedures.

Recent findings

We will review methods for computerized EZ assessment, summarize computational network approaches for outcome prediction and individualized surgical planning. We will discuss electrical stimulation as an option to reduce the time needed for presurgical work-up. We will summarize recent research regarding high-frequency oscillations, connectivity measures, and combinations of multiple markers using machine learning. This latter was shown to outperform single markers. The role of NREM sleep for best identification of the EZ interictally will be discussed. We will summarize recent large-scale studies using electrical or magnetic source imaging for clinical decision-making.

New approaches based on technical advancements paired with artificial intelligence are on the horizon for better EZ identification. They are ultimately expected to result in a more efficient, less invasive, and less time-demanding presurgical investigation.
Data science in neurodegenerative disease: its capabilities, limitations, and perspectives
Authors: Golriz Khatami Sepehr , Mubeen Sarah , Hofmann-Apitius Martin
Published: February 2020

Purpose of review

With the advancement of computational approaches and abundance of biomedical data, a broad range of neurodegenerative disease models have been developed. In this review, we argue that computational models can be both relevant and useful in neurodegenerative disease research and although the current established models have limitations in clinical practice, artificial intelligence has the potential to overcome deficiencies encountered by these models, which in turn can improve our understanding of disease.

Recent findings

In recent years, diverse computational approaches have been used to shed light on different aspects of neurodegenerative disease models. For example, linear and nonlinear mixed models, self-modeling regression, differential equation models, and event-based models have been applied to provide a better understanding of disease progression patterns and biomarker trajectories. Additionally, the Cox-regression technique, Bayesian network models, and deep-learning-based approaches have been used to predict the probability of future incidence of disease, whereas nonnegative matrix factorization, nonhierarchical cluster analysis, hierarchical agglomerative clustering, and deep-learning-based approaches have been employed to stratify patients based on their disease subtypes. Furthermore, the interpretation of neurodegenerative disease data is possible through knowledge-based models which use prior knowledge to complement data-driven analyses. These knowledge-based models can include pathway-centric approaches to establish pathways perturbed in a given condition, as well as disease-specific knowledge maps, which elucidate the mechanisms involved in a given disease. Collectively, these established models have revealed high granular details and insights into neurodegenerative disease models.

In conjunction with increasingly advanced computational approaches, a wide spectrum of neurodegenerative disease models, which can be broadly categorized into data-driven and knowledge-driven, have been developed. We review the state of the art data and knowledge-driven models and discuss the necessary steps which are vital to bring them into clinical application.
Chance and risk in epilepsy
Authors: Baud Maxime O. , Proix Timothée , Rao Vikram R. , Schindler Kaspar
Published: February 2020

Purpose of review

Epilepsy is a dynamical disorder of the brain characterized by sudden, seemingly unpredictable transitions to the ictal state. When and how these transitions occur remain unresolved questions in neurology.

Recent findings

Modelling work based on dynamical systems theory proposed that a slow control parameter is necessary to explain the transition between interictal and ictal states. Recently, converging evidence from chronic EEG datasets unravelled the existence of cycles of epileptic brain activity at multiple timescales – circadian, multidien (over multiple days) and circannual – which could reflect cyclical changes in a slow control parameter. This temporal structure of epilepsy has theoretical implications and argues against the conception of seizures as completely random events. The practical significance of cycles in epilepsy is highlighted by their predictive value in computational models for seizure forecasting.

The canonical randomness of seizures is being reconsidered in light of cycles of brain activity discovered through chronic EEG. This paradigm shift motivates development of next-generation devices to track more closely fluctuations in epileptic brain activity that determine time-varying seizure risk.
What has been the impact of new drug treatments on epilepsy?
Authors: Chen Zhibin , Brodie Martin J. , Kwan Patrick
Published: February 2020

Purpose of review

Nearly two dozen antiseizure medications (ASMs) with different mechanisms of action have been introduced over the past three decades with the aim of providing better efficacy or safety profile than the previous drugs. Several new ASMs with improvement on a classic drug family or have novel mechanisms of action have been recently approved for epilepsy. The present review explored recent studies or guidelines on new agents and discussed the potential impact of these novel treatments on epilepsy management and future directions of research.

Recent findings

Long-term cohort studies showed that, collectively, the second-generation did not improve the overall prognosis of epilepsy. Individual monotherapy studies showed similar efficacy of second-generation (levetiracetam and zonisamide) and third-generation (eslicarbazepine acetate and lacosamide) ASMs compared to controlled-release carbamazepine for the treatment of focal epilepsy. However, there appears to be no evidence to support any second-generation or third-generation ASMs to be as efficacious as valproate monotherapy for generalized and unclassified epilepsies. Cannabidiol adjunctive treatments were found to be efficacious for Dravet syndrome and Lennox–Gastaut syndrome. Although most newer generation ASMs are less prone to drug–drug interactions, stiripentol and cannabidiol can elevate the plasma concentration of N-desmethylclobazam, the active metabolite of clobazam. Generally speaking, the second-generation ASMs have lower teratogenic risk than the older drugs but there is scant study on neurodevelopmental effect of third-generation ASMs.

Although the newer generation ASMs may not have improved the overall seizure control they have advantages in terms of drug–drug interactions and teratogenicity, and thus offer valuable individualized options in the treatment of epilepsy.
Down syndrome and dementia: advances in the field
Authors: McGlinchey Eimear , McCallion Philip , McCarron Mary
Published: February 2020

Purpose of review

People with Down syndrome represent the world's largest population with a genetic risk for Alzheimer's disease. This review will provide a short summary of what is known and will include recent findings from the field.

Recent findings

There has been an increasing focus on biomarker research in this population, with a number of studies presenting findings on promising new markers – Neurofilament Light (NfL) appears to be one such promising marker that has emerged. Imaging studies have increased our knowledge on the progression of Alzheimer's disease in this population.

The inclusion of people with Down syndrome in dementia research is vital from a scientific and an equity perspective. Recent advances in the field can have further impact with multisite, cross country collaborative efforts. For this to happen, instruments need to be validated across language and cultures.
How can schools be integrated in promoting well-being, preventing mental health problems and averting substance-use disorders in urban populations?
Authors: Spanemberg Lucas , Salum Giovanni A. , Bado Patrícia
Published: February 2020

Purpose of review

Mental health and substance use problems are among the most prevalent and challenging problems faced by both high-income and low-income countries worldwide. This review will focus on summarizing scattered evidence of school-based interventions to promote well-being and prevent mental health problems and substance use disorders in children and adolescents.

Recent findings

We focus on two main areas of research: promotion of healthy school climate and prevention of bullying. Choosing among available interventions might be challenging, both because of the difficulties in assessing their efficacy and tailoring interventions to specific needs, but also because of the scarcity of intervention in low-resource settings. We provide some guidance on principles encompassed by the available evidence that can be used for policymakers and local communities aiming to integrate mental health promotion and prevention into their schools.

Developing, implementing, scaling and sustaining school-based interventions is a necessity of our field if we want to move closer to sustainable development goals.
Small within the largest: brain size and anatomy of the extinct
Neoepiblema acreensis
, a giant rodent from the Neotropics
Authors: Ferreira José D. , Negri Francisco R. , Sánchez-Villagra Marcelo R. , Kerber Leonardo
Published: February 2020

The ecomorphological diversity of caviomorph rodents in South America included giant forms, such as the chinchilloid
Neoepiblema acreensis
from the Upper Miocene of Brazil. The evolution of the brain anatomy and size of these animals can be now studied with non-invasive imaging techniques and exceptional fossils. Caviomorphs show diversity in the traits of the olfactory bulbs, cerebrum, cerebellum, cranial nerves, and blood vessels.
Neoepiblema acreensis
had a gyrencephalic brain, with an expansion of the frontal lobe, lacking an evident paraflocculus. Compared to the predictions based on extant taxa, even when considering taphonomical effects,
N. acreensis
, a rodent that weighted almost 80 kg, had a very low encephalization quotient compared to other rodents. The adaptive value of a low energetic cost and other ecological factors could explain the presence of a small brain in this giant rodent––a pattern we also hypothesize for other Neogene giant rodents.
A hybrid analytical–numerical algorithm for determining the neuronal current via electroencephalography
Authors: Hashemzadeh Parham , Fokas A. S. , Schönlieb C. B.
Published: February 2020

Specific mental processes are associated with brain activation of a unique form, which are, in turn, expressed via the generation of specific neuronal electric currents. Electroencephalography (EEG) is based on measurements on the scalp of the electric potential generated by the neuronal current flowing in the cortex. This specific form of EEG data has been employed for a plethora of medical applications, from sleep studies to diagnosing focal epilepsy. In recent years, there have been efforts to use EEG data for a more ambitious purpose, namely to determine the underlying neuronal current. Although it has been known since 1853, from the studies by Helmholtz, that the knowledge of the electric potential of the external surface of a conductor is insufficient for the determination of the electric current that gave rise to this potential, the important question of which part of the current can actually be determined from the knowledge of this potential remained open until work published in 1997, when it was shown that EEG provides information only about the irrotational part of the current, which will be denoted byΨ; moreover, an explicit formula was derived in the above work relating this part of the current, the measured electric potential, and a certain auxiliary function,vs, that depends on the geometry of the various compartments of the brain–head system and their conductivities. In the present paper: (i) Motivated by recent results which show that, in the case of ellipsoidal geometry, the assumption of theL2minimization of the current yields a unique solution, we derive an analogous analytic formula characterizing this minimization for arbitrary geometry. (ii) We show that the above auxiliary function can be computed numerically via a line integral from the values of a related functionvscomputed via OpenMEEG; moreover, we propose an alternative approach to computing the auxiliary functionvsbased on the construction of a certain surrogate model. (iii) By expandingΨin terms of an inverse multiquadric radial basis we implement the relevant formulae numerically. The above algorithm performs well for synthetic data; its implementation with real data only requires the knowledge of the coordinates of the positions where the given EEG data are obtained.
Evolution in the Debian GNU/Linux software network: analogies and differences with gene regulatory networks
Authors: Villegas Pablo , Muñoz Miguel A. , Bonachela Juan A.
Published: February 2020

Biological networks exhibit intricate architectures deemed to be crucial for their functionality. In particular, gene regulatory networks, which play a key role in information processing in the cell, display non-trivial architectural features such as scale-free degree distributions, high modularity and low average distance between connected genes. Such networks result from complex evolutionary and adaptive processes difficult to track down empirically. On the other hand, there exists detailed information on the developmental (or evolutionary) stages of open-software networks that result from self-organized growth across versions. Here, we study the evolution of the Debian GNU/Linux software network, focusing on the changes of key structural and statistical features over time. Our results show that evolution has led to a network structure in which the out-degree distribution is scale-free and the in-degree distribution is a stretched exponential. In addition, while modularity, directionality of information flow, and average distance between elements grew, vulnerability decreased over time. These features resemble closely those currently shown by gene regulatory networks, suggesting the existence of common adaptive pathways for the architectural design of information-processing networks. Differences in other hierarchical aspects point to system-specific solutions to similar evolutionary challenges.
A numerical study on oxygen adsorption in porous media of coal rock based on fractal geometry
Authors: Lv Xianzhe , Liang Xiaoyu , Xu Peng , Chen Linya
Published: February 2020

In order to explore the factors affecting coal spontaneous combustion, the fractal characteristics of coal samples are tested, and a pore-scale model for oxygen adsorption in coal porous media is developed based on self-similar fractal model. The liquid nitrogen adsorption experiments show that the coal samples indicate evident fractal scaling laws at both low-pressure and high-pressure sections, and the fractal dimensions, respectively, represent surface morphology and pore structure of coal rock. The pore-scale model has been validated by comparing with available experimental data and numerical simulation. The present numerical results indicate that the oxygen adsorption depends on both the pore structures and temperature of coal rock. The oxygen adsorption increases with increased porosity, fractal dimension and ratio of minimum to maximum pore sizes. The edge effect can be clearly seen near the cavity/pore, where the oxygen concentration is low. The correlation between the oxygen adsorption and temperature is found to obey Langmuir adsorption theory, and a new formula for oxygen adsorption and porosity is proposed. This study may help understanding the mechanisms of oxygen adsorption and accordingly provide guidelines to lower the risk of spontaneous combustion of coal.
Despotic aggression in pre-moulting painted buntings
Authors: Rohwer Vanya G. , Rohwer Sievert , Wingfield John C.
Published: February 2020

Aggression in territorial social systems is easy to interpret because the benefits of territorial defence mostly accrue to the territorial holder. However, in non-territorial systems, high aggression seems puzzling and raises intriguing evolutionary questions. We describe extreme rates of despotism between age classes in a passerine bird, the painted bunting (
Passerina ciris
), during the pre-moulting period. Aggressive encounters were not associated with aggressors gaining immediate access to resources. Instead, conspecifics, and even other species, were pursued as though being harassed; this aggression generated an ideal despotic habitat distribution such that densities of adult males were higher in high-quality sites. Aggression was not a by-product of elevated testosterone carried over from the breeding season but, rather, appeared associated with dehydroepiandrosterone, a hormone that changes rates of aggression in non-breeding birds without generating the detrimental effects of high testosterone titres that control aggression in the breeding season. This extraordinary pre-moult aggression seems puzzling because individual buntings do not hold defined territories during their moult. We speculate that this high aggression evolved as a means of regulating the number of conspecifics that moulted in what were historically small habitat patches with limited food for supporting the extremely rapid moults of painted buntings.
Control of synchronization ratios in clock/cell cycle coupling by growth factors and glucocorticoids
Authors: Almeida S. , Chaves M. , Delaunay F.
Published: February 2020

The cell cycle and the circadian clock are essential cyclic cellular processes often synchronous in healthy cells. In this work, we use previously developed mathematical models of the mammalian cell cycle and circadian cellular clock in order to investigate their dynamical interactions. Firstly, we study unidirectional cell cycle → clock coupling by proposing a mechanism of mitosis promoting factor (MPF)-controlled REV-ERB
α
degradation. Secondly, we analyse a bidirectional coupling configuration, where we add the CLOCK : BMAL1-mediated MPF repression via the WEE1 kinase to the first system. Our simulations reproduce ratios of clock to cell cycle period in agreement with experimental observations and give predictions of the system’s synchronization state response to a variety of control parameters. Specifically, growth factors accelerate the coupled oscillators and dexamethasone (Dex) drives the system from a 1 : 1 to a 3 : 2 synchronization state. Furthermore, simulations of a Dex pulse reveal that certain time regions of pulse application drive the system from 1 : 1 to 3 : 2 synchronization while others have no effect, revealing the existence of a responsive and an irresponsive system’s phase, a result we contextualize with observations on the segregation of Dex-treated cells into two populations.
Shock wave propagation along the central retinal blood vessels
Authors: Spelman T. A. , Stewart P. S.
Published: February 2020

Retinal haemorrhage is often observed following brain injury. The retinal circulation is supplied (drained) by the central retinal artery (vein) which enters (leaves) the eye through the optic nerve at the optic disc; these vessels penetrate the nerve immediately after passing through a region of cerebrospinal fluid (CSF). We consider a theoretical model for the blood flow in the central retinal vessels, treating each as multi-region collapsible tubes, where we examine how a sudden change in CSF pressure (mimicking an injury) drives a large amplitude pressure perturbation towards the eye. In some cases, this wave can steepen to form a shock. We show that the region immediately proximal to the eye (within the optic nerve where the vessels are strongly confined by the nerve fibres) can significantly reduce the amplitude of the pressure wave transmitted into the eye. When the length of this region is consistent with clinical measurements, the CSF pressure perturbation generates a wave of significantly lower amplitude than the input, protecting the eye from damage. We construct an analytical framework to explain this observation, showing that repeated rapid propagation and reflection of waves along the confined section of the vessel distributes the perturbation over a longer lengthscale.
Structure-preserving integrators for dissipative systems based on reversible– irreversible splitting
Authors: Shang Xiaocheng , Öttinger Hans Christian
Published: February 2020

We study the optimal design of numerical integrators for dissipative systems, for which there exists an underlying thermodynamic structure known as GENERIC (general equation for the nonequilibrium reversible–irreversible coupling). We present a frame-work to construct structure-preserving integrators by splitting the system into reversible and irreversible dynamics. The reversible part, which is often degenerate and reduces to a Hamiltonian form on its symplectic leaves, is solved by using a symplectic method (e.g. Verlet) with degenerate variables being left unchanged, for which an associated modified Hamiltonian (and subsequently a modified energy) in the form of a series expansion can be obtained by using backward error analysis. The modified energy is then used to construct a modified friction matrix associated with the irreversible part in such a way that a modified degeneracy condition is satisfied. The modified irreversible dynamics can be further solved by an explicit midpoint method if not exactly solvable. Our findings are verified by various numerical experiments, demonstrating the superiority of structure-preserving integrators over alternative schemes in terms of not only the accuracy control of both energy conservation and entropy production but also the preservation of the conformal symplectic structure in the case of linearly damped systems.
Discordant bioinformatic predictions of antimicrobial resistance from whole-genome sequencing data of bacterial isolates: an inter-laboratory study
Authors: Doyle Ronan M. , O'Sullivan Denise M. , Aller Sean D. , Bruchmann Sebastian , Clark Taane , Coello Pelegrin Andreu , Cormican Martin , Diez Benavente Ernest , Ellington Matthew J. , McGrath Elaine , Motro Yair , Phuong Thuy Nguyen Thi , Phelan Jody , Shaw Liam P. , Stabler Richard A. , van Belkum Alex , van Dorp Lucy , Woodford Neil , Moran-Gilad Jacob , Huggett Jim F. , Harris Kathryn A.
Published: February 2020

Antimicrobial resistance (AMR) poses a threat to public health. Clinical microbiology laboratories typically rely on culturing bacteria for antimicrobial-susceptibility testing (AST). As the implementation costs and technical barriers fall, whole-genome sequencing (WGS) has emerged as a ‘one-stop’ test for epidemiological and predictive AST results. Few published comparisons exist for the myriad analytical pipelines used for predicting AMR. To address this, we performed an inter-laboratory study providing sets of participating researchers with identical short-read WGS data from clinical isolates, allowing us to assess the reproducibility of the bioinformatic prediction of AMR between participants, and identify problem cases and factors that lead to discordant results. We produced ten WGS datasets of varying quality from cultured carbapenem-resistant organisms obtained from clinical samples sequenced on either an Illumina NextSeq or HiSeq instrument. Nine participating teams (‘participants’) were provided these sequence data without any other contextual information. Each participant used their choice of pipeline to determine the species, the presence of resistance-associated genes, and to predict susceptibility or resistance to amikacin, gentamicin, ciprofloxacin and cefotaxime. We found participants predicted different numbers of AMR-associated genes and different gene variants from the same clinical samples. The quality of the sequence data, choice of bioinformatic pipeline and interpretation of the results all contributed to discordance between participants. Although much of the inaccurate gene variant annotation did not affect genotypic resistance predictions, we observed low specificity when compared to phenotypic AST results, but this improved in samples with higher read depths. Had the results been used to predict AST and guide treatment, a different antibiotic would have been recommended for each isolate by at least one participant. These challenges, at the final analytical stage of using WGS to predict AMR, suggest the need for refinements when using this technology in clinical settings. Comprehensive public resistance sequence databases, full recommendations on sequence data quality and standardization in the comparisons between genotype and resistance phenotypes will all play a fundamental role in the successful implementation of AST prediction using WGS in clinical microbiology laboratories.
The insert sequence in SARS-CoV-2 enhances spike protein cleavage by TMPRSS
Authors: Meng Tong , Cao Hao , Zhang Hao , Kang Zijian , Xu Da , Gong Haiyi , Wang Jing , Li Zifu , Cui Xingang , Xu Huji , Wei Haifeng , Pan Xiuwu , Zhu Rongrong , Xiao Jianru , Zhou Wang , Cheng Liming , Liu Jianmin
Published: February 2020

At the end of 2019, the SARS-CoV-2 induces an ongoing outbreak of pneumonia in China1, even more spread than SARS-CoV infection2. The entry of SARS-CoV into host cells mainly depends on the cell receptor (ACE2) recognition and spike protein cleavage-induced cell membrane fusion3,4. The spike protein of SARS-CoV-2 also binds to ACE2 with a similar affinity, whereas its spike protein cleavage remains unclear5,6. Here we show that an insertion sequence in the spike protein of SARS-CoV-2 enhances the cleavage efficiency, and besides pulmonary alveoli, intestinal and esophagus epithelium were also the target tissues of SARS-CoV-2. Compared with SARS-CoV, we found a SPRR insertion in the S1/S2 protease cleavage sites of SARS-CoV-2 spike protein increasing the cleavage efficiency by the protein sequence aligment and furin score calculation. Additionally, the insertion sequence facilitates the formation of an extended loop which was more suitable for protease recognition by the homology modeling and molicular docking. Furthermore, the single-cell transcriptomes identified that ACE2 and TMPRSSs are highly coexpressed in AT2 cells of lung, along with esophageal upper epithelial cells and absorptive enterocytes. Our results provide the bioinformatics evidence for the increased spike protein cleavage of SARS-CoV-2 and indicate its potential target cells.
Classification of Indian States and Union Territories based on their Soil Macronutrient and Organic Carbon Profiles
Authors: Kaushik Prashant
Published: February 2020

Soil fertility determines the successful development of a plant, and therefore it is important to achieve food security. Imbalanced and inadequate use of chemical fertilizers, irregular irrigation and harmful cultural practices deplete the soil profile nutrient profile, which is critical for the successful crop production. This study presents the results of the classification of the states across India based on their soil macronutrient profile. The entanglement coefficient of Unweighted Pair Group Method with Arithmetic Mean (UPGMA) and the neighbour-joining method was 0.81. Absolute correlation values were determined among the different classes of the soil nitrogen content and the corresponding classes of the soil phosphorus content. The K-mean clustering method divided the states and union territories into the three clusters. Overall, this works represents the grouping of Indian soils based on their soil macronutrient and organic carbon content.
A Safe Harbor-Targeted CRISPR/Cas9 Homology Independent Targeted Integration (HITI) System for Multi-Modality Reporter Gene-Based Cell Tracking
Authors: Kelly John J , Saee-Marand Moe , Nyström Nivin N , Chen Yuanxin , Evans Melissa M , Hamilton Amanda M , Ronald John A
Published: February 2020

Imaging reporter genes can provide valuable, longitudinal information on the biodistribution, growth and survival of engineered cells in preclinical models and patients. A translational bottleneck to using reporter genes in patients is the necessity to engineer cells with randomly-integrating vectors. CRISPR/Cas9 targeted knock-in of reporter genes at a genomic safe harbor locus such as adeno-associated virus integration site 1 (AAVS1) may overcome these safety concerns. Here, we built Homology Independent Targeted Integration (HITI) CRISPR/Cas9 minicircle donors for precise AAVS1-targeted simultaneous knock-in of fluorescence, bioluminescence, and MRI (Oatp1a1) reporter genes. Our results showed greater knock-in efficiency at the AAVS1 site using HITI vectors compared to homology-directed repair donor vectors. Characterization of select HITI clones demonstrated functional fluorescence and bioluminescence reporter activity as well as significantly increased Oatp1a1-mediated uptake of the clinically-approved MRI agent gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid. As few as 106Oatp1a1-expressing cells in a 50 µl subcutaneous injection could be detectedin vivowith contrast-enhanced MRI. Contrast-enhanced MRI also improved the conspicuity of both sub-cutaneous and metastatic Oatp1a1-expressing tumours prior to them being palpable or even readily visible on pre-contrast images. Our work demonstrates the first CRISPR/Cas9 HITI system for knock-in of large DNA donor constructs at a safe harbor locus, enabling multi-modal longitudinalin vivoimaging of cells. This work lays the foundation for safer, non-viral reporter gene tracking of multiple cell types.