bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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.
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.

Summary
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.

Summary
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.

Summary
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 reviewNearly 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 findingsLong-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.SummaryAlthough 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.

Summary
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.

Summary
Developing, implementing, scaling and sustaining school-based interventions is a necessity of our field if we want to move closer to sustainable development goals.
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

AbstractAt 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

AbstractSoil 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

AbstractImaging 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.