bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of Nasoseptal Cartilage Graft Versus Titanium Mesh in Reconstruction of Pure Orbital Blowout Fractures
Authors: Mangan Mehmet Serhat , Goker Ayse Enise , Yurttaser Ocak Serap , Uyar Yavuz
Published: February 2021

Purpose:

To compare the efficacy of nasoseptal cartilage grafts versus titanium mesh implants in pure orbital blowout fractures.

Methods:

A retrospective review was performed on 48 patients who had surgical repair of an orbital fracture. Patients who underwent pure orbital blowout fracture repair with either nasoseptal cartilage grafts or titanium mesh implants and at least 1 year postoperative follow-up were included in the study. The clinical features and treatment outcomes were analyzed.

Results:

Twenty-five patients fulfilled our study criteria and were included in the analyses. Nasoseptal graft was used in 12 patients (48%) while titanium mesh was preferred in 13 patients (52%). Preoperative clinical features including age, size of the floor defect, and preoperative clinical findings (enophthalmos, diplopia, and restriction of ocular motility) were similar between 2 groups. Mean postoperative follow-up was 14.7 ± 2.3 months in the nasoseptal group while it was 16.1 ± 2.5 months in the titanium group (P = 0.84). Diplopia and ocular motility limitation were resolved in all patients at the last postoperative follow-up visit, while 1 patient in each group had enophthalmos (8.3% versus 7.6%, P = 1.0). No patient in the nasoseptal group experienced postoperative complications while 2 patients in the titanium group (15.3%) developed material-related complications (P = 0.48).

Conclusions:

Long-term clinical results of nasoseptal cartilage grafts and titanium mesh implants in pure orbital blowout fractures with preoperative floor defects smaller than 4 cm2 were comparable. Nasoseptal cartilage grafts may be preferred in patients with septal deviation and no spurs or turbinate hypertrophy.
Identification of a Novel Mutation in the Runt-Related Transcription Factor 2 Gene in a Chinese Family With Cleidocranial Dysplasia
Authors: Zhao Wenquan , Ye Guanchen , Yu Xiaowen , Xu Ji , Li Zhiyong
Published: February 2021

Cleidocranial dysplasia (CCD) is an uncommon autosomal dominant disease, characterized by hypoplasia of clavicles, delayed fontanelle closure, dental anomalies, and short stature. It has been reported in the literature that the pathogenic variants of Runt-related transcription factor 2 (RUNX2) gene are correlated with CCD patients.

Here, we report a consanguineous Chinese family with 2 patients suffering from CCD, presenting similar skeleton and dentition malformation. Upon whole-exome sequencing, 52863 variants were detected in the propositus. Based on the genotype phenotype correlation, a frameshift deletion c.1554delG p.(Trp518Cysfs∗61), located in exon 8 of RUNX2, remained after filtration. For Sanger sequencing, all exons of the RUNX2 gene in members of this Chinese family were amplified by polymerase chain reaction. Mutation mentioned above was confirmed in the propositus and his mother, which has not been reported previously and cannot be found in the publicly available databases. The present study expands the pathogenic variant spectrum of RUNX2 gene and contributes to molecular diagnosis.
Randomized Controlled Clinical Trial to Assess the Utility of Computer-Aided Intraoperative Navigation in Bimaxillary Orthognathic Surgery
Authors: Chen Chen , Sun Ningning , Jiang Chunmiao , Sun Jian
Published: February 2021

Accurate application of the preoperative surgical plan in actual surgical settings is of paramount importance in orthognathic surgery. This randomized controlled clinical trial aimed to evaluate the accuracy of computer-aided intraoperative navigation (Ci-Navi) compared with that of conventional navigation methods in bimaxillary orthognathic surgery. Fifty-two patients were randomly divided into 2 groups. Group A (n = 26) patients underwent surgery assisted with Ci-Navi and group B (n = 26) patients underwent surgery assisted with conventional intraoperative navigation methods. During the operation, after LeFort I osteotomy, the mobile maxilla was repositioned to the designated position either using assistance from real-time Ci-Navi (group A) or using an intermediate splint (group B). Intra- and intergroup linear and angular differences between preoperative planning and postoperative outcomes were calculated. In group A, the overall mean linear difference was 0.79 mm (0.62 mm for the maxilla and 0.88 mm for the mandible) and the overall mean angular difference was 1.20°. In 23 cases, the difference from the upper incisor point to the Frankfort horizontal plane, midfacial sagittal plane, and coronal plane was less than 1 mm. In group B, the overall mean linear difference was 1.98 mm (1.76 mm for the maxilla and 2.02 mm for the mandible) and the overall mean angular difference was 2.08°. The difference from the upper incisor point to the Frankfort horizontal plane, midfacial sagittal plane, and coronal plane was less than 1 mm in 15 cases. This study demonstrates the utility of Ci-Navi is superior to the conventional methods in aiding the accurate repositioning of bony segments in bimaxillary orthognathic surgery.
Supernumerary Teeth and Dental Development
Authors: Duman Sacide , Vural Handan , Duman Suayip Burak
Published: February 2021

Purpose:

The aims of this study were to compare the radiographic development of permanent teeth in a group of children with and without supernumerary teeth (ST), determine whether using cone-beam computed tomography or panoramic radiography improves the accuracy of dental age (DA) estimation and investigate the effects of factors including the numbers and positions of ST.

Methods:

One hundred fifty dental radiographs of children with and without ST at the ages of 6.0 to 14.9 years were included in this study. The children in both groups were age and sex-matched. The lower left-side 7 permanent teeth were evaluated according to the Demirjian method, DA was determined. The difference between chronological age (CA) and DA (CA-DA) for the children with and without ST and further based on the number and localization of ST were calculated.

Results:

For all groups, the mean DA values were higher than the mean CA values. The difference between the CA and DA values in the children with ST was higher than the difference in the children without ST. Supernumerary teeth in posterior localization, multiple ST and among boys were observed to increase the differences between the mean CA and DA values. The mean age difference between radiographies in the children with and without ST was similar.

Conclusion:

Panoramic radiography was found adequate in determination of dental development with the Demirjian method. Dental development was even more advanced in the children with ST in comparison to the control group. Clinicians should keep in mind that the dental developments of children with supernumerary teeth may be advanced.
Intraparotid Osteolipoma: Treatment Option and Surgical View
Authors: Battaglia Salvatore , Crimi Salvatore , Nocini Riccardo , Cicciù Marco , Cervino Gabriele , Gurrera Alessandra , Bianchi Alberto
Published: February 2021

Osteolipoma is a benign neoplasm originating from the mesenchymal fat tissue cells and characterized by the presence of bone formation. In the head and neck district osteolipoma has been described as parapharyngeal, nasopharinx, submandibular gland, eyelid, floor of the mouth, and skull base lesion. Only 1 case of osteolipoma was reported as a neoplasm of the parotid region. Considering the rarity of the osteolipoma, our purpose was to describe the first case of totally intraparotid gland localization of osteolipoma and summarize and review the actual literature concerning the presence of this tumor in the region of major salivary glands. A 56-years-old male patient was treated for intraparotid osteolipoma. Surgical removal of tumor was done with a standard preauricular/cervical incision and blunt dissection. The facial nerve was identified and preserved completely. In the reviewed series, all cases were reported in adult patients with a relative long history of slow progression. According to our paper and the review of the literature, we can assess that Osteolipoma is an extremely rare lesion affecting the major salivary glands, which should be considered along with common salivary gland tumors in the differential diagnosis.
Hemodynamic Instability During Liver Transplantation in Patients With End-stage Liver Disease: A Consensus Document from ILTS, LICAGE, and SATA
Authors: Bezinover Dmitri , Mukhtar Ahmed , Wagener Gebhard , Wray Christopher , Blasi Annabel , Kronish Kate , Zerillo Jeron , Tomescu Dana , Pustavoitau Aliaksei , Gitman Marina , Singh Anil , Saner Fuat H.
Published: February 2021

Hemodynamic instability (HDI) during liver transplantation (LT) can be difficult to manage and increases postoperative morbidity and mortality. In addition to surgical causes of HDI, patient- and graft-related factors are also important. Nitric oxide–mediated vasodilatation is a common denominator associated with end-stage liver disease related to HDI. Despite intense investigation, optimal management strategies remain elusive.

In this consensus article, experts from the International Liver Transplantation Society, the Liver Intensive Care Group of Europe, and the Society for the Advancement of Transplant Anesthesia performed a rigorous review of the most current literature regarding the epidemiology, causes, and management of HDI during LT. Special attention has been paid to unique LT-associated conditions including the causes and management of vasoplegic syndrome, cardiomyopathies, LT-related arrhythmias, right and left ventricular dysfunction, and the specifics of medical and fluid management in end-stage liver disease as well as problems specifically related to portal circulation. When possible, management recommendations are made.
Choanoflagellates and the ancestry of neurosecretory vesicles
Authors: Göhde Ronja , Naumann Benjamin , Laundon Davis , Imig Cordelia , McDonald Kent , Cooper Benjamin H. , Varoqueaux Frédérique , Fasshauer Dirk , Burkhardt Pawel
Published: February 2021

Neurosecretory vesicles are highly specialized trafficking organelles that store neurotransmitters that are released at presynaptic nerve endings and are, therefore, important for animal cell–cell signalling. Despite considerable anatomical and functional diversity of neurons in animals, the protein composition of neurosecretory vesicles in bilaterians appears to be similar. This similarity points towards a common evolutionary origin. Moreover, many putative homologues of key neurosecretory vesicle proteins predate the origin of the first neurons, and some even the origin of the first animals. However, little is known about the molecular toolkit of these vesicles in non-bilaterian animals and their closest unicellular relatives, making inferences about the evolutionary origin of neurosecretory vesicles extremely difficult. By comparing 28 proteins of the core neurosecretory vesicle proteome in 13 different species, we demonstrate that most of the proteins are present in unicellular organisms. Surprisingly, we find that the vesicular membrane-associated soluble N-ethylmaleimide-sensitive factor attachment protein receptor protein synaptobrevin is localized to the vesicle-rich apical and basal pole in the choanoflagellateSalpingoeca rosetta.Our 3D vesicle reconstructions reveal that the choanoflagellatesS. rosettaandMonosiga brevicollisexhibit a polarized and diverse vesicular landscape reminiscent of the polarized organization of chemical synapses that secrete the content of neurosecretory vesicles into the synaptic cleft. This study sheds light on the ancestral molecular machinery of neurosecretory vesicles and provides a framework to understand the origin and evolution of secretory cells, synapses and neurons.

This article is part of the theme issue ‘Basal cognition: multicellularity, neurons and the cognitive lens’.
Evolutionary transitions in learning and cognition
Authors: Ginsburg Simona , Jablonka Eva
Published: February 2021

We define a cognitive system as a system that can learn, and adopt an evolutionary-transition-oriented framework for analysing different types of neural cognition. This enables us to classify types of cognition and point to the continuities and discontinuities among them. The framework we use for studying evolutionary transitions in learning capacities focuses on qualitative changes in the integration, storage and use of neurally processed information. Although there are always grey areas around evolutionary transitions, we recognize five major neural transitions, the first two of which involve animals at the base of the phylogenetic tree: (i) the evolutionary transition from learning in non-neural animals to learning in the first neural animals; (ii) the transition to animals showing limited, elemental associative learning, entailing neural centralization and primary brain differentiation; (iii) the transition to animals capable of unlimited associative learning, which, on our account, constitutes sentience and entails hierarchical brain organization and dedicated memory and value networks; (iv) the transition to imaginative animals that can plan and learn through selection among virtual events; and (v) the transition to human symbol-based cognition and cultural learning. The focus on learning provides a unifying framework for experimental and theoretical studies of cognition in the living world.

This article is part of the theme issue ‘Basal cognition: multicellularity, neurons and the cognitive lens’.
Elementary nervous systems
Authors: Arendt Detlev
Published: February 2021

The evolutionary origin of the nervous system has been a matter of long-standing debate. This is due to the different perspectives taken. Earlier studies addressed nervous system origins at the cellular level. They focused on the selective advantage of the first neuron in its local context, and considered vertical sensory-motor reflex arcs the first nervous system. Later studies emphasized the value of the nervous system at the tissue level. Rather than acting locally, early neurons were seen as part of an elementary nerve net that enabled the horizontal coordination of tissue movements. Opinions have also differed on the nature of effector cells. While most authors have favoured contractile systems, others see the key output of the incipient nervous system in the coordination of motile cilia, or the secretion of antimicrobial peptides. I will discuss these divergent views and explore how they can be validated by molecular and single-cell data. From this survey, possible consensus emerges: (i) the first manifestation of the nervous system likely was a nerve net, whereas specialized local circuits evolved later; (ii) different nerve nets may have evolved for the coordination of contractile or cilia-driven movements; (iii) all evolving nerve nets facilitated new forms of animal behaviour with increasing body size.

This article is part of the theme issue ‘Basal cognition: multicellularity, neurons and the cognitive lens’.
Uncovering cognitive similarities and differences, conservation and innovation
Authors: Levin Michael , Keijzer Fred , Lyon Pamela , Arendt Detlev
Published: February 2021

This article is part of the theme issue ‘Basal cognition: multicellularity, neurons and the cognitive lens'.
Arthrobacter terricola sp. nov., isolated from forest soil
Authors: Trinh Ngoc Hoang , Kim Jaisoo
Published: February 2021

A Gram-stain-positive, aerobic and rod-shaped bacterial strain, designated JH1-1T, was isolated from a forest soil sample collected in Suwon, Gyeonggi-do, Republic of Korea. Strain JH1-1T could grow at 10–35 °C (optimum, 28–30 °C), pH 4.5–8.5 and tolerated 5 % (w/v) NaCl. Strain JH1-1T was most closely related to members of the genus

Arthrobacter

, namely

Arthrobacter alkaliphilus

LC6T (98.5 % similarity),

Arthrobacter methylotrophus

TGAT (98.4 %),

Arthrobacter ramosus

CCM 1646T (97.8 %),

Arthrobacter bambusae

THG-GM18T (97.5 %) and

Arthrobacter pokkalii

P3B162T (97.3 %). The strain grew well on Reasoner's 2A agar, tryptone soya agar, nutrient agar, Mueller–Hinton agar and Luria–Bertani agar. The major polar lipid profile comprised phosphatidylglycerol, diphosphatidylglycerol, unidentified phospholipid and unidentified glycolipids. The major respiratory quinone was MK-9(H2). The main fatty acids were C15 : 0 anteiso, C15 : 0 iso, C16 : 0 iso and C17 :0 anteiso. The DNA G+C content of the isolated strain based on the whole genome sequence was 63.6 mol%. The average nucleotide identity and digital DNA–DNA hybridization values between strain JH1-1T and its reference type strains ranged from 81.3 to 85.4 % and from 21.1 to 29.1 %, respectively. Based on phenotypic, chemotypic and genotypic evidence, strain JH1-1T could be differentiated phylogenetically and phenotypically from the recognized species of the genus

Arthrobacter

. Therefore, strain JH1-1T is considered to represent a novel species, for which the name Arthrobacter terricola sp. nov. is proposed. The type strain is JH1-1T (=KACC 21385T=JCM 33641T).
Winogradskyella ouciana sp. nov., isolated from the hadal seawater of the Mariana Trench
Authors: He Xinxin , Liu Ronghua , Liang Jinchang , Li Yuying , Zhao Xiuxiu , Ran Lingman , Ahmad Waqar , Zhang Xiao-Hua
Published: February 2021

A Gram-staining-negative, strictly aerobic, long-rod shaped with no flagellum and yellow-pigmented bacterium designated strain ZXX205T, was isolated from the hadal seawater at the depth of 7500 m in the Mariana Trench, Pacific Ocean. Phylogenetic analysis based on 16S rRNA gene sequences placed strain ZXX205T within the genus

Winogradskyella

and strain ZXX205T was most closely related to

Winogradskyella flava

KCTC 52348T and

Winogradskyella echinorum

KCTC 22026T with 96.9 % and 96.6 % sequence similarity, respectively. The sequence similarities to all other type strains were 96.3 % or less, and to the type strain

Winogradskyella thalassocola

LMG 22492T was 94.1 %. Growth occurred in the presence of 0–9.0 % (w/v) NaCl (optimum 3.0 %), at 4–45 °C (optimum 28 °C) and pH 6.0–9.0 (optimum pH 7.5). The sole respiratory quinone was menaquinone 6 (MK-6). The dominant cellular fatty acids (>10 %) of strain ZXX205T were iso-C15 : 0, iso-C15 : 1 G, iso-C16 : 0 3-OH and iso-C16 : 0. The polar lipids profile contained predominantly phosphatidylethanolamine, four glycolipids, four unidentified aminolipids and three unidentified lipids. The genomic DNA G+C content was 35.5 %. The DNA–DNA relatedness (DDH) values between strain ZXX205T and the most closely related species

Winogradskyella flava

and

Winogradskyella echinorum

were 21.1 and 20.4 %, respectively. Based on polyphasic taxonomic analysis, strain ZXX205T is considered to represent a novel species in the genus

Winogradskyella

of the family

Flavobacteriaceae

, for which the name Winogradskyella ouciana is proposed. The type strain is ZXX205T (=MCCC 1K03851T=JCM 33665T).
Clostridium vitabionis sp. nov., isolated from the large intestine of a mini-pig
Authors: Shin Yeseul , Paek Jayoung , Kim Hongik , Kook Joong-Ki , Chang Young Hyo
Published: February 2021

An obligately anaerobic, Gram-stain-negative, spore-forming, short rod-shaped bacterium, designated strain YH- T4B42T, was isolated from the large intestine of a mini-pig. Phylogenetic analysis based on 16S rRNA gene sequences indicated that the isolate belongs to the genus

Clostridium

and is most closely related to

Clostridium aminophilum

KCTC 5424T,

Clostridium symbiosum

KCTC 15329T and

Clostridium butyricum

KCTC 1871T, with 95.5, 92.4 and 83.0 % sequence similarity, respectively. The average nucleotide identity values for strain YH-T4B42T and the closest related strains were lower than 72 %. The G+C content of the isolate was 55.8 mol%. The cell-wall peptidoglycan was A1γ type and contained meso-diaminopimelic acid. The predominant fatty acids were C16 : 0, C18 : 1
cis 9, C14 : 0 and C18 : 0. The major end products of glucose fermentation were lactate, formate and acetate, with a minor amount of butyrate. Based on its phenotypic, phylogenetic and chemotaxonomic properties, a novel species, Clostridium vitabionis sp. nov., is proposed for strain YH-T4B42T (=KCTC 25105T=NBRC 114767T).
PA-X is an avian virulence factor in H9N2 avian influenza virus
Authors: Clements Anabel L. , Peacock Thomas P. , Sealy Joshua E. , Lee Hui Min , Hussain Saira , Sadeyen Jean-Remy , Shelton Holly , Digard Paul , Iqbal Munir
Published: February 2021

Influenza A viruses encode several accessory proteins that have host- and strain-specific effects on virulence and replication. The accessory protein PA-X is expressed due to a ribosomal frameshift during translation of the PA gene. Depending on the particular combination of virus strain and host species, PA-X has been described as either acting to reduce or increase virulence and/or virus replication. In this study, we set out to investigate the role PA-X plays in H9N2 avian influenza viruses, focusing on the natural avian host, chickens. We found that the G1 lineage A/chicken/Pakistan/UDL-01/2008 (H9N2) PA-X induced robust host shutoff in both mammalian and avian cells and increased virus replication in mammalian, but not avian cells. We further showed that PA-X affected embryonic lethality in ovo and led to more rapid viral shedding and widespread organ dissemination in vivo in chickens. Overall, we conclude PA-X may act as a virulence factor for H9N2 viruses in chickens, allowing faster replication and wider organ tropism.
Genetic Contributions to Alcohol Use Disorder Treatment Outcomes: A Genome-wide Pharmacogenomics Study
Authors: Biernacka J.M. , Coombes B.J. , Batzler A. , Geske J.R. , Ho A.M. , Frank J. , Hodgkinson C. , Skime M. , Colby C. , Zillich L. , Pozsonyiova S. , Ho M-F. , Kiefer F. , Rietschel M. , Weinshilboum R. , O’Malley S.S. , Mann K. , Anton R. , Goldman D. , Karpyak V.M.
Published: February 2021

Naltrexone can aid in reducing alcohol consumption, while acamprosate supports abstinence; however, not all patients with alcohol use disorder (AUD) benefit from these treatments. Here we present the first genome-wide association study of AUD treatment outcomes based on data from the COMBINE and PREDICT studies of acamprosate and naltrexone, and the Mayo Clinic CITA study of acamprosate. Primary analyses focused on treatment outcomes regardless of pharmacological intervention and were followed by drug-stratified analyses to identify treatment-specific pharmacogenomic predictors of acamprosate and naltrexone response. Treatment outcomes were defined as: (1) time until relapse to any drinking (TR) and (2) time until relapse to heavy drinking (THR; ≥5 drinks for men, ≥4 drinks for women in a day), during the first three months of treatment. Analyses were performed within each dataset, followed by meta-analysis across the studies (N=1090 European ancestry participants). Single nucleotide polymorphisms (SNPs) in the BRE gene were associated with THR (min p=1.6E-08) in the entire sample, while two intergenic SNPs were associated with medication-specific outcomes (naltrexone THR: rs12749274, p=3.9E-08; acamprosate TR: rs77583603, p=3.1E-09). The top association signals for TR (p=7.7E-08) and second strongest signal in the THR (p=6.1E-08) analysis of the naltrexone-treated subset map to PTPRD, a gene previously implicated in addiction phenotypes in human and animal studies. Leave-one-out polygenic risk score analyses showed significant associations with TR (p=3.7E-04) and THR (p=2.6E-04). This study provides the first evidence of a polygenic effect on AUD treatment response, and identifies genetic variants associated with potentially medication-specific effects on AUD treatment response.
Dental biofilm microbiota dysbiosis is associated with the risk of acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation
Authors: Heidrich Vitor , Bruno Julia S. , Knebel Franciele H. , de Molla Vinícius C. , Miranda-Silva Wanessa , Asprino Paula F. , Tucunduva Luciana , Rocha Vanderson , Novis Yana , Arrais-Rodrigues Celso , Fregnani Eduardo R. , Camargo Anamaria A.
Published: February 2021

Acute graft-versus-host disease (aGVHD) is one of the major causes of death after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Recently, aGVHD onset was linked to intestinal microbiota (IM) dysbiosis. However, other bacterial-rich gastrointestinal sites, such as the mouth, which hosts several distinctive microbiotas, may also impact the risk of GVHD. The dental biofilm microbiota (DBM) is highly diverse and, like the IM, interacts with host cells and modulates immune homeostasis. We characterized changes in the DBM of patients during allo-HSCT and evaluated whether the DBM could be associated with the risk of aGVHD. DBM dysbiosis during allo-HSCT was marked by a gradual loss of bacterial diversity and changes in DBM genera composition, with commensal genera reductions and potentially pathogenic bacteria overgrowths. High Streptococcus and high Corynebacterium relative abundance at preconditioning were associated with a higher risk of aGVHD (67% vs. 33%; HR = 2.89, P = 0.04 and 73% vs. 37%; HR = 2.74, P = 0.04, respectively), while high Veillonella relative abundance was associated with a lower risk of aGVHD (27% vs. 73%; HR = 0.24, P < 0.01). Enterococcus faecalis bloom during allo-HSCT was observed in 20% of allo-HSCT recipients and was associated with a higher risk of aGVHD (100% vs. 40%; HR = 4.07, P < 0.001) and severe aGVHD (60% vs. 12%; HR = 6.82, P = 0.01). To the best of our knowledge, this is the first study demonstrating that DBM dysbiosis is associated with the aGVHD risk after allo-HSCT.
Skin cancer high-risk patient screening from dermoscopic images via Artificial Intelligence: an online study
Authors: Coronado-Gutiérrez David , López Carlos , Burgos-Artizzu Xavier P.
Published: February 2021

Objectives

To evaluate a novel Artificial Intelligence (AI) method for the detection of malignant skin lesions from dermoscopic images.

Methods

58,457 dermoscopic images available online from the International Skin Imaging Collaboration (ISIC) Archive were downloaded. These images were acquired from different centers worldwide by recognized dermatologists and show varied clinical outcomes belonging to different types of benign and malign skin lesions. A state-of-the-art AI skin lesion classifier based on Deep Learning was designed. The method, fully automated, first locates and segments the nevus in the image and then classifies it into either benign or malign type.

Results

1,631 images (2.8%) were discarded due to bad quality. A total of 56,826 images were finally used. Two thirds of the images (37,688) were used to train the classifier, leaving the remaining 19,138 images for validation. In this set, malignant lesions had a prevalence of 15.4% (2,956/19,138). The AI skin lesion classifier reached an area under the curve (AUC) of 87.4%. Optimal cut-off point in terms of accuracy resulted in an 85.9% accuracy (16,439/19,138) and sensibility of 89.6% (2,648/ 2,956) at 85.2% (13,791/16,182) specificity. Negative predictive value (NPV) was 97.8% (13,791/14,099). Other training/validation splits were also evaluated, showing similar results.

Conclusions

A novel AI method showed promising results as skin lesion classifier from dermoscopic images. Its high NPV value could make it suited for high-risk patient screening. A large clinical study to confirm these results is needed and will be pursued.
Evolution and emergence of multidrug-resistant Mycobacterium tuberculosis in Chisinau, Moldova
Authors: Brown Tyler S. , Eldholm Vegard , Brynildsrud Ola , Osnes Magnus , Stennis Natalie , Stimson James , Colijn Caroline , Alexandru Sofia , Noroc Ecaterina , Ciobanu Nelly , Crudu Valeriu , Cohen Ted , Mathema Barun
Published: February 2021

1.

Background

Drug-resistant tuberculosis is a high priority threat to global public health. There are still critical gaps in understanding how novel drug-resistant M. tuberculosis strains emerge and, once emergent, what drives the differential propagation of certain epidemiologically-successful strains over others. This study sought to describe the joint evolutionary and epidemiological histories of a novel multidrug-resistant M. tuberculosis strain recently identified in the capital city of the Republic of Moldova (MDR Ural/4.2).

Methods

Using whole genome sequence data and Bayesian phylogenomic methods, we reconstruct the stepwise acquisition of drug-resistance mutations in the MDR Ural/4.2 strain, estimate its historical bacterial population size over time, and infer the migration history of this strain between Eastern European countries.

Results

We infer that MDR Ural/4.2 likely evolved (via acquisition of rpoB S450L, which confers resistance to rifampin) in the early 1990s, during a period of social turmoil following Moldovan independence from the Soviet Union. This strain subsequently underwent substantial population size expansion in the early 2000s, at a time when national guidelines encouraged in hospital treatment of TB patients. We infer exportation of this strain and its INH-resistant ancestral precursor from Moldova to neighboring countries starting as early as 1985.

Conclusions

Our findings underscore how public health practice and social determinants of health shape the conditions under which M. tuberculosis evolves, and demonstrates how historical changes in these conditions shape present-day challenges in TB control. These findings underscore the need for regional coordination in TB control across Eastern Europe.
Development of the NeuroFlow Severity Score and Comparison With Validated Measures for Depression and Anxiety
Authors: Lynch William , Platt Michael L. , Pardes Adam
Published: February 2021

Purpose

Although depression and anxiety are the leading causes of disability in the United States, respectively, fewer than half of people diagnosed with these conditions receive appropriate treatment, and fewer than 10% receive measurement-based care (MBC), which is defined as behavioral health care based on and adapted in response to patient outcomes data collected throughout treatment. The NeuroFlow platform was developed with the goal of making MBC easier to deliver and more accessible within integrated behavioral health care. Data from over 3,000 users of the NeuroFlow platform were used to develop the NeuroFlow Severity Score (NFSS), a potential new measure for depression and anxiety. To begin evaluating the potential usefulness of this new measure, NFSSs were compared with validated measures for depression and anxiety, the Personal Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) scale, and clinician assessment.

Methods

The NFSS platform is used to record patient-reported and passively collected data related to behavioral health. An artificial-intelligence derived algorithm was developed that condenses this large number of measurements into a single score for longitudinal tracking of an individual’s depression and anxiety symptoms. Linear regression and Bland-Altman analyses were used to evaluate relationships and differences between NFSS and PHQ-9 or GAD-7 scores from over 35,000 NeuroFlow users. The NFSS was also compared to assessment by a panel of expert clinicians for a subset of 250 individuals.

Results

Linear regression results showed a strong correlation between NFSS and PHQ-9 (r=.74, P<.001) and GAD-7 (r=.80, P<.001) changes. There was also a strong positive correlation between the NFSS and expert panel clinical assessment (r=.80-.84, P<.001). Bland-Altman analysis and evaluation of outliers on regression analysis, however, show that the NFSS has significant differences from the PHQ-9.

Conclusions

Clinicians can reliably use the NFSS as a proxy measure for monitoring symptoms of depression and anxiety longitudinally. The NFSS may identify at-risk individuals who are not identified by the PHQ-9. Further research is warranted to evaluate the sensitivity and specificity of the NFSS.
Enhancing Food Security for Families Vulnerable to COVID-19
Authors: Fabusuyi Tayo , Misra Aditi , Martinez Jonatan , Chen Andong , Jiang Vivian , Jagadish H. V. , Hampshire Robert C.
Published: February 2021

The COVID-19 pandemic has exposed some of the underlying inequities in our society. Vulnerable and low-income communities who have typically struggled with food insecurity have been further impacted by the COVID-19 pandemic. To make matters worse, transit dependent households in the City of Detroit that rely on SNAP benefits from the government have a 54% probability of not having internet access, reducing the possibility of online food delivery. Thus, the motivation for the Detroit Food Delivery Pilot Program, a prepared meal delivery service for food insecure households during the COVID-19 pandemic. Through this program, the City had aided 350 households; over 1,000 unique individuals and has served over 90,000 meals. This had all been made possible through the engagement of 575 volunteers, volunteering over 6,850 delivery miles. Our team helped to identify the magnitude and the needs of the City’s food insecure population; then partnered with the City of Detroit to modify existing food programs to address the crisis, and finally, assessed the impact of the program on the target population. Our analysis revealed that approximately 20,800 households will be classified as food insecure in Detroit and only a fraction of this population is benefitting from the food delivery pilot program. However, on average, the concerns about food sufficiency have abated appreciably from the surveys analyzed. Responses from the beneficiaries of the food delivery pilot program were positive though concerns about the travel behavior of individuals, particularly those from COVID-19 positive households remain.
Creating virtual H&E images using samples imaged on a commercial CODEX platform
Authors: Simonson Paul D. , Ren Xiaobing , Fromm Jonathan R.
Published: February 2021

Multiparametric fluorescence imaging via CODEX allows the simultaneous imaging of many biomarkers in a single tissue section. While the digital fluorescence data thus obtained can provide highly specific characterizations of individual cells and microenvironments, the images obtained are different from those usually interpreted by pathologists (i.e., H&E slides and DAB-stained immunohistochemistry slides). Having the fluorescence data plus co-registered H&E or similar data could facilitate adoption of multiparametric imaging into regular workflows, as well as facilitate the transfer of algorithms and machine learning previous developed around H&E slides. Since commercial CODEX instruments do not produce H&E-like images by themselves, we developed a staining protocol and associated image processing to make “virtual H&E” images that can be incorporated into the CODEX workflow. While there are many ways to achieve virtual H&E images, including use of a fluorescent nuclear stain and tissue autofluorescence to simulate eosin staining, we opted to combine fluorescent nuclear staining (via DAPI) with actual eosin staining. We also output images derived from fluorescent nuclear staining and autofluorescence images for additional evaluation.
Modeling the Effect of Population-Wide Vaccination on the Evolution of COVID-19 Epidemic in Canada
Authors: Berkane Soulaimane , Harizi Intissar , Tayebi Abdelhamid
Published: February 2021

Population-wide vaccination is critical for containing the COVID-19 pandemic when combined with effective testing and prevention measures. Since the beginning of the COVID-19 outbreak, several companies worked tirelessly for the development of an efficient vaccine that would put an end to this pandemic. Today, a number of COVID-19 vaccines have been approved for use by a number of national regulatory organizations. Vaccination campaigns have already started in several countries with different daily-vaccination rates depending on the country’s vaccination capacity. Therefore, we find it timely and extremely important to conduct a study on the effect of population-wide vaccination campaigns on the evolution of the COVID-19 epidemic. To this end, we propose a new deterministic mathematical model to forecast the COVID-19 epidemic evolution under the effect of vaccination and vaccine efficacy. This model, referred to as SIRV, consists of a compartmental SIR (susceptible, infectious and removed) model augmented with an additional state V representing the effectively vaccinated population as well as two inputs representing the daily-vaccination rate and the vaccine efficacy. Using our SIRV model, we predict the evolution of the COVID-19 epidemic in Canada and its most affected provinces (Ontario, Quebec, British Columbia, Alberta, Saskatchewan, and Manitoba), for different daily vaccination rates and vaccine efficacy. Projections suggest that, without vaccination, 219, 000 lives could be lost across Canada by the end of 2021 due to COVID-19. The ongoing vaccination campaign across Canada seems to unfold relatively slowly at an average daily rate close to 1/2 vaccine per 1, 000 population. At this pace, we could be saving more than 77, 496 lives by the end of the year. Doubling the current vaccination efforts (1 vaccine per day per 1, 000 population) could be sufficient to save 125, 839 lives in Canada during the current year 2021. We would like to point out that our study assumes that the vaccine is perfectly safe without any short or long term side-effects. This study has been conducted independently at arm’s length from vaccine manufacturers, using the available data from Canada health services. This study can be easily adapted to other places in the world.
The fragility index in randomised controlled trials of interventions for aneurysmal subarachnoid haemorrhage: a systematic review
Authors: Ramesh Aravind V , Munby Henry N P , Thomas Matt
Published: February 2021

Background

Fragility analysis supplements the p-value and risk of bias assessment in the interpretation of results of randomised controlled trials. In this systematic review we determine the fragility index (FI) and fragility quotient (FQ) of randomized trials in aneurysmal subarachnoid haemorrhage.

Methods

This is a systematic review registered with PROSPERO (ID: CRD42020173604). Randomised controlled trials in adults with aneurysmal subarachnoid haemorrhage were analysed if they reported a statistically significant primary outcome of mortality, function (e.g. modified Rankin Scale), vasospasm or delayed neurological deterioration.

Results

We identified 3809 records with 17 randomized trials selected for analysis. The median fragility index was 3 (inter-quartile range 0-5) and the median fragility quotient was 0.012 (IQR 0-0.034). Six of nineteen trial outcomes (31.6%) had an fragility index of 0. In seven trials (36.8%), the number of participants lost to follow-up was greater than or equal to the fragility index. Only 17.6% of trials are at low risk of bias.

Conclusions

Randomised controlled trial evidence supporting management of aneurysmal subarachnoid haemorrhage is weaker than indicated by conventional analysis using p-values alone. Increased use of fragility analysis by clinicians and researchers could improve the translation of evidence to practice.
Short-term functional outcome in psychotic patients. Results of the Turku Early Psychosis Study (TEPS)
Authors: Salokangas Raimo K. R. , From Tiina , Ilonen Tuula , Luutonen Sinikka , Heinimaa Markus , Armio Reetta-Liina , Laurikainen Heikki , Walta Maija , Paju Janina , Toivonen Anna , Jalo Päivi , Tuominen Lauri , Hietala Jarmo ,   the TEPS group
Published: February 2021

Background

Functional recovery of patients with clinical and sub-clinical psychosis is associated with clinical, neuropsychological and developmental factors. Less is known how these factors predict functional outcome in same models.

Aim

We investigated functional outcome and its predictors in patients with first-episode psychosis (FEP) or confirmed vs. non-confirmed clinical high risk to psychosis (CHR-P vs. CHR-N).

Methods

Altogether, 130 FEP, 60 CHR-P and 47 CHR-N patients were recruited and extensively examined at baseline (T0) and at 9 (T1) and 18 (T2) months after baseline. Global Assessment of Functioning (GAF) at T0, T1 and T2, and psychotic, depression and anxiety symptoms at T1 and T2 were assessed. Functional outcome was predicted in multivariate repeated ANOVA.

Results

During follow-up, GAF improved significantly in FEP and CHR-P but not in CHR-N patients. In FEP, single marital status, low basic education, poor work situation, disorganised symptoms, perceptual deficits and poor premorbid adjustment, in CHR-P, disorganised symptoms and poor premorbid adjustment and in CHR-N, low basic education, poor work situation and general symptoms predicted poor functional outcome. In FEP, psychotic symptoms at T1 and in CHR-P, psychotic and depression symptoms at T1 and anxiety symptoms at T2 associated with poor functioning.

Discussion

In FEP and CHR-P patients, poor premorbid adjustment and disorganised symptomatology are common predictors for functional outcome, while poor education and work situation predict poor functional outcome in FEP and CHR-N patients. Interventions aimed to improve studying and ability to work are most important in improving functioning of patients with clinical or subclinical psychosis.
Maximum likelihood perimetric progression analysis: Using raw (trial-by-trial) response data to estimate progression more robustly
Authors: Jones Pete R.
Published: February 2021

Purpose

To describe and demonstrate a more efficient (Maximum Likelihood) method for quantifying visual field progression.

Design

Monte Carlo simulation.

Methods

Trial-by-trial response data were simulated using a stochastic psychometric model (a “simulated observer”). Simulated Differential Light Sensitivity (DLS) decreased between tests to mimic long-term visual field progression. Progression slopes were fitted, either by fitting a regression slope to independent DLS estimates from each test (conventional method), or by fitting all the raw data combined in a single model (proposed maximum likelihood method).

Results

The proposed ML method seldom performed worse than a conventional, regression-based approach, and often performed better. For an idealized observer with a lapse (false negative) rate of 0 and a guess (false positive) rate of 0, both methods were equally precise. However, as lapse rate increased, the ML method exhibited less random measurement error. For small numbers of trials this increase in precision translated to a negative progression slope being detected with 95% confidence at least one year/assessment sooner. The only time the ML method was observed to perform worse was when very few trials (N = 4) were combined with very high lapse rates (λ = 0.3): an unlikely but not inconceivable scenario.

Conclusions

Combining raw, trial-by-trial response data in a single ML model can provide a more robust estimate of visual field progression than conventional methods (e.g., linear regression), at no additional cost to the patient or clinician (i.e., no additional trials).
Behavioral Responses to Risk Promote Vaccinating High-contact Individuals First
Authors: Rahmandad Hazhir
Published: February 2021

If COVID-19’s reproduction number was constant, vaccinating elderly first minimized deaths. However, incorporating risk-driven behavior/policy changes enhances fit to data and prioritizes vaccinating high-contact individuals. Deaths grow exponentially until people are compelled to reduce contacts, stabilizing at levels obliging higher-contact groups to sufficiently cut interactions. Vaccinating those groups out of transmission saves lives and speeds everybody’s return to normal life.
Disentangling the effects of climate change, landscape heterogeneity, and scale on phenological metrics
Authors: Newman Erica A. , Breckheimer Ian K. , Park Daniel S.
Published: February 2021

Phenology, the study of the timing of cyclical life history events and seasonal changes, is a fundamental aspect of how individual species, communities, and ecosystems will respond to climate change. Both biotic and abiotic phenological patterns are changing rapidly in response to changing seasonal temperatures and other climate-related drivers, and the consequences of these shifts for individual species and entire ecosystems are largely unknown. Landscape-scale simulations can address some of these needs for better predictions by demonstrating how phenology measures can vary with spatial and temporal grain of observations, and how phenological responses can vary with landscape heterogeneity and climate drivers. To explicitly examine the spatial and temporal scale-dependence of multiple phenology measures, we constructed simulated landscapes populated by virtual plant species with realistic phenologies and environmental sensitivities. This enabled us to examine phenology measures and environmental sensitivities along a continuum of spatial and temporal grains, while also controlling other aspects of sampling design. By relating measures of phenology calculated at a given spatiotemporal grain to average environmental conditions at that same grain size, we are able to determine observed environmental sensitivities for multiple phenological metrics at that spatial and temporal scale. We demonstrate that different phenological events change distinctly and predictably with spatial and temporal measurement scale, opening the way to incorporating scaling laws into predictions. Using plant flowering as our example, we identify that the timing of the beginnings or ends of an event (e.g., First Flower date, Last Flower date), can be especially sensitive to the spatial and temporal grain (or resolution) of observations. Our work provides an initial assessment of the role of observation scale in landscape phenology, and a general approach for incorporating scale-dependence into predictions of a variety of phenological time series.
Reducing the efforts to create reproducible analysis code with FieldTrip
Authors: van Es Mats W.J. , Spaak Eelke , Schoffelen Jan-Mathijs , Oostenveld Robert
Published: February 2021

The analysis of EEG and MEG data typically requires a lengthy and complicated sequence of analysis steps, often requiring large amounts of computations, which are ideally represented in analysis scripts. These scripts are often written by researchers without formal training in computer science, resulting in the quality and readability of these analysis scripts to be highly dependent on individual coding expertise and style. Even though the computational outcomes and interpretation of the results can be correct, the inconsistent style and quality of analysis scripts make reviewing the details of the analysis difficult for other researchers that are either involved in the study or not, and the quality of the scripts might compromise the reproducibility of obtained results. This paper describes the design and implementation of a strategy that allows complete reproduction of MATLAB-based scripts with little extra efforts on behalf of the user, which we have implemented as part of the FieldTrip toolbox. Starting from the researchers’ idiosyncratic pipeline scripts, this new functionality allows researchers to automatically create and publish analysis pipeline scripts in a standardized format, along with all relevant intermediate data. We demonstrate the functionality and validate its effectiveness by applying it to the analysis of a recently published MEG study.