Individualized multi-omic pathway deviation scores using multiple factor analysis.

Malignant progression of normal tissue is typically driven by complex networks of somatic changes, including genetic mutations, copy number aberrations, epigenetic changes, and transcriptional reprogramming. To delineate aberrant multi-omic tumor features that correlate with clinical outcomes, we present a novel pathway-centric tool based on the multiple factor analysis framework called padma. Using a multi-omic consensus representation, padma quantifies and characterizes individualized pathway-specific multi-omic deviations and their underlying drivers, with respect to the sampled population. We demonstrate the utility of padma to correlate patient outcomes with complex genetic, epigenetic, and transcriptomic perturbations in clinically actionable pathways in breast and lung cancer.

The impact of passive alveolar molding vs. nasoalveolar molding on cleft width and other parameters of maxillary growth in unilateral cleft lip palate.

OBJECTIVE: Passive alveolar molding (PAM) and nasoalveolar molding (NAM) are established presurgical infant orthodontic (PSIO) therapies for cleft lip palate (CLP) patients. PAM guides maxillary growth with a modified Hotz appliance, while NAM also uses extraoral taping and includes nasal stents. The effects of these techniques on alveolar arch growth have rarely been compared. MATERIAL AND METHODS: We retrospectively compared 3D-scanned maxillary models obtained before and after PSIO from infants with unilateral, non-syndromic CLP treated with PAM (n = 16) versus NAM (n = 13). Nine anatomical points were set digitally by four raters and transversal/sagittal distances and rotations of the maxilla were measured. RESULTS: Both appliances reduced the anterior cleft, but NAM percentage wise more. NAM decreased the anterior and medial transversal width compared to PAM, which led to no change. With both appliances, the posterior width increased. The alveolar arch length of the great and small segments and the sagittal length of the maxilla increased with PAM but only partially with NAM. However, NAM induced a significant greater medial rotation of the larger and smaller segment compared to PAM with respect to the lateral angle. CONCLUSIONS: NAM and PAM presented some significant differences regarding maxillary growth. While NAM reduced the anterior cleft and effectively rotated the segments medially, PAM allowed more transversal and sagittal growth. CLINICAL RELEVANCE: The results of this study should be taken into consideration when to decide whether to use PAM or NAM, since they show a different outcome within the first few months. Further studies are necessary regarding long-term differences.

Impact of dental restorations and removable prostheses on potentially malignant oral mucosal disorders in the general population.

STATEMENT OF PROBLEM: Dental restorations and removable dental prostheses have been considered as risk factors for potentially malignant disorders of the oral mucosa. It remains unclear whether amalgam, composite resins, and prosthesis materials can induce potentially malignant disorders. PURPOSE: The purpose of this clinical study was to determine the relationship between the presence of amalgam and composite resin restorations, crowns and fixed partial dentures, and removable prostheses in potentially malignant disorders. MATERIAL AND METHODS: The data of 6041 participants in the population-based Studies of Health in Pomerania (SHIP) were accessed. Potentially malignant disorders had been clinically diagnosed by calibrated dentists and documented with photographs. Dental treatment was subdivided into restored and replaced teeth. Dental restorations were subclassified as buccal composite resin or amalgam restorations. Prosthetic treatment was subclassified into removable partial or complete prostheses and definitive restorations with crowns and fixed partial dentures. RESULTS: In the maxilla, participants with removable prostheses had a higher incidence of potentially malignant disorders than participants not undergoing treatment with removable prostheses (OR 2.12; 95% CI: 1.08-4.18), but not in the mandible (OR 1.30; 95% CI: 0.67-2.53). The surfaces with composite resin restorations were associated with a slightly higher risk of mucosal lesions than those without the restorations (OR 1.04; 95% CI: 1.01-1.07). No significant association was found between amalgam restorations and mucosal lesions. CONCLUSIONS: Participants with removable prostheses have a higher risk of potentially malignant disorders. Composite resin restorations are associated with a higher risk of mucosal lesions, whereas no significant association was found between amalgam restorations and mucosal lesions.

Accounting for overlapping annotations in genomic prediction models of complex traits.

BACKGROUND: It is now widespread in livestock and plant breeding to use genotyping data to predict phenotypes with genomic prediction models. In parallel, genomic annotations related to a variety of traits are increasing in number and granularity, providing valuable insight into potentially important positions in the genome. The BayesRC model integrates this prior biological information by factorizing the genome according to disjoint annotation categories, in some cases enabling improved prediction of heritable traits. However, BayesRC is not adapted to cases where markers may have multiple annotations. RESULTS: We propose two novel Bayesian approaches to account for multi-annotated markers through a cumulative (BayesRC+) or preferential (BayesRC[Formula: see text]) model of the contribution of multiple annotation categories. We illustrate their performance on simulated data with various genetic architectures and types of annotations. We also explore their use on data from a backcross population of growing pigs in conjunction with annotations constructed using the PigQTLdb. In both simulated and real data, we observed a modest improvement in prediction quality with our models when used with informative annotations. In addition, our results show that BayesRC+ successfully prioritizes multi-annotated markers according to their posterior variance, while BayesRC[Formula: see text] provides a useful interpretation of informative annotations for multi-annotated markers. Finally, we explore several strategies for constructing annotations from a public database, highlighting the importance of careful consideration of this step. CONCLUSION: When used with annotations that are relevant to the trait under study, BayesRC[Formula: see text] and BayesRC+ allow for improved prediction and prioritization of multi-annotated markers, and can provide useful biological insight into the genetic architecture of traits.

Mendelian randomization analysis with survival outcomes.

Mendelian randomization (MR) is an established approach for assessing the causal effects of heritable exposures on outcomes. Outcomes of interest often include binary clinical endpoints, but may also include censored survival times. We explore the implications of both the Cox proportional hazard model and the additive hazard model in the context of MR, with a specific emphasis on two-stage methods. We show that naive application of standard MR approaches to censored survival times may induce significant bias. Through simulations and analysis of data from the Women's Health Initiative, we provide practical advice on modeling survival outcomes in MRs.

A unified linear mixed model for familial relatedness and population structure in genetic association studies.

Familial relatedness (FR) and population structure (PS) are two major sources for genetic correlation. In the human population, both FR and PS can further break down into additive and dominant components to account for potential additive and dominant genetic effects. In this study, besides the classical additive genomic relationship matrix, a dominant genomic relationship matrix is introduced. A link between the additive/dominant genomic relationship matrices and the coancestry (or kinship)/double coancestry coefficients is also established. In addition, a way to separate the FR and PS correlations based on the estimates of coancestry and double coancestry coefficients from the genomic relationship matrices is proposed. A unified linear mixed model is also developed, which can account for both the additive and dominance effects of FR and PS correlations as well as their possible random interactions. Finally, this unified linear mixed model is applied to analyze two study cohorts from UK Biobank.

Potential genetic robustness of Prnp and Sprn double knockout mouse embryos towards ShRNA-lentiviral inoculation.

The Shadoo and PrP prion protein family members are thought to be functionally related, but previous knockdown/knockout experiments in early mouse embryogenesis have provided seemingly contradictory results. In particular, Shadoo was found to be indispensable in the absence of PrP in knockdown analyses, but a double-knockout of the two had little phenotypic impact. We investigated this apparent discrepancy by comparing transcriptomes of WT, Prnp0/0 and Prnp0/0Sprn0/0 E6.5 mouse embryos following inoculation by Sprn- or Prnp-ShRNA lentiviral vectors. Our results suggest the possibility of genetic adaptation in Prnp0/0Sprn0/0 mice, thus providing a potential explanation for their previously observed resilience.

Differences in caecal microbiota composition and Salmonella carriage between experimentally infected inbred lines of chickens.

BACKGROUND: Salmonella Enteritidis (SE) is one of the major causes of human foodborne intoxication resulting from consumption of contaminated poultry products. Genetic selection of animals that are more resistant to Salmonella carriage and modulation of the gut microbiota are two promising ways to decrease individual Salmonella carriage. The aims of this study were to identify the main genetic and microbial factors that control the level of Salmonella carriage in chickens (Gallus gallus) under controlled experimental conditions. Two-hundred and forty animals from the White Leghorn inbred lines N and 61 were infected by SE at 7 days of age. After infection, animals were kept in isolators to reduce recontamination of birds by Salmonella. Caecal contents were sampled at 12 days post-infection and used for DNA extraction. Microbiota DNA was used to measure individual counts of SE by digital PCR and to determine the bacterial taxonomic composition, using a 16S rRNA gene high-throughput sequencing approach. RESULTS: Our results confirmed that the N line is more resistant to Salmonella carriage than the 61 line, and that intra-line variability is higher for the 61 line. Furthermore, the 16S analysis showed strong significant differences in microbiota taxonomic composition between the two lines. Among the 617 operational taxonomic units (OTU) observed, more than 390 were differentially abundant between the two lines. Furthermore, within the 61 line, we found a difference in the microbiota taxonomic composition between the high and low Salmonella carriers, with 39 differentially abundant OTU. Using metagenome functional prediction based on 16S data, several metabolic pathways that are potentially associated to microbiota taxonomic differences (e.g. short chain fatty acids pathways) were identified between high and low carriers. CONCLUSIONS: Overall, our findings demonstrate that the caecal microbiota composition differs between genetic lines of chickens. This could be one of the reasons why the investigated lines differed in Salmonella carriage levels under experimental infection conditions.

Prevalence of SARS-CoV-2 IgG antibodies among dental teams in Germany.

OBJECTIVES: During the corona pandemic, dental practices temporarily closed their doors to patients except for emergency treatments. Due to the daily occupational exposure, the risk of SARS-CoV-2 transmission among dentists and their team is presumed to be higher than that in the general population. This study examined this issue among dental teams across Germany. MATERIALS AND METHODS: In total, 2784 participants provided usable questionnaires and dry blood samples. Dry blood samples were used to detect IgG antibodies against SARS-CoV-2. The questionnaires were analyzed to investigate demographic data and working conditions during the pandemic. Multivariable logistic mixed-effects models were applied. RESULTS: We observed 146 participants with positive SARS-CoV-2 IgG antibodies (5.2%) and 30 subjects with a borderline finding (1.1%). Seventy-four out of the 146 participants with SARS-CoV-2 IgG antibodies did not report a positive SARS-CoV-2 PCR test (50.7%), while 27 participants without SARS-CoV-2 IgG antibodies reported a positive SARS-CoV-2 PCR test (1.1%). Combining the laboratory and self-reported information, the number of participants with a SARS-CoV-2 infection was 179 (6.5%). Though after adjustment for region, mixed-effects models indicated associations of use of rubber dams (OR 1.65; 95% CI: 1.01-2.72) and the number of protective measures (OR 1.16; 95% CI: 1.01-1.34) with increased risk for positive SARS-CoV-2 status, none of those variables was significantly associated with a SARS-CoV-2 status in fully adjusted models. CONCLUSIONS: The risk of SARS-CoV-2 transmission was not higher among the dental team compared to the general population. CLINICAL RELEVANCE: Following hygienic regulations and infection control measures ensures the safety of the dental team and their patients.

COVID-19 pandemic and its impact on dental education: digitalization - progress or regress? Example of an online hands-on course.

BACKGROUND: Due to the SARS-CoV-2 pandemic and the accompanying contact restrictions, a new challenge arose for dental education. Despite the limited overall situation, it must be ensured that, in addition to theoretical content, practical skills in particular continue to be taught. Therefore, the aim of this study was to develop and implement an online hands-on course for dental students that ensures practical training, even during the pandemic. METHODS: The newly developed course was held from April 2020 to March 2021. A total of six groups (each consisting of approximately 40-50 students) took part in the course. The participating students were in their 3rd, 4th or 5th year of study. The course taught theoretical basics (via an online platform) and promoted the learning of practical/surgical techniques on models such as bananas, pork bellies, or chicken thighs with live demonstrations (via ZOOM) and interactive post-preparation by students at home (and in a rotating small group of 3-7 students on site). Student self-evaluation (at the beginning and end of the course) and course evaluation were performed using questionnaires. The learning success was analyzed (through self-evaluations) using Wilcoxon signed-rank tests (significance level alpha = 0.05). RESULTS: Concerning students´ self-evaluations, the theoretical knowledge, general surgical skills (such as surgical instrument handling), and specific surgical skills (such as performing a kite flap) improved during the course, with significant results (p < 0.001 for each). About 60% of the students rated the course overall as excellent (grades 9 or 10 on a Likert scale of 1 to 10). The technical implementation of the course was rated with a median of 9 (= very good, on a Likert scale of 1 to 10). 38.5% described the applicability of the skills learned for their later professional life as extremely good. CONCLUSIONS: The results of this work suggest that, within the limitations of this study, the introduced concept of an online hands-on course could be an appropriate form of teaching practical dental skills, even during a pandemic. Further research is needed in the field of digital education for dental students.

A Retrospective Analysis of Postoperative Abscess Formation Following Wisdom Tooth Removal and Their Clinical Condition and Localization.

AIM: As a common procedure in oral surgery, the removal of wisdom teeth (3M) is associated with a variety of postoperative complications. This study reports of deep tissue abscesses after the removal of 3M in correlation to several factors. MATERIALS AND METHODS: Patients between 2012 and 2017 with removed 3M were retrospectively evaluated in terms of clinical condition and localization and thus assigned tog A (removal of asymptomatic 3M) or group B (removal of symptomatic 3M). Moreover, they were analyzed in terms of abscesses after the removal and correlation with various parameters: localization of the abscess, general diseases, perioperative antibiotic treatment, number of days from removal of the tooth to abscess formation, and postoperative complications after primary abscess incision. RESULTS: About 82 patients (male n = 44, female n = 38) were included, with 88 wisdom teeth removed and postoperative abscesses. Postoperative abscesses occurred more frequently in group B (n = 53) with n = 29 in IIB localization, without a significant correlation. Patients in this group were older, and there were more surgical abscess incisions needed, despite a longer treatment with oral and intravenous antibiosis that correlated with neurologic diseases and age. Younger patients reported significantly more pain. CONCLUSIONS: Detection of potential 3M pathologies at an early and asymptomatic stage is essential to avoid postoperative complications following 3M removal. Additional prospective studies are necessary to develop corresponding guidelines. CLINICAL SIGNIFICANCE: Wisdom tooth extraction is the most common operation in oral surgery, and therefore, adequate risk evaluation is still required.

NAM-help or burden? Intercultural evaluation of parental stress caused by nasoalveolar molding: a retrospective multi-center study.

OBJECTIVES: Nasoalveolar molding (NAM) was developed to facilitate easier treatment and better outcomes for cleft lip and palate (CLP) patients. The aim of this study was to investigate the parental burden and possible intercultural differences of this treatment modality, which is often argued to burden parents to an extraordinary amount. MATERIALS AND METHODS: Standardized questionnaires (available in English, Mandarin, and German) with 15 non-specific and 14 NAM-specific items to be retrospectively answered by Likert scales by parents of unilateral CLP patients with completed NAM treatment. RESULTS: The parents of 117 patients from two treatment centers in Taiwan and Germany were included. A very high level of overall satisfaction was found in both countries with significant intercultural differences in prenatal parent information, feeding problems, dealing with 3rd party's perception, and experienced personal effort. CONCLUSION: NAM is an effective treatment tool for children's CLP deformities and their caregivers in overcoming the feeling of helplessness. Intercultural differences may be due to infrastructural reasons, cultural attitudes and habits, or different public medical education. CLINICAL RELEVANCE: In addition to facilitating easier surgical treatment, NAM can be seen as a powerful coping strategy for parents dealing with a CLP deformity of their child and does not seem to burden them extraordinarily.

Hypervirulent Klebsiella pneumoniae Sequence Type 420 with a Chromosomally Inserted Virulence Plasmid.

BACKGROUND: Klebsiella pneumoniae causes severe diseases including sepsis, pneumonia and wound infections and is differentiated into hypervirulent (hvKp) and classic (cKp) pathotypes. hvKp isolates are characterized clinically by invasive and multiple site infection and phenotypically in particular through hypermucoviscosity and increased siderophore production, enabled by the presence of the respective virulence genes, which are partly carried on plasmids. METHODS: Here, we analyzed two K. pneumoniae isolates of a human patient that caused severe multiple site infection. By applying both genomic and phenotypic experiments and combining basic science with clinical approaches, we aimed at characterizing the clinical background as well as the two isolates in-depth. This also included bioinformatics analysis of a chromosomal virulence plasmid integration event. RESULTS: Our genomic analysis revealed that the two isolates were clonal and belonged to sequence type 420, which is not only the first description of this K. pneumoniae subtype in Germany but also suggests belonging to the hvKp pathotype. The latter was supported by the clinical appearance and our phenotypic findings revealing increased siderophore production and hypermucoviscosity similar to an archetypical, hypervirulent K. pneumoniae strain. In addition, our in-depth bioinformatics analysis suggested the insertion of a hypervirulence plasmid in the bacterial chromosome, mediated by a new IS5 family sub-group IS903 insertion sequence designated ISKpn74. CONCLUSION: Our study contributes not only to the understanding of hvKp and the association between hypervirulence and clinical outcomes but reveals the chromosomal integration of a virulence plasmid, which might lead to tremendous public health implications.

A prospective comparative study to assess the risk of postoperative bleeding after dental surgery while on medication with direct oral anticoagulants, antiplatelet agents, or vitamin K antagonists.

BACKGROUND: The aim of this prospective study was to investigate the occurrence and severity of postoperative bleeding following dentoalveolar surgery in patients with uninterrupted anticoagulation therapy (AT). METHODS: Patients receiving AT (vitamin k antagonist (VK), direct oral anticoagulants (DOAC) or antiplatelet therapy (APT) and in need of surgical intervention classified as A, B or C (single or serial tooth extraction, osteotomy, or implant placement) were studied between 2019 and 2021. A healthy, non-anticoagulated cohort (CG) served as a control group. The main outcomes measured were the frequency of postoperative bleeding, the classification of the severity of postoperative bleeding (1a, 1b, 1c, 2, 3), and the correlation with the AT surgical intervention classification. RESULTS: In total, 195 patients were included in the study, with 95 patients in the AT group and 100 in the CG. Postoperative bleeding was significant in the AT group vs. the CG (p = 0.000), with a significant correlation with surgical intervention class C (p = 0.013) and the severity class of bleeding 1a (p = 0.044). There was no significant correlation with procedures of type A, B or C for the other postoperative bleeding gradations (1b, 1c, 2 and 3). There was a statistically significant difference in the occurrence of postoperative bleeding events between the DOAC/APT group and the VK group (p = 0.036), but there were no significant differences regarding the other AT agents. CONCLUSION: The continuation of anticoagulation therapy for surgical interventions also seems reasonable for high-risk interventions. Although significantly more postoperative bleeding occurs, the severity of bleeding is low. The perioperative management of anticoagulated patients requires well-coordinated interdisciplinary teamwork and detailed instruction of patients. Clinical trial registration The study is registered (29.03.2021) at the German clinical trial registry (DRKS00024889).

Management of anticoagulated patients in dentoalveolar surgery: a retrospective study comparing bridging with heparin versus unpaused vitamin K antagonist medication.

BACKGROUND: The aim of this study was to investigate the occurrence of postoperative bleeding following dentoalveolar surgery in patients with either continued vitamin K antagonist medication or perioperative bridging using heparin. METHODS: A retrospective study was performed analyzing patients who underwent tooth extraction between 2012 and 2017. Patients were retrospectively allocated into two comparative groups: un-paused vitamin K antagonist medication versus bridging using heparin. A healthy, non-anticoagulated cohort with equivalent surgery served as a control group. Main outcome measures were: the occurrence and frequency of postoperative bleeding, the number of removed teeth, the surgical technique of tooth removal (extraction/osteotomy/combined extraction and osteotomy) and the prothrombin time. RESULTS: In total, 475 patients were included in the study with 170 patients in the group of un-paused vitamin K antagonist medication VG, 135 patients in the Bridging group BG and 170 patients in the control group CG. Postoperative bleeding was significant: CG versus VG p = 0.004; CG versus BG p < 0.001, BG versus VG p < 0.001. A significant correlation of number of the extracted teeth in the BG (p = 0.014) and no significance in VG (p = 0.298) and CG (p = 0.210) and in the BG versus VG and CG with p < 0.001 in terms of surgical intervention extraction. No difference observed in terms of prothrombin time. CONCLUSIONS: Bridging with heparin increases the risk for bleeding compared to un-paused vitamin K antagonist medication. The perioperative management of anticoagulated patients requires a well-coordinated interdisciplinary teamwork to minimize or at best avoid both: postoperative bleeding and thromboembolic incidences.

Transformation and model choice for RNA-seq co-expression analysis.

Although a large number of clustering algorithms have been proposed to identify groups of co-expressed genes from microarray data, the question of if and how such methods may be applied to RNA sequencing (RNA-seq) data remains unaddressed. In this work, we investigate the use of data transformations in conjunction with Gaussian mixture models for RNA-seq co-expression analyses, as well as a penalized model selection criterion to select both an appropriate transformation and number of clusters present in the data. This approach has the advantage of accounting for per-cluster correlation structures among samples, which can be strong in RNA-seq data. In addition, it provides a rigorous statistical framework for parameter estimation, an objective assessment of data transformations and number of clusters and the possibility of performing diagnostic checks on the quality and homogeneity of the identified clusters. We analyze four varied RNA-seq data sets to illustrate the use of transformations and model selection in conjunction with Gaussian mixture models. Finally, we propose a Bioconductor package coseq (co-expression of RNA-seq data) to facilitate implementation and visualization of the recommended RNA-seq co-expression analyses.

Synthetic data sets for the identification of key ingredients for RNA-seq differential analysis.

Numerous statistical pipelines are now available for the differential analysis of gene expression measured with RNA-sequencing technology. Most of them are based on similar statistical frameworks after normalization, differing primarily in the choice of data distribution, mean and variance estimation strategy and data filtering. We propose an evaluation of the impact of these choices when few biological replicates are available through the use of synthetic data sets. This framework is based on real data sets and allows the exploration of various scenarios differing in the proportion of non-differentially expressed genes. Hence, it provides an evaluation of the key ingredients of the differential analysis, free of the biases associated with the simulation of data using parametric models. Our results show the relevance of a proper modeling of the mean by using linear or generalized linear modeling. Once the mean is properly modeled, the impact of the other parameters on the performance of the test is much less important. Finally, we propose to use the simple visualization of the raw P-value histogram as a practical evaluation criterion of the performance of differential analysis methods on real data sets.

Exploring drivers of gene expression in the Cancer Genome Atlas.

Motivation: The Cancer Genome Atlas (TCGA) has greatly advanced cancer research by generating, curating and publicly releasing deeply measured molecular data from thousands of tumor samples. In particular, gene expression measures, both within and across cancer types, have been used to determine the genes and proteins that are active in tumor cells. Results: To more thoroughly investigate the behavior of gene expression in TCGA tumor samples, we introduce a statistical framework for partitioning the variation in gene expression due to a variety of molecular variables including somatic mutations, transcription factors (TFs), microRNAs, copy number alternations, methylation and germ-line genetic variation. As proof-of-principle, we identify and validate specific TFs that influence the expression of PTPN14 in breast cancer cells. Availability and implementation: We provide a freely available, user-friendly, browseable interactive web-based application for exploring the results of our transcriptome-wide analyses across 17 different cancers in TCGA at http://ls-shiny-prod.uwm.edu/edge_in_tcga. All TCGA Open Access tier data are available at the Broad Institute GDAC Firehose and were downloaded using the TCGA2STAT R package. TCGA Controlled Access tier data are available via controlled access through the Genomic Data Commons (GDC). R scripts used to download, format and analyze the data and produce the interactive R/Shiny web app have been made available on GitHub at https://github.com/andreamrau/EDGE-in-TCGA.

Multi-species annotation of transcriptome and chromatin structure in domesticated animals.

BACKGROUND: Comparative genomics studies are central in identifying the coding and non-coding elements associated with complex traits, and the functional annotation of genomes is a critical step to decipher the genotype-to-phenotype relationships in livestock animals. As part of the Functional Annotation of Animal Genomes (FAANG) action, the FR-AgENCODE project aimed to create reference functional maps of domesticated animals by profiling the landscape of transcription (RNA-seq), chromatin accessibility (ATAC-seq) and conformation (Hi-C) in species representing ruminants (cattle, goat), monogastrics (pig) and birds (chicken), using three target samples related to metabolism (liver) and immunity (CD4+ and CD8+ T cells). RESULTS: RNA-seq assays considerably extended the available catalog of annotated transcripts and identified differentially expressed genes with unknown function, including new syntenic lncRNAs. ATAC-seq highlighted an enrichment for transcription factor binding sites in differentially accessible regions of the chromatin. Comparative analyses revealed a core set of conserved regulatory regions across species. Topologically associating domains (TADs) and epigenetic A/B compartments annotated from Hi-C data were consistent with RNA-seq and ATAC-seq data. Multi-species comparisons showed that conserved TAD boundaries had stronger insulation properties than species-specific ones and that the genomic distribution of orthologous genes in A/B compartments was significantly conserved across species. CONCLUSIONS: We report the first multi-species and multi-assay genome annotation results obtained by a FAANG project. Beyond the generation of reference annotations and the confirmation of previous findings on model animals, the integrative analysis of data from multiple assays and species sheds a new light on the multi-scale selective pressure shaping genome organization from birds to mammals. Overall, these results emphasize the value of FAANG for research on domesticated animals and reinforces the importance of future meta-analyses of the reference datasets being generated by this community on different species.

Development of a template tool for facilitating fibula osteotomy in reconstruction of mandibular defects by digital analysis of the human mandible.

OBJECTIVES: Mandibular reconstruction after segmental mandibulectomy can be challenging without virtual surgical planning and osteotomy guides. The purpose of this study was to analyze anatomic parameters to facilitate the evaluation of ideal fibula wedge osteotomies to reconstruct the neomandibula in a simple and cost-effective manner without the need for preoperative virtual planning. MATERIALS AND METHODS: Computed tomography scans were acquired from randomly selected patients, and all images were obtained from routine clinical diagnostics, e.g., tumor staging, or preoperatively before reconstruction. Data was used to calculate stereolithographic models of the mandible for length and angle measurements. Statistical analysis was performed (p < 0.05). RESULTS: CT scans of 100 patients were analyzed: 39 were female and 61 were male patients, mean age was 59.08a. The mandibular arch angle proved to be constant with 241.07 ± 2.39°. The outside B-segment length was 80.05 ± 5.16 mm; the anterior S-segment length was 27.69 ± 3.16 mm. The angle of the mandibular arch showed differences in means (p = 0.004) between age groups, but effect was proved low. No relevant statistical significances were detected. CONCLUSIONS: The development of a mandible reconstruction template tool would benefit the majority of head and neck patients, which is due to a constant mandibular arch angle and symphysis segment length throughout the general patient population, allowing the mimicking of a harmonic mandibular arch with up to three fibula segments. CLINICAL RELEVANCE: The developed mandible reconstruction template tool can facilitate the fibula wedge osteotomies necessary for reconstruction of an ideal neomandibula providing a novel approach which is simple and cost-effective.