Machine and Deep Learning Methods for Predicting 3D Genome Organization.

Three-dimensional (3D) chromatin interactions, such as enhancer-promoter interactions (EPIs), loops, topologically associating domains (TADs), and A/B compartments, play critical roles in a wide range of cellular processes by regulating gene expression. Recent development of chromatin conformation capture technologies has enabled genome-wide profiling of various 3D structures, even with single cells. However, current catalogs of 3D structures remain incomplete and unreliable due to differences in technology, tools, and low data resolution. Machine learning methods have emerged as an alternative to obtain missing 3D interactions and/or improve resolution. Such methods frequently use genome annotation data (ChIP-seq, DNAse-seq, etc.), DNA sequencing information (k-mers and transcription factor binding site (TFBS) motifs), and other genomic properties to learn the associations between genomic features and chromatin interactions. In this review, we discuss computational tools for predicting three types of 3D interactions (EPIs, chromatin interactions, and TAD boundaries) and analyze their pros and cons. We also point out obstacles to the computational prediction of 3D interactions and suggest future research directions.

A Comparison of Two Versions of the CRISPR-Sirius System for the Live-Cell Visualization of the Borders of Topologically Associating Domains.

In recent years, various technologies have emerged for the imaging of chromatin loci in living cells via catalytically inactive Cas9 (dCas9). These technologies facilitate a deeper understanding of the mechanisms behind the chromatin dynamics and provide valuable kinetic data that could not have previously been obtained via FISH applied to fixed cells. However, such technologies are relatively complicated, as they involve the expression of several chimeric proteins as well as sgRNAs targeting the visualized loci, a process that entails many technical subtleties. Therefore, the effectiveness in visualizing a specific target locus may be quite low. In this study, we directly compared two versions of a previously published CRISPR-Sirius method based on the use of sgRNAs containing eight MS2 or PP7 stem loops and the expression of MCP or PCP fused to fluorescent proteins. We assessed the visualization efficiency for several unique genomic loci by comparing the two approaches in delivering sgRNA genes (transient transfection and lentiviral transduction), as well as two CRISPR-Sirius versions (with PCP and with MCP). The efficiency of visualization varied among the loci, and not all loci could be visualized. However, the MCP-sfGFP version provided more efficient visualization in terms of the number of cells with signals than PCP-sfGFP for all tested loci. We also showed that lentiviral transduction was more efficient in locus imaging than transient transfection for both CRISPR-Sirius systems. Most of the target loci in our study were located at the borders of topologically associating domains, and we defined a set of TAD borders that could be effectively visualized using the MCP-sfGFP version of the CRISPR-Sirius system. Altogether, our study validates the use of the CRISPR-Sirius technology for live-cell visualization and highlights various technical details that should be considered when using this method.

Deciphering the Mutilation: Skillful Orthodontic Treatment Using Temporary Anchorage Devices and Asymmetric Extractions for a Patient With a Knife-Edge Ridge.

One of the biggest challenges in orthodontic management of adult patients is the presence of mutilated dentition, which is characterized by severe tooth loss and subsequent tipping of adjacent teeth or extruding of antagonists, worsening the malocclusion. As they offer a solid anchor for intricate tooth movement, temporary anchorage devices (TADs) have proven invaluable to orthodontic treatment. In this case study, we highlight the importance of TADs in getting the best possible treatment outcomes while describing the effective management of a patient with mutilated dentition. TADs made it possible to control tooth movement precisely, restoring esthetics and functional occlusion. This case report emphasizes the value of TADs in contemporary orthodontic practice and shows their potential for correcting mutilated dentition.

What is the impact of patient attributes, implant characteristics, surgical techniques, and placement location on the success of orthodontic mini-implants in young adults? A Systematic Review and Meta-Analysis.

Background: Temporary anchorage devices (TADs) address challenges in traditional orthodontic anchorage like patient compliance and precision, showing significantly improved clinical outcomes, particularly for cases requiring maximum anchorage. Materials and Methods: A systematic electronic search was performed in five research databases, focusing on studies published between 2015 and 2023. The ROBINS-I tool from the Cochrane Bias Methods Group assessed the risk of bias. Data analysis included categorical and numerical variables, with categorical variables analyzed using Cohen's method in a random effects model to account for variability. Sensitivity and heterogeneity were evaluated using a 'leave-one-out' approach and the I 2 statistic, respectively. At the same time, publication bias was checked using Egger's test, with findings presented through Forest and Funnel plots. Numerical variables were subjected to weighted regression analysis. Results: Examination of 15 studies involving 1981 patients and 3272 orthodontic mini-implants identified key factors affecting implant stability. Failure rates varied significantly, influenced by factors such as the characteristics and insertion site of the orthodontic mini-implants (OMIs), patient-specific variables, and operator experience. Notably, the insertion site and implant characteristics like size did not significantly affect failure rates, but there was a negative correlation between the magnitude of force applied and failure rates. Conclusion: The success of orthodontic mini-implants is broadly consistent across patient demographics and is not significantly impacted by gender or age, though failure rates were higher in males and when implants were placed in the maxilla. These findings suggest that higher applied forces might reduce failure rates. Clinical Significance: This review underlines mini-implant efficacy across varied patient demographics, emphasizing the importance of site selection, jaw location, and force application in enhancing success rates and guiding tailored treatment strategies.PROSPERO ID CRD42023411955.

Transboundary viral diseases of pigs, poultry and ruminants in Southeast Asia: a systematic review.

Livestock is a strategic part of the small-farm economy in Southeast Asia's society, providing food income, clothing, fertilizer, and draught power. However, incidences or outbreaks of transboundary animal diseases (TADs) are due to converging factors such as the natural hazards' aftermath, climate change, deforestation, urban growth, changing production conditions, and market chains. Therefore, this affects productivity and impacts farmers' livelihoods with small holdings. The literature review was carried out to understand the current situation of TADs in Southeast Asia, identifying knowledge gaps to provide actions for disease control and prevention in the region. We have attempted to summarise the scientific literature in English on the prevalence data of TADs in Southeast Asia between 2011 and March 2022. Relatively few studies evaluated the distribution of TAD, where most of the studies focused on diseases that are important for international trade, such as avian influenza (AI), African swine fever (ASF), classical swine fever (CSF), foot-and-mouth disease (FMD) and Newcastle disease (ND). Traditional production systems have received little attention in such studies as they belonged to mainly smallholders. The outbreaks of ASF and lumpy skin disease (LSD) in 2019 resulted in increased research activity between 2019-2022, while the other TADs were ignored in this period. For new emerging TADs diseases such as ASF and LSD, there is only information about the first detection without prevalence information. Therefore, further epidemiological investigations are necessary to reduce the gaps in disease surveillance reporting systems and support the prevention and reduction of further outbreaks.

Stem-loop and circle-loop TADs generated by directional pairing of boundary elements have distinct physical and regulatory properties.

The chromosomes in multicellular eukaryotes are organized into a series of topologically independent loops called TADs. In flies, TADs are formed by physical interactions between neighboring boundaries. Fly boundaries exhibit distinct partner preferences, and pairing interactions between boundaries are typically orientation-dependent. Pairing can be head-to-tail or head-to-head. The former generates a stem-loop TAD, while the latter gives a circle-loop TAD. The TAD that encompasses the Drosophila even skipped (eve) gene is formed by the head-to-tail pairing of the nhomie and homie boundaries. To explore the relationship between loop topology and the physical and regulatory landscape, we flanked the nhomie boundary region with two attP sites. The attP sites were then used to generate four boundary replacements: λ DNA, nhomie forward (WT orientation), nhomie reverse (opposite of WT orientation), and homie forward (same orientation as WT homie). The nhomie forward replacement restores the WT physical and regulatory landscape: in MicroC experiments, the eve TAD is a 'volcano' triangle topped by a plume, and the eve gene and its regulatory elements are sequestered from interactions with neighbors. The λ DNA replacement lacks boundary function: the endpoint of the 'new' eve TAD on the nhomie side is ill-defined, and eve stripe enhancers activate a nearby gene, eIF3j. While nhomie reverse and homie forward restore the eve TAD, the topology is a circle-loop, and this changes the local physical and regulatory landscape. In MicroC experiments, the eve TAD interacts with its neighbors, and the plume at the top of the eve triangle peak is converted to a pair of 'clouds' of contacts with the next-door TADs. Consistent with the loss of isolation afforded by the stem-loop topology, the eve enhancers weakly activate genes in the neighboring TADs. Conversely, eve function is partially disrupted.

Chromosome structure in Drosophila is determined by boundary pairing not loop extrusion.

Two different models have been proposed to explain how the endpoints of chromatin looped domains ('TADs') in eukaryotic chromosomes are determined. In the first, a cohesin complex extrudes a loop until it encounters a boundary element roadblock, generating a stem-loop. In this model, boundaries are functionally autonomous: they have an intrinsic ability to halt the movement of incoming cohesin complexes that is independent of the properties of neighboring boundaries. In the second, loops are generated by boundary:boundary pairing. In this model, boundaries are functionally non-autonomous, and their ability to form a loop depends upon how well they match with their neighbors. Moreover, unlike the loop-extrusion model, pairing interactions can generate both stem-loops and circle-loops. We have used a combination of MicroC to analyze how TADs are organized, and experimental manipulations of the even skipped TAD boundary, homie, to test the predictions of the 'loop-extrusion' and the 'boundary-pairing' models. Our findings are incompatible with the loop-extrusion model, and instead suggest that the endpoints of TADs in flies are determined by a mechanism in which boundary elements physically pair with their partners, either head-to-head or head-to-tail, with varying degrees of specificity. Although our experiments do not address how partners find each other, the mechanism is unlikely to require loop extrusion.

Unraveling the three-dimensional (3D) genome architecture in Neurodevelopmental Disorders (NDDs).

The human genome, comprising millions of pairs of bases, serves as the blueprint of life, encoding instructions for cellular processes. However, genomes are not merely linear sequences; rather, the complex of DNA and histones, known as chromatin, exhibits complex organization across various levels, which profoundly influence gene expression and cellular function. Central to understanding genome organization is the emerging field of three-dimensional (3D) genome studies. Utilizing advanced techniques such as Hi-C, researchers have unveiled non-random dispositions of genomic elements, highlighting their importance in transcriptional regulation and disease mechanisms. Topologically Associating Domains (TADs), that demarcate regions of chromatin with preferential internal interactions, play crucial roles in gene regulation and are increasingly implicated in various diseases such as cancer and schizophrenia. However, their role in Neurodevelopmental Disorders (NDDs) remains poorly understood. Here, we focus on TADs and 3D conservation across the evolution and between cell types in NDDs. The investigation into genome organization and its impact on disease has led to significant breakthroughs in understanding NDDs etiology such ASD (Autism Spectrum Disorder). By elucidating the wide spectrum of ASD manifestations, researchers aim to uncover the underlying genetic and epigenetic factors contributing to its heterogeneity. Moreover, studies linking TAD disruption to NDDs underscore the importance of spatial genome organization in maintaining proper brain development and function. In summary, this review highlights the intricate interplay between genome organization, transcriptional control, and disease pathology, shedding light on fundamental biological processes and offering insights into the mechanisms underlying NDDs like ASD.

Stratifying TAD boundaries pinpoints focal genomic regions of regulation, damage, and repair.

Advances in chromatin mapping have exposed the complex chromatin hierarchical organization in mammals, including topologically associating domains (TADs) and their substructures, yet the functional implications of this hierarchy in gene regulation and disease progression are not fully elucidated. Our study delves into the phenomenon of shared TAD boundaries, which are pivotal in maintaining the hierarchical chromatin structure and regulating gene activity. By integrating high-resolution Hi-C data, chromatin accessibility, and DNA double-strand breaks (DSBs) data from various cell lines, we systematically explore the complex regulatory landscape at high-level TAD boundaries. Our findings indicate that these boundaries are not only key architectural elements but also vibrant hubs, enriched with functionally crucial genes and complex transcription factor binding site-clustered regions. Moreover, they exhibit a pronounced enrichment of DSBs, suggesting a nuanced interplay between transcriptional regulation and genomic stability. Our research provides novel insights into the intricate relationship between the 3D genome structure, gene regulation, and DNA repair mechanisms, highlighting the role of shared TAD boundaries in maintaining genomic integrity and resilience against perturbations. The implications of our findings extend to understanding the complexities of genomic diseases and open new avenues for therapeutic interventions targeting the structural and functional integrity of TAD boundaries.

Evaluation of the Co-Go-Me angle as a predictor in Class II patients treated with Herbst appliance and skeletal anchorage: a retrospective cohort study.

Introduction: A condylion-gonion-menton (Co-Go-Me) angle threshold of 125.5° has been introduced as a predictive parameter of cephalometric mandibular response in the orthopedic treatment of growing Class II patients with functional appliances, despite some contradictions in the literature. Considering the lack of studies evaluating the role of skeletal anchorage, this study aims to reassess the threshold of 125.5° in the Co-Go-Me angle as a useful predictor in growing skeletal Class II patients treated with acrylic splint Herbst appliance and two mini-screws in the lower arch (STM2). Methods: Thirty-five consecutively treated patients (20 males, 15 females; mean age, 11.37 years) with mandibular retrusion were classified into two groups according to their Co-Go-Me baseline values (Group 1, <125.5°; Group 2, >125.5°). The STM2 protocol involved the use of the MTH Herbst appliance with an acrylic splint in the lower arch and two interradicular mini-screws as anchorage reinforcement. Cephalometric analysis was performed by the same operator for each patient at baseline (T0) and at the end of the Herbst phase (T1). The effects of time and group on the variables were assessed by a repeated-measures analysis of variance. The primary research outcome was the difference between the groups in terms of mandibular responsiveness to treatment referred to as the relative difference (T1-T0) in Co_Gn. Results: The mean duration of the treatment was 9.5 months. No statistically significant differences between groups were detected at baseline, except from the expected SN/GoMe° (p < 0.001) and Co-Go mm (p = 0.028). No statistically significant changes between groups, which were caused by the treatment, were found considering the mandibular sagittal and vertical skeletal parameters. Similarly, no statistically significant differences were found in the dental changes between the high-angle and low-angle patients, apart from the upper molar sagittal position (p = 0.013). Discussion and conclusions: The 125.5° threshold in the Co-Go-Me value was not a reliable predictive parameter for the mandibular response in growing patients treated with the MTH Herbst appliance and lower skeletal anchorage. Due to its effective control in the sagittal and vertical planes, the STM2 technique might be an appropriate protocol to use in treating skeletal Class II patients, regardless of the growth pattern.

Mini-Screw-Assisted Orthodontic Retraction of Class I Malocclusion in a Bimaxillary Protrusion Patient Using Sliding Mechanics: A Case Report.

A condition known as bimaxillary protrusion occurs when the front teeth protrude due to the forward positioning of the lower and upper jaws. Temporary anchorage devices (TADs) are utilized to provide anchorage and facilitate the controlled retraction of maxillary and mandibular protruding teeth, helping to correct the patient's bite and facial aesthetics. A 27-year-old female with bimaxillary protrusion reported to the Department of Orthodontics. On examination, the facial profile of the patient was convex. The clinical FMA was high. With a deep mentolabial sulcus and an acute nasolabial angle, lips were potentially competent. An intraoral examination revealed proclined incisors with spacing in the maxillary arch and proclined anterior teeth in the mandibular arch. Space closure was done using sliding mechanics with direct anchorage from a mini-screw after the extraction of all four first premolars. There was a significant improvement in the patient's profile posttreatment.

Three-Dimensional Evaluation of Treatment Effects and Post-Treatment Stability of Maxillary Molar Intrusion Using Temporary Anchorage Devices in Open Bite Malocclusion.

Background: We investigated treatment outcomes and post-treatment stability in 10 patients with an anterior open bite and nonsurgical orthodontics. Methods: The patients underwent maxillary molar intrusion using temporary anchorage devices (TADs) to deepen the overbite due to mandibular autorotation. Lateral cephalograms and dental cast models were obtained before treatment (T0), immediately after it (T1), and >1 year after it (T2). Skeletal and dental cephalometric changes and three-dimensional movements of the maxillary dentitions were evaluated. Results: At T0, cephalometric analysis indicated that patients had skeletal class I with tendencies for a class II jaw relationship and a skeletal open bite. During active treatment (T0 to T1), the maxillary first molar intruded by 1.6 mm, the mandibular first molar extruded by 0.3 mm, the Frankfort-mandibular plane angle decreased by 1.1°, and the overbite increased by 4.1 mm. Statistically significant changes were observed in the amount of vertical movement of the maxillary first molar, Frankfort-mandibular plane angle, and overbite. Three-dimensional (3D) dental cast analysis revealed that the maxillary first and second molars intruded, whereas the anterior teeth extruded, with the second premolar as an infection point. In addition, the maxillary molar was tipped distally by 2.9° and rotated distally by 0.91°. Statistically significant changes were observed in the amount of vertical movement of the central incisor, lateral incisor, canine and first molar, and molar angulation. From T1 to T2, no significant changes in cephalometric measurements or the 3D position of the maxillary dentition were observed. The maxillary and mandibular dentitions did not significantly change during post-treatment follow-up. Conclusions: Maxillary molar intrusion using mini-screws is an effective treatment for open bite correction, with the achieved occlusion demonstrating 3D stability at least 1 year after treatment.

How palatal vault morphology and screw length influence the accuracy of dynamic computer-guided orthodontic miniscrew insertion. A prospective clinical study.

OBJECTIVES: The aim of this study was to evaluate the influence of palatal vault morphology and screw length on the accuracy of miniscrew insertion in dynamic computer-assisted surgery (d-CAS). METHODS: Twenty-four subjects were allocated into three groups, according to their palatal vault morphology (Group A: medium; Group B: steep/high; Group C: low/flat) and the length of miniscrew used. For each subject, two miniscrews were inserted using a dynamic navigation system. To assess the accuracy of insertion, a postoperative CBCT was performed, and the pre- and post-operative scans were superimposed. Five variables were evaluated: Entry-3D, Entry-2D, Apex-3D, Apex-vertical and angular deviation. Descriptive statistics, Shapiro-wilk, Kruskal-Wallis and Dunn's tests were used for the statistical analysis. The level of significance was P ≤ 0.05. RESULTS: The mean angular deviation values revealed strong discrepancies amongst the groups (Group A:7.11°±5.70°; Group B:13.30°±7.76°; Group C:4.92°±3.15°) and significant differences were found regarding the Apex-3D (P = 0.036) and angular deviations (P = 0.008). A Dunn's test revealed differences in angular deviation between the medium and high/steep palate group (P = 0.004), and between low/flat and high/steep palate group (P = 0.01) but did not confirm any significant difference in the Apex-3D parameter (Group A-B P = 0.10; Group B-C, P = 0.053; Group A-C, P = 1.00). No significant differences were found regarding the length of the miniscrews. CONCLUSIONS: Palatal vault morphology is a factor that influences the accuracy of miniscrew insertion in d-CAS. In subjects with steep and high palatal vaults, insertion accuracy is lower when considering the angular deviation value. Miniscrew length does not influence accuracy. CLINICAL SIGNIFICANCE: Although computer-guided surgery assists the clinician in preventing damage to nearby anatomical structures, individual anatomical variability is a crucial variable. In subjects with a high/steep palate, greater attention should be paid during the planning phase in order to allow for a wide margin from adjacent anatomical structures to achieve better outcomes.

The current overview of the devices of temporary anchorage placed on the palatal bone: CBCT study.

Temporary anchorage devices (TADs) are frequently applied to different anatomic areas with different protocols to increase skeletal effects and anchorage in orthodontic treatment planning. It has been reported in many literatures that primary stability for orthodontic TADs is significant for long-term survival rate. For this reason, different areas of the palatal region, which has many indications, have been widely used in the studies. In this evaluation where bone quality and thickness are important, density, bone thickness, and fractal dimension (FD) on cone beam computed tomography (CBCT) will provide more predictable clinical results. The aim of this study was to evaluate bone thickness, density, and FD in the palatal region of the first, and second premolars, and first molars. There was a remarkable difference (p < 0.05) between the parameters of FD, thickness and density of bone in the identified areas in the palatal region. In terms of thickness and FD, the 1st premolar region had significantly higher values than the other regions (p < 0.05). In terms of density, the values in the right 1st molar and right 1st premolar regions were significantly higher (p < 0.05). The 1st premolar region is an ideal site for placement of palatal TADs. CBCT-assisted preliminary evaluation of FD value, bone density, and thickness may increase clinical success when selecting the location of TADs to be applied to the palatal bone.

Evolutionary analysis of gene ages across TADs associates chromatin topology with whole-genome duplications.

Topologically associated domains (TADs) are interaction subnetworks of chromosomal regions in 3D genomes. TAD boundaries frequently coincide with genome breaks while boundary deletion is under negative selection, suggesting that TADs may facilitate genome rearrangements and evolution. We show that genes co-localize by evolutionary age in humans and mice, resulting in TADs having different proportions of younger and older genes. We observe a major transition in the age co-localization patterns between the genes born during vertebrate whole-genome duplications (WGDs) or before and those born afterward. We also find that genes recently duplicated in primates and rodents are more frequently essential when they are located in old-enriched TADs and interact with genes that last duplicated during the WGD. Therefore, the evolutionary relevance of recent genes may increase when located in TADs with established regulatory networks. Our data suggest that TADs could play a role in organizing ancestral functions and evolutionary novelty.

Is significant mandibular advancement possible after the peak of puberty? Dento-osseous palatal expansion and the STM4 technique (Skeletal Therapy Manni Telescopic Herbst 4 miniscrews): A case report.

INTRODUCTION: Treatment of skeletal class II growing patients often requires the use of functional appliances, aimed at promoting mandibular advancement. Among these, Herbst appliance is recommended for its effectiveness, efficiency, and reduced need for compliance. Despite its skeletal favourable effects, well-known dental compensations can occur, especially when the appliance is not used close to the pubertal peak: upper incisors retroclination, lower incisors proclination, upper molars distalization and lower molars mesialization could reduce the overjet needed for a proper mandibular advancement. To counteract these unfavourable effects skeletal anchorage could be crucial. AIM: The aim of this case report is to describe and evaluate the effects of using a skeletally anchored Herbst appliance in an 18-year-old (CVM5) male patient with skeletal Class II malocclusion and a convex profile. TREATMENT PROTOCOL: The treatment started with a tooth-bone-borne palatal expansion, then the upper arch was bonded with pre-adjusted ceramic brackets. After 2months, a Manni Telescopic Herbst (MTH) supported by 4 miniscrews (two in the maxilla and two in the mandible) was applied. To avoid anchorage loss, TADs were connected with elastic chains to the arches. Nine months later, the Herbst was removed, the lower teeth were bonded and the patient wore class 2 elastics to stabilise the occlusion. RESULTS AND CONCLUSIONS: After 24months the treatment goal was achieved with a considerable improvement of the profile and a clinically significant mandibular advancement (Pogonion moved forward 7mm). A one-year follow-up lateral X-rays showed a good stability of the result.

Integrating Dynamic 3D Chromatin Architecture and Gene Expression Alterations Reveal Heterosis in Brassica rapa.

Heterosis plays a significant role in enhancing variety, boosting yield, and raising economic value in crops, but the molecular mechanism is still unclear. We analyzed the transcriptomes and 3D genomes of a hybrid (F1) and its parents (w30 and 082). The analysis of the expression revealed a total of 485 specially expressed genes (SEGs), 173 differentially expressed genes (DEGs) above the parental expression level, more actively expressed genes, and up-regulated DEGs in the F1. Further study revealed that the DEGs detected in the F1 and its parents were mainly involved in the response to auxin, plant hormone signal transduction, DNA metabolic process, purine metabolism, starch, and sucrose metabolism, which suggested that these biological processes may play a crucial role in the heterosis of Brassica rapa. The analysis of 3D genome data revealed that hybrid F1 plants tend to contain more transcriptionally active A chromatin compartments after hybridization. Supplementaryly, the F1 had a smaller TAD (topologically associated domain) genome length, but the number was the highest, and the expression change in activated TAD was higher than that of repressed TAD. More specific TAD boundaries were detected between the parents and F1. Subsequently, 140 DEGs with genomic structural variants were selected as potential candidate genes. We found two DEGs with consistent expression changes in A/B compartments and TADs. Our findings suggested that genomic structural variants, such as TADs and A/B chromatin compartments, may affect gene expression and contribute to heterosis in Brassica rapa. This study provides further insight into the molecular mechanism of heterosis in Brassica rapa.

The Use of CAD/CAM Technology in Mandibular Canine Disimpaction: A Case Report.

This case report of an 11-year-old subject shows the digital workflow for the management of an impacted mandibular canine using Computer-Aided Design/Computer-Aided Manufacturing (CAD/CAM) technology along with Temporary Anchorage Devices (TADs). The miniscrew insertion site was planned using software, and a surgical guide was digitally designed and 3D printed. Orthodontic traction was performed using a 3D-designed and -printed device. In a single sitting, the miniscrew was inserted and the disimpaction device was also delivered. The primary objective of recovery and the repositioning of the impacted mandibular canine in the axis with its eruptive path was achieved. The space available and the subject's early stage of mixed dentition was considered favourable to a spontaneous eruption. This case report shows how CAD/CAM digital technology, combined with 3D printing, enables the creation of a surgical guide to position the miniscrew and the customized devices used for mandibular canine disimpaction. CAD/CAM surgical guides can help clinicians to position TADs with more accuracy and predictability, ensuring high quality bone support offering primary stability. Although orthodontic traction is the most complex therapeutic choice to implement, with the aid of CAD/CAM technology it is possible to proceed with accurate and minimally invasive orthodontic traction in order to recover a mandibular canine.

Structural basis for the preservation of a subset of topologically associating domains in interphase chromosomes upon cohesin depletion.

Compartment formation in interphase chromosomes is a result of spatial segregation between euchromatin and heterochromatin on a few megabase pairs (Mbp) scale. On the sub-Mbp scales, topologically associating domains (TADs) appear as interacting domains along the diagonal in the ensemble averaged Hi-C contact map. Hi-C experiments showed that most of the TADs vanish upon deleting cohesin, while the compartment structure is maintained, and perhaps even enhanced. However, closer inspection of the data reveals that a non-negligible fraction of TADs is preserved (P-TADs) after cohesin loss. Imaging experiments show that, at the single-cell level, TAD-like structures are present even without cohesin. To provide a structural basis for these findings, we first used polymer simulations to show that certain TADs with epigenetic switches across their boundaries survive after depletion of loops. More importantly, the three-dimensional structures show that many of the P-TADs have sharp physical boundaries. Informed by the simulations, we analyzed the Hi-C maps (with and without cohesin) in mouse liver and human colorectal carcinoma cell lines, which affirmed that epigenetic switches and physical boundaries (calculated using the predicted 3D structures using the data-driven HIPPS method that uses Hi-C as the input) explain the origin of the P-TADs. Single-cell structures display TAD-like features in the absence of cohesin that are remarkably similar to the findings in imaging experiments. Some P-TADs, with physical boundaries, are relevant to the retention of enhancer-promoter/promoter-promoter interactions. Overall, our study shows that preservation of a subset of TADs upon removing cohesin is a robust phenomenon that is valid across multiple cell lines.

Biomechanical analysis of total arch maxillary distalization using infrazygomatic crest miniscrews: a finite element analysis study.

AIM: To evaluate the maxillary incisors and canine's immediate movement tendency using three different power arms (PA) height levels during total arch maxillary distalization supported on infrazygomatic crest (IZC) miniscrews according to finite element analysis (FEA). METHODS: Three finite element models of the maxilla were developed based on CBCT imaging of a teenage male patient presenting a Class II Division 1 malocclusion in the early permanent dentition. Maxillary complex, periodontium, orthodontic accessories, IZC miniscrews and an orthodontic wire were digitally created. The PAs were placed between canines and lateral incisors and projected at 4, 7, and 10 mm height distances. After that, distalization forces were simulated between PA and IZC miniscrews. RESULTS: The anterior teeth deformation produced in the FEA models was assessed according to a Von Mises equivalent. The stress was measured, revealing tendencies of initial maxillary teeth movement. No differences were found between the right and left sides. However, there was a significant difference among models in the under-stress areas, especially the apical and cervical root areas of the maxillary anterior teeth. More significant extrusion and lingual tipping of incisors were observed with the 4 mm power arm compared to the 7 mm and 10 mm ones. The 10 mm power arm did not show any tendency for extrusion of maxillary central incisors but a tendency for buccal tipping and intrusion of lateral incisors. CONCLUSION: The maxillary incisors and canines have different immediate movement tendencies according to the height of the anterior point of the en-masse distalization force application. Based on the PA height increase, a change from lingual to buccal tipping and less extrusion tendency was observed for the incisors, while the lingual tipping and extrusion trend for canines increased.