Multi-omics profiling of mouse gastrulation at single-cell resolution.

Formation of the three primary germ layers during gastrulation is an essential step in the establishment of the vertebrate body plan and is associated with major transcriptional changes1-5. Global epigenetic reprogramming accompanies these changes6-8, but the role of the epigenome in regulating early cell-fate choice remains unresolved, and the coordination between different molecular layers is unclear. Here we describe a single-cell multi-omics map of chromatin accessibility, DNA methylation and RNA expression during the onset of gastrulation in mouse embryos. The initial exit from pluripotency coincides with the establishment of a global repressive epigenetic landscape, followed by the emergence of lineage-specific epigenetic patterns during gastrulation. Notably, cells committed to mesoderm and endoderm undergo widespread coordinated epigenetic rearrangements at enhancer marks, driven by ten-eleven translocation (TET)-mediated demethylation and a concomitant increase of accessibility. By contrast, the methylation and accessibility landscape of ectodermal cells is already established in the early epiblast. Hence, regulatory elements associated with each germ layer are either epigenetically primed or remodelled before cell-fate decisions, providing the molecular framework for a hierarchical emergence of the primary germ layers.

Estrogen regulates divergent transcriptional and epigenetic cell states in breast cancer.

Breast cancers are known to be driven by the transcription factor estrogen receptor and its ligand estrogen. While the receptor's cis-binding elements are known to vary between tumors, heterogeneity of hormone signaling at a single-cell level is unknown. In this study, we systematically tracked estrogen response across time at a single-cell level in multiple cell line and organoid models. To accurately model these changes, we developed a computational tool (TITAN) that quantifies signaling gradients in single-cell datasets. Using this approach, we found that gene expression response to estrogen is non-uniform, with distinct cell groups expressing divergent transcriptional networks. Pathway analysis suggested the two most distinct signatures are driven separately by ER and FOXM1. We observed that FOXM1 was indeed activated by phosphorylation upon estrogen stimulation and silencing of FOXM1 attenuated the relevant gene signature. Analysis of scRNA-seq data from patient samples confirmed the existence of these divergent cell groups, with the FOXM1 signature predominantly found in ER negative cells. Further, multi-omic single-cell experiments indicated that the different cell groups have distinct chromatin accessibility states. Our results provide a comprehensive insight into ER biology at the single-cell level and potential therapeutic strategies to mitigate resistance to therapy.

Smile dynamics: A comparative study of Fijians and NZ Europeans.

BACKGROUND: The Fijian 'Bula Smile' is often described as the world's friendliest; however, its description remains anecdotal. OBJECTIVE: This study aimed to describe and compare the dynamics of Fijians' smiles with those of New Zealand Europeans. METHODS: An observational study was conducted on two ethnic groups, Fijians (FJ; N = 23) and New Zealand Europeans (NZ; N = 23), age- and gender-matched. All participants were asked to watch amusing videos, and their reactions were video recorded. The videos were analysed by software to assess the frequency, duration, intensity and genuineness of smiling episodes. Based on the Facial Action Coding System, Action Unit 6 (AU6-cheek raiser), Action Unit 12 (AU12-lip corner puller) and Action Unit 25 (AU25-lips apart) were assessed. Data were analysed by generalised linear models after adjusting for personality traits. RESULTS: Fijians smiled longer than New Zealand Europeans (+19.9%; p = .027). Mean intensity of AU6 (+1.0; 95%CIs = 0.6-1.5; p < .001), AU12 (+0.5; 95%CIs = 0.1-0.9; p = .008) and AU25 (+22.3%; 95%CIs = 7.3%-37.3%; p = .005) were significantly higher in FJ group than the NZ group. CONCLUSION: Smiling features of Fijians and New Zealanders showed objective differences, the most distinctive being a higher activation of the Duchenne's marker (AU6) in the Fijian group, which is regarded as a sign of smile genuineness.

The performance of artificial intelligence models in generating responses to general orthodontic questions: ChatGPT vs Google Bard.

INTRODUCTION: This study aimed to evaluate and compare the performance of 2 artificial intelligence (AI) models, Chat Generative Pretrained Transformer-3.5 (ChatGPT-3.5; OpenAI, San Francisco, Calif) and Google Bidirectional Encoder Representations from Transformers (Google Bard; Bard Experiment, Google, Mountain View, Calif), in terms of response accuracy, completeness, generation time, and response length when answering general orthodontic questions. METHODS: A team of orthodontic specialists developed a set of 100 questions in 10 orthodontic domains. One author submitted the questions to both ChatGPT and Google Bard. The AI-generated responses from both models were randomly assigned into 2 forms and sent to 5 blinded and independent assessors. The quality of AI-generated responses was evaluated using a newly developed tool for accuracy of information and completeness. In addition, response generation time and length were recorded. RESULTS: The accuracy and completeness of responses were high in both AI models. The median accuracy score was 9 (interquartile range [IQR]: 8-9) for ChatGPT and 8 (IQR: 8-9) for Google Bard (Median difference: 1; P <0.001). The median completeness score was similar in both models, with 8 (IQR: 8-9) for ChatGPT and 8 (IQR: 7-9) for Google Bard. The odds of accuracy and completeness were higher by 31% and 23% in ChatGPT than in Google Bard. Google Bard's response generation time was significantly shorter than that of ChatGPT by 10.4 second/question. However, both models were similar in terms of response length generation. CONCLUSIONS: Both ChatGPT and Google Bard generated responses were rated with a high level of accuracy and completeness to the posed general orthodontic questions. However, acquiring answers was generally faster using the Google Bard model.

Somatosensory cortex of macaque monkeys is designed for opposable thumb.

The evolution of opposable thumb has enabled fine grasping ability and precision grip, therefore the ability to finely manipulate the objects and refined tool use. Since tactile inputs to an opposable thumb are often spatially and temporally out of sync with inputs from the fingers, we hypothesized that inputs from the opposable thumb would be processed in an independent module in the primary somatosensory cortex (area 3b). Here we show that in area 3b of macaque monkeys, most neurons in the thumb representation do not respond to tactile stimulation of other digits and receive few intrinsic cortical inputs from other digits. However, neurons in the representations of other 4 digits respond to touch on any of the 4 digits and interconnect significantly more. The thumb inputs are thus processed in an independent module, whereas there is a significantly more interdigital information exchange between the other digits. This cortical organization reflects behavioral use of a hand with an opposable thumb.

Effect of chlorhexidine mouthwash on gingival health around orthodontic miniscrew implants: A pilot placebo-controlled randomized trial.

OBJECTIVE: This randomized controlled trial (RCT) aims to investigate the short-term effects of chlorhexidine mouthwash (MW) on gingival health surrounding orthodontic miniscrew implants (OMIs) and their overall survivability. MATERIALS AND METHODS: Thirty-two participants (mean age, 22.8 years) undergoing fixed orthodontic appliance treatment after maxillary premolar extraction were randomly allocated in a parallel fashion to either receive (1) MW with an active component of chlorhexidine or (2) a placebo. Each participant received two maxillary buccal OMIs for anchorage reinforcement purposes. Participants were assessed for their gingival oral health status around all inserted OMIs and had their OMI survivability recorded at three time points; T1 = 1 month, T2 = 3 months, and T3 = 6 months after OMI placement. A Kaplan-Meier plot was used to estimate the survival function of OMIs. RESULTS: All randomized participants completed the follow-up period. In terms of gingival oral health, there were no statistically significant differences at any time point between the chlorhexidine MW group and the placebo-controlled group (P > .05). One OMI was lost in the chlorhexidine MW group and another two OMIs in the control group. There was no significant difference between both groups in terms of survivability (P = .585). CONCLUSION: The use of chlorhexidine MW does not seem to have a significant clinical impact on gingival health around OMIs or their survivability in this pilot study.

Malocclusion severity and smile features: Is there an association?

INTRODUCTION: This observational study investigated the relationship between malocclusion and smiling. METHODS: Adolescents and young adults (n = 72; aged 16-25 years) were identified according to their Dental Aesthetic Index (DAI) and allocated to 3 groups: (1) malocclusion group (n = 24; DAI ≥31), (2) retention group (n = 24; pretreatment DAI ≥31) with a prior malocclusion that had been corrected by orthodontic treatment, (3) control group with no-to-minor malocclusion (n = 24; DAI ≤25). Participants were requested to watch an amusing video. Based on the Facial Action Coding System, automated pattern recognition was used to detect smile episodes and assess their frequency, duration, genuineness, intensity, and extent of tooth show. Demographics, Big Five personality dimensions, and self-perceived smile esthetics-related quality of life were collected from all participants via questionnaires. Data were analyzed by mixed-model analysis and adjusted for possible confounders. RESULTS: Patients from the malocclusion and retention groups smiled significantly less than participants from the control group, with the duration of smiles and smiling time being around half those of control subjects. Smile genuineness, smile intensity, and teeth shown did not differ across groups. Personality traits did not differ significantly among the 3 groups, whereas the malocclusion group scored around 30% less for dental self-confidence than the other 2 groups. CONCLUSIONS: Patients with severe malocclusion tend to smile less, but the features of their smiles are similar to those without malocclusion. A lower propensity to smile in patients with a corrected malocclusion may persist after orthodontic treatment.

Tele-orthodontics and sensor-based technologies: a systematic review of interventions that monitor and improve compliance of orthodontic patients.

BACKGROUND: Recent advances in orthodontics offer appealing tools to monitor compliance and designate protocols to enhance it. OBJECTIVE: This systematic review of systematic reviews (SRs) aimed to assess the effectiveness of digitized communication methods and sensor-based devices that track compliance in orthodontic patients. SEARCH METHODS: Five electronic databases (PubMed, Web of Science, MEDLINE, PsycINFO, and EMBASE) were searched from database inception up to 4 December 2022. SELECTION CRITERIA: SRs using digitized systems and sensor-based technologies to monitor and/or improve compliance with orthodontic treatment or during an active retention phase were included. DATA COLLECTION AND ANALYSIS: Study selection, data extraction, and risk of bias assessment using the AMSTAR 2 tool were performed independently by two review authors. A qualitative synthesis of outcomes from moderate- and high-quality SRs was provided, and evidence was graded in accordance with a scale of statements. RESULTS: A total of 846 unique citations were retrieved. After study selection, 18 SRs met the inclusion criteria, and 9 moderate- and high-quality reviews were further integrated into the qualitative synthesis. Digitized communication methods were found to be effective in improving compliance with oral hygiene practices and adherence to orthodontic appointments. Monitoring removable appliance wear with microsensors revealed sub-optimal levels of compliance with wear instructions of intra-oral and extra-oral appliances. One review discussed the informational value of social media platforms and their importance in guiding the decision-making process to seek orthodontic treatment and compliance-related experiences. LIMITATIONS: The variability in the quality of included SRs and the limited number of primary studies on certain outcomes present as limitations within this overview. CONCLUSIONS: The integration of tele-orthodontics and sensor-based technologies to improve and monitor compliance within orthodontic practices is promising. There is sufficient evidence that establishing communication channels with orthodontic patients through reminders and audiovisual systems positively impact their oral hygiene practices throughout orthodontic treatment. However, understanding the informational value of social media as communication channels between clinicians and their patients, and their overall effect on modulating compliance is still insufficient. REGISTRATION: CRD42022331346.

Response and resistance to BET bromodomain inhibitors in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a heterogeneous and clinically aggressive disease for which there is no targeted therapy. BET bromodomain inhibitors, which have shown efficacy in several models of cancer, have not been evaluated in TNBC. These inhibitors displace BET bromodomain proteins such as BRD4 from chromatin by competing with their acetyl-lysine recognition modules, leading to inhibition of oncogenic transcriptional programs. Here we report the preferential sensitivity of TNBCs to BET bromodomain inhibition in vitro and in vivo, establishing a rationale for clinical investigation and further motivation to understand mechanisms of resistance. In paired cell lines selected for acquired resistance to BET inhibition from previously sensitive TNBCs, we failed to identify gatekeeper mutations, new driver events or drug pump activation. BET-resistant TNBC cells remain dependent on wild-type BRD4, which supports transcription and cell proliferation in a bromodomain-independent manner. Proteomic studies of resistant TNBC identify strong association with MED1 and hyper-phosphorylation of BRD4 attributable to decreased activity of PP2A, identified here as a principal BRD4 serine phosphatase. Together, these studies provide a rationale for BET inhibition in TNBC and present mechanism-based combination strategies to anticipate clinical drug resistance.

The effect of ligation methods on biofilm formation in patients undergoing multi-bracketed fixed orthodontic therapy - A systematic review.

BACKGROUND: Many modifications to fixed orthodontic appliances have been introduced to manage biofilm formation. The aim of this review was to investigate elastomeric ligation in comparison with stainless steel ligation and self-ligation with regard to microbiological and clinical indicators of biofilm formation in patients wearing multi-bracketed fixed orthodontic appliances. METHODS: The MEDLINE and the EMBASE databases were searched up to February 2021 and supplemented by additional manual searches of bibliographies. Parallel-group and split-mouth randomized controlled trials (RCTs) comparing different ligation methods were identified. The Cochrane Risk of Bias-2 tool was applied to assess the quality of evidence. RESULTS: A total of 11 RCTs were included in this review. Nine RCTs compared self-ligation and elastomeric ligation; two compared elastomeric ligation and stainless steel ligation. The included studies had either some concerns or were at a high risk of bias. Qualitative assessment of the studies identified that there were no significant differences in biofilm formation between elastomeric ligation and self-ligation, but that stainless steel ligation was less susceptible to biofilm formation than elastomeric ligation. CONCLUSIONS: There were no significant differences between self-ligation and elastomeric ligation for biofilm formation in patients wearing multi-bracketed fixed orthodontic appliances. Stainless steel ligation may accumulate less biofilm than elastomeric ligation; however, the clinical significance of the difference could not be evaluated. Further high-quality studies are required in order to determine which ligation method is better for managing biofilm formation in patients wearing multi-bracketed fixed orthodontic appliances.

Automated detection of smiles as discrete episodes.

BACKGROUND: Patients seeking restorative and orthodontic treatment expect an improvement in their smiles and oral health-related quality of life. Nonetheless, the qualitative and quantitative characteristics of dynamic smiles are yet to be understood. OBJECTIVE: To develop, validate, and introduce open-access software for automated analysis of smiles in terms of their frequency, genuineness, duration, and intensity. MATERIALS AND METHODS: A software script was developed using the Facial Action Coding System (FACS) and artificial intelligence to assess activations of (1) cheek raiser, a marker of smile genuineness; (2) lip corner puller, a marker of smile intensity; and (3) perioral lip muscles, a marker of lips apart. Thirty study participants were asked to view a series of amusing videos. A full-face video was recorded using a webcam. The onset and cessation of smile episodes were identified by two examiners trained with FACS coding. A Receiver Operating Characteristic (ROC) curve was then used to assess detection accuracy and optimise thresholding. The videos of participants were then analysed off-line to automatedly assess the features of smiles. RESULTS: The area under the ROC curve for smile detection was 0.94, with a sensitivity of 82.9% and a specificity of 89.7%. The software correctly identified 90.0% of smile episodes. While watching the amusing videos, study participants smiled 1.6 (±0.8) times per minute. CONCLUSIONS: Features of smiles such as frequency, duration, genuineness, and intensity can be automatedly assessed with an acceptable level of accuracy. The software can be used to investigate the impact of oral conditions and their rehabilitation on smiles.

Antidepressant Effect of Crocin in Mice with Chronic Mild Stress.

This study aimed to investigate the antidepressant property of crocin (Crocetin digentiobiose ester) using a chronic mild stress (CMS)-induced depression model in experimental mice. The tail suspension test (TST) and the sucrose preference test were used to evaluate the antidepressant effect on albino mice of either sex after three weeks of CMS. The period of immobility in the TST and percentage preference for sucrose solution were recorded. By monitoring brain malondialdehyde (MDA) level, catalase (CAT) activity, and reduced glutathione (GSH) level, the antioxidant potential was assessed. Three dosages of crocin (4.84, 9.69, and 19.38 mg/kg) were evaluated. When compared to controls, animals that received crocin administration during three periods of CMS had considerably shorter immobility times during the TST. Crocin treatment also raised the percentage preference for sucrose solution in a dose-dependent manner, bringing it to parity with the conventional antidepressant, imipramine. Animals that received a high dose of crocin had a much greater spontaneous locomotor activity. Furthermore, a high dose of crocin remarkably lowered plasma corticosterone and nitrite levels brought on by CMS. Additionally, high doses of crocin given during CMS greatly enhanced reduced glutathione levels while considerably reducing the brain's MDA and catalase activities. In conclusion, high doses of crocin may have an antidepressant effect in an animal model through several mechanisms. However, further studies should be carried out to explore the role of neurotransmitters for their antidepressant property.

A qualitative study of orthodontic patients' experiences in quarantine during the COVID-19 pandemic outbreak.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) is one of the most formidable challenges that influenced all domains of health care delivery. This research explored the experiences and challenges orthodontic patients faced in quarantine during the COVID-19 outbreak. The goal was to learn from patients about their oral health and general practices during this time to provide optimal delivery of orthodontic treatment care. METHODS: A phenomenographic qualitative design involving semistructured face-to-face interviews. A purposive sampling strategy was deployed to collect qualitative data from 24 orthodontic patients who quarantined during the COVID-19 pandemic. All interviews were digitally recorded, and afterwards, they were transcribed verbatim. RESULTS: Four main themes and associated subthemes were identified. The themes were (1) oral-health-related behavioral changes, (2) impact on treatment progression, (3) psychosocial impact and attitude changes, and (4) areas for future enhancements in health care delivery. Overall findings revealed both positive and negative behavioral changes in orthodontic patients regarding their adjustment during the quarantine and its implications to general health and well-being. CONCLUSIONS: Findings from this study suggest that COVID-19 impacted dental health care delivery to orthodontic patients during the quarantine. Patients reported psychosocial and behavioral changes as a consequence of treatment disruption and pandemic lockdown. The implications of these findings to the clinical dental environment and patient education are pivotal to further target areas in dental health care delivery that require strengthening. As such, clinicians could expect behavioral changes from orthodontic patients and identify better strategies to mitigate clinical challenges resulting from such changes.

A qualitative meta-synthesis of research into patients' past experiences and perceptions of orthodontic treatment outcomes.

BACKGROUND: There is a growing body of evidence emphasizing the importance of research into patient-centred experience in orthodontics. Benefits following orthodontic treatment are mainly related to improved aesthetics and psychosocial outcomes. However, treatment experience from the perspective of orthodontic patients is yet to be fully understood. OBJECTIVE: To understand the past experiences and current perceptions of treatment outcomes of orthodontic patients. STUDY DESIGN: A qualitative meta-ethnography. SELECTION CRITERIA: Qualitative studies and mixed-methods articles with a distinct qualitative component presenting patients' perception of outcomes and overall experiences after an active course of orthodontic treatment were included. SEARCH METHODS: Comprehensive electronic searches were conducted in MEDLINE, Scopus, Web of Science, PsycINFO, and EMBASE up to May 2021, supplemented by grey literature and manual searches. DATA COLLECTION AND ANALYSIS: Two independent reviewers were involved in study selection, data extraction, and quality appraisal. The Critical Appraisal Skills Programme tool for qualitative research was used to assess the quality of included studies. Analysis of data was conducted using meta-ethnographic methods. RESULTS: Out of 801 retrieved search hits, six studies fulfilled the inclusion criteria and were included in the synthesis. The analysis revealed three main themes and associated sub-themes: (1) Reflection on the past treatment experience, (2) Patient satisfaction with treatment outcomes, and (3) Learning to live with retainers. LIMITATIONS: Results express patients' opinions shortly after treatment, and the long-term impact of orthodontic treatment is yet to be understood. CONCLUSIONS: Orthodontic patients mainly viewed their experiences and treatment results positively. Desirable aesthetic outcomes, psychosocial outcomes, and satisfaction with smiles were often reported in the studies reviewed. However, some barriers to optimal experiences were noticed concerning orthodontic retention. REGISTRATION: PROSPERO (CRD42020180121).

Single cell transcriptome analysis of human, marmoset and mouse embryos reveals common and divergent features of preimplantation development.

The mouse embryo is the canonical model for mammalian preimplantation development. Recent advances in single cell profiling allow detailed analysis of embryogenesis in other eutherian species, including human, to distinguish conserved from divergent regulatory programs and signalling pathways in the rodent paradigm. Here, we identify and compare transcriptional features of human, marmoset and mouse embryos by single cell RNA-seq. Zygotic genome activation correlates with the presence of polycomb repressive complexes in all three species, while ribosome biogenesis emerges as a predominant attribute in primate embryos, supporting prolonged translation of maternally deposited RNAs. We find that transposable element expression signatures are species, stage and lineage specific. The pluripotency network in the primate epiblast lacks certain regulators that are operative in mouse, but encompasses WNT components and genes associated with trophoblast specification. Sequential activation of GATA6, SOX17 and GATA4 markers of primitive endoderm identity is conserved in primates. Unexpectedly, OTX2 is also associated with primitive endoderm specification in human and non-human primate blastocysts. Our cross-species analysis demarcates both conserved and primate-specific features of preimplantation development, and underscores the molecular adaptability of early mammalian embryogenesis.

Progesterone receptor modulates ERα action in breast cancer.

Progesterone receptor (PR) expression is used as a biomarker of oestrogen receptor-α (ERα) function and breast cancer prognosis. Here we show that PR is not merely an ERα-induced gene target, but is also an ERα-associated protein that modulates its behaviour. In the presence of agonist ligands, PR associates with ERα to direct ERα chromatin binding events within breast cancer cells, resulting in a unique gene expression programme that is associated with good clinical outcome. Progesterone inhibited oestrogen-mediated growth of ERα(+) cell line xenografts and primary ERα(+) breast tumour explants, and had increased anti-proliferative effects when coupled with an ERα antagonist. Copy number loss of PGR, the gene coding for PR, is a common feature in ERα(+) breast cancers, explaining lower PR levels in a subset of cases. Our findings indicate that PR functions as a molecular rheostat to control ERα chromatin binding and transcriptional activity, which has important implications for prognosis and therapeutic interventions.

Stability of single-jaw vs two-jaw surgery following the correction of skeletal class III malocclusion: A systematic review and meta-analysis.

This review aims to compare the stability of sagittal skeletal and overjet anteroposterior correction of skeletal class III malocclusion in single-jaw and two-jaw orthognathic procedures. An unrestricted comprehensive electronic search was undertaken on Embase, Cochrane's CENTRAL, Web of Science, Medline, Scopus and LILACs databases up to October 2020. The bibliographies of relevant studies, ongoing, unpublished and grey literature were screened. Two independent reviewers performed study selection, bias assessment and data extraction; a third reviewer mediated inconsistencies. Randomized clinical trials, prospective cohort, retrospective cohort and series with a minimum of 1 year follow-up were eligible for inclusion. Additional subgroup analyses were undertaken. The generated effects were scored using the GRADE approach. Nine articles met the inclusion criteria and eight studies were subsequently analysed quantitatively. No significant difference in sagittal stability at the ANB angle, A-point or B-point on a short-term was detected. However, a statistically significant difference, indicating a greater short-term relapse in overjet with mandibular setbacks alone, was found (MD: -0.40 mm; 95% CI -0.77 to -0.04; I2 : 0%; P = .03). Long-term follow-up (≥5 years) revealed a statistically non-significant difference in stability of sagittal skeletal and overjet corrections. Within the limitations of this review, both procedures seem to offer comparable skeletal and overjet stability outcomes; however, further high-quality research is required to confirm these findings.

Are developmentally missing teeth a predictive risk marker of malignant diseases in non-syndromic individuals? A systematic review.

BACKGROUND: Different genes and loci that are associated with non-syndromic developmental tooth agenesis (TA) have the same causation pathway in the development of tumours including breast cancer (BC), epithelial ovarian cancer (EOC), colorectal cancer (CRC) and lung cancer (LC). OBJECTIVES: To assess the link between TA and the development of cancer. SEARCH SOURCES: This registered review included a comprehensive search of electronic databases (Cochrane Central Register of Controlled Trials [CENTRAL], LILACS, Scopus, Web of Science and Medline via Ovid) until 1 April 2020, supplemented by manual, grey literature and reference lists search. There was no restriction in term of date of publication, gender, race or type of hypodontia. DATA SELECTION: The primary outcome was the relationship between TA and cancer. The secondary outcome was to identify the genetic correlation between TA and cancer. DATA EXTRACTION: Study selection, data extraction and risk of bias assessment were performed independently and induplicate by two reviewers, with disputes resolved by a third reviewer. RESULTS: Eight studies with a moderate-high risk of bias were included in the final review, with a total of 5821 participants. Due to the heterogeneity among the included studies, the data were presented narratively. Limited studies reported a high prevalence of EOC (19.2%-20%) and CRC (82%-100%) in individuals with TA (depending on the study) compared to those without TA (3% for EOC and 0% for CRC). While others reported a weak correlation between EOC and CRC and TA (P > 0.05). Weak evidence suggested a strong correlation between breast, cervical uterine and prostate cancers and TA (P < 0.05). CONCLUSIONS: Though low-quality evidence suggests a link between TA and cancer, it was not possible to verify that TA can hold a predictive value as a marker for cancers. Further research is needed to confirm the association. REGISTRATION: PROSPERO (CRD42020139751).

Three-dimensional nasolabial changes after maxillary advancement osteotomy in class III individuals: a systematic review and meta-analysis.

Background Class III malocclusions with maxillary retrognathia are commonly treated with single jaw Le Fort I maxillary advancement. The three-dimensional (3D) effects of surgery on the nasolabial region varies among the clinical studies. Quantifying these changes is of great importance for surgical planning and obtaining valid consent. Objectives To investigate the 3D relationship between soft tissue and skeletal changes secondary to Le Fort I maxillary advancement surgery in skeletal class III patients.Search methods Comprehensive search of multiple electronic databases supplemented by a manual and grey literature search were undertaken from inception to 9 June 2020.Selection criteria Studies that evaluated the 3D soft tissue changes of patients before and after maxillary advancement surgery alone.Data collection and analysis Study selection, data extraction and risk of bias assessment were performed independently by two reviewers, with disputes resolved by a third reviewer. A quantitative synthesis of the data was pre-planned for pooling similar outcome measures.Results Four studies were included in the final review and meta-analysis, with a total of 105 patients (mean age 16.7 + 33.9 years). The mean maxillary advancement of the included studies was 5.58 mm (95% CI 5.20-5.96). The sagittal effects of surgery on nose tip projection and prominence were insignificant (P >0.05, two studies); however, subnasal projection (MD 1.7 mm, two studies) and upper lip projection (MD 2.90 mm, four studies) increased significantly in a forward direction after surgery (P <0.05). Le Fort I osteotomy widens the upper philtrum width (MD 0.84 mm, two studies) (P <0.05). Inconsistencies among the included studies were identified; therefore, the results should be interpreted with caution.Conclusions There is weak evidence based on quantitative assessments that Le Fort I maxillary advancement significantly affects the nasolabial soft tissue envelope mainly in a sagittal dimension. These changes are concentrated around the central zone of the nasolabial region. Future prospective studies on maxillary advancement osteotomy with a standardised method of assessment, taking into consideration the confounding factors, are required.

Proteogenomic analysis of Inhibitor of Differentiation 4 (ID4) in basal-like breast cancer.

BACKGROUND: Basal-like breast cancer (BLBC) is a poorly characterised, heterogeneous disease. Patients are diagnosed with aggressive, high-grade tumours and often relapse with chemotherapy resistance. Detailed understanding of the molecular underpinnings of this disease is essential to the development of personalised therapeutic strategies. Inhibitor of differentiation 4 (ID4) is a helix-loop-helix transcriptional regulator required for mammary gland development. ID4 is overexpressed in a subset of BLBC patients, associating with a stem-like poor prognosis phenotype, and is necessary for the growth of cell line models of BLBC through unknown mechanisms. METHODS: Here, we have defined unique molecular insights into the function of ID4 in BLBC and the related disease high-grade serous ovarian cancer (HGSOC), by combining RIME proteomic analysis, ChIP-seq mapping of genomic binding sites and RNA-seq. RESULTS: These studies reveal novel interactions with DNA damage response proteins, in particular, mediator of DNA damage checkpoint protein 1 (MDC1). Through MDC1, ID4 interacts with other DNA repair proteins (γH2AX and BRCA1) at fragile chromatin sites. ID4 does not affect transcription at these sites, instead binding to chromatin following DNA damage. Analysis of clinical samples demonstrates that ID4 is amplified and overexpressed at a higher frequency in BRCA1-mutant BLBC compared with sporadic BLBC, providing genetic evidence for an interaction between ID4 and DNA damage repair deficiency. CONCLUSIONS: These data link the interactions of ID4 with MDC1 to DNA damage repair in the aetiology of BLBC and HGSOC.