Detecting Mandible Fractures in CBCT Scans Using a 3-Stage Neural Network.

After nasal bone fractures, fractures of the mandible are the most frequently encountered injuries of the facial skeleton. Accurate identification of fracture locations is critical for effectively managing these injuries. To address this need, JawFracNet, an innovative artificial intelligence method, has been developed to enable automated detection of mandibular fractures in cone-beam computed tomography (CBCT) scans. JawFracNet employs a 3-stage neural network model that processes 3-dimensional patches from a CBCT scan. Stage 1 predicts a segmentation mask of the mandible in a patch, which is subsequently used in stage 2 to predict a segmentation of the fractures and in stage 3 to classify whether the patch contains any fracture. The final output of JawFracNet is the fracture segmentation of the entire scan, obtained by aggregating and unifying voxel-level and patch-level predictions. A total of 164 CBCT scans without mandibular fractures and 171 CBCT scans with mandibular fractures were included in this study. Evaluation of JawFracNet demonstrated a precision of 0.978 and a sensitivity of 0.956 in detecting mandibular fractures. The current study proposes the first benchmark for mandibular fracture detection in CBCT scans. Straightforward replication is promoted by publicly sharing the code and providing access to JawFracNet on grand-challenge.org.

Transgender and Gender-Diverse People's Experiences of Minority Stress, Mental Health, and Resilience in Relation to Perceptions of Sociopolitical Contexts.

Purpose: The sociopolitical context in which transgender and gender-diverse (TGD) people live has significant effects on mental health. We examined whether perceptions of context (TGD people's perceptions of how TGD people were viewed) differed across four United States (U.S.) states and associations with mental health and identity pride, the mediational effects of minority stressors, and potential buffering effects of resilience. Methods: TGD individuals in Oregon, Michigan, Nebraska, and Tennessee (n=158; ages 19-70, mean=33.06) completed questionnaires assessing their perceptions of how TGD people were viewed in their local area and in the U.S., as well as scales assessing minority stressors, pride, resilience, and mental health. Data were collected during Fall 2019 to Spring 2020. Results: Oregon participants viewed perceptions in their state the most positively, with no state-level differences in terms of broader U.S. perceptions. Tennessee participants experienced more expectations of rejection; however, there were no differences across the states in other minority stress variables, identity pride, resilience, or mental health. Participants who viewed their area as having more negative views of TGD people reported higher levels of discrimination, expectations of negative events, internalized stigma, and anxiety, as well as less pride. The effects of perceptions of local context on mental health were partially explained by enacted stigma and internalized stigma. Resilience did not buffer the effects of perceptions of the local context on mental health or pride. Conclusion: Context is important to shaping exposure to minority stressors and mental health, potentially through increasing enacted and internalized stigma.

Gender minority stress and diurnal cortisol profiles among transgender and gender diverse people in the United States.

The field of behavioral neuroendocrinology has only begun to explore the lived experiences of transgender and gender diverse (TGD) people exposed to stigma. In light of escalating attacks and legislation targeting TGD people in the United States, it is crucial to examine the physiological pathways through which gender minority stressors become embodied, impact health, and contribute to health inequities. The Trans Resilience and Health Study included baseline data collection from fall 2019 to spring 2020 from a sample of 124 TGD people, reflecting a diversity of gender identities (e.g., trans masculine, trans feminine, and nonbinary) and ages (range = 19-70 years old; M = 34.10), living in Michigan, Nebraska, Oregon, and Tennessee. These analyses examine experiences of gender-related enacted stigma in association with hypothalamic-pituitary-adrenal (HPA)-axis functioning. Among those experiencing the highest levels of enacted stigma, findings show a blunted cortisol awakening response and sluggish daily decline that resulted in elevated concentrations at bedtime compared to those experiencing less enacted stigma. These results of flattened diurnal activity are consistent with an emergent literature on discrimination as a social determinant of potential stress pathophysiology. In contrast, community connectedness was associated with a larger, more dynamic cortisol awakening response. These findings emphasize the importance of incorporating gender-minority stress and resilience measures when studying HPA-axis functioning among TGD people.

Caffeic Acid Phenethyl Ester (CAPE), a natural polyphenol to increase the therapeutic window for lung adenocarcinomas.

BACKGROUND AND PURPOSE: Lung cancers are highly resistant to radiotherapy, necessitating the use of high doses, which leads to radiation toxicities such as radiation pneumonitis and fibrosis. Caffeic Acid Phenethyl Ester (CAPE) has been suggested to have anti-proliferative and pro-apoptotic effects in tumour cells, while radioprotective anti-inflammatory and anti-oxidant effects in the normal tissue. We investigated the radiosensitizing and radioprotective effects of CAPE in lung cancer cell lines and normal tissue in vitro and ex vivo, respectively. MATERIALS AND METHODS: The cytotoxic and radiosensitizing effects of CAPE in lung cancer were investigated using viability and clonogenic survival assays. The radioprotective effects of CAPE were assessed in vitro and ex vivo using precision cut lung slices (PCLS). Potential underlying molecular mechanisms of CAPE focusing on cell cycle, cell metabolism, mitochondrial function and pro-inflammatory markers were investigated. RESULTS: Treatment with CAPE decreased cell viability in a dose-dependent manner (IC50 57.6 ± 16.6 µM). Clonogenic survival assays showed significant radiosensitization by CAPE in lung adenocarcinoma lines (p < 0.05), while no differences were found in non-adenocarcinoma lines (p ≥ 0.13). Cell cycle analysis showed an increased S-phase (p < 0.05) after incubation with CAPE in the majority of cell lines. Metabolic profiling showed that CAPE shifted cellular respiration towards glycolysis (p < 0.01), together with mitochondrial membrane depolarization (p < 0.01). CAPE induced a decrease in NF-κB activity in adenocarcinomas and decreased pro-inflammatory gene expression in PCLS. CONCLUSION: The combination of CAPE and radiotherapy may be a potentially effective approach to increase the therapeutic window in lung cancer patients.

Transgender and gender diverse adults' self-reported mental health diagnoses, engagement in mental health services, and perceptions of therapists.

OBJECTIVE: Transgender and gender diverse (TGD) people face various challenges when seeking therapy. Given this, we wanted to understand more about TGD people's perceptions of providers and how these compare to researcher ratings of providers on metrics of affirming practice. METHOD: The sample included 158 TGD adults (Mage = 33.06); 57.6% were in therapy. Participants completed measures about mental health, resilience, and therapy. We systematically coded provider websites and intake forms. RESULTS: Participants in therapy were older, had higher depression, and lower resilience than participants not in therapy. Non-binary/genderqueer participants rated providers as less knowledgeable compared to trans feminine participants. Overall, participants appeared satisfied (71.4% extremely satisfied) and viewed providers as at least moderately knowledgeable (89.1%). Provider coding revealed variation across the markers of affirmation; 66.04% identified a TGD-specialty and only 26.42% shared provider pronouns. Higher frequency of inclusivity (via coding) was related to higher ratings of provider knowledge and more of a focus on gender, however, there was not a significant association with satisfaction. CONCLUSIONS: Providers who engaged in more affirming practices were more knowledgeable compared to those who engaged in fewer affirming practices. This may influence the content of therapy and whether clients feel comfortable discussing gender.

An Examination of Predictors of Prejudice against Transgender Individuals.

We examined associations between prejudice toward transgender people, aggression proneness, history of family violence, contact and closeness with transgender people, and education about issues that impact transgender individuals. We also examined the moderating effects of contact, education, and closeness on the relations between aggression and history of family violence with prejudice. There were 360 participants (M age = 31.34, SD = 12.47, range 18-75) who completed the survey online. Participants were recruited through social media, websites, and MTurk. Higher levels of aggression proneness were related to higher levels of prejudice. Higher levels of education about issues that impact transgender people and prior contact with a transgender person were associated with less prejudice. In a multiple regression analysis, the strongest predictor of prejudice was education about transgender people and topics. Moderation analyses revealed that prior contact may buffer the effects of aggression proneness on prejudiced beliefs.

Development of the Gender Embodiment Scale: Trans Masculine Spectrum.

Transgender and gender diverse (TGD) people have a variety of ways of embodying their gender. We present preliminary work on The Gender Embodiment Scale for trans masculine individuals as a collaborative product from a trans-identified community-engaged team. This scale provides researchers and clinicians a survey to diversify ways gender is understood and counteracts assumptions of a singular gender experience for TGD people. This scale reflects gender embodiment as individually unique and inclusive of the body, behavior, and social treatment. Use of the scale can enhance discussion and enable assessments regarding relative importance and satisfaction across items in these domains.

Lived experience and allostatic load among transmasculine people living in the United States.

BACKGROUND: Transgender and gender diverse people face significant stigma that can adversely affect their physical and mental health. However, the psychobiological link between lived experience and health has been underexplored in this population. We thus examine perceived distress, mental health, and physiological 'wear and tear' by indexing allostatic load (AL) and assess associations with a range of contextual and experiential factors from transmasculine people living in the United States. METHODS: Sixty-five people who identified as transgender men or along a transmasculine spectrum, living in Massachusetts, Vermont, and Rhode Island participated in The Transition Experience Study (age: M=31.8, range 18-55), which examines lived experience of social and medical transition and embodied gender minority/marginalization stress among a sample of transmasculine people. Based on in-depth in-person interview and survey data and inspired by an ecological systems model, we created indices representing (1) perceived progressive geopolitical climate; (2) socio-demographic advantage; (3) social support and resources; (4) gender minority and marginalization stressors; and (5) health behaviors. The Perceived Stress Scale and psychological symptoms (depression, anxiety, insomnia) were also assessed. AL indexed 10 neuroendocrine, immune, cardiovascular, and metabolic biomarkers. RESULTS: Regressions revealed that perceived stress and psychological symptoms were negatively correlated with progressive geopolitical climate (respectively B=-1.47, p = 0.19; B=-.77, p < .001) and positively correlated with gender minority and marginalization stressors (respectively B=1.51, p < .001; B =.38, p = .005). AL was negatively associated with perceived progressive geopolitical climate (B=-.55, p = .007) and socio-demographic advantage (B=-3.2, p = .001). DISCUSSIONS: These findings underline the importance of assessing geopolitical context and indexing lived experiences and life domains along with biomarker sampling. Together, these enable the identification of psychobiological pathways to better nuance multi-level contributors to health and well-being and understand embodied inequalities. These analyses of embodied stigma inclusive of AL biomarkers thus provide a model to further research centering transgender people's health from youth through old age.

[Importance of early identification of a deep neck abscess]. / Het belang van tijdige (h)erkenning van een logeabces.

Treatment of odontogenic infections, such as drainage of submucosal abscesses, should be carried out by the dental practitioner. However, when an odontogenic infection deteriorates into a deep neck abscess, treatment should be carried out by the oral maxillofacial surgeon. Based on two cases, this article describes the clinical presentation, course, and necessary treatment of a deep neck abscess. It also points out that timely recognition of the disease is key in treatment. In any case of delay, there is a possibility for fast deterioration by complications, such as airway obstruction, development of descending necrotizing mediastinitis, or sepsis. Oral health practitioners play an important role in early identification of a deep neck abscess. This article proposes recommendations for dentists when to suspect a deep neck infection, which could be useful in quick and adequate referral to an OMF surgeon.

[The dentogenic inflammation, diagnosis, course and treatment]. / De dentogene ontsteking: diagnose, beloop en behandeling.

Inflammation begins as a response of the immune system to an external, harmful stimulus. This stimulus can be chemical, mechanical or bacterial in nature. The inflammatory response is necessary to create optimal conditions for healing. In case of pulpitis, a peri-apical granuloma, peri-coronitis or periodontitis, complaints arise as a result of an inflammatory reaction. With further progression, such as an infiltrate or a submucosal abscess, the bacteria will eventually invade the tissues and develop an infection. Given the high prevalence of dental diseases, oral health care providers are regularly confronted with the consequences of dentogenic inflammation and subsequent infections. Each specific stage of dentogenic inflammation presents symptoms that are important for making the correct diagnosis. This is important in applying the optimal dental, surgical or medical treatment.

[A human bite wound caused a severe life threatening infection]. / Een mensenbeet met desastreuze gevolgen.

Within 24 hours after a human bite trauma, a 34-year-old male patient became septic and ended up at an intensive care unit. The combination of a local damage of the skin or mucosa, aggressive micro-organisms, local host factors, and some bad luck resulted in necrotizing fasciitis for this patient. This is a very rapid progressive infection which can spread via fat tissue and the muscle fascia. The occurrence of extensive necrosis releases a lot of cytokines and acute-phase proteins, resulting in a systemic reaction. The consequential vasodilatation makes it necessary for the heart to pump harder in order to maintain the circular volume. The patient will soon become septic and hemodynamically unstable. This can also lead to multiple organ failure with potentially fatal consequences. Because necrotizing fasciitis can be caused by commensal bacteria, even young healthy patients are at risk for this invasive life threatening disease. Early recognition of the clinical manifestations can prevent a fatal outcome.

[Inflammation and infection: cellular and biochemical processes]. / Ontsteking en infectie: de cellulaire en biochemische processen.

The terms inflammation and infection are often used interchangeably. Technically this is incorrect. Inflammation is defined as the body's response to a potentially damaging stimulus. Infection involves tissue invasion by microorganisms. An inflammatory reaction will be provoked when infection occurs in an otherwise healthy patient. Inflammation can be recognized clinically by 5 cardinal signs: rubor (redness), calor (warmth), tumor (swelling), dolor (pain), and functio laesa (loss of function). These clinical signs can be explained by the biochemical and cellular processes activated during the inflammatory response. Rubor and calor are the result of local vasodilation. Tumor, dolor and functio laesa result from extravasation of blood plasma, white blood cells, and inflammatory mediators. Pulpitis is an example of inflammation; a periapical abscess is an example of infection.

Critical appraisal of patient-specific implants for secondary post-traumatic orbital reconstruction.

In orbital reconstruction, a patient-specific implant (PSI) may provide accurate reconstruction in complex cases, since the design can be tailored to the anatomy. Several design options may be embedded, for ease of positioning and precision of reconstruction. This study describes a cohort of 22 patients treated for secondary orbital reconstruction with a PSI; one patient received two PSI. The preoperative clinical characteristics and implant design options used are presented. When compared to preoperative characteristics, the postoperative clinical outcomes showed significant improvements in terms of enophthalmos (P < 0.001), diplopia (P < 0.001), and hypoglobus (P = 0.002). The implant position in all previous reconstructions was considered inadequate. Quantitative analysis after PSI reconstruction showed accurate positioning of the implant, with small median and 90th percentile deviations (roll: median 1.3°, 90th percentile 4.6°; pitch: median 1.4°, 90th percentile 3.9°; yaw: median 1.0°, 90th percentile 4.4°; translation: median 1.4 mm, 90th percentile 2.7 mm). Rim support proved to be a significant predictor of roll and rim extension for yaw. No significant relationship between design options or PSI position and clinical outcomes could be established. The results of this study show the benefits of PSI for the clinical outcomes in a large cohort of secondary post-traumatic orbital reconstructions.

Trans and Gender Diverse People's Experience Wearing Face Masks During the COVID-19 Pandemic: Findings from Data Across 4 States in the USA.

Introduction: Social isolation and reduced access to public life in response to SARS-CoV-2 (COVID-19) challenges health and well-being for many. Marginalized communities, including transgender and gender diverse (TGD) people, have been disproportionally impacted. Experiences of TGD people should be centered in pandemic-related research to better inform policy. Methods: A diverse sample of TGD people (N = 158) were recruited from Michigan, Nebraska, Oregon, and Tennessee to participate in the Trans Resilience and Health Study. Participants ranged from 19 to 70 years old (M = 33.06; SD = 12.88) with 27.2% identifying as trans men/men, 26% identifying as trans women/women, and remaining identifying with terms like genderqueer and nonbinary. Thirty percent identified as people of color. Participants completed a monthly COVID-19-related questionnaire April 2020-March 2021 including open-ended questions to learn what contributed to resilience during this time. Thematic analyses of responses enabled identification of salient themes. Results: Analyses revealed pandemic-related changes in social experiences of marginalization and mask-wearing. Twenty-six participants mentioned face masks as contributing to resilience while also elaborating the influence of masks on experiences of misgendering. Participants identifying as trans women reported decreased misgendering while trans men and nonbinary participants reported increased misgendering. Conclusions and Policy Implications: Mask-wearing helps reduce transmission of COVID-19. For some trans women, masks also reduce the threat of misgendering and possibly other forms of enacted stigma. However, increased risk for misgendering, as noted by trans men in our study, should be considered and increased supports should be provided.

Registration-free workflow for electromagnetic and optical navigation in orbital and craniofacial surgery.

The accuracy of intra-operative navigation is largely dependent on the intra-operative registration procedure. Next to accuracy, important factors to consider for the registration procedure are invasiveness, time consumption, logistical demands, user-dependency, compatibility and radiation exposure. In this study, a workflow is presented that eliminates the need for a registration procedure altogether: registration-free navigation. In the workflow, the maxillary dental model is fused to the pre-operative imaging data using commercially available virtual planning software. A virtual Dynamic Reference Frame on a splint is designed on the patient's fused maxillary dentition: during surgery, the splint containing the reference frame is positioned on the patient's dentition. This alleviates the need for any registration procedure, since the position of the reference frame is known from the design. The accuracy of the workflow was evaluated in a cadaver set-up, and compared to bone-anchored fiducial, virtual splint and surface-based registration. The results showed that accuracy of the workflow was greatly dependent on tracking technique used: the workflow was the most accurate with electromagnetic tracking, but the least accurate with optical tracking. Although this method offers a time-efficient, non-invasive, radiation-free automatic alternative for registration, clinical implementation is hampered by the unexplained differences in accuracy between tracking techniques.

Surgical instrument to improve implant positioning in orbital reconstruction: a feasibility study.

Adequate positioning of an orbital implant during orbital reconstruction surgery is essential for restoration of the pre-traumatised anatomy, but visual appraisal of its position is limited by the keyhole access and protruding soft tissues. A positioning instrument that attaches to the implant was designed to provide feedback outside the orbit. The goal of this study was to evaluate the accuracy of placement with the instrument and compare it with the accuracy of placement by visual appraisal. Ten orbits in five human cadaver heads were reconstructed twice: once using visual appraisal and once using the instrument workflow. No significant improvement was found for the roll (5.8° vs 3.4°, respectively, p=0.16), pitch (2.1° vs 1.5°, p=0.56), or translation (2.9 mm vs 3.3 mm, p=0.77), but the yaw was significantly reduced if the instrument workflow was used (15.3° vs 2.9°, p=0.02). The workflow is associated with low costs and low logistical demands, and may prevent outliers in implant positioning in a clinical setting when intraoperative navigation or patient-specific implants are not available.

Challenging the binary: Gender/sex and the bio-logics of normalcy.

BACKGROUND: We are witnessing renewed debates regarding definitions and boundaries of human gender/sex, where lines of genetics, gonadal hormones, and secondary sex characteristics are drawn to defend strict binary categorizations, with attendant implications for the acceptability and limits of gender identity and diversity. AIMS: Many argue for the need to recognize the entanglement of gender/sex in humans and the myriad ways that gender experience becomes biology; translating this theory into practice in human biology research is essential. Biological anthropology is well poised to contribute to these societal conversations and debates. To do this effectively, a reconsideration of our own conceptions of gender/sex, gender identity, and sexuality is necessary. METHODS: In this article, we discuss biological variation associated with gender/sex and propose ways forward to ensure we are engaging with gender/sex diversity. We base our analysis in the concept of "biological normalcy," which allows consideration of the relationships between statistical distributions and normative views. We address the problematic reliance on binary categories, the utilization of group means to represent typical biologies, and document ways in which binary norms reinforce stigma and inequality regarding gender/sex, gender identity, and sexuality. DISCUSSION AND CONCLUSIONS: We conclude with guidelines and methodological suggestions for how to engage gender/sex and gender identity in research. Our goal is to contribute a framework that all human biologists can use, not just those who work with gender or sexually diverse populations. We hope that in bringing this perspective to bear in human biology, that novel ideas and applications will emerge from within our own discipline.

Virtual splint registration for electromagnetic and optical navigation in orbital and craniofacial surgery.

In intra-operative navigation, a registration procedure is performed to register the patient's position to the pre-operative imaging data. The registration process is the main factor that determines accuracy of the navigation feedback. In this study, a novel registration protocol for craniofacial surgery is presented, that utilizes a virtual splint with marker points. The accuracy of the proposed method was evaluated by two observers in five human cadaver heads, for optical and electromagnetic navigation, and compared to maxillary bone-anchored fiducial registration (optical and electromagnetic) and surface-based registration (electromagnetic). The results showed minimal differences in accuracy compared to bone-anchored fiducials at the level of the infra-orbital rim. Both point-based techniques had lower error estimates at the infraorbital rim than surface-based registration, but surface-based registration had the lowest loss of accuracy over target distance. An advantage over existing point-based registration methods (bone-anchored fiducials, existing splint techniques) is that radiological imaging does not need to be repeated, since the need for physical fiducials to be present in the image volume is eradicated. Other advantages include reduction of invasiveness compared to bone-achnored fiducials and a possible reduction of human error in the registration process.

Microbial community changes in a female rat model of Rett syndrome.

Rett syndrome (RTT) is an X-linked neurodevelopmental disorder that is predominantly caused by alterations of the methyl-CpG-binding protein 2 (MECP2) gene. Disease severity and the presence of comorbidities such as gastrointestinal distress vary widely across affected individuals. The gut microbiome has been implicated in neurodevelopmental disorders such as Autism Spectrum Disorder (ASD) as a regulator of disease severity and gastrointestinal comorbidities. Although the gut microbiome has been previously characterized in humans with RTT compared to healthy controls, the impact of MECP2 mutation on the composition of the gut microbiome in animal models where the host and diet can be experimentally controlled remains to be elucidated. By evaluating the microbial community across postnatal development as behavioral symptoms appear and progress, we have identified microbial taxa that are differentially abundant across developmental timepoints in a zinc-finger nuclease rat model of RTT compared to WT. We have additionally identified p105 as a key translational timepoint. Lastly, we have demonstrated that fecal SCFA levels are not altered in RTT rats compared to WT rats across development. Overall, these results represent an important step in translational RTT research.

The hypoxia-sensor carbonic anhydrase IX affects macrophage metabolism, but is not a suitable biomarker for human cardiovascular disease.

Hypoxia is prevalent in atherosclerotic plaques, promoting plaque aggravation and subsequent cardiovascular disease (CVD). Transmembrane protein carbonic anhydrase IX (CAIX) is hypoxia-induced and can be shed into the circulation as soluble CAIX (sCAIX). As plaque macrophages are hypoxic, we hypothesized a role for CAIX in macrophage function, and as biomarker of hypoxic plaque burden and CVD. As tumor patients with probable CVD are treated with CAIX inhibitors, this study will shed light on their safety profile. CAIX co-localized with macrophages (CD68) and hypoxia (pimonidazole), and correlated with lipid core size and pro-inflammatory iNOS+ macrophages in unstable human carotid artery plaques. Although elevated pH and reduced lactate levels in culture medium of CAIX knock-out (CAIXko) macrophages confirmed its role as pH-regulator, only spare respiratory capacity of CAIXko macrophages was reduced. Proliferation, apoptosis, lipid uptake and expression of pro- and anti-inflammatory genes were not altered. Plasma sCAIX levels and plaque-resident CAIX were below the detection threshold in 50 and 90% of asymptomatic and symptomatic cases, respectively, while detectable levels did not associate with primary or secondary events, or intraplaque hemorrhage. Initial findings show that CAIX deficiency interferes with macrophage metabolism. Despite a correlation with inflammatory macrophages, plaque-resident and sCAIX expression levels are too low to serve as biomarkers of future CVD.