Storylines of family medicine IX: people and places-diverse populations and locations of care.

Storylines of Family Medicine is a 12-part series of thematically linked mini-essays with accompanying illustrations that explore the many dimensions of family medicine as interpreted by individual family physicians and medical educators in the USA and elsewhere around the world. In 'IX: people and places-diverse populations and locations of care', authors address the following themes: 'LGBTQIA+health in family medicine', 'A family medicine approach to substance use disorders', 'Shameless medicine for people experiencing homelessness', '''Difficult" encounters-finding the person behind the patient', 'Attending to patients with medically unexplained symptoms', 'Making house calls and home visits', 'Family physicians in the procedure room', 'Robust rural family medicine' and 'Full-spectrum family medicine'. May readers appreciate the breadth of family medicine in these essays.

Sexual dimorphism in aipysurine sea snakes (Elapidae, Hydrophiinae).

The transition from terrestrial to aquatic life by hydrophiine elapid snakes modified targets of natural selection and likely affected sexual selection also. Thus, the shift to marine life also might have affected sexual dimorphism. Our measurements of 419 preserved specimens of six species of aipysurine snakes (genera Emydocephalus and Aipysurus) revealed sexual dimorphism in mean adult snout-vent length (SVL), body width relative to SVL, lengths and widths of heads and tails relative to SVL, and eye diameter relative to head length. Females averaged larger than males in all taxa, and generally were wider-bodied with shorter and wider tails and smaller eyes. For other traits, sexual dimorphism varied among species: for example, relative head length ranged from male-biased to female-biased, and head shape (width relative to length) was highly dimorphic only in A. laevis. The transition to marine life may have eliminated male-male combat (reducing selection for large males) and favoured visual rather than pheromone-based mate-searching (favouring larger eyes in males). Variation in head-size dimorphism may reflect intersexual niche partitioning, with different taxa following different trajectories. Repeated evolutionary transitions from terrestrial to aquatic life in snakes provide a powerful opportunity to explore selective forces on sexually dimorphic traits.

Large Scale Comparative Deconvolution Analysis of the Canine and Human Osteosarcoma Tumor Microenvironment Uncovers Conserved Clinically Relevant Subtypes.

Osteosarcoma is a relatively rare but aggressive cancer of the bones with a shortage of effective biomarkers. Although less common in humans, Osteosarcomas are fairly common in adult pet dogs and have been shown to share many similarities with their human analogs. In this work, we analyze bulk transcriptomic data of 213 primary and 100 metastatic Osteosarcoma samples from 210 pet dogs enrolled in nation-wide clinical trials to uncover three Tumor Microenvironment (TME)-based subtypes: Immune Enriched (IE), Immune Enriched Dense Extra-Cellular Matrix-like (IE-ECM) and Immune Desert (ID) with distinct cell type compositions, oncogenic pathway activity and chromosomal instability. Furthermore, leveraging bulk transcriptomic data of canine primary tumors and their matched metastases from different sites, we characterize how the Osteosarcoma TME evolves from primary to metastatic disease in a standard of care clinical setting and assess its overall impact on clinical outcomes of canines. Most importantly, we find that TME-based subtypes of canine Osteosarcomas are conserved in humans and predictive of progression free survival outcomes of human patients, independently of known prognostic biomarkers such as presence of metastatic disease at diagnosis and percent necrosis following chemotherapy. In summary, these results demonstrate the power of using canines to model the human Osteosarcoma TME and discover novel biomarkers for clinical translation.

Preclinical development of a chimeric antigen receptor T cell therapy targeting FGFR4 in rhabdomyosarcoma.

Pediatric patients with relapsed or refractory rhabdomyosarcoma (RMS) have dismal cure rates, and effective therapy is urgently needed. The oncogenic receptor tyrosine kinase fibroblast growth factor receptor 4 (FGFR4) is highly expressed in RMS and lowly expressed in healthy tissues. Here, we describe a second-generation FGFR4-targeting chimeric antigen receptor (CAR), based on an anti-human FGFR4-specific murine monoclonal antibody 3A11, as an adoptive T cell treatment for RMS. The 3A11 CAR T cells induced robust cytokine production and cytotoxicity against RMS cell lines in vitro. In contrast, a panel of healthy human primary cells failed to activate 3A11 CAR T cells, confirming the selectivity of 3A11 CAR T cells against tumors with high FGFR4 expression. Finally, we demonstrate that 3A11 CAR T cells are persistent in vivo and can effectively eliminate RMS tumors in two metastatic and two orthotopic models. Therefore, our study credentials CAR T cell therapy targeting FGFR4 to treat patients with RMS.

A Randomised Clinical Feasibility Trial of a Breast Immobilisation Device: The SuPPORT 4 All Bra.

AIMS: Despite the breast being a mobile organ, there is currently no standard suitable immobilisation device to optimise radiotherapy for women with larger breasts treated after a wide local excision. The SuPPORT 4 All (S4A) bra was co-designed with patients and radiotherapy professionals. The purpose of this study was to test the feasibility of using the S4A bra in the existing breast cancer radiotherapy pathway. MATERIALS AND METHODS: A randomised feasibility trial was conducted in a single institution; the primary feasibility endpoint was the recruitment of 50 participants. Efficacy endpoints were also tested, including assessment of skin reactions, dose to organs at risk and patient comfort. Fifty women were randomised to receive either standard radiotherapy with no immobilisation (control) or radiotherapy with the S4A bra (intervention). A separate planning study was undertaken on the cases randomised to receive the S4A bra. Participants in the intervention arm (S4A bra) underwent two planning computed tomography scans, one with the bra on and one without the bra; allowing direct comparison of organs at risk data for S4A bra versus no bra. RESULTS: All women who started radiotherapy wearing the S4A bra completed treatment with the bra; patient comfort did not change across the 3 weeks of treatment. Positional accuracy using the bra was comparable with existing published accuracy for methods without immobilisation. The mean ipsilateral lung doses showed some improvement when positioning with the S4A bra was compared with the no bra set-up (3.72 Gy versus 4.85 Gy for right-sided cases, 3.23 Gy versus 3.62 Gy for left-sided cases). CONCLUSIONS: The S4A bra is feasible to use in the radiotherapy pathway with good patient adherence. The S4A bra has potential to reduce dose to organs at risk (specifically ipsilateral lung dose) while maintaining good breast tissue coverage, and improved patient dignity, warranting further investigation on a larger scale.

More than mateship: exploring how Australian male expatriates, longer-term and frequent travellers experience social support.

PURPOSE: Those travelling overseas for work or leisure including male expatriates, longer-term and frequent travellers (ELoFTs) may be at heightened risk for a range of health and wellbeing issues. Social support may mediate this risk. However, from a public health perspective, little is written about how ELoFTs access health information and support and the role of their social networks in facilitating health and wellbeing outcomes. This research was part of a study examining social network processes of Australian male ELoFTs travelling, living, or working in Southeast Asia (SEA). METHODS: Symbolic Interactionism and Grounded Theory were the conceptual framework and methodology supporting semi-structured, in-depth interviews (n = 25) conducted in Australia and Thailand with Australian male ELoFTs to SEA, aged 18 years or older. RESULTS: Findings highlight supports that assist ELoFT transition and adjustment to country of destination or manage their transnational experience. Influential places, people, and points in the migration journey mediated engagement with social support. CONCLUSIONS: ELoFT social networks and the support provided within them may provide a mechanism for intervention across a range of public health issues. Findings may support the development of policy and practice across industries charged with supporting successful ELoFT adjustment.

Stress indicators in minorities with multiple sclerosis.

Black Americans with multiple sclerosis (MS) experience higher levels of disease-related disability compared to White Americans (Marrie et al., 2006). Comorbidities such as depression and anxiety, which are underdiagnosed and undertreated in this population, negatively impact quality of life and treatment outcomes for people living with multiple sclerosis (plwMS) (D'Alisa et al., 2006; Marrie et al., 2009; Stepleman et al., 2014). Acts of discrimination toward Black Americans is associated with stress, which is a contributing factor for depression (Carter, 2017; Nadimpalli, 2015; Williams and Mohammed, 2009). This study compared the severity of multiple sclerosis symptoms amongst Black Americans and White Americans, and whether worsened MS symptoms in Black Americans are associated with increased experiences of discrimination. Data was analyzed from 143 plwMS in the Stress Indicators in Minorities with Multiple Sclerosis (SiMMS) study. Using the Mann-Whitney U test, significant differences were found on the NIH Emotional Distress - Anxiety measure (U = 1466.500, p = 0.045) and NIH Sleep Disturbance measure (U = 1467.000, p = 0.044) between the Black participant and the White participant groups. Discrimination was significantly correlated with both NIH Emotional Distress - Anxiety (r = 0.677, p < .001) and NIH Sleep Disturbance (r = 0.446, p = .007) in Black MS individuals. Additionally, several physiological condition and psychological outcome measures were correlated with the NIH Emotional Distress - Anxiety and NIH Sleep Disturbance measures. This study contributes to literature highlighting the negative impacts of discrimination and race related stress on the physical and mental health of Black Americans.

Dual inhibition of EZH2 and G9A/GLP histone methyltransferases by HKMTI-1-005 promotes differentiation of acute myeloid leukemia cells.

All-trans-retinoic acid (ATRA)-based differentiation therapy of acute promyelocytic leukemia (APL) represents one of the most clinically effective examples of precision medicine and the first example of targeted oncoprotein degradation. The success of ATRA in APL, however, remains to be translated to non-APL acute myeloid leukemia (AML). We previously showed that aberrant histone modifications, including histone H3 lysine 4 (H3K4) and lysine 27 (H3K27) methylation, were associated with this lack of response and that epigenetic therapy with small molecule inhibitors of the H3K4 demethylase LSD1/KDM1A could reprogram AML cells to respond to ATRA. Serving as the enzymatic component of Polycomb Repressive Complex 2, EZH2/KMT6A methyltransferase plays a critical role in normal hematopoiesis by affecting the balance between self-renewal and differentiation. The canonical function of EZH2 is methylation of H3K27, although important non-canonical roles have recently been described. EZH2 mutation or deregulated expression has been conclusively demonstrated in the pathogenesis of AML and response to treatment, thus making it an attractive therapeutic target. In this study, we therefore investigated whether inhibition of EZH2 might also improve the response of non-APL AML cells to ATRA-based therapy. We focused on GSK-343, a pyridone-containing S-adenosyl-L-methionine cofactor-competitive EZH2 inhibitor that is representative of its class, and HKMTI-1-005, a substrate-competitive dual inhibitor targeting EZH2 and the closely related G9A/GLP H3K9 methyltransferases. We found that treatment with HKMTI-1-005 phenocopied EZH2 knockdown and was more effective in inducing differentiation than GSK-343, despite the efficacy of GSK-343 in terms of abolishing H3K27 trimethylation. Furthermore, transcriptomic analysis revealed that in contrast to treatment with GSK-343, HKMTI-1-005 upregulated the expression of differentiation pathway genes with and without ATRA, while downregulating genes associated with a hematopoietic stem cell phenotype. These results pointed to a non-canonical role for EZH2, which was supported by the finding that EZH2 associates with the master regulator of myeloid differentiation, RARα, in an ATRA-dependent manner that was enhanced by HKMTI-1-005, possibly playing a role in co-regulator complex exchange during transcriptional activation. In summary, our results strongly suggest that addition of HKMTI-1-005 to ATRA is a new therapeutic approach against AML that warrants further investigation.

Philosophies of Family Medicine: Piloting an Innovative Clerkship Curriculum.

Background and Objectives: In order to emphasize the role family medicine plays in providing robust primary care in functioning health care systems, we piloted a novel online curriculum for third-year medical students. Using a digital documentary and published articles as prompts, this flipped-classroom, discussion-based Philosophies of Family Medicine curriculum (POFM) highlighted concepts that have either emerged from or been embraced by family medicine (FM) over the past 5 decades. These concepts include the biopsychosocial model, the therapeutic importance of the doctor-patient relationship, and the unique nature of FM. The purpose of this mixed-methods pilot study was to assess the effectiveness of the curriculum and assist in its further development. Methods: The intervention-POFM-consisted of five 1-hour, online discussion sessions with 12 small groups of students (N=64), distributed across seven clinical sites, during their month-long family medicine clerkship block rotations. Each session focused on one theme fundamental to the practice of FM. We collected qualitative data through verbal assessments elicited at the end of each session and written assessments at the end of the entire clerkship. We collected supplementary quantitative data via electronically distributed anonymous pre- and postintervention surveys. Results: The study qualitatively and quantitatively demonstrated that POFM helped students understand philosophies fundamental to the practice of FM, improved their attitudes toward FM, and aided in their appreciation of FM as an essential element of a functioning health care system. Conclusion: The results of this pilot study show effective integration of POFM into our FM clerkship. As POFM matures, we plan to expand its curricular role, further evaluate its influence, and use it to increase the academic footing of FM at our institution.

Dental Public Health in Action: Delivering a domestic violence and abuse screening and identification training programme in North Staffordshire-based dental practices.

Domestic violence and abuse (DVA) is a significant public health problem both globally and in the UK. Dental professionals are aptly place to detect the signs of DVA and support patients to disclose DVA. However, dental professionals may lack confidence to identify and refer patients experiencing DVA; training needs in these areas were identified in Staffordshire. Glow DVA charity and the local Dental Public Health teams worked collaboratively to develop DVA training and resources specific to the needs to the dental team; these were provided to participating dental practices in the North-Staffordshire region. Feedback from the training was positive and the training was refined to better meet the needs of the dental team.mKey challenges included obtaining dental team buy in, securing funding for the continuation of the initiative and minimising the disruption to the dental team when attending training sessions or when managing a DVA disclosure. The implementation of the training highlighted the importance of DVA champions within the third sector organisations to develop and evolve the project, within dental practices to support implementation, and within the local Dental Public Health team to facilitate dental team buy-in and sustained engagement. Future plans include developing the patient-facing resources, finding ways to formally accredit dental teams for taking part in the DVA programme, and evaluating the impact of the training programme on DVA screening, identification and referral.

Deep Domain Adversarial Learning for Species-Agnostic Classification of Histologic Subtypes of Osteosarcoma.

Osteosarcomas (OSs) are aggressive bone tumors with many divergent histologic patterns. During pathology review, OSs are subtyped based on the predominant histologic pattern; however, tumors often demonstrate multiple patterns. This high tumor heterogeneity coupled with scarcity of samples compared with other tumor types render histology-based prognosis of OSs challenging. To combat lower case numbers in humans, dogs with spontaneous OSs have been suggested as a model species. Herein, a convolutional neural network was adversarially trained to classify distinct histologic patterns of OS in humans using mostly canine OS data during training. Adversarial training improved domain adaption of a histologic subtype classifier from canines to humans, achieving an average multiclass F1 score of 0.77 (95% CI, 0.74-0.79) and 0.80 (95% CI, 0.78-0.81) when compared with the ground truth in canines and humans, respectively. Finally, this trained model, when used to characterize the histologic landscape of 306 canine OSs, uncovered distinct clusters with markedly different clinical responses to standard-of-care therapy.

Atlas of 35 patient reported outcome measures (PROMs) in andrology: a comprehensive overview of literature.

INTRODUCTION: Disorders of male sexual health and functioning are complex and can have significant deleterious effects on patients psychological wellbeing and interpersonal relationships. It is well recognised that clinicians have an overall poor understanding of the true effect that disease has on their patients and self-reported patient-reported outcome measures (PROMs) aim to better communicate these issues. PROMs are generally welcomed by patients and their use in this highly sensitive area of clinical practice is well recognised. An atlas of available PROMs for key conditions in andrology is presented in this article. METHODS: A comprehensive search of world literature was conducted from the inception of databases to June 2022, to identify male-specific PROMs relevant to four key andrological disorders: hypogonadism, erectile dysfunction, penile curvature and disorders of ejaculation. Each tool was evaluated in narrative format. RESULTS: 35 PROMs were identified. 6 were designed for the assessment of hypogonadism, 18 for erectile dysfunction, one for penile curvature and 10 for ejaculatory disorders. In general, PROMs were brief, self-administered and user-friendly. There was sufficient scope and variety in all categories (apart from penile curvature) to give the clinician flexibility in tool selection and find an appropriate tool for different scenarios. CONCLUSION: A number of PROMs exist within andrology that can be utilised in both research and clinical settings. PROMs enable subjective evaluation of difficult-to-assess aspects of the patient experience.

Predicting Molecular Subtype and Survival of Rhabdomyosarcoma Patients Using Deep Learning of H&E Images: A Report from the Children's Oncology Group.

PURPOSE: Rhabdomyosarcoma (RMS) is an aggressive soft-tissue sarcoma, which primarily occurs in children and young adults. We previously reported specific genomic alterations in RMS, which strongly correlated with survival; however, predicting these mutations or high-risk disease at diagnosis remains a significant challenge. In this study, we utilized convolutional neural networks (CNN) to learn histologic features associated with driver mutations and outcome using hematoxylin and eosin (H&E) images of RMS. EXPERIMENTAL DESIGN: Digital whole slide H&E images were collected from clinically annotated diagnostic tumor samples from 321 patients with RMS enrolled in Children's Oncology Group (COG) trials (1998-2017). Patches were extracted and fed into deep learning CNNs to learn features associated with mutations and relative event-free survival risk. The performance of the trained models was evaluated against independent test sample data (n = 136) or holdout test data. RESULTS: The trained CNN could accurately classify alveolar RMS, a high-risk subtype associated with PAX3/7-FOXO1 fusion genes, with an ROC of 0.85 on an independent test dataset. CNN models trained on mutationally-annotated samples identified tumors with RAS pathway with a ROC of 0.67, and high-risk mutations in MYOD1 or TP53 with a ROC of 0.97 and 0.63, respectively. Remarkably, CNN models were superior in predicting event-free and overall survival compared with current molecular-clinical risk stratification. CONCLUSIONS: This study demonstrates that high-risk features, including those associated with certain mutations, can be readily identified at diagnosis using deep learning. CNNs are a powerful tool for diagnostic and prognostic prediction of rhabdomyosarcoma, which will be tested in prospective COG clinical trials.

Standards of Care for the Health of Transgender and Gender Diverse People, Version 8.

Background: Transgender healthcare is a rapidly evolving interdisciplinary field. In the last decade, there has been an unprecedented increase in the number and visibility of transgender and gender diverse (TGD) people seeking support and gender-affirming medical treatment in parallel with a significant rise in the scientific literature in this area. The World Professional Association for Transgender Health (WPATH) is an international, multidisciplinary, professional association whose mission is to promote evidence-based care, education, research, public policy, and respect in transgender health. One of the main functions of WPATH is to promote the highest standards of health care for TGD people through the Standards of Care (SOC). The SOC was initially developed in 1979 and the last version (SOC-7) was published in 2012. In view of the increasing scientific evidence, WPATH commissioned a new version of the Standards of Care, the SOC-8. Aim: The overall goal of SOC-8 is to provide health care professionals (HCPs) with clinical guidance to assist TGD people in accessing safe and effective pathways to achieving lasting personal comfort with their gendered selves with the aim of optimizing their overall physical health, psychological well-being, and self-fulfillment. Methods: The SOC-8 is based on the best available science and expert professional consensus in transgender health. International professionals and stakeholders were selected to serve on the SOC-8 committee. Recommendation statements were developed based on data derived from independent systematic literature reviews, where available, background reviews and expert opinions. Grading of recommendations was based on the available evidence supporting interventions, a discussion of risks and harms, as well as the feasibility and acceptability within different contexts and country settings. Results: A total of 18 chapters were developed as part of the SOC-8. They contain recommendations for health care professionals who provide care and treatment for TGD people. Each of the recommendations is followed by explanatory text with relevant references. General areas related to transgender health are covered in the chapters Terminology, Global Applicability, Population Estimates, and Education. The chapters developed for the diverse population of TGD people include Assessment of Adults, Adolescents, Children, Nonbinary, Eunuchs, and Intersex Individuals, and people living in Institutional Environments. Finally, the chapters related to gender-affirming treatment are Hormone Therapy, Surgery and Postoperative Care, Voice and Communication, Primary Care, Reproductive Health, Sexual Health, and Mental Health. Conclusions: The SOC-8 guidelines are intended to be flexible to meet the diverse health care needs of TGD people globally. While adaptable, they offer standards for promoting optimal health care and guidance for the treatment of people experiencing gender incongruence. As in all previous versions of the SOC, the criteria set forth in this document for gender-affirming medical interventions are clinical guidelines; individual health care professionals and programs may modify these in consultation with the TGD person.

Quantifying electron temperature distributions from time-integrated x-ray emission spectra.

K-shell x-ray emission spectroscopy is a standard tool used to diagnose the plasma conditions created in high-energy-density physics experiments. In the simplest approach, the emissivity-weighted average temperature of the plasma can be extracted by fitting an emission spectrum to a single temperature condition. It is known, however, that a range of plasma conditions can contribute to the measured spectra due to a combination of the evolution of the sample and spatial gradients. In this work, we define a parameterized model of the temperature distribution and use Markov Chain Monte Carlo sampling of the input parameters, yielding uncertainties in the fit parameters to assess the uniqueness of the inferred temperature distribution. We present the analysis of time-integrated S and Fe x-ray spectroscopic data from the Orion laser facility and demonstrate that while fitting each spectral region to a single temperature yields two different temperatures, both spectra can be fit simultaneously with a single temperature distribution. We find that fitting both spectral regions together requires a maximum temperature of 1310-70 +90 eV with significant contributions from temperatures down to 200 eV.

Accuracy of Palpation Procedures for Locating the C1 Transverse Process and Masseter Muscle as Confirmed by Computed Tomography Images.

OBJECTIVE: The purpose of this study was to examine the accuracy of palpation methods for locating the transverse processes of the first cervical vertebra and masseter muscle using radiographic images as the gold-standard method and the association between personal characteristics with the observed accuracy. METHODS: This was a single-blinded, diagnostic accuracy study. Ninety-five participants (49 women, 58 ± 16 years of age) were enrolled in this study. A single examiner palpated the neck and face region of all participants to identify the transverse processes of the first cervical vertebra and masseter muscles bilaterally. In sequence, participants underwent a multislice computed tomography scan for assessment of the superimposed inner body structure. Two radiologists assessed the computed tomography images using the same criteria and were blinded regarding each other's assessment and the anatomic landmarks under investigation. The palpation accuracy was calculated as the proportion of the correctly identified landmarks in the studied sample. The correlation of the palpation outcome (correct = 1; incorrect = 0) with age, sex (male = 1; female = 0), and body mass index was investigated using the point-biserial correlation coefficient. RESULTS: The right and left transverse processes were correctly located in 76 (80%) and 81 (85%) participants, respectively, and bilaterally in 157 events (83%), as evaluated by the consensus of the 2 radiologists. The masseter muscles were correctly localized bilaterally in 95 of 95 (100%) participants. Body mass showed statistical evidence of a weak, positive correlation with the correct location of the transverse processes of the first cervical vertebra at the right body side (r = .219; 95% confidence interval, 0.018-0.403; P = .033). CONCLUSION: Palpation methods used in this study accurately identified the location of the first cervical vertebra spinous processes and the masseter muscles.

A new benchmark of soft X-ray transition energies of Ne , CO 2 , and SF 6 : paving a pathway towards ppm accuracy.

Abstract: A key requirement for the correct interpretation of high-resolution X-ray spectra is that transition energies are known with high accuracy and precision. We investigate the K-shell features of Ne , CO 2 , and SF 6 gases, by measuring their photo ion-yield spectra at the BESSY II synchrotron facility simultaneously with the 1s-np fluorescence emission of He-like ions produced in the Polar-X EBIT. Accurate ab initio calculations of transitions in these ions provide the basis of the calibration. While the CO 2 result agrees well with previous measurements, the SF 6 spectrum appears shifted by ∼ 0.5 eV, about twice the uncertainty of the earlier results. Our result for Ne shows a large departure from earlier results, but may suffer from larger systematic effects than our other measurements. The molecular spectra agree well with our results of time-dependent density functional theory. We find that the statistical uncertainty allows calibrations in the desired range of 1-10 meV, however, systematic contributions still limit the uncertainty to ∼ 40-100 meV, mainly due to the temporal stability of the monochromator energy scale. Combining our absolute calibration technique with a relative energy calibration technique such as photoelectron energy spectroscopy will be necessary to realize its full potential of achieving uncertainties as low as 1-10 meV.

Artificial Intelligence-based Tumor Segmentation in Mouse Models of Lung Adenocarcinoma.

BACKGROUND: Mouse models are highly effective for studying the pathophysiology of lung adenocarcinoma and evaluating new treatment strategies. Treatment efficacy is primarily determined by the total tumor burden measured on excised tumor specimens. The measurement process is time-consuming and prone to human errors. To address this issue, we developed a novel deep learning model to segment lung tumor foci on digitally scanned hematoxylin and eosin (H&E) histology slides. METHODS: Digital slides of 239 mice from 9 experimental cohorts were split into training (n=137), validation (n=37), and testing cohorts (n=65). Image patches of 500×500 pixels were extracted from 5× and 10× magnifications, along with binary masks of expert annotations representing ground-truth tumor regions. Deep learning models utilizing DeepLabV3+ and UNet architectures were trained for binary segmentation of tumor foci under varying stain normalization conditions. The performance of algorithm segmentation was assessed by Dice Coefficient, and detection was evaluated by sensitivity and positive-predictive value (PPV). RESULTS: The best model on patch-based validation was DeepLabV3+ using a Resnet-50 backbone, which achieved Dice 0.890 and 0.873 on validation and testing cohort, respectively. This result corresponded to 91.3 Sensitivity and 51.0 PPV in the validation cohort and 93.7 Sensitivity and 51.4 PPV in the testing cohort. False positives could be reduced 10-fold with thresholding artificial intelligence (AI) predicted output by area, without negative impact on Dice Coefficient. Evaluation at various stain normalization strategies did not demonstrate improvement from the baseline model. CONCLUSIONS: A robust AI-based algorithm for detecting and segmenting lung tumor foci in the pre-clinical mouse models was developed. The output of this algorithm is compatible with open-source software that researchers commonly use.

Trialling a novel socially-distanced teaching approach for OMFS dental core trainees: case-based discussions through WhatsApp©.

In our tertiary level centre, the oral and maxillofacial (OMFS) rotas often change at short- notice due to service requirements and the development of guidance relating to the COVID-19 pandemic. Consequently, we have developed a novel teaching method for our dental core trainees (DCTs) to accommodate hectic schedules and conflicting availability between junior and senior staff. Here, we describe the innovative teaching approach we have established using case-based discussions via WhatsApp©. Feedback has been excellent. Respondents have stated that the most useful aspect is flexibility to participate in between tasks and across multiple sites, and 87% stated that they use the searchable summaries when managing patients. This teaching method is highly beneficial for OMFS DCTs. It allows flexibility for fluctuating schedules, is interactive, and provides an easily accessible resource whilst on call. We believe that other teams may benefit from the method if scheduling the time for regular didactic teaching is difficult, or they wish to supplement existing practices.

Interobserver variation in the classification of tumor deposits in rectal cancer-is the use of histopathological characteristics the way to go?

The focus on lymph node metastases (LNM) as the most important prognostic marker in colorectal cancer (CRC) has been challenged by the finding that other types of locoregional spread, including tumor deposits (TDs), extramural venous invasion (EMVI), and perineural invasion (PNI), also have significant impact. However, there are concerns about interobserver variation when differentiating between these features. Therefore, this study analyzed interobserver agreement between pathologists when assessing routine tumor nodules based on TNM 8. Electronic slides of 50 tumor nodules that were not treated with neoadjuvant therapy were reviewed by 8 gastrointestinal pathologists. They were asked to classify each nodule as TD, LNM, EMVI, or PNI, and to list which histological discriminatory features were present. There was overall agreement of 73.5% (κ 0.38, 95%-CI 0.33-0.43) if a nodal versus non-nodal classification was used, and 52.2% (κ 0.27, 95%-CI 0.23-0.31) if EMVI and PNI were classified separately. The interobserver agreement varied significantly between discriminatory features from κ 0.64 (95%-CI 0.58-0.70) for roundness to κ 0.26 (95%-CI 0.12-0.41) for a lone arteriole sign, and the presence of discriminatory features did not always correlate with the final classification. Since extranodal pathways of spread are prognostically relevant, classification of tumor nodules is important. There is currently no evidence for the prognostic relevance of the origin of TD, and although some histopathological characteristics showed good interobserver agreement, these are often non-specific. To optimize interobserver agreement, we recommend a binary classification of nodal versus extranodal tumor nodules which is based on prognostic evidence and yields good overall agreement.